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 
Emrush Rexhaj, MD; Stefano F. Rimoldi, MD; Lorenza Pratali, MD; Roman Brenner, MD; Daniela Andries; Rodrigo Soria, MD; Carlos Salinas Salmón, MD; Mercedes Villena, MD; Catherine Romero, BS; Yves Allemann, MD; Alban Lovis, MD; Raphaël Heinzer, MD; Claudio Sartori, MD; Urs Scherrer, MD
Topics: , ,

Background:  Chronic mountain sickness (CMS) is often associated with vascular dysfunction, but the underlying mechanism is unknown. Sleep disordered breathing (SDB) frequently occurs at high altitude. At low altitude SDB causes vascular dysfunction. Moreover, in SDB, transient elevations of right-sided cardiac pressure may cause right-to-left shunting in the presence of a patent foramen ovale (PFO) and, in turn, further aggravate hypoxemia and pulmonary hypertension. We speculated that compared to healthy high-altitude dwellers, in patients with CMS, SDB and nocturnal hypoxemia are more pronounced and related to vascular dysfunction.

Methods:  We performed overnight sleep recordings, and measured systemic and pulmonary-artery pressure in 23 patients with CMS (mean±SD age 52.8±9.8 y) and 12 healthy controls (47.8±7.8 y) at 3600 m. In a subgroup of 15 subjects with SDB, we searched for PFO with transesophagal echocardiography.

Results:  The major new findings were that in CMS patients, a) SDB and nocturnal hypoxemia was more severe (P<0.01) than in controls (apnea/hypopnea index, AHI, 38.9±25.5 vs. 14.3±7.8[nb/h]; SaO2, 80.2±3.6 vs. 86.8±1.7[%], CMS vs. controls), and b) AHI was directly correlated with systemic blood pressure (r=0.5216, P=0.001) and pulmonary-artery pressure (r=0.4497, P=0.024). PFO was associated with more severe SDB (AHI 48.8±24.7 vs. 14.8±7.3[nb/h], P=0.013, PFO vs. no PFO) and hypoxemia.

Conclusion:  SDB and nocturnal hypoxemia are more severe in CMS patients than in controls and are associated with systemic and pulmonary vascular dysfunction. The presence of a PFO appeared to further aggravate SDB. Closure of PFO may improve SDB, hypoxemia and vascular dysfunction in CMS patients.

Clinical Trials Gov Registration:  NCT01182792

original research 
A.B. Chang, MBBS, PhD; J.J. Oppenheimer, MD; M. Weinberger, MD, FCCP; B.K. Rubin, MD; R.S. Irwin, MD, Master FCCP

Background:  We undertook systematic reviews to examine key questions (KQs) related to pediatric chronic wet cough. In children with chronic (>4-weeks) wet/productive cough not related to bronchiectasis; (KQ1)-how effective are antibiotics in improving the resolution of cough? If so, what and for how long? and; (KQ2)-when should they be referred for further investigations?

Methods:  We used the CHEST expert cough panel’s protocol. Two authors screened searches, selected and extracted data. Systematic reviews, randomized controlled trials (RCTs), cohort (prospective and retrospective) and cross-sectional studies published in English were included.

Results:  Data were presented in PRISMA flowcharts and summaries tabulated. Fifteen studies were included in KQ1 (systematic reviews=3, RCTs=3, prospective studies=5, retrospective studies=4) and 17 in KQ2 (RCT=1, prospective=11, retrospective=5). Combining data from RCTs (KQ1), the number needed to treat for benefit was 3 (95%CI 2.0-4.3) in achieving cough resolution. In general, findings from prospective and retrospective studies were consistent but there were minor variations.

Conclusion:  There is high quality evidence that in children aged ≤14-years with chronic (>4-weeks duration) wet or productive cough, the use of appropriate antibiotics improves cough resolution. There is also high quality evidence that when specific cough pointers (e.g. digital clubbing) are present in children with wet cough, further investigations (e.g. flexible bronchoscopy, chest CTs and immunity tests) should be undertaken. When the wet cough does not improve by 4-weeks of antibiotics, there is moderate quality evidence that children should be referred to a major center for consideration of further investigations to determine whether an underlying lung or other disease are present.

original research 
Pablo E. Brockmann, MD, PhD; Felipe Damiani; David Gozal, MD, MBA, FCCP
Topics: ,

Background and Objectives:  Prevalence and potential risk contributors of sleep-disordered breathing (SDB) in adolescents and younger adults remain unclear. We hypothesized that SDB prevalence in younger Hispanic adults is higher than the limited evidence indicates.

Methods:  Population-based study of Hispanic subjects surveyed as part of the Chilean National Health Survey database. For this study, only subjects aged 15-40 years were included. Sleep and demographic questionnaires were used to assess SDB prevalence and its risk factors. Anthropometric measurements were performed in each subject. Prevalence was calculated for each SDB-related symptom. A regression model was constructed to investigate demographic risk factors of SDB.

Results:  A total of 2,147 subjects were included. Mean age (± SD) was 27.2 ± 7.2 years, n=899 (42%) were males. Habitual snoring was highly prevalent with an average of 53.8% in men, and 38.3% in women. Snoring, witnessed apneas, and daytime somnolence increased continuously with age with an abnormal SDB questionnaire score detected in 2.5%. Reported sleep duration was 7.61± 1.67 hours during weekdays, and 8.27 ± 2.11 hours during weekends. Snoring frequency was significantly higher in men than women at nearly all age groups, and an adjusted regression model (Odds ratio [95% confidence interval]) identified male gender (2 [1.6-2.5]; p<0.001), and BMI (1.08 [1.03-1.12]; p<0.001) as independent risk factors for snoring.

Discussion:  The risk of SDB is highly prevalent in younger adults, even in females, and increases with age and BMI. The high prevalence and low awareness justify active screening and treatment of SDB in this population.

recent advances in chest medicine 
Jessica A. Cooksey, M.D.; Jay S. Balachandran, M.D.

In-lab, attended polysomnography has long been the gold standard for the diagnosis of sleep disordered breathing. In recent years, economic pressures and long wait times have driven interest in home sleep testing, which has in turn led to the development of algorithms that bypass the sleep lab in favor of portable monitoring studies and in-home initiation of positive airway pressure therapy. For appropriately selected outpatients, evidence is accumulating that portable monitors are a reasonable substitute for in-lab polysomnography. In the inpatient setting, where sleep disordered breathing is both highly prevalent and associated with adverse outcomes in certain populations, there is evolving literature on the use of portable monitors to expedite diagnosis and treatment of sleep disordered breathing in the inpatient setting. This review will discuss society guidelines and recent research in the growing field of portable monitoring.

original research 
Harold J. Farber, MD, MSPH; Richard R. Batsell, PhD; Edwin A. Silveira; Rose T. Calhoun, RN, MEd, CPHQ, LSSMBB; Angelo P. Giardino, MD, PhD
Topics: , , , ,

Background:  Tobacco smoke exposure increases breathing problems of children. Texas Children’s Health Plan (TCHP) is a Managed Medicaid and Children’s Health Insurance Program (CHIP) managed care provider. The aim of this study is to determine associations between tobacco smoke exposure, asthma prevalence, and asthma health care utilization.

Methods:  TCHP conducts an annual survey of members who have a physician visit. Questions were added to the survey in March 2010 about asthma and tobacco smoke exposure. Survey results for children <18 years were matched to health plan claims data for the 12 months following the date of the physician visit.

Results:  22,470 parents of unique member/patients from birth to < 18 years participated in the survey. More Caucasians than African Americans or Hispanics report that the child’s mother is a smoker (19.5% vs. 9.1%% and vs. 2.3% respectively, p<0.001). Compared to children whose mother does not smoke, parent report of asthma diagnosis and claims for dispensing of short acting beta agonist medication are greater if the mother is a smoker (adjusted Odds Ratio 1.20 (95% CI 1.03-1.40) and 1.24 (95% CI 1.08-1.42) respectively). In contrast to Medicaid where there are no out of pocket costs, the CHIP line of business requires co-pays for emergency department visits. Emergency department visits are influenced by maternal smoking only in the CHIP line of business (aOR 4.40 (95% CI 1.69-11.44).

Conclusion:  Maternal smoking increases risk for asthma diagnosis and prescription of asthma quick relief medication. Maternal smoking predicted asthma-related Emergency Department visits only for the CHIP line of business.

original research 
Manuela Karloh, PT, MSc; Anamaria F. Mayer, PT, PhD; Rosemeri Maurici, MD, PhD; Marcia M. M. Pizzichini, MD, PhD; Paul W. Jones, MD, PhD; Emilio Pizzichini, MD, PhD
Topics: ,

Background:  the COPD Assessment Test (CAT) was developed as simple instrument to assess health status in COPD. This study aimed to systematically review the determinants of the CAT score, its ability to predict clinical outcomes and the agreement between CAT (≥10) and the Medical Research Council scale (mMRC,≥2) to categorize patients into the new GOLD classification system.

Methods:  from January 1, 2009 to June 30, 2015 databases were searched for studies using CAT in adults with COPD and in general population aiming to detect COPD. Two investigators independently screened, selected and extracted data using a standardized form. Where appropriate the results were combined in a random effects meta-analysis.

Results:  of 453 studies, 17 were included and 8 were used in the meta-analysis. The models to predict the CAT score were able to explain less than 50% of its variance. CAT score can indicate risk of exacerbation, depression, acute deterioration in health status and mortality. All studies found a different proportion of patients in each GOLD category using CAT≥10 or mMRC≥2. In average, the distribution was 13% different according to the instrument used. The kappa agreement between CAT and mMRC ranged from 0.13 to 0.77.

Conclusions:  CAT may be used as a complementary tool in patient´s clinical assessment to predict COPD exacerbation, health status deterioration, depression and mortality. The interpretation of this meta-analysis do not support the use of the recommended cut-off points of ≥10 for CAT and ≥2 for mMRC as equivalents for the purpose of assess patient´s symptoms.

original research 
Julie Jarand, MD; J. Paul Davis, MD; Robert L. Cowie, MD; Stephen K. Field, MD; Dina A. Fisher, MD
Topics: , , , , ,

BACKGROUND:  Mycobacterium avium complex (MAC) lung disease requires prolonged treatment with multiple antibiotics. Drug intolerances and interactions are common with current recommended treatment. There is limited information on outcomes with alternative medications.

METHODS:  Retrospective review including adult patients with MAC lung disease who were treated and followed for at least 6 months post treatment. The aim was to evaluate the clinical and microbiologic outcomes in patients treated with regimens including clofazimine and/or rifampin.

RESULTS:  107 patients were included; 79% female; mean age 67 years. Sputa were smear positive in 54% of patients. The majority were treated with clofazimine (85%) in combination with a macrolide and ethambutol. Fourteen patients (13%) were treated with rifampin, macrolide and ethambutol. The vast majority (95%) of patients converted sputum culture to negative in an average of 4.5 months ± 4.2 (range 0-30 months). A significantly greater proportion of patients treated with clofazimine converted cultures to negative compared to those treated with rifampin (100% vs 71%; p=0.0002). Microbiologic relapse occurred in 49% (52/107). 36% of patients required re-treatment. There was no difference in microbiologic relapse or re-treatment rates between the two treatment groups.

CONCLUSIONS:  The majority of MAC lung disease patients achieve negative sputum cultures. Re-treatment is needed in approximately one third of patients. In our cohort, both initial outcomes and re-treatment rates were at least as good in patients treated with clofazimine-containing regimens as in patients with rifampin-containing regimens. Clofazimine should be considered as an alternative drug for treatment of MAC lung disease.

original research 
Fumitaka Ito, MD; Masanori Kawasaki, MD, PhD; Yasushi Ohno, MD, PhD; Sayaka Toyoshi, MD; Megumi Morishita, MD; Daizo Kaito, MD; Komei Yanase, MD; Norihiko Funaguchi, MD, PhD; Masahiro Asano, MD; Junki Endo, MD, PhD; Hidenori Mori, MD, PhD; Kazuhiro Kobayashi, MD; Kazuhiko Nishigaki, MD, PhD; Tatsuhiko Miyazaki, MD, PhD; Genzou Takemura, MD, PhD; Shinya Minatoguchi, MD, PhD
Topics: ,

Background:  Endobronchial ultrasonography (EBUS) facilitates lung cancer diagnosis. However, qualitative tissue characterization of lung tumors is difficult using EBUS. Integrated backscatter (IBS) is an ultrasound technique that calculates the power of ultrasound signal to characterize tissue components in coronary arteries. We hypothesized that qualitative diagnosis of lung tumors is possible using the IBS technique. The aim of the present study was to elucidate whether IBS technique can be used in lung tissues diagnosis.

Methods:  We prospectively enrolled 35 consecutive patients who underwent surgery for lung cancer. We measured IBS values of lung and tumor tissues that were obtained during surgery within 48 hours. We compared histological images of lung and tumor tissues with IBS values. We determined the relative interstitial area by Masson’s trichrome stain using an imaging processor.

Results:  The IBS values in tumor tissue were significantly lower than those in normal lung tissue (-50.9±2.6 and -47.6±2.6 dB, respectively, p<0.001). The IBS values of adenocarcinomas associated with a good 5-year survival rate were higher than those of non-adenocarcinomas (-48.1±1.6 and -52.6±1.4 dB, respectively, p <0.001). There were significant correlations between the IBS values and the relative interstitial area or micro air area in tumor (r=0.53 and r=0.67, p<0.01, respectively). After combining normal lung tissue and adenocarcinomas with good prognosis, the sensitivity and specificity for establishing the presence of lung tumors were 84% and 85%, respectively.

Conclusion:  Qualitative diagnosis of lung tumors was possible with a sensitivity of 84% and a specificity of 85% using the ultrasound IBS technique.

original research 
Juan P. de-Torres, MD; Jose M. Marín, MD; Ciro Casanova, MD; Victor Pinto-Plata, MD; Miguel Divo, MD; Bartolome R. Celli, MD; Javier J. Zulueta, MD
Topics: , , ,

Background:  The COPD Lung Cancer Screening Score (COPD-LUCSS) is a novel tool designed to help identify COPD patients with the highest risk of developing lung cancer (LC). The COPD-LUCSS includes the determination of radiological emphysema, a potential limitation for its implementation in clinical practice. The diffusing capacity for carbon monoxide (DLCO) is a surrogate marker of emphysema and correlates well with CT-determined emphysema.

Objective:  To explore the use of the COPD-LUCSS using the DLCO instead of radiological emphysema, as a tool to identify COPD patients at higher risk of LC death.

Methods:  The BODE international cohort database was analyzed. By logistic regression analysis we confirmed that the other parameters included in the COPD-LUCSS (age>60, pack-years>60, BMI<25) were independently associated with LC death. We selected the best cut-off value for DLCO that independently predicted LC death. We then integrated the new COPD-LUCSS-DLCO assigning points to each parameter according to its hazard ratio value in the Cox regression model. The score ranges from 0 to 8 points.

Results:  By regression analysis, age>60, BMI<25 kg/m2, pack-years history>60, and DLCO<60% were independently associated with LC diagnosis. Two COPD-LUCSS-DLCO risk categories were identified: low risk (scores 0-3) and high risk (scores 3.5-8). In comparison to low risk patients, risk of death from LC increased 2.4 fold (95% CI: 2.0-2.7) in the high-risk category.

Conclusions:  The COPD-LUCSS using DLCO instead of CT-determined emphysema is a useful tool to identify COPD patients at risk of LC death and may help in its implementation in clinical practice.

original research 
Ana C. Zamora, MD; Darin B. White, MD; Anne-Marie G. Sykes, MD; Sumedh S. Hoskote, MBBS; Teng Moua, MD; Eunhee S. Yi, MD; Jay H. Ryu, MD
Topics: , ,

Background:  Amyloid-associated cystic lung disease is rare. It can be associated with collagen vascular disease (CVD). We aimed to describe the clinical, radiologic and pathologic findings of this entity.

Methods:  We reviewed subjects having biopsy-proven pulmonary amyloidosis with cystic lung disease demonstrated by high-resolution chest computed tomography (HRCT). Demographics, association with CVD and lymphoproliferative disorders, pulmonary function, and pathology results were reviewed. HRCT appearance was analyzed for number, size, distribution, and morphology of cysts and nodules.

Results:  Twenty-one subjects (13 female/8 male; median age 61 years) with cystic pulmonary amyloidosis were identified. Most common pulmonary function patterns were normal (42%) and obstructive (32%). Most common associated CVD was Sjögren’s syndrome (10/12). Nine subjects had no CVD. Cysts tended to be multiple (≥10 in 14/21, 67%), round (21/21, 100%) or lobulated (20/21, 95%), thin-walled (<2 mm in 17/21, 81%), and of small (<1 cm in 21/21, 100%) to moderate (1-2 cm in 17/21, 81%) size. Peribronchovascular (19/21, 90%) and subpleural cysts (19/21, 90%) were typically present.. Seventeen (81%) subjects had lung nodules, which tended to be numerous (≥10 in 10/17 [59%], 4-9 in 6/17 [35%]). At least one calcified nodule was present in 14/17 (82%) subjects. Pulmonary mucosa-associated lymphoid tissue (MALT) lymphoma was diagnosed in 7 (33%) subjects.

Conclusion:  Amyloid–associated cystic lung disease can occur with or without underlying CVD. Cystic lesions in the lung are commonly numerous, often peribronchovascular or subpleural, and are frequently associated with nodular lesions which are often calcified. MALT lymphoma was a relatively frequent association.

original research 
Stefan E. Richter, MD; Kari E. Roberts, MD; Ioana R. Preston; Nicholas S. Hill
Topics: , ,

Background  One of the foremost diagnostic challenges in clinical pulmonary hypertension (PH) is discriminating between pulmonary arterial hypertension (PAH, Group 1) and heart failure with preserved ejection fraction (HFpEF, Group 2.2). Group 2.2 is defined as a normal left ventricular ejection fraction (>50%) and a pulmonary arterial wedge pressure (PAWP) of >15mmHg. We aimed to determine whether patient history, demographics, and non-invasive measures could predict PAWP prior to right-heart catheterization (RHC).

Methods  Data were prospectively collected on 350 consecutive patients at a single, tertiary-care medical center; of these, 151 met criteria for entry into our study (88 in Group 1 and 63 in Group 2.2). Data included historical features, demographics, and transthoracic echocardiogram. A multivariate regression model was developed to predict PAWP >15mmHg.

Results  Univariate predictors of PAWP >15mmHg included older age, higher BMI and weight, systemic systolic blood pressure (SBP) and pulse pressure (PP), more features of the metabolic syndrome, presence of hypertension and left atrial (LA) enlargement, absence of right ventricular (RV) enlargement, and lower glomerular filtration rate and six-minute walk distance. The optimal model for predicting PAWP >15mmHg was composed of age (>68 years), body mass index (>30 kg/m2), absence of RV enlargement, and presence of LA enlargement (AUC 0.779).

Conclusion  Clinical characteristics obtained prior to diagnostic RHC accurately predict probability of elevation of PAWP above 15mmHg in patients with preserved ejection fraction. These clinical characteristics combined can be used a priori to predict the likelihood of Group 2.2 Pulmonary Hypertension.

original research 
Christian Gerges, MD; Mario Gerges, MD; Nika Skoro-Sajer, MD; Yi Zhou, PhD; Lixia Zhang, PhD; Roela Sadushi-Kolici, MD; Johannes Jakowitsch, PhD; Marie B. Lang, MD; Irene M. Lang, MD
Topics: ,

Background:  Hemodynamic differentiation between pulmonary arterial hypertension (PAH) and post-capillary pulmonary hypertension (PH) is key because treatment options are strikingly different for the two disease subsets. While patients with PAH can be effectively treated with "targeted therapies", their use in post-capillary PH is currently not recommended. Our aim was to establish an algorithm for the identification of patients who are likely to experience a significant hemodynamic treatment response.

Methods:  We determined hemodynamic cut-offs for the discrimination between idiopathic PAH and post-capillary PH in a large database of 4363 stable all-comers undergoing first diagnostic right and left heart catheterizations. In a second step, we performed a patient-level pooled analysis of 4 randomized, placebo-controlled trials including 541 PAH patients receiving treprostinil or placebo to validate hemodynamic cut-offs with regard to treatment response.

Results:  Receiver operating characteristic analysis identified mean pulmonary arterial wedge pressure (mPAWP) <12mmHg and diastolic pulmonary vascular pressure gradient (DPG) ≥7mmHg as best hemodynamic discriminators between idiopathic PAH and post-capillary PH. In our treatment study, only patients with mPAWP <12mmHg, DPG >20mmHg or a combination of both had a significant placebo-corrected improvement in hemodynamics.

Conclusions:  mPAWP <12mmHg and DPG >20mmHg identify PAH cases who are likely to have a significant hemodynamic improvement under prostacyclin treatment.

original research 
Michael Klompas, MD, MPH; Lingling Li, PhD; Paul Szumita, PharmD; Ken Kleinman, ScD; Michael V. Murphy, BA; for the CDC Prevention Epicenters Program
Topics: , , , ,

Background:  Current sedation guidelines recommend avoiding benzodiazepines but express no preference for propofol versus dexmedetomidine. In addition, there are limited data on how well randomized controlled trials on sedatives generalize to routine practice where conditions tend to be more varied and complex.

Methods:  We gathered daily sedative exposure data from all patients on mechanical ventilation for ≥3 days over a 7-year period in a large academic medical center. We compared hazard ratios for ventilator-associated events (VAEs), extubation, hospital discharge, and hospital death amongst benzodiazepines, propofol, and dexmedetomidine using proportional subdistribution hazard models with competing risks. We adjusted all analyses for ICU type, demographics, comorbidities, procedures, severity of illness, hypotension, oxygenation, renal function, opioids, neuroleptics, neuromuscular blockers, awakening and breathing trials, and calendar year.

Results:  We evaluated 9,603 consecutive episodes of mechanical ventilation. Benzodiazepines and propofol were associated with increased VAE risk whereas dexmedetomidine was not. Propofol was associated with less time to extubation compared to benzodiazepines (HR for extubation 1.4, 95% CI 1.3-1.5). Dexmedetomidine was associated with less time to extubation compared to both benzodiazepines (HR 2.3, 95% CI 2.0-2.7) and propofol (HR 1.7, 95% CI 1.4-2.0) but there were relatively few dexmedetomidine exposures available for analysis. There were no differences between any two agents in hazards for hospital discharge or mortality.

Conclusions:  In this large, real-world cohort, propofol and dexmedetomidine were associated with less time to extubation compared to benzodiazepines but dexmedetomidine was also associated with less time to extubation compared to propofol. These possible differences merit further study.

original research 
J. Michael Wells, M.D.; Joshua B. Morrison, M.D.; Surya P. Bhatt, M.D.; Hrudaya Nath, M.D.; Mark T. Dransfield, M.D.
Topics: , , ,

Background:  Relative pulmonary arterial enlargement, defined by a pulmonary artery to aorta (PA/A)>1 on computed tomography (CT), predicts hospitalization for acute exacerbations of COPD (AECOPD). However, it is unclear how AECOPD impact the PA/A ratio. We hypothesized that the PA/A would increase at the time of AECOPD and that a ratio>1 would be associated with worse clinical outcomes.

Methods:  We identified patients discharged with an ICD-9 diagnosis of AECOPD from a single center over a 5-year period. We included subjects who had a CT performed during in the stable state prior to the index AECOPD as well as a CT at the time of hospitalization. A subset of patients also had post-exacerbation CT scans. The PA and aortic diameters as well as PA/A were measured on CT. Demographic data, comorbidities, troponin, and hospital outcome data were analyzed.

Results:  134 patients were included; they were 65±10 years old, 47% male, and 69% Caucasian with a mean forced expiratory volume in 1-second of 47±19%. The PA/A increased from baseline at the time of exacerbation (0.97±0.15 from 0.91±0.17, P<0.001). Younger age and known pulmonary hypertension were independently associated with an exacerbation PA/A>1. Patients with PA/A>1 had higher troponin values. Those with a PA/A>1 and troponin >0.01ng/ml had increased acute respiratory failure, intensive care admission, or inpatient mortality compared to those without both (P=0.0028). The PA/A returned to baseline values following AECOPD.

Conclusions:  The PA/A increases at the time of severe AECOPD and a ratio>1 predicts cardiac injury and a more severe hospital course.

original research 
You-Dong Wan, MD; Tong-Wen Sun, MD, PhD; Zi-Qi Liu, MD; Shu-Guang Zhang, MD; Le-Xin Wang, MD, PhD; Quan-Cheng Kan, MD, PhD
Topics: , , , ,

Background:  Corticosteroids are an option in the treatment of community-acquired pneumonia (CAP). However, the benefits and adverse effects of corticosteroids, especially in severe CAP, have not been well assessed.

Methods:  Pubmed, Embase, and Cochrane library databases from inception to May 2015 were searched. Randomized controlled trials (RCTs) and cohort studies that evaluated use of corticosteroids in adult patients with CAP were included. The quality of outcomes was evaluated using GRADE methodology. The Mantel–Haenszel method with random-effects modeling was used to calculate pooled relative risks (RRs) and 95% confidence intervals(CIs).

Results:  Nine eligible RCTs (1667 patients) and six cohort studies(4095 patients), were identified. The mean corticosteroid dose and treatment duration were 30 mg/day methylprednisolone for 7 days. Corticosteroids did not have a statistically significant effect on mortality (RR, 0.72; 95% CI: 0.43–1.21; evidence rank: low) in CAP patients, and severe CAP patients (RCTs; RR, 0.72; 95% CI: 0.43–1.21; evidence rank: low; cohort studies; RR, 1.00; 95% CI, 0.86–1.17 ). Corticosteroids treatment was associated with an decreased risk of adult respiratory distress syndrome (RR, 0.21; 95% CI, 0.08–0.59), and may reduce the lengths of hospital and intensive care unit stay, the duration of intravenous antibiotic treatment, and the time to clinical stability. Corticosteroid were not associated with increased rates of adverse events.

Conclusions:  Short-term treatment with corticosteroids is safe, and may reduce the risk of adult respiratory distress syndrome, shorten the length of the disease in CAP patients.

original research 
Susan M. Tarlo, MB BS, FCCP; Kenneth W. Altman, MD, PhD; Cynthia T. French, PhD, FCCP; Rebecca L. Diekemper, MPH; Richard S. Irwin, MD, Master FCCP
Topics: ,

BACKGROUND:  Several recent cough guidelines have advised consideration of occupational or environmental causes for chronic cough, but it is unclear how frequently this recommendation has been routinely applied. Therefore we undertook a systematic review to address this aspect.

METHODS:  Cough guidelines and protocols were reviewed to identify recommendations for assessment of occupational and environmental aspects of chronic cough. The systematic search previously used to identify intervention fidelity to the use of protocols for diagnosis and management of chronic cough in adults 1 was used for this review after extension to June 2015. PubMed, Scopus and the Cochrane Library were searched using the same search terms and inclusion criteria as previously. Papers that met our criteria were then reviewed to identify methods used in these papers to assess occupational and environmental aspects of chronic cough, and the outcomes of these assessments.

RESULTS:  Among the 10 general chronic cough guidelines and protocols identified, only the 3 published since 2006 included details advising detailed occupational and environmental assessments. One additional cough statement focused entirely on occupational cough. Of the 28 cohort studies of patients with chronic cough that specifically noted that they followed guidelines or protocols, none provided details of occupational and environmental assessments.

CONCLUSIONS:  Despite published recommendations, it is not apparent that occupational and environmental causes for chronic cough are addressed in detail during assessments of patients with chronic cough. This leaves open to speculation that lack of recognition of an occupational cause may delay important preventive measures, put additional workers at risk, and/or be the reason why a chronic cough may remain unexplained.

translating basic research into clinical practice 
Pieter S. Hiemstra; Gimano D. Amatngalim; Anne M. van der Does; Christian Taube
Topics: , , ,

Respiratory infections are a major clinical problem, and treatment is increasingly complicated by the emergence of microbial antibiotic resistance. Development of new antibiotics is notoriously costly and slow, and therefore alternative strategies are needed. Antimicrobial peptides, central effector molecules of the immune system, are being considered as an alternative to conventional antibiotics. These peptides display a range of activities, including not only direct antimicrobial activity but also immunomodulation and wound repair. In the lung, especially airway epithelial cells and neutrophils contribute to their synthesis. The relevance of antimicrobial peptides for host defense against infection has been demonstrated in animal models, and is also supported by observations in patient studies, showing altered expression and/or unfavorable circumstances for their action in a variety of lung diseases. Importantly, antimicrobial peptides are active against micro-organisms that are resistant against conventional antibiotics, including multidrug resistant bacteria. Several strategies have been proposed to use these peptides in the treatment of infections, including direct administration of antimicrobial peptides, enhancement of their local production and creation of more favorable circumstances for their action. In this review, recent developments in antimicrobial peptides research in the lung and clinical applications for novel therapies of lung diseases are discussed.

recent advances in chest medicine 
Kevin Gibbs, M.D.; Joseph M. Collaco, M.D., M.P.H; Sharon A. McGrath-Morrow, M.D., M.B.A.
Topics: , , ,

Tobacco smoke and nicotine exposure during prenatal and postnatal life can impair lung development, alter the immune response to viral infections and increase the prevalence of wheezing during childhood. The following review examines recent discoveries in the fields of lung development and tobacco/nicotine exposure, emphasizing studies published within the last five years. In utero tobacco/nicotine exposure remains common, occurring in approximately 10% of pregnancies within the United States. Exposed neonates are at increased risk for diminished lung function, altered central and peripheral respiratory chemoreception and increased asthma symptoms throughout childhood. Recently, genomic and epigenetic risk factors, such as alterations in DNA methylation, have been identified that may influence the risk for long-term disease. This review examines the impact of prenatal tobacco/ nicotine exposure on lung development with a particular focus on nicotinic acetylcholine receptors. In addition this review examines the role of prenatal and postnatal tobacco smoke/nicotine exposure and its association with augmenting infection risk, skewing the immune response towards a Th2 bias and increasing risk for developing an allergic phenotype and asthma-like symptoms during childhood. Finally this review outlines the respiratory morbidities associated with childhood secondhand smoke/nicotine exposure and examines genetic and epigenetic modifiers that may influence respiratory health in infants and children exposed to in utero or postnatal tobacco smoke.

recent advances in chest medicine 
Timothy J. Vece, MD; Lisa R. Young, MD

Diffuse lung diseases in children, also called children’s interstitial lung disease, are a diverse group of rare disorders that cause disturbance of gas exchange in the lungs. Although individually rare, there are many different forms of diffuse lung disease in children and collectively these disorders are associated with significant morbidity and mortality, as well as health care resource utilization. In the past several years, there have been many significant advances in the field, including genetic discoveries and the development of clinical practice guidelines. This review summarizes recent advances in the understanding, diagnosis, and treatment of diffuse lung diseases in children.

medical ethics 
Courtenay R. Bruce, JD, MA; Trevor Bibler, PhD; Andrew M. Childress, PhD; Ashley L. Stephens, MA; Adam M. Pena, MA; Nathan G. Allen, MD
Topics: , ,

There is little guidance on what clinicians should do when advance directives (or living wills, specifically) are challenged, particularly when surrogate decision-makers’ interpretations of patients’ wishes conflict with the living will. In our commentary, we make a controversial argument, suggesting that overriding living wills can be ethically preferable to the alternative of strictly adhering to them. We propose 4 ethical considerations for determining whether it is ethically supportable to override living wills.

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