Current Issue


Chest. 2015;148(1):3-4. doi:10.1378/chest.15-0395

For many years, a practice known as vanity sizing has been increasing the physical dimensions of women’s clothing relative to its nominal size, resulting from the lack of an industry standard that is adhered to.1 Vanity sizing impedes the reliable selection of properly fitting garments without donning them since similarly labeled clothing may be proportioned using different scales and vary significantly in size. An analogous predicament faces clinicians and researchers when they attempt to properly tailor tidal volume for a patient with ARDS who is mechanically ventilated. Unlike fashion where actual weight determines fit, tidal volumes are best indexed to predicted, not actual, body weight; being overweight does not grow lung and being underweight does not shrink lung. Yet, even knowing the major determinants of predicted body weight (height, age, and sex), there is no accepted standard for predicted body weight calculation and, in the past, researchers have used several different equations.2-5

Chest. 2015;148(1):4-6. doi:10.1378/chest.14-2987

Section 3025 of the Affordable Care Act created the Hospital Readmission Reduction Program (HRRP).1 Under the HRRP, the Centers for Medicare & Medicaid Services (CMS) is charged with working to reduce hospital readmissions for select conditions. The initial focus of the HRRP was on acute myocardial infarction, congestive heart failure, and pneumonia.1,2 Recently, conditions covered by the HRRP initiative have expanded to include other diseases, such as COPD and coronary artery bypass grafting, whose patients are cared for by pulmonary and critical care physicians. If a hospital’s actual readmission rate at 30 days for a specific disease covered by the HRRP exceeds the expected readmission rate, the penalty in fiscal year 2013 was an up to 1% payment reduction.1,2 In the first year of the program, nearly 2,200 hospitals faced payment penalties.3 Although the total savings to the CMS from this program are small in light of its huge budget, the implications for hospitals can be significant. Many institutions, be they community or academic, face substantial financial pressures under the changing health-care delivery environment and operate on small margins. The penalty rate increases to a 3% clawback by fiscal year 2015.1,2

Chest. 2015;148(1):6-8. doi:10.1378/chest.15-0340

Some political figures have made a point recently about the importance of civil liberties. These individuals point to the importance of freedom and discourage government interference in personal matters. Despite the known health risks, 20% of the US population smokes conventional tobacco cigarettes.1 Many smokers argue that they enjoy the habit and do not believe that others should have the right to regulate their behavior. Smokers represent a financial burden on the health-care system, but pay considerable consumption tax during their lifetime and, thus, their economic impact could be debated. The argument changed from one of personal freedom to include issues of public health when the impact of secondhand smoke (SHS) was recognized. No longer were smokers simply affecting themselves, but also their children, spouses, and other innocent bystanders. Indeed, roughly 40% of children worldwide are regularly exposed to SHS, and 600,000 people are predicted to die annually from SHS.2,3 Some data also suggest that smoke exposure may have transgenerational consequences such that an individual’s adult health may be affected by prior exposures experienced by one’s mother or grandmother.4

Topics: smoking , cigarettes

Point and Counterpoint

Chest. 2015;148(1):9-10. doi:10.1378/chest.15-0424

The ultimate goal for the management of malignant pleural effusion (MPE) is to relieve dyspnea and avoid multiple procedures that would interfere with a patient’s quality of life. Therapeutic options include the use of oxygen and morphine for patients with an extremely limited life expectancy, repeat thoracentesis, placement of a tunneled pleural catheter (TPC), and pleurodesis. Because nearly 100% of MPEs will recur within 1 month, repeat thoracentesis often is used for patients with an expected survival < 4 weeks. It stands to reason that the least invasive methods that will provide long-term relief should be used for patients expected to survive > 1 month. Not surprisingly, a small-bore TPC is recommended by British Thoracic Society guidelines1 for the management of MPE.

Chest. 2015;148(1):11-13. doi:10.1378/chest.15-0426

The question posed by the editorial staff at CHEST seems simple and straightforward, but unfortunately, its answer is complex. If a discreet dichotomous response is required, then our answer would be no. The essence of the question is small- vs large-bore chest tubes in the management of malignant pleural effusion (MPE). We contend that MPE represents a heterogeneous problem without a one-size-fits-all approach. Not all malignant effusions or the patients with them are the same, and much work needs to be done to sort out optimal management.

Chest. 2015;148(1):13-14. doi:10.1378/chest.15-0425

We compliment Drs Gillespie and DeCamp1 on their insightful thoughts on the topic of small- vs large-bore catheters for the management of malignant pleural effusions. Although their criticism of the existing literature in support of small-bore catheters is fair, there has been no mention of citations supporting large-bore catheters. Assuming no difference in benefit between catheter sizes, which would we choose as a patient if both are equally effective? Our personal opinion would be the smaller catheter, which requires the smallest incision and is functional. Although there are no large, prospective, head-to-head comparative studies, there are data from large prospective trials using small-bore catheters for chemical pleurodesis (including talc).2,3 In one prospective study using 12F catheters, 52 patients had talc pleurodesis with no reports of failure of the procedure due to catheter occlusion.3 Additionally, Drs Gillespie and DeCamp1 make a distinction saying that tunneled pleural catheters should be considered large bore because most of the literature defines small bore as ≤ 14F. Although this may be true, it does not get to the intent of the differentiation between large and small, and we would argue that the 0.48-mm difference in the diameter between a 14F and 15.5F catheter is clinically irrelevant.

Chest. 2015;148(1):14-15. doi:10.1378/chest.15-0427

We appreciate the comments and arguments put forth by our colleagues Drs Lee and Feller-Kopman1 from Johns Hopkins University and agree whole heartedly with their emphasis on the palliative goals in treating malignant pleural effusion (MPE). Where we continue to disagree is how best to achieve this. Much of the data they present actually supports our contention that MPEs represent a heterogeneous problem with multiple viable management options and, in the absence of lung entrapment, no gold standard for treatment.

Commentary: Ahead of the Curve

Chest. 2015;148(1):16-23. doi:10.1378/chest.15-0296

Despite massive investments in the development of novel treatments for heterogeneous diseases such as COPD, the resources spent have only benefited a fraction of the population treated. Personalized health care to guide selection of a suitable patient population already in the clinical development of new compounds could offer a solution. This review discusses past successes and failures in drug development and biomarker research in COPD, describes research in COPD phenotypes and the required characteristics of a suitable biomarker for identifying patients at higher risk of progression, and examines the role of extracellular matrix proteins found to be upregulated in COPD. Novel biomarkers of connective tissue remodeling that may provide added value for a personalized approach by detecting subgroups of patients with active disease suitable for pharmacologic intervention are discussed.

Evidence-Based Medicine

Chest. 2015;148(1):24-31. doi:10.1378/chest.15-0423

BACKGROUND:  We conducted a systematic review on the management of psychogenic cough, habit cough, and tic cough to update the recommendations and suggestions of the 2006 guideline on this topic.

METHODS:  We followed the American College of Chest Physicians (CHEST) methodologic guidelines and the Grading of Recommendations, Assessment, Development, and Evaluation framework. The Expert Cough Panel based their recommendations on data from the systematic review, patients’ values and preferences, and the clinical context. Final grading was reached by consensus according to Delphi methodology.

RESULTS:  The results of the systematic review revealed only low-quality evidence to support how to define or diagnose psychogenic or habit cough with no validated diagnostic criteria. With respect to treatment, low-quality evidence allowed the committee to only suggest therapy for children believed to have psychogenic cough. Such therapy might consist of nonpharmacologic trials of hypnosis or suggestion therapy, or combinations of reassurance, counseling, and referral to a psychologist, psychotherapy, and appropriate psychotropic medications. Based on multiple resources and contemporary psychologic, psychiatric, and neurologic criteria (Diagnostic and Statistical Manual of Mental Disorders, 5th edition and tic disorder guidelines), the committee suggests that the terms psychogenic and habit cough are out of date and inaccurate.

CONCLUSIONS:  Compared with the 2006 CHEST Cough Guidelines, the major change in suggestions is that the terms psychogenic and habit cough be abandoned in favor of somatic cough syndrome and tic cough, respectively, even though the evidence to do so at this time is of low quality.

Topics: cough , habits
Chest. 2015;148(1):32-54. doi:10.1378/chest.15-0164

BACKGROUND:  Successful management of chronic cough has varied in the primary research studies in the reported literature. One of the potential reasons relates to a lack of intervention fidelity to the core elements of the diagnostic and/or therapeutic interventions that were meant to be used by the investigators.

METHODS:  We conducted a systematic review to summarize the evidence supporting intervention fidelity as an important methodologic consideration in assessing the effectiveness of clinical practice guidelines used for the diagnosis and management of chronic cough. We developed and used a tool to assess for five areas of intervention fidelity. Medline (PubMed), Scopus, and the Cochrane Database of Systematic Reviews were searched from January 1998 to May 2014. Guideline recommendations and suggestions for those conducting research using guidelines or protocols to diagnose and manage chronic cough in the adult were developed and voted upon using CHEST Organization methodology.

RESULTS:  A total of 23 studies (17 uncontrolled prospective observational, two randomized controlled, and four retrospective observational) met our inclusion criteria. These articles included 3,636 patients. Data could not be pooled for meta-analysis because of heterogeneity. Findings related to the five areas of intervention fidelity included three areas primarily related to the provider and two primarily related to the patients. In the area of study design, 11 of 23 studies appeared to be underpinned by a single guideline/protocol; for training of providers, two of 23 studies reported training, and zero of 23 reported the use of an intervention manual; and for the area of delivery of treatment, when assessing the treatment of gastroesophageal reflux disease, three of 23 studies appeared consistent with the most recent guideline/protocol referenced by the authors. For receipt of treatment, zero of 23 studies mentioned measuring concordance of patient-interventionist understanding of the treatment recommended, and zero of 23 mentioned measuring enactment of treatment, with three of 23 measuring side effects and two of 23 measuring adherence. The overall average intervention fidelity score for all 23 studies was poor (20.74 out of 48).

CONCLUSIONS:  Only low-quality evidence supports that intervention fidelity strategies were used when conducting primary research in diagnosing and managing chronic cough in adults. This supports the contention that some of the variability in the reporting of patients with unexplained or unresolved chronic cough may be due to lack of intervention fidelity. By following the recommendations and suggestions in this article, researchers will likely be better able to incorporate strategies to address intervention fidelity, thereby strengthening the validity and generalizability of their results that provide the basis for the development of trustworthy guidelines.

Topics: cough, chronic , cough

Original Research: Antithrombotic Therapy

Chest. 2015;148(1):55-61. doi:10.1378/chest.14-1417

BACKGROUND:  Heparin-induced thrombocytopenia (HIT) is a serious complication of heparin utilization. An enzyme-linked immunosorbent assay (ELISA) is usually performed to assist in the diagnosis of HIT. ELISAs tend to be sensitive but lack specificity. We sought to use a new cutoff to define a positive HIT ELISA.

METHODS:  We conducted a prospective observational study of hospitalized patients undergoing ELISA testing. All patients who underwent ELISA testing were eligible for inclusion (n = 496). Irrespective of the results, all subjects had confirmatory testing with a serotonin release assay (SRA). We compared a threshold optical density (OD) > 1.00 to the current definition of a positive ELISA (OD > 0.40) as a screening test for a positive SRA. We used sensitivity, specificity, and area under the receiver operating curve to determine whether an OD > 1.00 would improve diagnostic accuracy for HIT.

RESULTS:  The SRA was positive in 10 patients (prevalence, 2.0%). Adjusting the definition of a positive HIT ELISA to > 1.00 maintained the sensitivity and negative predictive value at 100% in the cohort. The positive predictive value of the higher cutoff OD was more than triple the positive predictive value of an OD > 0.40 (41.7% vs 13.3%). No patient with a positive SRA had an OD measurement ≤ 1.00.

CONCLUSIONS:  Increasing the OD threshold enhances specificity without noticeably compromising sensitivity. Altering the definition of the HIT ELISA could prevent unnecessary testing and/or treatment with non-heparin-based anticoagulants in patients with possible HIT.

TRIAL REGISTRY:  ClinicalTrials.gov; No.: NCT00946400; URL: www.clinicaltrials.gov

Chest. 2015;148(1):62-72. doi:10.1378/chest.14-2018

BACKGROUND:  Much of the clinical epidemiology and treatment patterns for patients with atrial fibrillation (AF) are derived from Western populations. Limited data are available on antithrombotic therapy use over time and its impact on the stroke or bleeding events in newly diagnosed Chinese patients with AF. The present study investigates time trends in warfarin and aspirin use in China in relation to stroke and bleeding events in a Chinese population.

METHODS:  We used a medical insurance database involving > 10 million individuals for the years 2001 to 2012 in Yunnan, a southwestern province of China, and performed time-trend analysis on those with newly diagnosed AF. Cox proportional hazards time-varying exposures were used to determine the risk of stroke or bleeding events associated with antithrombotic therapy among patients with AF.

RESULTS:  Among the randomly sampled 471,446 participants, there were 1,237 patients with AF, including 921 newly diagnosed with AF, thus providing 4,859 person-years of experience (62% men; mean attained age, 70 years). The overall rate of antithrombotic therapy was 37.7% (347 of 921 patients), with 4.1% (38 of 921) on warfarin and 32.3% (298 of 921) on aspirin. Antithrombotic therapy was not related to stroke/bleeding risk scores (CHADS2 [congestive heart failure, hypertension, age ≥ 75 years, diabetes, stroke (doubled)] score, P = .522; CHA2DS2-VASc [congestive heart failure, hypertension, age ≥ 75 years (doubled), diabetes mellitus, stroke or transient ischemic attack (doubled), vascular disease, age 65 to 74 years, and female sex] score, P = .957; HAS-BLED [hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, labile international normalized ratio, elderly (> 65 years), drugs/alcohol concomitantly] score, P = .095). The use of antithrombotic drugs (mainly aspirin) increased in both women and men over time, with the rate of aspirin increasing from 4.0% in 2007 to 46.1% in 2012 in the former, and from 7.7% in 2007 to 61.9% in 2012 in the latter (P for trend for both, < .005). In the overall cohort, the annual stroke rate was approximately 6% and the annual major bleeding rate was about 1%. Compared with nonantithrombotic therapy, the hazard ratio for ischemic stroke was 0.68 (95% CI, 0.39-1.18) for aspirin and 1.39 (0.54-3.59) for warfarin.

CONCLUSIONS:  Aspirin use increased among Chinese patients newly diagnosed with AF, with no relationship to the patient’s stroke or bleeding risk. Warfarin use was very low. Given the health-care burden of AF and its complications, our study has major implications for health-care systems in non-Western countries, given the global burden of this common arrhythmia.

Original Research: Critical Care Medicine

Chest. 2015;148(1):73-78. doi:10.1378/chest.14-2843

BACKGROUND:  Recent recommendations for lung protective mechanical ventilation include a tidal volume target of 6 mL/kg predicted body weight (PBW). Different PBW equations might introduce important differences in tidal volumes delivered to research subjects and patients.

METHODS:  PBW equations use height, age, and sex as input variables. We compared National Institutes of Health (NIH) ARDS Network (ARDSNet), actuarial table (ACTUARIAL), and Stewart (STEWART) PBW equations used in clinical trials, across physiologic ranges for age and height. We used three-dimensional and two-dimensional surface analysis to compare these PBW equations. We then used age and height from actual clinical trial subjects to quantify PBW equation differences.

RESULTS:  Significant potential differences existed between these PBW predictions. The ACTUARIAL and ARDSNet surfaces for women were the only surfaces that intersected and produced both positive and negative differences. Mathematical differences between PBW equations at limits of height and age exceeded 30% in women and 24% in men for ACTUARIAL vs ARDSNet and about 25% for women and 15% for men for STEWART vs ARDSNet. The largest mathematical differences were present in older, shorter subjects, especially women. Actual differences for clinical trial subjects were as high as 15% for men and 24% for women.

CONCLUSIONS:  Significant differences between PBW equations for both men and women could be important sources of interstudy variation. Studies should adopt a standard PBW equation. We recommend using the NIH National Heart, Lung, and Blood Institute ARDS Network PBW equation because it is associated with the clinical trial that identified 6 mL/kg PBW as an appropriate target.

Chest. 2015;148(1):79-92. doi:10.1378/chest.14-2195

OBJECTIVE:  The purpose of this study was to systematically review the research on volume and outcome relationships in critical care.

METHODS:  From January 1, 2001, to April 30, 2014, MEDLINE and EMBASE were searched for studies assessing the relationship between admission volume and clinical outcomes in critical illness. Bibliographies were reviewed to identify other articles of interest, and experts were contacted about missing or unpublished studies. Of 127 studies reviewed, 46 met inclusion criteria, covering seven clinical conditions. Two investigators independently reviewed each article using a standardized form to abstract information on key study characteristics and results.

RESULTS:  Overall, 29 of the studies (63%) reported a statistically significant association between higher admission volume and improved outcomes. The magnitude of the association (mortality OR between the lowest vs highest stratum of volume centers), as well as the thresholds used to characterize high volume, varied across clinical conditions. Critically ill patients with cardiovascular (n = 7, OR = 1.49 [1.11-2.00]), respiratory (n = 12, OR = 1.20 [1.04-1.38]), severe sepsis (n = 4, OR = 1.17 [1.03-1.33]), hepato-GI (n = 3, OR = 1.30 [1.08-1.78]), neurologic (n = 3, OR = 1.38 [1.22-1.57]), and postoperative admission diagnoses (n = 3, OR = 2.95 [1.05-8.30]) were more likely to benefit from admission to higher-volume centers compared with lower-volume centers. Studies that controlled for ICU or hospital organizational factors were less likely to find a significant volume-outcome relationship than studies that did not control for these factors.

CONCLUSIONS:  Critically ill patients generally benefit from care in high-volume centers, with more substantial benefits in selected high-risk conditions. This relationship may in part be mediated by specific ICU and hospital organizational factors.

Chest. 2015;148(1):93-102. doi:10.1378/chest.14-2259

BACKGROUND:  In vitro studies suggested that circulating inflammatory cytokines cause septic myocardial dysfunction. However, no in vivo clinical study has investigated whether serum inflammatory cytokine concentrations correlate with septic myocardial dysfunction.

METHODS:  Repeated echocardiograms and concurrent serum inflammatory cytokines (IL-1β, IL-6, IL-8, IL-10, IL-18, tumor necrosis factor-α, and monocyte chemoattractant protein-1) and cardiac biomarkers (high-sensitivity [hs] troponin-T and N-terminal pro-B-type natriuretic peptide [NT-proBNP]) were examined in 105 patients with severe sepsis and septic shock. Cytokines and biomarkers were tested for correlations with systolic and diastolic dysfunction, sepsis severity, and mortality.

RESULTS:  Systolic dysfunction defined as reduced left ventricular ejection fraction (LVEF) < 50% or < 55% and diastolic dysfunction defined as e′-wave < 8 cm/s on tissue-Doppler imaging (TDI) or E/e′-ratio were found in 13 (12%), 24 (23%), 53 (50%), and 26 (25%) patients, respectively. Forty-four patients (42%) died in-hospital. All cytokines, except IL-1, correlated with Sequential Organ Failure Assessment and APACHE (Acute Physiology and Chronic Health Evaluation) II scores, and all cytokines predicted mortality. IL-10 and IL-18 independently predicted mortality among cytokines (OR = 3.1 and 28.3, P = .006 and < 0.0001). However, none of the cytokines correlated with LVEF, end-diastolic volume index (EDVI), stroke-volume index (SVI), or s′-wave and e′-wave velocities on TDI (Pearson linear and Spearman rank [ρ] nonlinear correlations). Similarly, no differences were found in cytokine concentrations between patients dichotomized to high vs low LVEF, EDVI, SVI, s′-wave, or e′-wave (Mann-Whitney U tests). In contrast, NT-proBNP strongly correlated with both reduced LVEF and reduced e′-wave velocity, and hs-troponin-T correlated mainly with reduced e′-wave.

CONCLUSIONS:  Unlike cardiac biomarkers, none of the measured inflammatory cytokines correlates with systolic or diastolic myocardial dysfunction in severe sepsis or septic shock.

Original Research: Chest Infections

Chest. 2015;148(1):103-111. doi:10.1378/chest.14-2129

BACKGROUND:  Hospital readmissions for pneumonia occur often and are difficult to predict. For fiscal year 2013, the Centers for Medicare & Medicaid Services readmission penalties have been applied to acute myocardial infarction, heart failure, and pneumonia. However, the overall impact of pneumonia pathogen characterization on hospital readmission is undefined.

METHODS:  This was a retrospective 6-year cohort study (August 2007 to September 2013).

RESULTS:  We evaluated 9,624 patients with a discharge diagnosis of pneumonia. Among these patients, 4,432 (46.1%) were classified as having culture-negative pneumonia, 1,940 (20.2%) as having pneumonia caused by antibiotic-susceptible bacteria, 2,991 (31.1%) as having pneumonia caused by potentially antibiotic-resistant bacteria, and 261 (2.7%) as having viral pneumonia. The 90-day hospital readmission rate for survivors (n = 7,637, 79.4%) was greatest for patients with pneumonia attributed to potentially antibiotic-resistant bacteria (11.4%) followed by viral pneumonia (8.3%), pneumonia attributed to antibiotic-susceptible bacteria (6.6%), and culture-negative pneumonia (5.8%) (P < .001). Multiple logistic regression analysis identified pneumonia attributed to potentially antibiotic-resistant bacteria to be independently associated with 90-day readmission (OR, 1.75; 95% CI, 1.56-1.97; P < .001). Other independent predictors of 90-day readmission were Charlson comorbidity score > 4, cirrhosis, and chronic kidney disease. Culture-negative pneumonia was independently associated with lower risk for 90-day readmission.

CONCLUSIONS:  Readmission after hospitalization for pneumonia is relatively common and is related to pneumonia pathogen characterization. Pneumonia attributed to potentially antibiotic-resistant bacteria is associated with an increased risk for 90-day readmission, whereas culture-negative pneumonia is associated with lower risk for 90-day readmission.

Original Research: Tobacco Cessation and Prevention

Chest. 2015;148(1):112-119. doi:10.1378/chest.14-2045

BACKGROUND:  The relative risk for cardiovascular diseases in passive smokers is similar to that of active smokers despite almost a 100-fold lower dose of inhaled cigarette smoke. However, the mechanisms underlying the surprising susceptibility of the vascular tissue to the toxins in secondhand smoke (SHS) have not been directly investigated. The aim of this study was to investigate directly vascular endothelial cell function in passive smokers.

METHODS:  Using a minimally invasive method of endothelial biopsy, we investigated directly the vascular endothelium in 23 healthy passive smokers, 25 healthy active smokers, and 23 healthy control subjects who had never smoked and had no regular exposure to SHS. Endothelial nitric oxide synthase (eNOS) function (expression of basal eNOS and activated eNOS [phosphorylated eNOS at serine1177 (P-eNOS)]) and expression of markers of inflammation (nuclear factor-κB [NF-κB]) and oxidative stress (nitrotyrosine) were assessed in freshly harvested venous endothelial cells by quantitative immunofluorescence.

RESULTS:  Expression of eNOS and P-eNOS was similarly reduced and expression of NF-κB was similarly increased in passive and active smokers compared with control subjects. Expression of nitrotyrosine was greater in active smokers than control subjects and similar in passive and active smokers. Brachial artery flow-mediated dilation was similarly reduced in passive and active smokers compared with control subjects, consistent with reduced endothelial NO bioavailability.

CONCLUSIONS:  Secondhand smoking increases vascular endothelial inflammation and reduces active eNOS to a similar extent as active cigarette smoking, indicating direct toxic effects of SHS on the vasculature.

Original Research: Sleep Disorders

Chest. 2015;148(1):120-127. doi:10.1378/chest.14-3207

BACKGROUND:  Approximately 8% of the world population resides above 1,600 m, with about 10 million people living above 2,500 m in Colombia. However, reference values for polysomnography (PSG) and oxygen saturation (Spo2) of children < 2 years old residing at high altitude are currently unavailable.

METHODS:  Healthy infants aged 1 to 18 months born and residing at high altitude (Bogotá: 2,640 m) underwent overnight PSG. Four age groups were defined: group 1, < 45 days; group 2, 3 to 4 months; group 3, 6 to 7 months; and group 4, 10 to 18 months. Of 122 children enrolled, 50 had three consecutive PSG tests and were analyzed as a longitudinal subcohort.

RESULTS:  A total of 281 PSG tests were performed in 122 infants (56% girls): group 1, 106 PSG tests; group 2, 89 PSG tests; group 3, 61 PSG tests; and group 4, 25 PSG tests. Active sleep diminished and quiet sleep increased with maturation. Apnea-hypopnea indexes (total, central, and obstructive) were highest in group 1 (21.4, 12.4, and 6.8/h total sleep time, respectively) and diminished with age (P < .001). Mean Spo2 during waking and sleep increased with age (P < .001). Nadir Spo2 values during respiratory events were lower in younger infants. Longitudinal assessments of 50 infants confirmed the temporal trends described for the cross-sectional dataset.

CONCLUSIONS:  Healthy infants (≤ 18 months old) born and residing at high altitude show preserved sleep architecture but higher apnea-hypopnea indexes and more prominent desaturation with respiratory events than do those living at low altitude. The current study findings can be used as reference values for infants at high altitude.

Original Research: COPD

Chest. 2015;148(1):128-137. doi:10.1378/chest.14-1466

BACKGROUND:  Low levels of physical activity (PA) are associated with poor outcomes in people with COPD. Interventions to increase PA could improve outcomes.

METHODS:  We tested the efficacy of a novel Internet-mediated, pedometer-based exercise intervention. Veterans with COPD (N = 239) were randomized in a 2:1 ratio to the (1) intervention group (Omron HJ-720 ITC pedometer and Internet-mediated program) or (2) wait-list control group (pedometer). The primary outcome was health-related quality of life (HRQL), assessed by the St. George’s Respiratory Questionnaire (SGRQ), at 4 months. We examined the SGRQ total score (SGRQ-TS) and three domain scores: Symptoms, Activities, and Impact. The secondary outcome was daily step counts. Linear regression models assessed the effect of intervention on outcomes.

RESULTS:  Participants had a mean age of 67 ± 9 years, and 94% were men. There was no significant between-group difference in mean 4-month SGRQ-TS (2.3 units, P = .14). Nevertheless, a significantly greater proportion of intervention participants than control subjects had at least a 4-unit improvement in SGRQ-TS, the minimum clinically important difference (53% vs 39%, respectively, P = .05). For domain scores, the intervention group had a lower (reflecting better HRQL) mean than the control group by 4.6 units for Symptoms (P = .046) and by 3.3 units for Impact (P = .049). There was no significant difference in Activities score between the two groups. Compared with the control subjects, intervention participants walked 779 more steps per day at 4 months (P = .005).

CONCLUSIONS:  An Internet-mediated, pedometer-based walking program can improve domains of HRQL and daily step counts at 4 months in people with COPD.

TRIAL REGISTRY:  Clinical Trials.gov; No.: NCT01102777; URL: www.clinicaltrials.gov

Chest. 2015;148(1):138-150. doi:10.1378/chest.14-2434

BACKGROUND:  The morbidity and mortality associated with COPD exacts a considerable economic burden. Comorbidities in COPD are associated with poor health outcomes and increased costs. Our objective was to assess the impact of comorbidities on COPD-associated costs in a large administrative claims dataset.

METHODS:  This was a retrospective observational study of data from the Truven Health MarketScan Commercial Claims and Encounters and the MarketScan Medicare Supplemental Databases from January 1, 2009, to September 30, 2012. Resource consumption was measured from the index date (date of first occurrence of non-rule-out COPD diagnosis) to 360 days after the index date. Resource use (all-cause and disease-specific [ie, COPD- or asthma-related] ED visits, hospitalizations, office visits, other outpatient visits, and total length of hospital stay) and health-care costs (all-cause and disease-specific costs for ED visits, hospitalizations, office visits, and other outpatient visits and medical, prescription, and total health-care costs) were assessed. Generalized linear models were used to evaluate the impact of comorbidities on total health-care costs, adjusting for age, sex, geographic location, baseline health-care use, employment status, and index COPD medication.

RESULTS:  Among 183,681 patients with COPD, the most common comorbidities were cardiovascular disease (34.8%), diabetes (22.8%), asthma (14.7%), and anemia (14.2%). Most patients (52.8%) had one or two comorbidities of interest. The average all-cause total health-care costs from the index date to 360 days after the index date were highest for patients with chronic kidney disease ($41,288) and anemia ($38,870). The impact on total health-care costs was greatest for anemia ($10,762 more, on average, than a patient with COPD without anemia).

CONCLUSIONS:  Our analysis demonstrated that high resource use and costs were associated with COPD and multiple comorbidities.

Chest. 2015;148(1):151-158. doi:10.1378/chest.14-1814

BACKGROUND:  Understanding ethnic differences in health status (HS) could help in designing culturally appropriate interventions. We hypothesized that racial and ethnic differences exist in HS between non-Hispanic whites and Mexican Americans with obstructive lung disease (OLD) and that these differences are mediated by socioeconomic factors.

METHODS:  We analyzed 826 US adults aged ≥ 30 years self-identified as Mexican American or non-Hispanic white with spirometry-confirmed OLD (FEV1/FVC < 0.7) who participated in the National Health and Nutrition Examination Survey 2007-2010. We assessed associations between Mexican American ethnicity and self-reported HS using logistic regression models adjusted for demographics, smoking status, number of comorbidities, limitations for work, and lung function and tested the contribution of education and health-care access to ethnic differences in HS.

RESULTS:  Among Mexican Americans with OLD, worse (fair or poor) HS was more prevalent than among non-Hispanic whites (weighted percentage [SE], 46.6% [5.0] vs 15.2% [1.6]; P < .001). In bivariate analysis, socioeconomic characteristics were associated with lower odds of reporting poor HS (high school graduation: OR, 0.24 [95% CI, 0.10-0.40]; access to health care: OR, 0.50 [95% CI, 0.30-0.80]). In fully adjusted models, a strong association was found between Mexican American ethnicity (vs non-Hispanic white) and fair or poor HS (OR, 7.52; 95% CI, 4.43-12.78; P < .001). Higher education and access to health care contributed to lowering the Mexican American ethnicity odds of fair or poor HS by 47% and 16%, respectively, and together, they contributed 55% to reducing the differences in HS with non-Hispanic whites.

CONCLUSIONS:  Mexican Americans with OLD report poorer overall HS than non-Hispanic whites, and education and access to health care are large contributors to the difference.

Chest. 2015;148(1):159-168. doi:10.1378/chest.14-2449

OBJECTIVE:  The modified Medical Research Council (mMRC) dyspnea, the COPD Assessment Test (CAT), and the Clinical COPD Questionnaire (CCQ) have been interchangeably proposed by GOLD (Global Initiative for Chronic Obstructive Lung Disease) for assessing symptoms in patients with COPD. However, there are no data on the prognostic value of these tools in terms of mortality. We endeavored to evaluate the prognostic value of the CAT and CCQ scores and compare them with mMRC dyspnea.

METHODS:  We analyzed the ability of these tests to predict mortality in an observational cohort of 768 patients with COPD (82% men; FEV1, 60%) from the COPD History Assessment in Spain (CHAIN) study, a multicenter observational Spanish cohort, who were monitored annually for a mean follow-up time of 38 months.

RESULTS:  Subjects who died (n = 73; 9.5%) had higher CAT (14 vs 11, P = .022), CCQ (1.6 vs 1.3, P = .033), and mMRC dyspnea scores (2 vs 1, P < .001) than survivors. Receiver operating characteristic analysis showed that higher CAT, CCQ, and mMRC dyspnea scores were associated with higher mortality (area under the curve: 0.589, 0.588, and 0.649, respectively). CAT scores ≥ 17 and CCQ scores > 2.5 provided a similar sensitivity than mMRC dyspnea scores ≥ 2 to predict all-cause mortality.

CONCLUSIONS:  The CAT and the CCQ have similar ability for predicting all-cause mortality in patients with COPD, but were inferior to mMRC dyspnea scores. We suggest new thresholds for CAT and CCQ scores based on mortality risk that could be useful for the new GOLD grading classification.

TRIAL REGISTRY:  ClinicalTrials.gov; No.: NCT01122758; URL: www.clinicaltrials.gov

Chest. 2015;148(1):169-175. doi:10.1378/chest.14-2150

BACKGROUND:  COPD is a chronic inflammatory disorder associated with oxidative stress. Serum bilirubin has potent antioxidant actions, and higher concentrations have been shown to protect against oxidative stress. The relation between serum bilirubin and COPD progression is unknown.

METHODS:  Serum bilirubin was measured in 4,680 smokers aged 35 to 60 years old with mild to moderate airflow limitation. The relationship of serum bilirubin to postbronchodilator FEV1 and rate of FEV1 decline over 3 to 9 years was determined using regression modeling. Total and disease-specific mortality were also ascertained.

RESULTS:  Serum bilirubin was positively related to FEV1 (P < .001). Serum bilirubin was also negatively related to the annual decline in FEV1 when adjusted for baseline demographics, pack-years smoked, and baseline measures of lung function (P = .01). Additionally, serum bilirubin was negatively associated with risk of death from coronary heart disease (P = .03); however, the relationships between bilirubin and other mortality end points were not statistically significant (P > .05).

CONCLUSIONS:  Bilirubin is inversely related to COPD disease severity and progression. Higher serum bilirubin concentration was associated with a higher FEV1 and less annual decline in FEV1. Bilirubin was also associated with less coronary heart disease mortality. These data support the hypothesis that bilirubin has a protective effect on COPD disease progression, possibly through its antioxidant actions. Bilirubin may prove useful as an easily accessible and readily available blood-based COPD biomarker.

Chest. 2015;148(1):176-184. doi:10.1378/chest.14-1556

BACKGROUND:  COPD has traditionally been defined by the presence of irreversible airflow limitation on spirometry using either the GOLD (Global Initiative for Chronic Obstructive Lung Disease) or American Thoracic Society/European Respiratory Society criteria (lower limit of normal [LLN]). We have observed that some patients with clinical COPD and emphysema on chest CT scan have no obstruction on spirometry. The purpose of this study was to assess the prevalence of obstruction by GOLD and LLN criteria in patients with emphysema on CT scan and determine which radiographic criteria were associated with a clinical diagnosis of COPD.

METHODS:  We retrospectively analyzed the clinical records and spirometry of all patients who had radiographically defined emphysema on chest CT scans completed at the University of Vermont in 2011. We compared spirometric criteria and CT scan factors with the presence of clinical COPD based on chart review.

RESULTS:  We identified 274 patients with CT scan-defined emphysema. GOLD criteria detected obstruction in 228 patients (83%), and LLN detected obstruction in 206 patients (75%). However, GOLD failed to correctly identify 19 patients (6.9%) and LLN failed to identify 38 patients (13.9%) (average 10.4%) who had radiographic emphysema and a clinical diagnosis of COPD. Obese patients had a lower prevalence of obstruction whether classified by LLN or GOLD. Among patients with spirometric obstruction, there were greater degrees of emphysema and more severely increased airway wall thickness. Factors that were independently associated with clinical COPD were lower FVC % predicted, lower FEV1/FVC ratio, and increasing airway wall thickness.

CONCLUSIONS:  Spirometry missed 10.4% of patients with clinical COPD who have significant emphysema on chest CT scan.

Chest. 2015;148(1):185-195. doi:10.1378/chest.14-2380

BACKGROUND:  Lung volume reduction (LVR) techniques improve lung function in selected patients with emphysema, but the impact of LVR procedures on the asynchronous movement of different chest wall compartments, which is a feature of emphysema, is not known.

METHODS:  We used optoelectronic plethysmography to assess the effect of surgical and bronchoscopic LVR on chest wall asynchrony. Twenty-six patients were assessed before and 3 months after LVR (surgical [n = 9] or bronchoscopic [n = 7]) or a sham/unsuccessful bronchoscopic treatment (control subjects, n = 10). Chest wall volumes were divided into six compartments (left and right of each of pulmonary ribcage [Vrc,p], abdominal ribcage [Vrc,a], and abdomen [Vab]) and phase shift angles (θ) calculated for the asynchrony between Vrc,p and Vrc,a (θRC), and between Vrc,a and Vab (θDIA).

RESULTS:  Participants had an FEV1 of 34.6 ± 18% predicted and a residual volume of 217.8 ± 46.0% predicted with significant chest wall asynchrony during quiet breathing at baseline (θRC, 31.3° ± 38.4°; and θDIA, −38.7° ± 36.3°). Between-group difference in the change in θRC and θDIA during quiet breathing following treatment was 44.3° (95% CI, −78 to −10.6; P = .003) and 34.5° (95% CI, 1.4 to 67.5; P = .007) toward 0° (representing perfect synchrony), respectively, favoring the LVR group. Changes in θRC and θDIA were statistically significant on the treated but not the untreated sides.

CONCLUSIONS:  Successful LVR significantly reduces chest wall asynchrony in patients with emphysema.

Original Research: Diffuse Lung Disease

Chest. 2015;148(1):196-201. doi:10.1378/chest.14-2817

BACKGROUND:  FVC outcomes in clinical trials on idiopathic pulmonary fibrosis (IPF) can be substantially influenced by the analytic methodology and the handling of missing data. We conducted a series of sensitivity analyses to assess the robustness of the statistical finding and the stability of the estimate of the magnitude of treatment effect on the primary end point of FVC change in a phase 3 trial evaluating pirfenidone in adults with IPF.

METHODS:  Source data included all 555 study participants randomized to treatment with pirfenidone or placebo in the Assessment of Pirfenidone to Confirm Efficacy and Safety in Idiopathic Pulmonary Fibrosis (ASCEND) study. Sensitivity analyses were conducted to assess whether alternative statistical tests and methods for handling missing data influenced the observed magnitude of treatment effect on the primary end point of change from baseline to week 52 in FVC.

RESULTS:  The distribution of FVC change at week 52 was systematically different between the two treatment groups and favored pirfenidone in each analysis. The method used to impute missing data due to death had a marked effect on the magnitude of change in FVC in both treatment groups; however, the magnitude of treatment benefit was generally consistent on a relative basis, with an approximate 50% reduction in FVC decline observed in the pirfenidone group in each analysis.

CONCLUSIONS:  Our results confirm the robustness of the statistical finding on the primary end point of change in FVC in the ASCEND trial and corroborate the estimated magnitude of the pirfenidone treatment effect in patients with IPF.

TRIAL REGISTRY:  ClinicalTrials.gov; No.: NCT01366209; URL: www.clinicaltrials.gov

Original Research: Pulmonary Vascular Disease

Chest. 2015;148(1):202-210. doi:10.1378/chest.14-2608

BACKGROUND:  Lung ultrasonography (LUS) has emerged as a noninvasive tool for the differential diagnosis of pulmonary diseases. However, its use for the diagnosis of acute decompensated heart failure (ADHF) still raises some concerns. We tested the hypothesis that an integrated approach implementing LUS with clinical assessment would have higher diagnostic accuracy than a standard workup in differentiating ADHF from noncardiogenic dyspnea in the ED.

METHODS:  We conducted a multicenter, prospective cohort study in seven Italian EDs. For patients presenting with acute dyspnea, the emergency physician was asked to categorize the diagnosis as ADHF or noncardiogenic dyspnea after (1) the initial clinical assessment and (2) after performing LUS (“LUS-implemented” diagnosis). All patients also underwent chest radiography. After discharge, the cause of each patient’s dyspnea was determined by independent review of the entire medical record. The diagnostic accuracy of the different approaches was then compared.

RESULTS:  The study enrolled 1,005 patients. The LUS-implemented approach had a significantly higher accuracy (sensitivity, 97% [95% CI, 95%-98.3%]; specificity, 97.4% [95% CI, 95.7%-98.6%]) in differentiating ADHF from noncardiac causes of acute dyspnea than the initial clinical workup (sensitivity, 85.3% [95% CI, 81.8%-88.4%]; specificity, 90% [95% CI, 87.2%-92.4%]), chest radiography alone (sensitivity, 69.5% [95% CI, 65.1%-73.7%]; specificity, 82.1% [95% CI, 78.6%-85.2%]), and natriuretic peptides (sensitivity, 85% [95% CI, 80.3%-89%]; specificity, 61.7% [95% CI, 54.6%-68.3%]; n = 486). Net reclassification index of the LUS-implemented approach compared with standard workup was 19.1%.

CONCLUSIONS:  The implementation of LUS with the clinical evaluation may improve accuracy of ADHF diagnosis in patients presenting to the ED.

TRIAL REGISTRY:  Clinicaltrials.gov; No.: NCT01287429; URL: www.clinicaltrials.gov

Chest. 2015;148(1):211-218. doi:10.1378/chest.14-2551

BACKGROUND:  For patients with acute symptomatic pulmonary embolism (PE), the Bova score classifies their risk for PE-related complications within 30 days after diagnosis. The original Bova score was derived from 2,874 normotensive patients with acute PE who participated in one of six prospective PE studies.

METHODS:  We retrospectively assessed the validity of the Bova risk model in normotensive patients with acute PE diagnosed in an academic urban ED. Two clinician investigators used baseline data for the model’s four prognostic variables to stratify patients into the three Bova risk stages (I-III) for 30-day PE-related complications. Intraclass correlation coefficient (ICC) and the κ statistic were used to assess interrater variability.

RESULTS:  The Bova risk score classified the majority of the cohort of 1,083 patients into the lowest Bova risk stage (stage I, 80%; stage II, 15%; stage III, 5%), The primary end point occurred in 91 of the 1,083 patients (8.4%; 95% CI, 6.7%-10%) during the 30 days after PE diagnosis. Risk stage correlated with the PE-related complication rate (class I, 4.4%; class II, 18%; class III, 42%; ICC, 0.93 [95% CI, 0.92-0.94]; κ statistic, 0.80; P < .001), in-hospital complication rate (class I, 3.7%; class II, 15%; class III, 37%), and 30-day PE-related mortality (class I, 3.1%; class II, 6.8%; class III, 10.5%).

CONCLUSIONS:  The Bova risk score accurately stratifies normotensive patients with acute PE into stages of increasing risk of PE-related complications that occur within 30 days of PE diagnosis.

Chest. 2015;148(1):219-225. doi:10.1378/chest.14-1992

BACKGROUND:  The hypoxic ventilatory response (HVR) at sea level (SL) is moderately predictive of the change in pulmonary artery systolic pressure (PASP) to acute normobaric hypoxia. However, because of progressive changes in the chemoreflex control of breathing and acid-base balance at high altitude (HA), HVR at SL may not predict PASP at HA. We hypothesized that resting oxygen saturation as measured by pulse oximetry (Spo2) at HA would correlate better than HVR at SL with PASP at HA.

METHODS:  In 20 participants at SL, we measured normobaric, isocapnic HVR (L/min · −%Spo2−1) and resting PASP using echocardiography. Both resting Spo2 and PASP measures were repeated on day 2 (n = 10), days 4 to 8 (n = 12), and 2 to 3 weeks (n = 8) after arrival at 5,050 m. These data were also collected at 5,050 m in life-long HA residents (ie, Sherpa [n = 21]).

RESULTS:  Compared with SL, Spo2 decreased from 98.6% to 80.5% (P < .001), whereas PASP increased from 21.7 to 34.0 mm Hg (P < .001) after 2 to 3 weeks at 5,050 m. Isocapnic HVR at SL was not related to Spo2 or PASP at any time point at 5,050 m (all P > .05). Sherpa had lower PASP (P < .01) than lowlanders on days 4 to 8 despite similar Spo2. Upon correction for hematocrit, Sherpa PASP was not different from lowlanders at SL but was lower than lowlanders at all HA time points. At 5,050 m, although Spo2 was not related to PASP in lowlanders at any point (all R2 ≤ 0.05, P > .50), there was a weak relationship in the Sherpa (R2 = 0.16, P = .07).

CONCLUSIONS:  We conclude that neither HVR at SL nor resting Spo2 at HA correlates with elevations in PASP at HA.

Chest. 2015;148(1):226-234. doi:10.1378/chest.14-2065

BACKGROUND:  Pulmonary hypertension, which is related to right ventricular (RV) failure, indicates a poor prognosis in heart failure (HF). Increased ventilatory response and exercise oscillatory ventilation (EOV) also have a negative impact. We hypothesized that the severity classification of HF and risk prediction could be improved by combining functional capacity with cardiopulmonary exercise testing (CPET) and RV-pulmonary circulation coupling, as evaluated by the tricuspid annular plane systolic excursion (TAPSE)-pulmonary artery systolic pressure (PASP) relationship.

METHODS:  Four hundred fifty-nine patients with HF were assessed with Doppler echocardiography and CPET and were tracked for outcome. The subjects were followed for major cardiac events (cardiac mortality, left ventricular assist device implant, or heart transplant). Cox regression and Kaplan-Meier analyses were performed with TAPSE and PASP as individual measures that were then combined into a ratio form.

RESULTS:  The TAPSE/PASP ratio (TAPSE/PASP) was the strongest predictor, whereas the New York Heart Association classification and EOV added predictive value. A four-quadrant group prediction risk was created based on TAPSE (< 16 mm or ≥ 16 mm) vs PASP (< 40 mm Hg or ≥ 40 mm Hg) thresholds and the CPET variables distribution as follows: group A (TAPSE > 16 mm and PASP < 40 mm Hg) presented the lowest risk (hazard ratio, 0.17) and best ventilation; group B exhibited a low risk (hazard ratio, 0.88) with depressed TAPSE (< 16 mm) and normal PASP, a preserved peak oxygen consumption (V. o2), but high ventilation. Group C had an increased risk (hazard ratio, 1.3; TAPSE ≥ 16 mm, PASP ≥ 40 mm Hg), a reduced peak V. o2, and a high EOV prevalence. Group D had the highest risk (hazard ratio, 5.6), the worse RV-pulmonary pressure coupling (TAPSE < 16 and PASP ≥ 40 mm Hg), the lowest peak V. o2, and the highest EOV rate.

CONCLUSIONS:  TAPSE/PASP, combined with exercise ventilation, provides relevant clinical and prognostic insights into HF. A low TAPSE/PASP with EOV identifies patients at a particularly high risk of cardiac events.

Original Research: Disorders of the Pleura

Chest. 2015;148(1):235-241. doi:10.1378/chest.14-2199

OBJECTIVE:  Malignant pleural effusion (MPE) incidence is increasing, and prognosis remains poor. Indwelling pleural catheters (IPCs) relieve symptoms but increase the risk of pleural infection. We reviewed cases of pleural infection in patients with IPCs for MPE from six UK centers between January 1, 2005, and January 31, 2014.

METHODS:  Survival in patients with pleural infection was compared with 788 patients with MPE (known as the LENT [pleural fluid lactate dehydrogenase, Eastern Cooperative Oncology Group performance status, serum neutrophil to lymphocyte ratio, and tumor type] cohort) and with national statistics.

RESULTS:  Of 672 IPCs inserted, 25 (3.7%) became infected. Most patients (20 of 25) had mesothelioma or lung cancer. Median survival in the pleural infection cohort appeared longer than in the LENT cohort, although this result did not achieve significance (386 days vs 132 days; hazard ratio, 0.67; P = .07). Median survival with mesothelioma and pleural infection was twice as long as national estimates for mesothelioma survival (753 days vs < 365 days) and double the median survival of patients with mesothelioma in the LENT cohort (339 days; 95% CI, nonoverlapping). Survival with lung and breast cancer did not differ significantly between the groups. Sixty-one percent of patients experienced early infection. There was no survival difference between patients with early and late infection (P = .6).

CONCLUSIONS:  This small series of patients with IPCs for MPE suggests pleural infection may be associated with longer survival, particularly in patients with mesothelioma. Results did not achieve significance, and a larger study is needed to explore this relationship further and investigate whether the local immune response, triggered by infection, is able to modulate mesothelioma progression.

Recent Advances in Chest Medicine

Chest. 2015;148(1):242-252. doi:10.1378/chest.14-2475

Idiopathic pulmonary fibrosis (IPF) is strongly associated with advanced age. Making an accurate diagnosis of IPF is critical, as it remains only one of many potential diagnoses for an elderly patient with newly recognized interstitial lung disease. Optimal management of IPF, especially in older-aged patients, hinges on such factors as balancing the application of standard-of-care measures with the patient’s overall health status (robustness vs frailty) and considering the patient’s wishes, desires, and expectations. IPF is known to be associated with certain comorbidities that tend to be more prevalent in the elderly population. Until recently, options for the pharmacologic management of IPF were limited and included therapies such as immunosuppressive agents, which may pose substantial risk to the elderly patient. However, the antifibrotic agents pirfenidone and nintedanib have now become commercially available in the United States for the treatment of IPF. The monitoring and treatment of patients with IPF, especially elderly patients with comorbid medical conditions, require consideration of adverse side effects, the avoidance of potential drug-drug interactions, treatment of comorbidities, and the timely implementation of supportive and palliative measures. Individualized counseling to guide decision-making and enhance quality of life is also integral to optimal management of the elderly patient with IPF.

Contemporary Reviews in Critical Care Medicine

Chest. 2015;148(1):253-261. doi:10.1378/chest.14-2871

Traditionally, nasal oxygen therapy has been delivered at low flows through nasal cannulae. In recent years, nasal cannulae designed to administer heated and humidified air/oxygen mixtures at high flows (up to 60 L/min) have been gaining popularity. These high-flow nasal cannula (HFNC) systems enhance patient comfort and tolerance compared with traditional high-flow oxygenation systems, such as nasal masks and nonrebreathing systems. By delivering higher flow rates, HFNC systems are less apt than traditional oxygenation systems to permit entrainment of room air during patient inspiration. Combined with the flushing of expired air from the upper airway during expiration, these mechanisms assure more reliable delivery of high Fio2 levels. The flushing of upper airway dead space also improves ventilatory efficiency and reduces the work of breathing. HFNC also generates a positive end-expiratory pressure (PEEP), which may counterbalance auto-PEEP, further reducing ventilator work; improve oxygenation; and provide back pressure to enhance airway patency during expiration, permitting more complete emptying. HFNC has been tried for multiple indications, including secretion retention, hypoxemic respiratory failure, and cardiogenic pulmonary edema, to counterbalance auto-PEEP in patients with COPD and as prophylactic therapy or treatment of respiratory failure postsurgery and postextubation. As of yet, very few high-quality studies have been published evaluating these indications, so recommendations regarding clinical applications of HFNC remain tentative.

Contemporary Reviews in Sleep Medicine

Chest. 2015;148(1):262-273. doi:10.1378/chest.14-1304

The central disorders of hypersomnolence are characterized by severe daytime sleepiness, which is present despite normal quality and timing of nocturnal sleep. Recent reclassification distinguishes three main subtypes: narcolepsy type 1, narcolepsy type 2, and idiopathic hypersomnia (IH), which are the focus of this review. Narcolepsy type 1 results from loss of hypothalamic hypocretin neurons, while the pathophysiology underlying narcolepsy type 2 and IH remains to be fully elucidated. Treatment of all three disorders focuses on the management of sleepiness, with additional treatment of cataplexy in those patients with narcolepsy type 1. Sleepiness can be treated with modafinil/armodafinil or sympathomimetic CNS stimulants, which have been shown to be beneficial in randomized controlled trials of narcolepsy and, quite recently, IH. In those patients with narcolepsy type 1, sodium oxybate is effective for the treatment of both sleepiness and cataplexy. Despite these treatments, there remains a subset of hypersomnolent patients with persistent sleepiness, in whom alternate therapies are needed. Emerging treatments for sleepiness include histamine H3 antagonists (eg, pitolisant) and possibly negative allosteric modulators of the gamma-aminobutyric acid-A receptor (eg, clarithromycin and flumazenil).

Special Features

Chest. 2015;148(1):274-287. doi:10.1378/chest.14-1788

The knowledge of airway anatomy is the most fundamental requirement of every bronchoscopist. There are numerous and frequent anatomic variations of the central airways making the examination unique for every individual. It is imperative for every bronchoscopist to be fully cognizant of the common congenital anomalies involving the central airways. Proper identification and reporting of these findings are a matter of the utmost importance, especially when surgical options in a patient with lung cancer or lung transplantation is under consideration. This article focuses on the congenital anomalies of central airway encountered among adults. Each of these anatomic variations has a characteristic appearance, yet requires bronchoscopic acumen for their identification. This review provides a comprehensive description of these anomalies and highlights their clinical implications.

Topics in Practice Management

Chest. 2015;148(1):288-293. doi:10.1378/chest.14-2630

There are currently > 230 million people in the world with asthma, and asthma attacks result in the hospitalization of someone every 7 min. The National Heart, Lung, and Blood Institute outlines four components of clinical practice guidelines for the diagnosis and management of asthma, which tend to take a biomedical focus: (1) measures of assessment and monitoring, obtained by objective tests, physical examination, patient history, and patient report, to diagnose and assess the characteristics and severity of asthma and to monitor whether asthma control is achieved and maintained; (2) education for a partnership in asthma care; (3) control of environmental factors and comorbid conditions that affect asthma; and (4) pharmacologic therapy. Many national guidelines include providing patients with asthma with (1) written action plans, (2) inhaler technique training, and (3) structured annual reviews. Although current guidelines help improve clinical processes of care for asthma, there is also a need to improve self-care of asthma by empowering individuals to take more control of their condition. There is a growing appreciation that a narrative approach with patients with asthma, which focuses on the illness experience and aims to enhance patient-clinician understanding, might improve self-care. We explore how a framework for clinicians to listen to patients’ stories, developed from research on individuals with asthma, might enhance communication, improve patient-clinician relationship, and foster better patient self-care. The article closes with the implications of this approach for clinical practice and future research.


Chest. 2015;148(1):294. doi:10.1378/chest.14-2886

Sounds a bit like a little girl asleep,
in a hammock on a porch,
or the aurora borealis, or Chinese
peonies. Not like this:
Chest closing like an angry fist,
newspaper falling in slow whispers to the floor, as
coffee cups, the green chair, the dog
turn to darkened air, a pinpoint of light
painfully blossoming in the sudden dusk.
A dim smell, something feared,
or half-forgotten. Why would I remember?
Who would I tell?

Chest. 2015;148(1):294. doi:10.1378/chest.14-2887

Mr. Jones stands outside the glass, looks in
at his foreign wife. Alien,
her only language numbers, her only song
variations on an oscilloscope. The audience
recognizes wild new rhythms:
she is pushing back frontiers, she
marches forward.
In this cool light,
eight floors above the parking lot,
she transforms.
A bag of bone and water,
flesh becomes irrelevant, she becomes
what she was not.
A silent grotesque, she sings her song.
The room sighs, is more alive than this centerpiece.
Her chest rises and falls in time with machines.
As the sun warms an aqua morning sky,
a hidden crescendo.
Mr. Jones tells Mrs. Jones good-bye.

Chest. 2015;148(1):295. doi:10.1378/chest.14-2885

We know the heart an electric thing.
That could be metaphor, but song
is not the tune we sing. Strictly
electricians marking square by square
as fact—
the dance, the points, the pirouettes,
offbeat rhythms, jazz, tap—
the heart’s choreography transcribed as graph.
A metronome of background noise
behind our days, our monitors reflect
an accidental poetry of line
in epic greens and grays.

Chest. 2015;148(1):295. doi:10.1378/chest.14-3025

Outside the wide window, the air
is full of birds and buds, of sunlight,
pale green through new leaves.
People gather
in yards, on lawn chairs, around
barbecues. Someone mows a lawn. Someone
is washing a car.
Inside, there are beige
walls, crisp sheets, quick steps
in the hall. There is the need
for oxygen in tubes. There is her
stillness. There is his heart,
He sits
mute, measuring
the precious, perfect rise and fall
of her breath.
Her hand loosens, and she
He needs everything
to stop.
He needs more
He still has to bring himself back
home, take the children
on his lap, find
a way to tell them.

Selected Reports

Chest. 2015;148(1):e1-e4. doi:10.1378/chest.14-2463

Tuberculin skin testing was performed on a 5-year-old girl in Phnom Penh, Cambodia. She had been immunized by Bacille de Calmette et Guérin. She was tested because of a palpable cervical node and a slightly elevated temperature. Within 48 h, a deep necrotic lesion appeared on the volar aspect of the left arm. The lesion was treated locally, and the child was not treated for suspected TB. To our knowledge, this is the first instance of necrosis in 11,392 people who received Tubersol doses since 1996 to date at our International Vaccination Center, for an estimated incidence of 0.18 per 1,000 (95% Poisson 0.04-0.70 per 1,000 doses used). At a follow-up consultation after 77 days, the lesion had scarred and the child showed no signs suggestive of active TB. Although latent TB infection remains the most likely diagnosis, other types of mycobacterial infection may be considered in the tropical setting and in the absence of signs suggestive of active TB.

Ultrasound Corner

Chest. 2015;148(1):e5-e7. doi:10.1378/chest.14-2201

A 62-year-old man with a past medical history of hepatitis C, liver cirrhosis, end-stage renal disease, and cerebrovascular accident was admitted to the medical wards with hepatic encephalopathy. Therapy with lactulose was initiated and resulted in resolution of the encephalopathy. On hospital day 3, the patient again became encephalopathic, less responsive, and developed hypotension. The primary team bolused the patient with 250 mL of 5% albumin, and a critical care medicine consultation was requested. At the time of evaluation the patient was awake but not following commands. Vital signs were BP of 75/45 mm Hg, pulse rate of 84/min, respiratory rate of 22/min, and temperature of 37.1°C. His finger stick was 180 mg/dL, and oxygen saturation was 99% on room air. Lungs were clear to auscultation bilaterally, and cardiac examination was unremarkable. The abdomen was distended and resonant, and there was no evidence of pedal edema. There were no overt signs of GI bleeding (hematemesis or melena). A sepsis workup sent on admission (blood cultures and urinalysis) was negative. Chest radiography was grossly clear (Fig 1). Laboratory specimens drawn 5 h prior to the evaluation were significant for a drop in hematocrit level from 37.2% to 28.6%. Arterial blood gas results at the time of evaluation showed the following values: pH 7.45; Pco2, 32 mm Hg; Po2, 101 mm Hg; potassium, 6.8 mEq/L; hematocrit, 26.3%; and lactic acid, 14 mM. The intensivist team prepared for intubation to protect the airway in the setting of worsening mental status and shock. Per report, the patient had not eaten since the prior day.

Chest Imaging and Pathology for Clinicians

Chest. 2015;148(1):e8-e13. doi:10.1378/chest.14-3124

We present a case of a 70-year-old man with enlarged mediastinal and cervical lymph nodes that provided interesting radiologic and pathologic observations. The 70-year-old black man was found to have enlarged mediastinal lymph nodes. He had symptoms of atypical chest pain and generalized weakness for 2 weeks prior to the diagnosis. He denied shortness of breath, fever, chills, or night sweats. He was treated for hypertension and onychomycosis. Basic laboratory findings were within normal limits. Pulmonary function tests at the time of presentation showed FEV1, FVC, and FEV1/FVC ratio of 123% predicted, 133% predicted, and 0.7, respectively. Meanwhile, total lung capacity and carbon monoxide diffusing capacity were 103% and 107% predicted, respectively. Two weeks before he presented to our institution, the patient underwent bronchoscopy with transbronchial biopsies of the right lower lobe and endobronchial ultrasound-guided transbronchial needle aspiration of the right hilar lymph nodes.

Pulmonary, Critical Care, and Sleep Pearls

Chest. 2015;148(1):e14-e17. doi:10.1378/chest.14-2298

A 50-year-old black man with newly diagnosed HIV/AIDS, genital herpes, and latent syphilis presented with a nonproductive cough. The patient received a diagnosis of HIV and started highly active antiretroviral therapy (HAART) with emtricitabine/tenofovir disoproxil fumarate, darunavir, and ritonavir 2 months prior to presentation. CD4+ count was 1/μL and viral load was 538,884 copies/mL prior to initiation of HAART. The patient endorsed compliance with all medications since diagnosis. The patient had a persistent, dry cough at time of HIV diagnosis that had acutely worsened during the 2 weeks leading to admission. He denied fevers, chills, hemoptysis, or dyspnea but did endorse drenching night sweats.

Chest. 2015;148(1):e18-e21. doi:10.1378/chest.14-2301

A 22-year-old previously healthy woman was evaluated in pulmonary clinic for shortness of breath and cough that had been slowly progressive over 3 months. She otherwise reported being fully functional and attended her college graduation a week prior to evaluation. She had no history of smoking, illicit drug use, connective tissue disease, or noxious exposures.

Topics: lung diseases , cyst
Chest. 2015;148(1):e22-e25. doi:10.1378/chest.14-1812

A 38-year-old man with history of diabetes, hypertension, hyperlipidemia, and obesity was referred to the electrophysiology clinic for evaluation of infrequent palpitations and remote history of syncope. The patient described a sensation of racing of the heart, which lasted about 30 min to 1 h and occurred several times over the past year. This was associated with a sense of anxiety and shortness of breath and appeared to resolve spontaneously. The patient also experienced one episode of syncope in the past while enjoying a barbecue on a hot summer day. He did not recall if this episode was accompanied by palpitations, however, the previously mentioned symptoms prompted the consultation. Upon further questioning the patient also reported experiencing fatigue. He stated that he noted decreased energy and frequent daytime sleepiness.


Chest. 2015;148(1):e26-e27. doi:10.1378/chest.15-0191
Chest. 2015;148(1):e27-e28. doi:10.1378/chest.15-0511
Chest. 2015;148(1):e29-e30. doi:10.1378/chest.15-0497
Chest. 2015;148(1):e30. doi:10.1378/chest.15-0830
Chest. 2015;148(1):e31. doi:10.1378/chest.15-0664
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Chest. 2015;148(1):e33. doi:10.1378/chest.15-0677
Chest. 2015;148(1):e33-e34. doi:10.1378/chest.15-0890

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