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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.

editorials  FREE TO VIEW
David Yankelevitz, MD
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Based on the U.S. Preventive Services Task Force (USPSTF) “B” recommendation for lung cancer screening, commercial insurers operating through the Affordable Care Act exchanges, with the exception of certain grandfathered plans, must cover those under 65 who meet the USPSTF criteria for CT screening without co-payments before the end of 2015. Thus, for these insurers the question regarding coverage is settled all that might be considered is whether or not the law is reasonable or whether the USPSTF made an improper recommendation. In regard to the Centers for Medicare and Medicaid Services (CMS), the decision will be based on whether they determine the test has a proven benefit to the covered population. In making this determination it is necessary to understand the benefit in terms of potential lives saved compared with potential harms. With lung cancer being the leading cause of cancer death in the Medicare population, the stakes are high. However, should CMS decide not to provide this coverage, the incongruous result would be that those younger and at lower risk would be covered while those at higher risk would not. In a somewhat analogous manner it would also allow for those over 65 years of age with means to pay on their own the opportunity to be screened while poor and probably even at higher risk populations would not have access.

editorials  FREE TO VIEW
Katherine Courtright, MD; Scott Manaker, MD, PhD, FCCP
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Primarily detected in an advanced stage, lung cancer is the leading cause of cancer-related death in the United States (US), and remains one of the most costly cancers with dismal 5-year survival rates. Recently, the National Lung Screening Trial (NLST) demonstrated a 20% relative (1% absolute) reduction in lung-cancer mortality by annual screening over 3 years with low-dose computed tomography (LDCT) compared with chest radiography (CXR). These results and the US Preventative Services Task Force (USPSTF) grade B recommendation fueled pressure for national insurance coverage of lung-cancer screening with LDCT. In contrast, the Medicare Evidence Development and Coverage Advisory Committee (MEDCAC) concluded the apparent benefits of LDCT screening did not clearly outweigh the harms among Medicare beneficiaries. While awaiting the Centers for Medicare and Medicaid Services (CMS) decision on coverage of LDCT screening (expected in 2015), we consider the extent and quality of the data currently available to make a reliable determination of the risk-benefit profile for this preventative service.

editorials  FREE TO VIEW
David Yankelevitz, MD
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In the editorial by Courtright and Manaker the pattern I had expressed concern about regarding overstating the harms and underestimating the benefits continues. Notably, the evidence regarding harms refers solely to NLST data neglecting all of the progress made in the past decade in technology as well as knowledge for developing more efficient and safer protocols. While the NLST was performed primarily at academic centers, there was no requirement that the follow up studies or treatments be performed there, or even requirements regarding following a protocol. Concerns expressed regarding implementation in the community setting including inability to utilize best practice guidelines seem unwarranted given the success that has been demonstrated in developing quality standards for mammography. There is every reason to believe similar types of implementation, by the same organizations, can also be accomplished for CT screening. Support for this also comes from the I-ELCAP report showing no difference in performance between the academic and community setting.

editorials  FREE TO VIEW
Katherine Courtright, MD; Scott Manaker, MD, PhD, FCCP
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We appreciate Dr Yankelevitz’s discussion favoring coverage for lung cancer screening with low-dose computed tomography (LDCT), and agree with many of his thoughtful points. The divergent viewpoints expressed in this debate stem from the philosophical question of whether the glass is half empty or half full. The former approach best aligns with the ethical principles underlying preventative medicine, specifically that all potential harms are held to the highest level of scrutiny. Thus we are obliged to confess, not underestimate or necessarily accept, the gaps in evidence for LDCT screening.

original research 
Julio C. Valencia, MD; Wendy K. Steagall, PhD; Yi Zhang, PhD; Patricia Fetsch, BS; Andrea Abati, MD; Katsuya Tsukada, MD, PhD; Eric Billings, PhD; Vincent J. Hearing, MD, PhD; Zu-Xi Yu, MD, PhD; Gustavo Pacheco-Rodriguez, PhD; Joel Moss, MD, PhD, FCCP
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Background:  Lymphangioleiomyomatosis (LAM) is characterized by the proliferation in the lung, axial lymphatics (e.g. lymphangioleiomyomas) and kidney (e.g., angiomyolipomas) of abnormal smooth muscle-like LAM cells, which express melanoma antigens such as Pmel17/gp100 and have dysfunctional tumor suppressor tuberous sclerosis complex (TSC) genes TSC2 or TSC1. Histopathological diagnosis of LAM in lung specimens is based on identification of the Pmel17 protein with the monoclonal antibody HMB-45.

Methods:  We compared the sensitivity of HMB-45 to that of anti-peptide antibody αPEP13h, which reacts with a carboxy terminal peptide of Pmel17. LAM lung nodules were laser-capture microdissected to identify proteins by Western blotting.

Results:  HMB-45 recognized ∼25% of LAM cells within the LAM lung nodules, whereas αPEP13h identified over 82% of LAM cells within these structures in ∼90% of patients. Whereas HMB-45 reacted with epithelioid but not with spindle-shaped LAM cells, αPEP13h identified both spindle-shaped and epithelioid LAM cells, providing greater sensitivity for detection of all types of LAM cells. HMB-45 recognized Pmel17 in premelanosomal organelles; αPEP13h recognized proteins in the cytoplasm as well as premelanosomal organelles. Both antibodies recognized a Pmel17 variant of ∼50-kDa.

Conclusions:  Based on its sensitivity and specificity, αPEP13h may be useful in the diagnosis of LAM and more sensitive than HMB45.

original research 
R. Nisha Aurora, MD; Rachel Swartz; Naresh M. Punjabi, MD, PhD
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Background:  The advent of home sleep testing has allowed for the development of an ambulatory care model for obstructive sleep apnea (OSA) that is easily deployed by most healthcare providers. While automated algorithms that accompany home sleep monitors can identify and classify disordered breathing events, it is unclear if manual scoring followed by expert review of home sleep recordings is of any value. Thus, the current study examined the agreement between automated and manual scoring of home sleep recordings.

Methods:  Two type III monitors (ApneaLink Plus and Embletta) with distinct study samples were used. Data from manual and automated scoring were available for 200 subjects. Two thresholds for oxygen desaturation (≥3% and ≥4%) were used to define disordered breathing events. Agreement between manual and automated scoring was examined using Pearson’s correlation coefficients and Bland-Altman analyses.

Results:  Automated scoring consistently underscored disordered breathing events compared with manual scoring for both sleep monitors irrespective of whether a ≥3% or ≥4% oxygen desaturation threshold was used to define the apnea-hypopnea index (AHI). Bland-Altman analyses revealed that for the ApneaLink Plus, the average AHI difference between the manual and automated scoring was 6.1 events/hr (95% CI: 4.9-7.3) and 4.6 events/hr (95% CI: 3.5-5.6) for the ≥3% and ≥4% oxygen desaturation threshold, respectively. Similarly, for the Embletta, the average difference between the manual and automated scoring was 5.3 events/hr (95% CI: 3.2-7.3) and 8.4 events/hr (95% CI: 7.2-9.6), respectively.

Conclusions:  While agreement between automated and manual scoring of home sleep recordings varies based on the device used, modest agreement was observed between the two approaches. However, manual review of HST recordings can decrease the misclassification of OSA severity, particularly for those with mild disease.

Study Registration:  http://www.clinicaltrials.gov (NCT01503164)

original research 
Yvette C. Cozier, D.Sc.; Patricia F. Coogan, D.Sc.; Praveen Govender, M.D.; Jeffrey S. Berman, M.D.; Julie R. Palmer, Sc.D.; Lynn Rosenberg, Sc.D.
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BACKGROUND:  Sarcoidosis, a systemic disorder characterized by chronic granulomatous inflammation, occurs more frequently among US black women, as do overweight and obesity. Little is known about the relation of overweight and obesity, which induce chronic inflammation, to incidence of sarcoidosis.

METHODS:  We assessed the relation of obesity and weight gain to the incidence of sarcoidosis in the Black Women’s Health Study, a follow-up study of 59,000 US black women aged 21-69 years at baseline in 1995. Information on weight at age 18, height, current weight, incident sarcoidosis, and covariates was collected at baseline and on biennial follow-up questionnaires. Cox regression models adjusted for age, education, geographic region, smoking, alcohol consumption, and physical activity were used to estimate incidence rate ratios (IRR) and 95% confidence intervals (CI).

RESULTS:  From 1995 through 2011, 454 incident cases of sarcoidosis occurred during 707,557 person-years of follow up. The incidence of sarcoidosis increased with increasing body mass index (BMI) and weight gain. The IRR was 1.40 (95% CI: 0.88-2.25) for body mass index (BMI) ≥30 kg/m2 at age18 relative to 20-24 kg/m2 (Ptrend=0.18), 1.42 (95% CI: 1.07-1.89) for BMI ≥35 kg/m2 at baseline relative to 20-24 kg/m2 (Ptrend=0.01), and 1.47 (1.10-1.97) for weight gain between age 18 and baseline of ≥30 kg relative to 0-9 kg (Ptrend=0.16). In stratified analyses, there were significant trends of sarcoidosis incidence with increasing BMI and weight gain in women aged 45 and older and ever-smokers.

CONCLUSION:  The present study provides evidence that weight gain and obesity during adulthood are associated with increased sarcoidosis incidence.

original research 
Feng Wang, MMSc; Zhen Wang, MD; Zhaohui Tong, MD; Lili Xu, MMSc; Xiaojuan Wang, MMSc; Yanbing Wu, MD
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Background:  Conventional medical thoracoscopy(MT),routinely performed in patients with pleural diseases, does not always give a conclusive diagnosis. The endoscopic appearance of pleural diseases under white light could be misleading. Autofluorescence has been shown to be an interesting and effective diagnostic tool, and in this study we will investigate its use during MT.

Objective:  To evaluate the diagnostic value of autofluorescence imaging during MT.

Methods:  Patients with undiagnosed pleural effusion, who were admitted to our clinical center from 2013.8 to 2014.2, were enrolled. MT was performed firstly with white light and followed by autofluorescence. Endoscopic results of different diseases were recorded and the biopsy specimens were obtained for pathological analysis. We calculated the diagnostic sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of the two methods by comparing them to the pathological results.

Results:  37 eligible patients were studied, including 21cases with malignancy, 9 cases with tuberculous pleurisy, 3 cases with infective pleurisy, and 4 undiagnosed cases. Autofluorescence found additional malignant lesions, which were missed under white light in 5cases. The diagnostic sensitivity, NPV and 95% confidence interval of autofluorescence was 100% (98.5%, 100%) and 100% (93.9%, 100%). Autofluorescence was superior over white light, which sensitivity and NPV was 92.8% (89.3%, 95.3%) and 76.8% (67.0%, 84.4%). For the specificity and PPV, there was no significant difference.

Conclusion:  The advantage of autofluorescence is its high sensitivity and NPV. It is useful to detect micro-lesions and delineating the pathological margins. Autofluorescence can benefit patients with its better visualization.

original research 
Ryan M. Kern; Jonathan P. Singer; Laura Koth; Joshua Mooney; Jeff Golden; Steven Hays; John Greenland; Paul Wolters; Emily Ghio; Kirk D. Jones; Lorriana Leard; Jasleen Kukreja; Paul D. Blanc
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Background:  Hypersensitivity pneumonitis (HP) is an inhaled antigen-mediated interstitial lung disease (ILD). Advanced disease may lead to lung transplantation. There are no published studies addressing lung transplant outcomes in HP. We characterized HP outcomes compared to referents undergoing lung transplantation for idiopathic pulmonary fibrosis (IPF).

Methods:  To identify HP cases, we reviewed records for all ILD lung transplantation cases at our institution from 2000-2013. We compared clinical characteristics, survival, and acute and chronic rejection for lung transplant recipients with HP to IPF referents. We also reviewed diagnoses of HP discovered only by explant pathology and looked for evidence of recurrent HP after transplant. Survival was compared using Kaplan-Meier methods and Cox proportional hazard modeling.

Results:  We analyzed 31 subjects with HP and 91 with IPF among 183 cases undergoing lung transplantation for ILD. Survival at 1, 3, and 5 years after lung transplant in HP compared to IPF was 96%, 89% and 89% vs. 86%, 67%, and 49%, respectively. HP subjects manifested a reduced adjusted risk of death compared to IPF subjects (HR 0.25, 95% CI 0.08-0.74; p=0.013). Of the 31 cases, the diagnosis of HP was unexpectedly made at explant in 5 (16%). Two subjects developed recurrent HP in their allografts.

Conclusions:  Overall, subjects with HP have excellent medium-term survival after lung transplantation and, relative to IPF, a reduced risk of death. HP may be initially discovered only by review of the explant pathology. Notably, HP may recur in the allograft.

original research 
Xiaofan Wu, MD; Shuzheng Lv, MD; Xiaohong Yu, MD; Linyin Yao, MD; Babak Mokhlesi, MD, M.Sc.; Yongxiang Wei, MD
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Background:  The impact of obstructive sleep apnea (OSA) treatment with continuous positive airway pressure (CPAP) on percutaneous coronary intervention (PCI) outcomes remains largely unknown.

Methods:  Between 2002 and 2012 we identified 390 patients with OSA who had undergone a PCI. OSA was diagnosed by in-laboratory sleep studies and defined by an apnea-hypopnea index (AHI) ≥5 events/h. The cohort was divided into 3 groups: 1) moderate-severe OSA successfully treated with CPAP (n=128); 2) untreated moderate-severe OSA (n=167); and 3) untreated mild OSA (n=95). Main outcomes included repeat revascularization, major adverse cardiac events (MACE) (i.e. death, nonfatal myocardial infarction and repeat revascularization), and major adverse cardiac or cerebrovascular events (MACCE). The median follow up was 4.8 years (interquartile range 3.0 to 7.1).

Results:  The untreated moderate-severe OSA group had a higher incidence of repeat revascularization than the treated moderate-severe OSA group (25.1% vs. 14.1%, P=0.019). There were no differences in mortality (P=0.64), MACE (P=0.33) and MACCE (P=0.76) amongst the 3 groups. In multivariate analysis adjusted for potential confounders untreated moderate-severe OSA was associated with increased risk of repeat revascularization (hazard ratio 2.13, 95% CI 1.19-3.81, P=0.011).

Conclusion:  Untreated moderate-severe OSA was independently associated with a significant increased risk of repeat revascularization after PCI. CPAP treatment reduced this risk.

original research 
Yonghua Gao, PhD; Weijie Guan, PhD; Gang Xu, PhD; Zhiya Lin, MD; Yan Tang, MD; Zhimin Lin, MM; Yang Gao, PhD; Huimin Li, MT; Nanshan Zhong, MD; Guojun Zhang, PhD; Rongchang Chen, MD
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Background:  Although viral infections are major cause of exacerbations in patients with chronic airway diseases, their roles in triggering bronchiectasis exacerbations in adults remain unclear. We therefore prospectively investigated the incidence and clinical impacts of viral infection in adults with bronchiectasis exacerbations.

Methods:  One hundred and nineteen adults with bronchiectasis were followed up prospectively for 12 months. Nasopharyngeal swab (NPS) and sputum were assayed for 16 respiratory viruses using polymerase chain reaction (PCR). Symptoms, spirometry, quality of life, bacterial culture and inflammatory makers were assessed, during steady-state and exacerbations.

Results:  A total of 100 exacerbations were captured from 58 patients during one-year follow-up. Respiratory viruses were found more frequently in NPS and sputum during bronchiectasis exacerbations (49/100, 49.0%) than steady-state (11/58, 18.9%, P<0.001). The most common viruses at exacerbations were coronavirus (19/65, 39.2%), rhinovirus (16/65, 24.6%) and influenza A/B (16/65, 24.6%). Virus-positive exacerbations were associated with a greater increase in makers of systemic and airway inflammation (serum IL-6 and TNF-a; sputum IL-1β and TNF-a) compared with virus-negative exacerbations, but the differences in spirometric indices, quality of life and bacterial density were unremarkable. In receiver operating characteristics analysis, serum interferon-γ-induced protein 10 (IP-10) yielded an area under curve of 0.67 (95%CI, 0.53-0.77; P=0.018). Furthermore, a greater proportion of patients with virus-positive exacerbations received intravenous antibiotics.

Conclusions:  Prevalence of viral infections, detected by PCR, is higher in exacerbations than in steady-state, suggesting that respiratory viruses play crucial roles in triggering bronchiectasis exacerbations. The potential mechanisms of virus-induced bronchiectasis exacerbations merit further investigations.

Trial registration:  clinicaltrials.gov; Identifier: NCT01801657.

original research 
Gregory Y. H. Lip, MD; Nicolas Clementy, MD; Bertrand Pierre, MD; Mathieu Boyer; Laurent Fauchier, MD, PhD
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Background  Diabetes mellitus is recognized as a stroke risk factor in atrial fibrillation (AF). Diabetics with retinopathy have an increased risk of systemic cardiovascular complications, and also, severe diabetic retinopathy predisposes to ocular bleeds.We hypothesised that diabetic AF patients with retinopathy have increased stroke/thromboembolism and severe bleeding risks in AF, when compared to diabetic AF patients without retinopathy, or to non-diabetics with AF.

Methods and Results  We tested our hypothesis in a large “real- world” cohort of individuals with AF from the Loire Valley Atrial Fibrillation project.Of 8962 patients with AF on our dataset, 1409 (16%) had documented diabetes mellitus, of which, 163 (1.8% of the whole cohort) were patients with diabetic retinopathy.After a followup of 31±36 months, when compared to non-diabetics, the risk of stroke/TE in diabetics with no retinopathy increased 1.3 fold (RR 1.30; 95%CI 1.07-1.59, p=0.01), and in diabetics with retinopathy, the risk of stroke/TE was increased 1.58 fold (RR 1.58; 95%CI 1.07-2.32, p=0.02). There was no significant difference when diabetics with no retinopathy were compared to diabetics with retinopathy (RR 1.21, 95%CI 0.80-1.84, p=0.37). A similar pattern was seen for mortality and severe bleeding. On multivariate analysis, the presence of diabetic retinopathy did not emerge as an independent predictor for stroke/TE or severe bleeding.

Conclusion  Crude rates of stroke/TE increased in a stepwise fashion when non-diabetic AF patients were compared to diabetics with no retinopathy and diabetics with retinopathy. However, we have shown for the first time that the presence of diabetic retinopathy did not emerge as an independent predictor for stroke/TE or severe bleeding on multivariate analysis.

original research 
Peter Brønnum Nielsen, MSc, PhD; Torben Bjerregaard Larsen, MD, PhD; Anders Gorst-Rasmussen, MSc, PhD; Flemming Skjøth, MSc, PhD; Lars Hvilsted Rasmussen, MD, PhD; Gregory Y.H. Lip, MD
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Background:  The risk of ischemic stroke/thromboembolic events after an intracranial haemorrhage (ICH) in atrial fibrillation (AF) patients on warfarin treatment is poorly characterised. The aim of this study was to assess the association between the risk of ischaemic stroke/thromboembolic events and ICH.

Methods:  Linkage of three Danish nationwide administrative registries in the period between 1999-2012 identified AF patients on warfarin treatment. Event rate ratios of stroke/thromboembolic events, major bleeding and all-cause mortality stratified by ICH were calculated, and Cox proportional hazard models were used to compare event rates among ICH survivors. A matched odds ratio (OR) was calculated for ICH occurrences within 0-3 months relative to 3-6 months prior to a stroke/thromboembolic event. A rate ratio of claimed warfarin prescriptions in a 3-month period pre- and post-ICH was also calculated.

Results:  We studied 58,815 AF patients (median age 72.6 years; 60% male). When compared to the non-ICH group, the ICH group was at increased risk for stroke/SE/TIA [Rate Ratio 3.67 (95% confidence interval [CI], 3.12 to 4.31] and mortality [5.55 (95% CI, 5.20 to 5.92)], but not for major bleeding [1.06 (95% CI, 0.81 to 1.39)]. The matched OR of ICH occurrences prior to a stroke/SE/TIA was 4.33 (95% CI, 2.44 to 8.15). The rate ratio of claimed warfarin prescriptions post and pre-ICH event was 0.28 (95% CI, 0.24 to 0.33).

Conclusion:  In this large-scale study of AF patients treated with warfarin, first-time ICH was associated with an increased rate of ischaemic stroke/SE/TIA and mortality compared to the non-ICH group. There was a decrease in the warfarin prescription purchase rate post-ICH period compared to pre-ICH, which may partly explain the excess risk.

original research 
Earl S. Ford, MD, MPH
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Background:  Chronic obstructive pulmonary disease (COPD) imposes a large public health burden internationally and in the United States. The objective of this study was to examine trends in mortality from COPD among US adults from 1968 to 2011.

Methods:  Data from the National Vital Statistics System from 1968 to 2011 for adults aged ≥25 years were accessed, and trends in mortality rates were examined with Joinpoint analysis.

Results:  Among all adults, age-adjusted mortality rose from 29.4 per 100,000 population in 1968 to 67.0 per 100,000 population in 1999 and then declined to 63.7 per 100,000 population in 2011 (annual percentage change [APC] 2000-2011: -0.2%, 95% confidence interval [CI]: -0.6, 0.2). The age-adjusted mortality among men peaked in 1999 and then declined (APC 1999-2011: -1.1%, 95% CI: -1.4, -0.7), whereas the age-adjusted mortality rate among women peaked in 2008 and subsequently increased slowly (APC 2000-2011: 0.4%, 95% CI: 0.0, 0.9). Despite a narrowing of the gender gap, mortality rates in men continued to exceed those in women. Evidence of a decline in the APC was noted for African American (1999-2011: -1.5%, 95% CI: -2.1, -1.0) and white men (1999-2011: -0.9%, 95% CI: -1.3, -0.6), adults aged 55-64 years (1989-2011: -1.0%, 95% CI: -1.2, -0.8), and adults aged 65-74 years (1999-2011: -1.2%, 95% CI: -1.6, -0.9).

Conclusions:  In the United States, the mortality rate from COPD has declined since 1999 in men and some age groups but appears to be still rising in women, albeit at a reduced pace.

original research 
David S. Hui, MD; Benny K. Chow, PhD; Thomas Lo, MSc; Susanna Ng, MRCP; Fanny W. Ko, MD; Tony Gin, MD; Matthew TV. Chan, MD
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Background:  Non-invasive ventilation via helmet or total facemask is an option for managing patients with respiratory infections in respiratory failure. However the risk of nosocomial infection is unknown.

Methods:  We examined exhaled air dispersion during non-invasive ventilation using a human-patient simulator reclined at 45° in a negative pressure room with 12 air changes/hour by two different helmets via a ventilator, and a total facemask via a bilevel positive airway pressure device. Exhaled air was marked by intrapulmonary smoke particles, illuminated by laser light sheet, and captured by a video camera for data analysis. Significant exposure was defined as where there was ≥ 20% of normalized smoke concentration.

Results:  During non-invasive ventilation via a helmet with the simulator programmed in mild lung injury, exhaled air leaked through the neck-helmet interface with a radial distance of 150 to 230 mm when inspiratory positive airway pressure was increased from 12 to 20 cmH2O, respectively, while keeping the expiratory pressure at 10 cmH2O. During non-invasive ventilation via a helmet with air cushion around the neck, there was negligible air leakage. During non-invasive ventilation via a total facemask for mild lung injury, air leaked through the exhalation port to 618 and 812 mm when inspiratory pressure was increased from 10 to 18 cmH2O, respectively, with the expiratory pressure at 5 cmH2O.

Conclusion:  Helmet with a good seal around the neck is needed to prevent nosocomial infection during non-invasive ventilation for patients with respiratory infections.

original research 
Sydney E.S. Brown, M.D., Ph.D.; Sarah J. Ratcliffe, Ph.D.; Scott D. Halpern, M.D., Ph.D.
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Background:  ICU readmissions are associated with increased mortality and costs; however, it is unclear whether these outcomes are caused by readmissions as opposed to residual confounding by illness severity. An assessment of temporal changes in ICU readmission in response to a specific policy change could help disentangle these possibilities. We sought to determine whether ICU readmission rates changed after 2003 ACGME Resident Duty Hours reform (“reform”), and whether there were temporally corresponding changes in other ICU outcomes.

Methods:  We utilized a difference-in-differences approach using Project IMPACT. Piecewise regression models estimated changes in outcomes immediately before and after reform in 274,491 critically ill medical and surgical patients in 151 community and academic U.S. ICUs. Outcome measures included ICU readmission, ICU mortality, and in-hospital post-ICU-discharge mortality.

Results:  In ICUs with residents ICU readmissions increased before reform (OR: 1.5 (1.22, 1.84), p<0.01), and decreased after (OR: 0.85 (0.73, 0.98), p=0.03). This abrupt decline in ICU readmissions after reform differed significantly from an increase in readmissions observed in ICUs without residents at this time (difference-in-differences p<0.01). No comparable changes in mortality were observed between ICUs with versus without residents.

Conclusions:  The changes in ICU readmission rates after reform, without corresponding changes in mortality, suggest that ICU readmissions are not causally related to other untoward patient outcomes. Instead, ICU readmission rates likely reflect operational aspects of care that are not patient-centered, making them less useful indicators of ICU quality.

original research 
Amany F. Elbehairy, MD, MSc; Natya Raghavan, MD; Sicheng Cheng, BSc; Ling Yang, MD; Katherine A. Webb, MSc; J. Alberto Neder, MD; Jordan A. Guenette, PhD; Mahmoud I. Mahmoud, MD, PhD; Denis E. O’Donnell, MD, FCCP; on behalf of the Canadian Respiratory Research Network
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Background:  Smokers with persistent cough and sputum production [chronic bronchitis (CB)] represent a distinct clinical phenotype, consistently linked to negative clinical outcomes. However, the mechanistic link between physiological impairment, dyspnea and exercise intolerance in CB has not been studied, particularly in those with mild airway obstruction. We therefore compared physiological abnormalities during rest and exercise in CB to those in patients without symptoms of mucus hypersecretion (non-CB) but with similar mild airway obstruction.

Methods:  Twenty CB (≥3 months cough/sputum in 2 successive years), 20 non-CB patients with GOLD grade 1-B COPD and 20 age/sex-matched healthy controls underwent detailed physiological testing including tests of small airway function and a symptom-limited incremental cycle exercise test.

Results:  CB patients (post-bronchodilator FEV1= 93±12 %predicted; mean±SD) had greater chronic activity-related dyspnea, poorer health-related quality of life and reduced habitual physical activity compared to both non-CB and controls (all p<0.05). The degree of peripheral airway dysfunction and pulmonary gas trapping was comparable in both patient groups. Peak oxygen uptake was similarly reduced in CB and non-CB compared with controls (70±26, 71±29 and 106±43 %predicted, respectively) but those with CB had higher exertional dyspnea ratings and greater respiratory mechanical constraints at a standardized work rate than non-CB patients (p<0.05).

Conclusion:  Patients with CB reported greater chronic dyspnea and activity restriction than non-CB patients with similar mild airway obstruction. The CB group had greater dynamic respiratory mechanical impairment and dyspnea during exercise than non-CB patients, which may help explain some differences in important patient-centered outcomes between the groups.

original research 
Horiana B. Grosu, MD; Rodolfo C. Morice, MD; Mona Sarkiss; Lara Bashoura, MD; George A. Eapen, MD; Carlos A. Jimenez, MD; Saadia Faiz, MD; Donald R. Lazarus; Roberto F. Casal; David E. Ost, MD, MPH
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Background:  Bronchoscopy in patients with space-occupying brain lesions is anecdotally felt to carry a high risk of neurologic complications.

Methods:  We conducted a retrospective cohort study of patients with evidence of malignant space-occupying brain lesion that were referred for flexible or rigid bronchoscopy or endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA). The primary outcome of interest was the incidence of neurologic complications following the procedures in these patients.

Results:  Of the 103 enrolled patients, flexible bronchoscopy was performed in 41, rigid bronchoscopy in 12 and EBUS-TBNA in 50. Among these patients, 41 (40%) had evidence suggestive of increased ICP on imaging. Among all study patients, 0 (95% CI 0-0.035) had neurologic, procedure-specific, or sedation-specific complications, and the level of care was not escalated in any of these patients.

Conclusion:  On the basis of our findings, we recommend that procedures such as flexible or rigid bronchoscopy or EBUS-TBNA in patients with malignant space-occupying brain lesions should be considered reasonably safe in patients with space-occupying brain lesions as long as neurologic findings are stable.

original research 
Gautam George, MD; Ivan O. Rosas, MD; Ye Cui, MD, PhD; Caitlin McKane, RN; Gary M. Hunninghake, MD; Phillip C. Camp, MD; Benjamin A. Raby, MD; Hilary J. Goldberg, MD, MPH; Souheil El-Chemaly, MD, MPH
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Background:  Human telomere disease consists of a wide spectrum of disorders, including pulmonary, hepatic and bone marrow abnormalities. The extent of bone marrow and liver abnormalities in patients with interstitial lung disease (ILD) and short telomeres is unknown.

Methods:  The lung transplant clinic established a prospective protocol to identify short telomeres in patients with ILD not related to connective tissue or sarcoidosis. Patients with short telomeres underwent bone marrow and/or liver biopsies as part of the evaluation for transplant candidacy.

Results:  127 patients met ILD categorization for inclusion. 30 were suspected to have short telomeres, and 15 had the diagnosis confirmed. Eight of 13 patients (53.3%) had bone marrow abnormalities. Four patients had hypocellular marrow associated with macrocytosis and relatively normal blood counts, which resulted in changes to planned immunosuppression at the time of transplant. Four patients with more severe hematologic abnormalities were not listed due to; myelodysplastic syndrome (2), monoclonal gammopathy of unclear significance (1), and hypocellular marrow, decreased megakaryocyte lineage associated with thrombocytopenia (1). Seven patients underwent liver biopsies and 6 had abnormal liver pathology. These abnormalities did not affect listing for lung transplant and liver biopsies are no longer routinely obtained.

Conclusion:  Subclinical bone marrow and liver abnormalities can be seen in patients with ILD and short telomeres, in some cases in the absence of clinically significant abnormalities in peripheral blood counts and liver function tests. A larger study examining the implication of these findings on the outcome of patients with ILD and short telomeres is needed.

original research 
Roman Brenner, (MD); Lorenza Pratali, (MD); Stefano F. Rimoldi, (MD); Carla Ximena Murillo Jauregui, (MD); Rodrigo Soria, (MD); Emrush Rexhaj, (MD); Carlos Salinas Salmón, (MD); Mercedes Villena, (MD); Catherine Romero; Claudio Sartori, (Prof); Yves Allemann, (Prof); Urs Scherrer, (Prof)
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Background  There is considerable inter-individual variability of pulmonary artery pressure among high altitude dwellers, but the underlying mechanism is not known. At low altitude, a patent foramen ovale (PFO) is present in ∼25% of the general population. Its prevalence is increased in clinical conditions associated with pulmonary hypertension and arterial hypoxemia and thought to aggravate these problems.

Methods  We searched for a PFO (transesophageal echocardiography) in healthy high altitude dwellers (n=22) and patients with chronic mountain sickness (n=35) at 3600 m above sea level and studied its effects (transthoracic echocardiography) on right ventricular function, pulmonary artery pressure and vascular resistance at rest and during mild exercise (50 W), an intervention designed to further increase pulmonary artery pressure.

Results  The prevalence of PFO (32 %) was similar to the one reported in low altitude populations and was not different in participants with/without chronic mountain sickness. Its presence was associated with right ventricular enlargement at rest and an exaggerated increase in right-ventricular-to-right-atrial pressure gradient (25±7 vs. 15±9 mm Hg, p<0.001) and a blunted increase of fractional area change of the right ventricle (3 [-1, 5] vs 7 [3, 16] %, p=0.008) during mild exercise.

Conclusion  These findings show for the first time that while the prevalence of PFO is not increased in high altitude dwellers, its presence appears to facilitate pulmonary vasoconstriction and right ventricular dysfunction during a mild physical effort frequently associated with daily activity.

Trial Registration:  ClinicalTrials.gov Identifier: NCT01182792

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