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Peter Mazzone, MD; Charles A. Powell, MD; Douglas Arenberg, MD; Peter Bach, MD; Frank Detterbeck, MD; Michael Gould, MD; Michael T. Jaklitsch, MD; James Jett, MD; David Naidich, MD; Anil Vachani, MD; Renda Soylemez Wiener, MD; Gerard Silvestri, MD
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Lung cancer screening with a low dose chest CT scan can result in more benefit than harm when performed in settings committed to developing and maintaining high quality programs. This project aimed to identify the components of screening that should be a part of all lung cancer screening programs. To do so, committees with expertise in lung cancer screening were assembled by the Thoracic Oncology Network of the ACCP and the Thoracic Oncology Assembly of the ATS. Lung cancer program components were derived from evidence-based reviews of lung cancer screening, and supplemented by expert opinion. This statement was developed and modified based on iterative feedback of the committees. Nine essential components of a lung cancer screening program were identified. Within these components twenty one Policy Statements were developed and translated into criteria that could be used to assess the qualification of a program as a screening facility. Two additional Policy Statements related to the need for multi-society governance of lung cancer screening were developed. High quality lung cancer screening programs can be developed within the presented framework of nine essential program components outlined by our committees. This document has been formally endorsed by several professional organizations (ACCP, ATS, American Association of Thoracic Surgery, American Cancer Society, American Society of Preventive Oncology).

original research 
Hana Müllerova, PhD; Diego J. Maselli, MD; Nicholas Locantore, PhD; Jørgen Vestbo, MD; John R. Hurst, PhD; Jadwiga Wedzicha, MD; Per Bakke, MD, PhD; Alvar Agusti, MD, PhD; Antonio Anzueto, MD; for the ECLIPSE investigators

Background:  Exacerbations of chronic obstructive pulmonary disease (COPD) requiring hospital admission have important clinical and societal implications.

Objective:  We sought to investigate the incidence, recurrence, risk factors, and mortality of COPD patients with exacerbations requiring hospital admission compared to those without hospital admission during 3-year follow-up in 2138 COPD patients from the ECLIPSE (Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints) observational cohort.

Methods:  Time to first event of hospital admission analysis using Kaplan-Meier curves and Cox proportional hazard regression adjusting for possible confounders.

Results:  670 (31%) patients reported a total of 1452 COPD exacerbations requiring hospital admission during the study period; 313 patients (15%) reported multiple (>1) events. A prior history of exacerbation of COPD requiring hospital admission was the factor associated with the highest risk of a new hospitalization for exacerbation (hazard ratio 2.71, 95% confidence interval: 2.24–3.29, P <.001). Other risk factors included more severe airflow limitation, poorer health status, older age, radiological evidence of emphysema, and higher white blood cell count. Having been hospitalized for exacerbation significantly increased the risk of mortality (P <.001).

Conclusions:  Exacerbations of COPD requiring hospital admission occur across all stages of airflow limitation and are a significant prognostic factor of reduced survival across all COPD stages. COPD patients at a high risk of hospitalization can be identified by their past history for similar events, and other factors, including the severity of airflow limitation, poor health status, age, presence of emphysema, and leukocytosis.

Trial registration:  clinicaltrials.gov/show/NCT00292552

original research 
Neil C. Thomson, MD; Rekha Chaudhuri, MD; Mark Spears, PhD; Claudia-Martina Messow, PhD; William MacNee, MD; Martin Connell, BSc; John T. Murchison, MD; Michael Sproule, MBChB; Charles McSharry, PhD
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Background  Cigarette smoking is associated with worse symptoms in asthma and abnormal segmental airways in healthy subjects. We tested the hypothesis that current symptom control in smokers with asthma is associated with altered segmental airway dimensions measured by computed tomography (CT).

Methods  In 93 asthmatics with mild, moderate and severe disease (smokers and never-smokers) we recorded the asthma control questionnaire (ACQ6) score, spirometry [FEV1, FEF25-75], residual volume (RV), total lung capacity (TLC), and CT measures of right bronchial (RB) and left bronchial (LB) segmental airway dimensions, [wall thickness, mm; lumen area, mm2] in RB3/LB3, RB6/LB6 and RB10/LB10 (smaller) airways.

Results  CT segmental airway (RB10 and LB10) lumen area was reduced in smokers with asthma compared to never smokers with asthma; RB10 16.6 mm2 (interquartile range (IQR), 12.4, 19.2) versus 19.6 mm2 (IQR 14.7, 24.2, p=0.01); LB10 14.8 mm2 (12.1, 19.0) versus 19.9 mm2 (14.5, 25.0), p=0.003, particularly in severe disease, with no differences in wall thickness or in larger airway (RB3 and LB3) dimensions. In smokers with asthma, a reduced lumen area in 5th generation airways (RB10 or LB10) was associated with poor symptom control (higher ACQ6 score) [-0.463 (-0.666, -0.196), p=0.001 and -0.401 (-0.619, -0.126), p=0.007 respectively] and reduced FEF25-75 post-bronchodilator [0.521 (0.292, 0.694), p<0.001 and [0.471 (0.236, 0.654), p=0.001] respectively] and higher RV/TLC %.

Conclusion  CT segmental airway lumen area is reduced in smokers with asthma compared to never smokers with asthma, particularly in severe disease and is associated with worse current symptom control and small airway dysfunction.

original research 
David E. Griffith, M.D.; Julie V. Philley, M.D.; Barbara A. Brown-Elliott, M.S.; Jeana Benwill, M.D.; Sara Shepherd, M.S.; Deanna York, R.N.; Richard J. Wallace, Jr., M.D.
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Background:  Isolation of Mycobacterium abscessus subsp abscessus (MAA) is common during Mycobacterium avium complex (MAC) lung disease therapy but there is limited information about the clinical significance of the MAA isolates.

Methods:  We identified 53/180 patients (29%) treated for MAC lung disease who had isolation of MAA during MAC lung disease therapy. Patients were divided into those withoutGroup 1) and those with (Group 2) MAA lung disease.

Results:  There were no significant demographic differences between patients with and without MAA isolation or between Groups 1 and 2. Group 1 and 2 patients had similar total sputum cultures obtained (p = 0.7; CI: -13.4 to 8.6) and length of follow-up (p = 0.8; CI: -21.5 to 16.1). Group 2 patients had significantly more total positive cultures for MAA, 15.0 ± 11.1 vs 1.2 ± 0.4 (p < 0.0001; CI: -17.7 to -9.9), were significantly more likely to develop new or enlarging cavitary lesions while on MAC therapy (p > 0.0001) and were significantly more likely to meet all 3 ATS diagnostic criteria for nontuberculous mycobacterial (NTM) disease, 21/21 (100%) vs 0/32 (0%) (p < 0.0001) compared to Group 1 patients. Group 1 patients were significantly more likely to have single positive MAA cultures than Group 2 patients, 25/31 vs 0/21 (p < 0.0001).

Conclusion:  Microbiologic and clinical follow-up after completion of MAC lung disease therapy is required to determine the significance of MAA isolated during MAC lung disease therapy. Single MAA isolates are not likely to be clinically significant.

original research 
Julia Thornton Snider, PhD; Anupam B. Jena, MD, PhD; Mark T. Linthicum, MPP; Refaat A. Hegazi, MD, PhD, MS, MPH; Jamie S. Partridge, PhD, MBA; Chris LaVallee, MS; Darius N. Lakdawalla, PhD; Paul E. Wischmeyer, MD
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Background:  Chronic obstructive pulmonary disease (COPD) is a leading cause of death and disability in the US. Patients with COPD are at high risk of nutritional deficiency, which is associated with declines in respiratory function, lean body mass and strength, and immune function. Although oral nutritional supplements (ONS) have been associated with improvements in some of these domains, the impact of hospital ONS on readmission risk, length of stay (LOS), and cost among hospitalized patients is unknown.

Methods:  We first identified Medicare patients aged 65+ hospitalized with a primary diagnosis of COPD in the Premier Research Database. We then identified hospitalizations in which ONS was provided and used propensity score matching to compare LOS, hospitalization cost and 30-day readmission rates in a 1-1 matched sample of ONS and non-ONS hospitalizations. To further address selection bias among patients prescribed ONS, we also utilized instrumental variables (IV) analysis to study the effects of ONS. Model covariates included patient and provider characteristics and a time trend.

Results:  Out of 10,322 ONS hospitalizations and 368,097 non-ONS hospitalizations, a one-to-one matched sample was created (N=14,326). IV analysis indicated that ONS use was associated with: a 1.88 day (21.5%) decrease in LOS, from 8.75 to 6.87 days (p<0.01); hospitalization cost reduction of $1,570 (12.5%), from $12,523 to $10,953 (p<0.01); and a 13.1% decrease in probability of 30-day readmission, from 0.335 to 0.291 (p<0.01).

Conclusions:  ONS may offer an inexpensive, effective means for reducing LOS, hospitalization cost, and readmission risk in hospitalized Medicare patients with COPD.

original research 
Alexander Chen, MD; Nicholas Pastis, MD; Brian Furukawa, MD; Gerard A. Silvestri, MD
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Background:  Electromagnetic navigation has improved the diagnostic yield of peripheral bronchoscopy for pulmonary nodules. For these procedures, a thin slice chest CT scan is performed prior to bronchoscopy at full inspiration and is used to create virtual airway reconstructions that are used as a map during bronchoscopy. Movement of the lung occurs with respiratory variation during bronchoscopy, and the location of pulmonary nodules during procedures may differ significantly from their location on the initial planning full inspiratory chest CT. This study was performed to quantify pulmonary nodule movement from full inspiration to end exhalation during tidal volume breathing in patients undergoing electromagnetic navigation procedures.

Methods:  A retrospective review of electromagnetic navigation procedures was performed for which two pre-procedure CT scans were performed prior to bronchoscopy. One CT scan was performed at full inspiration and a second CT scan was performed at end exhalation during tidal volume breathing. Pulmonary lesions were identified on both CT scans and distances between positions were recorded.

Results:  85 pulmonary lesions were identified in 46 patients. Average motion of all pulmonary lesions was 17.6mm. Pulmonary lesions located in the lower lobes moved significantly more than upper lobe nodules. Size and distance from the pleura did not significantly impact movement.

Conclusion:  Significant movement of pulmonary lesions occurs between full inspiration and end exhalation during tidal volume breathing. This movement from full inspiration on planning chest CT scan to tidal volume breathing during bronchoscopy may significantly affect the diagnostic yield of electromagnetic navigation bronchoscopy procedures.

original research 
David E. Ost, MD, MPH; Armin Ernst, MD; Horiana B. Grosu, MD; Xiudong Lei, PhD; Javier Diaz-Mendoza, MD; Mark Slade, MBBS; Thomas R. Gildea, MD, MS; Michael Machuzak, MD; Carlos A. Jimenez, MD; Jennifer Toth, MD; Kevin L. Kovitz, MD; Cynthia Ray, MD; Sara Greenhill, MD; Roberto F. Casal, MD; Francisco A. Almeida, MD, MS; Momen Wahidi, MD; George A. Eapen, MD; David Feller-Kopman; Rodolfo C. Morice, MD; Sadia Benzaquen, MD; Alain Tremblay, MDCM; Michael Simoff, MD On behalf of the AQuIRE Bronchoscopy Registry
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Background:  There is significant variation between physicians in terms of how they perform therapeutic bronchoscopy but there is little data on whether these differences impact effectiveness.

Methods:  This was a multicenter registry study of patients undergoing therapeutic bronchoscopy for malignant central airway obstruction. The primary outcome was technical success, defined as reopening the airway lumen to >50% of normal. Secondary outcomes were dyspnea as measured by the Borg score and health related quality of life (HRQOL) as measured by the SF-6D.

Results:  Fifteen centers performed 1,115 procedures on 947 patients. Technical success was achieved in 93% of procedures. Center success rates ranged from 90% to 98% (p=0.02). Endobronchial obstruction and stent placement were associated with success while ASA >3, renal failure, primary lung cancer, left mainstem disease, and tracheoesophageal fistula were associated with failure. Clinically significant improvements in dyspnea occurred in 90 of 187 patients measured (48%). Greater baseline dyspnea was associated with greater improvements in dyspnea while smoking, having multiple cancers, and lobar obstruction were associated with smaller improvements. Clinically significant improvements in HRQOL occurred in 76 of 183 patients measured (42%). Greater baseline dyspnea was associated with greater improvements in HRQOL while lobar obstruction was associated with smaller improvements.

Conclusions:  Technical success rates were high overall, with the highest success rates associated with stent placement and endobronchial obstruction. Therapeutic bronchoscopy should not be withheld from patients based solely on an assessment of risk, since patients with the most dyspnea and lowest functional status benefitted the most.

original research 
Kohei Hasegawa, MD, MPH; Rita K. Cydulka, MD, MS; Ashley F. Sullivan, MPH, MS; Mark I. Langdorf, MD, MHPE; Stephanie A. Nonas, MD; Richard M. Nowak, MD, MBA; Nancy E. Wang, MD; Carlos A. Camargo, Jr., MD, DrPH
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Background:  A multicenter study in the late 1990s demonstrated suboptimal emergency asthma care for pregnant women in US emergency departments (EDs). After a decade, follow-up data are lacking. We aimed to examine changes in emergency asthma care of pregnant women since the 1990s.

Methods:  We combined data from four multicenter observational studies of ED patients with acute asthma performed in 1996-2001 (three studies), and 2011-2012 (one study). We restricted the data so that comparisons were based on the same 48 EDs in both time periods. We identified all pregnant patients aged 18 to 44 years with acute asthma. Primary outcomes were treatment with systemic corticosteroids in the ED, and, among those sent home, at ED discharge.

Results:  Of 4895 ED patients with acute asthma, the analytic cohort comprised 125 pregnant women. Over the two time periods, there were no significant changes in patient demographics, chronic asthma severity, or initial peak expiratory flow. In contrast, ED systemic corticosteroids treatment increased significantly from 51% to 78% across the time periods (OR 3.11; 95%CI 1.27-7.60; P=0.01); systemic corticosteroids at discharge increased from 42% to 63% (OR 2.49; 95%CI 0.97-6.37; P=0.054). In the adjusted analyses, pregnant women in recent years were more likely to receive systemic corticosteroids, both in ED (OR 4.76; 95%CI 1.63-13.9; P=0.004) and at discharge (OR 3.18; 95%CI 1.05-9.61; P=0.04).

Conclusions:  Over the two time periods, emergency asthma care in pregnant women has significantly improved. However, with one in three pregnant women being discharged home without systemic corticosteroids, further improvement is warranted.

original research 
Zegabriel Tedla; Minh-Ly Nguyen; Thabisa Sibanda; Samba Nyirenda; Tefera B. Agizew; Sonali Girde; Charles E. Rose; Taraz Samandari
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Background:  The World Health Organization recommends 36 months of isoniazid preventive therapy (36IPT) for HIV-infected adults living in tuberculosis endemic countries. We determined the rates and risk factors for isoniazid-associated hepatitis with the use of 36IPT.

Methods:  1006 HIV-infected adults received 36IPT during a pragmatic randomized trial set in Botswana public health clinics providing HIV care. Enrollment exclusion criteria included jaundice or elevations of serum transaminases (EST) >2.5-fold the upper limit of normal (ULN). Participants with any CD4+ lymphocyte count were eligible and received antiretroviral therapy (ART) when CD4+ <200 cells/mm3. 36IPT was stopped for severe hepatitis (>5-fold ULN EST) but not for moderate hepatitis (2.5 to 5-fold ULN EST).

Results:  Pharmacy refill records showed 2237 person-years of isoniazid receipt; 48% of participants initiated ART by 36 months. 1.9% (19/1006) of participants were diagnosed with severe hepatitis; three were jaundiced and two of these developed hepatic encephalopathy. Another 3.1% (31/1006) of participants experienced moderate hepatitis. 38% (19/50) of participants with moderate-to-severe hepatitis concomitantly received ART. Forty percent (20/50) of moderate-to-severe cases occurred within the first two months of IPT and – during this period – were not associated with receipt of ART at baseline, hazard ratio 1.49 (95% confidence interval 0.20-11.1, P=0.70).

Conclusions:  HIV-infected adults receiving 36IPT did not have an increased incidence of moderate-to-severe hepatitis or hepatic encephalopathy compared with published reports among HIV-infected or -uninfected persons in trials or public health programs. Compared with participants not receiving ART, the risk of moderate-to-severe hepatitis was not increased by ART.

original research 
Robert M. Kaplan, Ph.D.; Qiankun Sun, PhD; Andrew L. Ries, M.D, M.P.H.
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Background:  Surgical and medical treatments for emphysema may affect both quality and quantity of life. The purpose of this paper is to report outcomes from the National Emphysema Treatment Trial (NETT) using an index that combines quality and quantity of life.

Design:  Prospective Randomized Clinical Trial. Following pulmonary rehabilitation, 1218 patients with severe emphysema were randomly assigned to maximal medical therapy or to lung volume reduction surgery (LVRS). A generic quality of life (QoL) measure, known as the Quality of Well-bing (QWB) Scale, was administered at baseline and again at 6, 12, 24, 36, 48, 60 and 72 months following treatment assignment.

Result:  At baseline, QWB scores were comparable for the Medical and LVRS groups. For both groups, scores significantly improved following the rehabilitation program. The QWB scores before death for patients in the LVRS group improved up to the Year 2 visit, while scores for the Medical group dropped significantly following the baseline visit. Imputing zeros (0) for death, QWB scores decreased significantly for both groups. With or without scoring death as 0, the LVRS group achieved better outcomes and the significant differences were maintained until the sixth year. Over six years of follow-up LVRS produced an average of 0.30 QALYs, or the equivalent of about 3.6 months of well life.

Conclusions:  In comparison to maximal medical therapy alone, patients undergoing maximal medical therapy plus LVRS experienced improved health related quality of life and gained more quality-adjusted life years.

ClinicalTrials.gov Identifier:  NCT00000606

original research 
Amédée Ego, MS; Jean-Charles Preiser, MD, PhD; Jean-Louis Vincent, MD, PhD, FCCP
Topics: ,

Background:  Ventilator-associated pneumonia (VAP) is a frequent complication of prolonged invasive ventilation. Because VAP is largely preventable, its incidence has been used as an index of quality-of-care in the intensive care unit (ICU). However, the incidence of VAP varies according to which criteria are used to identify it. We compared the incidence of VAP obtained with different sets of criteria.

Methods:  We collected data from all adult patients admitted to our 35-bed Dept of Intensive Care over a 7-month period who had no pulmonary infection on admission or within the first 48 hours and who required mechanical ventilation for >48 hours. To diagnose VAP, we applied six published sets of criteria and 89 combinations of criteria for hypoxemia, inflammatory response, purulence of tracheal secretions, chest radiography findings and microbiological findings of varying levels of severity. The variables used in each diagnostic algorithm were assessed daily.

Results:  Of 1,824 patients admitted to the ICU during the study period, 91 were eligible for inclusion. The incidence of VAP ranged from 4% to 42% when using the 6 published sets of criteria, and from 0-44% when using the 89 combinations. The delay before diagnosis of VAP increased from 4 to 8 days with increasingly stringent criteria and mortality from 50 to 80%.

Conclusions:  Applying different diagnostic criteria to the same patient population can result in wide variation in the incidence of VAP. The use of different criteria can also influence the time of diagnosis and the associated mortality rate.

original research 
Sadasivam Suresh, FRACP; Michael O’Callaghan, FRACP; Peter D. Sly, DSc; Abdullah A. Mamun, PhD
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Background:  Poor fetal growth rate is associated with lower respiratory function; however there is limited understanding of the impact of growth trends and body mass index(BMI) during childhood on adult respiratory function.

Methods:  The present study data are from the Mater-University of Queensland Study of Pregnancy birth cohort. Prospective data were available from 1740 young adults who performed standard spirometry at 21 years and birth weight, and weight, height and BMI was available at 5, 14 and 21 years of age. Catch-up growth was defined as increase of 0.67 Z-score in weight between measurements. The impact of catch-up growth on adult lung function and the relationship between childhood BMI trends and adult lung function was assessed using regression analyses.

Results:  Lung function was higher at 21 years in those demonstrating catch-up growth from birth to 5years;FVC [(males:5.33L v 5.54L), (females:3.78L v 4.03L)] and FEV1 [(males:4.52l/s v 4.64l/s), (females:3.31l/s v 3.45l/s)]. Subjects in the lowest quintile of birth [IUGR] also showed improved lung function if they had catch-up growth in the first five years of life.There was a positive correlation with increasing BMI and lung function at 5 years of age. However in the later measurements when BMI increases into the obese category a drop in lung function was observed.

Conclusion:  These data show evidence for a positive contribution of catch-up growth in early life to adult lung function. However, if weight gain or onset of obesity occurs after 5 years of age adverse impact on adult lung function is noted.

original research 
Bradley D. Freeman, MD; Kevin Butler, MS; Dragana Bolcic-Jankovic, MS; Brian R. Clarridge, PhD; Carie R. Kennedy, RN; Jessica LeBlanc, BA; Sara Chandros Hull, PhD
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Background:  Collection of genetic biospecimens as part of critical illness investigations is increasingly commonplace. Oversight bodies vary in restrictions imposed on genetic research, introducing inconsistencies in study design, potential for sampling bias, and the possibility of being overly prohibitive of this type of research altogether. We undertook this study to better understand whether restrictions on genetic data collection beyond those governing research on cognitively intact subjects reflect the concerns of surrogates for critically ill patients.

Methods:  We analyzed survey data collected from 1,176 patients in non-urgent settings and 437 surrogates representing critically ill adults. Attitudes pertaining to genetic data (familiarity, perceptions, interest in participation, concerns) and demographic information were examined using univariate and multivariate techniques.

Results:  We explored differences among respondents who were receptive (1,333) and non-receptive (280) to genetic sample collection. Whereas factors positively associated with receptivity to research participation were ‘complete trust’ in health care providers (OR 95%CI 2.091 (1.544-2.833)), upper income strata (2.319 (1.308-4.114)), viewing genetic research ‘very positively’ (3.524 (2.122-5.852)) and expressing ‘no worry at all’ regarding disclosure of results (2.505 (1.436-4.369)), African American race was negatively associated with research participation (0.410 (0.288-0.585)). We could detect no difference in receptivity to genetic sample collection comparing ambulatory patients and surrogates (0.738 (0.511-1.066)).

Conclusions:  Expressing trust in health care providers and viewing genetic research favorably were associated with increased willingness for study enrollment while concern regarding breach of confidentiality and African American race had the opposite effect. Study setting had no bearing on willingness to participate.

original research 
Brian H. Rowe, MD, MSc; Cristina Villa-Roel, MD, MSc; Sumit R. Majumdar, MD, MPH; Riyad B. Abu-Laban, MD, MHSc; Shawn D. Aaron, MD, MSc; Ian G. Stiell, MD, MSc; Jeffrey Johnson, PhD; Ambikaipakan Senthilselvan, PhD; for the AIR Investigators
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Background:  Acute asthma is a common emergency department (ED) presentation. In a prospective multicenter cohort study we determined the frequency and factors associated with asthma relapse following discharge from the ED.

Methods:  Adults aged 18-55 years who were treated for acute asthma and discharged from 20 Canadian EDs underwent a structured ED interview and follow-up telephone interview four weeks later. Standardized anti-inflammatory treatment was offered at discharge. Multivariable analyses were performed.

Results:  Of 807 enrolled patients, 58% were female and the median age was 30 years. Relapse occurred in 144 patients (18%) within four weeks of ED discharge. Factors independently associated with relapse occurrence were: female sex (22% vs 12% males, adjusted odds ratio [aOR] = 1.9, 95% confidence interval [CI]: 1.2, 3.0), symptom duration of > 24 hours prior to ED visit (19% vs 13% short duration, aOR = 1.7, 95% CI: 1.3, 2.3), ever using oral corticosteroids (21% vs 12% for never use, aOR = 1.5, 95% CI: 1.1, 2.0), current use of an inhaled corticosteroids[ICS]/long-acting β-agonist combination product (25% vs 15% for ICS monotherapy, aOR = 1.9, 95% CI: 1.1, 3.2), and owning a spacer device (24% vs 15% not owning one aOR = 1.6, 95% CI: 1.3, 1.9).

Conclusions:  Despite receiving guideline-concordant anti-inflammatory treatments at ED discharge, almost one-in-five patients relapsed within four weeks. Female sex, prolonged symptoms, treatment-related factors and markers of prior asthma severity were significantly associated with relapse. These results may help clinicians target more aggressive interventions for patients at high risk of relapse.

original research 
Ali Akbar Velayati; Parissa Farnia; Mohadese Mozafari; Donya Malekshahian; Amir Masoud Farahbod; Shima Seif; Snaz Rahideh; Mehdi Mirsaeidi
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Background  The potential role of environmental M. tuberculosis in the epidemiology of tuberculosis (TB) remains unknown. We investigated the transmission of M. tuberculosis from humans to the environment and the possible transmission of M. tuberculosis from the environment to humans.

Methods  A total of 1,500 samples were collected from three counties of the Tehran metropolitan area, Iran from February 2012 to January 2014. A total of 700 (47%) water and 800 (53%) soil samples were collected. Spoligotypes and MIRU-VNTR typing method performed on DNA extracted from single colonies. Genotypes of M. tuberculosis strains isolated from the environment were compared with the genotypes obtained from 55 confirmed pulmonary TB patients diagnosed during the study period in the same three counties.

Results  M. tuberculosis was isolated from (11/800, 1%) of soil and (71/700, 10%) of water samples. T family (56/82; 68%) followed by Delhi/CAS (11/82; 13.4%) were the most frequent M. tuberculosis superfamilies in both water and soil samples. Overall, 27.7% of isolates in clusters were related. No related typing patterns were detected between soil, water and clinical isolates. The most frequent superfamily of M. tuberculosis in clinical isolates was Delhi/CAS (142; 30.3%) followed by NEW-1(127;27%). The bacilli in contaminated soil (36%) and damp water (8.4%) remained reculturable in some samples up to 9 months.

Conclusion  Although the dominant M. tuberculosis superfamilies in soil and water did not correspond to the dominant M. tuberculosis family in patients, the presence of circulating genotypes of MTB in soil and water highlight the risk of transmission.

original research 
Rachael A. Evans, MBChB, PhD; Eric Kaplovitch, BSc (H), MD; Marla K. Beauchamp, PhD; Thomas E. Dolmage, MSc; Roger S. Goldstein, MBChB; Clare L. Gillies, PhD; Dina Brooks, PhD; Sunita Mathur, PhD
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Background  Although the aerobic profile of the quadriceps muscle is reduced in COPD, there is conflicting evidence whether this leads to reduced quadriceps muscle endurance. We therefore performed a systematic review of studies comparing quadriceps endurance in individuals with COPD to healthy controls.

Methods  Relevant studies were identified by searching six electronic databases (1946-2011). Full text articles were obtained after two researchers independently reviewed the abstracts. The results were combined in a random effects meta-analysis and meta-regression models were fitted to assess the influence of type of measurement.

Results  Data were extracted from 21 studies involving 728 individuals with COPD and 440 healthy controls. Quadriceps endurance was reduced in COPD compared to healthy controls SMD 1.16 (95% CI: 1.02 to 1.30, p<0.001) with a 44.5 (4.5 to 84.5) second (p=0.029) reduction in COPD (large effect size) when measured using a non-volitional technique. The relationship between quadriceps endurance in COPD and controls did not differ when comparing non-volitional and volitional techniques (p = 0.22) or when high or low intensity tasks (p = 0.44) were used.

Conclusion  Quadriceps endurance is reduced in individuals with COPD compared to healthy controls independent of the type of task performed.

original research 
Jing Liu, MD, PhD; Shui-Wen Chen, MD; Fang Liu, MD; Qiu-Ping Li, MD, PhD; Xiang-Yong Kong, MD, PhD; Zhi-Chun Feng, MD, PhD
Topics: ,

BACKGROUND AND OBJECTIVES:  Generally,the diagnosis of neonatal pulmonary atelectasis (NPA) is based on history, clinical and chest x-ray (CXR) findings while ultrasound could not be used in lung disease diagnostics. Recently, ultrasound has been used for the diagnosis of many kinds lung conditions, but few studies have investigated ultrasound for the diagnosis of NPA. In this study, we evaluated the usefulness of lung ultrasound for the diagnosis of NPA.

METHODS:  From May 2012 to December 2013, 80 neonates with NPA and 50 neonates without lung disease were enrolled in this study. In a quiet state, infants were placed in the supine, lateral or prone position for the examination. Each lung of every infant was divided into the anterior, lateral and posterior regions by the anterior axillary and posterior axillary lines. Each region of both lungs was scanned carefully with the probe perpendicular or parallel to the ribs. The ultrasound findings were confirmed by CXR or computed tomography findings.

RESULTS:  Sixty of the 80 patients with signs of NPA on lung ultrasound also had signs of NPA on CXR (termed focal type of atelectasis), and the other 20 patients had signs of NPA on chest computed tomography (termed occult lung atelectasis). In NPA patients,the main ultrasound findings were large areas of lung consolidation with clearly demarcated borders, air bronchograms, pleural line abnormalities, and absence of A-lines, as well as presence of lung pulse and absence of lung sliding on real-time ultrasound. The sensitivity of lung ultrasound for the diagnosis of NPA was 100%, whereas the sensitivity of CXR was 75%. Large areas of lung consolidation with clearly demarcated borders were only observed in patients with NPA (specificity of 100% for NPA).

CONCLUSIONS:  Lung ultrasound is an accurate and reliable method for diagnosing NPA, most importantly, it can find those occult lung atelectasis that could not be detected on CXR. Routine lung ultrasound is a useful method of diagnosing or excluding NPA in neonates.

original research 
John H. Newman, MD; Evan L. Brittain, MD; Ivan M. Robbins, MD; Anna R. Hemnes, MD
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Background:  Pulmonary vascular capacitance (PVC) is reduced in pulmonary arterial hypertension (PAH). In normal lung PVC is largely a function of vascular compliance. In PAH, increased resistance (PVR) arises from the arterioles. PVR and PVC share pressure and volume variables. The dependency between the two qualities of the vascular bed is unclear in a state of intense vasoconstriction.

Methods:  We compared PVC and PVR before and during nitric oxide (NO) inhalation during right heart catheterization in 8 NO responsive PAH patients. NO only directly affects tone in parenchymal vessels.

Results:  During NO inhalation, Pa systolic decreased, 80± 20 STD to 48 ± 20 mmHg and stroke volume increased , 62 ± 19 to 86 ± 24 ml. (p<0.01). PVR dropped from 10 ± 4.4 to 4.7 ± 2.2 Wood units (p<0.012), and PVC increased from 1.4 ± 1.1 to 3.2 ± 1.8 ml/mmHg (p <0.018). The magnitude of PVR drop was 57± 6% and the decrease in 1/PVC was 54 ± 14%, p=ns.

Conclusions:  In vasoresponsive PAH, PVC is a function of the pressure response of the vasoconstricted arterioles to stroke volume. Immediately upon vasodilation, the capacitance increases markedly. The compliance vessels are thus the same as the resistance vessels. The immediate reduction in Pa pressure during NO suggests that large vessel remodeling is not a major contributor to systolic pressure in these patients.

original research 
Martina Bonifazi, MD; Francesca Bravi, PhD; Stefano Gasparini, MD; Carlo La Vecchia, MD; Armando Gabrielli, MD; Athol U. Wells, MD; Elisabetta A. Renzoni, MD
Topics: , ,

Background.  An increased cancer risk in sarcoidosis patients has been suggested, although results are conflicting in a number of case-control and cohort studies. We conducted a systematic review of all available data and performed a meta-analysis to better define and quantify the association between sarcoidosis and cancer.

Methods.  We searched Medline and Embase for all original articles on cancer and sarcoidosis published up to January 2013. Two independent authors reviewed all titles/abstracts to identify studies according to predefined selection criteria. We derived summary estimates using random effects model and reported as relative risk (RR). Publication bias was evaluated by using funnel plot and was quantified by Egger's test.

Results.  Sixteen original studies, involving more than 25,000 patients, were included in the present review. The summary RR to develop all invasive cancers was 1.19 (95% CI, 1.07-1.32). The results for selected cancer sites indicated a significant increased risk of skin (RR 2.00; 95% CI, 1.69-2.36), haematopoietic (RR 1.92; 95% CI, 1.41-2.62), upper digestive tract (RR 1.73; 95% CI, 1.07-2.79), kidney (RR 1.55; 95% CI, 1.21-1.99), liver (RR 1.79; 95% CI, 1.03-3.11) and colorectal cancers (1.33; 95% CI, 1.07-1.67). There was no evidence of publication bias for all cancers (p=0.8), nor for any specific cancer site.

Conclusions.  The present meta-analysis suggests a significant, though moderate, association between sarcoidosis and malignancy.

original research 
Alda Marques, PhD; Cristina Jácome, MSc; Joana Cruz, MSc; Raquel Gabriel, MSc; Dina Brooks, PhD; Daniela Figueiredo, PhD
Topics: , , ,

Background:  Involving family as part of the patient’s rehabilitation plan of care might enhance the management of Chronic Obstructive Pulmonary Disease (COPD). The primary aim of this study was to investigate the impact of a family-based pulmonary rehabilitation (PR) program on patients and family members’ coping strategies to manage COPD.

Methods:  Family dyads (patient and family member) were randomly assigned to family-based (experimental) or conventional PR (control). Patients from both groups underwent exercise training three times a week and psychosocial support and education once a week, during 12 weeks. Family members of the family-based PR attended the psychosocial support and education sessions together with patients. In the conventional PR, family members did not participate. Family coping and psychosocial adjustment to illness were assessed in patients and family members of both groups. Patients’ exercise tolerance, functional balance, muscle strength and health-related quality of life were also measured. All measures were collected pre/post-program.

Results:  Forty-two dyads participated (patients: FEV1 70.4±22.1% predicted). Patients (p=0.048) and family members (p=0.004) in the family-based PR had significantly greater improvements in family coping than the control group. Family members of the family-based PR had significantly greater changes in sexual relationships (p=0.026) and in psychological distress (p=0.033) compared to the control group. Patients from both groups experienced significant improvements in exercise tolerance, functional balance, knee extensors strength and health-related quality of life after intervention (p<0.001).

Conclusions:  This research supports family-based PR programs to enhance coping and psychosocial adjustment to illness of the family system.

Clinical Trials registration number:  NCT02048306

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  • CHEST Journal
    Print ISSN: 0012-3692
    Online ISSN: 1931-3543