Giants in Chest Medicine

Chest. 2016;150(4):759-760. doi:10.1016/j.chest.2016.08.1436


Chest. 2016;150(4):761-762. doi:10.1016/j.chest.2016.06.034

The recent Olympiad reminds us of the herculean efforts required by athletes to become “best in class.” The same can be said for anyone trying to achieve the pinnacle of success, including those of us in the field of medicine. Therefore, it is fitting that in this Olympic year, the American College of Chest Physicians (CHEST) cough guidelines have won a gold medal.

Topics: cough , gold , guidelines
Chest. 2016;150(4):763-765. doi:10.1016/j.chest.2016.06.035

More than 175 million years ago, Pangaea splintered and the continents drifted, carrying with them clusters of living organisms that would eventually develop into our myriad of current species. Like Darwin’s finches, the evolution of today’s human racial groups likely occurred as a result of both genetic inbreeding and local environmental selection pressures, such as differing climates, food resources, and endemic diseases. For this reason, it should come as no surprise that lung cancer can present and respond to therapy differently across diverse populations.

Chest. 2016;150(4):766-768. doi:10.1016/j.chest.2016.06.013

Asthma affects > 300 million people worldwide and is severe in 10% of these individuals. Advances in approaches to phenotype the heterogeneity of severe asthma have established the importance of eosinophilic inflammation, and several new therapies beyond corticosteroids and anti-immunoglobulin E are designed to target type 2-mediated immunity to inhibit this inflammation, with the aim of reducing exacerbation frequency. Current therapies against type 2 immunity include anti-IL-4Rα, IL-5, IL-5R, IL-13, and the type 2 prostaglandin D2 receptor.

Topics: asthma
Chest. 2016;150(4):769-771. doi:10.1016/j.chest.2016.07.017

Community-acquired pneumonia (CAP) is the third most common cause of death globally. The estimated costs for treating CAP exceeded $9 billion per year in the mid-1990s in the United States, more than half being attributed to inpatient care. Approximately 20% to 40% of patients with CAP are treated in the hospital, and 10% require admission to the ICU owing to the need for ventilator support or to septic shock. The mortality rate among patients treated in the ICU for severe CAP ranges from 19% to 50%. Survival depends on a combination of host factors (genetic, age, comorbidities, defenses), pathogens (virulence, serotypes), and therapy. A genome-wide association study of survivors of sepsis due to pneumonia demonstrated that common variants in the FER gene are strongly associated with survival, explaining why certain patients with low bacterial burden are still susceptible to fatal outcomes. It is widely accepted that clinical judgment is inadequate to assess disease severity. Accordingly, several severity scores have been developed and validated widely, with the aim of guiding the initial site of treatment and appropriate level of intervention. However, while clinical scores are recommended for clinical decision-making in the evaluation of patients with CAP, they are not exempt from weaknesses, in particular regarding positive predictive values. Accordingly, the PSI (pneumonia severity index) score and CURB-65 are clinical rules that identify a subset of individuals at low risk of death who could be treated on an ambulatory basis. All remaining patients are classified as “high risk,” for whom hospital admission is recommended despite the fact that a significant percentage of these patients can be safely treated at home. Most sensitive tests with a low false negative rate such as the PSI require that physicians gather data on 20 parameters including a detailed medical history, physical examination, and further investigations such as arterial blood gas measurements and chest radiograph, thus precluding their applicability in a busy ED setting. The CURB-65 score is easier to calculate. However, because it does not directly address comorbidities, it underestimates mortality risk in elderly patients with other underlying diseases. In contrast, SMART-COP (systolic blood pressure, multilobar chest radiography involvement, albumin level, respiratory rate, tachycardia, confusion, oxygenation, and arterial pH) performed better than both the CURB-65 and PSI but failed to identify younger patients (< 50 years of age) requiring mechanical ventilation and/or inotropic support due to CAP. In addition, the PSI and CURB-65 might have good discriminatory power for mortality, but their ability as predictors of ICU admission is no more than fair. Delayed ICU admission was identified as an important risk factor for short-term mortality, leading the Infectious Diseases Society of America and American Thoracic Society (ATS) to develop criteria to identify patients requiring direct ICU referral. It is clear that patients fulfilling major criteria (endotracheal intubation and mechanical ventilation; shock requiring vasopressors) should be considered for ICU admission; however, there is still controversy about the value of the minor criteria. ICU care is costly and a limited resource world-wide.


Chest. 2016;150(4):772-776. doi:10.1016/j.chest.2016.07.040

Ultrasonography is an essential imaging modality in the ICU used to diagnose and guide the treatment of cardiopulmonary failure. Critical care ultrasonography requires that all image acquisition, image interpretation, and clinical applications of ultrasonography are personally performed by the critical care clinician at the point of care and that the information obtained is combined with the history, physical, and laboratory information. Point-of-care ultrasonography is often compartmentalized such that the clinician will focus on one body system while performing the critical care ultrasonography examination. We suggest a change from this compartmentalized approach to a systematic whole-body ultrasonography approach. The standard whole-body ultrasonography examination includes thoracic, cardiac, limited abdominal, and an evaluation for DVT. Other elements of ultrasonography are used when clinically indicated. Each of these elements is reviewed in this article and are accompanied by a link to pertinent cases from the Ultrasound Corner section of CHEST.

Original Research: Education, Research, and Quality Improvement

Chest. 2016;150(4):777-788. doi:10.1016/j.chest.2016.04.028

Background  Clinical practice guidelines (CPGs) have been developed to provide health-care practitioners with the best possible evidence, but the quality of these CPGs varies greatly.

Objective  The goal of this study was to systematically evaluate the quality of cough CPGs and identify gaps limiting evidence-based practice.

Methods  Systematic searches were conducted to identify cough CPGs in guideline databases, developers’ Websites, and Medline. Four reviewers independently evaluated eligible guidelines by using the Appraisal of Guidelines for Research and Evaluation II assessment tool. Agreement among reviewers was measured by using the intraclass correlation coefficient. The number of recommendations, strength of recommendation, and levels of evidence were determined.

Results  Fifteen cough CPGs were identified. An overall high degree of agreement among reviewers was observed (intraclass correlation coefficient, 0.82 [95% CI, 0.79-0.85]). The quality ranged from good to acceptable in the scope and purpose (mean, 72%; range, 54%-93%) and clarity and presentation (mean, 68%; range, 50%-90%) domains but not in stakeholder involvement (mean, 36%; range, 18%-90%), rigor of development (mean, 36%; range, 9%-93%), applicability (mean, 23%; range, 9%-83%), and editorial independence domains (mean, 24%; range, 0-96%). Seven guidelines (46.7%) were considered “strongly recommended” or “recommended with modifications” for clinical practice. More than 70% of recommendations were based on nonrandomized studies (Level C, 30.4%) and expert opinion (Level D, 41.3%).

Conclusions  The quality of cough CPGs is variable, and recommendations are largely based on low-quality evidence. There is significant room for improvement to develop high-quality guidelines, which urgently warrants first-class research to minimize the vital gaps in the evidence for formulation of cough CPGs.

Original Research: Asthma

Chest. 2016;150(4):789-798. doi:10.1016/j.chest.2016.03.032

Background  This phase 3 study further characterizes the efficacy and safety of reslizumab (a humanized anti-IL-5 monoclonal antibody) in patients aged 12 to 75 years with asthma inadequately controlled by at least a medium-dose inhaled corticosteroid and with a blood eosinophil count ≥ 400 cells/μL.

Methods  Patients were randomized to receive reslizumab 0.3 or 3.0 mg/kg or placebo administered once every 4 weeks for 16 weeks (total four doses). The primary end point was change from baseline in pre-bronchodilator FEV1 over 16 weeks. Secondary end points included FVC, forced expiratory flow at 25% to 75% of FVC (FEF25%-75%), patient-reported control of asthma symptoms, short-acting β-agonist (SABA) use, blood eosinophil levels, and safety.

Results  Reslizumab significantly improved FEV1 (difference vs placebo [reslizumab 0.3 and 3.0 mg/kg], 115 mL [95% CI, 16-215; P = .0237] and 160 mL [95% CI, 60-259; P = .0018]). Clinically meaningful increases in FVC (130 mL) and FEF25%-75% (233 mL/s) were observed with reslizumab 3.0 mg/kg. Reslizumab improved scores on the Asthma Control Questionnaire (ACQ) and Asthma Quality of Life Questionnaire (AQLQ) vs placebo (greater effects seen with 3.0 mg/kg; P < .05). The minimally important difference was reached for the AQLQ (reslizumab 3.0 mg/kg) but not on the ACQ. Scores on the Asthma Symptom Utility Index and SABA use were improved with reslizumab. The most common adverse events were worsening of asthma, headache, and nasopharyngitis; most events were mild to moderate in severity.

Conclusions  Reslizumab improved lung function, asthma control and symptoms, and quality of life. It was well tolerated in patients with inadequately controlled asthma (despite standard therapy) and elevated blood eosinophil levels. Overall, the 3.0-mg/kg dose of reslizumab provided greater improvements in asthma outcomes vs the 0.3-mg/kg dose, with comparable safety.

Trial Registry  ClinicalTrials.gov; No.: NCT01270464; URL: www.clinicaltrials.gov.

Chest. 2016;150(4):799-810. doi:10.1016/j.chest.2016.03.018

Background  IL-5, a mediator of eosinophil activity, is an important potential treatment target in patients with uncontrolled asthma. The efficacy of reslizumab, a humanized anti-human IL-5 monoclonal antibody, has been characterized in patients with blood eosinophils ≥ 400 cells/μL. This study further characterizes the efficacy and safety of reslizumab in patients with poorly-controlled asthma, particularly those with eosinophils < 400 cells/μL.

Methods  Patients were randomly assigned to intravenous reslizumab 3.0 mg/kg or placebo once every 4 weeks for 16 weeks. The primary end point was the change in FEV1 from baseline to week 16. Secondary measures included Asthma Control Questionnaire-7 (ACQ-7) scores, use of short-acting β-agonists (SABAs), and FVC.

Results  Four hundred ninety-two patients received ≥ 1 dose of placebo (n = 97) or reslizumab (n = 395). In the overall population, mean FEV1 change from baseline to week 16 was not significantly different between reslizumab and placebo, and no significant relationship was detected between treatment, baseline blood eosinophils and change in FEV1. In the subgroup of patients with baseline eosinophils < 400 cells/μL, patients treated with reslizumab showed no significant improvement in FEV1 compared with those receiving placebo. In the subgroup with eosinophils ≥ 400 cells/μL, however, treatment with reslizumab was associated with much larger improvements in FEV1, ACQ-7, rescue SABA use, and FVC compared with the placebo group. Reslizumab was well tolerated, with fewer overall adverse events compared with placebo (55% vs 73%).

Conclusions  Reslizumab was well tolerated in patients with inadequately controlled asthma. Clinically meaningful effects on lung function and symptom control were not seen in patients unselected for baseline eosinophils.

Trial Registry  ClinicalTrials.gov; No.: NCT01508936; URL: www.clinicaltrials.gov

Chest. 2016;150(4):811-818. doi:10.1016/j.chest.2016.07.006

Background  Work-related asthma (WRA) is the most common chronic occupational lung disease in the developed world. Several factors including sociodemographic status and occupation/industry increase the risks of developing WRA. In this study, we sought to identify changes in patterns and characteristics among patients with WRA over a 15-year period in an occupational lung disease clinic.

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

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

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

Original Research: Critical Care

Chest. 2016;150(4):819-828. doi:10.1016/j.chest.2016.04.010

Background  Predicting the need for intensive care among adults with community-acquired pneumonia (CAP) remains challenging.

Methods  Using a multicenter prospective cohort study of adults hospitalized with CAP, we evaluated the association of serum procalcitonin (PCT) concentration at hospital presentation with the need for invasive respiratory or vasopressor support (IRVS), or both, within 72 h. Logistic regression was used to model this association, with results reported as the estimated risk of IRVS for a given PCT concentration. We also assessed whether the addition of PCT changed the performance of established pneumonia severity scores, including the pneumonia severity index and the American Thoracic Society minor criteria, for prediction of IRVS.

Results  Of 1,770 enrolled patients, 115 required IRVS (6.5%). Using the logistic regression model, PCT concentration had a strong association with IRVS risk. Undetectable PCT (< 0.05 ng/mL) was associated with a 4% (95% CI, 3.1%-5.1%) risk of IRVS. For concentrations < 10 ng/mL, PCT had an approximate linear association with IRVS risk: for each 1 ng/mL increase in PCT, there was a 1% to 2% absolute increase in the risk of IRVS. With a PCT concentration of 10 ng/mL, the risk of IRVS was 22.4% (95% CI, 16.3%-30.1%) and remained relatively constant for all concentrations > 10 ng/mL. When added to each pneumonia severity score, PCT contributed significant additional risk information for the prediction of IRVS.

Conclusions  Serum PCT concentration was strongly associated with the risk of requiring IRVS among adults hospitalized with CAP and is potentially useful for guiding decisions about ICU admission.

Chest. 2016;150(4):829-836. doi:10.1016/j.chest.2016.07.004

Background  Medically underserved areas are composed of vulnerable populations with reduced access to ambulatory care services. Our goal was to determine the association between residence in a medically underserved area and severe sepsis incidence and mortality.

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

Results  In 2010, 24,395 adults were admitted with severe sepsis and 1,446,987 (43%) adults lived in a medically underserved area. Residents of medically underserved areas were admitted more frequently with severe sepsis (8.6 vs 6.8 cases/1,000 people, P < .01) and were more likely to die (15.5 vs 11.9 deaths/10,000 people, P < .01), with increased odds of severe sepsis-related death (OR, 1.12) after adjustment for age, race, and severity of illness. ZIP code-based surrogates of socioeconomic status, including median income, proportion below poverty level, and educational attainment, however, had minimal association with sepsis mortality.

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

Original Research: COPD

Chest. 2016;150(4):837-859. doi:10.1016/j.chest.2016.05.038

Background  Acute exacerbation of COPD (AECOPD) has a significant impact on health-care use, including physician visits and hospitalizations. Previous studies and reviews have shown that pulmonary rehabilitation (PR) has many benefits, but the effect on hospitalizations for AECOPD is inconclusive.

Methods  A literature search was carried out to find studies that might help determine, using a meta-analysis, the impact of PR on AECOPD, defined as unscheduled or emergency hospitalizations and ED visits. Cohort studies and randomized controlled trials (RCTs) reporting hospitalizations for AECOPD as an outcome were included. Meta-analyses compared hospitalization rates between eligible PR recipients and nonrecipients before and after rehabilitation.

Results  Eighteen studies were included in the meta-analysis. Results from 10 RCTs showed that the control groups had a higher overall rate of hospitalization than did the PR groups (control groups: 0.97 hospitalizations/patient-year; 95% CI, 0.67-1.40; PR groups: 0.62 hospitalizations/patient-year; 95% CI, 0.33-1.16). Five studies compared admission numbers in the 12 months before and after rehabilitation, finding a significantly higher admission rate before compared with after (before: 1.24 hospitalizations/patient-year; 95% CI, 0.66-2.34; after: 0.47 hospitalizations/patient-year; 95% CI, 0.28-0.79). The pooled result of three cohort studies found that the reference group had a lower admission rate compared with the PR group (0.18 hospitalizations/patient-year; 95% CI, 0.11-0.32 for reference group vs 0.28 hospitalizations/patient-year; 95% CI, 0.25-0.32 for the PR group).

Conclusions  Although results from RCTs suggested that PR reduces subsequent admissions, pooled results from the cohort studies did not, likely reflecting the heterogeneous nature of individuals included in observational research and the varying standard of PR programs.

Chest. 2016;150(4):860-868. doi:10.1016/j.chest.2016.06.031

Background  COPD exacerbation incidence rates are often ascertained retrospectively through patient recall and self-reports. We compared exacerbation ascertainment through patient self-reports and single-physician chart review to central adjudication by a committee and explored determinants and consequences of misclassification.

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

Results  The AC identified 648 exacerbations, corresponding to an incidence rate of 0.60 ± 0.83 exacerbations/patient-year and a cumulative incidence proportion of 58.9%. Patients self-reported 841 exacerbations (incidence rate, 0.75 ± 1.01; incidence proportion, 59.7%). The sensitivity and specificity of self-reports were 84% and 76%, respectively, those of single-physician chart review were between 89% and 96% and 87% and 99%, respectively. The multinomial regression model and bootstrap selection showed that having experienced more exacerbations was the only factor consistently associated with underreporting and overreporting of exacerbations (underreporters: relative risk ratio [RRR], 2.16; 95% CI, 1.76-2.65 and overreporters: RRR, 1.67; 95% CI, 1.39-2.00).

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

Clinical Trial Registration  www.ClinicalTrials.gov, NCT00706602

Original Research: Tobacco Cessation and Prevention

Chest. 2016;150(4):869-876. doi:10.1016/j.chest.2016.06.011

Background  Smoking is associated with impaired health-related quality of life (HRQL) across all populations. Because decline in lung function and risk for COPD are lower in New Mexican Hispanic smokers compared with their non-Hispanic white (NHW) counterparts, the goal of this study was to ascertain whether HRQL differs between these two racial/ethnic groups and determine the factors that contribute to this difference.

Methods  We compared the score results of the Medical Outcomes Short-Form 36 Health Survey (SF-36) and St. George’s Respiratory Questionnaire (SGRQ) in 378 Hispanic subjects and 1,597 NHW subjects enrolled in the Lovelace Smokers’ Cohort (LSC) from New Mexico. The associations of race/ethnicity with SGRQ and SF-36 were assessed by using multivariable regression.

Results  Physical functioning (difference, –4.5; P = .0008) but not mental health or role emotional domains of the SF-36 was worse in Hispanic smokers than in their NWH counterparts in multivariable analysis. SGRQ total score and its activity and impact subscores were worse in Hispanic (vs NHW) smokers after adjustment for education level, current smoking, pack-years smoked, BMI, number of comorbidities, and FEV1 % predicted (difference range, 2.9-5.0; all comparisons, P ≤ .001). Although the difference in the SGRQ activity domain was above the clinically important difference of four units, the total score was not.

Conclusions  New Mexican Hispanic smokers have clinically relevant, lower HRQL than their NHW counterparts. A perception of diminished physical functioning and impairment in daily life activities contribute to the poorer HRQL among Hispanic subjects.

Evidence-Based Medicine

Chest. 2016;150(4):877-893. doi:10.1016/j.chest.2016.02.650

Background  American College of Chest Physicians (CHEST) clinical practice guidelines on the evaluation of pulmonary nodules may have low adoption among clinicians in Asian countries. Unique patient characteristics of Asian patients affect the diagnostic evaluation of pulmonary nodules. The objective of these clinical practice guidelines was to adapt those of CHEST to provide consensus-based recommendations relevant to practitioners in Asia.

Methods  A modified ADAPTE process was used by a multidisciplinary group of pulmonologists and thoracic surgeons in Asia. An initial panel meeting analyzed all CHEST recommendations to achieve consensus on recommendations and identify areas that required further investigation before consensus could be achieved. Revised recommendations were circulated to panel members for iterative review and redrafting to develop the final guidelines.

Results  Evaluation of pulmonary nodules in Asia broadly follows those of the CHEST guidelines with important caveats. Practitioners should be aware of the risk of lung cancer caused by high levels of indoor and outdoor air pollution, as well as the high incidence of adenocarcinoma in female nonsmokers. Furthermore, the high prevalence of granulomatous disease and other infectious causes of pulmonary nodules need to be considered. Therefore, diagnostic risk calculators developed in non-Asian patients may not be applicable. Overall, longer surveillance of nodules than those recommended by CHEST should be considered.

Conclusions  TB in Asia favors lesser reliance on PET scanning and greater use of nonsurgical biopsy over surgical diagnosis or surveillance. Practitioners in Asia are encouraged to use these adapted consensus guidelines to facilitate consistent evaluation of pulmonary nodules.

Chest. 2016;150(4):894-907. doi:10.1016/j.chest.2016.07.029

Background  In response to occupational and environmental exposures, cough can be an isolated symptom reflecting exposure to an irritant with little physiological consequence, or it can be a manifestation of more significant disease. This document reviews occupational and environmental contributions to chronic cough in adults, focusing on aspects not previously covered in the 2006 ACCP Cough Guideline or our more recent systematic review, and suggests an approach to investigation of these factors when suspected.

Methods  MEDLINE and TOXLINE literature searches were supplemented by articles identified by the cough panel occupational and environmental subgroup members, to identify occupational and environmental aspects of chronic cough not previously covered in the 2006 ACCP Cough Guideline. Based on the literature reviews and the Delphi methodology, the cough panel occupational and environmental subgroup developed guideline suggestions that were approved after review and voting by the full cough panel.

Results  The literature review identified relevant articles regarding: mechanisms; allergic environmental causes; chronic cough and the recreational and involuntary inhalation of tobacco and marijuana smoke; nonallergic environmental triggers; laryngeal syndromes; and occupational diseases and exposures. Consensus-based statements were developed for the approach to diagnosis due to a lack of strong evidence from published literature.

Conclusions  Despite increased understanding of cough related to occupational and environmental triggers, there remains a gap between the recommended assessment of occupational and environmental causes of cough and the reported systematic assessment of these factors. There is a need for further documentation of occupational and environmental causes of cough in the future.

Translating Basic Research Into Clinical Practice

Chest. 2016;150(4):908-915. doi:10.1016/j.chest.2016.06.045

In recent years, numerous studies have generated data supporting the hypothesis that extracellular adenosine 5′-triphosphate (ATP) plays a major role in obstructive airway diseases. Studies in animal models and human subjects have shown that increased amounts of extracellular ATP are found in the lungs of patients with COPD and asthma and that ATP has effects on multiple cell types in the lungs, resulting in increased inflammation, induction of bronchoconstriction, and cough. These effects of ATP are mediated by cell surface P2 purinergic receptors and involve other endogenous inflammatory agents. Recent clinical trials reported promising treatment with P2X3R antagonists for the alleviation of chronic cough. The purpose of this review was to describe these studies and outline some of the remaining questions, as well as the potential clinical implications, associated with the pharmacologic manipulation of ATP signaling in the lungs.

Recent Advances in Chest Medicine

Chest. 2016;150(4):916-926. doi:10.1016/j.chest.2016.05.002

Of those patients hospitalized for an exacerbation of COPD, one in five will require rehospitalization within 30 days. Many developed countries are now implementing policies to increase care quality while controlling costs for COPD, known as value-based health care. In the United States, COPD is part of Medicare’s Hospital Readmissions Reduction Program (HRRP), which penalizes hospitals for excess 30-day, all-cause readmissions after a hospitalization for an acute exacerbation of COPD, despite minimal evidence to guide hospitals on how to reduce readmissions. This review outlines challenges for improving overall COPD care quality and specifically for the HRRP. These challenges include heterogeneity in the literature for how COPD and readmissions are defined, difficulty finding the target population during hospitalizations, and a lack of literature to guide evidence-based programs for COPD readmissions as defined by the HRRP in the hospital setting. It then identifies risk factors for early readmissions after acute exacerbation of COPD and discusses tested and emerging strategies to reduce these readmissions. Finally, we evaluate the current HRRP and future policy changes and their effect on the goal to deliver value-based COPD care. COPD remains a chronic disease with a high prevalence that has finally garnered the attention of health systems and policy makers, but we still have a long way to go to truly deliver value-based care to patients.

Contemporary Reviews in Critical Care Medicine

Chest. 2016;150(4):927-933. doi:10.1016/j.chest.2016.03.043

Negative-pressure pulmonary edema (NPPE) or postobstructive pulmonary edema is a well-described cause of acute respiratory failure that occurs after intense inspiratory effort against an obstructed airway, usually from upper airway infection, tumor, or laryngospasm. Patients with NPPE generate very negative airway pressures, which augment transvascular fluid filtration and precipitate interstitial and alveolar edema. Pulmonary edema fluid collected from most patients with NPPE has a low protein concentration, suggesting hydrostatic forces as the primary mechanism for the pathogenesis of NPPE. Supportive care should be directed at relieving the upper airway obstruction by endotracheal intubation or cricothyroidotomy, institution of lung-protective positive-pressure ventilation, and diuresis unless the patient is in shock. Resolution of the pulmonary edema is usually rapid, in part because alveolar fluid clearance mechanisms are intact. In this review, we discuss the clinical presentation, pathophysiology, and management of negative-pressure or postobstructive pulmonary edema.

Contemporary Reviews in Sleep Medicine

Chest. 2016;150(4):934-944. doi:10.1016/j.chest.2016.05.022

Opioid use for chronic pain analgesia, particularly chronic noncancer pain, has increased greatly since the late 1990s, resulting in an increase in opioid-associated morbidity and mortality. A clear link between opioid use and sleep-disordered breathing (SDB) has been established, with the majority of chronic opioid users being affected by the condition, and dose-dependent severity apparent for some opioids. More evidence is currently needed on how to effectively manage opioid-induced SDB. This review summarizes the current state of knowledge relating to management of patients undergoing chronic opioid therapy who have SDB. Initial management of these patients requires a thorough biopsychosocial assessment of their need for opioid therapy, consideration of reduction or cessation of the opioid if possible, and analysis of alternative therapies for treatment of their pain. If opioid therapy must be continued, then management of the associated SDB may be important. Several small- to medium-scale studies have examined the efficacy of noninvasive ventilation, particularly adaptive servo-ventilation (ASV) for the treatment of opioid-associated SDB. This research is particularly important because opioids predispose predominantly to central sleep apnea and also, to a lesser extent, OSA. Generally, these studies have found positive results in treating opioid-associated SDB with ASV in terms of improving outcome measures such as central apnea index and the apnea-hypopnea index. Larger studies that measure longer term health outcomes, patient sleepiness, and compliance are needed, however. Registries of health outcomes of ASV-treated patients may assist with future treatment planning.

Special Features

Chest. 2016;150(4):945-965. doi:10.1016/j.chest.2016.04.026

Cysts are commonly seen on CT scans of the lungs, and diagnosis can be challenging. Clinical and radiographic features combined with a multidisciplinary approach may help differentiate among various disease entities, allowing correct diagnosis. It is important to distinguish cysts from cavities because they each have distinct etiologies and associated clinical disorders. Conditions such as emphysema, and cystic bronchiectasis may also mimic cystic disease. A simplified classification of cysts is proposed. Cysts can occur in greater profusion in the subpleural areas, when they typically represent paraseptal emphysema, bullae, or honeycombing. Cysts that are present in the lung parenchyma but away from subpleural areas may be present without any other abnormalities on high-resolution CT scans. These are further categorized into solitary or multifocal/diffuse cysts. Solitary cysts may be incidentally discovered and may be an age related phenomenon or may be a remnant of prior trauma or infection. Multifocal/diffuse cysts can occur with lymphoid interstitial pneumonia, Birt-Hogg-Dubé syndrome, tracheobronchial papillomatosis, or primary and metastatic cancers. Multifocal/diffuse cysts may be associated with nodules (lymphoid interstitial pneumonia, light-chain deposition disease, amyloidosis, and Langerhans cell histiocytosis) or with ground-glass opacities (Pneumocystis jirovecii pneumonia and desquamative interstitial pneumonia). Using the results of the high-resolution CT scans as a starting point, and incorporating the patient’s clinical history, physical examination, and laboratory findings, is likely to narrow the differential diagnosis of cystic lesions considerably.

Topics: cyst , lung , lung diseases

Topics in Practice Management

Chest. 2016;150(4):966-971. doi:10.1016/j.chest.2016.06.006

ICU-acquired weakness (ICUAW) occurs with reported incidence rates from 25% to 100%. Risk factors include immobility, sepsis, persistent systemic inflammation, multiorgan system failure, hyperglycemia, glucocorticoids, and neuromuscular blocking agents. The pathophysiology remains unknown. Clinical features may be neuropathic, myopathic, or a combination of both. Although manual muscle testing is more practical in diagnosing ICUAW, the “gold standard” for the diagnosis of ICUAW remains electromyography and nerve conduction studies. The only potential interventions known to date to prevent ICUAW include insulin therapy and early rehabilitation, but patients still may develop activity limitations in the acute care hospital. For these patients, rehabilitation may continue in long-term care hospitals, inpatient rehabilitation facilities, or skilled nursing facilities. ICUAW is a catastrophic and debilitating condition that potentially leaves patients with permanent residual activity limitations and participation restrictions. Further research on ICUAW needs to better understand its pathophysiology so that more definitive preventive and therapeutic interventions may be developed.


Chest. 2016;150(4):972. doi:10.1016/j.chest.2016.04.021

    A lazy, languid pressure in between
    the eyebrows. A small extension
    now covering the eyes, the forehead,
    the temples, and then a little more—
    an inclusion of the head, each
    hair root, the entire skull.

    And then a little more. The neck,
    the shoulders, then all along
    the body’s complex geometry.
    The crown of the head, under which
    the ill-blooded brain is, the mind
    and memory are supposed to be.

    And there are the prescribed pretensions
    of success and cure. Round, gray, pink, white.
    And still others, like a faithful hand’s
    magical pulling at the hair, anointing
    the forehead, the eyeballs, the skin
    under the earlobes with ancient remedies.
    A pressure on tired limbs with
    vastly experienced hands. And then, sleep.

    Even then, it is still there, all over the body.
    Dull, lengthening, like real hunger.
    No one knows, although they
    pretend to do so. It is so far from
    their own thoughts--so far, they can
    never know. And one can only
    blame oneself for going through it,
    for having come into this world.

Chest. 2016;150(4):973. doi:10.1016/j.chest.2016.04.022

    Life begins and ends here
    Laughter and muffled tears are all galore
    There is tranquility in one corner and anguish in another
    Uncertainty and hope are all mixed in

    At the crack of dawn
    Many healers come to this shrine
    The chaos is about to begin
    Aim is to reduce entropy, and hope for recovery

    The sirens blare, a gunshot victim is in
    There is a crew of people, waiting just for him
    Machines, lines, and a lot of chatter
    In the hope, that all of this will matter

    On the fourth floor, there is an old patient who is dying
    You cannot say whether he is happy or crying
    Cancer has been eating him for years
    And perhaps, he has finally conquered his fears

    Another corner, there is a baby being born
    Mother in tears of joy and pain
    Near the window, you can hear soft drops of rain
    In this sacred place, no effort goes vain

    As the sun is about to set
    You can hear this man’s breath
    All the cigarettes have corroded his lungs
    When you listen to him, it sounds like beat-up drums

    Drugs and bugs play at night
    Walking in the corridors might make you fright
    Radiographs and electrons zoom through the body
    And show the mystique at play

    There is a gift shop near the entrance
    Where you see a toy giraffe and colorful balloons
    As visitors leave, they see the smiling moon
    At this place, magic happens again and again

Chest. 2016;150(4):974-975. doi:10.1016/j.chest.2016.05.030

    I am ground glass opacity (GGO) in the lung,
    A vague figure shrouded in mystery and strangeness,
    Like looking at the moon through clouds,
    Like seeing beautiful flowers in the fog.

    I long to be king,
    With my fellows swimming in every vessel.
    My people crawl in your organs and body,
    Holding the rights for life or death, I tremble with excitement.

    When young you called me “atypical adenomatous hyperplasia”,
    Then when I had matured, you declared me “adenocarcinoma in situ”,
    When fully developed, your fearful denomination: “invasive adenocarcinoma”.
    You forgot my strenuous journey to become the king.

    From tiny to strong,
    From humble to arrogant.
    None cared when I was young,
    But all fear me we when full grown.

    I’ve been nourished on the delicious mist and haze,
    That sweetly warmed my heart,
    Always loving when you were heavy drunk and smoking,
    Creating me a cozy home.

    When I was less than eight millimeters, I was so fragile,
    Waiting for a chance to grow up.
    Now, more than eight millimeters, I am more mature,
    And considered worthy of notice.

    My continuous growth gives me a chance to be king,
    As I break through layers of obstacles,
    Spanning the mountains and waters.
    My fellows march to every corner and occupy every region.

    My quest to become king was full of obstacles,
    I was cut until almost dead in childhood,
    Burned once I’d matured,
    And poisoned when older.

    Happiness after sorrow, rainbow after rain.
    I faced surgery, radiotherapy, and chemotherapy,
    But continued to chase my dream,
    Some would have given up, but I will be the king.

    I long to be king, with fellows and subordinates,
    I long to be king, to have people’s fear and respect
    I long to be king, to dominate my domain,
    I long to be king, to direct your fate.

Chest. 2016;150(4):976. doi:10.1016/j.chest.2016.05.027

    She sat in the waiting room,
    Skinny, depressed, wrinkled.
    Regretted being there.
    Daughter-the-nurse INSISTED.

    Abnormal x ray.
    “Short-of-breath, sometimes”
    She panted around words of denial.

    I spoke of
    crackles, and clubbing.
    Daughter-the-nurse glared,
    index finger inflicting the radiological verdict:
    “Pulmonary fibrosis cannot be excluded”.

    A little laugh from under the table…
    “Sarah, come out now, meet the doctor”.
    “Meet my granddaughter”
    She said.

    Beneath the table gleamed two eyes,
    brown as chestnuts,
    framed by an impish face,
    intent on staring at my stethoscope.

    I was about to launch into
    the “Pulmonary-Fibrosis-not-good-Prognosis”
    Grandma interrupted.

    “You know, Sarah had brain cancer at age one.
    They said she was inoperable and gave her radiation.
    Didn’t think she’d live beyond four,
    here she is, six, and the brightest student
    in first grade,
    plays the piano and sings…
    She’s my pride and joy.
    I plan to be at her high school graduation.”
    She said.

    “Well, it may just be you have had this pulmonary fibrosis for
    some time, and who knows how often people stay the same
    or… get worse, or improve…
    How about you come back to see me after Sara graduates?”,
    said I.

    She winked
    And for the first time,
    felt understood.


Chest. 2016;150(4):977-978. doi:10.1016/j.chest.2016.06.048

Liu et al investigated the possible use of thoracic ultrasonography (TUS) to diagnose transient tachypnea of the newborn in a large sample of infants. In such patients, the use of TUS, a safe radiation-free repeatable technique that is easy to perform, would be extremely appealing; it can also be used in emergency settings with portable devices. However, Liu et al's study raises relevant concerns.

Chest. 2016;150(4):978-979. doi:10.1016/j.chest.2016.07.018

I appreciate Dr Sperandeo et al for their attention and insightful comments in response to the recent publication by my colleagues and me on the use of lung ultrasonography (LUS) to diagnose transient tachypnea of the newborn (TTN). Sperandeo et al's professional knowledge of LUS, their publications, and comments on our publication have expanded my understanding in this field.

Chest. 2016;150(4):979-980. doi:10.1016/j.chest.2016.07.038

In their recent article in CHEST (May 2016) regarding the management of inferior vena cava (IVC) filters, Drs Arous and Messina recommend that filters be implanted on the basis of best available evidence, and be removed at 25 to 54 days postimplantation. By not distinguishing between high-risk and low-risk populations that receive IVC filters, the authors propagate an often inappropriate case report-driven obsession for filter removal. The patients at higher risk for pulmonary embolism (PE) are those who have filters placed for DVT, and the patients at lower risk are those who have filters placed because they had a transient elevated risk for the development of DVT. Differentiating these groups is important in any consideration on filter removal. In the cost/benefit analysis of whether to remove a filter, the costs, or complication risk of a filter over time, may be similar between those groups, but the benefit of a filter is different, as it is dependent on the risk of a patient developing a PE.

Chest. 2016;150(4):980-981. doi:10.1016/j.chest.2016.08.1434

In response to our commentary “Temporary inferior vena cava filters: how do we move forward?” in CHEST, we received a letter from Dr Hoffer expressing concern regarding the recommendation for retrieval of inferior vena cava (IVC) filters in select high-risk patients. In our original publication, we cited the decision analysis work by Morales et al, for a goal retrieval of IVC filters 29 to 54 days postimplantation in patients at transient risk of pulmonary embolism (PE). Furthermore, in 2010 the US Food and Drug Administration (FDA) recommended that in “patients with retrievable IVC filters consider removing the filter as soon as protection from PE is no longer needed.” A subsequent update in 2014 encouraged all physicians to “consider the risks and benefits of filter removal for each patient. A patient should be referred for IVC filter removal when the risk/benefit profile favors removal and the procedure is feasible given the patient’s health status.”

Chest. 2016;150(4):981. doi:10.1016/j.chest.2016.07.021

The recent meta-analysis by Dahal et al concludes that warfarin therapy for atrial fibrillation (AF) may have an unfavorable risk/benefit ratio in patients with end-stage renal disease. Although meta-analyses represent the highest level of evidence for formulating recommendations for clinical practice, the robustness of conclusions depends on the quality of available studies. The design and observational nature of studies included in this meta-analysis portend important biases that must be brought to the front in the interpretation of their conclusions.

Chest. 2016;150(4):981-982. doi:10.1016/j.chest.2016.07.022

In a letter to the editor by Meuwese et al regarding our recent paper, they mentioned two important known biases of observational studies, that is, confounding and survival biases. Because of those and other biases, the results of any meta-analysis of observational studies need cautious interpretation. The meta-analyses of randomized trials have been considered to provide robust and, at times, contradictory results in comparison with the meta-analyses of observational studies. However, in the absence of randomized trials to address the question being asked, meta-analyses of observational studies have been long performed, understanding that there may be limitations. At times, the meta-analyses of observational studies provide crucial answers to the questions being asked, as the randomized trials may have restrictive inclusion/exclusion criteria and a limited duration of follow-up. They also provide real-world data.

Chest. 2016;150(4):982-983. doi:10.1016/j.chest.2016.07.039

We read with great interest the study by Whitson et al in CHEST (June 2016), examining the feasibility, utility, and safety of midodrine during the recovery phase from septic shock. In the study, the authors conclude that midodrine may reduce the duration of intravenously administered vasopressors, and may be associated with a reduction of ICU length of stay. While we understand the limitations of a retrospective study in avoiding any confounders, we cannot help but question the statistical tools used to compare both groups.

Chest. 2016;150(4):983-984. doi:10.1016/j.chest.2016.08.1437

We appreciate the interest of Drs Sagar and Vijhani regarding our study, which reported our experience with midodrine use in patients recovering from septic shock. In answer to their questions:

  • 1.

    Median ICU length of stay (LOS) was 8 days in the IV vasopressor-only group and 4 days in the IV vasopressor with midodrine group (P = .017). ICU LOS was calculated using midnight bed occupancy days as recommended by Marik and Hedman (Table 1).

  • 2.

    Median Acute Physiology and Chronic Health Evaluation (APACHE IV) scores were 83 in the IV vasopressor-only group and 77.5 in the IV vasopressor with midodrine group (P = .55) (Table 2).

  • 3.

    Regarding the 18 patients discharged on midodrine, disposition and dosing were varied. Seven patients were discharged to hospice care, and one patient was transferred to another facility. Four patients were discharged home taking midodrine during hemodialysis only, which is a common safe practice. Six patients were discharged to rehabilitation centers, and the highest dosage at discharge was 10 mg tid. As these patients were discharged after transfer to the primary team from the ICU, we cannot comment on the treatment or discharge decisions regarding midodrine use. We also cannot comment on the outpatient duration, down titration, or outcomes of midodrine therapy in these patients. For a hospital inpatient, we recommend decremental titration of midodrine by 5 to 10 mg per dose on a daily basis until discontinuation while monitoring for hypotension or symptoms. If hypotension occurs, the prior stable midodrine dose should be reinstated. We do not recommend the routine use of daily midodrine for outpatients during recovery from septic shock.

Chest. 2016;150(4):984-985. doi:10.1016/j.chest.2015.10.023

We read with great interest in a recent issue of CHEST (May 2015) the study by Oki and colleagues who compared mediastinal nodal sampling by endoscopic ultrasound (EUS; transesophageal) with endobronchial ultrasound (EBUS; transbronchial) using the same endoscope. Sampling by EUS resulted in similar diagnostic yield but was associated with fewer doses of anesthetics and sedatives, less oxygen desaturation and cough, a shortened procedure time, and higher operator satisfaction. We congratulate Oki and colleagues as they have proven what each EBUS/EUS endoscopist already knew from clinical practice but was never systematically investigated.

Chest. 2016;150(4):985-986. doi:10.1016/j.chest.2015.10.025

We thank Drs Annema and Konge for their enlightening comments regarding our study comparing the tolerance, efficacy, and safety of endobronchial ultrasound (EBUS)-guided transbronchial needle aspiration (EBUS-TBNA) with transesophageal endoscopic ultrasound (EUS)-guided fine-needle aspiration (EUS-FNA) with an EBUS scope for the diagnosis of mediastinal lesions.

Chest. 2016;150(4):986-987. doi:10.1016/j.chest.2015.10.029

We read with great interest the recent article by Bataille et al in CHEST (December 2014) exploring the added diagnostic value of combined lung and cardiac ultrasonographic examinations compared with lung ultrasonography alone. While we also believe that an integrated cardiopulmonary approach is needed, we were rather surprised by the poor diagnostic performance of lung ultrasonography for the diagnosis of pneumonia and cardiogenic pulmonary edema.


Chest. 2016;150(4):988. doi:10.1016/j.chest.2016.08.1429

“Mechanical Ventilation as a Therapeutic Tool to Reduce ARDS Incidence”, published in the December 2015 issue of CHEST (2015;148(6):1396-1404), was retracted after the Journal determined that the authors had not conformed to the Journal's Instructions to Authors to disclose all relevant conflicts of interest by failing to disclose major competing interests that are, in the judgment of the Journal, likely to influence interpretations or recommendations.

Chest. 2016;150(4):988. doi:10.1016/j.chest.2016.08.1442

The authors have reported to CHEST that a grade error appears in the text in “Antithrombotic Therapy for VTE Disease: CHEST Guideline and Expert Panel Report” (Chest 2016; 149(2):315-352). The error appears in Recommendation 3 on pages 316 and 325.

Chest. 2016;150(4):988. doi:10.1016/j.chest.2016.08.1454

The authors have reported to CHEST that data errors appear in the text in “The Presence of Diffuse Alveolar Damage on Open Lung Biopsy Is Associated With Mortality in Patients With Acute Respiratory Distress Syndrome: A Systematic Review and Meta-Analysis” (Chest 2016; 149(5):1155-1164).

Selected Reports

Chest. 2016;150(4):e93-e98. doi:10.1016/j.chest.2016.03.009

Cystic fibrosis (CF) patients are at risk for life-threatening hemoptysis, sometimes necessitating bronchial arterial embolization (BAE). Spinal artery embolization and pulmonary infarction are commonly cited procedural risks, yet respiratory failure and death are underappreciated. We conducted a retrospective institutional review of our outcomes after BAE for hemoptysis in CF and present three cases highlighting this complication. From 2007 to 2015, 12 patients underwent 17 BAE procedures for hemoptysis at our institution. Three patients experienced respiratory failure and died within 3 months of BAE. Nonsurvivors had significantly lower baseline FEV1 values than survivors (21.8% vs 52.6%, P < .05). BAE as a treatment for life-threatening hemoptysis may precipitate respiratory failure in end-stage CF and should accelerate the evaluation for lung transplantation. Institutions should reevaluate their BAE practices to ensure preservation of the bronchial circulation, which contributes to gas exchange in these patients.

Chest. 2016;150(4):e99-e103. doi:10.1016/j.chest.2016.02.655

Extrapulmonary tuberculosis refers to Mycobacterium tuberculosis involving organs other than the lungs (eg, pleura, lymph nodes, genitourinary tract, abdomen, skin, joints and bones, or meninges). In non-HIV-endemic areas, where reactivation is the predominant mechanism of tuberculosis, pleural involvement occurs in 4% of cases. We present an extremely rare case of a 62-year-old immunocompetent patient with pleural tuberculosis confirmed by surgical pleural biopsies, who presented with a large mediastinal mass and evidence of pulmonary artery invasion on CT scanning and endobronchial ultrasonography imaging, highlighting a unique and malignant-like character of the disease.

Ultrasound Corner

Chest. 2016;150(4):e105-e107. doi:10.1016/j.chest.2016.03.066

A previously healthy 33-year-old pregnant woman gravida 4, para 1, with good prenatal care, presented to an obstetric clinic at 34 weeks' gestation with new-onset shortness of breath, activity intolerance, and worsening lower-extremity edema. The patient had had an uncomplicated pregnancy 10 years earlier as well as a remote history of methamphetamine abuse. Pulse oximetry revealed oxygen saturation in the low 80% range with a mild response to oxygen supplementation through a nonrebreather mask. A heparin drip was started because of a concern about pulmonary embolism (PE), and the patient was admitted to the ICU for further management.

Chest Imaging and Pathology for Clinicians

Chest. 2016;150(4):e109-e115. doi:10.1016/j.chest.2016.07.002

A 66-year-old man presented with dry cough and shortness of breath on exertion of 6 months' duration. There were no complaints of fever and hemoptysis. His history was significant for recurrent episodes of respiratory tract infections over the previous 4 years. He had also had episodes of recurrent otitis media and pus discharge from the left ear for 3 years, with progressive loss of hearing. There was no history of recurrent skin infections or diarrhea. He was treated symptomatically with antibiotics by local general practitioners. He was a nonsmoker and did not drink alcohol, and there was no history of environmental or occupational exposure. He had been known to have diabetes for 10 years. He had negative results for the presence of HIV and hepatitis B surface antigen.

Pulmonary, Critical Care, and Sleep Pearls

Chest. 2016;150(4):e117-e120. doi:10.1016/j.chest.2016.03.039

A 43-year-old man was referred to our tertiary sleep center for the initiation of sleep apnea treatment. A prior diagnostic overnight polysomnography (Fig 1) had revealed an apnea-hypopnea index (AHI) of 22/h of sleep. The apneas were predominantly central (central AHI, 18.2/h; obstructive AHI, 3.8/h), more pronounced in the supine position (AHI supine, 36.6/h; AHI nonsupine, 11/h) and during non-rapid eye movement (non-REM) sleep (REM, 15.8/h; non-REM, 23.5/h). A continuous positive airway pressure (CPAP) trial in an outpatient setting had failed, as the fixed CPAP of 11 cm H2O was not tolerated by the patient because of a feeling of lightheadedness when wearing the mask. At referral, the patient complained about falling asleep in front of the computer in the afternoons despite regular bedtimes and 7 to 8 h of sleep per night. His Epworth Sleepiness Scale score was 11. He had no significant past history including cardiopulmonary disease. He was not taking any medication but had noticed a slow decline in general physical performance in the last year, with dyspnea (New York Heart Association class I) after running distances of 1 to 2 km. He had never experienced syncope. His family history was unremarkable.

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