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CHEST publishes select peer-reviewed, accepted manuscripts Online First each week. The media embargo is lifted on the date of Online First publication. Final, edited versions will appear in a numbered issue of CHEST and may contain substantive changes. We encourage readers to check back for the final article. Online First papers are indexed in PubMed and by search engines, but the information, including the final title and author list, may be updated on final publication.

original research 
Edmund M.T. Lau, MD, PhD; Denis Chemla, MD, PhD; Laurent Godinas, MD; Kaixian Zhu, MSc; Olivier Sitbon, MD, PhD; Laurent Savale, MD, PhD; David Montani, MD, PhD; Xavier Jaïs, MD; David S. Celermajer, MD, PhD; Gérald Simonneau, MD; Marc Humbert, MD, PhD; Philippe Hervé, MD, PhD
Topics: , , ,

Background:  Exercise can distend the normally compliant, thin-walled pulmonary vessels. Loss of distensibility has been suggested as an early marker of pulmonary vascular remodeling. We hypothesized that in mild pulmonary vascular disease (PVD), a reduction in vascular distensibility during exercise occurs prior to the development of overt resting pulmonary hypertension (PH).

Methods:  Distensibility α during exercise (% change in vessel diameter per mmHg increase in transmural pressure) was estimated in 90 subjects using a model of the pulmonary circulation and invasive hemodynamic data. Distensible properties in mild PVD without resting PH (PVD-noPH) (n=33) were compared to controls (n=26) and PVD with overt resting PH (PVD-PH) (n=31).

Results:  Resting mean pulmonary artery pressure (mPpa) was 14±4, 20±3 and 34±10 mmHg with corresponding exercise mPpa-cardiac output slopes of 1.5±0.6, 3.5±0.9 and 5.7±3.2 for controls, PVD-noPH and PVD-PH groups, respectively. The distensible model produced high accuracy and precision with no mean bias and 95% limits of agreement of -4.5 to 4.5 mmHg between calculated and measured mPpa. Distensibility α was lowest in PVD-PH, intermediate in PVD-noPH, and highest in controls (0.25±0.14 vs. 0.45±0.24 vs. 1.40±0.45%/mmHg, p<0.0001). Distensibility α discriminated PVD-noPH from controls with sensitivity of 88% and specificity of 100%. The discriminatory performance of α was similar for the subgroup of PVD-noPH with strictly normal resting mean Ppa ≤20 mmHg.

Conclusions:  Loss of pulmonary vascular distensibility during exercise occurs prior to resting PH in PVD. The utility of α as a novel vascular index for the early detection of PVD warrants further validation.

original research 
Kai K. Lee, MD; Katie Ward, PhD; Gerrard F. Rafferty, PhD; John Moxham, MD; Surinder S. Birring, MD

Background:  The intensity of cough is an important determinant of cough severity. Few studies have quantified cough intensity in patients with chronic cough with objective measures. We investigated the intensity of voluntary, induced and spontaneous cough in patients with chronic cough and normal subjects.

Methods:  Patients with chronic cough and healthy subjects underwent physiological assessment of the intensity of maximum voluntary, capsaicin-induced and spontaneous cough. Assessments included measurement of gastric (Pga) and esophageal pressure (Pes) during cough, peak cough flow (PCF), expiratory muscle strength (twitch gastric pressure, TwPga) and cough compressive phase duration (CPD). Subjective perception of cough intensity was assessed using a visual analogue scale (VAS).

Results:  Pes, Pga and PCF during maximum voluntary cough were significantly greater in patients with chronic cough compared with controls (p=0.003 to 0.042). There was no difference in TwPga between patients and controls. CPD was increased in female patients compared to controls (mean±SD CPD 0.50±0.22 vs. 0.28±0.17 seconds; p=0.007). Mean±SD Pes during spontaneous cough was comparable to induced cough (128±28 vs. 122±37 cmH2O, p=0.686) but less than maximum voluntary cough (170±46 cmH2O, p=0.020). Median within-subject correlation coefficients between cough intensity VAS and Pes, Pga and PCF were r=0.82 to 0.86.

Conclusions:  Maximum voluntary cough intensity was increased in patients with chronic cough compared with healthy controls. There was no significant difference in expiratory muscle contractility. Further studies should evaluate the compressive phase of cough in more detail. Physiological measures of cough intensity correlated strongly with subjective perception of intensity in patients with chronic cough, and may be relevant objective outcome measures for clinical studies.

original research 
Mari Herigstad, DPhil.; Anja Hayen, DPhil; Eleanor Evans, MSc; Frances M. Hardinge, MD; Robert J. Davies, MD; Katja Wiech, PhD; Kyle T. S. Pattinson, DPhil.
Topics: , , , ,

Background:  Dyspnea is the major source of disability in chronic obstructive pulmonary disease (COPD). In COPD, environmental cues (e.g. the prospect of having to climb stairs) become associated with dyspnea, and may trigger dyspnea even before physical activity commences. We hypothesised that brain activation relating to such cues would be different between COPD patients and healthy controls, reflecting greater engagement of emotional mechanisms in patients.

Methods:  Using FMRI, we investigated brain responses to dyspnea-related word cues in 41 COPD patients and 40 healthy age-matched controls. We combined these findings with scores of self-report questionnaires thus linking the FMRI task with clinically relevant measures. This approach was adapted from studies in pain that enables identification of brain networks responsible for pain processing despite absence of a physical challenge.

Results:  COPD patients demonstrate activation in the medial prefrontal cortex (mPFC), and anterior cingulate cortex (ACC) which correlated with the visual analogue scale (VAS) response to word cues. This activity independently correlated with patient-reported questionnaires of depression, fatigue and dyspnea vigilance. Activation in the anterior insula, lateral prefrontal cortex (lPFC) and precuneus correlated with the VAS dyspnea scale but not the questionnaires.

Conclusions:  Our findings suggest that engagement of the brain's emotional circuitry is important for interpretation of dyspnea-related cues in COPD, and is influenced by depression, fatigue, and vigilance. A heightened response to salient cues is associated with increased symptom perception in chronic pain and asthma, and our findings suggest such mechanisms may be relevant in COPD.

recent advances in chest medicine 
Laura E. Crotty Alexander, M.D.; Stephanie Shin, M.D.; John H. Hwang, M.S.
Topics: , ,

Smoking induced lung diseases were extremely rare prior to the twentieth century. With commercialization and introduction of machine-made cigarettes, worldwide use skyrocketed and several new pulmonary diseases have been recognized. The majority of pulmonary diseases caused by cigarette smoke (CS) are inflammatory in origin. Airway epithelial cells and alveolar macrophages have altered inflammatory signaling in response to CS, which leads to recruitment of lymphocytes, eosinophils, neutrophils, and mast cells to the lungs – depending on the signaling pathway (NFκB, AMPK, JNK, p38 and STAT3) activated. Multiple proteins are up-regulated and secreted in response to CS exposure, and many of these have immunomodulatory activities which contribute to disease pathogenesis. In particular, metalloproteases (MMP)-9 and -12, surfactant (SP-D), antimicrobial peptides (LL-37 and human beta defensin 2), and interleukins (IL)-1, -6, -8 and -17 have been found in higher quantities in the lungs of smokers with ongoing inflammation. However, many underlying mechanisms of smoking induced inflammatory diseases are not yet known. We review here the known cellular and molecular mechanisms of CS induced diseases, including chronic obstructive pulmonary disease (COPD), respiratory bronchiolitis-interstitial lung disease (RB-ILD), desquamative interstitial pneumonia (DIP), acute eosinophilic pneumonia, chronic rhinosinusitis, pulmonary Langerhans’ cell histiocytosis, and chronic bacterial infections. We also discuss inflammation induced by second-hand and third-hand smoke exposure, and the pulmonary diseases that result. New targeted anti-inflammatory therapeutic options are currently under investigation, and hopefully will yield promising results for the treatment of these highly prevalent smoking induced diseases.

ahead of the curve 
Gary F. Nieman, BS; Louis A. Gatto, PhD; Jason H.T. Bates, PhD; Nader M. Habashi, MD
Topics: ,

Trauma, hemorrhagic shock or sepsis can incite the systemic inflammatory response syndrome (SIRS), which can result in early acute lung injury (EALI). As EALI advances, improperly set mechanical ventilation can amplify early injury into a secondary ventilator induced lung injury (VILI) that invariably develops into overt acute respiratory distress syndrome (ARDS). Once established, ARDS is refractory to most therapeutic strategies, which have not been able to lower ARDS mortality below the current unacceptably high 40%. Low tidal volume ventilation (LVt) is one of the few treatments shown to have a moderate positive impact on ARDS survival, presumably by reducing VILI. There is thus a compelling case to be made that the focus of ARDS management should switch from treatment once this syndrome has become established to the application of preventative measures while patients are still in the EALI stage. Indeed, recent studies have shown that ARDS incidence is markedly reduced when conventional mechanical ventilation is applied preemptively using a combination of LVt and PEEP in both ICU patients and in surgery patients at high risk for developing ARDS. Furthermore, there is evidence from animal models and high-risk trauma patients that superior prevention of ARDS can be achieved using preemptive airway pressure release ventilation (APRV) with a very brief duration of pressure release. Preventing rather than treating ARDS may be the way forward in dealing with this recalcitrant condition, and would represent a paradigm shift in the way that mechanical ventilation is currently practiced.

ahead of the curve 
Nancy L. Geller, PhD; Dong-Yun Kim, PhD; Xin Tian, PhD

This paper describes the use of smart technology by investigators and patients to facilitate lung disease clinical trials and make them less costly and more efficient. By “smart technology” we include various electronic media, such as computer databases, the Internet, and mobile devices. We first describe the use of electronic health records (EHRs) for identifying potential subjects and then discuss electronic informed consent (eIC). We give several examples of using the Internet and mobile technology in clinical trials. Interventions have been delivered via the World Wide Web or via mobile devices and both have been used to collect outcome data. We discuss examples of new electronic devices that recently have been introduced to collect health data. While use of smart technology in clinical trials is an exciting development, comparison with similar interventions applied in a conventional manner is still in its infancy. We discuss advantages and disadvantages of using this omnipresent, powerful tool in clinical trials, as well as directions for future research.

original research 
Joao de Andrade, MD; Marvin Schwarz, MD; Harold R. Collard, MD; Tedryl Gentry-Bumpass; Thomas Colby, MD; David Lynch, MD; Robert Kaner, MD; for the IPFnet Investigators
Topics: ,

Background:  The NHLBI-sponsored IPF Clinical Research Network (IPFnet) studies enrolled subjects with idiopathic pulmonary fibrosis (IPF) to evaluate drug therapies in treatment trials. An Adjudication Committee (AC) provided a structured review of cases where there was uncertainty or disagreement regarding diagnosis or clinical event classification. This manuscript describes the diagnosis and adjudication processes.

Methods:  The diagnostic process was based on review of clinical data and HRCTs with central review of lung biopsies when available. The AC worked closely with the data coordinating center to obtain clinical, radiologic, and histologic data and to communicate with the clinical centers. AC utilized a multidisciplinary discussion model with four clinicians, one radiologist, and one pathologist to adjudicate diagnosis and outcome measures.

Results:  The IPFnet trials screened 1015 subjects; of these, 23 cases required review by the AC to establish eligibility. The most common diagnosis for exclusion was suspected chronic hypersensitivity pneumonitis. AC reviewed 88 suspected acute exacerbations (AEx), 93 non-elective hospitalizations, and 16 cases of bleeding. Determination of AEx presented practical challenges to adjudicators as necessary clinical data was often not collected, particularly when subjects were evaluated outside of the primary study site.

Conclusions:  The IPFnet diagnostic process was generally efficient, but a multidisciplinary adjudication committee was critical to assure correct phenotype for study enrollment. The AC was key in adjudicating all adverse outcomes in two IPFnet studies terminated early due to safety issues. Future clinical trials in IPF should consider logistical and cost issues as they incorporate AEx and hospitalizations as outcome measures.

original research 
David Kaplan; T. Charles Casper; C. Gregory Elliott; Shaohua Men; Robert C. Pendleton; Larry W. Kraiss; Andrew S. Weyrich; Colin K. Grissom; Guy A. Zimmerman; Matthew T. Rondina
Topics: , ,

Background:  Prospective studies on the incidence of VTE during severe sepsis and septic shock remain absent, hindering efficacy assessments regarding VTE prevention strategies in sepsis.

Methods:  We prospectively studied 113 consecutively enrolled ICU patients with severe sepsis and septic shock at three hospitals. All patients provided informed consent. VTE thromboprophylaxis was recorded for all patients. Patients underwent ultrasonography and were followed for VTE prior to ICU discharge. All-cause 28-day mortality was recorded. Variables from univariate analyses that were associated with VTE (including CVC insertion, age, length of stay, and mechanical ventilation) were included in a multivariable logistic regression analysis using backward stepwise elimination to determine VTE predictors.

Results:  Mean APACHE II score was 18.2±7.0 and age was 50±18 years. Despite all patients receiving guideline-recommended thromboprophylaxis, the incidence of VTE was 37.2% (95% CI 28.3-46.8). Most VTE events were clinically significant (defined as PE, proximal DVT, and/or symptomatic distal DVT) and associated with an increased length of stay (18.2±9.9 vs. 13.4±11.5 days, p<0.05). Mortality was higher in patients with acute VTE but did not reach statistical significance. Insertion of a CVC and longer mechanical ventilation duration were significant VTE risk factors. VTE incidence did not differ by thromboprophylaxis type.

Conclusions:  This is the first multicenter prospective study to identify a high incidence of VTE in patients with severe sepsis and septic shock, despite the use of universal, guideline-recommended thromboprophylaxis. Our findings suggest that the systemic inflammatory milieu of sepsis may uniquely predispose septic patients to VTE. More effective VTE prevention strategies are necessary in septic patients.

original research 
Azmy Faisal, Ph.D.; Zaid Zoumot, MD, Ph.D.; Pallav L. Shah, MD; J. Alberto Neder, MD, Ph.D.; Michael I. Polkey, MD, Ph.D.; Nicholas S. Hopkinson, MD, Ph.D.
Topics: , , , ,

Background:  The impact of bronchoscopic lung volume reduction (BLVR) on physiological responses to exercise in patients with advanced emphysema remains incompletely understood. We hypothesised that effective BLVR (e-BLVR), defined as a reduction in residual volume >350mL, would improve cardiovascular responses to exercise and accelerate oxygen uptake (V. O2) kinetics.

Methods:  Thirty-one patients (FEV1: 36±9% predicted; residual volume: 219±57% predicted) underwent a constant intensity exercise test at 70% peak work-rate to the limit of tolerance before and after treatment bronchoscopy (n=24) or sham bronchoscopy (n=7). Physiological responses in e-BLVR patients (n=16) were compared with controls (ineffective BLVR or sham bronchoscopy; n=15).

Results:  e-BLVR reduced residual volume (-1.1±0.5L, p=0.001), improved lung diffusing capacity by 12±13% (p=0.001) and increased exercise tolerance by 181±214s (p=0.004). V. O2 kinetics were accelerated in the e-BLVR group but remained unchanged in controls (∆ mean response time: -20±29% vs. 1±25%, p=0.04). Acceleration of V. O2 kinetics was associated with reductions in heart rate and O2-pulse response half-times by 8% (84±14 to 76±15s, p=0.04) and 20% (49±16 to 34±16s, p=0.01), respectively. There were also increases in heart rate and O2-pulse amplitudes during the cardiodynamic phase post e-BLVR. Faster V. O2 kinetics in e-BLVR group were significantly correlated with reductions in residual volume (r=0.66, p=0.005), and improvements in inspiratory reserve volume (r=0.56, p=0.024) and exercise tolerance (r=0.63, p=0.008).

Conclusion:  Lung deflation induced by e-BLVR accelerated exercise V. O2 kinetics in patients with emphysema. This beneficial effect appears to be related mechanistically to an enhanced cardiovascular response to exercise which may contribute to improved functional capacity.

original research 
Man-Hui Li, MD; Li-Chao Fan, MD; Bei Mao, MD; Jia-Wei Yang, MD; Augustine M.K. Choi, MD, PhD; Wei-Jun Cao, MD, PhD; Jin-Fu Xu, MD, PhD
Topics: , ,

Background:  Many epidemiologic studies have documented variable relationships between ambient particulate matter (PM) and chronic obstructive pulmonary disease (COPD) hospitalizations and mortality in cities worldwide.

Methods:  Comprehensive and systematic searches were performed in the electronic reference databases (PubMed, EMBASE, Google Scholar, Ovid, and Web of Science) with specific search terms and selection criteria for relevant studies. Summary odds ratios (ORs) and 95% confidence intervals (CIs) were performed to evaluate the relationship between short-term PM2.5 exposure and COPD hospitalizations and mortality. The sources of heterogeneity and the effect of potential confounders were explored using subgroup analyses. Study findings were analyzed using random-effect model and fixed effect model in COPD hospitalizations and mortality, respectively.

Results:  The search yielded 12 studies suitable for meta-analysis of hospitalizations and six studies for the mortality meta-analysis during the period. A 10 ug/m3 increase in daily PM2.5 (lag days 0-7) was associated with a 3.1% (95% CI: 1.6%-4.6%) increase in COPD hospitalizations, and a 2.5% (95% CI: 1.5%-3.5%) increase in COPD mortality. Significant publication bias was not found in studies focusing on the relationship between short-term PM2.5 exposure and COPD hospitalizations and mortality.

Conclusions:  Our combined analysis indicated that short-term exposure to 10 μg/m3 increment of ambient PM2.5 is associated with increased COPD hospitalizations and mortality. Further study is needed to elucidate to which extent this relationship is causal together with other factors and to elucidate the mechanism by which PM2.5 induces activation of cellular processes promoting COPD exacerbations.

original research 
A.M. Yohannes; P.J. Raue; D. Kanellopoulos; A. McGovern; J.A. Sirey; D.N. Kiosses; S. Banerjee; J.K. Seirup; R.S. Novitch; G.S. Alexopoulos
Topics: , , ,

Background  Chronic obstructive pulmonary disease (COPD) is a major cause of all-cause mortality. We examined predictors of one-year mortality in patients with severe COPD and major depression after inpatient treatment in a rehabilitation hospital.

Methods  We screened 898 consecutively admitted patients. Of these, 138 patients received the diagnoses of COPD according to American Thoracic Society Guidelines and major depression by DSM-IV and signed consent; 67 were randomized to a treatment adherence enhancement intervention and 71 to usual care. We assessed history of falls, dyspnea related disability, severity of depression, medical burden and cognitive functioning. Following discharge form inpatient rehabilitation, participants were prospectively followed and mortality was ascertained over 52 weeks from hospital notes and reports of primary care physicians and relatives.

Results  One-year, all-cause mortality was 22% (31/138). Multivariate Cox regression analysis showed that history of falls in the six months preceding hospital admission was the strongest predictor of mortality (OR: 3.05, 95% CI: 1.40-6.66, p<0.005). Dyspnea during activities (PFSDQ-M Domain) was also associated with mortality (OR: 1.05, 95% CI 1.02-1.08, p <0.002). Depression severity, medical burden, and cognitive impairment were not predictors of mortality.

Conclusions  Recent falls and dyspnea during activities identify subgroups of depressed COPD patients at increased risk for all-cause mortality. These subgroups are in need of clinical attention and follow-up and can serve as targets for prevention research aiming to inform clinical strategies and public health planning.

original research 
Samy Suissa, PhD; Janie Coulombe, MSc; Pierre Ernst, MD, MSc
Topics: , , ,

Background:  The widespread use of inhaled corticosteroids for COPD treatment has been questioned. Recent studies of weaning some COPD patients off inhaled corticosteroids found little or no loss in adverse consequences compared with long-acting bronchodilators. It is however unclear whether their discontinuation reduces the elevated risk of pneumonia associated with these drugs.

Methods:  Using the Quebec health insurance databases, we formed a new-user cohort of COPD patients treated with inhaled corticosteroids during 1990-2005 and followed through 2007 or until a serious pneumonia event, defined as a first hospitalisation for or death from pneumonia. A nested case-control analysis of the cohort was used to estimate the rate ratio of serious pneumonia associated with discontinuation of inhaled corticosteroid use, compared with continued use, adjusted for age, sex, respiratory disease severity and co-morbidity.

Results:  The cohort included 103,386 users of ICS, of which 14,020 had a serious pneumonia event during 4.9 years of follow-up (incidence rate 2.8/100/year). Discontinuation of inhaled corticosteroids was associated with a 37% decrease in the rate of serious pneumonia (rate ratio (RR) 0.63; 95% confidence interval (CI): 0.60-0.66). The risk reduction was rapidly evident, going from 20% in the first month to 50% by the fourth month after discontinuation. The risk reduction was particularly marked with fluticasone (RR 0.58; 95% confidence interval (CI): 0.54-0.61), but less so with budesonide (RR 0.87; 95% CI: 0.78-0.97).

Conclusions:  Discontinuation of inhaled corticosteroid use in COPD is associated with a reduction in the elevated risk of serious pneumonia, particularly so with fluticasone.

point and counterpoint  FREE TO VIEW
Nichole T. Tanner, MD, MSCR, FCCP; Gerard A. Silvestri, MD, MS, FCCP
Topics: ,

Nearly 36,000 Americans a year present with locally advanced stage IIIA lung cancer, with an overall 5 year survivorship of 19%. Superior sulcus tumors are either stage IIB (T3N0), IIIA (T3,N1-2, or T4, N0-1), or IIIB (T4,N2) with only a slightly better 5-year survival rates (25 to 30% ). With such a grim outlook, physicians are inclined to extrapolate the available literature in an effort to provide the best chance for cure. The concept of surgery after induction therapy for superior sulcus tumors posits that if you could get a response from chemoradiotherapy that “shrinks” the tumor away from critical structures in the apex of the lung near the brachial plexus and vertebral column, the addition of surgery could add benefit and potentially cure the patient. However a closer look at the available evidence does not support this approach in patients with superior sulcus tumors and N2 disease. Unfortunately, there is no level 1 evidence to support the use of induction therapy in patients with stage IIIA (N2) non-small cell lung cancer without superior sulcus involvement and only feasibility data to support its use in those with Pancoast tumors with N0- N1 disease. Further, induction therapy has never been tested in patients with superior sulcus tumors with N2 disease and therefore cannot be recommended.

point and counterpoint  FREE TO VIEW
Wilson W. Li, MD; Jacobus A. Burgers, MD, PhD; Houke M. Klomp, MD, PhD; Koen J. Hartemink, MD, PhD
Topics: ,

For patients with superior sulcus tumors (SST), i.e. lung cancer invading the apical chest wall structures, trimodality therapy has become the mainstay of treatment as recommended by the 2013 American College of Chest Physicians (ACCP) lung cancer guidelines. It also stated that involvement of mediastinal lymph nodes (N2-disease) is associated with poor survival after resection, contraindicating surgical treatment. However, the association of N2-disease with poor survival is based on results derived mainly from the era before the advent of trimodality therapy. Furthermore, this focus on survival bypasses potential palliative indications for resections of SSTs, which can induce severe, disabling pain symptoms. Pain control may be improved by additional surgical resection. As the treatment of pain in these patients is a major priority, a well-balanced surgical approach should thus still be considered, even in the presence of potential negative prognostic factors for survival such as N2-disease.

point and counterpoint  FREE TO VIEW
Nichole T. Tanner, MD, MSCR, FCCP; Gerard A. Silvestri, MD, MS, FCCP
Topics: , , , , , , , , , ,

Dr. Li and colleagues make four arguments in favor of adding surgery to current guideline directed standard of care chemoradiotherapy alone for treatment of patients who present with Superior Sulcus tumor (SS) and mediastinal (N2) lymphadenopathy. The first assertion is that research regarding treatment strategies in this population occurred prior the “trimodality era” and therefore should be revisited. We agree, patients with SS treated prior to trimodality therapy did not do well and those with N2 disease did even worse. The trials that did utilize trimodality therapy for SS had better outcomes, but the vast majority excluded patients with N2 disease. These findings led to the 2013 ACCP lung cancer guidelines recommending this approach for those with SS and N0-1 disease. It was also the rationale for why the guidelines recommend against surgery in patients with SS and N2 disease. Armed with this data, our colleagues suggest that the “promising results” from the aforementioned trials should have us consider broadening patient selection strategy to include N2 disease and point to several studies to augment their position – the second tenant of their argument.

point and counterpoint  FREE TO VIEW
Wilson W. Li, MD; Jacobus A. Burgers, MD, PhD; Houke M. Klomp, MD, PhD; Koen J. Hartemink, MD, PhD
Topics: , , , , , , ,

Dr. Tanner and dr. Silvestri make a compelling argument regarding the lack of high-grade evidence in supporting the use of adjuvant surgical resection in patients with superior sulcus tumors (SST) with mediastinal lymph node involvement (N2-disease). Indeed, there are no randomized trials on trimodality treatment in SST with N2-disease. However, the subsequent conclusion stating induction therapy followed by surgical treatment in these patients is not supported by current evidence seems to be the partial truth.

topics in practice management 
Alan L. Plummer, MD, FCCP
Topics: , ,

After a patient encounter, the physician uses two coding systems to bill for the service rendered to the patient. CPT is used to describe the encounter or procedure. ICD-9-CM is used to describe the diagnosis(es) of the patient. On October 1, 2015, ICD-9-CM will end and all physicians will be required to use a new diagnostic coding system, ICD-10-CM. This paper describes the new diagnostic coding system and how it differs from old system. There are resources and costs involved for physicians and physician practices in order to prepare properly for ICD-10-CM. Similar to other important events, the more thorough the preparation, the more likely a positive outcome will occur. Resource utilization is very important in preparation for the transition from ICD-9-CM to ICD-10-CM. The greater familiarity with ICD-10-CM plus a thorough, effective preparation will lead to reduced costs and a smooth transition. Coding descriptor changes and additional codes occur in ICD-10-CM codes for chronic bronchitis and emphysema, asthma, respiratory failure and sleep apnea. These changes will affect the coding of these diseases and disorders by physicians. Because the number of codes will increase over five-fold, the complexity of documentation to support ICD-10-CM will increase substantially. The documentation in the patient’s chart to support the ICD-10-CM codes used will need to be enhanced. The requirement for accurate and comprehensive documentation cannot be emphasized enough. All of the coding and documentation changes will be a challenge to the pulmonary, critical care and sleep physicians. They will need to be prepared fully when ICD-10-CM begins and ICD-9-CM stops abruptly on October 1, 2015.

original research  FREE TO VIEW
MyMy C. Buu, MD; Lee M. Sanders, MD, MPH; Jonathan Mayo, MPH; Carlos E. Milla, MD; Paul H. Wise, MD, MPH
Topics: , ,

Background:  Over the past 30 years, therapeutic advances have extended the median life span of patients with cystic fibrosis (CF). Hispanic patients are a vulnerable subpopulation with high of prevalence of risk factors for worse health outcomes. The consequences of these differences on health outcomes have not been well described. The objective of this study is to characterize the difference in health outcomes, including mortality rate, between Hispanic and non-Hispanic patients with CF.

Methods:  Retrospective analysis of CF Foundation patient registry data of California residents with CF, diagnosed during or after 1991, from 1991-2010. Ethnicity was self-reported. Primary outcome was mortality. Hazard ratios were estimated from a Cox regression model, stratified by gender and adjusted for socioeconomic status, clinical risk factors, and year of diagnosis.

Results:  Of 1719, 485 (28.2%) self-identified as Hispanic. Eighty-five deaths occurred, with an overall mortality rate of 4.9%. Unadjusted mortality rate was higher among Hispanic patients than non-Hispanic patients (9.1% vs. 3.3%, p<0.0001). Compared with non-Hispanic patients, Hispanic patients had lower survival rate 18 years post-diagnosis (75.9% vs. 91.5%, p<0.0001). Adjusted for socioeconomic status and clinical risk factors, Hispanic patients had increased rate of death compared to non-Hispanic patients (HR 2.81, 95% CI 1.70-4.63).

Conclusion:  Hispanic patients with CF have a higher mortality rate than non-Hispanic patients, even after adjusting for socioeconomic status and clinical severity. Further investigation of mechanism for the measured difference in lung function will help inform interventions and improve the health of all CF patients.

original research  OPEN ACCESS
Nichole T. Tanner, MD, MSCR; Jyoti Aggarwal, MHS; Michael K. Gould, MD, MS; Paul Kearney, PhD; Gregory Diette, MD, MHS; Anil Vachani, MD, MS; Kenneth C. Fang, MD; Gerard A. Silvestri, MD, MS
Topics: ,

Background:  Pulmonary nodules (PNs) are a common reason for referral to pulmonologists. The majority of data for evaluation and management of PNs are derived from studies performed in academic medical centers. Little is known about prevalence, diagnosis, use of diagnostic testing and management of PNs by community pulmonologists.

Methods:  This multicenter observational record review evaluated 377 patients ages 40-89 referred to 18 geographically diverse community pulmonary practices for intermediate PN (8-20mm). Study measures included prevalence of malignancy, procedure/test utilization, and nodule pretest probability for malignancy as calculated by to previously validated models. The relationship between calculated pre-test probability and management decisions was evaluated.

Results:  The prevalence of malignancy was 25% (n=94). Nearly half of patients (46%, n=175) had surveillance alone. Biopsy was performed in 125 (33.2%) patients. A total of 77 patients (20.4%) underwent surgery, of whom 35% (n=27) had benign disease. PET scan was used in 141 patients (37%). The false positive rate for PET was 39% (95%CI: 27.1%, 52.1%). Pre-test probability for malignancy calculations showed 9.5% (n=36) were low-risk, 79.6% (n=300) were moderate risk, and 10.8% (n=41) were high risk for malignancy. The rate of surgical resection was similar between the three groups (17%, 21%, 17%, respectively; p-value =0.69).

Conclusion:  A substantial fraction of intermediate sized nodules referred to pulmonologists ultimately prove to be lung cancer. Despite advances in imaging and non-surgical biopsy techniques, invasive sampling of low-risk nodules and surgical resection of benign nodules remains common, suggesting a lack of adherence to guidelines for management of PNs.

original research 
Peggy S. Lai, MD; William J. Sheehan, MD; Jonathan M. Gaffin, MD; Carter R. Petty, MA; Brent A. Coull, PhD; Diane R. Gold, MD; Wanda Phipatanakul, MD
Topics: , ,

BACKGROUND:  Endotoxin exposure is associated with airway inflammation. Children spend 6-8 hours a day in school, yet the effect of school-specific endotoxin exposure on asthma morbidity is not well understood.

METHODS:  In this longitudinal cohort study, 248 students with asthma from 38 inner-city schools underwent baseline phenotyping and follow-up. Clinical outcomes were evaluated throughout the academic school year and linked to classroom-specific dust and air endotoxin levels as well as home dust endotoxin levels. The primary outcome was maximum asthma symptom days per two week period.

RESULTS:  Classrooms had higher settled dust endotoxin levels compared to homes (14.3 vs. 11.3 EU/mg, p=0.02). 22.0% of classrooms had airborne endotoxin levels exceeding recommended occupational exposure limits for adults. Classroom air endotoxin levels were independently associated with increased maximum symptom days in non-atopic, but not in atopic asthmatics (interaction p-value 0.03). Adjusting for home exposures, classroom endotoxin exposure was independently associated with a dose-dependent increase in asthma symptom days for non-atopics (adjusted IRR 1.16 [1.03 – 1.31, p=0.02]. In these subjects, maximum symptom days increased by 1.3 days for each 14 day period when comparing students in classrooms with the lowest endotoxin levels compared to average measured levels.

CONCLUSIONS:  Inner-city children with asthma are exposed to high levels of airborne endotoxin at school, resulting in increased asthma symptoms in non-atopic children. Mitigation of school-related exposures may represent a strategy to decrease asthma morbidity in this population.

Clinicaltrials.gov identifier:  NCT01756391

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