Chest. 2016;149(4):887-888. doi:10.1016/j.chest.2015.08.022

COPD is a major cause of increased morbidity, hospital readmission, mortality, and health-care use. In 2010, the direct cost of COPD in the United States was estimated to be in excess of $49 billion per year. Data from the United States inpatient nationwide sample from 2001 to 2012 revealed that hospitalization rates for common cardiovascular disorders, pneumonia, and lung cancer were reduced significantly, whereas for COPD the rehospitalization rate increased during the same period. The primary cause of hospitalization and emergency health-care admissions in patients with COPD is severe acute exacerbation, defined by increased dyspnea, increased cough, and purulent sputum present for at least 48 h. Readmission to short-term care for this group of patients is common and costly and is associated with impaired quality of life and increased burden to the caregiver. Furthermore, severe exacerbations that trigger hospital readmission may represent a life-threatening event and use of the ICU.

Chest. 2016;149(4):889-890. doi:10.1016/j.chest.2015.09.015

The American Board of Internal Medicine Foundation’s Choosing Wisely campaign is intended to promote discussion and to help patients choose care that is supported by evidence, not duplicative of other tests or procedures, free from harm, and deemed truly necessary. National organizations, including the American College of Chest Physicians (CHEST) and the Society of Thoracic Surgeons (STS), have identified commonly used tests and procedures whose necessity should be questioned and discussed. One recommendation from the STS is that brain imaging is not required prior to definitive care in the absence of neurologic symptoms in patients with suspected or proven stage I non-small cell lung cancer (NSCLC). Brain imaging to evaluate for possible metastatic disease as part of the initial evaluation is recommended in other situations.,, The CHEST lung cancer guidelines support brain imaging in patients with specific symptoms suggestive of central nervous system involvement (Grade 1B) and in asymptomatic patients with clinical stage III or IV NSCLC (Grade 2C). These recommendations were based on an evidence review of 18 studies with 1,830 patients that was part of the 2007 CHEST lung cancer guidelines. Nine of the 18 studies limited enrollment to patients with negative clinical evaluations. The median prevalence of brain metastasis was 3% (range, 0%-21%) and the median negative predictive value (NPV) of the clinical evaluation was 97% (range, 79%-100%). In nine studies that enrolled patients with positive and negative clinical evaluations, the pooled sensitivity and specificity of the clinical evaluation were 73% and 85%, respectively. These studies were predominantly retrospective, however, and the guidelines correctly note that the use of routine MRI in staging disease in patients with NSCLC and negative clinical evaluations has not been sufficiently studied.,,

Topics: lung cancer
Chest. 2016;149(4):891-892. doi:10.1016/j.chest.2015.09.026

Atrial fibrillation (AF) and chronic kidney disease (CKD) commonly coexist in the same patient, and presence of AF does increase the relative risk of stroke in patients with CKD at least to the same extent as in those with normal renal function. Based on these considerations, stroke prevention with oral anticoagulation (OAC) appears essential in patients with AF and CKD. However, patients with CKD also have a higher risk of both intracranial and extracranial haemorrhage. A delicate balance is therefore needed to shift the overall risk-to-benefit ratio toward stroke prevention with minimal possible risk of harm from serious bleeding with OAC use. However, do we have sufficient evidence to suggest best practice in these settings? Unfortunately, there are no clinical trials to unambiguously answer this important question and insight from observational studies and meta-analyses are important.

Editorials: Point and Counterpoint

Chest. 2016;149(4):893-895. doi:10.1016/j.chest.2016.01.011

We will argue that the best interest of American graduate medical education (GME) and the US health-care system will be served by continuing to provide training to graduates of international medical graduate (IMG) schools.

Chest. 2016;149(4):895-897. doi:10.1016/j.chest.2016.01.009

For many decades, international medical graduates (IMGs) have had a major role in staffing the health-care system of the United States. This occurs despite the great difficulty that non-citizens have in enrolling in US medical schools. Rather, many IMGs enter the US health-care system as postgraduate trainees at the residency or fellowship level. As an example, in the 2013 National Residency Match, IMGs comprised 36.8% of the 34,355 match registrants and 5,775 IMGs matched into their preferred specialties that year. IMGs comprise an even greater proportion of the fellowship application pool, representing 43% of applicants in 2011 to the adult subspecialties of cardiovascular disease; endocrinology, diabetes, and metabolism; gastroenterology; hematology and oncology; infectious diseases; nephrology; pulmonary and critical care medicine; and rheumatology; as well as neonatal-perinatal medicine.

Chest. 2016;149(4):897-898. doi:10.1016/j.chest.2016.01.010

Dr Mandel’s case for not exploiting international medical graduates (IMGs) is a strong one and we appreciate his historical overview. We concur that deficient programs that historically may have recruited IMGs served neither the educational needs of their residents nor the medical needs of the community. However, we do not make the leap to a view that the best way to prevent this exploitation is to limit entry of IMGs to graduate medical education (GME). Rather, we argue that strong oversight as provided by the Accreditation Council for Graduate Medical Education ensures that GME is fulfilling the highest standards. In addition, the lesser appeal of internal medicine and some of its subspecialties to USMGs has rendered Dr Mandel’s argument less compelling.

Chest. 2016;149(4):898-899. doi:10.1016/j.chest.2016.01.012

I thank Drs Allman, Perelas, and Eiger for their excellent arguments in favor of continuing to offer postgraduate training in the United States to international medical graduates (IMGs). We clearly agree on a number of important points: that IMGs currently comprise a significant portion of the US physician workforce, that the current US medical education infrastructure is incapable of fully meeting the nation’s need for physicians, and that IMGs are a convenient (for our country) source of physicians for meeting this shortfall.


Chest. 2016;149(4):900-904. doi:10.1016/j.chest.2015.12.021

The recent online publication of the SERVE-HF trial that evaluated the effect of treating central sleep apnea (CSA) with an adaptive servoventilation (ASV) device in patients with heart failure and reduced ejection fraction (HFrEF) has raised serious concerns about the safety of ASV in these patients. Not only was ASV ineffective but post hoc analysis found excess cardiovascular mortality in treated patients. The authors cited as one explanation an unfounded notion that CSA is a compensatory mechanism with a protective effect in HFrEF patients. We believe that there are several possible considerations that are more likely to explain the results of SERVE-HF. In this commentary, we consider methodological issues including the use of a previous-generation ASV device that constrained therapeutic settings to choices that are no longer in wide clinical use. Patient selection, data collection, and treatment adherence as well as group crossovers were not discussed in the trial as potential confounding factors. We have developed alternative reasons that could potentially explain the results and that can be explored by post hoc analysis of the SERVE-HF data. We believe that our analysis is of critical value to the field and of particular importance to clinicians treating these patients.

Topics: heart failure

Original Research: COPD

Chest. 2016;149(4):905-915. doi:10.1378/chest.15-0449

Background  There is a growing understanding of the prevalence and impact of psychological disorders on COPD. However, the role of these disorders in early readmission is unclear.

Methods  We analyzed data from 5% fee-for-service Medicare beneficiaries diagnosed with COPD (International Classification of Diseases, Ninth Revision code, 491.xx, 492.xx, 493.xx, and 496.xx) between 2001 and 2011 who were hospitalized with a primary discharge diagnosis of COPD or a primary discharge diagnosis of respiratory failure (518.xx and 799.1) with secondary diagnosis of COPD. We hypothesized that such psychological disorders as depression, anxiety, psychosis, alcohol abuse, and drug abuse are independently associated with an increased risk of 30-day readmission in patients hospitalized for COPD.

Results  Between 2001 and 2011, 135,498 hospitalizations occurred for COPD in 80,088 fee-for-service Medicare beneficiaries. Of these, 30,218 (22.30%) patients had one or more psychological disorders. In multivariate analyses, odds of 30-day readmission were higher in patients with COPD who had depression (OR, 1.34; 95% CI, 1.29-1.39), anxiety (OR, 1.43; 95% CI, 1.37-1.50), psychosis (OR, 1.18; 95% CI, 1.10-1.27), alcohol abuse (OR, 1.30; 95% CI, 1.15-1.47), and drug abuse (OR, 1.29; 95% CI, 1.11-1.50) compared with those who did not have these disorders. These psychological disorders increased amount of variation in 30-day readmission attributed to patient characteristics by 37%.

Conclusions  Psychological disorders like depression, anxiety, psychosis, alcohol abuse, and drug abuse are independently associated with higher all-cause 30-day readmission rates for Medicare beneficiaries with COPD.

Chest. 2016;149(4):916-926. doi:10.1016/j.chest.2015.10.081

Background  There is insufficient evidence about the long-term course of depressive symptom trajectories and their impact among patients with COPD.

Methods  We analysed 3-year data obtained from patients with COPD participating in the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints study. Patients were split into four groups on the basis of Center for Epidemiologic Studies Depression Scale score (< 16 vs ≥ 16) and antidepressant use (yes vs no) at baseline and at 3 years: never depressed, new onset, remittent, and persistent depression. Baseline characteristics were used to assess factors associated with the group by using logistic regression.

Results  A total of 1,589 patients with COPD completed the 3-year follow-up. Of these, 55% (n = 869) were classified as never depressed, 24% (n = 377) were classified as persistently depressed, 14% (n = 226) developed new onset of depression, and 7% (n = 117) had depression that remitted. Female sex and history of stroke were associated with substantial increases in the odds of persistent depression (OR, 2.95; 95% CI, 2.05-4.24 and OR, 3.09; 95% CI, 1.43-6.67, respectively). Odds of new onset depression increased with worse health status (OR, 1.10; 95% CI, 1.04-1.17 per 4-point increase in St. George’s Respiratory Questionnaire score) and moderate to severe dyspnea (OR, 1.57; 95% CI, 1.07-2.31 for modified Medical Research Council score ≥ 2 vs 0 or 1). During follow-up, patients with persistent or new-onset depression experienced more exacerbations and more pronounced loss in performance as assessed by reduction in the 6-min walk distance (6MWD) test score.

Conclusions  About one in four patients with COPD had persistent depressive symptoms over 3 years. Clinicians should be aware of the characteristics of persistent and new onset depressive symptoms, which are associated with risk of exacerbations and loss of performance on the 6MWD test. Interventions that ameliorate the course of depression are needed.

Trial Registry  ClinicalTrials.gov; No.: NCT00292552; URL: www.clinicaltrials.gov.

Chest. 2016;149(4):927-935. doi:10.1016/j.chest.2015.11.025

Objective  Younger persons with COPD report worse health-related quality of life (HRQL) than do older individuals. The factors explaining these differences remain unclear. The objective of this article was to explore factors associated with age-related differences in HRQL in COPD.

Methods  Cross-sectional analysis of participants with COPD, any Global Initiative for Chronic Obstructive Lung Disease grade of airflow limitation, and ≥ 50 years old in two cohorts: the Genetic Epidemiology of COPD (COPDGene) study and the Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS). We compared St. George’s Respiratory Questionnaire (SGRQ) scores by age group: middle-aged (age, 50-64) vs older (age, 65-80) adults. We used multivariate linear modeling to test associations of age with HRQL, adjusting for demographic and clinical characteristics and comorbidities.

Results  Among 4,097 participants in the COPDGene study (2,170 middle-aged and 1,927 older adults) SGRQ total scores were higher (worse) among middle-aged (mean difference, −4.2 points; 95% CI, −5.7 to −2.6; P < .001) than older adults. Age had a statistically significant interaction with dyspnea (P < .001). Greater dyspnea severity (modified Medical Research Council ≥ 2, compared with 0-1) had a stronger association with SGRQ score among middle-aged (β, 24.6; 95% CI, 23.2-25.9) than older-adult (β, 21.0; 95% CI, 19.6-22.3) participants. In analyses using SGRQ as outcome in 1,522 participants in SPIROMICS (598 middle-aged and 924 older adults), we found similar associations, confirming that for the same severity of dyspnea there is a stronger association with HRQL among younger individuals.

Conclusions  Age-related differences in HRQL may be explained by a higher impact of dyspnea among younger subjects with COPD.

Trial Registry  ClinicalTrials.gov; No.: NCT00608764 and No.: NCT01969344; URL: www.clinicaltrials.gov.

Chest. 2016;149(4):936-942. doi:10.1378/chest.15-1868

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

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

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

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

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

Original Research: Lung Cancer

Chest. 2016;149(4):943-950. doi:10.1378/chest.15-1140

Background  The Choosing Wisely recommendations from the Society of Thoracic Surgeons include avoiding brain imaging in asymptomatic patients with early-stage non-small cell lung cancer (NSCLC). We aimed to describe use of brain imaging among National Lung Screening Trial participants with stage IA NSCLC and to identify factors associated with receipt of brain imaging.

Methods  We identified patients with clinical stage IA NSCLC who received CT scans or magnetic resonance brain imaging within 60 days after diagnosis, but before definitive surgical staging. Using multivariate logistic regression, we identified variables associated with undergoing brain imaging.

Results  Among 643 patients with clinical stage IA NSCLC, 77 patients (12%) received at least one brain imaging study. Of seven patients (1.1%) who were upstaged to stage IV, only two underwent brain imaging and neither had documentation of brain metastasis. Brain imaging frequency by enrollment center varied from 0% to 80%. All patients who underwent brain imaging subsequently underwent surgery with curative intent, suggesting strongly that imaging revealed no evidence of intracranial metastases. In multivariate analyses, primary tumor size >20 mm (OR, 2.50; 95% CI, 1.50-4.16; P < .001) and age 65 to 69 (OR, 2.78; 95% CI, 1.38-5.57; P < .01) were independently associated with greater use of brain imaging.

Conclusions  Among National Lung Screening Trial patients with stage IA NSCLC, one in eight underwent brain imaging, but none ultimately had intracranial metastases. Larger tumor size and older age were associated with greater use of brain imaging. Wide variation in use between centers suggests either lack of awareness or disagreement about this Choosing Wisely recommendation.

Original Research: Cardiovascular Disease

Chest. 2016;149(4):951-959. doi:10.1378/chest.15-1719

Background  The use of warfarin in patients with atrial fibrillation (AF) and chronic kidney disease (CKD) can be problematic because of increased bleeding risk. We performed a systematic review and meta-analysis of observational studies that evaluated the use of warfarin in patients with AF and CKD to evaluate the risks of ischemic stroke/thromboembolism, major bleeding, and mortality.

Methods  PUBMED, EMBASE, CINAHL, ProQuest, and Google Scholar databases were electronically searched through January 12, 2015. Additionally, a manual search was performed for relevant references. Random-effects model was used to estimate the pooled hazard ratio (HR) with 95% CI. CKD was divided into non-end-stage CKD and end-stage CKD (on renal replacement therapy) and separate analyses were performed.

Results  Thirteen publications from 11 cohorts (six retrospective and five prospective) including >48,500 total patients with >11,600 warfarin users were included in the meta-analysis. In patients with AF and non-end-stage CKD, warfarin resulted in a lower risk of ischemic stroke/thromboembolism (HR, 0.70; 95% CI, 0.54-0.89; P = .004) and mortality (HR, 0.65; 95% CI, 0.59-0.72; P < .00001), but had no effect on major bleeding (HR, 1.15; 95% CI, 0.88-1.49; P = .31). In patients with AF and end-stage CKD, warfarin had no effect on the risks of stroke (HR, 1.12; 95% CI, 0.69-1.82; P = .65) and mortality (HR, 0.96; 95% CI, 0.81-1.13; P = .60), but increased the risks of major bleeding (HR, 1.30; 95% CI, 1.08-1.56; P = .005).

Conclusions  Based on this meta-analysis, the use of warfarin for AF may have an unfavorable risk/benefit ratio in patients with end-stage CKD but not in those with non-end-stage CKD.

Chest. 2016;149(4):960-968. doi:10.1378/chest.15-1622

Background  It remains uncertain whether patients with atrial fibrillation (AF) and a single additional stroke risk factor (congestive heart failure, hypertension, age ≥ 75 years, diabetes mellitus, prior stroke or thromboembolism, vascular disease, age 65-74 years, and sex category [CHA2DS2-VASc] score = 1 in men, 2 in women) should be treated with oral anticoagulation (OAC). We investigated the risk of ischemic stroke, systemic embolism, and death in a community-based cohort of unselected patients with AF with zero to one stroke risk factor based on the CHA2DS2-VASc score.

Methods  Among 8,962 patients with AF seen between 2000 and 2010, 2,177 (24%) had zero or one additional stroke risk factor, of which 53% were prescribed OAC.

Results  Over a follow-up of 979 ± 1,158 days, 151 (7%) had a major adverse event (stroke/systemic thromboembolism/death). Prescription of OAC was not associated with a better prognosis for stroke/systemic thromboembolism/death for patients in the “low-risk” category (ie, CHA2DS2-VASc score = 0 for men or 1 for women; adjusted hazard ratio [HR], 0.68; 95% CI, 0.35-1.31; P = .25). OAC use was independently associated with a better prognosis in patients with AF with a single additional stroke risk factor (ie, CHA2DS2-VASc score = 1 in men, 2 in women; adjusted HR, 0.59; 95% CI, 0.40-0.86; P = .007).

Conclusions  Among patients with AF with a single additional stroke risk factor (CHA2DS2-VASc score = 1 in men, 2 in women), OAC use was associated with an improved prognosis for stroke/systemic thromboembolism/death.

Original Research: Critical Care

Chest. 2016;149(4):969-980. doi:10.1016/j.chest.2015.12.012

Background  Lung ultrasound (LUS) has been successfully applied for monitoring aeration in ventilator-associated pneumonia (VAP) and to diagnose and monitor community-acquired pneumonia. However, no scientific evidence is yet available on whether LUS reliably improves the diagnosis of VAP.

Methods  In a multicenter prospective study of 99 patients with suspected VAP, we investigated the diagnostic performance of LUS findings of infection, subpleural consolidation, lobar consolidation, and dynamic arborescent/linear air bronchogram. We also evaluated the combination of LUS with direct microbiologic examination of endotracheal aspirates (EA). Scores for LUS findings and EA were analyzed in two ways. First, the clinical-LUS score (ventilator-associated pneumonia lung ultrasound score [VPLUS]) was calculated as follows: ≥ 2 areas with subpleural consolidations, 1 point; ≥ 1 area with dynamic arborescent/linear air bronchogram, 2 points; and purulent EA, 1 point. Second, the VPLUS-direct gram stain examination (EAgram) was scored as follows: ≥ 2 areas with subpleural consolidations, 1 point; ≥ 1 area with dynamic arborescent/linear air bronchogram, 2 points; purulent EA, 1 point; and positive direct gram stain EA examination, 2 points.

Results  For the diagnosis of VAP, subpleural consolidation and dynamic arborescent/linear air bronchogram had a positive predictive value of 86% with a positive likelihood ratio of 2.8. Two dynamic linear/arborescent air bronchograms produced a positive predictive value of 94% with a positive likelihood ratio of 7.1. The area under the curve for VPLUS-EAgram and VPLUS were 0.832 and 0.743, respectively. VPLUS-EAgram ≥ 3 had 77% (58-90) specificity and 78% (65-88) sensitivity; VPLUS ≥ 2 had 69% (50-84) specificity and 71% (58-81) sensitivity.

Conclusions  By detecting ultrasound features of infection, LUS was a reliable tool for early VAP diagnosis at the bedside.

Trial Registry  ClinicalTrials.gov; No.: NCT02244723; URL: www.clinicaltrials.gov.

Original Research: Sleep Disorders

Chest. 2016;149(4):981-990. doi:10.1378/chest.15-2112

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

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

Results  A total of 2,147 subjects were included. Mean age (± SD) was 27.2 ± 7.2 years, n = 899 (42%) were men. Habitual snoring was highly prevalent, with an average of 53.8% in men and 38.3% in women. Snoring, witnessed apneas, and daytime somnolence increased continuously with age, with an abnormal SDB questionnaire score detected in 2.5%. Reported sleep duration was 7.61 ± 1.67 hours during weekdays and 8.27 ± 2.11 hours during weekends. Snoring frequency was significantly higher in men than women at nearly all age groups, and an adjusted regression model (OR [95% CI]) identified male sex (2 [1.6-2.5]; P < .001) and BMI (1.08 [1.03-1.12]; P < .001) as independent risk factors for snoring.

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

Chest. 2016;149(4):991-998. doi:10.1378/chest.15-1450

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

Methods  We performed overnight sleep recordings, and measured systemic and pulmonary artery pressure in 23 patients with CMS (mean ± SD age, 52.8 ± 9.8 y) and 12 healthy control subjects (47.8 ± 7.8 y) at 3,600 m. In a subgroup of 15 subjects with SDB, we assessed the presence of a PFO with transesophageal echocardiography.

Results  The major new findings were that in patients with CMS, (1) SDB and nocturnal hypoxemia was more severe (P < .01) than in control subjects (apnea-hypopnea index [AHI], 38.9 ± 25.5 vs 14.3 ± 7.8 number of events per hour [nb/h]; arterial oxygen saturation, 80.2% ± 3.6% vs 86.8% ± 1.7%, CMS vs control group), and (2) AHI was directly correlated with systemic blood pressure (r = 0.5216; P = .001) and pulmonary artery pressure (r = 0.4497; P = .024). PFO was associated with more severe SDB (AHI, 48.8 ± 24.7 vs 14.8 ± 7.3 nb/h; P = .013, PFO vs no PFO) and hypoxemia.

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

Trial Registry  ClinicalTrials.gov; No.: NCT01182792; URL: www.clinicaltrials.gov;

Chest. 2016;149(4):999-1010. doi:10.1378/chest.15-1543

Background  OSA associates with insulin resistance (IR), hyperglycemia, and dyslipidemia consistently in adults, but inconsistently in children. We set out to quantify the impact of OSA treatment upon obesity and metabolic outcomes and thus assess causality.

Methods  Sixty-nine children with OSA; mean age, 5.9 years (range, 3-12.6); 55% boys; and 68% nonobese (NOB) underwent baseline overnight polysomnography, anthropometric and metabolic measurements, adenotonsillectomy (T&A), and follow-up testing a mean 7.9 months (range, 2-20) later.

Results  Fifty-three children (77% of study cohort; 91% of obese children) had residual OSA (apnea-hypopnea index > 1 event/h) post-T&A. Fasting plasma insulin (FPI, 14.4 ± 9.4 → 12.6 ± 9.7 μIU/mL, P = .008), homeostasis model assessment-IR (3.05 ± 2.13 → 2.62 ± 2.22, P = .005), and high-density lipoprotein (HDL) (51.0 ± 12.9 → 56.5 ± 14.4 mg/dL, P = .007) improved despite increased BMI z score (1.43 ± 0.78 → 1.52 ± 0.62, P = .001); changes did not differ significantly between sexes or NOB and obese participants; however, post-T&A BMI z score rather than apnea-hypopnea index was the main predictor of levels of follow-up FPI, HDL, and other metabolic parameters. Higher baseline FPI and BMI-z predicted likelihood of residual OSA; conversely, on regression analysis, follow-up IR, HDL, and triglycerides were predicted by BMI z score, not residual OSA.

Conclusions  T&A improved IR and HDL, and residual OSA is predicted by baseline FPI and BMI z score, indicating a causal relationship; however, following T&A, residual metabolic dysfunction related to underlying adiposity rather than remaining sleep-disordered breathing. Finally, T&A cured OSA in < 25% of all children and only 10% of obese children; post-T&A polysomnography is indicated to assess which children still require treatment.

Original Research: Asthma

Chest. 2016;149(4):1011-1020. doi:10.1016/j.chest.2015.12.002

Background  Asthma-COPD overlap syndrome (ACOS) has been described and acknowledged as a distinct clinical entity; however, its characteristics in daily clinical practice are largely unknown. The aim of this study was to identify the prevalence of ACOS in the real-life population, its pattern of comorbidities, and its impact on hospitalization risk.

Methods  Data for this retrospective cohort study were extracted from the Majorca Real-Life Investigation in COPD and Asthma cohort, including primary care, hospitalization, and pharmacy data from the Balearic Islands, Spain. Patients who had received a physician-confirmed diagnosis of both asthma and COPD were identified as having ACOS and compared with a COPD-only population. In subanalyses, more stringent diagnostic criteria (Global Initiative for Asthma-Global Initiative for Chronic Obstructive Lung Disease) were applied. The pattern and impact of comorbidities on all-cause hospitalization were compared by multivariate logistic regression.

Results  In total, 5,093 patients with ACOS (prevalence, 5.55 per 1,000 inhabitants) were compared with 22,778 patients with COPD (30.40 per 1,000 inhabitants). Patients with ACOS were more frequently female (53.4%) than were patients with COPD (30.8%), younger (ACOS, 64.0 years; COPD, 65.8 years), and differed by nonsmoking status (ACOS, 41.4%; COPD, 22.1%) (all, P < .001). In adjusted analyses, allergic rhinitis (OR, 1.81; 95% CI, 1.63-2.00), anxiety (OR, 1.18; 95% CI, 1.10-1.27), gastroesophageal reflux disease (OR, 1.18; 95% CI, 1.04-1.33), and osteoporosis (OR, 1.14; 95% CI, 1.04-1.26) were more frequent in ACOS than COPD. In contrast, chronic kidney disease (OR, 0.79; 95% CI, 0.66-0.95) and ischemic heart disease (OR, 0.88; 95% CI, 0.79-0.98) were less frequent. In patients with ACOS, cardiovascular diseases showed the strongest association with hospitalization.

Conclusions  ACOS is prevalent in the general population, and it affects to a large extent females with less smoking exposure compared with patients with COPD only. Cardiovascular comorbidities in particular contribute most to overall hospitalization risk of patients with ACOS.

Chest. 2016;149(4):1021-1029. doi:10.1016/j.chest.2015.12.039

Background  Reducing hospital readmissions has attracted attention from many stakeholders. However, the characteristics of 30-day readmissions after asthma-related hospital admissions in adults are not known. It is also unclear whether older adults are at higher risk of 30-day readmission.

Objectives  To investigate the rate, timing, and principal diagnosis of 30-day readmissions in adults with asthma and to determine age-related differences.

Methods  Retrospective cohort study of adults hospitalized for asthma exacerbation using the population-based inpatient samples of three states (California, Florida, and Nebraska) from 2005 through 2011. Patients were categorized into three age groups: younger (18-39 years), middle aged (40-64 years), and older (≥ 65 years) adults. Outcomes were 30-day all-cause readmission rate, timing, and principal diagnosis of readmission.

Results  Of 301,164 asthma-related admissions at risk for 30-day readmission, readmission rate was 14.5%. Compared with younger adults, older adults had significantly higher readmission rates (10.1% vs 16.5%; OR, 2.15 [95% CI, 2.07-2.23]; P < .001). The higher rate attenuated with adjustment (OR, 1.19 [95% CI, 1.13-1.26]; P < .001), indicating that most of the age-related difference is explained by sociodemographics and comorbidities. For all age groups, readmission rate was highest in the first week after discharge and declined thereafter. Overall, only 47.1% of readmissions were assigned respiratory diagnoses (asthma, COPD, pneumonia, and respiratory failure). Older adults were more likely to present with nonrespiratory diagnoses (41.7% vs 53.8%; P < .001).

Conclusions  After asthma-related admission, 14.5% of patients had 30-day readmission with wide range of principal diagnoses. Compared with younger adults, older adults had higher 30-day readmission rates and proportions of nonrespiratory diagnoses.

Chest. 2016;149(4):1030-1041. doi:10.1016/j.chest.2015.12.028

Background  Environmental factors may play important roles in asthma, but findings have been inconsistent.

Objective  The goal of this study was to determine the associations between early life exposures, environmental factors, and asthma in urban and rural children in southeast China.

Methods  A screening questionnaire survey was conducted in 7,164 children from urban Guangzhou and 6,087 from rural Conghua. In the second stage, subsamples of 854 children (419 from Guangzhou, 435 from Conghua) were recruited for a case-control study that included a detailed questionnaire enquiring on family history, early life environmental exposures, dietary habits, and laboratory tests (including histamine airway provocation testing, skin prick tests, and serum antibody analyses). House dust samples from 76 Guangzhou families and 80 Conghua families were obtained to analyze levels of endotoxins, house dust mites, and cockroach allergens.

Results  According to the screening survey, the prevalence of physician-diagnosed asthma was lower in children from Conghua (3.4%) than in those from Guangzhou (6.9%) (P < .001). A lower percentage of asthma was reported in rural subjects compared with urban subjects (2.8% vs. 29.4%; P < .001) in the case-control study. Atopy (OR, 1.91 [95% CI, 1.58-2.29]), parental atopy (OR, 2.49 [95% CI, 1.55-4.01]), hospitalization before 3 years of age (OR, 2.54 [95% CI, 1.37-4.70]), high consumption of milk products (OR, 1.68 [95% CI, 1.03-2.73]), and dust Dermatophagoides farinae group 1 allergen (OR, 1.71 [95% CI, 1.34-2.19]) were positively associated with asthma. Living in a crop-farming family at < 1 year of age (OR, 0.15 [95% CI, 0.08-0.32]) and dust endotoxin levels (OR, 0.69 [95% CI, 0.50-0.95]) were negatively associated with asthma.

Conclusions  Rural children from an agricultural background exhibited a reduced risk of asthma. Early life exposure to crop farming and high environmental endotoxin levels might protect the children from asthma in southern China.

Original Research: Signs and Symptoms of Chest Diseases

Chest. 2016;149(4):1042-1051. doi:10.1016/j.chest.2016.01.006

Background  Whether fractional exhaled nitric oxide (FeNO) measurement alone or combined with sputum eosinophil and atopy is useful in predicting corticosteroid-responsive cough (CRC) and non-CRC (NCRC) is not clear.

Methods  A total of 244 patients with chronic cough and 59 healthy subjects as control were enrolled. The causes of chronic cough were confirmed according to a well-established diagnostic algorithm. FeNO measurement and induced sputum for differential cell were performed in all subjects.

Results  CRC occurred in 139 (57.0%) patients and NCRC occurred in 105. The FeNO level in CRC significantly correlated with sputum eosinophils (rs = 0.583, P < .01). The median (quarter) of FeNO level in CRC was significantly higher than NCRC (32.0 ppb [19.0-65.0 ppb] vs 15.0 ppb [11.0-22.0 ppb], P < .01). FeNO of 31.5 ppb had a sensitivity and specificity of 54.0% and 91.4%, respectively, in predicting CRC from chronic cough, with a positive predictive value of 89.3% and a negative predictive value of 60.0%. If the patients had a combination of low level of FeNO ( < 22.5 ppb), normal sputum eosinophil ( < 2.5%), and absence of atopy, the sensitivity and specificity would be 30.3% and 93.5% for predicting NCRC.

Conclusions  In our cohort, a high level (≥ 31.5 ppb) of FeNO indicates more likelihood of CRC, but the sensitivity is insufficient to rule out a diagnosis of CRC. A combination of low-level FeNO, normal sputum eosinophil, and absence of atopy suggests a lower likelihood of CRC.

Chest. 2016;149(4):1052-1060. doi:10.1016/j.chest.2015.12.036

Background  Chronic cough is a common clinical problem worldwide. Although many patients have underlying precipitating conditions such as asthma, gastroesophageal reflux, or rhinitis, many remain symptomatic despite treating these conditions. New approaches are needed for the treatment of this group of patients.

Methods  We conducted a randomized, double-blind, placebo-controlled trial to determine whether 250 mg of azithromycin three times a week for 8 weeks would affect the Leicester Cough Questionnaire (LCQ) score in 44 patients with treatment-resistant cough. Cough severity on a visual analog scale and bronchial exhaled nitric oxide were measured as secondary outcomes.

Results  There was a clinically important improvement in LCQ score with azithromycin (mean change, 2.4; 95% CI, 0.5 to 4.2) but not placebo (mean change, 0.7; 95% CI, −0.6 to 1.9), but the between-group difference was not statistically significant (P = .12). There were no significant between-group differences for any of the secondary outcome measures. Looking at subgroups of responders, there was a large and significant improvement in LCQ score in patients with chronic cough and a concurrent diagnosis of asthma who were treated with azithromycin (mean, 6.19; 95% CI, 4.06 to 8.32).

Conclusions  Treatment with low-dose azithromycin for 8 weeks did not significantly improve LCQ score compared with placebo. The use of macrolides for treatment-resistant cough cannot be recommended from this study, but they may have a place in the treatment of chronic cough associated with asthma; this is worthy of further investigation.

Trial Registry  WHO International Clinical Trials Registry; No.: ISRCTN75749391. URL: http://apps.who.int

Original Research: Pulmonary Vascular Disease

Chest. 2016;149(4):1061-1073. doi:10.1378/chest.15-0928

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

Methods  We determined hemodynamic cutoffs to discriminate between idiopathic PAH and postcapillary PH in a large database of 4,363 stable patients undergoing first diagnostic right and left heart catheterizations. In a second step, we performed a patient-level pooled analysis of four randomized, placebo-controlled trials including 541 patients with PAH who received treprostinil or placebo, to validate hemodynamic cutoffs with regard to treatment response.

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

Conclusions  mPAWP < 12 mm Hg and DPG > 20 mm Hg identify patients with PAH who are likely to have significant hemodynamic improvement with prostacyclin treatment.

Recent Advances in Chest Medicine

Chest. 2016;149(4):1074-1081. doi:10.1378/chest.15-1076

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

Contemporary Reviews in Critical Care Medicine

Chest. 2016;149(4):1082-1093. doi:10.1016/j.chest.2015.12.016

In spite of significant strides in the treatment of sickle cell disease (SCD), SCD crises are still responsible for high morbidity and early mortality. While most patients initially seek care in the acute setting for a seemingly uncomplicated pain episode (pain crisis or vaso-occlusive crisis), this initial event is the primary risk factor for potentially life-threatening complications. The pathophysiological basis of these illnesses is end-organ ischemia and infarction combined with the downstream effects of hemolysis that results from red blood cell sickling. These pathological changes can occur acutely and lead to a dramatic clinical presentation, but are frequently superimposed over a milieu of chronic vasculopathy, immune dysregulation, and decreased functional reserve. In the lungs, acute chest syndrome is a particularly ominous lung injury syndrome with a complex pathogenesis and potentially devastating sequelae, but all organ systems can be affected. It is, therefore, critical to understand the SCD patients' susceptibility to acute complications and their risk factors so that they can be recognized promptly and managed effectively. Blood transfusions remain the mainstay of therapy for all severe acute crises. Recommendations and indications for the safest and most efficient implementation of transfusion strategies in the critical care setting are therefore presented and discussed, together with their pitfalls and potential future therapeutic alternatives. In particular, the importance of extended phenotypic red blood cell matching cannot be overemphasized, due to the high prevalence of severe complications from red cell alloimmunization in SCD.

Topics in Practice Management

Chest. 2016;149(4):1094-1101. doi:10.1016/j.chest.2015.12.025

Interventional pulmonology (IP) is a field that uses minimally invasive techniques to diagnose, treat, and palliate advanced lung disease. Technology, formal training, and reimbursement for IP procedures have been slow to catch up with other interventional subspecialty areas. A byproduct of this pattern has been limited IP integration in private practice settings. We describe the key aspects and programmatic challenges of building an IP program in a community-based setting. A philosophical and financial buy-in by stakeholders and a regionalization of services, within and external to a larger practice, are crucial to success. Our experience demonstrates that a successful launch of an IP program increases overall visits as well as procedural volume without cannibalizing existing practice volume. We hope this might encourage others to provide this valuable service to their own communities.


Chest. 2016;149(4):1102. doi:10.1016/j.chest.2015.08.013

    Dear Supervisor,
    This weekend I ravaged the ivory tulip wallpaper
    in my breakfast-room with black permanent markers,
    but didn’t have time to kill myself.
    May I please take Monday off?
    I minored in dragonfly needlework
    but pills don’t do the trick.
    Neither do lids of sweet potato cans.
    Gran got mad when I stood for four hours
    on the roof of her 30-floor condo building,
    when she asked me to vac her bean Persian rug.
    I should have been efficient in my decision
    if I should jump
    but dying wasn’t the question.
    The cement at the bottom
    looked like it would hurt so much,
    I thought this wasn’t how Sylvia Plath ended it.
    Two red paramedic trucks waited closeby,
    ready to take me to HCMC,
    or to fool me into thinking
    I’d still have bones left to injure.
    Dr. Ells scolded me on the phone afterward,
    I was ready to end my life over a job.
    God won’t let me resign.

Chest. 2016;149(4):1103. doi:10.1016/j.chest.2015.09.007

    when you have brought a child into this world
    who has a chronic illness
    a painful crippling disease

    there is sadness and sympathy and sorrow of course there is
    but a strange weight is this gristle of guilt
    borne in a new part of your body with each degree of his decline
    a metastasizing remorse that cannot be cut out
    or reasoned with or prayed away

    a mutinous familiar flies at your throat
    every time the phone rings
    when he is hospitalized

    always the lava surges acrid from the gut
    when you must hold him down for painful punctures
    a fisted stone drops in your chest with bad results

    so when a cheerful receptionist
    from the chronic care nursing service chirps the happy news
    that his condition has improved and he is ready for discharge
    one would think you would be overjoyed

    and you would be
    if the funeral had not been yesterday


Chest. 2016;149(4):1104. doi:10.1016/j.chest.2015.11.018

A systematic review and meta-analysis by Wan et al in CHEST concerning adjunctive corticosteroid therapy for patients with community-acquired pneumonia (CAP) impressed us greatly, because our meta-analysis on exactly the same topic was just published in September 2015. There has been heated discussion concerning the efficacy and safety of corticosteroid treatment of CAP since Torres et al and Blum et al reported results from moderate- and large-size randomized trials in early 2015. Siemieniuk et al also conducted a systematic review and meta-analysis on the same topic, published in October 2015.

Chest. 2016;149(4):1105. doi:10.1016/j.chest.2015.11.019

We thank Dr Horita and colleagues for their interest in our article in CHEST. We agree with their views that adjunctive corticosteroid treatment may be indicated for severe community-acquired pneumonia (CAP) because of its beneficial effects on the length of hospital stay, the length of time to clinical stability, and the risk of acute respiratory distress syndrome. Allowing for the risk of infection escalation due to corticosteroid use before effective antimicrobial drugs are administered, and the negative results of early meta-analyses, current guidelines do not recommend the use of corticosteroids in CAP., More recently, with the publication of large-size randomized trials and meta-analyses, some benefits of corticosteroids have been found in the management of CAP, especially in patients with severe CAP.

Chest. 2016;149(4):1105-1106. doi:10.1016/j.chest.2015.12.041

We read with great interest the recent study published by Farber et al in CHEST (March 2016) on the relationship of maternal smoking and childhood asthma. The authors demonstrated that maternal smoking was associated with a diagnosis of asthma, prescription of quick-relief medication, and visit to the ED, even after adjusting several confounders including age, sex, ethnicity, and insurance type. However, we would like to bring up two points of concern.

Chest. 2016;149(4):1106-1107. doi:10.1016/j.chest.2016.01.017

I thank Kashiura and colleagues for their careful review of the article on the effect of maternal smoking on childhood asthma. They correctly note that there are different phenotypes of childhood wheezing, and that phenotype varies by age. In our sample, the mean age of children at which maternal smoking was reported was greater than the mean age with no maternal smoking. As our sample was selected from health plan members with a health-care encounter, it is possible that tobacco-related illness increases the need for medical attention disproportionately for older children.

Chest. 2016;149(4):1107. doi:10.1016/j.chest.2015.12.040

We read with great interest the article entitled, “VTE Incidence and Risk Factors in Patients With Severe Sepsis and Septic Shock,” published a recent issue of CHEST (November 2015). This well-conducted prospective study investigated the incidence of VTE in 113 patients presenting to three academic ICUs with severe sepsis or septic shock. Despite all patients receiving guideline-recommended thromboprophylaxis, the incidence of VTE at ICU discharge was 37.2%, a marked increase in VTE compared with previous studies that did not focus specifically on patients with sepsis.,, This interesting outcome raises three questions for us.

Chest. 2016;149(4):1107-1108. doi:10.1016/j.chest.2016.01.016

We appreciate the thoughtful questions raised by Drs Sorenson and McCurdy and the support of our article investigating the incidence of VTE in severe sepsis and septic shock. Our finding of a VTE incidence of 37.2% is higher than in prior reports, perhaps owing in part to our study design in which all patients were evaluated with ultrasound imaging.

Chest. 2016;149(4):1108-1109. doi:10.1016/j.chest.2015.10.083

I read with interest the study by Sekiguchi et al in a recent issue of CHEST (October 2015) that focused on combined cardiac and lung ultrasound to evaluate the etiology of acute hypoxic respiratory failure. The authors reported good diagnostic utility in differentiating ARDS from cardiogenic pulmonary edema (CPE) by evaluating the amount of left pleural effusion, the severity of left ventricular dysfunction, and the diameter of the inferior vena cava. In the Supplemental Materials section of the online article, the authors describe that both C (consolidative)-pattern and pleural effusion were assessed in examination point 5 (posterolateral zone of the lung), but only data regarding pleural effusion were reported in e-Table 1. Whether posterior consolidation exists may be important in differentiating ARDS from CPE. Copetti et al identified consolidation by using lung ultrasound in 83% of patients with ARDS but in no patients with CPE. In contrast, posterior consolidation and/or atelectasis have been known to be a classic finding in ARDS, documented by using CT scan results. In a study evaluating lung ultrasound for the assessment of lung recruitment in patients with ARDS, Bouhemad et al also reported that consolidation was the predominant ultrasound pattern in the lower part of the posterior thoracic region. Could Sekiguchi et al provide the detailed information about the ultrasound pattern in examination point 5, especially the consolidation pattern?

Chest. 2016;149(4):1109. doi:10.1016/j.chest.2016.01.022

We appreciate the insightful comments about our article made by Dr Keng. The information on consolidative (C)-pattern in examination point 5 was missing in e-Table 1. The revised e-Table 1 is attached to this response letter. We defined C-pattern as areas of tissue hepatization with or without air bronchogram. C-pattern in zone R5 was seen in 36 patients (61%) in the group with cardiogenic pulmonary edema (CPE), 23 (55%) in the group with ARDS, and 12 (38%) in the miscellaneous group (P = .093). C-pattern in zone L5 was seen in 44 patients (75%) in the group with CPE group, 22 (52%) in the group with ARDS, and 13 (41%) in the miscellaneous group (P = .004). These variables were not selected as statistically significant in a prediction model for CPE in the multivariate analysis.

Chest. 2016;149(4):1109-1110. doi:10.1016/j.chest.2015.12.043

We read with interest the article by Alikhan et al in a recent issue of CHEST (December 2015). The authors describe a case of allergic bronchopulmonary mycosis secondary to colonization of a patient’s clarinet by Alternaria. In this article, the authors incorrectly describe high-attenuation mucus as mucus with attenuation higher than that of water.

Chest. 2016;149(4):1110. doi:10.1016/j.chest.2016.02.644

In response to our recent article in CHEST, Agarwal et al aptly point out the radiologic criteria for the diagnosis of high-attenuation mucus in allergic bronchopulmonary aspergillosis. High-attenuation mucus is a very specific finding for allergic pulmonary aspergillosis (ABPA). The mucus in ABPA is often of higher attenuation. However, mucus with an attenuation > 70 Hounsfield units is much more specific for ABPA, as noted in the correspondence from Agarwal et al, and is associated with poor outcomes., We thank the authors for this clarification, as well as the helpful citations for the interested reader.

Chest. 2016;149(4):1111-1113. doi:10.1016/j.chest.2016.01.014

The diagnostic yield of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) in sarcoidosis has been shown to vary from 54% to 93% with a pooled diagnostic accuracy of 79%., It remains unclear whether the use of a larger bore aspiration needle during EBUS-TBNA increases the diagnostic yield in sarcoidosis.,,,, In a prospective, double-blind, randomized controlled trial, subjects with clinicoradiologic suspicion of sarcoidosis were assigned (1:1) to undergo EBUS-TBNA with either a 21- or 22-gauge needle. Endobronchial biopsy and transbronchial lung biopsy (TBLB) were performed at the discretion of the bronchoscopist. The primary outcome was the diagnostic yield (detection of granulomas) of EBUS-TBNA in subjects finally receiving a diagnosis of sarcoidosis. The secondary outcomes were adequacy of samples, granuloma density, and adverse events during the procedure. The study protocol (e-Table 1) was approved by the ethics review committee (1Trg/PG-2014/12543-54), and written informed consent was obtained from all subjects. The trial was registered at www.clinicaltrials.gov (NCT02459431).

Chest. 2016;149(4):1113. doi:10.1016/j.chest.2015.12.042

I read with great interest the article by McShane and Glassroth in a recent issue of CHEST (December 2015). The authors cite the following as predisposing factors to the development of the nodular bronchiectasis phenotype of pulmonary disease due to Mycobacterium avium complex (NB-PMAC): genetic predisposition, body habitus, fibrillin abnormalities, mitral regurgitation, isolated CFTR gene mutation, and ciliary abnormalities. It is difficult to identify a pathway by which these factors might lead to its defining features, which include: disease confined to the lingula and/or middle lobe, female (largely postmenopausal) exclusivity, and absence of a predisposing pulmonary disorder. Genetic predisposition for an exclusively female disorder implies a sex linkage, which affects male subjects only. If a tall, lean habitus, mitral valve prolapse, and pectus excavatum are markers of an undefined, predisposing, connective tissue disorder, how might this account for susceptibility to these organisms and for the circumscribed localization? Why are male subjects with the referenced abnormalities in body habitus and mitral valve prolapse spared? Marfan’s syndrome, which is not associated with NB-PMAC, is the sole fibrillin malady with which I am acquainted. It has an autosomal dominant inheritance. The authors did not describe a pathway by which a CFTR gene mutation would predispose to NB-PMAC in the absence of clinical manifestations of cystic fibrosis. There is no gender preference for cystic fibrosis or ciliary abnormalities, both typically present in childhood, and neither exhibits circumscribed pulmonary involvement.

Chest. 2016;149(4):1113-1115. doi:10.1016/j.chest.2016.01.034

I applaud the prescription of Liss et al for reducing wasteful medical spending on ineffective and/or overpriced medications. To remind readers, they wrote a letter praising Mark Metersky’s denunciation of Mallinckcrodt Pharmaceutical’s campaign to promote use of their very expensive products (Acthar, adrenocorticotropic hormone) to treat sarcoidosis. I agree wholeheartedly with their conclusion that physicians who prescribe useless medications are unprofessional.

Selected Reports

Chest. 2016;149(4):e95-e97. doi:10.1016/j.chest.2015.09.016

Bronchial thermoplasty has been found to be a safe and effective therapy for severe asthma. We report the case of a mediastinal hematoma and hemothorax developing in a 66-year-old woman several days after an uneventful bronchial thermoplasty of the right lower lobe. Evaluation revealed a bleeding right bronchial artery pseudoaneurysm. Pseudoaneuryms have been reported in association with other procedures involving the therapeutic application of thermal energy, and a single case of hemoptysis requiring bronchial artery embolization occurred in a clinical trial of bronchial thermoplasty. However, bronchial artery pseudoaneurysm with hemomediastinum and hemothorax has not previously been reported after bronchial thermoplasty.

Chest. 2016;149(4):e99-e101. doi:10.1016/j.chest.2015.09.017

Chronic thromboembolic pulmonary hypertension (CTEPH) is an uncommon disease that is the most serious complication associated with unresolved pulmonary embolism. This disease has several risk factors, but no familial pattern has been described. Few thrombophilic conditions have been reported to increase risk of CTEPH, and none of the hereditary thrombophilias causes this disease. The reason CTEPH develops in some patients after pulmonary embolism remains unknown. We describe a 54-year-old woman and her maternal aunt who both underwent pulmonary thromboendarterectomy for CTEPH. This represents the first description of familial CTEPH.

Chest. 2016;149(4):e103-e105. doi:10.1016/j.chest.2015.09.008

Trastuzumab emtansine (T-DM1) is a Food and Drug Administration–approved novel agent for the treatment of HER-2 positive advanced breast cancer. We report a case of pulmonary arterial hypertension (PAH) that we attribute to the use of T-DM1. A 43-year-old woman with stage IV breast cancer presented with dyspnea on exertion. After excluding other secondary causes of pulmonary hypertension, a diagnosis of moderately severe PAH was made based on right heart catheterization. History revealed that the patient had been on T-DM1 before presentation. During T-DM1 treatment, the patient experienced hereditary hemorrhagic telangiectasia–like symptoms consisting of spider angiomata-skin lesions, epistaxis, and hematochezia, which resolved with discontinuation of T-DM1. Temporal associations of T-DM1 use with the development of PAH in the patient, and the reported association between hereditary hemorrhagic telangiectasia and PAH via genetic linkage, led us to suspect T-DM1 as the cause of PAH.

Ultrasound Corner

Chest. 2016;149(4):e107-e110. doi:10.1016/j.chest.2015.10.084
Chest. 2016;149(4):e111-e114. doi:10.1016/j.chest.2015.11.032

An 83-year-old man with a history of chronic kidney disease (stage V) as a result of hypertensive nephrosclerosis and coronary artery disease was admitted to the hospital with dyspnea and bilateral lower extremity edema. Owing to oliguria and progressive renal dysfunction, hemodialysis was initiated the following day via a previously-placed left arm arteriovenous fistula. As a result of delirium and bradycardia, he required prolonged hospitalization. Three weeks into his course, he became hypothermic and obtunded.

Pulmonary, Critical Care, and Sleep Pearls

Chest. 2016;149(4):e115-e117. doi:10.1016/j.chest.2015.09.021

A woman in her 30s with alcoholic liver disease presented with an intracerebral hemorrhage with intraventricular extension, hydrocephalus, and an intracerebral hemorrhage score of 3. In the ICU, she was comatose with a flexion withdrawal as a best motor response. The ICU team, after 6 days of care, informed the family that the prognosis for any recovery of meaningful neurological function was dismal and that the family should consider withdrawal of life support. The family resisted any consideration of limitation of care, citing religious beliefs.

Chest. 2016;149(4):e119-e122. doi:10.1016/j.chest.2015.10.080

A white woman in her 80s presented to the ED with nonproductive cough, fever, and 2 weeks of progressive generalized weakness. Previously ambulatory, she now was so weak she required assistance out of bed.

Chest. 2016;149(4):e123-e126. doi:10.1016/j.chest.2015.10.013

A 45-year-old man with a medical history that included asthma and chronic nasal congestion presented for an evaluation of possible OSA. He reported loud snoring, witnessed apneas in sleep, and daytime sleepiness. The patient’s score on the Epworth Sleepiness Scale was 12 of 24, indicating excessive sleepiness. His nasal congestion had been treated with frequent use of an over-the-counter nasal decongestant.

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