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Allergy and Airway

Chest. 2014;146(4_MeetingAbstracts):1A. doi:10.1378/chest.1994482

SESSION TITLE: Asthma Posters I

SESSION TYPE: Original Investigation Poster

PRESENTED ON: Wednesday, October 29, 2014 at 01:30 PM - 02:30 PM

PURPOSE: Tiotropium Respimat®, a once-daily long-acting anticholinergic bronchodilator, has been shown to be an efficacious and well tolerated add-on to at least ICS in adult patients with symptomatic asthma. We present key safety data from five Phase III, randomized, double-blind, parallel-group trials that evaluated the efficacy and safety of once-daily tiotropium Respimat® as add-on to at least ICS versus placebo Respimat® in adult patients with symptomatic asthma.

METHODS: 2 × 48-week trials of tiotropium Respimat® 5 µg (PrimoTinA-asthma®: NCT00776984; NCT00772538) in patients on high-dose ICS (≥800 µg budesonide or equivalent) plus LABA; 2 × 24-week trials of tiotropium Respimat® 5 µg and 2.5 µg (MezzoTinA-asthma®: NCT01172808, NCT01172821) in patients on medium-dose ICS (400-800 µg budesonide or equivalent); 1 × 12-week trial of tiotropium Respimat® 5 µg and 2.5 µg (GraziaTinA-asthma®: NCT01316380) in patients on low-dose ICS (200-400 µg budesonide or equivalent).

RESULTS: 3476 patients were treated. The incidence of any adverse events was similar across treatment groups within each trial, with the majority being mild or moderate in severity. Adverse events reported by ≥5% of patients were similar across all treatment groups within each trial. Adverse events reported by ≥5% of patients across all treatment groups within each trial included asthma, decreased peak expiratory flow, nasopharyngitis, upper respiratory tract infection, headache, and bronchitis. Overall, a low frequency of serious adverse events was observed: PrimoTinA-asthma® tiotropium Respimat® 5 µg 8.1%, placebo Respimat® 8.8%; MezzoTinA-asthma® tiotropium Respimat® 5 µg 2.1%, tiotropium Respimat® 2.5 µg 2.3%, placebo Respimat® 2.7%; GraziaTinA-asthma® tiotropium Respimat® 5 µg 0.6%, tiotropium Respimat® 2.5 µg 0%, placebo Respimat® 0.6%. No deaths occurred.

CONCLUSIONS: Once-daily tiotropium Respimat® add-on to at least ICS is well tolerated and has a safety profile comparable to placebo Respimat® in adult patients with symptomatic asthma.

CLINICAL IMPLICATIONS: Once-daily tiotropium Respimat® may provide an alternative add-on therapy to at least ICS in adult patients with symptomatic asthma. Funding: Boehringer Ingelheim. Editorial assistance: Complete HealthVizion.

DISCLOSURE: Mark Vandewalker: Grant monies (from industry related sources): Research grant from Boehringer-Ingelheim Eli Meltzer: Grant monies (from industry related sources): Alcon, Amgen, AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, HRA, Kalypsys, Merck, Novartis, Ono, Proctor & Gamble, Rigel, Shionogi, Sunovion, Teva, Consultant fee, speaker bureau, advisory committee, etc.: Alcon, Alexza, AstraZeneca, Bausch + Lomb, Boehringer Ingelheim, Johnson & Johnson, Kalypsys, Meda, Merck, Mylan, Proctor & Gamble, Rigel, Sanofi, Sunovion, Teva Michael Engel: Employee: Boehringer-Ingelheim Ralf Sigmund: Employee: Boehringer-Ingelheim Petra Moroni-Zentgraf: Employee: Boehringer-Ingelheim Huib Kerstjens: Consultant fee, speaker bureau, advisory committee, etc.: From Boerhringer an d Pfizer, in relation to the work presented. As consultant, advisory baord member, and as principal investigator and recruiter., Consultant fee, speaker bureau, advisory committee, etc.: From Almirall, to my institution for consultancies, Consultant fee, speaker bureau, advisory committee, etc.: From Novartis, to my institution for consultancies

This abstract includes data from clinical trials of tiotropium in asthma. However, tiotropium is not approved for use in asthma and its safety and efficacy have not yet been established in asthma.

Chest. 2014;146(4_MeetingAbstracts):2A. doi:10.1378/chest.1993299

SESSION TITLE: Asthma Posters I

SESSION TYPE: Original Investigation Poster

PRESENTED ON: Wednesday, October 29, 2014 at 01:30 PM - 02:30 PM

PURPOSE: Methacholine challenge testing (MCT) has been the primary test used to identify non-specific airway hyperresponsiveness (AHR) related to either asthma or exercise-induced bronchospasm (EIB). Inhalation mannitol has been demonstrated to be a more accurate predictor of underlying asthma based on its properties. We compared mannitol vs. MCT in a group of individuals, primarily military with normal baseline spirometry.

METHODS: Patients referred for MCT underwent repeat bronchoprovocation testing with mannitol no sooner than 48 hrs post MCT. Methacholine was administered with increasing dosages to 16 mg/ml or PC20 and mannitol was given with increasing dosages to 160 mg/ml or PC15 per guidelines. Impulse oscillometry (IOS) resistance values (R5, R20, X5) were recorded at baseline and after maximum dose during each study.

RESULTS: A total of 39 patients have completed both testing modalities. The group is 72% males with mean age of 35.4 ±10.8 years. Mean baseline spirometry values included: FEV1(% pred): 93.2±12.5; FVC(% pred): 95.0±11.6; and FEV1/FVC = 80.2±6.5. There were 8 positive and 31 negative MCT studies, while only 7 reactive mannitol with 32 negative studies. Only 50% of positive MCT correlated with a reactive mannitol. IOS resistance values (R5 and X5-X5pred) post MCT showed significant changes for positive studies (p =0.05) while mannitol values were non-significant.

CONCLUSIONS: Discussion: There is a clear discordance with reactive MCT and mannitol in this population with normal spirometry being evaluated for exertional dyspnea. Currently, there is no trend in this study favoring one methodology for determining AHR vs inflammation as the underlying mechanism for symptoms. The use of IOS resistance values did not help discriminate positive studies especially with mannitol. Conclusions: In a military population evaluated for exertional dyspnea, reactive MCT indicates underlying AHR alone favoring the diagnosis of EIB while the remaining 50% may have underlying inflammation c/w asthma.

CLINICAL IMPLICATIONS: Methacholine should remain a primary testing modality to evaluate for non-specific AHR especially in military personnel to diagnose EIB. Further comparison is warranted between modalities.

DISCLOSURE: The following authors have nothing to disclose: Michelle Alders, Heather Arellano, Jackie Hayes, Michael Morris

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Chest. 2014;146(4_MeetingAbstracts):3A. doi:10.1378/chest.1991486

SESSION TITLE: Asthma Posters I

SESSION TYPE: Original Investigation Poster

PRESENTED ON: Wednesday, October 29, 2014 at 01:30 PM - 02:30 PM

PURPOSE: That in asthma there is a certain involvement of small airways is out of doubt. One question arises if the technique of impulse oscillometriy (IOS) is able to reveal with enough sensitivity the inflammatory abnormalities in small airways, as detected from the increase of flow resistances, in asthma. To do this consecutive asthmatic patients were enrolled during a stable phase of their disease.

METHODS: IOS were measured according the standard technique on the basis of tidal breathing by means of small impulses-shaped signals continuously superimposed on the patient's breathing flow utilizing the Jager Impulse Oscillating System (Care Fusion Product). After a minimum of 4 regular breaths the data recordings were collected at functional residual capacity, in a seated position. Parameters included resistances at oscillation-frequencies of 5 Hz (R5) and 20 Hz (R20), frequency dependence of resistance calculated as the difference between resistance at 5 and 20 Hz (R5-20) and reactance at 5 Hz (X5). R5 and R20 were assumed to reflect respiratory resistance at 5 and 20 Hz, respectively, R5-R20 reflecting the non uniform distribution of airflow in the distal airways and X5 reflecting the dynamic elastance. Spirometry was also executed. Seventyfour patients with asthma (21 males and 53 female, age range 19-73 years) performed the test. Moreover, a group control consisting of 13 healthy subjects was considered. Sensitivity and specificity, as well as positive and negative predictive values (PPV and NPV) and accuracy were calculated according to treshold values of R5-R20 ≥ to 0.07 Kpa/lL/s and X5 > -0.12 Kpa/L/s

RESULTS: Mostly of patients exhibited spirometry above normal range (FEV1/FVC > 70%). Out of 74 pts with asthma 48 resulted positive for the test whereas 26 patients had values of R5-R20 below the treshold limit. It turned out that sensitivity was 65 % whereas specificity resulted 100%. PPV resulted 100% whereas NPV resulted 33%, and, finally, the real prevalence of the test was 55%. Accuracy was 70%. As to X5, 65% of patients had values below the threshold, which is specular to R5-R20 values.

CONCLUSIONS: Our preliminary results seem to suggest that values of R5-R20 < to 0.07 and of X5 > -0.12 Kpa/L/s may allow to exclude with extreme accuracy the presence of increased flow resistances at the level of small airways and thus the existence of inflammation.

CLINICAL IMPLICATIONS: These observations suggest caution to interpret this test in the clinical work-up, when employed as unique tool to evaluate the disease.

DISCLOSURE: The following authors have nothing to disclose: Rudina Ndreu, Ivana Pavlickova, Edo Fornai, Simonetta Monti, Renato Prediletto

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Chest. 2014;146(4_MeetingAbstracts):4A. doi:10.1378/chest.1990469

SESSION TITLE: Asthma Posters I

SESSION TYPE: Original Investigation Poster

PRESENTED ON: Wednesday, October 29, 2014 at 01:30 PM - 02:30 PM

PURPOSE: In two, 12-week, double-blind, placebo- and active-controlled pivotal trials in asthmatic patients with flunisolide HFA (Aerospan™, a small-particle ICS with a built-in spacer to optimize delivery of flunisolide HFA throughout the lung, while minimizing oral deposition). In these trials, various sub-group analyses were performed based on demographic parameters and asthma severity.

METHODS: Efficacy and safety of flunisolide HFA doses of: 80 mcg (1 puff) BID, 160 (2 puffs) mcg BID and 320 mcg (4 puffs) BID in adults/adolescents 12 years and older and 80 (1 puff) and 160 (2 puffs) mcg BID in pediatric patients 4 years and older were evaluated. Specifically, sub-group evaluations based on demographics (age-4-5 years, 6-11 years, 12-17 years, greater than 18 years, gender and race) and asthma disease severity (percent predicted FEV1 less than population median of 73.9% in adult/adolescent trial and 83.3% predicted FEV1 in the pediatric 4-11 trial compared with those with percent predicted FEV1 greater than or equal to the population median).

RESULTS: Deterioration of percent predicted FEV1 from baseline was observed in the placebo group, whereas minimal changes or improvements were observed in the flunisolide HFA groups after being switched from 2 weeks of flunisolide CFC (500 mcg BID) during a 2-week run-in. No significant changes in percent predicted FEV1 were noted for other sub-groups analyzed (based on gender, race, or asthma severity). Flunisolide HFA did not increase the incidence of any treatment-emergent adverse events (TEAEs) by age, gender, race, or baseline asthma severity, either within the flunisolide HFA treatment groups or by comparison to placebo.

CONCLUSIONS: Treatment with Aerospan was efficacious and safe across the entire age range of patients and across subpopulations determined by gender, race, and disease severity.

CLINICAL IMPLICATIONS: The unique properties of flunisolide HFA, with its small particle size and built-in spacer, offer an advanced treatment option for asthmatics. The flunisolide HFA product attributes may be particularly beneficial for pediatric patients.

DISCLOSURE: John Karafilidis: Employee: Meda Pharmaceutical Employee William Berger: Consultant fee, speaker bureau, advisory committee, etc.: Meda Pharmaceutical Consultant Larry Gever: Employee: Meda Pharmaceutical Employee Nancy Ruiz: Employee: Meda Pharmaceutical Employee

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Topics: asthma , safety , flunisolide
Chest. 2014;146(4_MeetingAbstracts):5A. doi:10.1378/chest.1990432

SESSION TITLE: Asthma Posters I

SESSION TYPE: Original Investigation Poster

PRESENTED ON: Wednesday, October 29, 2014 at 01:30 PM - 02:30 PM

PURPOSE: Negative systemic effects (including HPA-axis suppression, cataract formation/glaucoma, and increased bone metabolism) have been seen with higher doses of inhaled steroids in adult patients. A 12-week trial performed with flunisolide HFA (Aerospan™; a new, small-particle inhaled steroid with a built-in spacer for asthma) included various assessments for potential systemic effects.

METHODS: In a double-blind, placebo-controlled 12-week trial in adult and adolescent patients 12 years and older, asthmatic patients were treated with: placebo, flunisolide HFA (80 mcg, 160 mcg or 320 mcg BID) or flunisolide CFC (250 mcg, 500 mcg or 100 mcg BID). Various assessments of potential systemic effects of flunisolide HFA were performed in this trial, including: HPA-axis function (24-hr urine cortisol and creatinine, plasma cortisol and cosyntropin stimulation tests), serum osteocalcin, clinical laboratory (evaluating shifts in various related assessments, including-white blood cell counts and glucose levels) and physical examinations (including eyes, ears, nose and throat).

RESULTS: Urinary and plasma cortisol results were similar between placebo and each of the doses of flunisolide HFA (up to 320 mcg BID). Mean values for hematology assessments performed (including white blood cell counts) were all within normal ranges. The number of clinically significant abnormal chemistry test results (including changes in glucose, calcium, alkaline phosphatase and phosphate levels) and changes in physical examination findings were also similar between the placebo and flunisolide HFA treatment groups. Changes in serum osteocalcin levels for those treated with flunisolide HFA were similar to those for placebo.

CONCLUSIONS: After 12 weeks of treatment, doses of flunisolide HFA up to 320 mcg BID (maximum approved dose) did not result in any significant (negative) systemic effects.

CLINICAL IMPLICATIONS: Flunisolide HFA has a limited potential for significant systemic effects (due to its favorable metabolic profile), allowing for chronic use in asthmatics down to the age of 6 years.

DISCLOSURE: William Berger: Consultant fee, speaker bureau, advisory committee, etc.: Consultant for Meda Pharmaceuticals John Karafilidis: Employee: Employee Meda Pharmaceuticals Larry Gever: Employee: Meda Pharmaceuticals Employee Nancy Ruiz: Employee: Meda Pharmaceuticals Employee

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Topics: asthma , flunisolide
Chest. 2014;146(4_MeetingAbstracts):6A. doi:10.1378/chest.1990081

SESSION TITLE: Asthma Posters I

SESSION TYPE: Original Investigation Poster

PRESENTED ON: Wednesday, October 29, 2014 at 01:30 PM - 02:30 PM

PURPOSE: Bronchial Asthma(BA) is an airway disease manifested by increased airway reactivity. A 20% or more of improvement in PEFR after inhalation of bronchodilator(BD) can be used to confirm the diagnosis of BA. Ozturk, et al suggest that the clinical value of PEFR measurements in the diagnosis of reversible obstructive airway disease was less reliable than FEV1. FEF 25-75 is a reflection of small airway patency. Pediatric studies by Devika S Rao, et al have shown that variability of FEF 25-75 by 30% should be considered a potentially important spirometric variable that can be used as a marker of BD responsiveness. Our objective was to compare which one between PEFR 20% variability vs FEF 25-75 variability of 30% correlates better with presence of BD response defined by ATS as an increase in FEV1 by 12% and 200mls in patients with BA.

METHODS: Inclusion criteria were non smokers, with a diagnosis of BA, normal DLCO on Pulmonary Function Tests(PFT). Exclusion criteria were smokers, COPD, CT chest suggestive of emphysema, low DLCO. 161 PFT’s conducted at Interfaith Medical Center between 2008-2013 were obtained. Patients were divided into groups with and without BD response respectively as defined by ATS criteria. Out of 161 patients included in our study 142 patients did not show BD response. The changes in PEFR & FEF25-75 in response to bronchodilator were compared among these two groups. Statistical analysis was done using SPSS 17.0.

RESULTS: Changes in mean PEFR & FEF 25-75 between these two study groups were statistically significant (40.2 vs -.8 and 91.8 vs 22.4 respectively, p<0.05). PEFR variability with bronchodilator had a better positive correlation with the improvement in FEV1 when compared to FEF25-75 variability (r=. 53 & .22 respectively p<0.05). Increment in PEFR by 20% and FEF25-75 by 30% both had a specificity of 86.6% to anticipate adequate response to bronchodilators with a negative predictive value(NPV) of 95.3% and 93.8% respectively.

CONCLUSIONS: Based on these results, PEFR and FEF 25-75 variability correlate well with BD response however PEFR has better correlation.

CLINICAL IMPLICATIONS: FEF25-75 can be used to identify reversible airway obstruction with good specificity and NPV although it has lesser correlation than PEFR. Further studies need to be done comparing them in patients without bronchodilator response.

DISCLOSURE: The following authors have nothing to disclose: Vikram Oke, Rakesh Vadde, Abhisekh Sinha Ray, Mohammad Raihan Azad, Prajakta Mungikar, Sai Wan, Meenakshi Ghosh, Saurav Pokharel, Bikash Bhattarai, Bhradeev Sivasambu, Santu Saha, Rawshan Basunia, Charles Agu, Ramchander Eluri, Francis Schmidt

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Chest. 2014;146(4_MeetingAbstracts):7A. doi:10.1378/chest.1989237

SESSION TITLE: Asthma Posters I

SESSION TYPE: Original Investigation Poster

PRESENTED ON: Wednesday, October 29, 2014 at 01:30 PM - 02:30 PM

PURPOSE: Purpose: Although asthma control is achievable in most patients, it is far from optimal globally. This study aims at evaluating the relationship of asthma medication to the level of its control in Ilorin, Nigeria.

METHODS: Methods: A cross-sectional survey was conducted on113 physician-diagnosed asthma patients attending public and private health care facilities in Ilorin, Nigeria. Asthma control was assessed using the ACT questionnaire and information on medication was obtained from the patients.

RESULTS: Results: The patients were 113 with age range of 17-80 and mean age of 45.6±16.0 years. Nearly all the patients, 103 (91.2%) had uncontrolled asthma (ACT score <19). No patient was on inhaled corticosteroid (ICS) alone. Those with uncontrolled asthma were less likely to be on ICS in combination with long acting β2 agonists (36.8% versus 100%, p<0.001), more likely to be on medication judged by investigators to be inappropriate (72.8% versus 0%, p<0.001) and required rescue medications ≥2-3 times a week (87.4% versus 0%, p<0.001).

CONCLUSIONS: Conclusion: The asthma of more than ninety per cent of our patients was poorly controlled and inadequate use of recommended prophylactic treatments and inappropriate medication may have contributed to this outcome.

CLINICAL IMPLICATIONS: Clinical implications: Appropriate treatment could improve the level of asthma control in Nigeria.

DISCLOSURE: The following authors have nothing to disclose: Ademola Fawibe, Louis Odeigah, Olufemi Desalu

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Chest. 2014;146(4_MeetingAbstracts):8A. doi:10.1378/chest.1989122

SESSION TITLE: Asthma Posters I

SESSION TYPE: Original Investigation Poster

PRESENTED ON: Wednesday, October 29, 2014 at 01:30 PM - 02:30 PM

PURPOSE: Allergic bronchopulmonary aspergillosis (ABPA) is a complex immunological pulmonary disorder caused by hypersensitivity to Aspergillus species mainly Aspergillus fumigatus. The presence of asthma is one of the minimal essential diagnostic criteria for ABPA. Cases of ABPA in nonasthmatic patients have been occasionally reported in the literature.

METHODS: This study was conducted in patients presenting to the Department of Pulmonary Medicine in tertiary centre where diagnoses of ABPA was established using Rosenberg-Patterson criteria and each case was analysed for presence or absence of asthma

RESULTS: During study period , 22 cases were diagnosed to have allergic bronchopulmonary aspergillosis conforming to the usual Rosenberg-Patterson criteria. Out of them in 6 patients, there was no history of asthma and there was no clinical evidence of airflow obstruction at the time of the diagnosis either. Symptom duration in these patients varied from 2 months to 1 year. On investigations, chest x-ray revealed lesions and peripheral blood eosinophilia was present. Then they were subjected to total and specific IgE antibodies and other investigations to prove the diagnosis of ABPA

CONCLUSIONS: The diagnosis of ABPA is based on hematological, radiological and immunological criteria along with presence of asthma, and occasionally, cystic fibrosis. ABPA is rarely thought of in the absence of asthma, as this is the first criterion for diagnosis. Because of the absence of bronchial asthma, these cases are often mistaken initially for other pulmonary disorders. This leads to unnecessary delay in the diagnosis and treatment initiation. Furthermore, the remarkable radiologic similarity to pulmonary tuberculosis has important clinical implications in high tuberculous prevalent areas. This cases reflects the difficulty in recognizing ABPA in the absence of clinical asthma Therefore, ABPA should be included in the differential diagnosis in patients with radiographic abnormalities and peripheral eosinophilia even in those patients who have no history of asthma.

CLINICAL IMPLICATIONS: ABPA most commonly occurs in patients with pre-existing bronchial asthma, a high index of suspicion should be maintained in the absence of asthma. ABPA without clinical asthma can and does pose diagnostic difficulties as in our case. Thus ABPA should be kept as a diagnostic possibility in patients with radiographic abnormalities and peripheral eosinophilia but no history or symptoms related to bronchial asthma.

DISCLOSURE: The following authors have nothing to disclose: Gopal Chawla, Amrit Pal Kansal, Komaldeep Kaur, Kamal Deep, Prabhleen Kaur

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Topics: asthma
Chest. 2014;146(4_MeetingAbstracts):9A. doi:10.1378/chest.1976057

SESSION TITLE: Asthma Posters I

SESSION TYPE: Original Investigation Poster

PRESENTED ON: Wednesday, October 29, 2014 at 01:30 PM - 02:30 PM

PURPOSE: Angiopoietin-1 (ANGPT1) is an essential mediator of angiogenesis that establishes vascular integrity, and angiopoietin-2 (ANGPT2) acts as its natural inhibitor. We considered that angiopoietin might be important in bronchial asthma.

METHODS: Thirty-five patients with asthma and 20 healthy subjects were studied using ELISA.

RESULTS: ANGPT1 levels were significantly elevated in patients with asthma compared to control subjects (293.9 ± 13.8 pg/ml vs. 248.3 ± 16.2 pg/ml, p=0.04). The area under the curve (AUC) for serum angiopoietin revealed that the level of ANGPT1 (0.68) was more sensitive and specific than the determination of ANGPT2 levels (0.55) for differentiating patients with asthma from control subjects. ANGPT2 levels were not different between the two groups. The ANGPT1/ANGPT2 ratio correlated with FEV1/FVC (r=-0.312, p=0.02). ANGPT2 correlated with body mass index.

CONCLUSIONS: Our results reveal that ANGPT1 levels were higher in asthma patients compared with healthy subjects. Because the ANGPT1/ANGPT2 ratio was related to lung function, the data suggest that serum angiopoietin may be associated with lung function in patients with asthma.

CLINICAL IMPLICATIONS: Serum angiopoietin may be a marker for asthma evaluation and monitor.

DISCLOSURE: The following authors have nothing to disclose: An Soo Jang, PuReun-HaNeul Lee, Kuk-Young Moon, Sung-Woo Park, Ae-Rin Baek, Do-Jin Kim, Choon-Sik Park

disscus as done

Chest. 2014;146(4_MeetingAbstracts):10A. doi:10.1378/chest.1971101

SESSION TITLE: Asthma Posters I

SESSION TYPE: Original Investigation Poster

PRESENTED ON: Wednesday, October 29, 2014 at 01:30 PM - 02:30 PM

PURPOSE: Bronchial thermoplasty is an FDA approved procedure for the treatment of severe asthma. Previous studies have not documented an improvement in FEV1 or FVC after thermoplasty, although these studies did not enroll patients with moderate to severe obstruction on spirometry. We sought to determine the effect of bronchial thermoplasty on pulmonary function in patients with documented obstruction on spirometry.

METHODS: Baseline spirometric data from severe asthma patients who underwent bronchial thermoplasty were compared to data obtained one to three months after the procedure.

RESULTS: All patients had a preprocedure FEV1 of less than 60%. In all five patients, FEV1 and FVC improved after the procedure. Mean FEV1 preprocedure was 52% (range 46-60%) predicted, which improved to 67% (range 54-77%) predicted (p=0.02). Mean FVC preprocedure was 76% (range 63-107%) predicted which improved to 88% (range 70-109%) predicted (p=0.03).

CONCLUSIONS: This small observational study indicates that bronchial thermoplasty can improve spirometric values in those patients who have moderate to severe obstruction.

CLINICAL IMPLICATIONS: Bronchial thermoplasty can improve spirometry as well as asthma control and asthma quality of life in patients with severe asthma and moderate to severe obstruction.

DISCLOSURE: The following authors have nothing to disclose: Andrew Porter, Brent Brown

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Chest. 2014;146(4_MeetingAbstracts):11A. doi:10.1378/chest.1993432

SESSION TITLE: Asthma Posters II

SESSION TYPE: Original Investigation Poster

PRESENTED ON: Wednesday, October 29, 2014 at 01:30 PM - 02:30 PM

PURPOSE: International guidelines dictate goals for optimizing asthma management. In real life, there is a gap between treatment regimens and asthma guidelines in how physicians deal with sub-optimal asthma control. Misperceptions on the level of asthma control both from physicians and patients’ perspectives partially explain this gap. The aim of this prospective study is to compare asthma control status in real life determined by asthma control tools, and primary care and chest physicians’ opinions.

METHODS: 50 Physicians randomly chosen (25 primary care and 25 chest specialists) were asked to enroll all their asthmatic patients encountered in the timeframe of one month of a spring season. Data collected looked on patients’ demographics and asthma types. Asthma tools (Asthma control test (ACT)) and GINA guidelines) and physicians perceptions of patient control were recorded.

RESULTS: 746 asthmatic patients (55.3% female) were listed. 517 patients (69.3%) had an age between 20-60 years old. 39% of the asthma visits were unscheduled and 89% of the visits were outpatients. Perennial asthma and pulmonary function tests reversibility were 54.8% and 44.6% respectively. 34% of the patients were smokers. Uncontrolled asthma was detected in 64% and 76% by chest and primary care physician’s opinions respectively. ACT scores and GINA guidelines detected uncontrolled asthma in 65% and 72% respectively.

CONCLUSIONS: Two third of asthmatic patients had uncontrolled asthma control. Organized medical records applied by physicians and asthma control tools are both effective in determining control.

CLINICAL IMPLICATIONS: Chest physicians’ opinions were closely correlated with ACT results whereas primary care physicians’ opinions were closer to GINA guidelines.

DISCLOSURE: The following authors have nothing to disclose: Moussa Riachy, Georges Juvelikian, Marie Louise Koussa, Nadim Kanj

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Chest. 2014;146(4_MeetingAbstracts):12A. doi:10.1378/chest.1967106

SESSION TITLE: Asthma Posters II

SESSION TYPE: Original Investigation Poster

PRESENTED ON: Wednesday, October 29, 2014 at 01:30 PM - 02:30 PM

PURPOSE: We undertook a study to delineate the magnitude of temporal change in serum IgE levels over the course of a year and its relationship to lung function, asthma control, asthma pharmacotherapy, body mass index and demographic variables in a group of patients with moderate to severe persistent asthma and atopy.

METHODS: 11 patients with chronic moderate to severe persistent asthma and history of atopy were followed for one year at 2 month intervals. In addition to baseline demographic data and pulmonary function, serum IgE levels (ImmunoCAP Total IgE, Phadia AB, Uppsala, Sweden), asthma control test score, peak expiratory flow rate, asthma pharmacotherapy, body mass index were recorded. Variability in serum IgE was explored utilizing intraclass correlation calculation and linear mixed regression model assuming 10% change in serum level as statistically significant.

RESULTS: For consecutive bimonthly visits, the mean absolute percentage change in serum IgE was 22.6% (SD=3.3%) (p= 0.001). Odds ratio of having a change greater than 10 % change in serum IgE in the subsequent visit was 2.28 (95% C.I. 1.23, 4.21, p=0.009). Intraclass correlation coefficient approached zero for change in serum IgE as outcome variable. Multivariate regression analysis did not show significant associations with baseline demographics, lung function, serial asthma control test score, peak expiratory flow rate, asthma pharmacotherapy and body mass index.

CONCLUSIONS: Serum IgE levels have significant variability over time (when determined every 2 months) among patients with moderate to severe asthma and history of atopy. Lack of association between variable studied and serum IgE level may be a consequence of inadequate sample size. Low intraclass correlation coefficient suggests that variability is mostly intrasubject and not between individuals.

CLINICAL IMPLICATIONS: Temporal variability in serum IgE levels may have phenotypical and therapeutic consequences for patients with extrinsic asthma, particularly in the context of anti-IgE treatment.

DISCLOSURE: Ahila Subramanian: Grant monies (from industry related sources): This study was conducted utilizing funds from a Novartis investigator initiated research protocol grant (Dr. Umur Hatipoglu, the recipient). The protocol of the study does not involve the use of a commercial product. Umur Hatipoglu: Grant monies (from industry related sources): This study was conducted utilizing funds from a Novartis investigator initiated research protocol grant obtained by myself. The protocol of the study does not involve the use of a commercial product. Timothy Campbell: Grant monies (from sources other than industry): This study was conducted utilizing funds from a Novartis investigator initiated research protocol grant (Dr. Umur Hatipoglu, the recipient). The protocol of the study does not involve the use of a commercial product. Richard Rice: Grant monies (from industry related sources): This study was conducted utilizing funds from a Novartis investigator initiated research protocol grant (Dr. Umur Hatipoglu, the recipient). The protocol of the study does not involve the use of a commercial product. Mary Bossard: Grant monies (from industry related sources): This study was conducted utilizing funds from a Novartis investigator initiated research protocol grant (Dr. Umur Hatipoglu, the recipient). The protocol of the study does not involve the use of a commercial product.

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Chest. 2014;146(4_MeetingAbstracts):13A. doi:10.1378/chest.1987575

SESSION TITLE: Asthma Posters II

SESSION TYPE: Original Investigation Poster

PRESENTED ON: Wednesday, October 29, 2014 at 01:30 PM - 02:30 PM

PURPOSE: Montelukast is an agent approved by FDA for the treatment of asthma and allergic rhinitis. Post marketing studies have suggested depressive symptoms and anxiety in some patient while on this agent. We designed a prospective study to access wheather or not patients on this agent developed depression.

METHODS: This was a prospective study with patient serving as their own control.This study was approved by the institutional Review Board. Forty patients were enrolled (11male and 29 female patients). The study population included patients with asthma and allergic rhinitis,with or without history of depression. Patients who had symptoms of depression in the previous six months were excluded. An initial HAM-D score was obtained by the prinicipal investigator on the first day of the study for each patient.Subsequently the patients were prescribed monteleukast 10 mg orally once daily. The patients were followed during office visits or via telephone calls. Patients had to have been on montelukast therapy for at least one month prior to evaluation for a subsequent HAM-D score. Paired Student's t-test was was used for statistical analysis with the Graphpad Prism software.

RESULTS: Twenty-four patients sucessfully completed the study. Of these 24 cases, 5 were males and 19 were females.The mean age of patient population that completed the study was 53.62 ±17.83 (range18-84). Out of these 24 patients, 2 had a history of depression. The mean HAM-D score during the initial office visit for these patients was 4.29 ± 3.76. The mean HAM-D score upon completion of the study was 3.75 ± 3.82. The two-tailed P value equaled 0.566. Based on conventional criteria this difference was not considered to be statistically significant.

CONCLUSIONS: The above study demonstrates that montelukast is not asociated with symptoms depression,contrary to data from post marketing surveillance reports.

CLINICAL IMPLICATIONS: Montelukast is a safe drug for use in asthma patients,with and without symptoms of depression.

DISCLOSURE: The following authors have nothing to disclose: Rajeev Narang, Shreya Narang, Devina Narang, Grorge Udeani

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Chest. 2014;146(4_MeetingAbstracts):14A. doi:10.1378/chest.1988079

SESSION TITLE: Asthma Posters II

SESSION TYPE: Original Investigation Poster

PRESENTED ON: Wednesday, October 29, 2014 at 01:30 PM - 02:30 PM

PURPOSE: To evaluate the influence of patient characteristics and mood disorders on asthma control.

METHODS: This is a pilot Cross sectional study on 100 patients with asthma attending asthma clinic and the ER of a tertiary hospital in Central Kerala. We collected data of age, sex, BMI, smoking history, socioeconomic status, pulmonary function, asthma control using ACT, history of anxiety or depression using Hospital Anxiety and Depression test. The data obtained was analyzed using Epi Info Software and Chi Square test (or Fisher’s exact test for variables with less than 5 frequencies per category) was used to find the significance of the correlations.

RESULTS: From our study it was found that poor asthma control was commonly seen in older age groups (51-65 yrs(100%) and >65 yrs (100%), p=0.0288), Women (89.4% women vs 73.5% men p= 0.0262), people with higher BMI (25-29.9(96.3%), >30(100%), p=0.0175) and people with mood disorders(94.6% vs 70.5%, p=0.0067). PFT was available for only for 79 patients, as the rest of the patients had come to the ER for acute exacerbation of bronchial asthma and hence were unable to perform the PFT. Of the 79 patients we found that poor pulmonary function was associated with poor asthma control. (FEV1<80%(16.45%), FEV1<70%, 22.85%, FEV1<60%, 35.45). We could find no correlation between socio economic status and control of asthma (p=0.0571).

CONCLUSIONS: There is positive correlation between mood disorders, older age, female sex, higher BMI and asthma control. We propose that correlation between mood disorders and asthma control could be bidirectional, which calls for further studies in this subject.

CLINICAL IMPLICATIONS: Assessing the presence or absence of moon disorders and appropriately treating the condition is important. Underlying anxiety and depression if not considered may lead to poor adherence, higher rate of exacerbation, higher medical costs, unnecessary medication changes and testing and potentially higher mortality.

DISCLOSURE: The following authors have nothing to disclose: Veena Iyer, Babilu Co, Sobha Subramaniam

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Chest. 2014;146(4_MeetingAbstracts):14B. doi:10.1378/chest.1994586

SESSION TITLE: Asthma Posters II

SESSION TYPE: Original Investigation Poster

PRESENTED ON: October 29, 2014 from 1:30 PM to 2:30 PM

PURPOSE: The present study was aimed at a comprehensive analysis of IgA, IgM and IgG levels and their protective or causative association with asthma in adult lung patients. All the adult patients examined at Ayass Lung Clinic & Sleep Center at San Angelo, Texas, who consented for the blood test were included in the study. Socio-demographic, laboratory and clinical information were obtained from medical records. Two hundred and ninety seven asthmatic patients (median age 64 years) were screened for the levels of immunoglobulin. We also studied Ninety seven non- asthmatic patients (median age 70 years) as controls.

METHODS: The present study was aimed at a comprehensive analysis of IgA, IgM and IgG levels and their protective or causative association with asthma in adult lung patients. All the adult patients examined at Ayass Lung Clinic & Sleep Center at San Angelo, Texas, who consented for the blood test were included in the study. Socio-demographic, laboratory and clinical information were obtained from medical records. Two hundred and ninety seven asthmatic patients (median age 64 years) were screened for the levels of immunoglobulin. We also studied Ninety seven non- asthmatic patients (median age 70 years) as controls.

RESULTS: The prevalence of higher IgA>453, IgG>1560, and IgM>305 levels in our study population were, 17%, 17% and 15% respectively. Similarly the higher levels of immunoglobulins IgA, IgG, and IgM as independent risk factors were observed in 62%, 64% and 68% in the asthmatic patients as against 38%, 36% and 32% in the controls. Multivariate logistic regression analysis showed association of asthma with higher level of IgA and IgG after controlling for age, gender and ethnicity were as follow; IgA OR 0.50; 95% CI, 0.28-0.90; P<0.05), IgG OR 0.53; 95% CI, 0.29-0.93; P<0.05. Higher levels of IgA and IgG immunoglobulin were shown to be less likely to develop asthma.

CONCLUSIONS: So higher levels of IgA and IgG are more likely to be protective in terms of development of asthma but additional prospective studies will help to further understand the underlying mechanism of negative association/protection.

CLINICAL IMPLICATIONS: These results indicates that high level of IgG and IgA correlate with asthma and the phenomenon can be utilized in preventive measures through vaccination.

DISCLOSURE: The following authors have nothing to disclose: Mohammad Ayass

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Chest. 2014;146(4_MeetingAbstracts):15A. doi:10.1378/chest.1990335

SESSION TITLE: Asthma

SESSION TYPE: Original Investigation Slide

PRESENTED ON: Wednesday, October 29, 2014 at 08:45 AM - 10:00 AM

PURPOSE: Persistent asthma symptoms have been associated with chronic airway inflammation. Further, longer duration of asthma may portend small airway remodeling. However, Spirometry has not been useful in assessing small airway dysfunction. Recently, we reported abnormal lung volume indices in presence of normal spirometry variables in mild to moderate persistent asthma. In this prospective cross sectional study, we investigated the association between lung volume indices and chronicity of asthma.

METHODS: Subjects with asthma symptoms for more than a year and on therapy were included. Subjects consented for study, had a full lung function done within 11 months and were administered a questionnaire. Further, subjects’ charts were reviewed for additional data. Exclusion criteria: DLCO <70%, presence of CHF, any lung parenchymal disease and pregnancy. Data was analyzed using general linear model. Outcome variables were FEV1/FVC ratio and RV/RLC ratio. Fixed factors: gender, ethnicity, and tobacco use. Co-variables: age, height, weight and asthma duration. Full factor analysis with interactions was used.

RESULTS: Mean age of 95 patients was 57.14 years SD±15.55 with 33% male and 66% female. Ethnicity was Caucasian 64%, Hispanic 28% and others 10%. Smoking status was non-smokers 67%, current smokers 5% and ex-smokers 27%. Mean asthma duration was 21.75 years SD±18.60. The Mean FEV1% predicted was 82.19 SD±21.65, FEV1/FVC ratio 73.59 SD±10.31; RV% predicted 118.85 SD±30.07 and RV/TLC was 42.48 SD±8.55. When FEV1/FVC ratio was used as a dependent variable, the model was not significant (p 0.122). However, when RV/TLC ratio was used as a dependent variable, the following variables were found to be significant: Age. ß 0.27 CI 95% (0.17 - 0.38) P <0.001; duration of asthma. ß 0.15 CI 95% (0.07 - 0.24) p <0.001. There were no significant interactions among gender, ethnicity and smoking.

CONCLUSIONS: Abnormal RV/TLC ratio was significantly associated with longer duration of asthma; FEV1/FVC was not.

CLINICAL IMPLICATIONS: RV/TLC may be a better indicator for assessing small airway dysfunction related to chronicity of asthma than FEV1/FVC.

DISCLOSURE: The following authors have nothing to disclose: Kazi Rahman, Anupama Tiwari, Belayneh Abejie, Vipul Jain, Jose Joseph

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Chest. 2014;146(4_MeetingAbstracts):16A. doi:10.1378/chest.1993500

SESSION TITLE: Asthma

SESSION TYPE: Original Investigation Slide

PRESENTED ON: Wednesday, October 29, 2014 at 08:45 AM - 10:00 AM

PURPOSE: Asthma control test (ACT) is a reliable and valid method to evaluate lung function. This study analyses the impact of asthma disease duration on percentage predicted forced expiratory volume in 1 second (FEV1 %) in patients who are well controlled (ACT ≥ 20).

METHODS: Spirometry, disease duration and treatment of 71 nonsmoker well controlled bronchial asthma (ACT≥ 20) patients were analysed retrospectively. Patients were divided into 4 groups according to their duration of disease viz. 13 patients in group 1 (< 1 yr), 27 in group 2 (1-5 year), 13 in group 3 (5-10 year), and 18 in group 4 (>10 year). Statistical analysis was done using correlation analysis, unpaired t tests, analysis of variance (ANOVA)

RESULTS: Out of 71 patients 31 (43.6 %) were men and 40 (56.4%) women, their age ranged from 11 to 72 years and asthma symptoms duration ranged from 6 months to 50 years. Primary analysis of data without grouping revealed percentage predicted FEV 1% correlated with age (p = 0.001, r = - 0.381), asthma duration (p = 0.0003, r = - 0.42) and asthma control test (p = 0.03, r = 0.253). Secondary analysis between groups done showed mean percentage predicted FEV1% in group 1: 74.85 ± 8.72, group 2: 75.04 ± 11.47, group 3: 81.38 ± 15.61 and group 4: 58.61 ± 16.22. The difference in percentage predicted FEV1 % in group1, 2 and 3 was statistically insignificant (p = 0.258), whereas that in group 4 was significantly lower (p < 0.0001)

CONCLUSIONS: Patients with higher age and long duration of asthma (>10 years) have significantly lower percentage predicted FEV1 % than of lesser duration disease despite being well controlled (ACT ≥ 20).

CLINICAL IMPLICATIONS: As spirometry does not truly reflect the controlled status, both spirometry and ACT are essential for step-care management of asthma.

DISCLOSURE: The following authors have nothing to disclose: Dipti Gothi, Mayank Saxena, Ram babu Sah

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Chest. 2014;146(4_MeetingAbstracts):17A. doi:10.1378/chest.1994056

SESSION TITLE: Asthma

SESSION TYPE: Original Investigation Slide

PRESENTED ON: Wednesday, October 29, 2014 at 08:45 AM - 10:00 AM

PURPOSE: ABPA is an immunologic pulmonary disorder caused by hypersensitivity to Aspergillus fumigatus. The prevalence of ABPA in patients with bronchial asthma remains unclear. Contemporary reports suggest that ABPA occurs in upto 11% of patients with asthma. We made an attempt to find out prevalence of ABPA in patients of bronchial asthma using minimal essential criteria laid down by Greenberger et al.

METHODS: 100 consecutive asthmatic patients, who visited our hospital were subjected to Aspergillus fumigatus skin test(intradermal). Those patients who showed positive Type I hypersensitivity reaction, were further investigated for ABPA (viz. total serum IgE, IgE specific-A.fumigatus and HRCT scan).

RESULTS: Among 100 patients, 34 patients showed positive response to A.fumigatus skin test. Elevated serum total IgE levels (>417 IU/ml) was observed in 30 patients, raised serum IgE specific-A.fumigatus (>0.35 kUA/l) was observed in 31 patients. 26 patients out of 34 skin test positivity patients provide consent for HRCT chest scan, of which 25 had bronchiectactic changes present (includes central as well as peripheral). A diagnosis of ABPA (both ABPA-S and CB) was established in 30 patients of bronchial asthma.

CONCLUSIONS: Our study showed prevalence of 30% in patients of bronchial asthma. We observed female preponderance (17/30), mostly affected was younger age group (18/30 in 15-30 years). Elevated serum total IgE levels were observed in all ABPA patients with a mean of 6747.10±6235.13, is significant. Mean specific IgE-A.fumigatus was 44.68±46.27. We also observed that elevated serum absolute eosinophilic count (>1000 cells/cumm) was present in 15 (50%) patients of ABPA, which is not significant. Moreover, 6 (20%) patients had AEC levels less than 500 cells/cumm. Among other HRCT findings mucoid impaction was observed in 14 patients, pleural thickening, consolidation, nodules/tree in bud appearance and cavitory lesions were seen in 5,5, 9 and 1 patient respectively.

CLINICAL IMPLICATIONS: Early suspicion of ABPA especially in patients of bronchial asthma can prevent the the progression of the disease to bronchiectasis.

DISCLOSURE: The following authors have nothing to disclose: Vishal Chopra, Kalpeshkumar Patel, Ashrafjit Chahal, Don Mascarenhas, Prabhleen Kaur

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Chest. 2014;146(4_MeetingAbstracts):18A. doi:10.1378/chest.1994283

SESSION TITLE: Asthma

SESSION TYPE: Original Investigation Slide

PRESENTED ON: Wednesday, October 29, 2014 at 08:45 AM - 10:00 AM

PURPOSE: To evaluate the effect of once-daily tiotropium Respimat® (TioR) 5 µg on severe exacerbations, asthma worsening, and symptom control in patients (pts) with asthma who are symptomatic despite receiving at least ICS+LABA, by degree of airflow limitation.

METHODS: Two replicate, double-blind, placebo-controlled studies (NCT00772538; NCT00776984). Eligible pts had: ≥5-year history of asthma diagnosed before age 40 years; Asthma Control Questionnaire (ACQ)-7 score ≥1.5; experienced ≥1 exacerbation during previous year. Pts were either lifelong non-smokers or ex-smokers (<10 pack-years) who quit smoking ≥1 year before study enrollment. Co-primary endpoint: time to first severe exacerbation in pooled data at 48 weeks (asthma deterioration necessitating initiation or doubling of systemic glucocorticosteroids for ≥3 days). Secondary endpoints in pooled data at 48 weeks included time to first asthma worsening (either progressive increase in ≥1 symptoms, outside usual range, or ≥30% decline in best morning peak expiratory flow [PEF], for ≥2 consecutive days), PEF responses, and ACQ-7 response at 24 weeks. Pre-specified analyses were performed in subgroups defined by <60% and ≥60−<80% of predicted post-bronchodilator forced expiratory volume in 1 second (FEV1) values at screening.

RESULTS: 912 pts were randomized 1:1 to TioR or placebo Respimat® (pboR); TioR <60% n=178, ≥60−<80% n=272; pboR <60% n=182, ≥60−<80% n=263. At Week 48, time to first severe exacerbation and time to asthma worsening were longer with TioR vs pboR in the <60% and ≥60−<80% subgroups (HR 0.79 vs 0.82 [no significant interaction] and HR 0.73 vs 0.68 [no significant interaction], respectively). Significant improvements in PEF response vs pboR were seen for TioR in both the <60% (PEFAM 11.4 L/min, P=0.024; PEFPM 18.8 L/min, P<0.001) and ≥60−<80% subgroups (PEFAM 22.7 L/min, P<0.001; PEFPM 28.8 L/min, P<0.001). At Week 24, ACQ-7 responder rate was significantly higher with TioR vs pboR in the <60% subgroup only (55.1% vs 39.6%, respectively; OR 1.87, P=0.005).

CONCLUSIONS: Once-daily tiotropium Respimat® add-on to ICS+LABA reduced both risk of severe exacerbation and asthma worsening and improved PEF vs pboR, independent of degree of airflow obstruction; pts with a greater level of obstruction also showed improvements in asthma symptom control.

CLINICAL IMPLICATIONS: Once-daily tiotropium Respimat® add-on to ICS+LABA reduces risk of severe exacerbation and asthma worsening in pts with symptomatic asthma, independent of degree of airflow limitation.

DISCLOSURE: Donald Tashkin: Grant monies (from industry related sources): Grant from BIPI to UCLA re UPLIFT trial, Consultant fee, speaker bureau, advisory committee, etc.: Boehringer Ingelheim Speak Bureau Petra Moroni-Zentgraf: Employee: Boehringer Ingelheim Michael Engel: Employee: Boehringer Ingelheim Hendrik Schmidt: Employee: Boehringer Ingelheim Huib Kerstjens: Consultant fee, speaker bureau, advisory committee, etc.: From Boerhringer an d Pfizer, in relation to the work presented. As consultant, advisory baord member, and as principal investigator and recruiter., Consultant fee, speaker bureau, advisory committee, etc.: From Almirall, to my institution for consultancies, Consultant fee, speaker bureau, advisory committee, etc.: From Novartis, to my institution for consultancies

Presenting results from clinical trials in asthma patients of tiotropium delivered via the Respimat inhaler. Tiotropium is not approved for use in asthma. Tiotropium’s safety and efficacy have not yet been established in asthma.

Chest. 2014;146(4_MeetingAbstracts):19A. doi:10.1378/chest.1992514

SESSION TITLE: Asthma

SESSION TYPE: Original Investigation Slide

PRESENTED ON: Wednesday, October 29, 2014 at 08:45 AM - 10:00 AM

PURPOSE: Severe asthma requires treatment with high dose inhaled corticosteroids plus a second controller to prevent which remain uncontrolled despite this therapy. It has been previously demonstrated exhaled NO (FeNO) is higher during a deterioration in asthma control and would be related with eosinophilic inflammation. Despite potential utility as a biomarker, the induced sputum eosinophil count measurements has not been widely recommended by ERS/ATS guidelines. The aim of this study was to determine whether levels of FeNO could be related with the sputum eosinophils in different phenotypes of severe and mild to moderate asthma.

METHODS: We performed a study of admissions to a respiratory hospital. We collected sputum samples from 6 patients with mild to moderate asthma (MMA) female/male: 3/3, with an average of age of 33.5±5.4 years old; 30 patients with difficult to treatment severe asthma (DTTSA), female/male: 15/15, with 37,4±2.6 years old and 8 patients with treatment resistance severe asthma (TRSA), female/male: 7/1, with 51.4±3.8 years old. Patients were diagnosed according to World Health Organization criteria. Sputum samples were processed with 0.1% dithiotreitol, cytospined and eosinophils were counted. All subjects underwent exhaled nitric oxide measure. Data were analyzed with Kruskall Wallis test and linear regression analyses.

RESULTS: We found a significant relationship between FeNO and the percentage of eosinophils only in TRSA group (Spearman r=0.7 and p<0.05). Moreover, we found an increase of eosinophils in TRSA patients respect to DTTSA and MMA groups (12.4±5.8 % vs 6.4±1.4% and 4.2±2.4 % respectively). We observed persistent eosinophilia in TRSA despite higher doses of inhaled corticosteroid therapy.

CONCLUSIONS: Our results have shown that FeNO measured could be related with the increase of sputum eosinophils in TRSA but not in DTTSA or MMA.

CLINICAL IMPLICATIONS: Sputum is a non-invasive technique for the assessment of bronchial inflammation, and for detecting the cellular and inflammatory profile. The observations presented in this abstract could be important for understaning the role of FeNo and eosinophils as biomarkers in different phenotypes of asthma.

DISCLOSURE: The following authors have nothing to disclose: Glenda Ernst, Fabian Caro, Martín Fernandez, Guillermo Menga, Daniel Colodenco, Eduardo Schiavi

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Chest. 2014;146(4_MeetingAbstracts):20A. doi:10.1378/chest.1976421

SESSION TITLE: COPD Diagnosis and Evaluation Posters I

SESSION TYPE: Original Investigation Poster

PRESENTED ON: Wednesday, October 29, 2014 at 01:30 PM - 02:30 PM

PURPOSE: To assess proportion of non-smokers among COPD patients attending a COPD Clinic at a tertiary level medical college hospital and to evaluate associated risk factors, clinical characteristics and spirometric indices in these non-smoking COPD subjects.

METHODS: We assessed 507 COPD patients (men, 404 and women, 103) attending a COPD Clinic and diagnosed as per GOLD guidelines. 63 out of 507 patients (men, 16 and women, 47) had no smoking history. Risk factors associated with COPD in these non-smoking patients were assessed. Patients` clinical data was collected and spirometric indices were studied.

RESULTS: Out of all 507 COPD patients, 12.4% were non-smokers; 45.6% of women and 3.9% of men were non-smokers. The mean age of non-smoking COPD patients was 58.43 ± 11.75 years. The duration of illness was 7.81 ± 7.06 years. 45/63 patients had a semi-urban background. The risk factors associated with non-smoking COPD were: cooking using solid fuel (85.7%), occupational exposure (84.1%), passive smoking (ETS) (76.2%), heating using solid fuel (74.6%), and air pollution only in (23.8%) of patients. In women, most frequent risk factor was cooking smoke followed by occupational exposure, whereas in men, most frequent risk factor was occupational exposure followed by passive smoking. Organic dust related occupations were most commonly related to COPD. 7.9% of non-smoking COPD patients had a past history of respiratory problems prior to age 10. Dyspnoea was most frequent (95.2%) symptom, followed by cough (93.75%). Wheezing was observed in 25.4% of non-smoking COPD patients. FEV1 in non-smoking COPD patients had inverse correlations with passive smoking, occupational exposure, exposure to cooking smoke, exposure to heating smoke and prior history of asthma; however, there was no correlation with BMI or socioeconomic status. Regression analysis showed that model of all risk factors taken strongly predicted FEV1 in these patients.

CONCLUSIONS: We observed that 12.4% of COPD patients had no smoking history. Non-smoking COPD was more frequent in women. We were able to assess various risk factors related to COPD in non-smoker patients and predicting its severity.

CLINICAL IMPLICATIONS: The identification of risk factors and clinical characteristics in non-smoking COPD patients is important for prevention, early diagnosis and better management of COPD including avoidance of causative agents wherever feasible.

DISCLOSURE: The following authors have nothing to disclose: Prem Parkash Gupta, Rohtas Yadav, Sumit Mittal, Dipti Agarwal

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Chest. 2014;146(4_MeetingAbstracts):21A. doi:10.1378/chest.1986873

SESSION TITLE: COPD Diagnosis and Evaluation Posters I

SESSION TYPE: Original Investigation Poster

PRESENTED ON: Wednesday, October 29, 2014 at 01:30 PM - 02:30 PM

PURPOSE: Chronic obstructive pulmonary disease (COPD) is a disease of lung airways and parenchyma defined by airflow limitation due to inflammatory response to noxious fumes and gases. Systemic inflammation seen in patients with COPD is characterized by systemic oxidative stress that is associated with abnormalities like weight loss. We hypothesized that patients with higher grades of COPD will have greater loss of bodyweight. So, we evaluated the variation in body mass index (BMI) in different grades of COPD.

METHODS: This cross-sectional study was conducted in a teaching hospital in rural Nepal. Study duration was three months. Patients visiting medicine outpatient department or admitted in ward with the diagnosis of COPD were included and those with pleural effusion, bronchiectasis, lung abscess and lung cancer were excluded. Patients underwent spirometry evaluation by hand held spirometer (Helios 401, Recorders and Medicare Systems) and diagnosis of COPD was made when ratio of post bronchodilator forced expiratory volume at 1 second (FEV1) to forced vital capacity (FVC) was less than 70%. Patients with COPD were graded on Global Initiative for Chronic Obstructive Lung Disease (GOLD) grades based on post bronchodilator FEV1. BMI was measured and was compared among grades of COPD.

RESULTS: Out of 48 patients screened, 14 were excluded and 34 were included in the study.The mean age was 66 years and 70% were females. None of the patients were in GOLD grade 4. Number of patients in Grade 1 was eight (23.5%), in Grade 2 was 20(58.8%) and in Grade 3 was six (17.6%). The difference in age of the patients (p=0.375) and in duration of illness before presentation (p=0.103) was not different among the groups. The BMI of patients in grade 1 was 21.6kg/m2, grade 2 was 20.8kg/m2 and grade 3 was 16.3kg/m2. The decline in BMI seen in higher grades of COPD was statistically significant (p=0.001).

CONCLUSIONS: In this first study from rural western region of Nepal, we have looked for the presence of poor nutrition in patients with COPD by calculating BMI. We found that patients with higher grades of COPD have lower BMI and thus show that advanced COPD is associated with greater degree of weight loss.

CLINICAL IMPLICATIONS: Malnourished patients of COPD have increased risk of in-hospital deaths and of readmission. This cross sectional study provides data on the nutritional status of patients suffering with COPD in rural Nepal.This study also provokes further studies in the area of nutritional intervention in patients of COPD.

DISCLOSURE: The following authors have nothing to disclose: Mukesh Paudel, Bishal Chhetri, Sahadeb Dhungana, Shamsuddin Amin

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Chest. 2014;146(4_MeetingAbstracts):22A. doi:10.1378/chest.1987878

SESSION TITLE: COPD Diagnosis and Evaluation Posters I

SESSION TYPE: Original Investigation Poster

PRESENTED ON: Wednesday, October 29, 2014 at 01:30 PM - 02:30 PM

PURPOSE: To assess cognitive functions using an electrophysiological tool, P300, in COPD patients with frequent acute exacerbations and to compare with cognitive functions in COPD patients who had infrequent acute exacerbations.

METHODS: We included 92 eligible COPD patients attending a COPD Clinic at a tertiary level medical college hospital and diagnosed as per GOLD guidelines. These patients were divided into 2 groups on the basis of exacerbations during preceding one year: Group 1 (FECOPD Group) included 48 patients who had ≥ 2 acute exacerbations, and Group 2 (I-FECOPD Group) included 44 patients with < 2 acute exacerbations. To assess cognitive functions event related potential, P300 was used. We used oddball paradigm, acoustic stimuli were presented by tone burst method; randomly delivering rare stimulus during the presentation of other frequent stimuli. P300 latency and amplitude were analyzed as study variables.

RESULTS: The mean age of patients in FECOPD group and I-FECOPD group was 62.58±9.61 year and 55.80±11.12 year, respectively. Mean exacerbations in both groups were 2.98±1.25 and 0.55±0.730, respectively. FECOPD group and I-FECOPD group differed significantly with respect to duration of illness (21.73±5.53 year vs. 17.07±5.22 year), FEV1 (1.270±0.247 L vs. 1.711±0.306 L) and PEFR (247.04±49.40 L/min vs. 335.32±61.15 L/min) but not regarding smoking (35.40±10.90 pack years vs. 30.06±10.52 pack years). Mean rare tone P300 latency was significantly increased in FECOPD group compared to I-FECOPD group (330.45±18.64 ms vs. 303.06±15.71 ms); there was no statistically significant difference between two groups regarding mean P300 amplitude (4.82±2.95 µV vs. 4.89±6.47 µV). P300 latency correlated directly with number of exacerbations, age, duration of illness and clinical scores. P300 correlated inversely with spirometric indices and there was no correlation with smoking pack years. Regression model showed frequent acute exacerbations being the strongest predictor of increase in P300 latency.

CONCLUSIONS: Cognitive functions assessed using event related potentials P300 were impaired in frequent acute exacerbations group. P300 latency correlated with exacerbations, age, duration of illness and spirometric indices. Frequent acute exacerbations parameter was the strongest predictor of cognitive impairment.

CLINICAL IMPLICATIONS: Event related potentials, P300 is widely used for assessment of cognitive functions; however, in present study we evaluated its usefulness in COPD patients with frequent acute exacerbations.

DISCLOSURE: The following authors have nothing to disclose: Dipti Agarwal, Sushma Sood, Prem Parkash Gupta

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Chest. 2014;146(4_MeetingAbstracts):23A. doi:10.1378/chest.1988325

SESSION TITLE: COPD Diagnosis and Evaluation Posters I

SESSION TYPE: Original Investigation Poster

PRESENTED ON: Wednesday, October 29, 2014 at 01:30 PM - 02:30 PM

PURPOSE: To provide a skill-transfer teaching technique to patients with severe COPD.

METHODS: Written consent was obtained from 23 Veterans Affairs patients. All subjects had severe COPD (FEV1<50% predicted, mean FEV1/FVC 49%). Subjects were randomized to routine care or a three-hour, multidisciplinary class including pulmonary medicine, pulmonary rehabilitation, respiratory therapy, nursing care, and physiotherapy. The session incorporated HPS in different clinical scenarios with interactive teaching sessions about COPD pathophysiology, medications, breathing techniques, dyspnea crisis, and aerobic exercise/strength training. Participants completed pre- and post-education session questionnaires on their experiences.

RESULTS: Eight subjects attended the education class with HPS. All participants rated the class as good to excellent; 6/8 reported increased understanding about COPD; 7/8 reported improved knowledge about proper inhaler use technique; 5/8 reported wanting to increase exercise/activity as part of their self-management; 3/8 reported wanting to change the way they use their inhalers; 6/8 reported wanting to attend another HPS class; and 7/8 would recommend HPS classes to others.

CONCLUSIONS: Use of HPS was well received by the participants. We propose the use of HPS as a didactical tool for group settings to improve patient understanding about COPD with the goal of providing the skills necessary for optimal COPD self-management. Ultimately, better knowledge about COPD and its treatment can help this high risk COPD cohort better manage dyspnea crisis and avoid subsequent hospitalizations.

CLINICAL IMPLICATIONS: Current studies show conflicting results about the benefits of COPD self-management and the use of concomitant COPD education and pulmonary rehabilitation. So far, self-management has focused on the recognition and treatment of COPD exacerbations. We present a novel approach focusing on a skill-transfer technique to improve understanding of the disease, medication use, medication adherence, and development of coping skills that can help avoid unnecessary hospitalizations due to episodic breathlessness. Larger studies are needed to validate these conclusions and assess whether HPS is a viable educational tool that can lead to better outcomes in COPD self-management and reduce hospitalizations due to dyspnea crisis.

DISCLOSURE: The following authors have nothing to disclose: Juan Rojas-Gomez, Perry Nystrom, Robert Gauder, Debi Sampsel, Steve Wetzel, Kim Bloch, Shelly Duckworth, Tonia Taylor

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Chest. 2014;146(4_MeetingAbstracts):24A. doi:10.1378/chest.1989320

SESSION TITLE: COPD Diagnosis and Evaluation Posters I

SESSION TYPE: Original Investigation Poster

PRESENTED ON: Wednesday, October 29, 2014 at 01:30 PM - 02:30 PM

PURPOSE: According to the report of Ministry of Health, COPD is ranked as third disease causing death at national level in Turkey and chronic airway diseases have a very big influence on the health expenses. Although effective guidelines are developed systematically to be used easily in busy practices and to ensure scientifically valid outcomes, guidelines alone cannot improve patient care. Physicians must be committed to guideline dissemination and implementation for patient outcomes to improve. Nevertheless, it is not exactly known whether COPD patients are adequately diagnosed, treated or followed in long term. There is growing evidence that the care of COPD patients may vary according to hospitals or countries and the accordance with the published guidelines usually seems to be inadequate. In this respect, Turkish Thoracic Society (TTS) decided to participate in European COPD Audit project which gave us the chance to face the problems related to the patients' admission to hospital and treatment of a COPD exacerbation.In this study, we wanted to point out positive and negative aspects in care of exacerbated COPD patients in Turkey.

METHODS: This study was based on the data of Turkey obtained from the results of the first European COPD Audit Report. The data collection was specified to patients experiencing an acute COPD exacerbation over a 60-day period who were hospitalized, following up for 90 days to assess outcomes. From Turkey, 22 hospitals (21 teaching/university hospital) participated to the study and 612 patients were evaluated for this study.

RESULTS: The overall mortality was 10.1% and more than half of patients were in GOLD stage III and IV. Dissimilarity in patient care resources observed among the hospitals, eg. only 22.7% of the hospitals had a pulmonary rehabilitation programme available for discharged patients. Only 49.3% of the patients had spirometry results before admission whose FEV1 results 36% predicted. The current smokers were 15.9 % of the patients.

CONCLUSIONS: The data ensured the importance of collecting data to make some recommendations for COPD care quality and raise the standard of care delivered to patients. Increasing spirometry and rehabilitation programme availability is important and the admission should be considered as an opportunity to quit smoking.

CLINICAL IMPLICATIONS: Increasing spirometry and rehabilitation programme availability is important and the admission should be considered as an opportunity to quit smoking.

DISCLOSURE: Mehmet Polatli: Fiduciary position (of any organization, association, society, etc, other than ACCP: Turkish Thoracic Society and British Thoracic Society sponsorship for attending to the ERS COPD Audit National Experts meeting The following authors have nothing to disclose: Turkish Thoracic Society COPD Audit Turkey Study Group

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Chest. 2014;146(4_MeetingAbstracts):25A. doi:10.1378/chest.1989979

SESSION TITLE: COPD Diagnosis and Evaluation Posters I

SESSION TYPE: Original Investigation Poster

PRESENTED ON: Wednesday, October 29, 2014 at 01:30 PM - 02:30 PM

PURPOSE: Measuring physical activity in COPD is desirable since physical inactivity is common and predicts increased health care utilization and mortality risk. While most studies have used motion detectors placed near the center of the body (such as a lateral position on the waist), a device worn on the wrist like a wrist watch would be far more convenient to the patient during long-term measurement. Unfortunately, validation studies of movement output that correspond to energy expenditure are generally available only for devices worn on the waist, not the wrist.

METHODS: After Institutional Review Board approval, we asked 20 patients to wear ActiGraph GT3X+ triaxial accelerometer devices simultaneously on the waist and ipsilateral wrist for at least 24 awake hours. We considered the output from the waist site to be the “gold standard”. Vector Magnitude Units (VMU, the minute-by-minute sum of movements in 3 planes) from the device worn at the waist that corresponded to VMU > 3000 from the device on the wrist were determined. We had previously used this threshold to separate higher from lower intensity physical activity in COPD.

RESULTS: The sample mean age was 70 ± 10 years and the FEV1 was 45 ± 18%. Activity data from over 40,000 minutes were compared using mixed modeling. Physical activity intensity above this threshold was present in16% of the recorded minutes. Mean VMU from the wrist device above the 3000 threshold were 4953 (95% confidence interval (CI), 4850 to 5055), while corresponding VMU from the waist device were 951 (95% CI, 916 to 986). Using a proprietary software equation developed for the waist location, activity intensity above this threshold corresponded to 1.66 metabolic units (METs) (95% CI, 1.55 to 1.77).

CONCLUSIONS: Movements detected from an activity monitor worn on a wrist site are considerably higher than from a waist site.

CLINICAL IMPLICATIONS: Activity monitoring from a conveniently-worn wrist site can provide meaningful data providing the above differences in activity counts are taken into consideration.

DISCLOSURE: The following authors have nothing to disclose: Chinthaka Bulathsinghala, John Tejada, Richard Zuwallack

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Chest. 2014;146(4_MeetingAbstracts):26A. doi:10.1378/chest.1990862

SESSION TITLE: COPD Diagnosis and Evaluation Posters I

SESSION TYPE: Original Investigation Poster

PRESENTED ON: Wednesday, October 29, 2014 at 01:30 PM - 02:30 PM

PURPOSE: Non-invasive ventilation (NIV) is increasingly used in the management of acute respiratory failure due to decompensated chronic cardiorespiratory disease. The increasing burden of chronic disease and focus on person-centred care, necessitates frank discussions of the benefits and burdens of treatment and an understanding of the patients’ perspective. We aimed to describe the subjective experience of individuals undergoing NIV for acute hypercapnic respiratory failure.

METHODS: Face-to-face interviews, analysed using qualitative thematic analysis

RESULTS: Thirteen participants were interviewed. Six interrelated themes emerged: A passenger on a journey dominated by chronic illness; Balancing benefits and burdens of NIV; Looking to another chance; Knowing what alleviates my distress; Struggling and suffering; Feeling vulnerable and trusting staff. Participants viewed NIV as a two-edged sword; providing substantial relief from symptoms, but engendering discomfort and burden. No participant would forgo this treatment in the future. While participants sometimes appeared passive, they often had significant insight into what relieved their subjective distress. Participants expressed both a sense of compulsion to accept NIV and gratitude for NIV as it facilitated another chance at life. Many participants described minimal recollection of their acute hospitalisation, and placed a great amount of trust in health care providers.

CONCLUSIONS: Participants described balancing benefits and burdens of NIV, with the goal of achieving ‘another chance’ at life. This goal was highly valued despite their description of their life as one of struggle and suffering. While many knew what might alleviate their distress they often appeared passive, like passengers on a journey dominated by their chronic illness.

CLINICAL IMPLICATIONS: Enhancing health care providers’ understanding of the complex subjective physical and emotional experience of treatment with NIV may facilitate frank discussions of treatment, enhance patient centred decision making and improve providers’ capacity to relieve patient distress. Leveraging patients’ unique self-knowledge may lead to novel self-management strategies.

DISCLOSURE: The following authors have nothing to disclose: Tracy Smith, Meera Agar, Patricia Davidson, Christine Jenkins, Jane Ingham

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Chest. 2014;146(4_MeetingAbstracts):27A. doi:10.1378/chest.1993650

SESSION TITLE: COPD Diagnosis and Evaluation Posters I

SESSION TYPE: Original Investigation Poster

PRESENTED ON: Wednesday, October 29, 2014 at 01:30 PM - 02:30 PM

PURPOSE: Chronic Obstructive Pulmonary Disease (COPD) is the third leading cause of death in America. Recent observation reveals a downward trend of inpatient admissions for COPD (IACOPD) exacerbation. The purpose of this study is to quantify and evaluate the inpatient admissions for COPD (IACOPD) exacerbation in a community hospital.

METHODS: We retrospectively reviewed inpatient admissions for COPD exacerbation and total inpatient admissions from 2005 to 2013. The data set represents more than 3,000 admissions over an 8 year period at a rural community hospital. Inpatient admissions were noted on a monthly and yearly basis. The percentage of inpatient COPD admissions out of total inpatient admissions was observed annually from 2005 to 2013. Linear regression analysis was then conducted in order to demonstrate and quantify the annual decrease in IACOPD. Respective p values were calculated in order to validate the COPD admission data found via the linear regression model.

RESULTS: The number of IACOPD exacerbation for years 2005, 2010, 2011, 2012, and 2013 are respectively 598, 405, 283, 216, and 210. The percentage of IACOPD (COPD admissions/Total Admissions) for the above mentioned years are respectively 8.27%, 5.16%, 3.66%, 2.96%, and 3.33%. IACOPD exacerbation dropped 59% from 2005 to 2013. The linear regression analysis percentage of IACOPD resulted in a p-value of 0.00225.

CONCLUSIONS: There is a significant decline in the inpatient admissions for COPD exacerbation from 2005 to 2013.

CLINICAL IMPLICATIONS: Several factors might have contributed to the decrease in IACOPD. Such factors include newer inhaler medications, reimbursement regulations, COPD awareness, cost of tobacco, palliative care services. Further studies are needed to assess the contribution of each factor.

DISCLOSURE: Ravi Chandran: Consultant fee, speaker bureau, advisory committee, etc.: For GSK, and Forrest The following authors have nothing to disclose: Anirudh Chandra

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Chest. 2014;146(4_MeetingAbstracts):28A. doi:10.1378/chest.1993849

SESSION TITLE: COPD Diagnosis and Evaluation Posters I

SESSION TYPE: Original Investigation Poster

PRESENTED ON: Wednesday, October 29, 2014 at 01:30 PM - 02:30 PM

PURPOSE: Steroids can cause leukocytosis by both demarginalization and increased release from bone marrow reserve. Leukocytosis is a potential confounder in COPD/BA patients (pts) who are on steroid therapy and are suspected of having a concomitant bacterial infection. In these pts, it is often unclear whether the leukocytosis is due to steroids or to the infection; with this in mind we designed the following study.

METHODS: Data from 1200 pts admitted with obstructive lung disease was collected. Indicators for infection included radiological evidence of lung infiltrate, positive cultures (blood, sputum or other) and fever (T>100.40F). Serial WBC count was done to document leukocyte trends. 1064 pts with acute exacerbation were divided into 3 groups based on presence of infection and institution of steroid therapy. The groups included pts with infection and on steroids (n=362), pts with infection and not on steroids (n=58), and pts without infection and on steroids (n=644). The remaining 136 pts were admitted for non-infectious reasons, were not given steroids and were used as a control group. Empiric antibiotics and steroids were given as indicated and a one-way ANOVA was used to compare mean changes in WBC counts between these 4 groups.

RESULTS: Our study population was 44% male and 88% African American. Mean age was 62.7. 34% of pts had infection (based on radiology 21%, blood culture 12%, other culture 9% and fever 5.3%). Mean increase in WBC count in the control group was 500/µL, in the steroid only group it was 4100/µL and in the steroid and infection group it was 2990/µL. There was a decrease of 1600/µL in mean WBC count in the infection only group. The change in mean WBC counts among these four groups [F(3,1193)=14.531, p<.05] was statistically significant. Tukey post-hoc comparisons indicated that the infection plus steroid group and the steroid only group were the only two groups to have statistically significant changes in WBC counts when compared to the control group

CONCLUSIONS: Steroid therapy significantly increases WBC count. Our study indicated that pts with infection who were on steroid therapy had a blunted leukocyte response in comparison to those without infection and on steroid therapy. However, we attribute this finding to the use of empiric antibiotics with presumed infection.

CLINICAL IMPLICATIONS: Based on our results, we conclude that leukocytosis alone is not a reliable predictor of infection in COPD/BA pts on steroid therapy.

DISCLOSURE: The following authors have nothing to disclose: Bikash Bhattarai, Meenakshi Ghosh, Abhisekh Sinha Ray, Mohammed Raihan Azad, Bhradeev Sivasambu, Sai Kwan Wan, Santu Saha, Saroj Kandel, Prakash Kharel, Saurav Pokharel, Rakesh Vadde, Vikram Oke, Marie Frances Schmidt, Danilo Enriquez, Joseph Quist, Anita Pandey, Saveena Manhas

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Chest. 2014;146(4_MeetingAbstracts):29A. doi:10.1378/chest.1995239

SESSION TITLE: COPD Diagnosis and Evaluation Posters I

SESSION TYPE: Original Investigation Poster

PRESENTED ON: Wednesday, October 29, 2014 at 01:30 PM - 02:30 PM

PURPOSE: To identify clinical characteristics, outcome and cost of treatment of COPD patients with pneumonic exacerbations requiring hospitalization in comparison with nonpneumonic exacerbations.

METHODS: Retrospective study of hospitalized patients with diagnosis code of J441 from electronic medical record files during 2012 -2013. Chest radiography and clinical presentation were reviewed for the presence of clinically compatible pneumonia at the first 72 hours of admission. SPSS version 17 was used for data analysis

RESULTS: Total 61 episodes of hospitalized COPD exacerbation in Ramathibodi Hospital were reviewed. Patients mean age was 81.2 ±8.7 years and male patients were 72%. The previously prescribed ICS or ICS-LABA therapies were noted in 77% while LAMA was 44% of those patients. Clinically compatible pneumonia was diagnosed in 39.3% of exacerbation episodes within 72 hours of the admission. Endotracheal tube intubations were used in 29% while NIPPV uses were used 61% of admission episodes. Approximately 85.2% of patients were discharged from hospital while death was only 14.5%. However re-admissions were observed in 26% of exacerbated patients. There was no significant difference in length of stay between pneumonic and non-pneumonic COPD exacerbation (p 0.54). Furthermore, no association between history of ICS and ICS-LABA uses and the presence of pneumonic exacerbation was demonstrated (p 0.35). Regarding outcomes, deaths were noted in 6 from 18 pneumonic exacerbations while 3 from 34 in non pneumonic exacerbations died however there was not statistically significant difference (p 0.06). The significantly higher median cost of treatment for hospitalized pneumonic exacerbation was 2,679 USD (135-11,986) versus 1,357 USD (164-9,333) in patients with nonpneumonic exacerbation (p 0.04).

CONCLUSIONS: Pneumonic cause was observed in one-third of hospitalized COPD exacerbation. There was trend of an increased mortality in exacerbated patients with pneumonia. The higher hospitalization cost was observed in pneumonic than nonpneumonic exacerbation.

CLINICAL IMPLICATIONS: The attention on COPD patients presenting with exacerbation with pneumonia must be paid due to poor treatment outcome, the longer duration of stay and the increased healthcare cost utilization.

DISCLOSURE: The following authors have nothing to disclose: Theerasuk Kawamatawong, Tananchai Petnak

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Chest. 2014;146(4_MeetingAbstracts):30A. doi:10.1378/chest.1992644

SESSION TITLE: COPD Diagnosis and Evaluation Posters I

SESSION TYPE: Original Investigation Poster

PRESENTED ON: Wednesday, October 29, 2014 at 01:30 PM - 02:30 PM

PURPOSE: COPD is a common disease characterized by airflow limitation which is irreversible or partially reversible & usually progressive. The prognosis is inversely related to age & directly related to post bronchodilator FEV1.Weight loss, pulmonoary hypertension & co-morbidities are act as additional factors for poor prognosis. The risk of death in patients with COPD is traditionally graded with the use of the FEV1, but it correlates better with the BODE index. The BODE is a multi-dimensional index which combines four important variables into a single score- (B) Body mass index; (O) airflow obstruction measured by the forced expiratory volume in one second (FEV1); (D) dyspnoea measured by the modified MRC scale; and (E) exercise capacity measured by the 6 minutes walk distance (6MWD). Each variable is graded and a score out of 10 is obtained, with higher scores indicating greater risk. The risk of death from respiratory causes increases by more than 60% for each one point increases in BODE index (Celli et al 2003). We use BODE index in our study.

METHODS: A prospective study during the period of January 2010 to December 2012 was conducted in outpatient. Total 252 patients were included who were COPD patients defined by FEV1 < 80% and FEV1/FVC ratio < 70% measured 20 minutes after the administration of salbutamol. A regular follow-up was given as per study protocol.

RESULTS: Among total 252 patients, mean age was 60.63±10.05, male 188 and female 64; 188 smoker, 64 non smoker all of them were exposed to biomass fuel except 2 who were male. During the study period of 3 years, 40 patients died which comprised 15.87% of study population that was lower than the original study. 24 (60% of death) died from non respiratory causes and 16 (40%) from pulmonary causes (Corpulmonale and Respiratory failure). All patients died from respiratory causes had BODE score points 10.

CONCLUSIONS: (1) A recognizable number of patients suffer from COPD due to exposed of biomass fuel particularly females of Bangladesh. (2) Co-morbidities are accountable for the death of COPD patients in addition to variables in BODE index. (3) The higher the BODE score points, higher the risk of death from respiratory causes.

CLINICAL IMPLICATIONS: COPD is a heterogeneous disease without a simple prognostic trajectory. The BODE index measures functional limitation, nutritional status and symptoms, in addition to airflow obstruction, and is therefore well placed to assess clinical risk and the integrated response to treatment.

DISCLOSURE: The following authors have nothing to disclose: Md.Siddiqur Rahman

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Chest. 2014;146(4_MeetingAbstracts):31A. doi:10.1378/chest.1990173

SESSION TITLE: COPD Diagnosis and Evaluation Posters I

SESSION TYPE: Original Investigation Poster

PRESENTED ON: Wednesday, October 29, 2014 at 01:30 PM - 02:30 PM

PURPOSE: To assess the efficacy of budesonide/formoterol (BUD/FM) or FM in chronic obstructive pulmonary disease (COPD) patients with moderate vs severe/very severe airflow limitation (AL) on lung function; rescue medication (RM) use; breathlessness, cough, and sputum score (BCSS); dyspnea score; and St. George’s Respiratory Questionnaire (SGRQ) total score.

METHODS: In a post-hoc analysis of pooled data from 3 double-blind, randomized studies (A: 12-month; NCT00206167; B: 12-month, NCT00419744; and C: 6-month, NCT00206154), COPD patients (aged ≥40 years) with ≥1 COPD exacerbation in the past year were stratified by moderate AL (forced expiratory volume in 1 second [FEV1] % predicted ≥50%) and severe/very severe AL (FEV1 % predicted <50%) and assigned to twice-daily BUD/FM via pressurized metered-dose inhaler 320/9 μg (n = 197, moderate AL; n = 975, severe/very severe AL) or FM via dry-powder inhaler 9 μg (n = 211, moderate AL; n = 963, severe/very severe AL). Changes from baseline to treatment period mean in predose FEV1 (L), RM use (inhalations/d), BCSS, dyspnea score, and change to end of treatment in SGRQ scores are reported. For BCSS, dyspnea, and SRGQ, higher scores indicate greater severity/impairment.

RESULTS: Increases in predose FEV1 were greater in the BUD/FM vs FM group (0.13 vs 0.06 L, moderate AL; 0.07 vs 0.04 L, severe/very severe AL). Decrease in RM use was greater with BUD/FM vs FM (−1.33 vs −1.08, moderate AL; −1.13 vs -0.60, severe/very severe AL). BCSS improvements with BUD/FM were less than FM in moderate AL (−0.95 vs −1.13) but greater in severe/very severe AL patients (−0.76 vs −0.60). Dyspnea improvements were equal with BUD/FM vs FM in moderate AL patients (−0.44) but greater for BUD/FM vs FM in severe/very severe AL patients (−0.33 vs −0.23). Mean SGRQ improvements were also greater with BUD/FM vs FM (−6.88 vs −6.10, moderate AL; −5.13 vs −2.96, severe/very severe AL).

CONCLUSIONS: A robust response to BUD/FM vs FM was observed for all outcomes in all AL patients. Differential improvements with BUD/FM relative to FM alone were numerically better in moderate vs severe/very severe AL patients for lung function and more evident for severe/very severe vs moderate AL patients for patient-centered outcomes.

CLINICAL IMPLICATIONS: Patients with both moderate and severe/very severe AL benefit from BUD/FM vs FM alone. The relative magnitude of improvement with BUD/FM vs FM alone in lung function and patient-centered outcomes differs depending on AL severity. Supported by AstraZeneca LP.

DISCLOSURE: Donald Tashkin: Consultant fee, speaker bureau, advisory committee, etc.: AstraZeneca – speaker, advisory board; Sunovion –advisory board; Theravance – consultant; Pearl – advisory board; Boehringer-Ingelheim – speaker; Forest – speaker, Grant monies (from industry related sources): Sunovion – research grant; Pearl – research grant; GlaxoSmithKline – research grant Stephen Rennard: Consultant fee, speaker bureau, advisory committee, etc.: Consultations: GlaxoSmith-Kline, Boehringer Ingelheim, Forestweb program, AstraZeneca, Chiesi, Takeda, Regeneron, Pearl, CIPLA, CSA, ABIM, Merck, Medimmune, Synapse, Nycomed, DaiIchio Sankyo, Novartis, J&J, Quadrant, GersonLehman, Able Assoc, CSL Behring, Decision Resources, FirstWord, Gilead, Guidepoint Global, Pulmatrix, Saatchi and Saatchi, Schlesinger Assoc, Cory Paety, Frankel group, Medical Knowleged, Pro Ed Comm, LEK Consulting, Consultant fee, speaker bureau, advisory committee, etc.: Speaking Fees: AstraZeneca, CME Incite, CTS Carmel, Nycomed Frank Trudo: Employee: Employee of AstraZeneca LP, Shareholder: Shareholder of AstraZeneca stock

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Chest. 2014;146(4_MeetingAbstracts):32A. doi:10.1378/chest.1962825

SESSION TITLE: COPD Diagnosis and Evaluation Posters II

SESSION TYPE: Original Investigation Poster

PRESENTED ON: Wednesday, October 29, 2014 at 01:30 PM - 02:30 PM

PURPOSE: The Centers for Medicare & Medicaid Services (CMS) require that a patient’s saturation value read ≤ 88% before that patient can be reimbursed for home oxygen. It is commonly assumed that: 1) a saturation of 88% coincides with an arterial oxygen tension (paO2) value of about 60 torr; and 2) pulse oximeters are highly accurate/precise.

METHODS: A computer spreadsheet (Numbers®; Apple, Inc., Cupertino, CA) incorporating a polynomial expression for oxygen saturation1 was used to calculate the actual saturation of a blood sample as a function of paO2. Spreadsheet functionality allows users to generate plots of numerical parameters incorporated within any tables which it creates. The software was employed to generate the plot (shown below) of percent saturation (ordinate) versus oxygen tension (abscissa) for adult hemoglobin for paO2 values ranging between 50 and 60 torr. In addition, the specification sheet2 for a typical pulse oximeter (Radical-7®; Masimo, Irvine, CA) was consulted in order to determine the typical accuracy of that type of device.

RESULTS: The plot of hemoglobin saturation versus arterial oxygen tension revealed that the saturation corresponding to oxygen tensions of 50 and 60 torr were 85% and 91%, respectively. The specifications for the pulse oximeter revealed that the tolerance of that category of device, under ideal circumstances (no motion), and when applied to an adult patient/subject, was ± 2%. It is entirely possible, then, that a pulse oximeter might furnish a readout of 88% when, in fact, the patient’s actual saturation were 86%. That saturation level corresponds to an arterial oxygen tension of only 51 torr.

CONCLUSIONS: Hypoxemia-induced dyspnea, triggered by activation of the hypoxic ventilatory drive, elicits severe discomfort and anxiety when the prevailing paO2 falls into the 50-to-60-torr range3. Clinicians would be well advised to administer oxygen to their patients such that the observed oximeter reading is at least 93%. In that instance, even if the oximeter reading were falsely high (by 2%), the patient’s paO2 would still be 60 torr.

CLINICAL IMPLICATIONS: ​The current threshold value which CMS sets for reimbursement for home oxygen is far too low.

DISCLOSURE: The following authors have nothing to disclose: Robert Demers, Wayne Wallace

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Chest. 2014;146(4_MeetingAbstracts):33A. doi:10.1378/chest.1978679

SESSION TITLE: COPD Diagnosis and Evaluation Posters II

SESSION TYPE: Original Investigation Poster

PRESENTED ON: Wednesday, October 29, 2014 at 01:30 PM - 02:30 PM

PURPOSE: Depressive symptoms are common in patients with COPD. They are related with impaired quality of life, decreased physical activity and higher health-care utilization. Identifying risk factors of persistent of depression may help clinicians in targeting interventions in high risk population.

METHODS: We analyzed prospective cohort of COPD patients participating in the ECLIPSE. Depression was defined using the Epidemiologic Studies Depression Scale (CES-D) score (≥16) and antidepressant [AD] use. Patients with complete baseline (BL) and 3-year follow-up (3Y) were split into 4 groups: never depressed, new onset, remittent and persistent depression. Logistic regression was used to assess factors (clinical characteristics at BL) associated with persistent depression (CES-D ≥16 or AD use at BL and 3Y) group.

RESULTS: 1580 COPD patients completed the follow-up study. Out of these, 17% (N=368) were determined as persistently depressed. Predictors of persistent depression (CESD≥16 or antidepressant use at baseline and 3-years) are shown in the Table. Variables Odds ratio 95% confidence interval P-value Gender (female) 2.56 1.86-3.52 <0.0001 CESD score at BL per 1 unit worsening 1.18 1.15-1.21 <0.0001 Reversibility (FEV1) per 1% increase 1.01 1.00-1.03 <0.002 Higher SGRQ at BL per 4 units worsening 1.06 1.02-1.11 <0.003 CCL18/PARC per 1 log SD increase 1.02 1.02-1.04 <0.008 History of stroke 3.68 1.78-7.62 <0.0004

CONCLUSIONS: About one fifths of COPD patients remained with a persistent course of depressive symptoms over the 3-years. Females, in patients with reversibility in FEV1, higher baseline depressive symptoms and poorer health status, higher levels of CCL18/PARC and history of stroke were predictors of persistent depression after 3 years baseline assessment.

CLINICAL IMPLICATIONS: Clinician should be aware of the characteristics of persistent depressive symptoms; there is a need to develop targeted management strategies with long-term effectiveness evaluation.

DISCLOSURE: The following authors have nothing to disclose: Abebaw Yohannes, Hana Mülerova, Hao Li, Nicola Hanania, Kim Lavoie, Ruth Tal-Singer, Jorgen Vestbo, Emiel Wouters

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Chest. 2014;146(4_MeetingAbstracts):34A. doi:10.1378/chest.1987594

SESSION TITLE: COPD Diagnosis and Evaluation Posters II

SESSION TYPE: Original Investigation Poster

PRESENTED ON: Wednesday, October 29, 2014 at 01:30 PM - 02:30 PM

PURPOSE: Chronic obstructive pulmonary disease (COPD) is a disease of aging adults. Models investigating health status (HS) and health-related quality of life (QOL) in COPD have included the roles of sociodemographics, lung function, smoking status, and comorbid diseases. However, key geriatric conditions have been overlooked: geriatric syndromes (GS) and dependency in activities of daily living (ADL-dep). We investigated (1) the prevalence of GS and ADL-dep among American adults ≥51 years reporting COPD and (2) the association of GS and ADL-dep with baseline and 2-year change in HS.

METHODS: We analyzed participants age ≥51 years (n=16,785) in wave 2008 of the Health and Retirement Study, a nationally-representative longitudinal health interview survey, and followed them for 2 years. COPD, GS (falls/incontinence/vision impairment/hearing impairment) and ADL-dep (bathing, dressing, eating, transferring, using toilet) were self-reported using previously validated questions. Respondents reported baseline (2008) HS (excellent to poor) and 2-year (2010) HS, compared to previous interview (better/same/worse). We used logistic regression to examine the effect of GS/ADL-dep on baseline/change in HS among respondents with COPD. Covariates included: sociodemographics; smoking status; oxygen use, and persistent respiratory symptoms (as COPD severity proxies); 7 comorbidities (hypertension, heart, cancer, diabetes, stroke, musculoskeletal and psychiatric disease); and cognitive function.

RESULTS: COPD was reported by 10.9% of respondents (n=1,839, representing 7.6 million nationally), 34.7% of whom had ≥2 GS and 9.2%, ≥2 ADL-dep. In fully adjusted models, presence of ≥2 GS was associated with higher odds of fair/poor baseline HS (odds ratio [OR] 3.1; 95% confidence interval [CI] 2.3-4.3) and with 2-year worsening HS (OR 2.0; 95% CI 1.4-2.7). ADL-dep was also associated with higher odds of fair/poor baseline HS (OR 2.0; 95% CI 1.0-4.1), but not with 2-year worsening HS (OR 1.2, 95% CI 0.6-2.7). The impact GS/ADL-dep was greater than that due to individual comorbid diseases and comparable to having ≥3 comorbid diseases.

CONCLUSIONS: Beyond comorbid diseases, sociodemographics, and pulmonary factors, geriatric syndromes and ADL dependencies are important factors impacting HS in COPD. GS and ADL-dep should be a target for identification of COPD patients at high risk for worsening HS.

CLINICAL IMPLICATIONS: Geriatric conditions (GS/ADL-dep) impact HS/QOL in COPD, and could be used to identify subjects at risk of further deterioration.

DISCLOSURE: The following authors have nothing to disclose: Carlos Martinez, Caroline Richardson, MeiLan Han, Christine Cigolle

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Chest. 2014;146(4_MeetingAbstracts):35A. doi:10.1378/chest.1988533

SESSION TITLE: COPD Diagnosis and Evaluation Posters II

SESSION TYPE: Original Investigation Poster

PRESENTED ON: Wednesday, October 29, 2014 at 01:30 PM - 02:30 PM

PURPOSE: The aims of the study: To study the correlation of ICFS as clinical indicator in COPD patients with severity, risk of hospitalization and duration of hospital stay.

METHODS: We study 56 patients attending assessment clinics during hospitalization and 85 patients during outpatient visits. Both questionnaire and physiologic data were collected. The correlations, multiple linear regressions, ANOVA and Cox proportional hazard models/negative binomial regressions were used.

RESULTS: Mean of ICFS in outpatients was 47.73 . Five sub scale mean values of feelings of fatigue, vigor, impact on concetration, on energy and daily acitivity were 64.42, 63.94, 27.72, 46.74, 47.73 respectively. Mean ICFS in hospitalized patients and sub scale mean values were 56.34, 67.29, 69.64, 49.71, 39.91, 55.10 respectively. Mean ICFS according to A, B, C, D stages of COPD patients were 44.54, 46.09, 51.76, 57.36 respectively. According to the ICFS values one patient had ICFS between 20 - 30, five patients 31 - 40, nine patientes 41 - 50, fifteen patients 51 - 60, fourteen patients 61 - 70, and six patients >70. The mean ICFS for day staying 1-7, 7-10, 10-15, >15 days was 46.45, 58.35, 60.28 and 67.65 respectively.

CONCLUSIONS: A significant relationship exist between ICFS values and COPD severity. ICFS values predict hospitalization risk and length of stay. ICFS must be another important instrument in predicting the severity and treatment strategy of COPD.

CLINICAL IMPLICATIONS: During the evaluation of severity of COPD exacerbations and treatment approach we have to measure and consider the ICFS which is a safe instrument in correct treatment of COPD exacerbations

DISCLOSURE: The following authors have nothing to disclose: Juli Gjerazi, Eritjan Tashi, Sofiela Telo, Arben Tanka, Edlira Ndreu, Esmeralda Nushi, Dhimitraq Argjiri, Eugerta Dilka, Elenka Shehu, Mirela Tabaku, Perlat Kapisyzi

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Chest. 2014;146(4_MeetingAbstracts):36A. doi:10.1378/chest.1990397

SESSION TITLE: COPD Diagnosis and Evaluation Posters II

SESSION TYPE: Original Investigation Poster

PRESENTED ON: Wednesday, October 29, 2014 at 01:30 PM - 02:30 PM

PURPOSE: The aim of this study was to determine cut-off value for forced expiratory volume in one second/forced expiratory volume in six second (FEV1/FEV6) as an alternative for FEV1/forced vital capacity (FVC) in the detection of airway obstruction of the Korean population.

METHODS: In this study, we analyzed data provided by the forth and fifth Korean National Health and Nutrition Survey (KNHANES IV-V), a cross-sectional survey of the Korean population regarding health related behavior, health condition, and nutritional state of Koreans. The pre-bronchodilator data from subjects who performed spirometry adequately aged above 40 years were analyzed. We determined the corresponding FEV1/FEV6 and FEV6 values to the gold standard cutoff values of FEV1/FVC and FVC for the diagnosis of airflow obstruction by generating a receiver-operator characteristic (ROC) curve to determine the greatest sum of sensitivity and specificity.

RESULTS: Total 9,281 spirometry data were included in this study. Among them 4,024 were male and 5,257 were female. 1,271 were confirmed as having chronic obstructive lung disease (COPD) according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) Guidelines. The data from this study indicate that FEV1/FEV6 <75% can be used as a valid alternative for the FEV1/FVC <70% cut-off points for the detection of airway obstruction. The statistical analysis demonstrated very good agreement between the two criteria. For the diagnosis of airflow limitation, new criteria of FEV1/FEV6 sensitivity was 95.1% and specificity was 94.6%; the positive predictive value (PPV) and negative predictive value (NPV) were 73.8% and 99.2%, respectively. Similar results were obtained for male, female and age subjects.

CONCLUSIONS: This study demonstrates that forced expiratory volume in one second/forced expiratory volume in six seconds <75% can be used as valid alternatives to forced expiratory volume in one second/forced vital capacity <70% as fixed cut-off point for the detection of an obstructive spirometric pattern in Korean adults above 40 years old.

CLINICAL IMPLICATIONS: This result may add a new information to develop a new guideline of COPD of the Korea.

DISCLOSURE: The following authors have nothing to disclose: HeeJin Park, JuHan Song, YoungSam Kim

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Chest. 2014;146(4_MeetingAbstracts):37A. doi:10.1378/chest.1994126

SESSION TITLE: COPD Diagnosis and Evaluation Posters II

SESSION TYPE: Original Investigation Poster

PRESENTED ON: Wednesday, October 29, 2014 at 01:30 PM - 02:30 PM

PURPOSE: Patient-perceived COPD symptoms vary over the day and the week with impact on daily activities, morning being the worst time of day. The study aimed to identify the correlation between patient perceptions of their ability to perform morning activities and the general health status visual scale, as assessed by the physician during physical examination. This was the first Romanian study to assess this correlation.

METHODS: RELIEF (CorRELation Between PatIent PErception and Findings on Clinical Examination, NCT01627743) was a non-interventional, multicenter, prospective, 12-weeks study of patients aged at least 40 years with COPD stage C or D treated with ICS/LABA combined therapy. Patients were current or ex-smokers. In order to evaluate patients’ perception on ability to perform morning activities, the validated Capacity of Daily Living during the Morning (CDLM) Questionnaire was used. Investigators used a 5-items visual scale for assessing the health status (5=very good, 1=very bad).

RESULTS: 505 patients were included in the final analysis. The majority of patients were male (85.1%), with a mean age of 65 years. 74.7% were reported as being ex-smokers with a mean of 20 cigarettes (1 pack) per day. The average duration of COPD was 5.31 years and more than half of the patients enrolled had COPD stage C (61%). The mean duration of inhaled combined therapy before study was 36 months. 67.9% patients reported comorbidities, majority being from the cardio-vascular area with hypertension the most frequent condition (38.2%). The mean score of CDLM increased during the prospective follow-up from 3.68 to 3.94, as well as the percentage of patients with a general health status of 4/5 from 41.2% to 57.4%. A positive correlation, weak-to-moderate, was found between the CDLM total score and the general health status (Kendall tau-b values from 0.2269 to 0.3181).

CONCLUSIONS: These results indicate a general improvement of subjective perceptions of both patients and health care providers and complete the COPD landscape in Romania, being the first study on quality of life.

CLINICAL IMPLICATIONS: The regular contact with the health care provider might lead to a general health improvement and might represent an important motivational tool to be taken into account in treating severe COPD patients.

DISCLOSURE: Florin Mihaltan: Consultant fee, speaker bureau, advisory committee, etc.: consultant fee, speaker fee for ASTRA ZENECA Dragos Ungureanu: Consultant fee, speaker bureau, advisory committee, etc.: Consultant fee. speaker fee for Astra Zeneca

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Chest. 2014;146(4_MeetingAbstracts):38A. doi:10.1378/chest.1994417

SESSION TITLE: COPD Diagnosis and Evaluation Posters II

SESSION TYPE: Original Investigation Poster

PRESENTED ON: Wednesday, October 29, 2014 at 01:30 PM - 02:30 PM

PURPOSE: Anxiety and depressive symptoms are common in patients with chronic obstructive pulmonary disease (COPD). However, the prevalence of major depression and clinical anxiety is uncertain. We examined the prevalence of major depression and anxiety disorders in COPD patients attending outpatient pulmonary rehabilitation and acute respiratory assessment service.

METHODS: 56 COPD patients agreed to participate in the study. Inclusion criteria: FEV1 < 70% predicted and Mini Mental State Examination > 23. Depression and anxiety were assessed using the Hospital Anxiety Depression Scale (HAD), health status was examined using the COPD assessment test (CAT), physical disability was evaluated using the Manchester Respiratory Activities of Daily Living questionnaire (MRADL). Patients that exhibited high level of HAD depressive or anxiety symptoms > 8 had further clinical interview using the Mini International Neuropsychiatric Interview (MINI).

RESULTS: In 56 COPD patients, the prevalence of anxiety HAD was 29 (52%) and depression HAD was 24 (43%). Out of these, 22 COPD patients (female = 16) underwent the MINI assessment. The mean (SD) age was 71.1 (5.7) years. FEV1 % predicted mean (SD) was 44.85 (18.31). Ten patients (45%) had an anxiety disorder. The most common anxiety disorders were panic disorder with or without agoraphobia 8 (36%) and generalised anxiety disorder was 5 (23%) whilst current major depression was 9 (41%). Seven (32%) patients had both a clinical anxiety disorder and a mood disorder. Major depression was related with increased physical disability [r = -0.56, p < ooo1], and clinical anxiety was associated with poorer health status [r = 0.68, p < 0.001]. Patients smoking status: current 27%, previous smoker 63% and never smoked 20%. The mean (SD) pack years was 37.63 (20.53).

CONCLUSIONS: Clinical anxiety and depression are common in patients with COPD. The most common anxiety disorders were panic disorder with or without agoraphobia and generalised anxiety disorder. Increased physical disability and impaired quality of life are associated with major depression and anxiety, respectively.

CLINICAL IMPLICATIONS: Untreated major depression and anxiety increased physical disability and impaired quality of life of patients with COPD. Clinicians should be vigilant in detection and treatment of these comorbid-disorders in patients with COPD.

DISCLOSURE: The following authors have nothing to disclose: Abebaw Yohannes, Thomas Willgoss

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Chest. 2014;146(4_MeetingAbstracts):39A. doi:10.1378/chest.1994789

SESSION TITLE: COPD Diagnosis and Evaluation Posters II

SESSION TYPE: Original Investigation Poster

PRESENTED ON: Wednesday, October 29, 2014 at 01:30 PM - 02:30 PM

PURPOSE: Patients with cardiorespiratory disease have a high symptom burden when assessed in inpatient or outpatient settings. Such patients may develop to acute exacerbations, complicated by respiratory failure. Non-invasive ventilation (NIV) is increasingly used to manage acute respiratory failure due to decompensated cardiorespiratory disease. Little is known about the distress experienced by patients undergoing NIV, including symptom burden and delirium point prevalence. To date, no studies have quantified either of these important clinical endpoints.

METHODS: Consecutive consenting, English speaking, cognitively intact patients treated outside ICU with NIV for hypercapnic respiratory failure were recruited. Assessment occurred within 36 hours of starting NIV. Symptom burden over the previous 72 hours was assessed measured using the Condensed Memorial Symptom Assessment Scale (CMSAS). This scale assesses the peak bothersomeness of 11 physical symptoms (rated 0-4) and frequency of 3 psychological symptoms (rated 0-4). Delirium point prevalence was assessed using the Confusion Assessment Method for ICU (CAM-ICU).

RESULTS: Fifty participants (64% female, mean age 71.9yrs, SD 13.1) were recruited. Prior to NIV, mean arterial pH was 7.30(SD 0.08) and a mean arterial pCO2 58.1mmHg(SD 11.9). Of these, 38% had obstructive lung disease, 14% had heart failure, 30% had both these conditions. The remainder had other causes of respiratory failure. The most prevalent symptoms were breathlessness(92%), dry mouth(88%) and lack of energy(86%). These were also the most bothersome symptoms. The most frequent psychological symptom was worry(64%). The mean total CMSAS score was 1.60(SD 0.66), with the mean physical symptom score of 1.62(SD 0.63) and the mean psychological score of 1.57(SD1.22). Four(8%) patients screened positive for delirium on the CAM-ICU.

CONCLUSIONS: Breathlessness, dry mouth and lack of energy are highly prevalent and bothersome in NIV patients. Psychological symptoms are also highly distressing. The point prevalence of delirium was 8%, however this may be an underestimate.

CLINICAL IMPLICATIONS: Understanding physical symptoms allows clinicians to target symtpom relief as a clinical priority, while simultaneously managing NIV. An understanding of psychological symptom burden requires further work to facilitate holistic, patient centred care. Further examination of delirium prevalence is required given the prognostic implications and impact it may have on both patient and family distress and co-operation with NIV.

DISCLOSURE: The following authors have nothing to disclose: Tracy Smith, Mary Dunford, Meera Agar, Patricia Davidson, Christine Jenkins, Jane Ingham

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Chest. 2014;146(4_MeetingAbstracts):40A. doi:10.1378/chest.1995278

SESSION TITLE: COPD Diagnosis and Evaluation Posters II

SESSION TYPE: Original Investigation Poster

PRESENTED ON: Wednesday, October 29, 2014 at 01:30 PM - 02:30 PM

PURPOSE: Recent studies have shown that lower body mass index (BMI) is associated with higher mortality rate in many conditions such as in ICU patients, pneumonia patients, so called, obesity paradox. We aimed to examine the association between BMI and mortality in acute COPD exarcerbation (AECOPD) patients.

METHODS: This study is a retrospective review of 136 patients hospitalized for AECOPD from January 1, 2011 to December 31, 2011. The demographic data, clinical manifestation, laboratory findings, and treatment were collected from medical record. The length of hospital stay (LOS) and 1-year mortality rate (MR) were compared between obese group and non-obese group.

RESULTS: From 136 patients (mean 69.7±11.7 years old, 47.1 % male), 80 patients (58.8%) were categorized into obese group defined by BMI > 25, whereas 56 patients (47.2) were in non-obese group. When compared between 2 groups, the 1-year MR were 12.5% and 30.4% (p=0.01), LOS were indifferent, 3.43 days and 3.8 days (p=0.56). The number of total visit are 2.3 and 1 (p=0.047) in obese and non-obese group respectively.

CONCLUSIONS: Multiple studies have revealed the association between BMI and outcome in patients in many populations. In our study, we found that being overweight or obese is associated with surviving at 3 months. The exact mechanism is unknown but many hypotheses have been proposed. This study suggests that obesity is associated with better survival rate of COPD patients (lower 1-year MR), although the LOS is nonstatistical significant and the number of revisit is higher in obese COPD patients.

CLINICAL IMPLICATIONS: Obesity paradox in COPD patients in term of mortality rate is consistent with previous studies. Obesity does not effect length of hospital stay and number of revisit.

DISCLOSURE: The following authors have nothing to disclose: Prangthip Charoenpong

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Chest. 2014;146(4_MeetingAbstracts):41A. doi:10.1378/chest.1994762

SESSION TITLE: COPD Diagnosis and Evaluation Posters II

SESSION TYPE: Original Investigation Poster

PRESENTED ON: Wednesday, October 29, 2014 at 01:30 PM - 02:30 PM

PURPOSE: Oxygen therapy is provided to patients with an acute exacerbation of COPD,however,oxygen induced hypercapnea is a common side effect of such therapy especially in COPD patients who have chronic CO2 retention. In assessing this side effect,particularly regarding morbidity and mortality,one needs to take into consideration the concentration of oxygen therapy delivered by different delivery systems.The use of titrated oxygen systems (i.e.Venturi masks) has shown fewer instances of worsening respiratory acidosis,a lower requirement for assisted ventilation,and reduced mortality. In light of the above,we investigated the incidence of patients in our hospital system, who were found to have an acute exacerbation of COPD,and required invasive mechanical ventilation after having received treatment with oxygen in excess concentrations (i.e. >28%).

METHODS: A retrospective analysis was conducted on patients admitted between 2001-2014 to St. Joseph’s Health Care System in New Jersey,with diagnoses of COPD exacerbation and respiratory failure. Medical records were reviewed to ascertain if high concentrations of oxygen (FIO2>28%) were received prior to initiation of invasive mechanical ventilation. Data was subdivided into yearly incidence and method of oxygen delivery.

RESULTS: A total of 590 patient admissions were coded for diagnoses of COPD exacerbation and respiratory failure.Of these,approximately 100 were identified as instances in which high concentrations of supplemental oxygen may have played a role in the need for subsequent invasive mechanical ventilation. The most common methods of oxygen delivery in these cases were 100% non-rebreather masks and Bipap,followed by nasal cannula and Venturi-mask, respectively. A total of 21 subsequently died.

CONCLUSIONS: Identification of patients with COPD presenting with acute exacerbations is crucial in proper management. Adequate oxygen supplementation potentially prevents unwanted complications,the most concerning of which is invasive mechanical ventilation. In addition to the adverse effects to the patient,there is a protracted hospital course which has its own set of consequences,primarily cost. Better education and training to all those involved in administering oxygen therapy can help prevent such incidents.

CLINICAL IMPLICATIONS: The use of controlled oxygen delivery systems,such as the Venturi mask,in the setting of acute exacerbation of COPD,can potentially result in decreased number of intubations,decreased morbidity and mortality,as well as decreased hospital stay.

DISCLOSURE: The following authors have nothing to disclose: Jacob Mathew, Ayham Aboeed, Suresh Kumar Manickavel, Muhammad Khan

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Chest. 2014;146(4_MeetingAbstracts):42A. doi:10.1378/chest.1987927

SESSION TITLE: COPD Treatment Posters

SESSION TYPE: Original Investigation Poster

PRESENTED ON: Wednesday, October 29, 2014 at 01:30 PM - 02:30 PM

PURPOSE: Administration of Alpha-1 Antitrypsin (AAT) protein to patients with severe AAT deficiency may prevent the progression of emphysema, improve lung function and reduce mortality. Although there has been no data to support the use of augmentation therapy in patients with the PiMZ genotype (carriers), such patients are occasionally treated with augmentation therapy. The purpose of this study was to document the demographics and clinical profile of AAT-deficient COPD patients with PiMZ genotype started on augmentation therapy.

METHODS: We performed a retrospective review of all COPD patients with PiMZ genotype who were started on augmentation therapy from 2004 to 2013, as registered in the data-base of Coram, a US national specialty infusion company. All patients were diagnosed and treated by their own clinicians within United States.

RESULTS: At the initiation of augmentation therapy, there were 101 subjects: 58 men, 43 women, mean age 57, age range 18-84. All were PiMZ heterozygotes with a mean serum AAT level of 82 mg/dL (range 42-159 mg/dL). 70% were former smokers, 25% nonsmokers and 5% current smokers. Their mean FEV1 was 53% predicted (range 19-100% predicted). Their mean weight was 80 kg (range 39-139 kg). 81% were on oxygen supplementation. All received augmentation therapy with weekly IV infusions except 6 who had biweekly infusions. All were treated at home except 12 who were treated at the outpatient infusion centers.

CONCLUSIONS: This group of PiMZ heterozygotes started on augmentation therapy tended to be older, former smokers with moderately severe COPD, had a below normal serum AAT level and needed oxygen supplementation.

CLINICAL IMPLICATIONS: There is a need for prospective trials with long follow up periods, assessing meaningful clinical end points examining the role of augmentation therapy in AAT-deficient COPD patients with PiMZ genotype.

DISCLOSURE: Navid Zaidi: Grant monies (from industry related sources): Reseach grant: CSL Behring, Consultant fee, speaker bureau, advisory committee, etc.: CSL Behring Debra Greek: Employee: Coram Employee The following authors have nothing to disclose: Crystal Piepenbrink

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Chest. 2014;146(4_MeetingAbstracts):43A. doi:10.1378/chest.1989286

SESSION TITLE: COPD Treatment Posters

SESSION TYPE: Original Investigation Poster

PRESENTED ON: Wednesday, October 29, 2014 at 01:30 PM - 02:30 PM

PURPOSE: Asymptomatic individuals may not seek medical attention despite early lung damage from exposure to air pollutants. We sought to determine the utility of a digital stethoscope in detecting early lung damage in individuals exposed to noxious air pollutants.

METHODS: Study participants were given a questionnaire to determine the absence of symptoms and their pollutant exposure. They were recruited from the local fire department and a medical practice in a small community. Participants were divided into three groups smokers (n=16), firefighters (n=13) and non-smokers (n=25). A single breath for each hemithorax was recorded using a digital stethoscope. Fast Fourier transformation was done using Mathlab software. Frequency peaks were used to subsequently analyze the amplitude frequency distribution of breath sounds. Differences of peaks above 125 Hz were analyzed using student T-test.

RESULTS: Using a cut off of 125 Hz the number of peaks were higher in smokers vs. non-smokers and was statistically significant (p=.013). Firefighters also showed a higher number of peaks when compared to non-smokers (p=.002). There was no significant difference between the number of peaks above 125 Hz between firefighters and smokers (p=.70). In addition there was a rightward shift in the average frequency of the breath sounds with the normal being 52.8 Hz and smokers 65.9 Hz (p=0.028) and firefighters 66.6 Hz (p=0.01).

CONCLUSIONS: Early detection of lung disease is key to prevention of further damage in vulnerable individuals when exposed to noxious air pollutants. Sound frequency analysis using a digital stethoscope may be used to detect early changes in lung function in asymptomatic individuals.

CLINICAL IMPLICATIONS: Sound frequency analysis using a digital stethoscope may be a useful technique in identifying individuals vulnerable to cigarette smoke. This may have important public health implications as it can be used as an effective screening tool. This may also be used as part of a comprehensive screening protocol in workplaces with significant airborne toxin exposure.

DISCLOSURE: The following authors have nothing to disclose: Ilina Krishen, Mary Lynn Zaremba, Kristin Elliott, Sridhar Reddy

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Chest. 2014;146(4_MeetingAbstracts):44A. doi:10.1378/chest.1989842

SESSION TITLE: COPD Treatment Posters

SESSION TYPE: Original Investigation Poster

PRESENTED ON: Wednesday, October 29, 2014 at 01:30 PM - 02:30 PM

PURPOSE: This study compared COPD-related HRU and costs among COPD patients receiving arformoterol or formoterol, the only two FDA approved nebulized LABAs for COPD maintenance.

METHODS: Eligible patients for this retrospective cohort study were identified from the IMS PharMetrics Plus claims database: aged≥35 years, with ≥2 fills of arformoterol or formoterol between 01/01/2008-12/31/2012 (first nebulized LABA defined as index), ≥2 outpatient or ≥1 inpatient claims with COPD diagnosis (ICD-9-CM 491.x, 492.x, 496.x), continuous enrollment 180-day pre- and 360-day post-index, and no nebulized LABA or asthma diagnosis pre-index. Adherence to index drug was computed using proportion of days covered (PDC) in 360-day post-index. To assess the impact of treatment on study outcome, the study was limited to those adherent or partially adherent (A/PA, PDC≥60%) to their index drug. Costs were reported in 2012 USD. Chi-square and t-test/Wilcoxon rank-sum were used for comparison (alpha=0.05). Generalized linear models (GLM) with negative binomial (for HRU) and gamma (for cost) distributions were used to compare the two index cohorts in 360-day post-index, with covariates of demographic and clinical characteristics and pre-index COPD-related healthcare service use.

RESULTS: 417 patients A/PA to their index drug (arformoterol=274, formoterol=143; mean age=70.7, 45% females) were selected. Both cohorts had similar COPD-related HRU across all care settings (inpatient, outpatient, pharmacy). Costs in most settings were similar, except for inpatient care: compared to formoterol users, arformoterol users had significantly lower per-stay cost in those with ≥1 admission (median $9,542 vs. $14,025, p=0.009) or further with ≥1 re-admission within 30 days since discharge (median $7,392 vs. $18,018, p=0.006). Controlling for confounders, arformoterol users were predicted to have 14.4% marginally lower COPD-related total costs than formoterol users (p=0.066). The GLM results also suggest that pre-index COPD-related hospitalization and pre-index use of oral corticosteroids were significant predictors of higher total COPD-related costs.

CONCLUSIONS: In this study on COPD-related burden among A/PA users, patients receiving arformoterol had lower inpatient costs compared to patients receiving formoterol, which led to lower total disease related costs.

CLINICAL IMPLICATIONS: This study suggests that the choice of nebulized LABA may influence economic outcomes, such as some COPD-related costs.

DISCLOSURE: Yaozhu Chen: Employee: IMS Health Charles Maken: Employee: IMS Health Vamsi Bollu: Employee: Sunovion

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Chest. 2014;146(4_MeetingAbstracts):45A. doi:10.1378/chest.1991652

SESSION TITLE: COPD Treatment Posters

SESSION TYPE: Original Investigation Poster

PRESENTED ON: Wednesday, October 29, 2014 at 01:30 PM - 02:30 PM

PURPOSE: To evaluate the pharmacokinetics (PK), safety, and tolerability of aclidinium 400µg/formoterol 12µg fixed-dose combination (FDC) via Pressair®/Genuair®* and formoterol (FOR) 12µg via Foradil® Aerolizer® in patients with moderate to severe chronic obstructive pulmonary disease (COPD).

METHODS: In this Phase 2a, randomized, open-label, 2-way crossover study, 24 patients (male and female) were randomized to 1 of 2 treatment sequences with FDC via Pressair® or FOR via Aerolizer® administered twice daily for 4 days followed by 1 morning inhalation on day 5 and a 7-day washout. Plasma samples were analyzed using validated LC-MS/MS. Cmax and AUC for FOR were compared using ANCOVA. Safety also was evaluated.

RESULTS: All 24 patients completed the study. Following single-dose administration of Pressair® and Aerolizer®, mean FOR Cmax was 9.55 and 8.23pg/mL; mean AUC0-τ was 42.27 and 41.63pg•h/mL. Median FOR tmax was shorter with Pressair® than Aerolizer® (0.38 vs 1.0h). Mean day 1 FOR t½ and Day 5 FOR AUC0-τ,ss, Cmin,ss, Cavg,ss and t½ were comparable between devices. Mean FOR Cmax,ss was numerically greater with Pressair® than Aerolizer® (16.72 vs 14.90pg/mL); 90% CIs for the geometric means ratio (Pressair®/Aerolizer®) for Cmax,ss and AUC0-τ,ss were within 80%-125%. Mean steady-state FOR accumulation ratios were comparable between inhalers. Following single-dose FDC administration, mean aclidinium (ACL) Cmax and AUC0-τ were 101.98pg/mL and 228.30pg•h/mL. In most patients, ACL tmax was achieved 5 min post-dose, mean ACL t½ was ~5h. Day 5 mean ACL Cmax,ss and AUC0-τ,ss were 128.43pg/mL and 404.25pg•h/mL. Mean steady-state ACL accumulation ratio (1.38) was expected due to its ~5h half-life. Six (25.0%) FDC patients and 2 (8.3%) FOR patients reported a total of 11 treatment-emergent adverse events, none led to discontinuation.

CONCLUSIONS: Aclidinium steady state was reached following 5 days of twice daily administration via Pressair® inhaler. Formoterol steady-state was achieved within 5 days regardless of inhaler type. Formoterol PK is bioequivalent between Pressair® and Aerolizer®. All treatments were well tolerated.

CLINICAL IMPLICATIONS: PK and safety of aclidinium/formoterol FDC via Pressair® and formoterol via Aerolizer® are similar. *Registered trademarks of Almirall S.A., Barcelona, Spain; for use within the USA as Pressair® and Genuair® within all other licensed territories. This study was funded by Almirall S.A. and by Forest Research Institute, Inc., a wholly owned subsidiary of Forest Laboratories, Inc.

DISCLOSURE: Stephan Ortiz: Employee: Forest Research Institute The following authors have nothing to disclose: Charles Fogarty

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Chest. 2014;146(4_MeetingAbstracts):46A. doi:10.1378/chest.1994369

SESSION TITLE: COPD Treatment Posters

SESSION TYPE: Original Investigation Poster

PRESENTED ON: Wednesday, October 29, 2014 at 01:30 PM - 02:30 PM

PURPOSE: To determine whether combining long-acting β-agonists (LABAs) with long-acting muscarinic antagonists (LAMAs) once daily will improve the health status of patients with chronic obstructive pulmonary disease (COPD).

METHODS: We report on two replicate, double-blind, randomized, 12-week studies comparing the effects of (a) the free combination of the LABA olodaterol 5 µg once daily (via Respimat®) and the LAMA tiotropium 18 µg once daily (via HandiHaler®) [T+O] with (b) tiotropium 18 µg once daily (HandiHaler®) in combination with placebo (Respimat®) [T+P] on health status in patients with moderate to severe COPD (ANHELTO-1 [NCT01694771] and ANHELTO-2 [NCT01696058]). Health-related quality of life was evaluated using St. George’s Respiratory Questionnaire (SGRQ) total scores, and symptoms, activity, and impact sub-scores; these were assessed on Day 1 and Week 12. SGRQ total score at Week 12 from the combined dataset was identified as a key secondary end point.

RESULTS: The mean SGRQ was lower (improved) at Week 12 with T+O (41.2) than with T+P (43.1); the mean (standard error) difference between treatments was -1.85 (0.46; p<0.0001). SGRQ subscale scores were also lower with T+O than T+P at Week 12: mean (95% confidence interval) differences between treatments were ‑3.771 (-5.232, -2.309) for SGRQ symptom score, -1.791 (-2.945, -0.636) for SGRQ activity score, and -1.145 (-2.125, -0.165) for SGRQ impact score.

CONCLUSIONS: Compared with tiotropium alone, the use of olodaterol with tiotropium once daily resulted in a significant, further improvement in health-related quality of life in patients with COPD.

CLINICAL IMPLICATIONS: Combining tiotropium (HandiHaler®) and olodaterol (Respimat®) once daily provides benefits for patients’ health status versus T+P in COPD. Funding: Boehringer Ingelheim. Editorial assistance: Complete HealthVizion.

DISCLOSURE: Richard ZuWallack: Consultant fee, speaker bureau, advisory committee, etc.: Honoraria from Boehringer-Ingelheim paid to my hospital, Grant monies (from industry related sources): Investigator initiated grants from Boehringer-Ingelheim to my institution, Consultant fee, speaker bureau, advisory committee, etc.: Honoraria from GSK for speaking paid to me Lisa Allen: Employee: Boehringer-Ingelheim Gemzel Hernandez: Employee: Boehringer-Ingelheim Naitee Ting: Employee: Boehringer-Ingelheim Roger Abrahams: Grant monies (from industry related sources): Clinical Research Grant from Boehringer-Ingelheim, Consultant fee, speaker bureau, advisory committee, etc.: Boehringer-Ingelheim steering committee

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Chest. 2014;146(4_MeetingAbstracts):47A. doi:10.1378/chest.1994418

SESSION TITLE: COPD Treatment Posters

SESSION TYPE: Original Investigation Poster

PRESENTED ON: Wednesday, October 29, 2014 at 01:30 PM - 02:30 PM

PURPOSE: To evaluate the safety of combination therapy with the long-acting bronchodilators tiotropium 18 µg (via HandiHaler®) and olodaterol 5 µg (via Respimat®) [T+O], both given once daily in patients with moderate to severe chronic obstructive pulmonary disease (COPD). Tiotropium 18 µg once daily (HandiHaler®) and placebo (Respimat®) served as the comparator [T+P] (ANHELTO-1 [NCT01694771] and ANHELTO-2 [NCT01696058]).

METHODS: Adverse events (AEs) in the two treatment groups were evaluated throughout the 12-week treatment and 21-day safety follow-up periods.

RESULTS: In ANHELTO-1, 45.3% (T+O; n=567) and 42.8% (T+P; n=565) of patients reported AEs and 7.1% and 4.6% reported serious AEs (SAEs), respectively. In ANHELTO-2, 40.1% (n=566) and 43.2% (n=569), respectively, reported AEs and 4.2% and 4.7% reported SAEs. Most events were mild to moderate in intensity and not considered related to study treatment. In total, 12 deaths occurred: there was a numerical imbalance in ANHELTO-1 (one T+P, five T+O) that was not seen in ANHELTO-2 (two T+P, three T+O). Three of the 12 occurred during randomized treatment: one with T+P (due to natural causes) and two with T+O (myocardial ischemia, cocaine/oxycodone toxicity). The remaining deaths occurred after discontinuation of study treatment: eight occurred during follow-up (two with T+P [convulsions and myocardial infarction] and six with T+O [hemorrhagic cerebral infarction, myocardial infarction/arteriosclerosis, acute respiratory failure (COPD during study treatment period also cited), COPD, cardiac arrest, and sudden death]); one further death occurred after the 21-day post-treatment follow-up (T+P [subarachnoid hemorrhage]).

CONCLUSIONS: The results of these two large-scale randomized studies demonstrate that the incidence of AEs was generally low and similar with T+O and T+P. These data support the established safety profile of olodaterol 5 μg once daily via Respimat® and its use in combination with tiotropium HandiHaler®.

CLINICAL IMPLICATIONS: These studies of the combination of tiotropium (HandiHaler®) and olodaterol (Respimat®) support the established safety profile of olodaterol 5 μg once daily via Respimat®. Funding: Boehringer Ingelheim. Editorial assistance: Complete HealthVizion.

DISCLOSURE: Roger Abrahams: Grant monies (from industry related sources): Clinical Research Grant from Boehringer-Ingelheim, Consultant fee, speaker bureau, advisory committee, etc.: Boehringer-Ingelheim steering committee Lisa Allen: Employee: Boehringer-Ingelheim Gemzel Hernandez: Employee: Boehringer-Ingelheim Naitee Ting: Employee: Boehringer-Ingelheim Richard ZuWallack: Consultant fee, speaker bureau, advisory committee, etc.: Honoraria from Boehringer-Ingelheim paid to my hospital, Grant monies (from industry related sources): Investigator initiated grants from Boehringer-Ingelheim to my institution, Consultant fee, speaker bureau, advisory committee, etc.: Honoraria from GSK for speaking paid to me

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Chest. 2014;146(4_MeetingAbstracts):48A. doi:10.1378/chest.1994476

SESSION TITLE: COPD Treatment Posters

SESSION TYPE: Original Investigation Poster

PRESENTED ON: Wednesday, October 29, 2014 at 01:30 PM - 02:30 PM

PURPOSE: Tiotropium, a long-acting muscarinic antagonist, has recently been assessed in fixed-dose combination (FDC) with olodaterol, a once-daily, long-acting β2-agonist, for treatment of chronic obstructive pulmonary disease (COPD). We present pooled safety data from two pivotal, replicate, Phase III studies assessing efficacy and safety of FDCs of tiotropium and olodaterol(T+O) delivered via Respimat® inhaler in patients with GOLD stage 2-4 COPD.

METHODS: In these 52-week, double-blind, parallel-group studies, patients were randomized to five arms: once-daily olodaterol 5 µg, tiotropium 2.5 µg, tiotropium 5 µg, T+O 2.5/5 µg, T+O 5/5 µg. Key inclusion criteria included: age ≥40 years, diagnosis of COPD, smoking history >10 pack-years. Patients with a history of asthma or significant disease other than COPD were excluded; however, patients with stable cardiovascular co-morbidities were included. Adverse events (AEs) were reported throughout.

RESULTS: In total, 5162 patients were randomized and treated. AEs, serious AEs, and fatal AEs were generally balanced across treatment groups. AE incidence was 76.6% (olodaterol 5 µg), 73.4% (tiotropium 2.5 µg), 73.3% (tiotropium 5 µg), 74.7% (T+O 2.5/5 µg), and 74.0% (T+O 5/5 µg). The most frequently reported AEs were respiratory events (according to MedDRA System Organ Class), including COPD exacerbations (34.1-35.6% with monotherapies versus 29.2-32.3% with FDCs) and dyspnea (3.7-4.9% with monotherapies versus 3.9-4.2% with FDCs). Frequencies of cardiac disorders were generally balanced across groups (4.5-5.8%), while respiratory events were more frequent among patients treated with monotherapies (42.7-45.3%) than FDCs (38.2-39.4%). Most events were mild to moderate in severity and not considered related to study treatment. Groups receiving T+O FDCs reported fewer rescue medication usages compared to groups receiving single components.

CONCLUSIONS: T+O FDCs were well tolerated with no increase in incidence of AEs compared to individual components.

CLINICAL IMPLICATIONS: The equivalent tolerability of T+O FDCs compared to the monotherapies suggests there are no safety signals with the combined therapy in patients with COPD. Funding: Boehringer Ingelheim. Editorial assistance: Complete HealthVizion.

DISCLOSURE: Roland Buhl: Consultant fee, speaker bureau, advisory committee, etc.: Astra Zeneca, Consultant fee, speaker bureau, advisory committee, etc.: Boehringer Ingelheim, Consultant fee, speaker bureau, advisory committee, etc.: Chiesi, Consultant fee, speaker bureau, advisory committee, etc.: Grifols, Consultant fee, speaker bureau, advisory committee, etc.: GSK, Consultant fee, speaker bureau, advisory committee, etc.: Novartis, Consultant fee, speaker bureau, advisory committee, etc.: Roche, Consultant fee, speaker bureau, advisory committee, etc.: Takeda Roger Abrahams: Grant monies (from industry related sources): Clinical Research Grant from Boehringer Ingelheim, Consultant fee, speaker bureau, advisory committee, etc.: Boehringer Ingelheim steering committe Leif Bjermer: Fiduciary position (of any organization, association, society, etc, other than ACCP: Principle Investigator, Consultant fee, speaker bureau, advisory committee, etc.: Boehringer Advisory Board Eric Derom: Consultant fee, speaker bureau, advisory committee, etc.: Consultant - Boehringer Ingelheim & Actelion, Consultant fee, speaker bureau, advisory committee, etc.: Speaker - - Boehringer Ingelheim and GSK, Consultant fee, speaker bureau, advisory committee, etc.: Advisory Board - Chiesi & Astra Zeneca Matjaz Flezar: Consultant fee, speaker bureau, advisory committee, etc.: Boehringer Ingelheim Advisory Board, Grant monies (from industry related sources): Principle Investigator in Boehringer Ingelheim Clinical Trials Jacques Hébert: Other: Board Memeber: Novartis, King (Pfizer), Palladin, Merck, CSL Behring, Other: Centre de Recherche involved with clinical trials sponsored by Boehringer Ingelheim, Merck, Novartis, Circassia CSL Behring Lars Groenke: Employee: Boehringer Ingelheim Kay Tetzlaff: Employee: Boehringer Ingelheim Lawrence Korducki: Employee: Boehringer Ingelheim Holger Huisman: Employee: Boehringer Ingelheim Stella Waitere-Wijker: Employee: Boehringer Ingelheim Lorcan McGarvey: Consultant fee, speaker bureau, advisory committee, etc.: Consultant fees for adjudication activity on COPD clinical trials The following authors have nothing to disclose: Anthony Veale

This presentation will describe the Phase III study investigating the safety and efficacy of a tiotropium plus olodaterol fixed dose combination therapy for the treatment of COPD

Chest. 2014;146(4_MeetingAbstracts):49A. doi:10.1378/chest.1994521

SESSION TITLE: COPD Treatment Posters

SESSION TYPE: Original Investigation Poster

PRESENTED ON: Wednesday, October 29, 2014 at 01:30 PM - 02:30 PM

PURPOSE: To assess the effects of maintenance therapy with tiotropium, a long-acting anticholinergic, on health-related quality of life (HRQoL) in COPD patients using data from 16 clinical trials.

METHODS: Trials included patients with moderate-to-very severe COPD, ≥40 years, smoking history >10 pack-years. Tiotropium was delivered via HandiHaler® (Tio HH; 13 trials) or Respimat® inhaler (Tio R; 3 trials). In the HandiHaler trials, patients were randomized to daily tiotropium 18 μg (13 trials; n=5646), placebo (11 trials; n=4853) and (2 trials) /or (2 trials) active comparator (n=584). In the Respimat trials, patients were randomized to tiotropium 5 μg (Tio R5; 3 trials; n=2219), tiotropium 10 μg (Tio R10; 2 trials, n=619) or placebo (3 trials; n=2318). Treatment duration was 12 weeks to 4 years in the HandiHaler trials and 48 weeks in the Respimat trials. Assessments included: HRQoL, evaluated using the St George’s Respiratory Questionnaire (SGRQ) total score, and the proportion of patients with a minimal clinically important difference (MCID) of ≥4 decrease in SGRQ total score from baseline to trial end.

RESULTS: In the majority of the trials, the mean change in SGRQ total score was statistically significant (P<0.05; tiotropium vs placebo, 12/14 trials; tiotropium vs active comparator, 1/4 trials). Mean change in SGRQ for Tio HH compared with placebo ranged from -1.37 to -6.52 (P<0.05 to <0.0001, 9 trials; P>0.05, 2 trials) and from -1.24 to -4.86 compared with active control (P<0.01, 1 trial; P>0.05, 3 trials). The SGRQ MCID was met in 6 out of 13 HandiHaler trials (5 placebo-controlled, 1 active comparator). In the Respimat trials, the mean change in SGRQ compared with placebo ranged from -2.94 to -3.71(P<0.01, 3 trials) for Tio R5 and -3.45 to -4.24 (P<0.01, 2 trials) for Tio R10. In the HandiHaler trials, responder rate differences for Tio HH vs placebo ranged from 4.4-13.2% at 6 months (9 trials), 7.4-20.4% at 12 months (5 trials) and 8.3-9.0% at 24 months (2 trials). In the Respimat trials responder rate differences at 48 weeks ranged from 7.8-11.8% for Tio R5 (3 trials) and 8.4-13.0% for Tio R10 (2 trials).

CONCLUSIONS: Similar improvements in HRQoL were seen in COPD patients on maintenance therapy with tiotropium whether delivered via HandiHaler or Respimat. Treatment effects differed slightly between trials, possibly due to variations in study design.

CLINICAL IMPLICATIONS: Maintenance therapy with tiotropium delivered via HandiHaler or Respimat can significantly and consistently improve HRQoL in COPD patients.

DISCLOSURE: Donald Tashkin: Grant monies (from industry related sources): BI, Pearl, Sunovion, GSK , Consultant fee, speaker bureau, advisory committee, etc.: BI, AZ, Novartis, Pearl, Sunovion, Forest, Pfizer Paul Jones: Consultant fee, speaker bureau, advisory committee, etc.: BI Thomas Leonard: Employee: BI Dacheng Liu: Employee: BI Norbert Metzdorf: Employee: BI Valentina Zubek: Employee: BI Robert Wise: Grant monies (from industry related sources): GSK, BIPI, Merck, Pearl, Consultant fee, speaker bureau, advisory committee, etc.: GSK, BIPI, Mylan, Spiration, Sunovion, Pulmonx, Intermmune, Merck, Janssen, Medimmune, AZ, Novartis, Genentech

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Chest. 2014;146(4_MeetingAbstracts):50A. doi:10.1378/chest.1994921

SESSION TITLE: COPD Treatment Posters

SESSION TYPE: Original Investigation Poster

PRESENTED ON: Wednesday, October 29, 2014 at 01:30 PM - 02:30 PM

PURPOSE: Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines recommend oral steroids to be used for acute exacerbations of Chronic Obstructive Pulmonary Disease (COPD). This has endorsed by professional societies including American Thoracic Society and European Respiratory Society. We conducted a survey to check the route and dose of steroids used for non-ICU in-patients with acute exacerbations of COPD (AECOPD).

METHODS: Physicians were asked about the dose and route of steroids they order for non-ICU inpatient AECOPD, and if they practice in private or academic hospital. Questions were conducted through ACCP e-community network where discussions have been posted on 4 networks including Critical Care, Interstitial and Lung Disease, Respiratory Care, and Clinical Research.

RESULTS: The discussion topics were accessible to more than 5000 members and they were viewed by 167 members. We had a total of 26 replies including 18 from United Stated, India 1, Pakistan 1, Brazil 1, Lebanon 2, United Kingdom 1, Germany 1, and France 1. Response rate 15.6%. IV steroids were more frequently than oral steroids by 16 out of 26 responders (61.5%); twelve of these surveys were from Unites States. Oral steroids were used by 9 (34.6%), and inhaled steroids by 1 3.9%(France). 18 out 26 surveys came from physicians who practice in an academic settings and 11 out of 18 use IV steroids. Methylprednisolone 60mg every 6 hours was the most frequently used intravenous steroid (11 out of 14 surveys), followed by hydrocortisone 100-200 mg every 8 hours. Prednisone 40-60 mg daily for 5 to 10 days was the most commonly used oral steroid.

CONCLUSIONS: View and response rates for surveys in ACCP e-communities remain low. Initial pilot results show intravenous (IV) steroids continued to be used commonly for AECOPD exacerbations especially in the United States in our small sample although guidelines have not shown benefit of IV over oral steroids.

CLINICAL IMPLICATIONS: The results of this survey warrants further studies and large scale survey that is planned later during the year.

DISCLOSURE: The following authors have nothing to disclose: Ali Eskandar, Feras Mahdi, Amanda Keith, Akram Khan

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Chest. 2014;146(4_MeetingAbstracts):51A. doi:10.1378/chest.1994030

SESSION TITLE: COPD Treatment Posters

SESSION TYPE: Original Investigation Poster

PRESENTED ON: Wednesday, October 29, 2014 at 01:30 PM - 02:30 PM

PURPOSE: COPD exacerbations can significantly worsen patients' disease-related morbidity and mortality. Arformoterol and formoterol are the only two FDA approved nebulized LABAs for COPD maintenance. The real-world comparative evidence on their impact on COPD exacerbations is lacking.

METHODS: This retrospective cohort study used data from a large claims database. Included patients were: age≥35 years, with ≥2 fills of arformoterol or formoterol between 01/01/2008-12/31/2012 (first nebulized LABA as index), COPD diagnosis (ICD-9-CM 491.x, 492.x, 496.x) on ≥2 outpatient or ≥1 inpatient claims, continuous enrollment 180-day pre- and 360-day post-index, and no nebulized LABA or asthma diagnosis during the pre-index period. Adherence to index drug was computed using proportion of days covered (PDC) in the 360-day post-index. To assess the impact of treatment on study outcome, the study was limited to those adherent or partially adherent (A/PA, PDC≥60%) to their index drug. Exacerbations were measured by COPD-related hospitalizations, emergency room visits, or office visits accompanied by antibiotics or corticosteroids fills within 30 days. Chi-square and t-test were used to compare the two cohorts (alpha=0.05). A Cox proportional hazards model estimated the risk of exacerbations as a function of index nebulized LABA and demographic and clinical characteristics.

RESULTS: A total of 417 (arformoterol=274, formoterol=143) patients (mean age=70.7, 45% females) were included. Compared to formoterol users, arformoterol users had lower pre-index COPD exacerbations (57% vs. 69%), lower pre-index use of oral antibiotics (62% vs. 73%) and nebulized SABA (33% vs. 47%), higher Charlson Comorbidity Index score (mean 2.6 vs. 2.3), all p<0.05. Patients receiving arformoterol had lower post-index incidence of exacerbations (70.4% vs. 80.4%, p<0.05), and fewer post-index exacerbations (mean 3.1 vs. 3.8, p=0.099). After controlling for patients’ baseline demographics, pre-index COPD-related comorbidities and healthcare use, arformoterol users had a 19% marginally lower risk of exacerbations than formoterol users (HR 0.81, 95% CI 0.64-1.03).

CONCLUSIONS: In this study focusing on A/PA users, COPD patients on arformoterol were found to have a lower incidence of exacerbations after controlling for other confounders, compared to those on formoterol.

CLINICAL IMPLICATIONS: This study suggests that the choice of nebulized LABA may influence the occurrence of COPD exacerbations.

DISCLOSURE: Charles Maken: Employee: IMS Health Yaozhu Chen: Employee: IMS Health Vamsi Bollu: Shareholder: Sunovion Pharmaceuticals Inc.

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Chest. 2014;146(4_MeetingAbstracts):52A. doi:10.1378/chest.1991671

SESSION TITLE: COPD

SESSION TYPE: Original Investigation Slide

PRESENTED ON: Wednesday, October 29, 2014 at 08:45 AM - 10:00 AM

PURPOSE: High Resolution Computed Tomography Scan (HRCT) is now being used as an important diagnostic test in COPD patients. Various new patterns like emphysema (centriacinar, panacinar, and paraseptal) bronchial wall thickening, bronchiectasis, bullous disease, pulmonary hypertension and other vascular changes are being identified in these patients. In this present study, we have evaluated various HRCT features to identify morphological patterns in COPD and correlated the same with clinical features.

METHODS: 50 patients (42 males and 8 females) of stable COPD attending a tertiary referral hospital were included. According to HRCT findings, 3 predominant patterns were identified as Emphysema, Bronchial wall thickening and Bronchiectasis. This was correlated with smoking status, Body Mass Index, 6 min walk test (6MWT), frequency of exacerbations, and spirometry parameters including bronchodilator reversibility.

RESULTS: COPD patients with Emphysema phenotype on HRCT were more severely affected i.e. they had severe COPD as per GOLD guidelines (55%) with lower (<250m) 6MWT values (55%) and poor bronchodilator reversibility (82.50%) on spirometry. 52% COPD patients with bronchial wall thickening phenotype predominantly had severe COPD as per GOLD guidelines with lower (<250m) 6MWT values (72.22%) and poor bronchodilator reversibility (63.88%) on spirometry. 52% COPD patients with bronchiectasis phenotype predominantly had moderate COPD as per GOLD guidelines. They had better (>250m) 6MWT values (73.68%) with good bronchodilator reversibility (68.42%) on spirometry. However, these patients had higher frequency of infective exacerbation compared with other two groups (52.63%). Correlation of 6 min walk test values among 3 phenotypes of COPD was significant (F value 4.341, P value 0.016).

CONCLUSIONS: Our study results indicate that airway limitation derived from three spirometrically gated thin section CT scans obtained at defined anatomic levels can enable the differentiation of patients who have COPD with emphysema, bronchial wall thickening and bronchiectasis, which is a distinction that correlates with pulmonary functional impairment.

CLINICAL IMPLICATIONS: Spirometry and FEV1 is currently used to diagnose severity of COPD. However this is less accurate for small airway dysfunction (i.e. airflow in airways with internal diameter <2mm). The application of CT imaging provided additionally clinically important information as a non-invasive biomarker of COPD and is crucial for determining the appropriate therapeutic strategy.

DISCLOSURE: The following authors have nothing to disclose: Umang Shah, Jayalakshmi Tk, Girija Nair, Lavina Mirchandani, Aparna Iyer, Abhay Uppe

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Chest. 2014;146(4_MeetingAbstracts):53A. doi:10.1378/chest.1988150

SESSION TITLE: COPD

SESSION TYPE: Original Investigation Slide

PRESENTED ON: Wednesday, October 29, 2014 at 08:45 AM - 10:00 AM

PURPOSE: The purpose of this study is to investigate the unsettled relationship between resting hyperinflation and exercise ventilation among patients with chronic obstructive pulmonary disease (COPD) undergoing incremental treadmill exercise testing.

METHODS: Fifty five patients with COPD and 25 normal subjects underwent resting pulmonary function testing and incremental exercise test (IET) on treadmill. Ventilation and gas exchange data were collected on all subjects and exercise duration determined.

RESULTS: Inspiratory capacity/total lung capacity (IC/TLC) ratio was lower in COPD patients compared to normal subjects (0.39 vs 0.47 P=0.009) and so was exercise duration (5.4 vs 8.5 minutes, P=0.0001). The tidal volumes during exercise were lower in COPD patients compared to normal subjects (1.27L vs 2.01L, P < 0.001). There was a correlation between a reduced IC/TLC and peak oxygen consumption (peak VO2) among COPD patients (r=0.35) but not among controls. The reduced exercise capacity in COPD patients was associated with a reduced forced expiratory volume in one second (FEV1) and lower IC/TLC. Also among COPD patients, those with an IC/TLC < 0.25 had lower exercise capacity compared to those with an IC/TLC > 0.25 (peak VO2 0.95 L/min vs 1.26 L/min; P=0.05). The low IC/TLC ratio group had lower FEV1 (0.94L vs 1.5L; p=0.01) and lower tidal volumes (0.93 L vs 1.33 L; P=0.01) compared to high IC/TLC group.

CONCLUSIONS: The mechanisms of reduced exercise tolerance in patients with COPD are several and include combination of airflow obstruction, static and dynamic hyperinflation and dead space ventilation during exercise. A low resting IC/TLC, FEV1 and low exercise tidal volume are predictors of reduced exercise tolerance among patients with COPD.

CLINICAL IMPLICATIONS: Physicians who take care of COPD patients should consider combination of low resting IC/TLC, low FEV1 and low exercise tidal volume as marker of reduced exercise tolerance. The potential explanation of these finding is exercise related increased respiratory system resistance.

DISCLOSURE: The following authors have nothing to disclose: Mumtaz Zaman

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Chest. 2014;146(4_MeetingAbstracts):54A. doi:10.1378/chest.1980555

SESSION TITLE: COPD

SESSION TYPE: Original Investigation Slide

PRESENTED ON: Wednesday, October 29, 2014 at 08:45 AM - 10:00 AM

PURPOSE: To assess high resolution computed tomography (HRCT) characteristics in non-smoking COPD patients attending a COPD Clinic at a tertiary level medical college hospital.

METHODS: Out of 507 COPD patients (men, 404 and women, 103) diagnosed as per GOLD guidelines and who were attending the COPD Clinic at our Institute during the study period, 63 patients (men, 16 and women, 47) had no smoking history. HRCT characteristics in these non-smoking COPD patients were studied and their correlations with risk factors other than smoking were analyzed.

RESULTS: Out of 507 COPD patients, 63 were non-smokers; 45.63% of women and 3.9% of men had no smoking history. The mean age of non-smoking COPD patients was 58.43 ± 11.75 years. The duration of illness was 7.81 ± 7.06 years. The FEV1 was 1.05 ± 0.44 L. The risk factors in non-smoking COPD were: cooking using solid fuel (85.7%), occupational exposure (84.1%), passive smoking (ETS) (76.2%), heating using solid fuel (74.6%), and air pollution only in (23.8%) of patients. Features of emphysema were observed in 27/63 non-smoking COPD patients. Centriacinar emphysema was most frequent type (25.4%) followed by panacinar (19.0%) and paraseptal (6.3%) emphysema. The emphysema extent was related to duration of exposure to air pollution. The characteristic patterns observed over HRCT were: directly visible small airways (66.5%), vascular attenuation (30.2%), mosaic attenuation (23.8%), vascular distortion (11.1%), saber sheath trachea (11.1%), increased thoracic cross sectional area (76.2%), increased thoracic cage ratio (28.6%), increased sterno-aortic distance (7.9%). Exposure to cooking smoke, past history of asthma and BMI strongly correlated with major airway wall thickness. Extent of occupational exposure was strongly related to hyperinflation features of HRCT. Regression analysis revealed the risk factors in non-smoking COPD patients predicted major airway wall thickness but did not predict variations in features of hyperinflation or extent of emphysema.

CONCLUSIONS: We observed HRCT characteristics distinct to COPD in significant proportion of non-smoking COPD patients. Many of these HRCT features had strong correlations with associated risk factors in these nonsmoking COPD subjects.

CLINICAL IMPLICATIONS: This is perhaps first study that has characterized HRCT features in non-smoking COPD patients and their correlations with risk factors other than smoking. HRCT has been observed to be an important diagnostic tool in smoking related COPD in prior studies.

DISCLOSURE: The following authors have nothing to disclose: Prem Parkash Gupta, Rohtas Yadav, Sumit Mittal

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Chest. 2014;146(4_MeetingAbstracts):55A. doi:10.1378/chest.1994427

SESSION TITLE: COPD 30-Day Readmission

SESSION TYPE: Original Investigation Slide

PRESENTED ON: Tuesday, October 28, 2014 at 11:00 AM - 12:15 PM

PURPOSE: To compare COPD Assessment Test (CAT) scores & OSA STOPBANG scores with severe, oxygen dependant COPD patients while enrolled in a home respiratory program focused on readmission reduction.

METHODS: The Discharge, Assessment, and Summary @ Home (D.A.S.H., Klingensmith HealthCare, Ford City, PA) program was implemented for home oxygen dependent patients throughout Western Pennsylvania. The program uses face-to-face visits with a respiratory therapist at days 2, and 30 following hospital discharge. Additionally an enhanced DASH is available for patients who qualify for home health services which incorporates Nursing and OT/PT/RT services over 60 days. Weekly care coordinator phone interviews supplement the respiratory therapy visits during that same time period. The program uses educational, behavioral modification, skills training, oxygen titration during activities of daily living, clinical & medication assessment, and adherence data collection. The program has had over 1200 patients enrolled over the last four years and has reduced 30 COPD readmission rate from the mid twenties to below 12%. Patients entering the program were screened for OSA by the respiratory therapist or home care nurse using the STOPBANG questionnaire & additionally the patient completed a COPD dyspnea survey (CAT).

RESULTS: 396 consecutive patients with COPD were enrolled into the DASH program. The thirty day readmission rate (all cause) for this group was 48 (12.1%). 94 of the 396 patients had no STOPBANG score on their initial home visit, of the remaining 302 patients, 15 (5%) were currently on PAP therapy. 287 patients were screened for OSA resulting in 109 (38%) scoring a 3 or higher on the 8 questions. Additionally the 109 patient’s CAT scores were surveyed and 65 (60%) scored a 10 or higher (20/65 were greater than 20), indicating a higher risk of exacerbations according to evaluations of the GOLD 2011 guidelines1.

CONCLUSIONS: A significant (65%) portion of post exacerbation oxygen dependant COPD patients who screened positive (3/8 questions) for OSA, had CAT scores above 10, indicating unresolved dyspnea symptoms and potentially a higher risk of exacerbations according to the COPD 2011 guidelines.

CLINICAL IMPLICATIONS: OSA overlap with COPD is a significant portion of the severe oxygen dependant COPD population. Screening for OSA and identifying unresolved dyspnea can potentially lead to reduced exacerbations, readmissions and mortality.

DISCLOSURE: Dan Easley: Employee: Employee of Klingensmith HealthCare Kimberly Wiles: Employee: Employee of Klingensmith HealthCare The following authors have nothing to disclose: Lyndave Francis, Tariq Cheema, Daniel Shade, Anil Singh

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Chest. 2014;146(4_MeetingAbstracts):56A. doi:10.1378/chest.1993272

SESSION TITLE: COPD 30-Day Readmission

SESSION TYPE: Original Investigation Slide

PRESENTED ON: Tuesday, October 28, 2014 at 11:00 AM - 12:15 PM

PURPOSE: Efforts to reduce 30-day readmissions are resource intensive. Healthcare systems need to target interventions at patients with the highest risk. The addition of physical functioning has been found to increase the performance of previously published risk prediction models. We examined whether functional status documented during routine nursing care in the 24 hours prior to discharge was an independent predictor of 30-day readmission risk in patients with COPD.

METHODS: Patients from a large integrated healthcare system were included in this retrospective cohort study if they were hospitalized for COPD (following the Centers for Medicare and Medicaid Services and National Quality Forum proposed criteria) and discharged between January 1, 2011, and December 31, 2012, age 40+, on a bronchodilator or steroid inhaler, alive at discharge, and continuously enrolled in the health plan 12 months prior to the index admission and at least 30-days post discharge. Our main outcome was 30-day all-cause readmission. Functional status was documented as part of routine nursing care within 24 hours prior to discharge as follows: bed bound (Level 1), able to sit (Level II), stand next to bed (Level III), walk <50 feet (Level IV), and walk >50 feet (Level V).

RESULTS: The sample included a total of 2,831 patients (n=3,536 index admissions) with a mean age of 72±11. The 30-day readmission rate was 20%. Multivariate analyses showed that patients who were non-ambulatory at discharge (Levels 1-III) were more than twice as likely to be re-admitted within 30-days compared to patients who were able to walk more than 50 feet (RR: 2.12, 95% CI 1.60 to 2.82, p<.001). There was no significant difference in readmission risk between patients who were classified as Level IV or V (p>.05).

CONCLUSIONS: Patients with COPD who were non-ambulatory within 24 hours prior to discharge were at significantly greater risk of readmission compared to ambulatory patients.

CLINICAL IMPLICATIONS: When available, functional status should be used to risk stratify patients for more intensive supportive interventions post discharge.

DISCLOSURE: The following authors have nothing to disclose: Annie Harrington, June Rondinelli, Cecelia Crawford, Smita Desai, In-Liu Liu, Janet Lee, Michael Gould, Huong Nguyen

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Chest. 2014;146(4_MeetingAbstracts):57A. doi:10.1378/chest.1993327

SESSION TITLE: COPD 30-Day Readmission

SESSION TYPE: Original Investigation Slide

PRESENTED ON: Tuesday, October 28, 2014 at 11:00 AM - 12:15 PM

PURPOSE: The average readmission rate in the U.S per Medicare was estimated to be 18.4% in 2012. According to data released in 2013, 2,213 hospitals were penalized about $280 million due to readmissions. The published thirty-day readmission rate for patients discharged after COPD exacerbations is 23%. The purpose of our study was to determine whether patients who kept primary care appointments within two weeks of hospital discharge were less likely to be readmitted for COPD.

METHODS: A retrospective chart review was performed on all patients discharged from Nashville General Hospital (NGH), starting on August 1st 2013, looking at the first 100 patients with a primary diagnosis of COPD exacerbation. These patients were all given an appointment with a primary care provider (PCP) within 2 weeks of discharge. The thirty-day readmission rate was compared for patients who kept their appointment with their PCP with those who didn’t. Other variables collected included baseline characteristics, insurance status and use of controller medications.

RESULTS: 100 patients were discharged from NGH with a primary discharge diagnosis of COPD exacerbation. Twenty-three of these patients were readmitted within thirty days (23%). Between August 1st 2013 and December 31st 2013, 64 patients kept their PCP appointments. Six of these patients required readmission within 30 days (9%). Thirty-six patients did not follow up as scheduled. Seventeen of these patients required readmission within 30 days (47%). Statistically significant factor(s) for 30 day readmission rate included: seeing PCP within 2 weeks of hospital discharge (P<0.001), and number of COPD exacerbation admissions between 2011 and 2012 (p=0.036). No other factors were found to be significant including: age, insurance status, use of controller medications, or FEV1.

CONCLUSIONS: 30 day readmission rates are a large problem in the US, and recent legislation plans to link reimbursement to readmission rates. Patients who returned to visit their PCP at NGH within 2 weeks of hospital discharge for COPD exacerbation had lower risk of readmission within 30 days. Other factors such as FEV1, age and insurance status did not affect the 30-day readmission rate.

CLINICAL IMPLICATIONS: We found that in our patient population, those patients with COPD exacerbations who were seen by a PCP within 2 weeks of hospital discharge were less likely to be readmitted in 30 days. Hospital interventions that could improve follow up rates maybe a low cost way to lower 30 day readmission rates.

DISCLOSURE: The following authors have nothing to disclose: Bimaje Akpa, Todd Rice, Richard Fremont

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Chest. 2014;146(4_MeetingAbstracts):58A. doi:10.1378/chest.1991911

SESSION TITLE: COPD 30-Day Readmission

SESSION TYPE: Original Investigation Slide

PRESENTED ON: Tuesday, October 28, 2014 at 11:00 AM - 12:15 PM

PURPOSE: There is limited data on the epidemiologic characteristics and outcomes of patients with severe COPD requiring invasive mechanical ventilation. The prognosis of acute respiratory failure requiring invasive mechanical ventilation is believed to be grim in this population. The purpose of this study was to illustrate the epidemiologic characteristics and outcomes of patients with severe COPD requiring mechanical ventilation.

METHODS: Retrospective study of patients admitted to a quaternary referral medical intensive care unit between January 2008 and December 2012 with a diagnosis of severe COPD (based on clinical history & chronic hypercapnea/hypoxia) and requiring invasive mechanical ventilation for acute respiratory failure.

RESULTS: We evaluated 677 patients with an established diagnosis of severe COPD who were mechanically ventilated over the study period. 47% were males, and the mean age was 63.7±12.4 years. 122 (17.9%) were given a trial of NIPPV prior to IPPV. 456 (67.35%) were intubated because of a respiratory etiology, but of these only n=73 (16%) had a primary diagnosis of COPD exacerbation as the cause of intubation. Non-pulmonary causes of admission were rare. The median duration of mechanical ventilation was 3 days (IQR 2-7). Duration of ICU stay was 4.9 days (IQR 2.3-9.3). 165 (24.4%) patients died in the ICU. ICU mortality for COPD exacerbation was lower than patients admitted for other reasons (16.4% vs 25.1%). Ultimately, 69.9% patients survived the hospitalization of which 25.2% patients were discharged home while the reminder went to LTAC or SNF. The median duration of hospitalization was 12.5 days (IQR 7- 21.6). 123 (18.16%) (n=123) patients were readmitted for respiratory failure requiring mechanical ventilation during the study period. The mean number of readmissions for these patients was 1.69± 1.3 episodes. There was a higher rate of readmission (30.13 vs 16.7%) in patients where COPD exacerbation was identified as the primary diagnosis at each admission.

CONCLUSIONS: Overall survival in patients with severe COPD undergoing mechanical ventilation is similar to other groups of patients undergoing mechanical ventilation described in the literature.

CLINICAL IMPLICATIONS: Patients with severe COPD have a favorable ICU survival after mechanical ventilation for acute respiratory failure. These patients have a similar rate of failure of non-invasive mechanical ventilation, and share overall functional outcomes with previous descriptions of mechanically ventilated patients with critical illness.

DISCLOSURE: The following authors have nothing to disclose: Shruti Gadre, Abhijit Duggal, Jorge Guzman

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Chest. 2014;146(4_MeetingAbstracts):59A. doi:10.1378/chest.1987013

SESSION TITLE: COPD 30-Day Readmission

SESSION TYPE: Original Investigation Slide

PRESENTED ON: Tuesday, October 28, 2014 at 11:00 AM - 12:15 PM

PURPOSE: COPD affects over 13 million adults in the United States and is the third leading cause of death. Hospitalizations due to acute exacerbations of COPD (AECOPD) and early re-admission are major contributors to morbidity, mortality, and the economic impact of this chronic disease. We evaluated the following modifiable risk factors: post-discharge symptom reporting, post-discharge follow-up and medication adherence to assess whether these factors contribute to re-admission rates.

METHODS: After approval by the institutions Human Subjects Committee, discharge data were analyzed on 47 patients re-admitted within 30 days of discharge for an AECOPD between March 2012 and February 2013. Measures included post-discharge symptom reporting by the patient, completion of a follow-up visit with the patient's PCP or pulmonary physician, and medication adherence at time of re-admission. Descriptive statistics were generated when applicable.

RESULTS: Forty seven re-admissions were evaluated which represented 22 percent of AECOPD admissions for the study period. Sixty-two percent of re-admissions occurred within 2 weeks of discharge. Sixty and 89 percent of patients reported symptoms within 3 days of hospital discharge and one day of re-admission, respectively. Only 24 percent of patients contacted a provider prior to re-admission. Seventy-seven percent of subjects were provided a follow-up appointment within 4 weeks of discharge, and 40 percent of patients were re-admitted prior to this follow-up. There was no significant difference in providing follow-up appointment based on discharge day of the week. Eighty percent of patients were adherent to their discharge medications.

CONCLUSIONS: Post-discharge symptom reporting, discharge follow-up, and adherence to medications are modifiable risk factors that could be areas of focus to reduce re-admissions for AECOPD. Our results indicate that a significant percentage of patients do not report symptoms to providers and are re-admitted prior to follow-up. It is conceivable that patient centered education programs focused on symptom reporting and COPD action plans as well as improved discharge planning to arrange earlier follow-up, including phone contact within 3 days of discharge, may improve patient care and reduce AECOPD re-admissions.

CLINICAL IMPLICATIONS: These results will guide a multidisciplinary team to formalize a care pathway for our institution's COPD population with goals of limiting care variation, improving patient satisfaction, and reducing re-admission rates.

DISCLOSURE: The following authors have nothing to disclose: Jessica Barks, Edward Ellerbeck, Patrick Harper, Travis Gratton, John Meyer, Matthew Wilson, Heath Latham

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Chest. 2014;146(4_MeetingAbstracts):60A. doi:10.1378/chest.1991580

SESSION TITLE: COPD Biomarkers

SESSION TYPE: Original Investigation Slide

PRESENTED ON: Monday, October 27, 2014 at 07:30 AM - 08:30 AM

PURPOSE: COPD is an independent risk factor for lung cancer. The pathogenesis of both diseases plays a crucial role specific microenvironment created by chronic inflammation. COPD is characterized by increased accumulation of granulocytes, macrophages, lymphocytes and dendritic cells. Little is known about the impact of COPD on the microenvironment of different subpopulations of T lymphocytes other than Th1 i Th2 (Th9, Th17, Th22). Their role in the pathogenesis of diseases in which inflammation is a substrate depends on the specific secretion of mediators, such as IL-17, which promotes secretion by the respiratory epithelium chemokines CXCL1, CXCL6, CXCL8 receptor ligands which CXCR2 and GM-CSF i G-CSF. These factors affect the survival of neutrophils, which are becoming important drivers of promoting them dependent inflammation in COPD. In contrast, for the maintenance of peripheral immune tolerance are responsible, among others, regulatory T cells. The aim: To attempt to characterize the pro-inflammatory microenvironment in the course of COPD in terms of lymphocyte profile.

METHODS: We reviewed cytometric evaluation immunophenotyping bronchial lavage (BAL) and peripheral blood collected from 17 patients with COPD.

RESULTS: In assessing the profile of lymphocyte in peripheral blood and BAL revealed the presence of lymphocytes Th1 (CCR5), Th17 (CCR6), Th22 (CCR10) and T reg. It has been shown a higher percentage of Th1, Th17 and Th22 in peripheral blood, in BAL higher percentage of lymphocytes T reg.

CONCLUSIONS: The attempt to characterize the pro-inflammatory microenvironment in the course of COPD in terms of lymphocyte profile confirms the presence of an active peripheral and local inflammatory process in the field of lymphocyte profile. Further work is necessary taking into account the profile of monocyte, granulocyte and granulocyte and lymphocyte regulatory cells.

CLINICAL IMPLICATIONS: The preliminary results of this study and its continuation in the future mays allow a more accurate assessment of inflammation and predisposition to carcinogenesis in COPD patients

DISCLOSURE: The following authors have nothing to disclose: Halina Batura-Gabryel, Beata Brajer-Luftmann, Agata Nowicka, Mariusz Kaczmarek, Jan Sikora

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Chest. 2014;146(4_MeetingAbstracts):61A. doi:10.1378/chest.1992264

SESSION TITLE: COPD Biomarkers

SESSION TYPE: Original Investigation Slide

PRESENTED ON: Monday, October 27, 2014 at 07:30 AM - 08:30 AM

PURPOSE: Pulmonary and activation-regulated chemokine (PARC)/CC-chemokine ligand-18(CCL-18) is mainly expressed by the antigen presenting cells in lungs.Serum CCL-18 levels were found to be elevated in COPD patients. We aimed to study if serum CCL-18 level can differentiate the frequent exacerbator phenotype of COPD from the infrequent exacerbators.

METHODS: This case-control study was conducted in a tertiary reference center in Turkey.Clinically stable COPD patients and HCs were enrolled.Subjects willing to participate underwent a questionnaire including disease characteristics. Severity of dyspnea and symptoms were assessed by the modified Medical Research Council (mMRC) Dyspnea Scale, and COPD Assessment Test (CAT).Spirometry and six-minute walking test (6MWT) were performed.Serum CCL-18 levels were measured with a commercial ELISA Kit.

RESULTS: Sixty COPD patients and 29 HCs were recruited (mean age:58.4±15.5 years old). COPD patients were grouped as frequent exacerbators (FE-COPD,n=33) and infrequent exacerbators (IE-COPD,n=27) based on exacerbation frequency (≥2/year vs.<2/year). CCL18 levels were elevated in COPD patients when compared with the HCs (p=0.0001).CCL18 values did not differ significantly among IE-COPD and FE-COPD groups, though there was an increasing trend between these groups (p=0.09). The number of COPD exacerbations were associated with the serum CCL-18 levels (r=0.30,p=0.026). Serum CCL-18 levels were inversely correlated with the postbronchodilatorFEV1/FVC, postbronchodilatorFEV1%predicted, and the postbronchodilatorFVC %predicted (r=-0.36,p=0.002;r=-0.42,p=0.001and r= -0.47,p<0.0001,respectively). Elevated serum CCL-18 levels were associated with higher mMRC and CAT scores (r=0.46,p<0.0001;r=0.40,p<0.0001,respectively).Decreased exercise capacity as measured by 6MWD was inversely related with serum CCL-18 levels (r=-0.29, p=0.02.

CONCLUSIONS: We have shown that serum PARC/CCL-18 levels are elavated in COPD patients. Although we observed an increasing trend in CCL-18 levels between IE-COPD and FE-COPD groups, the difference was not significant. Nevertheless, a moderate correlation between frequency of COPD exacerbations and serum CCL-18 level were observed. Further studies are needed to explore these results

CLINICAL IMPLICATIONS: PARC/CCL-18 could be a useful biomarker in COPD, since it is associated with frequency of exacerbations in addition to functional parameters and symptom scores.

DISCLOSURE: The following authors have nothing to disclose: Asli Gorek Dilektasli, Ezgi Demirdogen Cetinoglu, Esra Uzaslan, Ferah Budak, Funda Coskun, Ahmet Ursavas, Ercument Ege

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Chest. 2014;146(4_MeetingAbstracts):62A. doi:10.1378/chest.1987617

SESSION TITLE: COPD Exacerbation Risk

SESSION TYPE: Original Investigation Slide

PRESENTED ON: Wednesday, October 29, 2014 at 02:45 PM - 04:15 PM

PURPOSE: To assess cognitive functions using Mini Mental State Examination (MMSE) questionnaire in COPD patients who had frequent acute exacerbations in past and to compare them with those COPD patients who had infrequent acute exacerbations in past.

METHODS: The diagnosis of COPD was made as per recent GOLD guidelines. We included 92 eligible COPD patients attending a COPD Clinic at a tertiary level medical college hospital. They were divided into 2 groups on the basis of history of COPD exacerbations during preceding one year: Group 1 (FECOPD Group) included 48 patients who had ≥ 2 acute exacerbations, and Group 2 (I-FECOPD Group) included 44 patients with < 2 acute exacerbations. Patients` clinical data was collected. Spirometric indices were assessed in both groups. MMSE questionnaire was used to assess and compare cognitive functions in both groups.

RESULTS: The mean age of patients in FECOPD group and I-FECOPD group was 62.58±9.61 year and 55.80±11.12 year, respectively. Mean exacerbations in both groups were 2.98±1.25 and 0.55±0.730, respectively. FECOPD group and I-FECOPD group differed significantly with respect to duration of illness (21.73±5.53 year vs. 17.07±5.22 year), FEV1 (1.270±0.247 L vs. 1.711±0.306 L) and PEFR (247.04±49.40 L/min vs. 335.32±61.15 L/min) but not regarding smoking (35.40±10.90 pack years vs. 30.06±10.52 pack years). Cough, expectoration, wheezing and dyspnoea scores were significantly more in FECOPD group. In FECOPD group, MMSE total scores (21.77±2.13 compared to 24.34±1.39) were significantly reduced; all MMSE subset scores were significantly reduced individually. MMSE scores correlated inversely with number of exacerbations, age, duration of illness and correlated directly with spirometric indices. There was no correlation with smoking pack years. Regression model showed frequent acute exacerbations being the strongest predictor of reduction in MMSE score followed by FEV1.

CONCLUSIONS: In our study, cognitive functions were impaired in frequent acute exacerbations group detected using MMSE questionnaire. MMSE scores correlated with number of exacerbations, age, duration of illness and spirometric indices. Frequent acute exacerbations parameter was the strongest predictor of cognitive impairment.

CLINICAL IMPLICATIONS: It is interesting to observe that a simple questionnaire tool, MMSE, was able to provide significant information regarding cognitive dysfunctions in COPD patients with frequent acute exacerbations that may help to improve COPD management.

DISCLOSURE: The following authors have nothing to disclose: Dipti Agarwal, Sushma Sood, Prem Parkash Gupta

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Chest. 2014;146(4_MeetingAbstracts):63A. doi:10.1378/chest.1994339

SESSION TITLE: COPD Exacerbation Risk

SESSION TYPE: Original Investigation Slide

PRESENTED ON: Wednesday, October 29, 2014 at 02:45 PM - 04:15 PM

PURPOSE: GOLD strategy recommends treating patients with recurrent exacerbations of chronic obstructive pulmonary disease (COPD) with inhaled corticosteroids (ICS). The Withdrawal of Inhaled Steroids during Optimized bronchodilator Management (WISDOM) study was designed to evaluate the effects of stepwise withdrawal of ICS in patients with GOLD grade 3-4 COPD and a history of exacerbation who are treated with long-acting muscarinic antagonists + long-acting β-agonists (LAMA+LABA).

METHODS: All patients in the 12-month, double-blind, parallel-group, active-controlled study (NCT00975195) received triple therapy (tiotropium18 µg QD, salmeterol 50 µg BID, and fluticasone 500 µg BID) for a 6-week run-in period. Following this, baseline assessments were made and patients randomized 1:1 to continue triple therapy or stepwise withdrawal of ICS over 12 weeks, with dose reduction every 6 weeks. We report time to first moderate to severe on-treatment exacerbation (primary end point; non-inferiority margin pre-defined as a hazard ratio of <1.2), along with results for the following subgroups: geographic region, age, sex, smoking status, baseline body mass index, and previous COPD therapy.

RESULTS: 2485 patients were treated (2049 male), with a mean age of 63.8 years and mean forced expiratory volume in 1 second of 0.98 L (34.2%) at baseline. The risk of experiencing an on-treatment COPD exacerbation with ICS withdrawal was non-inferior to continued ICS therapy (hazard ratio 1.058; 95% CI 0.941, 1.189). Similar results were seen in a sensitivity analysis that included post-treatment exacerbations (hazard ratio 1.061; 95% CI 0.945, 1.192), and in all pre-defined sub-groups analyzed. No significant safety signals were identified.

CONCLUSIONS: The risk of moderate to severe exacerbation after stepwise ICS withdrawal was comparable to continued ICS treatment in patients with GOLD grade 3-4 COPD receiving LAMA+LABA.

CLINICAL IMPLICATIONS: ICS may be successfully withdrawn in patients receiving LAMA+LABA without significantly increasing the risk of COPD exacerbation. Funding: Boehringer Ingelheim. Editorial assistance: Complete HealthVizion.

DISCLOSURE: Helgo Magnussen: Consultant fee, speaker bureau, advisory committee, etc.: Almirall, Boehringer Ingelheim, Chiesi, Berlin-Chemie, Novartis, Other: I am an employee of PRI. PRI recieved payments for the conduct of this study Bernd Disse: Employee: Boehringer Ingelheim Roberto Rodriguez-Roisin: Consultant fee, speaker bureau, advisory committee, etc.: Boehringer Ingelheim - Speaker - Fee for lecturing, Consultant fee, speaker bureau, advisory committee, etc.: Novartis - Speaker - Fee for lecturing, Consultant fee, speaker bureau, advisory committee, etc.: TEVA - Chair - Fee for participating, Consultant fee, speaker bureau, advisory committee, etc.: BI - Consultant - Fee for advisory board, Consultant fee, speaker bureau, advisory committee, etc.: PEARL - Consultant - Fee for advisory board, Consultant fee, speaker bureau, advisory committee, etc.: TEVA - Consultant - Fee for advisory board Anne Kirsten: Other: I am an employee of PRI. PRI recieved payment for the conduct of this study Henrik Watz: Consultant fee, speaker bureau, advisory committee, etc.: Almirall, Boehringer Ingelheim, Novartis, Astra Zeneca, GSK, Berlin-Chemie, Chiesi, Other: Iam an employee of PRI. PRI recieved payment for the conduct of this study Kay Tetzlaff: Employee: Boehringer Ingelheim Lesley Towse: Employee: Boehringer Ingelheim Helen Finnigan: Employee: Boehringer Ingelheim Ronald Dahl: Consultant fee, speaker bureau, advisory committee, etc.: Advised on study design and conduct of trails sponsored by Boehringer Ingelheim, Novartis, ALK-Abello and Vectura, Consultant fee, speaker bureau, advisory committee, etc.: Spoken at meetings sponsored by Boehringer Ingelheim, Novartis, ALK-Abello and Vectura Peter Calverley: Consultant fee, speaker bureau, advisory committee, etc.: Boehringer Ingelheim, GSK, Novartis, AZ, Takeda, Grant monies (from industry related sources): Boehringer Ingelheim & Takeda, University grant monies: UK NIHR The following authors have nothing to disclose: Marc Decramer, Pascal Chanez, Emiel Wouters

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Chest. 2014;146(4_MeetingAbstracts):64A. doi:10.1378/chest.1983717

SESSION TITLE: COPD Exacerbation Risk

SESSION TYPE: Original Investigation Slide

PRESENTED ON: Wednesday, October 29, 2014 at 02:45 PM - 04:15 PM

PURPOSE: Although substantial advances have been made in the treatment of chronic obstructive pulmonary disease (COPD), little information is available on whether any change in inpatient outcomes have been exhibited over time in these patients. The aim of this study was to examine temporal trends in outcomes among patients hospitalized with exacerbations of COPD.

METHODS: The Healthcare Cost and Utilization Project’s National Inpatient Sample was utilized to identify a cohort of 5,481,306 adults hospitalized with COPD in the U.S. from 2006-2010. Demographic data and clinical history were recorded in these patients. Outcomes of interest included all-cause inpatient mortality, mechanical ventilation, non-invasive positive pressure ventilation, hospital length of stay, and total hospital charges.

RESULTS: Over the 5-year study period, the average age of hospitalized COPD patients decreased with the greatest percentage of patients less than age 65 years being hospitalized in 2010. Hospitalization rates for women also increased. Diabetes mellitus became increasingly prevalent over the 5-year period while renal failure and myocardial infarction became decreasingly prevalent. With respect to outcomes, in-hospital all-cause mortality significantly decreased (p < 0.001). Mechanical ventilation use decreased over the study period, accompanied by a nearly 2-fold increase in non-invasive positive pressure ventilation use. While average hospital length of stay decreased, total hospital charges increased over the study period.

CONCLUSIONS: In patients hospitalized with COPD exacerbation, a significant decrease was noted in rates of in-hospital mortality between the period of 2006-2010, accompanied by less frequent use of mechanical ventilation, more frequent use of non-invasive positive pressure ventilation, shorter hospital length of stay, and higher total hospital charges.

CLINICAL IMPLICATIONS: Increased utilization of non-invasive positive pressure ventilation appears to be linked to earlier hospital discharge and reduced rates of mechanical ventilation. Trends suggest a shifting paradigm in the patient population presenting with COPD exacerbation that recently includes younger, female, diabetic patients.

DISCLOSURE: The following authors have nothing to disclose: Fabio Lima, Tzyy Yun Yen, Jignesh Patel

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Chest. 2014;146(4_MeetingAbstracts):65A. doi:10.1378/chest.1994799

SESSION TITLE: COPD Exacerbation Risk

SESSION TYPE: Original Investigation Slide

PRESENTED ON: Wednesday, October 29, 2014 at 02:45 PM - 04:15 PM

PURPOSE: Prior data suggested that among Anthonisen criteria only an increase in sputum purulence was a predictor of clinical failure among mild to moderate COPD outpatients who did not receive antibiotics. In addition the use of a point-of-care C-reactive protein (CRP) test (cutoff > 40 mg/L) significantly increased the predictive accuracy of failure. However, limited data are available regarding the translation of these findings among hospitalized acutely exacerbated COPD (AECOPD) patients who did not receive antibiotics. Our aim was to determine the risk factors associated with not receiving antibiotics among hospitalized AECOPD patients and the impact on 1-year pneumonia hospitalization rate.

METHODS: We used a prospectively collected dataset included in the EXODUS (Exacerbations of Obstructive Lung disease managed in UK Secondary care) study of COPD patients admitted to one of 12 hospitals around the United Kingdom between 2009 and 2011. Inclusion criteria were hospitalized AECOPD who did not receive antibiotics during admission. Primary outcomes were prediction of receiving antibiotics during hospital admission and 1-year pneumonia hospitalization rate as the dependent variable in the multivariate logistic regression analysis.

RESULTS: Our cohort identified 1421 hospitalized AECOPD patients, of whom n=259 (18%) did not receive antibiotics on admission. There were no statistical significant differences regarding age, gender, comorbid conditions, lung function and COPD therapies among AECOPD patients who did not receive antibiotics and the patients who received antibiotic therapy. However, patients who did not receive antibiotics were more likely to have Anthonisen criteria Type 3 (mild exacerbation) (31% vs. 19%, p<0.001). After correcting for severity of AECOPD by Anthonisen criteria, AECOPD patients who did not receive antibiotics were more likely to have a 1-year pneumonia related hospitalization (13.5% vs. 7.7%, Odds ratio 2.04, 95% Confidence Interval 1.34, 3.10; p=0.001).

CONCLUSIONS: Hospitalized AECOPD had different Anthonisen criteria, but not receiving antibiotics was associated with higher 1-year pneumonia related hospitalization rate. Further studies should assess if colonization with potentially pathogenic bacteria may influence these results.

CLINICAL IMPLICATIONS: Understanding antibiotic selection and initiation in AECOPD hospitalized patients may predict need for hospitalization in COPD patients.

DISCLOSURE: The following authors have nothing to disclose: Luis Reyes, Marcos Restrepo, Oriol Sibila, Stuart Schembri, Peter Williamson, Philip Short, Ahsan Akram, Aran Singanayagam, James Chalmers

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Chest. 2014;146(4_MeetingAbstracts):66A. doi:10.1378/chest.1994300

SESSION TITLE: COPD Exacerbation Risk

SESSION TYPE: Original Investigation Slide

PRESENTED ON: Wednesday, October 29, 2014 at 02:45 PM - 04:15 PM

PURPOSE: To examine seasonal variations in mortality and exacerbations in COPD patients in the TIOtropium Safety and Performance In Respimat® (TIOSPIR®) trial (NCT01126437).

METHODS: TIOSPIR was a large, multinational, randomized, double-blind, double-dummy, event-driven, parallel-group trial in COPD patients age ≥40 years, smoking history ≥10 pack-years, post-bronchodilator FEV1 ≤70% and FEV1/FVC ≤0.70. Patients with a respiratory infection/COPD exacerbation within 4 weeks before randomization were excluded. Inclusion/exclusion criteria allowed study of a broad COPD population. Maintenance therapy, except inhaled anticholinergics, was allowed. Patients were randomized to tiotropium Respimat® 2.5 or 5 μg qd or tiotropium HandiHaler® 18 μg qd. Primary outcomes were times to death (all-cause) and first exacerbation; secondary outcomes included: total exacerbations and those leading to hospitalization. Death rates were calculated from the vital status set (VSS; full follow-up period) and exacerbation rates from the treated set (TS; on-treatment period), taking into account time at risk and treatment duration, respectively. Southern hemisphere (SH) data were shifted by 6 months to compare with northern hemisphere (NH) data; eg, winter: Jun-Aug (SH) and Dec-Feb (NH). Data were pooled since mortality and exacerbations did not differ significantly between treatments.

RESULTS: 17,182 patients were randomized and 17,135 received ≥1 dose of tiotropium at >1200 sites in 43 NH (VSS: n=15,987; TS: n=15,968) and 7 SH (VSS/TS: n=1148) countries (recruitment: May 2010-Apr 2011; study end: May 2013). Overall, death rates were highest in winter (peak 3.38/1000 patient-months) and lowest in the first fall and mid-summer months (2.24 and 2.25, respectively). Overall, first exacerbation rates were highest in winter (peak 25.7) vs summer (lowest 12.2) as were total exacerbation rates (peak 58.9 vs lowest 31.3). First and total exacerbation rates leading to hospitalization were highest in the last winter month (8.64 and 12.6) and lowest in the last summer month (3.37 and 5.50), respectively. NH and SH data examined separately had similar seasonality profiles.

CONCLUSIONS: Overall, in COPD patients, rates of death, exacerbations and exacerbations leading to hospitalization were greatest in winter and lowest in summer.

CLINICAL IMPLICATIONS: The data suggest clinical trials of COPD exacerbation reduction should be conducted in winter and patients and healthcare workers should be educated to increased awareness of these events.

DISCLOSURE: Robert Wise: Grant monies (from industry related sources): GSK, BIPI, Merck, Pearl, Consultant fee, speaker bureau, advisory committee, etc.: GSK, BIPI, Mylan, Spiration, Sunovion, Pulmonx, Intermune, Merck, Janssen, Medimune, AZ, Novartis, Genentech Peter Calverley: Consultant fee, speaker bureau, advisory committee, etc.: GSK, BI, Nycomed, Novartis, Forest, AZ, Takeda Nycomed Kerstine Carter-Scherer: Employee: BI Emmanuelle Clerisme-Beaty: Employee: BI Norbert Metzdorf: Employee: BI Antonio Anzueto: Consultant fee, speaker bureau, advisory committee, etc.: AstraZeneca, Boehringer Ingelheim, Forest Laboratories, GlaxoSmithKline, and Novartis, Grant monies (from industry related sources): Forest, GSK

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Chest. 2014;146(4_MeetingAbstracts):67A. doi:10.1378/chest.1992742

SESSION TITLE: COPD Exacerbation Risk

SESSION TYPE: Original Investigation Slide

PRESENTED ON: Wednesday, October 29, 2014 at 02:45 PM - 04:15 PM

PURPOSE: To investigate the annualized rate of comorbidities in patients with moderate to severe chronic obstructive pulmonary disease (COPD) enrolled in the Understanding the Potential Long-term Impacts on Function with Tiotropium (UPLIFT®) trial (NCT00144339).

METHODS: UPLIFT® was a 4-year, randomized, double-blind, placebo-controlled, parallel-group trial of tiotropium HandiHaler® 18 μg or placebo once daily, involving 5993 patients with moderate to very severe COPD.1 The use of all COPD medications except for inhaled anticholinergics was permitted. The Medical Dictionary for Regulatory Activities (MedDRA) version 13.1 was used to code relevant medical history/concomitant diagnoses (within the past 5 years) as reported by the Investigator at baseline and throughout the 4-year trial period; specific terms (preferred terms [PTs]), standardized MedDRA queries [SMQs] were categorized under system organ classes within MedDRA. For conditions that are known to have a high prevalence in patients with COPD, MedDRA PTs denoting similar conditions and SMQs were pooled.

RESULTS: At baseline 87.8% of patients had documented comorbidities compared with 98.2% at the end of the 4-year study (95.4%, 97.2% and 97.9% patients after years 1, 2 and 3). The cumulative increase in nine comorbidities most frequently observed in patients with COPD, at baseline and years 1 to 4 were: SOC cardiac disease (26.0, 29.6, 32.5, 34.9, and 37.0%); myocardial infarction (SMQ broad; 2.8, 3.8, 4.4, 5.1, and 5.5%); SMQ other ischaemic heart disease (broad; 15.4, 16.4, 17.7, 18.4, and 19.1%); SMQ cardiac arrhythmias (6.4, 8.1, 9.5, 10.8, and 11.8%); SMQ cardiac arrhythmias sub-SMQ tachyarrhythmias (4.4, 5.8, 7.0, 8.0, and 8.9%); PT hypertension (39.6, 42.2, 43.8, 45.4, 46.6%); stroke (2.3, 3.0, 3.8, 4.3, 4.7%); PT diabetes mellitus (5.6, 6.2, 6.7, 7.3, 7.8%); SMQ depression (8.8, 9.6, 10.6, 11.3, 11.9%). There were no notable differences in the incidences of comorbidities between the active treatment and placebo at baseline and during the trial.

CONCLUSIONS: The incidence of comorbidities increased considerably (11.8%) during the 4-year duration of the study.

CLINICAL IMPLICATIONS: Large-scale, long-term studies like UPLIFT® may illustrate how patients with COPD are likely to develop comorbidities over time, by mirroring what happens in daily clinical practice. Reference1Tashkin DP, et al. N Engl J Med. 2008;359:1543-1554. Funded by Boehringer Ingelheim and Pfizer

DISCLOSURE: Donald Tashkin: Consultant fee, speaker bureau, advisory committee, etc.: Boehringer Ingelheim Marc Miravitlles: Consultant fee, speaker bureau, advisory committee, etc.: Boehringer Ingelheim David Price: Consultant fee, speaker bureau, advisory committee, etc.: Boehringer Ingelheim Norbert Metzdorf: Employee: Boehringer Ingelheim Katrin Kupas: Consultant fee, speaker bureau, advisory committee, etc.: Boehringer Ingelheim Bartolome Celli: Consultant fee, speaker bureau, advisory committee, etc.: Boehringer Ingelheim

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Chest. 2014;146(4_MeetingAbstracts):68A. doi:10.1378/chest.1990041

SESSION TITLE: COPD LAMA/LABA

SESSION TYPE: Original Investigation Slide

PRESENTED ON: Monday, October 27, 2014 at 01:30 PM - 02:30 PM

PURPOSE: Studies with SUN-101 (Glycopyrrolate Inhalation Solution) delivered via a novel nebulizer have evaluated once-daily dosing in COPD subjects. This study evaluated the efficacy and safety of twice daily treatment.

METHODS: This was a double‑blind, randomized, placebo‑controlled, parallel group study. Subjects meeting inclusion criteria (35-70 years old with COPD, baseline FEV1 ≥ 30% and ≤70% of predicted and ≥10 pack‑year smoking history) were randomized to one of four doses of SUN-101 (12.5 mcg, n=55; 25 mcg, n=54; 50 mcg n=57; 100 mcg n=59) or placebo (n=57) BID for 28 days. Subjects receiving LABA or LAMA therapy had their treatment replaced with albuterol MDI as “rescue therapy”. Inhaled corticosteroids and roflumilast were continued throughout the study. The primary assessment was change from baseline in morning trough FEV1 after 28 days of treatment.

RESULTS: All doses were associated with rapid onset of bronchodilation which persisted throughout the 24 hour dosing interval. Improvements in trough FEV1 after 28 days of treatment (placebo adjusted LS [95% CI]) were 116.8 mL(36.9, 196.6), 128.4 mL (47.9, 208.9), 146.2 mL (66.7, 225.7) and 177.0 mL (99.2, 254.8) for the 12.5, 25, 50 and 100 mcg doses respectively (p<0.05 vs placebo). Improvements were seen in FEV1 AUC0-12 with changes from baseline (mean [95% CI]) of 135.7 (70.9, 200.5) mL, 163.2 (98.2, 228.3) mL, 105.4 (41.5, 169.4) mL and 183.1 (119.9, 246.2) mL for the 12.5 mcg, 25 mcg. 50 mcg and 100 mcg groups respectively (p<0.05 vs placebo). The most commonly reported adverse events were COPD exacerbations and headache, reported by 3.2% and 2.8% of the population respectively.

CONCLUSIONS: Twice daily treatment with SUN-101 produced dose-dependent increases in trough FEV1 and FEV1 AUC0-12. Although all doses were associated with a mean increase above the MCID of 100 mL, the lower bound of the 95% confidence intervals suggest that lower doses (e.g., 12.5 mcg bid) may be less consistently beneficial. FEV1 AUC0-12 may be a useful endpoint for the assessment of twice daily bronchodilators. Additional work is required to further define the appropriate dose regimen for SUN-101.

CLINICAL IMPLICATIONS: Nebulized glycopyrrolate delivered via the eFlow may represent an additional treatment option for patients with moderate to severe COPD.

DISCLOSURE: Edward Kerwin: Grant monies (from industry related sources): Grants received from Sunovion Pharmaceuticals Inc. Alistair Wheeler: Employee: Employee of Sunovion Pharmaceuticals Inc. Kendyl Schaefer: Employee: Employee of Sunovion Pharmaceuticals Inc. Raymond Claus: Employee: Employee of Sunovion Pharmaceuticals Inc. Ahmet Tutuncu: Other: Clinical Consultant to Sunovion Pharmaceuticals. Nicola Hanania: Grant monies (from industry related sources): Grants received from Sunovion Pharmaceuticals Inc.

Nebulized glycopyrrolate is not approved for the treatment of COPD in any country.

Chest. 2014;146(4_MeetingAbstracts):69A. doi:10.1378/chest.1959389

SESSION TITLE: COPD LAMA/LABA

SESSION TYPE: Original Investigation Slide

PRESENTED ON: Monday, October 27, 2014 at 01:30 PM - 02:30 PM

PURPOSE: To assess long-term safety and efficacy of aclidinium bromide (AB) in moderate to severe COPD patients.

METHODS: In this open-label, 40-week extension study, patients completing a 12-week double-blind lead-in trial (ACCORD II) were transitioned from randomized treatment (twice-daily [BID] placebo [PBO], AB 200µg, or AB 400µg) to AB 400µg BID. Safety, the primary outcome, was assessed via adverse events (AEs) of new or increased intensity during this extension study. Efficacy parameters included change from baseline (visit 2 lead-in) to week 52 in morning predose (trough) FEV1, peak FEV1, and SGRQ total score. Efficacy was analyzed using an ANCOVA.

RESULTS: Of 454 patients completing the lead-in, 448 continued to the extension. Baseline characteristics (visit 2 lead-in) were similar across sequences, except for unexpected imbalances in FEV1 (1.46L PBO-AB400; 1.40L AB200-AB400; 1.25L AB400-AB400) and in the distribution of severe, stage III COPD (37.4% PBO-AB 400; 45.5% AB200-AB400; 53.1% AB400-AB400). The percentage of patients reporting ≥1 AE was similar across groups; the most common (≥5%) were COPD exacerbation (18.1%) and upper respiratory tract infection (5.8%). Most AEs were mild or moderate, and few were related to treatment (~8% in each sequence): 7.5% PBO-AB400; 8.4% AB200-AB400; and, 8.8% AB400-AB400. Discontinuations due to AEs occurred in 6.8% PBO- AB400, 6.5% AB200-AB200, and 4.8% (AB400-AB400) of patients. Most frequently reported potential anticholinergic events (≥1%) were urinary tract infection (2.5%) and constipation (1.3%), with similar rates across groups. At 52 weeks, changes from baseline in trough FEV1 were 44 mL (PBO-AB400), 29 mL (AB200-AB400) and 48 mL (AB400-AB400). Changes from baseline to week 52 in peak FEV1 were 184mL (PBO-AB400), 176mL (AB200-AB400) and 172mL (AB400-AB400). Changes from baseline to week 52 in SGRQ were -8.25 (PBO-AB400), -6.19 (AB200-AB400) and -6.82 (AB400-AB400) units.

CONCLUSIONS: AB 400µg was well-tolerated over 1 year, with a similar safety profile among treatment sequences. Although unexpected baseline imbalances across groups may have affected the observed treatment benefits of AB, improvements from baseline in efficacy endpoints during the lead-in were generally sustained over 52 weeks.

CLINICAL IMPLICATIONS: Aclidinium 400µg BID is a well-tolerated and effective treatment option for moderate to severe COPD patients. This study was funded by Almirall S.A. and by Forest Research Institute, Inc., a wholly owned subsidiary of Forest Laboratories, Inc.

DISCLOSURE: Stephen Rennard: Other: Honoraria for lectures from AARC, Almirall, Am Col Osteopathic Physicians, Asan Medical Center, American Thoracic Society, California Society of Allergy, CME Incite, COPD Foundation, Creative Educational Concepts, Dey, Duke University, Forest, France Foundation, HSC Medical Education, Information TV, Lung Association, Novartis, Horsham, Nycomed, Otsuka, PeerVoice, Pfizer, Shaw Science, University of Washington, University of Alabama Birmingham, VA Sioux Falls, Consultant fee, speaker bureau, advisory committee, etc.: ABIM, Able Associates, Adelphi Research, Align2Action, Almirall, APT Pharma/Britnall, Astra-Zeneca, American Thoracic Society, Beilenson, Boehringer Ingelheim, Boehringer Ingelheim (ACCP), BoomCom, Britnall and Nicolini, Capital Research, Chiesi, Clarus Acuity, CommonHealth, Complete Medical Group, Consult Complete, COPDForum, DataMonitor, Decision Resources, Dunn Group, Easton Associates, Equinox, Forest, Frankel Group, Fulcrum, Gerson Lehman, Globe Life Sciences, Guidepoint, Health Advanced, Hoffman LaRoche, Informed, Insyght, KOL Connection, Leerink Swan, M. Pankove, McKinsey, MDRxFinancial, Medimmune, Merck, Novartis, Nycomed, Oriel, Osterman, Peal, Penn Technology, Pennside, Pfizer, PharmaVentures, Pharmaxis, Prescott, Price Waterhouse, Propagate, Pulmonary Reviews, Pulmatrix, Reckner Associates, Recruiting Resource, Roche, Sankyo, Schering, Schlesinger Medical, Scimed, Smith Research, Sudler and Hennessey, Summer Street Research, Talecris, Think Equity, UBC, Uptake Medical, Vantage Point Management Gary Ferguson: Grant monies (from industry related sources): Forest Research Institute, Consultant fee, speaker bureau, advisory committee, etc.: Forest Research Institute Edward Kerwin: Consultant fee, speaker bureau, advisory committee, etc.: Amphastar, Astra Zeneca, Forest, Ironwood, Merck, Mylan, Novartis, Pearl, Pfizer, Sanofi Aventis, Sunovion, Targacept, Teva and Theravance, Other: Conducted multicenter clinical research trials for approximately seventy pharmaceutical companies Ludmyla Rekeda: Employee: Forest Research Institute Esther Garcia Gil: Employee: Almirall S.A.

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Chest. 2014;146(4_MeetingAbstracts):70A. doi:10.1378/chest.1994318

SESSION TITLE: COPD LAMA/LABA

SESSION TYPE: Original Investigation Slide

PRESENTED ON: Monday, October 27, 2014 at 01:30 PM - 02:30 PM

PURPOSE: To evaluate the bronchodilator effectiveness of combining two classes of long-acting bronchodilators (tiotropium and olodaterol) in separate devices in clinically stable patients with chronic obstructive pulmonary disease (COPD).

METHODS: In two replicate, double-blind, randomized, 12-week studies, we compared the effects of (a) olodaterol 5 µg once daily (qd) (via Respimat®) in combination with tiotropium 18 µg qd (via HandiHaler®) [T+O] with (b) tiotropium 18 µg qd (HandiHaler®) in combination with placebo (Respimat®) [T+P] in patients with moderate to severe COPD (ANHELTO-1 [NCT01694771] and ANHELTO-2 [NCT01696058]). Primary efficacy end points were area under the curve from 0-3 hours of forced expiratory volume in 1 second (FEV1 AUC0-3) and trough FEV1 responses (ie, change from baseline) after 12 weeks. Secondary end points included peak FEV1, AUC0-3 of forced vital capacity (FVC), and peak and trough FVC responses and rescue medication usage.

RESULTS: 1132 patients enrolled in ANHELTO-1 and 1135 in ANHELTO-2. Mean age was 64.6 and 64.1 years, respectively; 49.8% and 53.6%, respectively, were male. Mean baseline post-bronchodilator FEV1 was 54.0% and 53.3%, respectively. T+O resulted in significant improvements in lung function compared with T+P after 12 weeks. Mean FEV1 AUC0-3 responses were 0.196 L with T+P and 0.313 L with T+O in ANHELTO-1 (mean difference 0.117 L; p<0.0001); responses in ANHELTO‑2 were 0.191 and 0.297 L, respectively (mean difference 0.106 L; p<0.0001). Mean trough FEV1 responses were 0.133 L with T+P and 0.195 L with T+O in ANHELTO-1 (mean difference 0.062 L; p<0.0001); responses in ANHELTO‑2 were 0.135 and 0.175 L, respectively (mean difference 0.040 L; p=0.0029). Results of secondary end points supported these data.

CONCLUSIONS: Combining olodaterol (Respimat®) and tiotropium (HandiHaler®) qd provided significant bronchodilation above that achieved with tiotropium alone in patients with COPD.

CLINICAL IMPLICATIONS: Combination of tiotropium (HandiHaler®) and olodaterol (Respimat®) qd provides additional lung function improvement versus T+P in COPD. Funding: Boehringer Ingelheim. Editorial assistance: Complete HealthVizion.

DISCLOSURE: Richard ZuWallack: Consultant fee, speaker bureau, advisory committee, etc.: Honoraria from Boehringer-Ingelheim paid to my hospital, Grant monies (from industry related sources): Investigator initiated grants from Boehringer-Ingelheim to my institution, Consultant fee, speaker bureau, advisory committee, etc.: Honoraria from GSK for speaking paid to me Lisa Allen: Employee: Boehringer-Ingelheim Gemzel Hernandez: Employee: Boehringer-Ingelheim Naitee Ting: Employee: Boehringer-Ingelheim Roger Abrahams: Grant monies (from industry related sources): Clinical Research Grant from Boehringer-Ingelheim, Consultant fee, speaker bureau, advisory committee, etc.: Boehringer-Ingelheim steering committee

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Chest. 2014;146(4_MeetingAbstracts):71A. doi:10.1378/chest.1993054

SESSION TITLE: COPD Treatment

SESSION TYPE: Original Investigation Slide

PRESENTED ON: Sunday, October 26, 2014 at 01:30 PM - 03:00 PM

PURPOSE: RAPID (Randomized, placebo-controlled trial in Alpha-1 Proteinase Inhibitor Deficiency, NCT00261833) was the single largest clinical trial of alpha-1 proteinase inhibitor (A1-PI) augmentation therapy, including 180 A1-PI-deficient patients. RAPID demonstrated that A1-PI therapy (Zemaira®, CSL Behring, 60 mg/kg/week) slows progression of emphysema, as assessed by CT lung densitometry. Here we evaluate the effects of baseline parameters on change in lung density at study end.

METHODS: Subjects received A1-PI or placebo for 2 years. The primary endpoint was CT-measured lung density. The effects of baseline parameters on the mean annual rate of change in adjusted P15 lung density (g/L/y) at total lung capacity were investigated in the intention-to-treat population (N=180) by analyzing the lung density decline in each of several subgroups.

RESULTS: The strongest treatment differences in favor of A1-PI were observed for females (n=79, 1.45 g/L/y; p=0.004), and subjects with high (>66 percentile) functional (n=60, 1.08 g/L/y; p=0.022) or antigenic A1-PI levels (n=58, 1.23 g/L/y; p=0.016), or intermediate functional A1-PI levels (33-66 percentile, n=59; 1.38 g/L/y; p=0.025). Subjects with higher BMI (≥30 kg/m2, n=21; 2.21 g/L/y), lower age (<54 years, n=86; 0.97 g/L/y), lower DLCO (≤ median at baseline, n=87; 0.90 g/L/y), lower exercise capacity (≤ 400 m walked, n=88; 0.99 g/L/y), or lower SGRQ symptoms score (≤ median at baseline, n=88; 0.93 g/L/y) also tended to show greater differences in favor of A1-PI.

CONCLUSIONS: A1-PI augmentation was efficacious across a wide range of subgroups. Patients with higher baseline antigenic/functional A1-PI levels had greater reductions in lung density decline vs. placebo than did those with lower baseline levels. Patients with higher BMI tended to have a greater treatment benefit, possibly due to the greater amount of A1-PI they received. Younger patients tended to have a greater treatment benefit, possibly because they were in the earlier stages of disease and had less emphysematous lung damage/lung density loss.

CLINICAL IMPLICATIONS: A1-PI therapy appears to be beneficial in reducing the rate of lung density decline in A1-PI-deficient patients presenting with diverse baseline characteristics; some characteristics seem to be associated with greater treatment benefit.

DISCLOSURE: James Stocks: Other: Received funds as an investigator on a commercially sponsored clinical trial Robert Sandhaus: Other: Received funds as an investigator on a commercially sponsored clinical trial Kenneth Chapman: Other: Received funds as an investigator on a commercially sponsored clinical trial Jonathan Burdon: Other: Received funds as an investigator on a commercially sponsored clinical trial Eeva Piitulainen: Other: Received funds as an investigator on a commercially sponsored clinical trial Niels Seersholm: Other: Received funds as an investigator on a commercially sponsored clinical trial Liping Huang: Employee: Employed by CSL Behring Jonathan Edelman: Employee: Employed by CSL Behring N. Gerard McElvaney: Other: Received funds as an investigator on a commercially sponsored clinical trial

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Topics: lung , demography
Chest. 2014;146(4_MeetingAbstracts):72A. doi:10.1378/chest.1993435

SESSION TITLE: COPD Treatment

SESSION TYPE: Original Investigation Slide

PRESENTED ON: Sunday, October 26, 2014 at 01:30 PM - 03:00 PM

PURPOSE: GOLD guidelines recommend use of long-acting muscarinic antagonist (LAMA) monotherapy as an early treatment option for patients with COPD. However, some patients initiate free combination therapy of LAMA and long-acting beta agonist (LABA) while still in the early stages of COPD. This study aims to identify treatment outcomes and costs associated with LAMA+LABA use in patients with predominantly low to moderate complexity COPD, as defined by a claims based algorithm.

METHODS: Patients initiating LAMA alone or LAMA+LABA were identified in the MarketScan database (1/1/09-3/31/12). Included patients were >40 years, had medical and pharmacy claims data for 12 months before and after index date, had ≥1 claim for COPD (ICD-9 491, 492, 496), no claims for asthma, non-specified bronchitis, respiratory cancer or cystic fibrosis ≤1 year, and no LABA or LAMA use ≤1 year. Patients taking LAMA+LABA were identified first due to limited sample size. LAMA patients were randomly selected using the same criteria in a 5:1 ratio. Demographic and clinical characteristics were compared between groups using chi-square and t-tests. Logistic regression models were used to adjust for baseline variability and assess differences in the likelihood of utilization between groups. Multivariate generalized linear regression models were used to compare all-cause and COPD-related healthcare costs.

RESULTS: Inclusion criteria identified 274 LAMA+LABA patients; 1,370 LAMA monotherapy patients were then randomly selected. Patients in both groups were similar in terms of age, geographic region, and disease complexity, while patients on LAMA+LABA had more comorbidities. Adjusting for observed differences in baseline characteristics, LAMA+LABA patients had greater all-cause healthcare resource utilization and associated costs; however, only drug costs were significantly different, with higher costs for patients on LAMA+LABA compared with patients on LAMA alone ($7,902 vs $5,808, p<0.0001). Results were similar for COPD-related healthcare resource utilization.

CONCLUSIONS: COPD patients taking LAMA+LABA therapy had similar healthcare resource utilization and costs when compared to patients taking LAMA alone, despite controlling for baseline characteristics like disease complexity and comorbidities.

CLINICAL IMPLICATIONS: The addition of LABA to LAMA therapy in low or moderate complexity COPD patients may result in higher drug costs with no significant reduction in all-cause and COPD-related healthcare resource utilization.

DISCLOSURE: Michelle Mocarski: Employee: Forest Research Institute Wenyi Wang: Consultant fee, speaker bureau, advisory committee, etc.: Forest Research Institute Shawn Sun: Employee: Forest Research Institute Mona Khalid: Consultant fee, speaker bureau, advisory committee, etc.: Forest Research Institute Ronald Aubert: Consultant fee, speaker bureau, advisory committee, etc.: Forest Research Institute Shailja Dixit: Employee: Forest Research Institute

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Chest. 2014;146(4_MeetingAbstracts):73A. doi:10.1378/chest.1991492

SESSION TITLE: COPD Treatment

SESSION TYPE: Original Investigation Slide

PRESENTED ON: Sunday, October 26, 2014 at 01:30 PM - 03:00 PM

PURPOSE: UMEC (LAMA) plus VI (LABA) is an approved combination bronchodilator maintenance treatment for COPD in the USA. FSC (ICS/LABA) is indicated as a maintenance therapy for COPD. Two replicate studies (930, 951) compared the efficacy and safety of UMEC/VI inhalation powder with FSC in patients with moderate-to-severe COPD and infrequent COPD exacerbations (defined as none in previous year).

METHODS: In two 12-week, multicentre, double-blind, parallel-group, double-dummy studies, patients with FEV1 ≥30% and ≤70% pred. were randomized 1:1 to UMEC/VI 62.5/25mcg OD (via ELLIPTA™ inhaler) or FSC 250/50µg BD (via DISKUS inhaler™). The primary endpoint was weighted mean (wm) FEV1 over 0-24h on Day 84; trough FEV1 on Day 85 was the secondary endpoint. Other endpoints included symptomatic measures (TDI focal score; SGRQ). Safety assessments included incidence of AEs.

RESULTS: ITT: N=706 (study 930); N=697 (study 951). UMEC/VI significantly improved all lung function measures, including peak, onset and duration over 12 weeks vs FSC. For 0-24h wmFEV1 on Day 84, improvements with UMEC/VI vs FSC were 74mL (95% CI: 38,110) in study 930 and 101mL (95% CI: 63,139) in study 951 (both p<0.001). UMEC/VI improved trough FEV1 on Day 85 vs FSC in study 930 (82mL [95% CI: 45,119]) and in study 951 (98mL [95% CI: 59,137]) (both p<0.001). Both UMEC/VI and FSC demonstrated clinically meaningful improvements in dyspnoea (TDI focal score >1 unit) and quality of life (change from baseline in SGRQ score >4 unit decrease) over 12 weeks in both studies; no treatments differences between UMEC/VI and FSC were observed. Incidence of on-treatment AEs (UMEC/VI, FSC) was 26%, 27% (study 930) and 30%, 31% (study 951). Headache and nasopharyngitis were the most commonly reported AEs. Incidence of on-treatment SAEs was 2%, 3% (study 930) and 3%, 4% (study 951). There was 1 death in study 930 (FSC group; not drug related) and 5 deaths in study 951 (2 UMEC/VI group; 3 FSC group; 1 death (FSC, due to pneumonia) was reported as drug related by the investigator).

CONCLUSIONS: UMEC/VI 62.5/25mcg OD over 12 weeks led to statistically significant and clinically meaningful improvements in lung function vs FSC 250/50mcg BD in patients with moderate-to-severe COPD and infrequent COPD exacerbations. No new safety findings were reported for UMEC/VI or FSC.

CLINICAL IMPLICATIONS: LAMA/LABA therapy with UMEC/VI 62.5/25mcg OD is an effective therapeutic option in this COPD patient population. Funding: GSK (DB2114930 [NCT01817764]; DB2114951 [NCT01879410])

DISCLOSURE: James Donohue: Consultant fee, speaker bureau, advisory committee, etc.: Almirall, AstraZeneca, Boehringer Ingelheim, Dey, Elevation Pharmaceuticals, Forest Laboratories, GlaxoSmithKline, Novartis, Pearl Pharmaceuticals, Pfizer and Sunovion, Other: Served as member of Drug Safety Monitoring Boards for: NIH, Novartis, Otsuda, Pearl and Teva Sally Worsley: Employee: GlaxoSmithKline, Shareholder: GlaxoSmithKline Chang-Qing Zhu: Employee: GlaxoSmithKline, Shareholder: GlaxoSmithKline Liz Hardaker: Employee: GlaxoSmithKline, Shareholder: GlaxoSmithKline Alison Church: Employee: GlaxoSmithKline, Shareholder: GlaxoSmithKline

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Chest. 2014;146(4_MeetingAbstracts):74A. doi:10.1378/chest.1990182

SESSION TITLE: COPD Treatment

SESSION TYPE: Original Investigation Slide

PRESENTED ON: Sunday, October 26, 2014 at 01:30 PM - 03:00 PM

PURPOSE: To assess the efficacy of budesonide/formoterol (BUD/FM) or FM in chronic obstructive pulmonary disease (COPD) patients with moderate vs severe/very severe airflow limitation (AL), with regard to exacerbation rates (defined as COPD worsening requiring treatment with oral corticosteroids [OCS] and/or hospitalization [HOSP], including or excluding antibiotics [ABX]), and the percentage of patients with clinically meaningful improvements in lung function.

METHODS: In a post-hoc analysis of pooled data from 3 double-blind, randomized studies, (A: 12-month; NCT00206167; B: 12-month, NCT00419744; and C: 6-month, NCT00206154), COPD patients (aged ≥40 years) who had ≥1 COPD exacerbation in the past year were stratified as having moderate AL (forced expiratory volume in 1 second [FEV1] % predicted ≥50%) and severe/very severe AL (FEV1 % predicted <50%). Treatments were twice daily: BUD/FM via pressurized metered-dose inhaler 320/9 μg (n = 197, moderate AL; n = 975, severe/very severe AL) and FM via dry-powder inhaler 9 μg (n = 211, moderate AL; n = 963, severe/very severe AL). Exacerbations per patient-treatment year and responders with ≥100-mL improvement in predose FEV1 are reported.

RESULTS: The lowest rate of OCS/HOSP exacerbations excluding ABX occurred with BUD/FM vs FM alone (moderate AL, 0.4 vs 0.7 per patient-treatment year [P = .0013]; severe/very severe AL, 0.8 vs 1.0 [P < .0001]). OCS/HOSP exacerbations including ABX were also lowest with BUD/FM vs FM (moderate AL, 0.5 vs 0.8 [P = .0034]; severe/very severe AL, 0.9 vs 1.2 [P < .0001]). The percentages of patients who met responder criteria for ≥100-mL predose FEV1 improvement were greater with BUD/FM vs FM alone in moderate AL (46.9% vs 38.6%) and severe/very severe AL patients (33.7% vs 28.6%).

CONCLUSIONS: Exacerbation rates (OCS/HOSP), including or excluding ABX, in COPD patients were reduced with BUD/FM vs FM alone irrespective of AL severity and despite an overall lower exacerbation rate in moderate vs severe/very severe AL. Overall, a greater percentage of patients receiving BUD/FM met responder criteria for ≥100-mL improvement in predose FEV1 vs FM alone and was more pronounced in moderate vs severe/very severe AL.

CLINICAL IMPLICATIONS: COPD patients with moderate and severe/very severe airflow limitation benefit from BUD/FM vs FM alone, with improvements in lung function and lower exacerbation rates. Supported by AstraZeneca LP.

DISCLOSURE: Donald Tashkin: Consultant fee, speaker bureau, advisory committee, etc.: AstraZeneca – speaker, advisory board; Sunovion – advisory board; Theravance – consultant; Pearl – advisory board; Boehringer-Ingelheim – speaker; Forest – speaker, Grant monies (from industry related sources): Sunovion – research grant; Pearl – research grant; GlaxoSmithKline – research grant Stephen Rennard: Consultant fee, speaker bureau, advisory committee, etc.: Consultations: GlaxoSmith-Kline, Boehringer Ingelheim, Forestweb program, AstraZeneca, Chiesi, Takeda, Regeneron, Pearl, CIPLA, CSA, ABIM, Merck, Medimmune, Synapse, Nycomed, DaiIchio Sankyo, Novartis, J&J, Quadrant, GersonLehman, Able Assoc, CSL Behring, Decision Resources, FirstWord, Gilead, Guidepoint Global, Pulmatrix, Saatchi and Saatchi, Schlesinger Assoc, Cory Paety, Frankel group, Medical Knowleged, Pro Ed Comm, LEK Consulting, Consultant fee, speaker bureau, advisory committee, etc.: Speaking Fees: AstraZeneca, CME Incite, CTS Carmel, Nycomed Frank Trudo: Employee: Employee of AstraZeneca LP, Shareholder: Shareholder of AstraZeneca stock

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    Print ISSN: 0012-3692
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