Current Issue


Chest. 2015;147(2):281-282. doi:10.1378/chest.14-2377

The triage of patients for admission to ICUs is a topic of intense focus by researchers and clinicians.1 But the process of discharging a patient from the ICU also involves multiple parties and steps, starting with the decision of whether a patient is ready for discharge, progressing to discharge planning and actual discharge, and ending with follow-up after discharge.2,3 Because of the complexity of care requirements for critically ill patients, and the fact that this discharge transition occurs from a resource-rich to a relatively resource-poor environment, discharge from the ICU represents a potentially vulnerable time for patients. The decision to discharge may be premature, transfer itself may create medical errors, and patients and families may experience fear or dissatisfaction with care.4,5 A scoping review by Stelfox and colleagues3 in this issue of CHEST (see page 317) provides an impressive overview of the discharge process for a patient from the ICU to the hospital ward, highlights the many facets of the issue, and catalogs tools that have been previously reported to facilitate this process.

Chest. 2015;147(2):282-284. doi:10.1378/chest.14-1970

The obesity hypoventilation syndrome (OHS) is defined by obesity (BMI > 30 kg/m2) and awake arterial hypercapnia (Paco2 > 45 mm Hg) in the absence of other causes of hypoventilation and is generally associated with sleep-disordered breathing such as OSA, nocturnal hypoventilation, or both.1,2 Compared with eucapnic obese individuals, patients with OHS have a lower quality of life, greater health-care expenditure, greater risk for pulmonary hypertension, and higher mortality rate,3,4 thus emphasizing the importance of early disease recognition as a pathway to improved management outcomes. In this regard, the article by Manuel and colleagues5 in this issue of CHEST (see page 362) offers some direction toward that goal. They propose that obese eucapnic individuals with an isolated elevation in blood bicarbonate measured only several hours after awakening and not explained by diuretics, mineralocorticoids, or alkaline ingestion, may, in fact, be a patient population in the earliest stage of OHS.

Chest. 2015;147(2):284-286. doi:10.1378/chest.14-1813

This famous quote was made by Chevalier Jackson in the Boston Medical Quarterly in 1865.1 At the time, Jackson, an otolaryngologist, was concerned about foreign body aspiration causing wheezing and being misdiagnosed as asthma. Today, this adage reminds us that there are many causes of wheezing and shortness of breath besides the common and classic diagnosis of asthma. Among these causes is COPD. In fact, COPD is probably one of the most common diagnoses made in the older patient with a smoking history who complains of shortness of breath, wheezing, or chest tightness. However, COPD is frequently underdiagnosed and overdiagnosed. Patients are underdiagnosed when spirometry is not used to search for objective evidence of obstruction, and patients are overdiagnosed when spirometry is not used to confirm the “obstruction” in COPD. Overdiagnosis mislabels the patient with a disease they do not have, which can result in inappropriate prescription and use of costly medications that may have side effects. In addition, the focus on COPD shifts attention away from the possibility of other causes of the patient’s symptoms, such as obesity, deconditioning, heart disease, or depression, which may lead to a worsening of their true underlying condition.

Point and Counterpoint

Chest. 2015;147(2):287-289. doi:10.1378/chest.14-2812

Based on the US Preventive Services Task Force (USPSTF) grade B recommendation for lung cancer screening,1 commercial insurers operating through Affordable Care Act exchanges, with the exception of certain grandfathered plans, must cover individuals aged < 65 years who meet the USPSTF criteria for CT scan screening without copayments before the end of 2015.2 Thus, for these insurers, the question regarding coverage is settled; all that might be considered is whether the law is reasonable or whether the USPSTF made an improper recommendation. With regard to the Centers for Medicare & Medicaid Services (CMS), the decision will be based on whether they determine the test has a proven benefit to the covered population.3 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, whereas those at higher risk would not. In a somewhat analogous manner it would also allow for those aged > 65 years with means to pay on their own the opportunity to be screened, whereas poor and probably higher-risk populations would not have access.

Chest. 2015;147(2):289-292. doi:10.1378/chest.14-2815

Primarily detected in an advanced stage, lung cancer is the leading cause of cancer-related death in the United States and remains one of the most costly cancers, with dismal 5-year survival rates.1,2 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 CT (LDCT) scanning compared with chest radiography (CXR).3 These results and the US Preventive Services Task Force (USPSTF) grade B recommendation4 fueled pressure for national insurance coverage of lung cancer screening with LDCT scanning. In contrast, the Medicare Evidence Development and Coverage Advisory Committee concluded that the apparent benefits of LDCT scan screening did not clearly outweigh the harms among Medicare beneficiaries. While awaiting the Centers for Medicare & Medicaid Services decision on coverage of LDCT scan 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 preventive service.

Chest. 2015;147(2):292-293. doi:10.1378/chest.14-2813

In the Counterpoint Editorial by Drs Courtright and Manaker,1 the pattern I had expressed concern about regarding overstating the harms and underestimating the benefits continues. Notably, the evidence regarding harms refers solely to National Lung Screen Trial (NLST) data, neglecting all the progress made in the past decade in technology as well as in developing more-efficient and safer protocols. Although the NLST was performed primarily at academic centers, there was no requirement that the follow-up studies or treatments be performed at these centers or that a certain protocol be followed. Concerns expressed about implementation in the community setting, including an inability to use best practice guidelines, seem unwarranted given the success demonstrated in developing quality standards for mammography. There is every reason to believe that similar types of implementation, by the same organizations, can also be accomplished for CT screening. Support for this also comes from the International Early Lung Cancer Action Program (I-ELCAP) report showing no difference in performance between the academic and community setting.2

Chest. 2015;147(2):293-294. doi:10.1378/chest.14-2816

We appreciate Dr Yankelevitz’s1 discussion favoring coverage for lung cancer screening with low-dose CT (LDCT) scanning 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 preventive 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 scan screening.


Chest. 2015;147(2):295-303. doi:10.1378/chest.14-2500

Lung cancer screening with a low-dose chest CT scan can result in more benefit than harm when performed in settings committed to developing and maintaining high-quality programs. This project aimed to identify the components of screening that should be a part of all lung cancer screening programs. To do so, committees with expertise in lung cancer screening were assembled by the Thoracic Oncology Network of the American College of Chest Physicians (CHEST) and the Thoracic Oncology Assembly of the American Thoracic Society (ATS). Lung cancer program components were derived from evidence-based reviews of lung cancer screening and supplemented by expert opinion. This statement was developed and modified based on iterative feedback of the committees. Nine essential components of a lung cancer screening program were identified. Within these components 21 Policy Statements were developed and translated into criteria that could be used to assess the qualification of a program as a screening facility. Two additional Policy Statements related to the need for multisociety governance of lung cancer screening were developed. High-quality lung cancer screening programs can be developed within the presented framework of nine essential program components outlined by our committees. The statement was developed, reviewed, and formally approved by the leadership of CHEST and the ATS. It was subsequently endorsed by the American Association of Throacic Surgery, American Cancer Society, and the American Society of Preventive Oncology.

Chest. 2015;147(2):304-308. doi:10.1378/chest.14-0974

Infectious diseases acquired by survivors of large-scale natural disasters complicate the recovery process. During events such as tsunamis, hurricanes, earthquakes, and tornados and well into the recovery period, victims often are exposed to water-soil mixtures that have relocated with indigenous microbes. Because nontuberculous mycobacteria (NTM) are ubiquitous in water and soil, there is potential for increased exposure to these organisms during natural disasters. In this hypothesis-driven commentary, we discuss the rise in NTM lung disease and natural disasters and examine the geographic overlap of NTM infections and disaster frequencies in the United States. Moreover, we show an increased number of positive NTM cultures from Louisiana residents in the years following three of the relatively recent epic hurricanes and posit that such natural disasters may help to drive the increased number of NTM infections. Finally, we advocate for increased environmental studies and surveillance of NTM infections before and after natural disasters.

Commentary: Ahead of the Curve

Chest. 2015;147(2):309-316. doi:10.1378/chest.14-1748

Lung transplantation has been the last of the solid organs to gain traction as a viable therapeutic option. Due to differing standards of care and the relatively low number of lung transplants performed, it has proven difficult to orchestrate prospective multicenter studies to determine best practice and explore novel therapies. Nonetheless, there have been incremental advances in lung transplantation, including liberalization of criteria for both suitable donor organs as well as acceptable recipients. This has resulted in increasing numbers of procedures being performed, and outcomes have improved despite an expanding cohort of sicker patients undergoing lung transplantation. This review will discuss current trends and future developments with a focus on the most pertinent of the pitfalls that may accompany lung transplantation.

Original Research: Critical Care

Chest. 2015;147(2):317-327. doi:10.1378/chest.13-2965

BACKGROUND:  We conducted a scoping review to systematically review the literature reporting patient discharge from ICUs, identify facilitators and barriers to high-quality care, and describe tools developed to improve care.

METHODS:  We searched Medline, Embase, CINAHL, and the Cochrane Central Register of Controlled Trials. Data were extracted on the article type, study details for research articles, patient population, phase of care during discharge, and dimensions of health-care quality.

RESULTS:  From 8,154 unique publications we included 224 articles. Of these, 131 articles (58%) were original research, predominantly case series (23%) and cohort (16%) studies; 12% were narrative reviews; and 11% were guidelines/policies. Common themes included patient and family needs/experiences (29% of articles) and the importance of complete and accurate information (26%). Facilitators of high-quality care included provider-patient communication (30%), provider-provider communication (25%), and the use of guidelines/policies (29%). Patient and family anxiety (21%) and limited availability of ICU and ward resources (26%) were reported barriers to high-quality care. A total of 47 tools to facilitate patient discharge from the ICU were identified and focused on patient evaluation for discharge (29%), discharge planning and teaching (47%), and optimized discharge summaries (23%).

CONCLUSIONS:  Common themes, facilitators and barriers related to patient and family needs/experiences, communication, and the use of guidelines/policies to standardize patient discharge from ICU transcend the literature. Candidate tools to improve care are available; comparative evaluation is needed prior to broad implementation and could be tested through local quality-improvement programs.

Chest. 2015;147(2):328-334. doi:10.1378/chest.14-0692

BACKGROUND:  Daily application of oral chlorhexidine gluconate (CHX) following intubation to reduce the risk of ventilator-associated pneumonia (VAP) is now the standard of care in many ICUs. This randomized clinical trial evaluated the benefit of adding a preintubation CHX dose to the known benefit of postintubation CHX to reduce the risk of early-onset VAP. A secondary aim was to test the effect of a preintubation oral application of CHX on early endotracheal tube (ETT) colonization.

METHODS:  Subjects (N = 314) were recruited from two teaching hospitals and were randomly assigned to oral application of 5 mL CHX 0.12% solution before intubation (intervention group, n = 157), or to a control group (n = 157) who received no CHX before intubation. All subjects received CHX bid after intubation. Groups were compared using a repeated-measures model with Clinical Pulmonary Infection Score (CPIS) as the response variable. In a planned subset of subjects, ETTs were cultured at extubation.

RESULTS:  Application of a preintubation dose of CHX did not provide benefit over the intervention period beyond that afforded by daily oral CHX following intubation. ETT colonization at extubation was < 20% in both groups (no statistically significant difference). Mean CPIS remained below 6 (VAP threshold score) in both groups.

CONCLUSIONS:  Although it is feasible to deliver CHX prior to intubation (including emergent or urgent intubation), the results suggest that preintubation CHX may be inconsequential when the ventilator bundle, including daily oral CHX, is in place. During the preintubation period, providers should focus their attention on other critical activities.

TRIAL REGISTRY:  ClinicalTrials.gov; No.: NCT00893763; URL: www.clinicaltrials.gov

Chest. 2015;147(2):335-346. doi:10.1378/chest.14-1012

BACKGROUND:  The effect of single-dose etomidate on mortality in patients with sepsis remains controversial. We systematically reviewed the literature to investigate whether a single dose of etomidate for rapid sequence intubation increased mortality in patients with sepsis.

METHODS:  PubMed, Embase, and CENTRAL (Cochrane Central Register of Controlled Trials) were searched for randomized controlled trials (RCTs) and observational studies regarding the effect of single-dose etomidate on mortality in adults with sepsis. The primary outcome was all-cause mortality. The Mantel-Haenszel method with random-effects modeling was used to calculate pooled relative risks (RRs) and 95% CIs.

RESULTS:  Eighteen studies (two RCTs and 16 observational studies) in 5,552 patients were included. Pooled analysis suggested that single-dose etomidate was not associated with increased mortality in patients with sepsis in both the RCTs (RR, 1.20; 95% CI, 0.84-1.72; P = .31; I2 = 0%) and the observational studies (RR, 1.05; 95% CI, 0.97-1.13; P = .23; I2 = 25%). When only adjusted RRs were pooled in five observational studies, RR for mortality was 1.05 (95% CI, 0.79-1.39; P = .748; I2 = 71.3%). These findings also were consistent across all subgroup analyses for observational studies. Single-dose etomidate increased the risk of adrenal insufficiency in patients with sepsis (eight studies; RR, 1.42; 95% CI, 1.22-1.64; P < .00001).

CONCLUSIONS:  Current evidence indicates that single-dose etomidate does not increase mortality in patients with sepsis. However, this finding largely relies on data from observational studies and is potentially subject to selection bias; hence, high-quality and adequately powered RCTs are warranted.

Chest. 2015;147(2):347-355. doi:10.1378/chest.14-0610

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

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

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

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

Chest. 2015;147(2):356-361. doi:10.1378/chest.14-0886

BACKGROUND:  Respiratory complications occur in 20% to 65% of patients who have undergone esophagectomy. While noninvasive positive pressure ventilation (NPPV) is associated with fewer complications than endotracheal intubation (ET), it is relatively contraindicated after esophagectomy due to potential injury to the anastomosis. We created ex vivo and in vivo pig models to determine the pressure tolerance of an esophagectomy anastomosis and compare it to esophageal pressure during NPPV.

METHODS:  We created a stapled side-to-side, functional end-to-end esophagogastric anastomosis. With continuous intraluminal pressure monitoring, we progressively insufflated the anastomosis with a syringe until we detected an anastomotic leak, and recorded the maximum pressure before leakage. We performed this experiment in 10 esophageal specimens and 10 live pigs. We then applied a laryngeal mask airway (LMA) to five live pigs and measured the pressure in the proximal esophagus with increasing ventilatory pressures.

RESULTS:  The perforation was always at the anastomosis. The ex vivo and in vivo anastomoses tolerated a mean of 101 ± 44 cm H2O and 84 ± 38 cm H2O before leak, respectively. There was no significant difference between the pressure thresholds of ex vivo and in vivo anastomoses (P = .51). When 20, 30, and 40 cm H2O of positive pressure via LMA were delivered, the esophagus sensed 5 ± 4 cm H2O (25%), 11 ± 11 cm H2O (37%), and 15 ± 9 cm H2O (38%), respectively.

CONCLUSIONS:  Our pig model suggests that an esophagectomy anastomosis can tolerate a considerably higher pressure than is transmitted to the esophagus during NPPV. NPPV may be a safe alternative to ET after esophagectomy.

Original Research: Sleep Disorders

Chest. 2015;147(2):362-368. doi:10.1378/chest.14-1279

BACKGROUND:  Obesity hypoventilation syndrome (OHS) conventionally includes awake hypercapnia, but an isolated raised bicarbonate, even in the absence of awake hypercapnia, may represent evidence of “early” OHS. We investigated whether such individuals exhibit certain features characteristic of established OHS.

METHODS:  Obese subjects (BMI > 30 kg/m2) were identified from a variety of sources and divided into those with (1) normal blood gas measurements and normal acid-base balance, (2) an isolated raised base excess (BE) (≥ 2 mmol/L), and (3) awake hypercapnia (> 6 kPa; ie, established OHS). Two-point ventilatory responses to hypoxia and hypercapnia were performed. Polygraphic sleep studies were done to identify intermittent and prolonged hypoxia.

RESULTS:  Seventy-one subjects (BMI, 47.2; SD, 9.8; age, 52.1 years; SD, 8.8 years) were recruited into three groups (33, 22, and 16 respectively). The Paco2 and BE values were 5.15, 5.42, 6.62 kPa, and +0.12, +3.01, +4.78 mmol/L, respectively. For nearly all the ventilatory response and sleep study measures, group 2 (with only an isolated raised BE) represented an intermediate group, and for some of the measures they were more similar to the third group with established OHS.

CONCLUSIONS:  These data suggest that obese individuals with a raised BE, despite normocapnia while awake, should probably be regarded as having early obesity-related hypoventilation. This has important implications for clinical management as well as randomized controlled treatment trials, as they may represent a group with a more reversible disease process.

TRIAL REGISTRY:  ClinicalTrials.gov; No.: NCT01380418; URL: www.clinicaltrials.gov

Original Research: COPD

Chest. 2015;147(2):369-376. doi:10.1378/chest.14-0672

BACKGROUND:  Despite guideline recommendations, patients suspected of having COPD often are treated empirically instead of undergoing spirometry to confirm airflow obstruction (AFO). Accurate diagnosis and treatment are essential to provide high-quality, value-oriented care. We sought to identify predictors associated with AFO among patients with and treated for COPD prior to performance of confirmatory spirometry.

METHODS:  We identified a cohort of veterans with spirometry performed at Pacific Northwest Department of Veterans Affairs medical centers between 2003 and 2007. We included only patients with empirically diagnosed COPD in the 2 years prior to spirometry who were also taking inhaled medication to treat COPD in the 1 year prior to spirometry. We used relative risk regression analysis to identify predictors of AFO.

RESULTS:  Among patients empirically treated for COPD (N = 3,209), 62% had AFO. Risk factors such as older age, prior smoking status, and underweight status were associated with AFO on spirometry. In contrast, comorbidities often associated with somatic symptoms were associated with absence of AFO and included congestive heart failure, depression, diabetes, obesity, and sleep apnea.

CONCLUSIONS:  Comorbidities associated with somatic complaints of dyspnea were associated with a lower risk of having airflow limitations, suggesting that empirical diagnosis and treatment of COPD may lead to inappropriate treatment of individuals who do not have AFO.

Chest. 2015;147(2):377-387. doi:10.1378/chest.14-0528

BACKGROUND:  Surgical and medical treatments for emphysema may affect both quality and quantity of life. The purpose of this article is to report outcomes from the National Emphysema Treatment Trial (NETT) using an index that combines quality and quantity of life.

METHODS:  This was a prospective randomized clinical trial. Following pulmonary rehabilitation, 1,218 patients with severe emphysema were randomly assigned to maximal medical therapy or to lung volume reduction surgery (LVRS). A generic quality-of-life measure, known as the Quality of Well-being Scale (QWB), was administered at baseline and again at 6, 12, 24, 36, 48, 60, and 72 months following treatment assignment.

RESULTS:  At baseline, QWB scores were comparable for the Medical and LVRS groups. For both groups, scores significantly improved following the rehabilitation program. The QWB scores before death for patients in the LVRS group improved up to the year 2 visit, whereas scores for the Medical group dropped significantly following the baseline visit. Imputing zeros (0) for death, QWB scores decreased significantly for both groups. With or without scoring death as 0, the LVRS group achieved better outcomes, and the significant differences were maintained until the sixth year. Over 6 years of follow-up, LVRS produced an average of 0.30 quality-adjusted life years (QALYs), or the equivalent of about 3.6 months of well life.

CONCLUSIONS:  Compared with maximal medical therapy alone, patients undergoing maximal medical therapy plus LVRS experienced improved health-related quality of life and gained more QALYs.

TRIAL REGISTRY:  ClinicalTrials.gov; No.: NCT00000606; URL: www.clinicaltrials.gov

Original Research: Asthma

Chest. 2015;147(2):388-396. doi:10.1378/chest.14-1698

BACKGROUND:  The role of tiotropium for the treatment of asthma has not yet been clearly defined. The aim of this systematic review was to assess the efficacy and safety of tiotropium in patients with asthma.

METHODS:  Randomized placebo-controlled trials were included. Primary outcomes were peak and trough FEV1 and morning and evening peak expiratory flow (PEF).

RESULTS:  Thirteen studies (4,966 patients) were included. Three different therapeutic protocols were identified. Tiotropium as an add-on to inhaled corticosteroids (ICSs) showed statistically and clinically significant increases in PEF (22-24 L/min) and FEV1 (140-150 mL). Additionally, tiotropium decreased the rate of exacerbations (number needed to treat for benefit [NNTB], 36) and improved asthma control. The use of tiotropium in patients poorly controlled despite the use of medium to high doses of ICS was not inferior to salmeterol. Finally, the use of tiotropium as an add-on to ICS/salmeterol combination increased pulmonary function to a clinically significant magnitude, reduced asthma exacerbations (relative risk, 0.70; 95% CI, 0.53-0.94; P < .02; I2 = 0%; NNTB, 17), and improved asthma control compared with ICS/salmeterol. Tiotropium was well tolerated, and no potential safety signals were observed.

CONCLUSIONS:  Tiotropium resulted noninferiorly to salmeterol and superiorly to placebo in patients with moderate to severe asthma who were not adequately controlled by ICS or ICS/salmeterol. Major benefits were concentrated in the increase in lung function and in the case of patients with severe asthma, in the reduction of exacerbations.

Chest. 2015;147(2):397-405. doi:10.1378/chest.14-1214

BACKGROUND:  Omega-3 fatty acid supplements have been reported to inhibit exercise-induced bronchoconstriction (EIB). It has not been determined whether omega-3 supplements inhibit airway sensitivity to inhaled mannitol, a test for bronchial hyperresponsiveness (BHR) and model for EIB in people with mild to moderate asthma.

METHODS:  In a double-blind, crossover trial, subjects with asthma who had BHR to inhaled mannitol (n = 23; 14 men; mean age, 28 years; one-half taking regular inhaled corticosteroids) were randomized to omega-3 supplements (4.0 g/d eicosapentaenoic acid and 2.0 g/d docosahexaenoic acid) or matching placebo for 3 weeks separated by a 3-week washout. The primary outcome was the provoking dose of mannitol (mg) to cause a 15% fall in FEV1 (PD15). Secondary outcomes were sputum eosinophil count, spirometry, Asthma Control Questionnaire (ACQ) score, serum triacylglyceride level, and lipid mediator profile in urine and serum.

RESULTS:  PD15 (geometric mean, 95% CI) to mannitol following supplementation with omega-3s (78 mg, 51-119 mg) was not different from placebo (88 mg, 56-139 mg, P = .5). There were no changes in sputum eosinophils (mean ± SD) in a subgroup of 11 subjects (omega-3, 8.4% ± 8.2%; placebo, 7.8% ± 11.8%; P = .9). At the end of each treatment period, there were no differences in FEV1 % predicted (omega-3, 85% ± 13%; placebo, 84% ± 11%; P = .9) or ACQ score (omega-3, 1.1% ± 0.5%; placebo, 1.1% ± 0.5%; P = .9) (n = 23). Omega-3s caused significant lowering of blood triglyceride levels and expected shifts in serum fatty acids and eicosanoid metabolites, confirming adherence to the supplements; however, no changes were observed in urinary mast cell mediators.

CONCLUSIONS:  Three weeks of omega-3 supplements does not improve BHR to mannitol, decrease sputum eosinophil counts, or inhibit urinary excretion of mast cell mediators in people with mild to moderate asthma, indicating that dietary omega-3 supplementation is not useful in the short-term treatment of asthma.

TRIAL REGISTRY:  ClinicalTrials.gov; No.: NCT00526357; URL: www.clinicaltrials.gov.

Chest. 2015;147(2):406-414. doi:10.1378/chest.14-1874

BACKGROUND:  A multicenter study in the late 1990s demonstrated suboptimal emergency asthma care for pregnant women in US EDs. After a decade, follow-up data are lacking. We aimed to examine changes in emergency asthma care of pregnant women since the 1990s.

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

RESULTS:  Of 4,895 ED patients with acute asthma, the analytic cohort comprised 125 pregnant women. Between the two time periods, there were no significant changes in patient demographics, chronic asthma severity, or initial peak expiratory flow. In contrast, ED systemic corticosteroid treatment increased significantly from 51% to 78% across the time periods (OR, 3.11; 95% CI, 1.27-7.60; P = .01); systemic corticosteroids at discharge increased from 42% to 63% (OR, 2.49; 95% CI, 0.97-6.37; P = .054). In the adjusted analyses, pregnant women in recent years were more likely to receive systemic corticosteroids, both in the ED (OR, 4.76; 95% CI, 1.63-13.9; P = .004) and at discharge (OR, 3.18; 95% CI, 1.05-9.61; P = .04).

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

Original Research: Diffuse Lung Disease

Chest. 2015;147(2):415-422. doi:10.1378/chest.14-0711

BACKGROUND:  Current understanding of the clinical course of diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) is poor and based predominantly on small case series. In our clinical experience, we have found that the diagnosis of DIPNECH is frequently delayed because respiratory symptoms are ascribed to other lung conditions. The objectives of this study were to collect and analyze longitudinal clinical data on pulmonary physiology, chest high-resolution CT (HRCT) imaging, and therapies to better delineate the course of disease.

METHODS:  We established a cohort of patients (N = 30) with DIPNECH seen at our institution. We used descriptive statistics to summarize cohort characteristics and longitudinal analytic techniques to model FEV1 % predicted (FEV1%) over time.

RESULTS:  All subjects were women who presented with long-standing cough and dyspnea. The majority had an FEV1% < 50% at the time of diagnosis. Forty percent were given a diagnosis of asthma as the cause for physiologic obstruction. The mean FEV1% for the entire cohort showed no statistically significant decline over time, but 26% of the subjects experienced a 10% decline in FEV1 within 2 years. Among the pathology samples available for review, 28% (five of 18) had typical carcinoids and 44% had associated constrictive bronchiolitis. We propose clinical diagnostic criteria for DIPNECH that incorporate demographic, pulmonary physiology, HRCT imaging, and transbronchial and surgical lung biopsy data.

CONCLUSIONS:  DIPNECH is a female-predominant lung disease manifested by dyspnea and cough, physiologic obstruction, and nodules on HRCT imaging. Additional research is needed to understand the natural history of this disease and validate the proposed diagnostic criteria.

Chest. 2015;147(2):423-429. doi:10.1378/chest.14-1127

BACKGROUND:  Palliative care, integrated early, may reduce symptom burden in patients with idiopathic pulmonary fibrosis (IPF). However, limited information exists on timing and clinical practice. The purpose of this study was to describe the time course of events prior to death in patients with IPF managed at a specialty center with a focus on location of death and timing of referral for palliative care.

METHODS:  Data were retrospectively extracted from the health system’s data repository and obituary listings. The sample included all decedents, excluding lung transplant recipients, who had their first visit to the center between 2000 and 2012.

RESULTS:  Median survival for 404 decedents was 3 years from diagnosis and 1 year from first center visit. Of 277 decedents whose location of death could be determined, > 50% died in the hospital (57%). Only 38 (13.7%) had a formal palliative care referral and the majority (71%) was referred within 1 month of their death. Decedents who died in the academic medical center ICU were significantly younger than those who died in a community hospital ward (P = .04) or hospice (P = .001).

CONCLUSIONS:  The majority of patients with IPF died in a hospital setting and only a minority received a formal palliative care referral. Referral to palliative care occurred late in the disease. These findings indicate the need to study adequacy of end-of-life management in IPF and promote earlier discussion and referral to palliative care.

Chest. 2015;147(2):430-437. doi:10.1378/chest.14-0453

BACKGROUND:  No study has determined whether the risk of mortality predicted by the GAP (gender, age, and physiologic variables) model matches the observed mortality from idiopathic pulmonary fibrosis (IPF) in non-Western populations. We evaluated the clinical course of IPF and validated the GAP model in Korean patients with IPF.

METHODS:  We included 268 patients who received a diagnosis of IPF at Seoul National University Hospital between 2005 and 2009. For each patient, demographics and clinical data, such as lung physiologic parameters at IPF diagnosis, were evaluated. We validated the GAP model using discrimination and calibration to predict the risk of death in Korean patients with IPF.

RESULTS:  The study population comprised 181 men and 87 women (mean age, 65.9 years). The mean baseline % predicted FVC was 77, and % predicted diffusing capacity of lung for carbon monoxide was 65.9. A total of 157 deaths (58.6%) occurred during follow-up, and the median time to death was 4.64 years. The observed cumulative mortality at 1, 2, and 3 years was 10.4%, 20.9%, and 31.0%, respectively. The GAP model produced estimates of 1-year mortality risk consistent with the observed data (C statistic: GAP calculator, 0.74; GAP index and staging system, 0.72; P < .29). However, calibration of the GAP model at 3 years was not satisfactory.

CONCLUSIONS:  The GAP model showed similar discrimination power compared with the original cohort but did not predict the 3-year risk of death accurately. Further multinational validation studies are needed.

Chest. 2015;147(2):438-449. doi:10.1378/chest.14-1120

BACKGROUND:  The clinical presentation and outcome of sarcoidosis varies by race. However, the race difference in mortality outcome remains largely unknown.

METHODS:  We studied mortality related to sarcoidosis from 1999 through 2010 by examining data on multiple causes of death from the National Center for Health Statistics. We compared the comorbid conditions between sarcoidosis-related deaths with deaths caused by car accidents (previously healthy control subjects) and rheumatoid arthritis (chronic disease control subjects) in both African Americans and Caucasians.

RESULTS:  From 1999 through 2010, sarcoidosis was reported as an immediate cause of death in 10,348 people in the United States with a combined overall mean age-adjusted mortality rate of 2.8 per 1 million person-years. Of these, 6,285 were African American and 3,984 Caucasian. The age-adjusted mortality rate for African Americans was 12 times higher than for Caucasians. African Americans died at an earlier age than Caucasians. African Americans living in the District of Columbia and North Carolina and Caucasians living in Vermont had higher mortality rates. Although the total sarcoidosis age-adjusted mortality rate had not changed over the 12 year period studied, this rate increased for Caucasians (R = 0.747, P = .005) but not for African Americans. Compared with the control groups, pulmonary hypertension was significantly more common in individuals with sarcoidosis.

CONCLUSIONS:  This nationwide population-based study exposes a significant difference in ethnicity and sex among people dying of sarcoidosis in the United States. Pulmonary hypertension investigation should be considered in all patients with sarcoidosis, especially African Americans.

Chest. 2015;147(2):450-459. doi:10.1378/chest.14-0976

BACKGROUND:  The current usual interstitial pneumonitis (UIP)/idiopathic pulmonary fibrosis CT scan classification system excludes probable UIP as a diagnostic category. We sought to determine the predictive effect of probable UIP on CT scan on histology and the effect of the promoter polymorphism in MUC5B (rs35705950) on histologic and CT scan UIP diagnosis.

METHODS:  The cohort included 201 subjects with pulmonary fibrosis who had lung tissue samples obtained within 1 year of chest CT scan. UIP diagnosis on CT scan was categorized as inconsistent with, indeterminate, probable, or definite UIP by two to three pulmonary radiologists. Tissue slides were scored by two expert pulmonary pathologists. All subjects with available DNA (N = 200) were genotyped for rs35705950.

RESULTS:  The proportion of CT scan diagnoses were as follows: inconsistent with (69 of 201, 34.3%), indeterminate (72 of 201, 35.8%), probable (34 of 201, 16.9%), and definite (26 of 201, 12.9%) UIP. Subjects with probable UIP on CT scan were more likely to have histologic probable/definite UIP than subjects with indeterminate UIP on CT scan (82.4% [28 of 34] vs 54.2% [39 of 72]; P = .01). CT scan and microscopic honeycombing were not associated with each other (P = .76). The minor (T) allele of the MUC5B polymorphism was associated with concordant CT scan and histologic UIP diagnosis (P = .03).

CONCLUSIONS:  Probable UIP on CT scan is associated with a higher rate of histologic UIP than indeterminate UIP on CT scan suggesting that they are distinct groups and should not be combined into a single CT scan category as currently recommended by guidelines. CT scan and microscopic honeycombing may be dissimilar entities. The T allele at rs35705950 predicts a UIP diagnosis by both chest CT scan and histology.

Chest. 2015;147(2):460-464. doi:10.1378/chest.14-0867

BACKGROUND:  Polymorphisms in the MUC5B promoter, TOLLIP, and nine additional genetic loci have been associated with idiopathic pulmonary fibrosis (IPF) within non-Hispanic white populations. It is unknown whether these variants account for risk of IPF in other racial/ethnic populations. We conducted a candidate single nucleotide polymorphism (SNP) association study in cohorts of Mexican and Korean patients with IPF.

METHODS:  We chose 12 SNPs from 11 loci that are associated with IPF among non-Hispanic whites and genotyped these SNPs in cohorts of Mexican (83 patients, 111 control subjects) and Korean (239 patients, 87 control subjects) people. Each SNP was tested for association with IPF, after adjusting for age and sex.

RESULTS:  The MUC5B promoter SNP rs35705950 was associated with IPF in the Mexican (OR = 7.36, P = .0001), but not the Korean (P = .99) cohort. The SNP in IVD (chromosome15, rs2034650) was significantly associated with pulmonary fibrosis in both the Mexican (OR = 0.40, P = .01) and Korean (OR = 0.13, P = .0008) cohorts. In the Korean cohort, there were no other variants associated with disease. In the Mexican cohort, SNPs on chromosomes 3, 4, and 11 were also associated with disease.

CONCLUSIONS:  The strongest identified genetic risk factor for IPF among the non-Hispanic white population, the MUC5B promoter polymorphism, is also a strong risk factor in a Mexican population, but is very rare in a Korean population. The majority of genetic variants that account for risk of IPF in groups other than non-Hispanic whites are unknown. Hispanic and Asian populations should be studied separately to identify genetic risk loci for IPF.

Chest. 2015;147(2):465-474. doi:10.1378/chest.14-0994

BACKGROUND:  Previous studies have investigated the relationship between occupational and environmental agents and idiopathic pulmonary fibrosis (IPF). However, there have been few studies regarding the prognosis of patients with IPF according to patient occupation.

METHODS:  We investigated whether occupational dust exposure was associated with clinically decreased lung function and poor prognosis. The Korean Interstitial Lung Disease Research Group conducted a national survey to evaluate the clinical, physiologic, radiologic, and survival characteristics of patients with IPF. A total of 1,311 patients with IPF were stratified into five groups according to their occupation: (1) unemployed or homemakers (n = 628); (2) farmers, fishers, or ranchers (n = 230); (3) sales or service personnel (n = 131); (4) clerical or professional personnel (n = 151); and (5) specific dust-exposed workers (n = 171).

RESULTS:  The mean age of subjects at diagnosis, was 67.5 ± 9.7 years. Current smokers were 336 patients, 435 were exsmokers, and 456 were never smokers. Dust-exposed workers showed early onset of IPF (61.3 ± 8.6 years; P < .001) and a longer duration of symptoms at diagnosis (17.0 ± 28.2 months; P = .004). Aging (P = .001; hazard ratio [HR], 1.034; 95% CI, 1.014-1.054), FVC % predicted at diagnosis (P = .004; HR, 0.984; 95% CI, 0.974-0.995), and dust-exposure occupation (P = .033; HR, 1.813; 95% CI, 1.049-3.133) were associated with mortality.

CONCLUSIONS:  These findings indicate that occupational dust may be an aggravating factor associated with a poor prognosis in IPF.

Original Research: Pulmonary Vascular Disease

Chest. 2015;147(2):475-483. doi:10.1378/chest.14-0402

BACKGROUND:  Direct oral anticoagulants (DOAs) have been shown to be as effective and at least as safe as conventional anticoagulation for the prevention of recurrences in patients with VTE. Whether this is the case in patients with cancer-associated VTE remains undefined.

METHODS:  We performed a meta-analysis of randomized controlled trials with the aim of assessing the efficacy and safety of DOAs in patients with VTE and cancer. MEDLINE, EMBASE, and CENTRAL were searched up to December 2013 with no language restriction. The primary outcome of the analysis was recurrent VTE. Data on major bleeding (MB) and clinically relevant nonmajor bleeding were analyzed. Data were pooled and compared by ORs and 95% CIs.

RESULTS:  Overall, 10 studies comparing DOAs with conventional anticoagulation for treatment of VTE including patients with cancer were included in the review. Six studies were included in the meta-analysis (two with dabigatran, two with rivaroxaban, one with edoxaban, and one with apixaban), accounting for a total of 1,132 patients. VTE recurred in 23 of 595 (3.9%) and in 32 of 537 (6.0%) patients with cancer treated with DOAs and conventional treatment, respectively (OR, 0.63; 95% CI, 0.37-1.10; I2, 0%). MB occurred in 3.2% and 4.2% of patients receiving DOAs and conventional treatment, respectively (OR, 0.77; 95% CI, 0.41-1.44; I2, 0%).

CONCLUSIONS:  DOAs seem to be as effective and safe as conventional treatment for the prevention of VTE in patients with cancer. Further clinical trials in patients with cancer-associated VTE should be performed to confirm these results.

Chest. 2015;147(2):484-494. doi:10.1378/chest.14-1004

BACKGROUND:  Few studies have prospectively reported outcomes in patients with pulmonary arterial hypertension (PAH) treated with epoprostenol in the modern-day era of oral therapy and combination treatments. The Registry to Prospectively Describe Use of Epoprostenol for Injection (Veletri, prolonged room temperature stable-epoprostenol [RTS-Epo]) in Patients with Pulmonary Arterial Hypertension (PROSPECT) was established to prospectively describe the course of PAH in patients prescribed RTS-Epo.

METHODS:  PROSPECT is a multicenter, US-based drug registry of primarily group 1 patients with PAH treated with RTS-Epo who were parenteral-naive or parenteral-transitioned at enrollment. Patients were followed until discontinuation of RTS-Epo, withdrawal, loss to follow-up, death, or end of study (maximum 1 year). One-year freedom from hospitalization (FH) and survival estimates were summarized by prostacyclin history (parenteral-naive or parenteral-transitioned), sex, and chronic renal insufficiency (CRI).

RESULTS:  A total of 336 patients were included. The overall 1-year FH estimate was 51.0% ± 2.8% and was lower in parenteral-naive patients than parenteral-transitioned patients (42.8% ± 4.3% vs 57.1% ± 3.7%, respectively; P = .002). FH estimates were lower in male patients than female patients (38.3% ± 5.9% vs 54.6% ± 3.2%, respectively; P < .015) and in patients with CRI than patients without CRI (17.0% ± 8.4% vs 53.7% ± 2.9%, respectively; P < .001). The overall 1-year survival estimate was 84.0% ± 2.1%. Survival was poorer in parenteral-naive patients, male patients, and patients with CRI.

CONCLUSIONS:  Risk of hospitalization and mortality remain high in patients with PAH. In particular, patients who are parenteral-naive at initiation of RTS-Epo therapy, male patients, and patients with CRI require close monitoring and aggressive clinical management.

Chest. 2015;147(2):495-501. doi:10.1378/chest.14-1036

BACKGROUND:  Pulmonary arterial hypertension (PAH) is a rare and ultimately fatal disorder of the pulmonary vasculature. There is increasing interest in the worldwide characteristics of patients with PAH, although data coming from the Southern Hemisphere remain scarce. The objective of this study was to describe a cohort of incident patients with PAH from a large reference center in Brazil.

METHODS:  All consecutive patients who received a diagnosis of PAH by right-sided heart catheterization between 2008 and 2013 were included in the study.

RESULTS:  A total of 178 patients with newly diagnosed PAH were enrolled in the study (mean age, 46 years; female/male ratio, 3.3:1; 45.5% in New York Heart Association functional class III or IV). Idiopathic PAH (IPAH), connective tissue disease (CTD), and schistosomiasis-associated PAH (Sch-PAH) accounted for 28.7%, 25.8%, and 19.7% of all cases, respectively. The patients were treated with phosphodiesterase type 5 inhibitors (66%), endothelin receptor antagonists (27%), or a combination of both (5%). For the PAH group as a whole, the estimated survival rate 3 years after diagnosis was 73.9%. The prognosis for the patients with CTD was worse than that for the patients with IPAH and Sch-PAH (P = .03).

CONCLUSIONS:  The distribution of PAH causes and the baseline characteristics in our registry clearly differ from the previously published European and US-based registries. These differences highlight the importance of regional registries and also raise questions regarding the need to better account for such differences in future clinical trials.

Original Research: Disorders of the Pleura

Chest. 2015;147(2):502-512. doi:10.1378/chest.14-0820

BACKGROUND:  The role of fluorodeoxyglucose (FDG)-PET imaging for diagnosing malignant pleural effusions is not well defined. The aim of this study was to summarize the evidence for its use in ruling in or out the malignant origin of a pleural effusion or thickening.

METHODS:  A meta-analysis was conducted of diagnostic accuracy studies published in the Cochrane Library, PubMed, and Embase (inception to June 2013) without language restrictions. Two investigators selected studies that had evaluated the performance of FDG-PET imaging in patients with pleural effusions or thickening, using pleural cytopathology or histopathology as the reference standard for malignancy. Subgroup analyses were conducted according to FDG-PET imaging interpretation (qualitative or semiquantitative), PET imaging equipment (PET vs integrated PET-CT imaging), and/or target population (known lung cancer or malignant pleural mesothelioma). Study quality was assessed using Quality Assessment of Diagnostic Accuracy Studies-2. We used a bivariate random-effects model for the analysis and pooling of diagnostic performance measures across studies.

RESULTS:  Fourteen non-high risk of bias studies, comprising 407 patients with malignant and 232 with benign pleural conditions, met the inclusion criteria. Semiquantitative PET imaging readings had a significantly lower sensitivity for diagnosing malignant effusions than visual assessments (82% vs 91%; P = .026). The pooled test characteristics of integrated PET-CT imaging systems using semiquantitative interpretations for identifying malignant effusions were: sensitivity, 81%; specificity, 74%; positive likelihood ratio (LR), 3.22; negative LR, 0.26; and area under the curve, 0.838. Resultant data were heterogeneous, and spectrum bias should be considered when appraising FDG-PET imaging operating characteristics.

CONCLUSIONS:  The moderate accuracy of PET-CT imaging using semiquantitative readings precludes its routine recommendation for discriminating malignant from benign pleural effusions.

Chest. 2015;147(2):513-519. doi:10.1378/chest.14-0013

BACKGROUND:  Chest CT scanning has become an integral part of the workup for undiagnosed pleural effusions. We aimed to develop a CT scan-based scoring system for differentiating between benign and malignant pleural effusions.

METHODS:  A number of chest CT scan abnormalities were compared between 228 patients with benign and 115 with malignant effusions (derivation cohort). A logistic regression analysis was used to identify the independent predictors of malignancy and generate CT scan scores, with more points assigned to those findings associated with higher β-coefficient values. The diagnostic accuracy of the CT scan scoring system was calculated for the derivation cohort and further evaluated in two independent populations (n = 80 and 42, respectively) by two radiologists.

RESULTS:  CT scan scores predicting malignancy included any pleural lesion (ie, nodule, mass, or thickening) ≥ 1 cm (5 points); the presence of liver metastases, an abdominal mass, or a lung mass or nodule ≥ 1 cm (3 points each); and the absence of either pleural loculations, pericardial effusions, or cardiomegaly (2 points each). In the first validation cohort, a sum score of ≥ 7 yielded a sensitivity of 88% (95% CI, 73%-95%), specificity of 94% (95% CI, 83%-98%), likelihood ratio positive of 13.8 (95% CI, 4.6-41.5), likelihood ratio negative of 0.13 (95% CI, 0.05-0.33), and area under the receiver operating characteristics curve of 0.919 (95% CI, 0.849-0.990). Moreover, 69% of 42 patients with pathologically unconfirmed malignant effusions from a second independent cohort would have been correctly labeled by the predictive score.

CONCLUSIONS:  A simple CT scan-based scoring system can help physicians to separate malignant from benign pleural effusions.

Original Research: Chest Infections

Chest. 2015;147(2):520-528. doi:10.1378/chest.14-0918

BACKGROUND:  Diabetes mellitus (DM) increases the risk of TB recurrence. This study investigated whether 9-month anti-TB treatment is associated with a lower risk of TB recurrence within 2 years after complete treatment than 6-month treatment in patients with DM with an emphasis on the impact of directly observed therapy, short course (DOTs).

METHODS:  Patients with pulmonary but not extrapulmonary TB receiving treatment of 173 to 277 days between 2002 and 2010 were identified from the National Health Insurance Research Database of Taiwan. Patients with DM were then selected and classified into two groups based on anti-TB treatment duration (9 months vs 6 months). Factors predicting 2-year TB recurrence were explored using Cox regression analysis.

RESULTS:  Among 12,688 patients with DM and 43,195 patients without DM, the 2-year TB recurrence rate was 2.20% and 1.38%, respectively (P < .001). Of the patients with DM, recurrence rate decreased from 3.54% to 1.19% after implementation of DOTs (P < .001). A total of 4,506 (35.5%) were classified into 9-month anti-TB treatment group. Although a 9-month anti-TB treatment was associated with a lower recurrence rate (hazard ratio, 0.76 [95% CI, 0.59-0.97]), the benefit disappeared (hazard ratio, 0.69 [95% CI, 0.43-1.11]) under DOTs. Other predictors of recurrence included older age, male sex, malignancy, earlier TB diagnosis year, culture positivity after 2 months of anti-TB treatment, and anti-TB treatment being ≤ 80% consistent with standard regimen.

CONCLUSIONS:  The 2-year TB recurrence rate is higher in a diabetic population in Taiwan and can be reduced by treatment supervision. Extending the anti-TB treatment by 3 months may also decrease the recurrence rate when treatment is not supervised.

Translating Basic Research Into Clinical Practice

Chest. 2015;147(2):529-537. doi:10.1378/chest.14-0862

Pulmonary arterial hypertension (PAH) is a disorder in which mechanical obstruction of the pulmonary vascular bed is largely responsible for the rise in mean pulmonary arterial pressure, resulting in a progressive functional decline despite current available therapeutic options. The fundamental pathogenetic mechanisms underlying this disorder include pulmonary vasoconstriction, in situ thrombosis, medial hypertrophy, and intimal proliferation, leading to occlusion of the small to mid-sized pulmonary arterioles and the formation of plexiform lesions. Several predisposing or promoting mechanisms that contribute to excessive pulmonary vascular remodeling in PAH have emerged, such as altered crosstalk between cells within the vascular wall, sustained inflammation and dysimmunity, inhibition of cell death, and excessive activation of signaling pathways, in addition to the impact of systemic hormones, local growth factors, cytokines, transcription factors, and germline mutations. Although the spectrum of therapeutic options for PAH has expanded in the last 20 years, available therapies remain essentially palliative. However, over the past decade, a better understanding of new key regulators of this irreversible pulmonary vascular remodeling has been obtained. This review examines the state-of-the-art potential new targets for innovative research in PAH, focusing on (1) the crosstalk between cells within the pulmonary vascular wall, with particular attention to the role played by dysfunctional endothelial cells; (2) aberrant inflammatory and immune responses; (3) the abnormal extracellular matrix function; and (4) altered BMPRII/KCNK3 signaling systems. A better understanding of novel pathways and therapeutic targets will help in the designing of new and more effective approaches for PAH treatment.

Special Features

Chest. 2015;147(2):538-551. doi:10.1378/chest.14-1403

In the past, thoracic and cardiac imaging were two distinct specialties of radiology. The technical evolution, however, has changed their boundaries with an important impact on CT imaging practices and has opened the new era of “cardiothoracic” imaging, due to the strong anatomic, mechanical, physiologic, physiopathologic, and therapeutic cardiopulmonary correlations. Modern thoracic radiologists can no longer avoid the assessment of heart and coronary arteries, as they used to do with earlier generations of CT scanner. The advent of ECG gating and state-of-art CT scanner faster rotation speed, high spatial and temporal resolution, high-pitch mode, shorter acquisition time, and dedicated cardiac reconstruction algorithms has opened new possibilities for chest imaging, integrating cardiac morphologic and even functional information within a diagnostic chest CT scan. The aim of this review is to briefly show and summarize the concept of integrated cardiothoracic imaging, which redefines the boundaries of chest CT imaging, opening the door to a new radiologic specialty.

Recent Advances in Chest Medicine

Chest. 2015;147(2):552-559. doi:10.1378/chest.14-0819

Routine lung function and respiratory muscle testing are recommended in children with neuromuscular disease (NMD), but these tests are based on noninvasive volitional maneuvers, such as the measurement of lung volumes and maximal static pressures, that young children may not always be able to perform. The realization of simple natural maneuvers such as a sniff or a cough, and the measurement of esophageal and gastric pressures during spontaneous breathing can add valuable information about the strength and endurance of the respiratory muscles in young children. Monitoring respiratory muscles in children with NMD may improve understanding of the natural history of NMD and the evaluation of disease severity. It may assist and guide clinical management and it may help the identification and selection of optimal end points, as well as the most informative parameters and patients for clinical trials.

Contemporary Reviews in Critical Care Medicine

Chest. 2015;147(2):560-569. doi:10.1378/chest.14-0993

Rapid response teams (RRTs) can effectively foster discussions about appropriate goals of care and address other emergent palliative care needs of patients and families facing life-threatening illness on hospital wards. In this article, The Improving Palliative Care in the ICU (IPAL-ICU) Project brings together interdisciplinary expertise and existing data to address the following: special challenges for providing palliative care in the rapid response setting, knowledge and skills needed by RRTs for delivery of high-quality palliative care, and strategies for improving the integration of palliative care with rapid response critical care. We discuss key components of communication with patients, families, and primary clinicians to develop a goal-directed treatment approach during a rapid response event. We also highlight the need for RRT expertise to initiate symptom relief. Strategies including specific clinician training and system initiatives are then recommended for RRT care improvement. We conclude by suggesting that as evaluation of their impact on other outcomes continues, performance by RRTs in meeting palliative care needs of patients and families should also be measured and improved.

Contemporary Reviews in Sleep Medicine

Chest. 2015;147(2):570-579. doi:10.1378/chest.14-0266

OSA is associated with significant adverse outcomes with far-reaching health-care implications. OSA is much more common and severe in patients with Down syndrome (DS) than in the general population, yet there is a striking lack of literature in this area. In this review article, we have summarized the current state of knowledge and presented the available data on OSA in DS. The higher prevalence and severity of OSA in patients with DS may be related to unique upper airway anatomic features as well as increased risk for obesity, hypothyroidism, gastroesophageal reflux disease, and generalized hypotonia. Although many of the manifestations of OSA in patients with DS are similar to those seen in the general population, the relative morbidity is significantly higher. For individuals with DS who already face cognitive challenges, the added impact of OSA on cognitive function may hinder their ability to function independently and reach their full potential. Screening and evaluation for OSA should be done in children and adults with DS. Treatment of OSA in DS involves the use of CPAP, upper airway surgery, and dental appliances, along with weight-reduction strategies, nasal steroids, and oral leukotriene modifiers as adjunctive treatments. The treatment plan should be individualized for each patient with DS, taking into account age, comorbid conditions, and barriers to treatment adherence. Future research should aim to better characterize OSA, further evaluate neurocognitive outcomes, and evaluate the efficacy of treatments in patients with DS.


Chest. 2015;147(2):580. doi:10.1378/chest.14-1872

Dr. Kreitman:
today is the Jewish New Year.
Today, I received peace greetings
from my comrades in Israel.
I received the last course
of the first cycle
of my treatment.
Poison for my personal war.
A petition for medical clemency.
Perhaps the metaphor
is not quite accurate.
I shouldn’t compare my life
to the sufferings of thousands.
People die in wars.
Bombs fly.
Busses explode.
Houses get bulldozed.
And me:
I lie here with chemicals
dripping through my veins
snuffing out blood cells
on both sides of the conflict.
But a metaphor is only a metaphor.
And a New Year is just this:
a time to reflect
to renew
to hope.
L’chaim, Dr. Kreitman.
To life:
mine, yours, everyone’s.
May all the wars we render
come to a fruitful end.

Chest. 2015;147(2):581. doi:10.1378/chest.14-1667

Overhead, the white sky holds unfallen snow.
I stand outside, shivering, and smoke.
Five blocks away, my father steps outside
to see the sky more clearly. As he looks up,
a few flakes fall. What is the word for this white
and cold? Somewhere between his brain and lips
the term he knows–he’s always known–is gone.
In the garage, he finds the object made
of wood and tin. A stick attached to metal.
A tool to move the white and cold.
He’ll bring it to my house and ask
its name. He wraps gloved fingers
around the stick. The handle, says his brain.
That’s right: the handle in his hand.
The white and cold comes harder
as he walks. He feels each bit bite
against his face. Seventy years ago
in second grade he learned each bit
is special and unique, entirely different
from each other bit. He wonders
if this fact is really true. Fingerprints, too,
are supposed to be distinct. And ears.
His own ears are covered by a cap.
Though he can’t marshal all the words
for what happens any more, he knows
this weather in his bones, he knows
the streets he walks along, the pavement
lumped with ice that cars’ tires have packed
hard, treacherous and slick. He walks with care.
Bits of white and cold land and freeze
against his face. His plan: to bring
the object made of aluminum and wood
(the wooden handle, says his brain. Yes, that’s
right) to his daughter–me–and say, You need this?
And she will take the handle from his hand
as I do when he appears through driving wind,
his moustache frozen white. I thought
you needed this, he says and waits.
I say, It’s snowing!
         And the word
snow is what he’s walked five blocks to find,
a word that pulls everything into place: the white and cold,
the shovel in his hand. He should have known. But now
he knows again. He tells himself he won’t forget. Yes,
he says. It’s snow.

Chest. 2015;147(2):582. doi:10.1378/chest.14-1920

“Two possibilities exist: either we are alone in the Universe or we are not.
Both are equally terrifying.” Arthur C. Clarke.
After they scraped the bed across the floor
to get at you, after they rolled you onto the stretcher,
after they carried you out, after I changed
out of my pajamas and found my shoes
and my wallet and my keys, after looking for your glasses
which I had taken from you when you fell
and could not move, after panicking, I walked
out into the quiet street to the car.
The block seemed strangely still, a concert hall
to which the audience had forgotten to come.
Getting in the car to follow you to the hospital,
I felt solitary, no one to see my performance,
I rehearsing myself, you must be careful,
you are driving under stress. I don’t remember
one stop light those numb miles—
but I do recall thinking to myself how odd
that no one noticed, no one came out of a house,
no one offered to drive me to the emergency room,
though the next day, when one by one I saw
neighbors on the street, when one by one
they asked what had happened, I knew
they had been at their windows watching.

Chest. 2015;147(2):583. doi:10.1378/chest.14-1760

“You should be dead,” I thought to myself
  Slowly regaining my breath
 Truly shocked by what I had found
  In preop on seeing his chest
 He’d lived hard – like me, but older
   (not wiser) in experience
 Midline scar from a stab, old trach
   Tattoos of overindulgence
  And the keloid from left to right
  Past the sternal depression
   From his ER thoracotomy and
     Pericardial decompression…
Does he have any grasp of his membership
   In the Order of the Lebsche Knife1
  The mark of those born-again
   Restored from a fast-ebbing life?
   Does he kneel every day in penance
   To atone – pray, sing, and dance
   For miraculous reanimation
   And impossible second chance?
So I ask, “Do you know how it happened?”
   A tale of betrayal and strife?
  Says he, “Big deal, I got stabbed,
  “Not the worst day of my life…”

Selected Reports

Chest. 2015;147(2):e27-e30. doi:10.1378/chest.14-1184

Therapeutic hypothermia favorably impacts neurologic outcomes in patients after cardiopulmonary arrest, although the appropriate target temperature is less clear. Its safety profile in patients with systemic sclerosis (SSc) and Raynaud phenomenon (RP), who may be at increased risk for ischemic complications, has not been addressed in the literature, to our knowledge. Digital lesions are commonly seen in patients with SSc, and cold-induced myocardial ischemia has also been reported. We describe a case of a man with SSc, RP, and digital ulcers who underwent therapeutic hypothermia after cardiopulmonary arrest. He regained full neurologic function, and except for digital necrosis, no hypothermia-associated adverse events were observed. Other risk factors for ischemia, such as cocaine use, may have contributed to the development of the digital necrosis. However, clinicians should be aware of the risk for ischemic complications in patients with SSc and RP when considering the appropriate target temperature after cardiopulmonary arrest.

Chest. 2015;147(2):e31-e33. doi:10.1378/chest.14-1338

Bronchiolitis obliterans organizing pneumonia (BOOP) is an inflammatory lung disease characterized by granulation tissue in the respiratory bronchioles, alveolar ducts and alveoli. BOOP can be caused by a number of etiologies including infection, toxic inhalation, medications, radiation, and collagen vascular disease, or it can be idiopathic. We report here a case of BOOP following inhalational exposure to a jalapeño grease fire. Capsaicin and other jalapeño-derived compounds are known causes of epithelial damage and airway inflammation but to our knowledge have never been implicated in the development of BOOP. This case adds to the growing list of exposures associated with BOOP and highlights the importance of taking a thorough exposure history in patients with lung injury of unknown etiology.

Ultrasound Corner

Chest. 2015;147(2):e34-e37. doi:10.1378/chest.14-0799

Chest Imaging and Pathology for Clinicians

Chest. 2015;147(2):e38-e43. doi:10.1378/chest.14-0841

A 40-year-old South Asian woman was admitted in active labor at 38 weeks’ gestation. She had an unremarkable medical history with routine prenatal care, negative HIV testing results, and an uneventful pregnancy. She received a Bacillus Calmette-Guérin vaccine during childhood and reportedly had a subsequent positive purified protein-derivative test result 1 year prior to conception. She never smoked and had seven normal term pregnancies.

Pulmonary, Critical Care, and Sleep Pearls

Chest. 2015;147(2):e44-e47. doi:10.1378/chest.14-1193

A 41-year-old Hispanic woman with a 20 pack-year smoking history presented with worsening shortness of breath on exertion that gradually started 2 years ago, then significantly deteriorated over the last 4 months. She was diagnosed with COPD 2 months prior to her presentation and started on treatment with fluticasone propionate and albuterol. Her medical history was relevant for undifferentiated connective tissue disorder diagnosed 5 years prior due to a positive antinuclear antibody test, arthralgia, recurrent urticarial skin rash, peripheral neuropathy, abdominal pain, and diffuse body swelling. She was started on treatment with prednisone and azathioprine at the time and had substantial improvement in the occurrence of her urticaria. She also had a history of recurrent laryngeal edema of unclear etiology. She had no history of IV drug abuse, no exposure to animals, was not sexually active, and had no recent travel outside of Florida. There was no significant family history of lung diseases.

Chest. 2015;147(2):e48-e51. doi:10.1378/chest.14-1215

A 60-year-old asymptomatic woman was referred to our hospital because of an abnormal chest roentgenogram during a routine medical checkup. The patient had no history of memorable infectious diseases, except a liver abscess caused by Serratia marcescens at age 46 years. Her son was diagnosed with chronic granulomatous disease at the age of 1 year. She had never smoked cigarettes and drank only occasionally.

Chest. 2015;147(2):e52-e55. doi:10.1378/chest.14-1393

An 81-year-old man presented with a 1-week history of dry cough. He also complained of mild dyspnea, wheezing, and low-grade fever. He denied hemoptysis, fever, rashes, or chest pain. The patient’s medical history included coronary artery bypass surgery, hypertension, gastroesophageal reflux disease, and COPD. The patient was a retired welder and an ex-smoker.


Chest. 2015;147(2):e56-e57. doi:10.1378/chest.14-2299
Chest. 2015;147(2):e57. doi:10.1378/chest.14-2507
Chest. 2015;147(2):e58-e59. doi:10.1378/chest.14-2347
Chest. 2015;147(2):e60. doi:10.1378/chest.14-2396
Chest. 2015;147(2):e61-e62. doi:10.1378/chest.14-2423
Chest. 2015;147(2):e63. doi:10.1378/chest.14-1792
Chest. 2015;147(2):e64. doi:10.1378/chest.14-2573
Chest. 2015;147(2):e65. doi:10.1378/chest.14-2444
Chest. 2015;147(2):e65-e66. doi:10.1378/chest.14-2603
Chest. 2015;147(2):e67. doi:10.1378/chest.14-2491
Chest. 2015;147(2):e67-e68. doi:10.1378/chest.14-2627
Chest. 2015;147(2):e69. doi:10.1378/chest.14-2543
Chest. 2015;147(2):e70-e71. doi:10.1378/chest.14-2534
Chest. 2015;147(2):e71-e72. doi:10.1378/chest.14-2600
Chest. 2015;147(2):e73-e74. doi:10.1378/chest.14-2296
Chest. 2015;147(2):e74-e75. doi:10.1378/chest.14-2456
ResponseEditor’s Note ONLINE EXCLUSIVES
Chest. 2015;147(2):e75. doi:10.1378/chest.14-3032

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