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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 
Asli Gorek Dilektasli, MD; Janos Porszasz, MD, PhD; Richard Casaburi, PhD, MD; William W. Stringer, MD; Surya P. Bhatt, MD; Youngju Pak, PhD; Harry B. Rossiter, PhD; George Washko, MD; Peter J. Castaldi, MD; Raul San Jose Estepar, PhD; James E. Hansen, MD

Rationale  In chronic obstructive pulmonary disease both smaller and larger airways are affected. Forced expiratory volume in one second (FEV1) mainly reflects large airways obstruction, while the later fraction of forced exhalation reflects reduction in terminal expiratory flow.

Objective  To evaluate the relationship between spirometric ratios, including the ratio of forced expiratory volume in 3 and 6 seconds (FEV3/FEV6), and small airway measures and gas trapping in quantitative chest computed tomography (CT), and clinical outcomes in the COPDGene cohort.

Methods  7,853 current and ex-smokers were evaluated for airflow obstruction using recently-defined linear iteratively-derived equations of Hansen et al.1 to determine lower limits of normal equations for pre-bronchodilator FEV1/FVC, FEV1/FEV6, FEV3/FEV6 and FEV3/FVC. General linear and ordinal regression models were applied to the relation between pre-bronchodilator spirometry and radiologic and clinical data.

Main Results  Of the 10,311 participants included in the COPDGene Phase 1 study, participants with incomplete quantitative CT or relevant spirometric data were excluded, resulting in 7,853 participants in the present study. Of 4,386 participants with ratio of FEV1 to forced vital capacity (FEV1/FVC) greater than lower limit of normal, 15.4% had abnormal FEV3/FEV6. Compared to participants with normal FEV3/FEV6 and FEV1/FVC, abnormal FEV3/FEV6 was associated with significantly greater gas trapping, St. George Respiratory Questionnaire score, mMRC dyspnea score, BODE index, and shorter six-minute walking distance (all P < 0.0001), but not CT-evidence of emphysema.

Conclusions  Current and ex-smokers with pre-bronchodilator FEV3/FEV6 < lower limit of normal as the sole abnormality identifies a distinct population with evidence of small airway disease in quantitative CT, impaired indices of physical function and quality of life otherwise deemed normal by current spirometric definition.

special features 
Tanmay S. Panchabhai, MD, FACP, FCCP; Sanjay Mukhopadhyay, MD; Sameep Sehgal, MD; Debabrata Bandyopadhyay, MD, MRCP, FACP; Serpil C. Erzurum, MD; Atul C. Mehta, MD, FACP, FCCP

Although mucus is a normal product of the tracheobronchial tree, some diseases of the respiratory tract are characterized by unusually thick (inspissated) forms of mucus that accumulate within the airways. These are known as mucus plugs. The pathologic composition of these plugs is surprisingly diverse and, in many cases, correlates with distinctive clinical, radiologic, and bronchoscopic findings. The best-known conditions that involve mucus plugs are allergic bronchopulmonary aspergillosis, plastic bronchitis, and asthma. Other lung diseases occasionally associated with plugs within the airways include Aspergillus tracheobronchitis, hyper-immunoglobulin E syndromes, exogenous lipoid pneumonia, pulmonary alveolar proteinosis, and chronic eosinophilic pneumonia. In this review, we describe and illustrate the bronchoscopic, pathologic, and imaging findings in respiratory disorders characterized by mucus plugs or plugs composed of other similar materials. Recognition of the characteristic appearance and differential diagnosis of mucus plugs will hopefully facilitate diagnosis and management of these diseases.

original research 
Andrew J. Goodwin, MD, MSCR; Nandita R. Nadig, MD; James T. McElligott, MD, MSCR; Kit N. Simpson, DrPh; Dee W. Ford, MD, MSCR
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Background  Medically underserved areas are comprised of vulnerable populations with reduced access to ambulatory care services. Our goal was to determine the association between residence in a medically underserved area and severe sepsis incidence and mortality.

Methods  Using administrative data, we identified adults admitted with severe sepsis to non-federal hospitals in South Carolina. We determined whether each resident lived in a medically underserved area or non-medically underserved area from US census and Department of Health and Human Services data. Age-adjusted severe sepsis incidence and mortality rates were calculated and compared between both residential classifications. Multivariate logistic regression measured the association between residence in a medically underserved area and mortality while adjusting for confounders.

Results  In 2010, 24,395 adults were admitted with severe sepsis and 1,446,987 (43%) adults lived in a medically underserved area. Residents of medically underserved areas were admitted more frequently with severe sepsis (8.6 vs. 6.8 cases/1,000 people, p<0.01) and were more likely to die (15.5 vs 11.9 deaths/10,000 people, p<0.01) with increased odds of severe sepsis-related death (OR 1.12) after adjustment for age, race, and severity of illness. ZIP Code-based surrogates of socioeconomic status including median income, proportion below poverty level, and educational attainment, however, had minimal association with sepsis mortality.

Conclusions  Residence in a medically underserved area is associated with higher incidence and mortality rates of severe sepsis and represents a novel method of access-to-care adjustment. Traditional access-to-care surrogates, however, are poorly associated with sepsis mortality.

original research 
Thomas K. Aldrich, MD; Jessica Weakley, MPH; Sean Dhar, MD; Charles B. Hall, PhD; Tesha Crosse, MS; Gisela I. Banauch, MD; Michael D. Weiden, MD; Gabriel Izbicki, MD; Hillel W. Cohen, DrPH; Aanchal Gupta, MD; Camille King, RRT; Vasilios Christodoulou, BA; Mayris P. Webber, DrPH; Rachel Zeig-Owens, DrPH; William Moir, MPH; Anna Nolan, MD; Kerry J. Kelly, MD; David J. Prezant, MD

Background  World Trade Center (WTC)-exposed rescue/recovery workers endured massive respiratory insult from inhalation of particulate matter and gases, resulting in respiratory symptoms, loss of lung function, and, for many, bronchial hyperreactivity (BHR). The persistence of respiratory symptoms and lung function abnormalities has been well-documented, while persistence of BHR has not been investigated.

Methods  173 WTC-exposed firefighters with bronchial reactivity measured within 2 years after 9/11/2001 (9/11), (baseline methacholine challenge test [MCT]), were re-evaluated in 2013-2014 (follow-up-MCT). FEV1 measurements were obtained from the late pre-9/11, early post-9/11 and late post-9/11 periods. Respiratory symptoms and corticosteroid treatment were recorded.

Results  Bronchial reactivity remained stable (within 1 doubling dilution) for most (n=101, 58%). 16 of 28 (57%) with BHR (PC20<8mg/ml) at baseline had BHR at follow up, and an additional 27 of the 145 (19%) without BHR at baseline had BHR at follow-up. In multivariable models, we found that BHR baseline was strongly associated with BHR follow-up (OR=6.46) and that BHR at follow-up was associated with an estimated 15.4 ml/year greater FEV1 decline than experienced by those without BHR at follow-up. Annual FEV1 decline was moderated by corticosteroid use.

Conclusions  Persistent BHR and its deleterious influence on lung function suggest a role for airway inflammation in perpetuation of WTC-associated airway disease. In future massive occupational exposure to inorganic dust/gases, we recommend early and serial pulmonary function testing, including measurements of bronchial reactivity, when possible, and inhaled corticosteroid therapy for those with symptoms or pulmonary function tests consistent with airway disease.

original research 
Simeon Gotzev, BMSc; Joshua C. Lipszyc, HBA; Dale Connor, MMath; Susan M. Tarlo, MB BS FRCPC
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Background  Work-related asthma (WRA) is the most common chronic occupational lung disease in the developed world. Several factors including socio-demographic status, and occupation / industry, increase the risks of developing WRA. In this study, we sought to identify changes in patterns and characteristics among WRA patients over a fifteen-year period in an occupational lung disease clinic.

Methods  We performed a retrospective analysis of WRA patient charts at the Occupational Lung Disease Clinic of a University Hospital in Toronto, Canada. Patients were divided into two periods classified by first attendance at the clinic 2000-2007 and 2008-2015. Comparisons between the two periods included: socio-demographic characteristics, smoking status, occupations, exposures, and submitted workers’ compensation claims.

Results  Fewer occupational asthma cases were seen in the more recent period versus the earlier period (40 vs. 74 cases), with a smaller reduction in work-exacerbated asthma cases (40 vs. 58). The recent period included a significantly smaller proportion employed in the manufacturing industry and isocyanate-induced cases compared with the earlier period. An increased proportion were employed in health care and education industries (primarily cleaners and teachers) in the recent period, consistent with a corresponding increased frequency of cleaning agents and dust exposures.

Conclusions  The changes observed in work sectors in our work-related asthma patients in this clinic in Toronto are consistent with reductions reported in Ontario workers’ compensation claims for occupational asthma, and may relate to preventive measures. Cleaners and teachers should be a focus of further intervention measures for work-related asthma.

original research 
Sameer S. Kadri, MD, MS; Chanu Rhee, MD, MPH; Jeffrey R. Strich, MD; Megan K. Morales, MD; Samuel Hohmann, PhD; Jonathan Menchaca, BA; Anthony F. Suffredini, MD; Robert L. Danner, MD; Michael Klompas, MD, MPH
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Background  Reports that septic shock incidence is rising and mortality rates declining may be confounded by improving recognition of sepsis and changing coding practices. We compared trends in septic shock incidence and mortality in academic hospitals using clinical versus claims data.

Methods  We identified all patients with concurrent blood cultures, antibiotics, and ≥2 consecutive days of vasopressors and all patients with ICD-9 codes for septic shock at 27 academic hospitals from 2005-2014. We compared annual incidence and mortality trends. We reviewed 967 records from 3 hospitals to estimate the accuracy of each method.

Results  Of 6.5 million adult hospitalizations, 99,312 (1.5%) were flagged by clinical criteria, 82,350 (1.3%) by ICD-9 codes, and 44,651 (0.7%) by both. Sensitivity for clinical criteria was higher than claims (74.8% vs. 48.3%, p<0.01), whereas positive predictive value was comparable (83% vs. 89%, p=0.23). Septic shock incidence using clinical criteria rose from 12.8 to 18.6 cases per 1000 hospitalizations (average 4.9% increase/year, 95% CI 4.0%-5.9%), while mortality declined from 54.9% to 50.7% (average 0.6% decline/year, 95% CI 0.4%-0.8%). In contrast, septic shock incidence using I0CD-9 codes increased from 6.7 to 19.3 per 1000 hospitalizations (19.8% increase/year, 95% CI 16.6%-20.9%), while mortality decreased from 48.3% to 39.3% (1.2% decline/year, 95% CI 0.9%-1.6%).

Conclusions  A clinical surveillance definition based on concurrent vasopressors, blood cultures, and antibiotics accurately identifies septic shock hospitalizations and suggests that the incidence of patients receiving treatment for septic shock has risen and mortality rates have fallen, but less dramatically than estimated using ICD-9 codes.

original research 
Alberto Alonso-Fernández, MD PhD; Angela García Suquia, BPharm; Mónica de la Peña, MD; Raquel Casitas, MD; Javier Pierola, PhD; Antonia Barceló, MD PhD, MD; Joan B. Soriano, MD PhD; Carmen Fernández-Capitán, MD; Elizabet Martinez-Ceron, MD; Miguel Carrera, MD PhD, MD; Francisco García-Río, MD PhD
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BackGround  Obstructive sleep apnea (OSA) is a risk factor for a first episode of pulmonary embolism (PE), although its impact on the risk of thromboembolism recurrence is uncertain. Our objective was to explore the prognostic value of OSA after discontinuing oral anticoagulation (OAC) in patients with a first episode of PE.

Methods  In 120 consecutive patients who had stopped OAC for a first episode of PE, we performed a home respiratory polygraphy and recorded sleep characteristics, classical risk factors for PE, blood pressure, spirometric parameters, physical activity and levels of D-dimer and prothrombin fragment 1+2. Patients were followed for 5 to 8 years, and the main end-point was PE recurrence. Restarting OAC for any thromboembolic event was evaluated as a secondary end-point.

Results  During the follow-up period, 19 patients had a PE recurrence, and 16 of them had an apnea-hypopnea index (AHI) ≥10 h-1. In a multivariate Cox regression model, an AHI ≥10 (hazard ratio [HR], 20.73; 95%CI, 1.71-251.28), mean nocturnal oxygen saturation (SaO2) (HR, 0.39; 95%CI, 0.20-0.78), time with SaO2<90% (HR, 0.90; 95%CI, 0.82-0.98) and D-dimer level (HR 1.001; 95%CI, 1.00-1.002) were identified as independent risk factors for recurrent PE. 24 patients resumed OAC, and AHI ≥10 (HR, 20.66; 95%CI, 2.27-188.35), mean nocturnal SaO2 (HR, 0.54; 95%CI, 0.32-0.94) and Epworth sleepiness score (HR, 0.73; 95%CI, 0.56-0.97) were retained as independent risk factors to resume OAC.

Conclusions  After a first episode of PE, OSA is an independent risk factor for PE recurrence or restarting OAC for a new thromboembolic event.

original research 
Esther I. Schwarz, MD; Christian Schlatzer, MD; Valentina A. Rossi, MD; John R. Stradling, MD; Malcolm Kohler, MD

Background  Based on meta-analyses, the blood pressure (BP) lowering effect of continuous positive airway pressure (CPAP) therapy in patients with obstructive sleep apnea (OSA) is reported to be approximately 2-3mmHg. This figure is derived from heterogeneous trials, often limited by poor CPAP-adherence, and thus possibly underestimating the treatment effect. We analyzed morning BP data from three randomized controlled CPAP withdrawal trials which included only patients with optimal CPAP-compliance.

Methods  Within the three trials, 149 OSA patients on CPAP were randomized to continue therapeutic CPAP (n=65) or to withdraw CPAP (n=84) for two weeks. Morning BP was measured at home before, and after sleep studies in hospital.

Results  CPAP-withdrawal was associated with a return of OSA (apnea-hypopnea index (AHI) at baseline 2.8/h, at follow-up 33.2/h). Systolic office BP increased in the CPAP-withdrawal group, compared to CPAP-continuation, by +5.4mmHg (95%CI 1.8-8.9mmHg, p=0.003), and systolic home BP by +9.0mmHg (95%-CI 5.7-12.3mmHg, p<0.001). Diastolic office BP increased by +5.0mmHg (95%CI 2.7-7.3mmHg, p<0.001), and diastolic home BP by +7.8mmHg (95%CI 5.6-10.4mmHg, p<0.001).AHI, baseline home systolic BP, statin usage, gender, and number of antihypertensive drugs were all independently associated with systolic BP change in multivariate analysis, controlling for age, BMI, smoking, diabetes, and sleepiness.

Conclusions  CPAP-withdrawal results in a clinically relevant increase in BP, which is considerably higher than in conventional CPAP trials, and is also underestimated when office BP is used. Greater OSA severity is associated with a higher BP rise in response to CPAP-withdrawal.

original research 
Shigeki Sawada, MD, PhD; Natsumi Yamashita, MD, PhD; Ryujiro Sugimoto, MD, PhD; Tsuyoshi Ueno, MD, PhD; Motohiro Yamashita, MD, PhD
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Background  The long-term outcomes of follow-up care for ground-glass opacity (GGO) need to be clarified.

Methods  Between 2000 and 2005, 226 patients with pure or mixed GGOs of 3 cm or smaller in size were registered. The CT findings and changes in the findings during the follow-up period and the outcomes of the 226 patients were subsequently reviewed.

Results  Overall, 124 patients underwent resections, 57 did not receive follow-up examinations after 68 months because of stable disease or disease reduction and 45 were continuing to receive follow-up examinations. Thirty-nine patients showed tumor growth during the follow-up period. Among the patients with a ratio of the diameter of consolidation relative to the tumor diameter (CTR) >0, all the cases with tumor growth were identified within 3 years; meanwhile, more than 3 years were required to identify tumor growth in 16% of the patients with a CTR =0. Aggressive cancer occurred in 4% of the patients with a CTR =0 and in 70% of the patients with a CTR >25%. Aggressive cancer was observed in 46% of the patients whose CTR increased during the follow-up period and in 8% of the patients whose tumors increased in size.

Conclusion  A higher CTR and an increase in the CTR during the follow-up were associated with invasive cancer. A follow-up period of 3 years is considered to be adequate for judging tumor growth in patients with a CTR >0, while a longer follow-up period might be needed for patients with a CTR =0.

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No abstract is available for this article
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No abstract is available for this article
editorial 
Harold J. Farber, MD, MSPH, FCCP
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No abstract is available for this article
original research 
Katherine O’Neill, PhD; Michael M. Tunney, PhD; Elinor Johnston, PhD; Stephen Rowan, PhD, MD; Damian G. Downey, MD; Jacqueline Rendall, MD; Alastair Reid, MD; Ian Bradbury, PhD; J. Stuart Elborn, PhD, MD; Judy. M. Bradley, PhD
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Background  Lung clearance index (LCI) has good clinimetric properties and an acceptable feasibility profile as a surrogate endpoint in Cystic Fibrosis (CF). Although most studies to date have been in children, increasing numbers of adults with CF also have normal spirometry. Further study of LCI as an endpoint in CF adults is required. Therefore, the purpose of this study was to determine the clinimetric properties of LCI over the complete age range of people with CF.

Methods  Clinically stable adults and children with CF and age matched healthy controls were recruited.

Results  LCI and spirometry data for 110 CF subjects and 61 controls were collected at a stable visit. CF Questionnaire-Revised (CFQ-R) was completed by 80/110 CF subjects. Fifty-six CF subjects completed a second stable visit. The LCI CV% was 4.1% in adults and 6.3% in children with CF. The coefficient of repeatability of LCI was 1.2 in adults and 1.3 in children. In both adults and children, LCI (AUCROC=0.93 and 0.84) had greater combined sensitivity and specificity to discriminate between people with CF and controls compared to FEV1 (AUCROC=0.88 and 0.60) and FEF25-75 (AUCROC=0.87 and 0.68). LCI correlated significantly with the CFQ-R treatment burden in adults (r=-0.37; p<0.01) and children (r=-0.50; p<0.01). Washout tests were successful in 90% of CF subjects and were perceived as comfortable and easy to perform in both adults and children.

Conclusions  These data support the use of LCI as a surrogate outcome measure in CF clinical trials in adults as well as children.

original research 
Danielle F. Wurzel, PhD; Julie M. Marchant, PhD; Stephanie T. Yerkovich, PhD; John W. Upham, PhD; Helen L. Petsky, PhD; Heidi Smith-Vaughan, PhD; Brent Masters, PhD; Helen Buntain, PhD; Anne B. Chang, PhD
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Background  Protracted bacterial bronchitis (PBB) and bronchiectasis are distinct diagnostic entities that share common clinical and laboratory features. It is postulated, but remains unproven, that PBB precedes a diagnosis of bronchiectasis in a subgroup of children. In a cohort of children with PBB, our objectives were to: (a) determine the medium-term risk of bronchiectasis and (b) identify risk factors for bronchiectasis and recurrent episodes of PBB.

Methods  161 children with PBB and 25 controls were prospectively recruited to this cohort study. A subset of 106 children was followed for 2 years. Flexible bronchoscopy, BAL and basic immune function tests were performed. CT chest was undertaken if clinical features were suggestive of bronchiectasis.

Results  Of 161 children with PBB (66% male), 13 (8.1%) were diagnosed with bronchiectasis over the study period. Almost half (43.5%) with PBB had recurrent episodes (>3/year). Major risk factors for bronchiectasis included: H. influenzae lower airway infection (in BAL) (p=0.013) and recurrent episodes of PBB (p=0.003). H. influenzae infection conferred >7 times higher risk of bronchiectasis [HR 7.55 (95%CI 1.66 - 34.28), p=0.009] compared to absence of H. influenzae. The majority of isolates (82%) were nontypeable H. influenzae. No risk factors for recurrent PBB were identified.

Conclusions  PBB is associated with a future diagnosis of bronchiectasis in a subgroup of children. H. influenzae lower airway infection and recurrent PBB are significant predictors. Clinicians should be cognisant of the relationship between PBB and bronchiectasis and appropriate follow-up measures should be taken in those with risk factors.

original research 
Anja Frei, PhD; Lara Siebeling, PhD; Callista Wolters, MD; Leonhard Held, Prof; Patrick Muggensturm, MD; Alexandra Strassmann, MSc; Marco Zoller, MD; Gerben ter Riet, PhD; Milo A. Puhan, Prof
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Background  COPD exacerbation incidence rates are often ascertained retrospectively, through patient recall and self-reports. We compared exacerbation ascertainment through patient self-reports and single physician chart review to central adjudication by a committee and explored determinants and consequences of misclassification.

Methods  Self-reported exacerbations (event-based definition) in 409 primary care COPD patients participating in the ICE COLD ERIC cohort were ascertained 6-monthly over 3 years. Exacerbations were adjudicated by single experienced physicians and an adjudication committee who had information from patient charts. We assessed the accuracy (sensitivities and specificities) of self-reports and single physician chart review against a central adjudication committee (reference standard). We used multinomial logistic regression and bootstrap stability analyses to explore determinants of misclassifications.

Results  The adjudication committee identified 648 exacerbations, corresponding with an incidence rate of 0.60±0.83 exacerbations/patient-year and a cumulative incidence proportion of 58.9%. Patients self-reported 841 exacerbations (incidence rate 0.75±1·01, incidence proportion 59.7%). Sensitivity/specificity of self-reports were 84%/76%, those of single physician chart review between 89-96% and 87-99%. The multinomial regression model and bootstrap selection showed that having experienced more exacerbations was the only factor consistently associated with under- and over-reporting of exacerbations (under-reporters: relative risk ratio 2.16, 95% CI 1.76-2.65; over-reporters: relative risk ratio 1.67, 95% CI 1.39-2.00).

Conclusions  Patient 6-month recall of exacerbation events are inaccurate. This may lead to inaccurate estimates of incidence measures and underestimation of treatment effects. The use of multiple data sources combined with event adjudication could substantially reduce sample size requirements and possibly cost of studies.

contemporary reviews in critical care medicine 
Eric L. Scholten, MD; Jeremy R. Beitler, MD, MPH; G. Kim Prisk, PhD, DSc; Atul Malhotra, MD
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Prone positioning was first proposed in the 1970s as a method to improve gas exchange in the acute respiratory distress syndrome (ARDS). Subsequent observations of dramatic improvement in oxygenation with simple patient rotation motivated the next several decades of research. This work elucidated the physiology mechanisms underlying changes in gas exchange and respiratory mechanics with prone ventilation. However, translating physiological improvements into a clinical benefit has proven challenging; several contemporary trials showed no major clinical benefits with proning. By optimizing patient selection and treatment protocols, the most recent Proning Severe ARDS Patients (PROSEVA) trial demonstrated a significant mortality benefit with prone ventilation. This trial, and subsequent meta-analyses, support the role of prone positioning as an effective therapy to reduce mortality in severe ARDS, particularly when applied early with other lung-protective strategies. This review discusses the physiological principles, clinical evidence, and practical application of prone ventilation in ARDS.

editorial 
Miles Weinberger, MD
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No abstract is available for this article
recent advances in chest medicine 
Edward M. Wolin, MD

Neuroendocrine tumors (NET) are a rare, heterogeneous group of malignancies that arise from neuroendocrine cells throughout the body, with the lungs and gastrointestinal tract being the most common sites of origin. Despite increasing incidence, awareness of lung NET remains low among thoracic specialists who are often involved in assessment and early treatment for these patients. Successful treatment requires accurate and timely diagnosis; however, classification can be challenging, particularly for well-differentiated and intermediate-differentiated lung NET types (typical carcinoids [TC] and atypical carcinoids [AC]). Diagnosis and management of lung NET are further complicated by the nonspecificity of symptoms, variable natural history, and lack of high-level clinical evidence requiring a multidisciplinary approach, which has been shown to improve prognosis. Currently, surgery remains the only curative option for TC/AC. Inconsistencies between guideline recommendations for systemic therapies, especially radiation and chemotherapy, result in a lack of consensus on a standardized treatment for unresectable disease. Recent data from the phase 3 RADIANT-4 trial, which contained a large population of patients with advanced, well-differentiated, nonfunctional lung NET in addition to those with gastrointestinal NET, showed a reduced risk of disease progression and death with everolimus compared with placebo, leading to US approval of everolimus in these patient populations. This is the first high-level therapeutic evidence in patients with TC/AC, and everolimus is currently the only agent approved for TC/AC treatment. Increased awareness, prompt diagnosis, and additional adequately powered controlled clinical trials of patients with well-differentiated and intermediate-differentiated lung NET are needed to further improve evidence-based care.

recent advances in chest medicine 
Poushali Bhattacharjee, MD; Dana P. Edelson, MD, MS; Matthew M. Churpek, MD, MPH, PhD
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Sepsis contributes to up to half of all deaths in hospitalized patients, and early interventions, such as appropriate antibiotics, have been shown to improve outcomes. Most research has focused on early identification and treatment of septic patients in the emergency department and the intensive care unit; however, many patients develop sepsis on the general wards. The goal of this review is to discuss recent advances in sepsis detection in patients on the hospital wards. It will discuss data highlighting the benefits and limitations of the systemic inflammatory response syndrome (SIRS) criteria for screening septic patients, such as its low specificity, as well as newly described scoring systems, including the proposed role of the quick Sepsis-related Organ Failure Assessment (qSOFA) score. Challenges specific to detecting sepsis on the wards will be discussed, and future directions that utilize big data approaches and automated alert systems will be highlighted.

original research 
Barret Rush, MD; Paul Hertz, MD; Alexandra Bond, MD; Robert McDermid, MD; Leo Anthony Celi, MD MPH MS
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Objective  To investigate the use of palliative care (PC) in patients with end-stage chronic obstructive pulmonary disease (COPD) on home oxygen hospitalized for an exacerbation

Methods  Retrospective nationwide cohort analysis utilising the Nationwide Inpatient Sample (NIS). All patients >18 years of age with a diagnosis of COPD on home oxygen admitted for an exacerbation were included.

Results  55,208,382 hospitalizations from the 2006-2012 NIS samples were examined. There were 181,689 patients with COPD on home oxygen admitted for an exacerbation, 3,145 (1.7%) patients also had a palliative care contact. There was a 4.5-fold relative increase in PC referral from 2006 (0.45%) to 2012 (2.56%, p<0.01). Patients receiving palliative care consultations compared to those who did not were: older (75.0 years SD 10.9 vs 70.6 years SD 9.7, p<0.01), had longer hospitalizations (4.9 days IQR 2.6-8.2 vs 3.5 days IQR 2.1-5.6) and more likely to die in hospital (32.1% vs 1.5%, p<0.01). Race was significantly associated with referral to palliative care, with White patients referred more often than minorities (p<0.01). Factors associated with PC referral were: age (OR 1.03, 95% CI 1.02-1.04, p<0.01), metastatic cancer (OR 2.40, 95% CI 2.02-2.87, p<0.01), non-metastatic cancer (OR 2.75, 95% CI 2.43-3.11, p<0.01), invasive mechanical ventilation (OR 4.89, 95% CI 4.31-5.55, p<0.01), non-invasive mechanical ventilation (OR 2.84, 95% CI 2.58-3.12, p<0.01), and DNR status (OR 7.95, 95% CI 7.29-8.67, p<0.01).

Conclusions  The use of PC increased dramatically during the study period, however PC contact occurs only in a minority of end-stage COPD patients admitted with an exacerbation.

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