Chest. 2012;141(2):285-286. doi:10.1378/chest.11-2906

Accompanying this issue of CHEST, readers will find the supplement containing the Executive Summary,1 Introduction,2 and Methodology3 articles from the Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (AT9). These broad articles, as well as those that address specific content areas covered by the latest guidelines, can also be accessed at http://chestjournal.chestpubs.org. There have been several noteworthy advances in the methodology used to produce these guidelines since the last edition was published in 2008.4 Additionally, AT9 marks the initial step of a transition in the American College of Chest Physicians (ACCP) process for guideline updating and publication.

Chest. 2012;141(2):286-288. doi:10.1378/chest.11-1424

A limitation to the recommendations on drug treatment made in asthma guidelines is that these are based on clinical studies performed in selected groups of patients.1 For example, in many trials, only 5% of adults with asthma fulfill the entry criteria; current smokers or former heavy smokers are usually excluded.2 The lack of information on the best approach to manage smokers is of considerable importance, given the high prevalence rates of active smoking in asthma and the poor levels of asthma control in this group.3 In developed countries, one-fifth to one-third of adults with asthma are smokers, and in some areas of the world, such as southeast Asia, almost one-half are smokers. Smokers experience increased morbidity from asthma compared with nonsmokers, including more severe symptoms, increased rates of admission to hospital with acute asthma, and accelerated rates of decline in lung function.3,4 Clinical trials are urgently required that will provide evidence on which drugs and treatment strategies are most appropriate for this group.

Chest. 2012;141(2):288-290. doi:10.1378/chest.11-2071

Let us begin with the premise that endobronchial ultrasound (EBUS) is the single most useful pulmonary procedure introduced in decades and should be available to all patients with thoracic adenopathy requiring evaluation. The question then becomes when and where rather than whether it should be offered. In this issue of CHEST (see page 506), Pastis and colleagues1 report an encouraging analysis showing positive downstream revenue resulting from their introduction of EBUS to their institution. The authors are based at an academic institution, but their results may be extrapolated to other settings. The authors do present the ideal: a quick, safe, efficient, and cost-effective procedure that benefits patients while financially benefiting the institution. It will be telling whether this encouraging information will be used to offer patients the best application of this outstanding technology.

Chest. 2012;141(2):290-292. doi:10.1378/chest.11-1339

The quote “It is better to be alone than in bad company,” by George Washington (1732-1799), can be applied to many situations but is particularly true for atrial fibrillation (AF). AF is the most common sustained arrhythmia in the adult population, and it is well known that its occurrence is linked to a series of risk factors, such as advanced age, hypertension, valvular or ischemic heart disease, heart failure, diabetes, and hyperthyroidism.1,2 The term “lone AF” was introduced by Evans and Swann in 19543 and is also used currently to describe the condition wherein AF develops in a young patient (<60 years of age) in whom clinical and laboratory assessment and testing exclude the presence of an overt structural cardiac disease or of other comorbidities (including systemic hypertension) known to facilitate the development of AF.4 Patients affected by lone or idiopathic AF have been traditionally identified as subjects with a favorable prognosis with regard to thromboembolic events and mortality.4

Second Opinion

Chest. 2012;141(2):293. doi:10.1378/chest.141.2.293
Topics: insurance


Chest. 2012;141(2):294-299. doi:10.1378/chest.11-2641

Patients with atrial fibrillation (AF) face an annual stroke risk of about 5%. Evidence that anticoagulants reduce the risk of stroke has evolved over the 20th century. The American College of Chest Physicians (ACCP) has played a critical role in presenting guidelines for stroke prevention in AF. This commentary highlights the role that the ACCP guidelines have played, from their inception to the ninth edition. The first ACCP Conference on Antithrombotic and Thrombolytic Therapy in 1986 developed evidence-based guidelines for the indications, dosage, and monitoring of antithrombotic therapy. The conference recommended that anticoagulants be monitored by the international normalized ratio, and the appropriate dosage was to increase the international normalized ratio to two to three times control. This recommendation was widely accepted. Anticoagulants were recommended for AF with mitral valve disease and for nonvalvular AF with a history of embolism. No recommendations were made for nonvalvular AF without a history of embolism. These recommendations stimulated numerous randomized controlled trials (RCTs). By the third ACCP conference in 1992, RCTs had demonstrated a dramatic 69% stroke reduction in patients with nonvalvular AF. The third ACCP conference was the first to strongly recommend anticoagulation for primary and secondary stroke prevention in nonvalvular AF. ACCP conferences since 1992 have refined recommendations for nonvalvular AF on the basis of associated risk factors. The most recent conference, in 2011, recommended a direct thrombin inhibitor, dabigatran, rather than warfarin as the anticoagulant of choice. These ACCP guidelines have played a critical role in changing physicians’ practice patterns. In 1980 only 7% of patients with AF in the United States received OA; by 2007, this had increased to 57%.

Chest. 2012;141(2):300-307. doi:10.1378/chest.11-1942

Performance measures (PMs) are specified metrics by which a health-care provider’s care can be compared with national benchmarks. The use of PMs is a key component of efforts to improve the quality and value of health care. The National Quality Forum (NQF) is the federally recognized endorser of PMs. From 2006 to 2009, the Quality Improvement Committee (QIC) of the American College of Chest Physicians engaged in the review of proposed PMs as a member of the NQF. This article provides a review of the QIC’s experience with PMs and NQF membership and the lessons learned, an overview of the enhancements made to the NQF endorsement process in 2010 and 2011, and a discussion of the next steps that would further strengthen the measure development and endorsement processes and increase the likelihood of measurement leading to better patient outcomes.


Chest. 2012;141(2):308-320. doi:10.1378/chest.11-1175

Background:  Postthrombotic syndrome (PTS) is a frequent, chronic complication of DVT. The effectiveness and safety of available treatments are unknown. The objective of this study was to systematically review the literature to assess whether pharmacologic and compression therapies are effective and safe for the treatment of PTS.

Methods:  We sought to identify randomized controlled trials (RCTs) via a search of PubMed, studies referenced in included publications, and studies that cited relevant literature.

Results:  A total of 121 titles were reviewed, 12 full-text publications were assessed for inclusion, and seven RCTs, including 703 patients, were selected for inclusion. Four trials assessed the effectiveness of drugs, including rutosides, hidrosmin, and defibrotide, and four trials assessed compression therapies for treatment of PTS. Systems for the diagnosis and classification of PTS severity varied across studies. Three of four drug therapy trials reported moderate improvement in selected PTS symptoms, minor changes in calf and ankle circumference, and some effects on ulcer healing. Two studies of compression stockings did not report benefit. Two studies that assessed compression devices reported improvement in PTS symptoms scores; one of these reported an improvement in quality-of-life score.

Conclusions:  There is limited and low-quality evidence for the effectiveness of rutosides, hidrosmin, defibrotide, and compression stockings, but moderate-quality evidence that supports the use of intermittent compression to provide at least short-term relief from PTS. More rigorous studies are needed to assess the short- and long-term effectiveness and safety of PTS therapies.

Chest. 2012;141(2):321-329. doi:10.1378/chest.11-0625

Background:  According to the Comparison of Arixtra in Lower Limb Superficial Vein Thrombosis with Placebo (CALISTO) study, a recent randomized, controlled trial, prophylactic fondaparinux can prevent thrombotic complications following superficial vein thrombosis (SVT). The cost-effectiveness of this treatment remains to be determined.

Methods:  We developed a decision-tree model comparing fondaparinux 2.5 mg daily for 45 days vs no treatment of SVT. It included all clinical events associated with SVT, its treatment, its complications, and all respective quality-adjustment factors. Data were mainly derived from the CALISTO study and the published literature. Measured outcomes comprised clinical events (VTE, major hemorrhage, death), quality-adjusted life-years (QALYs), costs, and incremental cost-effectiveness ratios (ICERs). The analysis was conducted using a lifetime time horizon from a health-care system perspective. We performed one-way and probabilistic sensitivity analyses to evaluate parameter uncertainty.

Results:  In 10,000 patients, we estimated that fondaparinux would prevent 123 VTE events and two deaths. On a per-patient basis, the incremental QALY compared with no treatment was 0.04 (1 day) at an incremental cost of $1,734, resulting in an ICER of $500,000 per QALY. This result remained robust in the one-way sensitivity analyses, with an ICER remaining > $100,000 per QALY throughout all ranges. Based on probabilistic sensitivity analyses, the probability that fondaparinux was cost-effective was 1% at a willingness-to-pay of $100,000 per QALY.

Conclusions:  Fondaparinux for 45 days does not appear to be cost-effective when treating patients with isolated SVT of the legs. A better value for money could be obtained in subgroups of patients with a higher incidence of VTE after SVT. Shorter durations of treatment should be further evaluated in future clinical studies.

Original Research: ASTHMA

Chest. 2012;141(2):330-338. doi:10.1378/chest.11-0392

Background:  Smoking induces airway inflammation and relative resistance to inhaled steroids. The objective of this study was to evaluate the effects on airway hyperresponsiveness of adding salmeterol to fluticasone vs doubling the dose of fluticasone in patients with asthma who smoked and patients with asthma who did not smoke.

Methods:  Sixteen patients with mild to moderate persistent asthma who did not smoke and 15 such patients who smoked completed a double-blind, randomized, placebo-controlled crossover study. They received either a fluticasone/salmeterol combination (FP/SM) (125/25 μg) two puffs bid (plus fluticasone placebo), or active fluticasone (250 μg) two puffs bid (plus FP/SM placebo), for 2 weeks each, with baselines after 1-week to 2-week run-in and washout periods. The primary outcome was the change from baseline in the provocative concentration of methacholine required to produce a 20% fall in FEV1 (PC20).

Results:  In the patients who did not smoke, there were similar improvements in the methacholine PC20 with the use of fluticasone and FP/SM. The patients who smoked gained a benefit from FP/SM but not fluticasone, amounting to a PC20 difference of 1.6 doubling dilutions (95% CI, 1.0-2.2), P < .01. The provocative dose of mannitol required to produce a 15% fall in FEV1 (PD15) showed greater improvements with FP/SM than fluticasone in both patients who smoked and did not smoke. Similar differences in airway caliber between those who smoked and did not smoke were observed in FEV1 and airway resistance.

Conclusions:  FP/SM confers greater improvements in airway hyperresponsiveness and airway caliber in patients with asthma who smoke compared with double the dose of fluticasone. We hypothesize that in the presence of relative steroid resistance, the smooth muscle stabilization conferred by salmeterol is of greater clinical importance in patients who smoke than in those who do not smoke.

Trial registry:  ClinicalTrials.gov: No.: NCT00830505; URL: www.clinicaltrials.gov


Chest. 2012;141(2):339-347. doi:10.1378/chest.11-0340

Background:  Lone atrial fibrillation (AF) has been suggested to have a favorable long-term prognosis. Significant interest has been directed at factors predicting arrhythmia progression, and the HATCH score (hypertension, age ≥ 75 years, transient ischemic attack or stroke [2 points], COPD, and heart failure [2 points]) recently has been proposed as a predictive score for AF progression. We investigated long-term outcomes in a large cohort of newly diagnosed lone AF and whether progression from paroxysmal to permanent AF confers an adverse impact on outcomes, including stroke and thromboembolism.

Methods:  The study was an observational cohort of 346 patients with newly diagnosed lone AF with a mean follow-up of 12.1 ± 7.3 years.

Results:  Baseline paroxysmal AF was confirmed in 242 patients, and of these, 65 (26.9%) subsequently experienced progression to permanent AF. Older age and development of congestive heart failure during follow-up were the multivariate predictors of AF progression (both P < .01), which was documented in 19.8% of patients with a HATCH score of 0 vs 63.2% with a score of 2 (P < .001), although the predictive validity of the HATCH score per se was modest (C statistic, 0.6). The annual rate of thromboembolism and heart failure during follow-up were low (0.4% each), and five patients (1.4%) died. AF progression, development of cardiac diseases, and older age were multivariate predictors of adverse outcomes, including thromboembolism (all P < .05). Baseline CHADS2 (congestive heart failure, hypertension, age ≥ 75, diabetes mellitus, prior stroke or transient ischemic attack) score was not predictive for thromboembolism (C statistic, 0.50; 95% CI, 0.31-0.69).

Conclusions:  This 12-year follow-up study provides confirmatory evidence of a generally favorable prognosis of lone AF, but adverse outcomes (including stroke and thromboembolism) are significantly influenced by age and the (new) development of underlying heart disease. Arrhythmia progression in lone AF is a marker of increased risk for adverse cardiovascular events.


Chest. 2012;141(2):348-353. doi:10.1378/chest.11-0426

Background:  Animal and human studies suggest that selective serotonin reuptake inhibitors (SSRIs) might be useful for the prevention or treatment of pulmonary arterial hypertension.

Methods:  We conducted a population-based, nested case-control study to explore the hypothesis that SSRIs might reduce the risk of pulmonary arterial hypertension. Cases were individuals who developed pulmonary arterial hypertension requiring pharmacologic treatment. For each case, we selected up to 10 matched control subjects. Exposure to SSRIs and non-SSRI antidepressants was ascertained using administrative data. The outcome of pulmonary arterial hypertension requiring pharmacologic therapy was defined as the receipt of a drug specific for the treatment of pulmonary arterial hypertension.

Results:  In contrast to our hypothesis, and likely because of residual confounding, we found a positive association between SSRI use and pulmonary arterial hypertension (adjusted OR, 1.55; 95% CI, 1.13-2.13).

Conclusions:  At conventional doses, SSRIs are not associated with a reduced risk of pulmonary arterial hypertension.

Chest. 2012;141(2):354-362. doi:10.1378/chest.11-0676

Background:  In pulmonary arterial hypertension (PAH), survival predictions can be important for optimization of therapeutic strategies. The present study aimed to validate a quantitative algorithm for predicting survival derived from the Registry to Evaluate Early and Long-term PAH Disease Management (REVEAL Registry) and develop a simplified calculator for everyday clinical use.

Methods:  Prospectively collected data from patients with newly diagnosed (< 3 months) World Health Organization group I pulmonary hypertension enrolled in the REVEAL Registry were used to validate a predictive algorithm for 1-year survival. Model calibration was evaluated by comparing algorithm-predicted survival with observed Kaplan-Meier estimates for the overall validation cohort and for five risk groups. Similarly, the risk discriminators for the simplified calculator were compared with those of the quantitative algorithm.

Results:  The validation cohort comprised 504 individuals with mean ± SD 6-min walk distance 308 ± 128 m, and 61.5% were functional class III. The proportion of patients surviving 1 year fell within the range predicted by the model (95.1%, 91.5%, 84.6%, 76.3%, and 58.2%, respectively) among patients in the low (predicted survival ≥ 95%), average (90% to < 95%), moderate (85% to < 90%), high (70% to < 85%), and very high (< 70%) risk strata. Predicted and observed 1-year survival were similar across risk stratum, and the c-index indicated good discrimination for both the full equation (0.726) and the simplified risk calculator (0.724).

Conclusions:  The REVEAL Registry predictive algorithm and simplified risk score calculator are well calibrated and demonstrate good discriminatory ability in patients with newly or previously diagnosed PAH.

Trial registry:  ClinicalTrials.gov; No.: NCT00370214; URL: www.clinicaltrials.gov

Chest. 2012;141(2):363-373. doi:10.1378/chest.10-3114

Background:  Pulmonary arterial hypertension (PAH) is a life-threatening disease that affects more women than men. The reasons for the female preponderance are unclear, and there are limited data available for men with PAH.

Methods:  Data from the Registry to Evaluate Early and Long-term PAH Disease Management (REVEAL Registry) were analyzed to explore sex differences among patients with PAH with regard to 2-year survival from enrollment and 5-year survival from time of diagnosis.

Results:  The data set included 2,318 women and 651 men. More women had PAH associated with connective tissue disease (P < .001), and more men had portopulmonary hypertension (P < .001) and HIV-associated PAH (P < .001). More women had congenital heart disease-associated PAH (P = .017), thyroid disease (P < .001), and depression reported (P ≤ .001). At diagnosis, men had higher mean pulmonary artery pressure (53 ± 14 vs 51 ± 14.3 mm Hg; P = .013) and mean right atrial pressure (10 ± 6 vs 9 ± 6 mm Hg; P = .031). Women had better survival estimates for 2 years from enrollment and for 5 years from diagnosis. Stratifying by age showed that survival from enrollment was similar between men and women aged < 60 years at enrollment, whereas men aged ≥ 60 years have lower survival rates compared with women aged ≥ 60 years.

Conclusions:  Our findings highlight similarities and differences between men and women with PAH, raising questions for future exploration regarding the role of hormones and sex in causation and survival in PAH.

Trial registry:  ClinicalTrials.gov; No.: NCT00370214; URL: www.clinicaltrials.gov

Chest. 2012;141(2):374-380. doi:10.1378/chest.10-3331

Background:  A prolonged QRS duration ( ≥ 120 milliseconds) predicts outcomes in patients with left-sided heart failure, but the impact in idiopathic pulmonary arterial hypertension (IPAH) and right-sided heart failure is unknown. We assessed the prognostic value of a prolonged ECG QRS duration in patients with IPAH in China.

Methods:  We retrospectively analyzed the initial 12-lead ECG for QRS duration in 212 consecutive patients with IPAH seen at our center between 2007 and 2009. Patients were divided according to QRS duration < 120 milliseconds or ≥ 120 milliseconds. The baseline characteristics and survival of the two groups were compared.

Results:  Thirty-five patients with IPAH (16.5%) had a QRS duration ≥ 120 milliseconds, including 21 (9.9%) with right bundle-branch block and 14 (6.6%) with nonspecific intraventricular conduction delay. Prolongation of the QRS duration was associated with a worse World Health Organization functional class and 6-min walk test distance and higher serum uric acid when compared with patients with normal QRS duration (P < .05). Prolonged QRS duration was an independent predictor of mortality and was associated with a 2.5-fold increased risk of death (P = .024).

Conclusion:  Prolongation of the QRS duration is associated with clinical severity in patients with IPAH. In addition, QRS prolongation has an independent association with cardiopulmonary mortality and could be a new predictor of adverse outcome in patients with IPAH.

Chest. 2012;141(2):381-387. doi:10.1378/chest.11-0090

Background:  Planar ventilation/perfusion (V˙/Q˙ ) lung scintigraphy is a validated tool for the diagnosis of pulmonary embolism (PE). Nevertheless, given the high rate of nonconclusive V˙/Q˙ , further investigation is often necessary. V˙/Q˙  single-photon emission CT (SPECT) scan could improve V˙/Q˙  performance, but sparse data are available on its accuracy. This study assessed the diagnostic performance of V˙/Q˙  SPECT scan in a cohort of consecutive patients with suspected PE.

Methods:  Three hundred twenty-one consecutive patients with a clinical suspicion of PE were prospectively included. Patients suspected of having PE were managed according to a reference diagnostic strategy validated by a 3-month follow-up. In addition to the reference strategy, patients had a V˙/Q˙  SPECT scan, the results of which were compared with the initial work-up results.

Results:  Prevalence of PE was 0 of 41 (0%; 95% CI, 0%-9%), six of 134 (4%; 95% CI, 2%-9%), 15 of 36 (42%; 95% CI, 27%-58%), and 28 of 32 (88%; 95% CI, 72%-95%) in the normal, low, intermediate, and high V˙/Q˙  SPECT scan probability groups, respectively. The combination of V˙/Q˙  SPECT scan with clinical probability was diagnostic in 88% of patients.

Conclusions:  V˙/Q˙  SPECT scan results show satisfactory accuracy for PE diagnosis. Validation of dedicated interpretation criteria is required, followed by outcome studies that use V˙/Q˙  SPECT scan as part of a diagnostic strategy to rule out PE.

Trial registry:  ClinicalTrials.gov; No.: NCT01183026; URL: www.clinicaltrials.gov

Chest. 2012;141(2):388-395. doi:10.1378/chest.11-0172

Background:  The relationship between obesity and right ventricular (RV) morphology is not well studied. We aimed to determine the association between obesity and RV structure and function in a large multiethnic population-based cohort.

Methods:  The MESA-Right Ventricle Study measured RV mass and volumes by cardiac MRI in participants aged 45 to 84 years without clinical cardiovascular disease in the Multi-Ethnic Study of Atherosclerosis (MESA). Participants were divided into three categories based on BMI: lean ( ≤ 24.9 kg/m2), overweight (25-29.9 kg/m2), and obese ( ≥ 30 kg/m2).

Results:  The study sample included 4,127 participants. After adjustment for demographics, height, education, and cardiovascular risk factors, overweight and obese participants had greater RV mass (6% and 9% greater, respectively), larger RV end-diastolic volume (8% and 18% greater, respectively), larger RV stroke volume (7% and 16% greater, respectively), and lower RV ejection fraction ( ≥ 1% lower) than lean participants (all P < .001). These findings persisted after adjusting for the respective left ventricular (LV) parameters.

Conclusions:  Overweight and obesity were independently associated with differences in RV morphology even after adjustment for the respective LV measure. This association could be explained by increased RV afterload, increased blood volume, hormonal effects, or direct obesity-related myocardial effects.

Original Research: COPD

Chest. 2012;141(2):396-405. doi:10.1378/chest.11-0495

Background:  Exacerbations of COPD (ECOPD) remain a major cause of mortality and morbidity. Despite advances in the understanding of their pathophysiology, their assessment relies primarily on clinical presentation, which can be variable and difficult to predict. A large number of biomarkers already have been assessed in this context, and some appear to be promising.

Methods:  An online search for articles published until December 2010 was conducted using three terms for ECOPD, five terms for biomarkers, and five terms for the sampling method. Biomarkers were evaluated for their potential role in the establishment and confirmation of the diagnosis of ECOPD, the evaluation of etiology and severity, the prediction of prognosis, and the guidance of treatment decisions.

Results:  Several systemic biomarkers have been measured in the context of ECOPD, and most have been found to increase at ECOPD onset and to subside during the course of exacerbations. Correlations have been reported among these biomarkers, but direct associations with clinical variables have been more difficult to establish. Although there are several limitations yet to be addressed, some of the biomarkers, most notably C-reactive protein for the identification of an ECOPD and procalcitonin for antibiotic guidance, may provide clinically relevant information.

Conclusions:  So far, no single biomarker has been able to gain wide acceptance, but some provide clinically useful information. The evaluation of such biomarkers in large decision-making studies is expected to become an area of intense investigation in the near future.

Chest. 2012;141(2):406-412. doi:10.1378/chest.11-0298

Background:  The aims of this study were to determine which tests of exercise capacity relate to average daily energy expenditure (DEE) and to quantify aerobic reserve during daily life in people with COPD.

Methods:  A cross-sectional study was undertaken in 26 people with COPD (16 men; FEV1, 50% ± 16%). Six-min walk distance (6MWD) and incremental shuttle walk distance (ISWD) measures were collected, and peak oxygen uptake (V˙ o2 peak) was measured during a symptom-limited ramp cycle ergometry test. The SenseWear Armband was worn during the waking hours for 4.4 ± 1.1 days to measure DEE. The intensity at which activities of daily living were undertaken was expressed as a percentage of V˙ o2 peak.

Results:  DEE was associated with 6MWD (r = 0.40, P = .046) and ISWD (r = 0.52, P = .007) but not V˙ o2 peak (mL/kg per min) (r = 0.07, P = .74). Stronger associations were observed between DEE and the body weight-walking distance product for the 6MWD (r = 0.73, P < .001) and ISWD (r = 0.75, P < .001). The average intensity of daily activity was equivalent to 58% ± 11% of V˙ o2 peak, leaving an average aerobic reserve of 42%.

Conclusions:  Both 6MWD and ISWD, but not V˙ o2 peak, were related to DEE. Because activities of daily living were performed at a high percentage of V˙ o2 peak, it may be more realistic to optimize habitual DEE in COPD by increasing the frequency or duration rather than the intensity of physical activity.

Chest. 2012;141(2):413-419. doi:10.1378/chest.11-1059

Background:  Walking is frequently used in the exercise rehabilitation of patients with COPD. Walking ability can be characterized by the two-parameter hyperbolic relationship between endurance and speed. One parameter, critical walk speed (s_critical), represents the maximum speed that can be endured indefinitely. The purpose of this study was to: (1) determine the effect of pulmonary rehabilitation on the critical speed and (2) compare the critical speed with the speed chosen during self-paced walking.

Methods:  We estimated critical speed in patients with COPD before and after rehabilitation. Patients completed four high-intensity constant-speed walk tests to intolerance on a 30-m course. The parameters of the hyperbolic relationship were determined using nonlinear regression of endurance on speed. Participants also completed self-paced walks: (1) for as long as they could, (2) at their “usual” and “fast” speeds, and (3) as a 6-min walk test.

Results:  Twelve participants (FEV1 [SD], 41 [16] % predicted; FEV1/FVC, 41 [12]) completed the study. At baseline, the critical speed (65 [12] m/min) was not significantly different from the self-paced, usual, or 6-min walk speeds (65 [12], 67 [14], and 63 [15] m/min, respectively). There was a significant increase in critical speed (6 [1-10] m/min) and 6-min speed (16 [10-21] m/min) after rehabilitation, without changes in the self-paced, usual, or fast speeds.

Conclusions:  Patients with COPD increase their critical walk speed after pulmonary rehabilitation. The pace chosen during common walk tasks is closely related to critical speed; this relationship is altered after rehabilitation.

Trial registry:  ClinicalTrials.gov; No.: NCT00781183; URL: www.clinicaltrials.gov

Original Research: LUNG CANCER

Chest. 2012;141(2):420-428. doi:10.1378/chest.10-3149

Background:  Thyroid transcription factor 1 (TTF-1) positivity correlates with a higher prevalence of epidermal growth factor receptor (EGFR) mutation in lung adenocarcinoma. It is unknown whether TTF-1 expression affects the clinical outcome of patients with advanced lung adenocarcinoma, who have received EGFR tyrosine kinase inhibitors (TKIs) during the treatment course.

Methods:  This study enrolled patients with advanced lung adenocarcinoma who had results of EGFR mutation analysis and TTF-1 immunostaining. The impact of TTF-1 expression on overall survival (OS) and progression-free survival (PFS) under EGFR TKI treatment was evaluated. Multivariate analyses were done to examine the independent predictors of OS and PFS.

Results:  Of 496 patients with advanced lung adenocarcinoma, 443 had TTF-1-positive adenocarcinoma. Patients with TTF-1-positive lung adenocarcinoma had longer OS than did those with TTF-1-negative lung adenocarcinoma (median survival, 27.4 vs 11.8 months, P = .001). In patients with EGFR TKI treatment, those with TTF-1-positive lung adenocarcinoma and mutant EGFR had longer OS. In patients with EGFR mutation, those with TTF-1-positive lung adenocarcinoma had longer PFS than did those with TTF-1-negative lung adenocarcinoma (median survival, 8.7 vs 5.7 months, P = .043). Multivariate analysis showed that negative TTF-1 expression is a predictor for shorter OS, and a predictor for shorter PFS under EGFR TKI treatment.

Conclusions:  TTF-1 shows independent prognostic significance in advanced lung adenocarcinoma. Patients with TTF-1-negative lung adenocarcinoma have not only shorter OS, but also shorter PFS under EGFR TKI treatment, despite the existence of mutant EGFR. Further studies are needed to investigate the optimal treatment of patients with TTF-1-negative lung adenocarcinoma.

Chest. 2012;141(2):429-435. doi:10.1378/chest.10-3013

Objective:  The objective of this study was to compare the safety, use, and cost profiles of open thoracotomy vs video-assisted thoracoscopic surgery (VATS) for wedge resection in lung cancer performed by thoracic surgeons in the United States.

Methods:  The Premier database, which contains complete patient billing, hospital cost, and coding histories from > 25 million inpatient discharges and > 175 million hospital outpatient visits, was used for this analysis. Eligible patients were those who underwent wedge resection by a thoracic surgeon for cancer diagnosis or treatment through open thoracotomy or VATS in 2007 or 2008. Multivariable logistic regression analyses were run for binary outcomes, and ordinary least squares regressions were used for continuous outcomes. All models were adjusted for patient demographics, comorbid conditions, and hospital characteristics.

Results:  Of 8,228 eligible procedures, 2,051 patients underwent wedge resections by a thoracic surgeon using the open technique (n = 999) or VATS (n = 1,052). Hospital costs remained significantly higher for open wedge resections than for VATS ($17,377 vs $14,795, P = .000). Surgery time was significantly longer for open resections vs VATS (3.16 vs 2.82 h). Length of stay was 6.34 days for open vs 4.44 days for VATS. Adverse events were significant in the multivariable analysis, with an OR of 1.57 (95% CI, 1.29-1.91) in favor of VATS.

Conclusions:  Although this retrospective database analysis could not address the issue of oncologic outcome equivalence, a clear advantage of VATS over open wedge lung cancer resection was found for both acute clinical outcomes and hospital costs.

Original Research: SLEEP DISORDERS

Chest. 2012;141(2):436-441. doi:10.1378/chest.11-0283

Background:  Unrecognized obstructive sleep apnea (OSA) is associated with unfavorable perio-perative outcomes among patients undergoing noncardiac surgery (NCS).

Methods:  The study population was chosen from 39,771 patients who underwent internal medicine preoperative assessment between January 2002 and December 2006. Patients undergoing NCS within 3 years of polysomnography (PSG) were considered for the study, whereas those < 18 years of age, with a history of upper airway surgery, or who had had minor surgery under local or regional anesthesia were excluded. Patients with an apnea-hypopnea index (AHI) ≥ 5 were defined as OSA and those with an AHI < 5 as control subjects. For adjusting baseline differences in age, sex, race, BMI, type of anesthesia, American Society of Anesthesiology class, and medical comorbidities, the patients were classified into five quintiles according to a propensity score.

Results:  Out of a total of 1,759 patients who underwent both PSG and NCS, 471 met the study criteria. Of these, 282 patients had OSA, and the remaining 189 served as control subjects. The presence of OSA was associated with a higher incidence of postoperative hypoxemia (OR, 7.9; P = .009), overall complications (OR, 6.9; P = .003), and ICU transfer (OR, 4.43; P = .069), and a longer hospital length of stay (LOS), (OR, 1.65; P = .049). Neither an AHI nor use of continuous positive airway pressure at home before surgery was associated with postoperative complications (P = .3 and P = .75, respectively) or LOS (P = .97 and P = .21, respectively).

Conclusions:  Patients with OSA are at higher risk of postoperative hypoxemia, ICU transfers, and longer hospital stay.

Original Research: TRANSPLANTATION

Chest. 2012;141(2):442-450. doi:10.1378/chest.10-2889

Background:  Most reports addressing pulmonary complications (PCs) in hematopoietic stem cell transplant (HSCT) recipients have focused on allogeneics. This study describes the PCs, their risk factors, and the impact on mortality in autologous recipients.

Methods:  We reviewed the medical records of 1,243 adult autologous HSCT recipients. We collected pretransplant and posttransplant data and data on PC after transplant and long-term mortality.

Results:  Four hundred eighty-seven PC developed in 343 patients (27.6%): 173 infectious (13.9%), 127 noninfectious (10.2%), and 43 both infectious and noninfectious (3.5%). Bacterial, fungal, and viral pneumonias were the most common infectious complications. The main noninfectious complications were acute pulmonary edema (APE) (59 [4.7%]), diffuse alveolar hemorrhage (DAH) (26 [2.1%]), peri-engraftment respiratory distress syndrome (PERDS) (31 [2.5%]), and idiopathic pneumonia syndrome (IPS) (12 [1.0%]). Independent factors associated with PC included diffusing capacity of lung for carbon monoxide and indications for transplant. Factors associated with mortality included sex, history of pulmonary disease, disease status at the time of transplant, FVC, Karnofsky score, and underlying diagnosis. A Cox proportional hazards regression model with separate time-dependent predictors for the first 1 month, 1 to 2 months, 2 to 6 months, and 6 or more months showed an association with mortality at hazard ratios (HRs) of 32.39, 10.13, 4.29, and 0.98, respectively, compared with persons without PC.

Conclusions:  More than 25% of autologous HSCT recipients develop PCs within 1 year of transplant. Most of the complications are infections. The most common noninfectious complications are APE, DAH, PERDS, and IPS. PCs increase the risk of death, with HR as high as 32.

Chest. 2012;141(2):451-460. doi:10.1378/chest.11-0767

Background:  Size mismatch between donor lungs and a recipient thorax could affect the major determinants of maximal expiratory airflow: airway resistance, propensity of airways to collapse, and lung elastic recoil.

Methods:  A retrospective review of 159 adults who received bilateral lung transplants was performed. The predicted total lung capacity (pTLC) for donors and recipients was calculated based on sex and height. Size matching was represented using the following formula: pTLC ratio = donor pTLC / recipient pTLC. Patients were grouped according to those with a pTLC ratio > 1.0 (oversized) or those with a pTLC ratio ≤ 1.0 (undersized). Allograft function was analyzed in relation to the pTLC ratio and to recipient and donor predicted function.

Results:  The 96 patients in the oversized cohort had a mean pTLC ratio of 1.16 ± 0.13 vs 0.89 ± 0.09 in the 63 patients of the undersized group. At 1 to 6 months posttransplant, the patients in the oversized cohort had higher FEV1/FVC ratios (0.895 ± 0.13 vs 0.821 ± 0.13, P < .01) and lower time constant estimates of lung emptying (0.38 ± 0.2 vs 0.64 ± 0.4, P < .01) than patients in the undersized cohort. Although the FVCs expressed as % predicted for the recipient were not different between cohorts, the FVCs expressed as % predicted for the donor organ were lower in the oversized cohort compared with the undersized cohort (at 1-6 months, 52.4% ± 17.1% vs 65.3% ± 18.3%, P < .001). Kaplan-Meier estimates for the occurrence of bronchiolitis obliterans syndrome (BOS) showed that patients in the oversized cohort had a lower probability of BOS (P < .001).

Conclusions:  A pTLC ratio > 1.0, suggestive of an oversized allograft, is associated with higher expiratory airflow capacity and a less frequent occurrence of BOS.

Original Research: BRONCHIECTASIS

Chest. 2012;141(2):461-468. doi:10.1378/chest.11-0180

Background:  The aim of this study is to evaluate the efficacy and safety of medium-dose formoterol-budesonide combined inhaled treatment in a single inhaler compared with high-dose budesonide treatment in patients with non-cystic fibrosis (non-CF) bronchiectasis.

Methods:  This is a 12-month randomized, double-blind, parallel-groups clinical trial, to run in 40 patients with non-CF bronchiectasis diagnosed by high-resolution CT scan of the chest, receiving formoterol-budesonide combined treatment (18/640 μg daily) or budesonide treatment (1,600 μg daily). Variables concerning clinical condition, health-related quality of life (HRQL), lung function, β2-adrenergic agonist use, potentially pathogenic microorganism (PPM) isolates, and medication side effects were analyzed by intention-to-treat analysis.

Results:  The study group receiving a formoterol-budesonide combined treatment showed a significant improvement, both clinically and statistically, of symptoms (dyspnea, number of coughs, and rescue β2-adrenergic agonist-free days). Furthermore, we observed an HRQL improvement, with no changes in functional parameters or in PPM isolates, together with an important reduction in overall side effects, especially for those related to inhaled steroids, compared with the high-dose budesonide treatment group.

Conclusions:  Inhaled medium-dose formoterol-budesonide combined treatment in a single inhaler is more effective and safe compared with high-dose budesonide treatment in patients with non-CF bronchiectasis.

Trial registry:  ClinicalTrials.gov; No.: NCT00728715; URL: www.clinicaltrials.gov

Original Research: RESPIRATORY CARE

Chest. 2012;141(2):469-476. doi:10.1378/chest.11-0485

Background:  Current bilevel positive-pressure ventilators for home noninvasive ventilation (NIV) provide physicians with software that records items important for patient monitoring, such as compliance, tidal volume (Vt), and leaks. However, to our knowledge, the validity of this information has not yet been independently assessed.

Methods:  Testing was done for seven home ventilators on a bench model adapted to simulate NIV and generate unintentional leaks (ie, other than of the mask exhalation valve). Five levels of leaks were simulated using a computer-driven solenoid valve (0-60 L/min) at different levels of inspiratory pressure (15 and 25 cm H2O) and at a fixed expiratory pressure (5 cm H2O), for a total of 10 conditions. Bench data were compared with results retrieved from ventilator software for leaks and Vt.

Results:  For assessing leaks, three of the devices tested were highly reliable, with a small bias (0.3-0.9 L/min), narrow limits of agreement (LA), and high correlations (R2, 0.993-0.997) when comparing ventilator software and bench results; conversely, for four ventilators, bias ranged from −6.0 L/min to −25.9 L/min, exceeding −10 L/min for two devices, with wide LA and lower correlations (R2, 0.70-0.98). Bias for leaks increased markedly with the importance of leaks in three devices. Vt was underestimated by all devices, and bias (range, 66-236 mL) increased with higher insufflation pressures. Only two devices had a bias < 100 mL, with all testing conditions considered.

Conclusions:  Physicians monitoring patients who use home ventilation must be aware of differences in the estimation of leaks and Vt by ventilator software. Also, leaks are reported in different ways according to the device used.


Chest. 2012;141(2):477-484. doi:10.1378/chest.11-0129

Background:  Soluble mesothelin (SM) and megakaryocyte potentiating factor (MPF) are serum biomarkers of mesothelioma. This study examined the effect of clinical covariates on biomarkers levels and their diagnostic and prognostic value.

Methods:  Five hundred ninety-four participants were enrolled in a multicenter study, including 106 patients with mesothelioma and 488 control subjects. Multiple linear regression analyses were used to identify which covariates were independently associated with SM and MPF levels. The effect of these covariates on the diagnostic accuracy was evaluated with receiver operating characteristics curve analysis. In patients with mesothelioma, survival analysis was performed with Cox regression.

Results:  SM and MPF levels were independently associated with age, glomerular filtration rate (GFR), and BMI in control subjects and with GFR and tumor stage in patients with mesothelioma. The diagnostic accuracy of SM and MPF was significantly affected by the distribution of these covariates in the study population. The patients with mesothelioma were best discriminated from the control subjects with either the youngest age, the highest GFR, or the largest BMI. Furthermore, the control subjects were significantly better differentiated from stage II to IV than from stage I mesothelioma. MPF, not SM, was an independent negative prognostic factor, but only if adjusted for the biomarker-associated covariates.

Conclusions:  SM and MPF levels were affected by the same clinical covariates, which also had a significant impact on their diagnostic and prognostic value. To improve the interpretation of biomarker results, age, GFR, and BMI should be routinely recorded. Approaches to account for these covariates require further validation, as does the prognostic value of SM and MPF.

Original Research: CYSTIC FIBROSIS

Chest. 2012;141(2):485-493. doi:10.1378/chest.11-0917

Background:  Pulmonary exacerbations (PEx) are responsible for much of the morbidity and mortality associated with cystic fibrosis (CF). However, there is a paucity of data on outcomes in CF PEx and factors influencing outcomes.

Methods:  We reviewed all PEx in patients infected with Pseudomonas aeruginosa treated with parenteral antibiotics over 4 years at our center. Treatment failures were categorized a priori as those PEx requiring antibiotic regimen change, prolongation of therapy > 20 days because of failure to respond, an early recurrent event within < 45 days, or failure to recover lung function to > 90% of baseline FEV1.

Results:  A total of 101 patients were followed for 452 PEx. Treatment failures were observed in 125 (28%) of PEx; antibiotic regimen change was observed in 27 (6%), prolongation of therapy in 29 (6%), early recurrent events in 63 (14%), and failure to recover lung function to > 90% of baseline FEV1 in 66 (15%). Demographic factors associated with one or more treatment failures per year included advanced airways disease, use of enteric feeds, CF-related diabetes, and CF liver disease but did not include female sex or F508del homozygosity. Increased treatment failure risk was associated with lower admission FEV1 and increased markers of inflammation. At therapeutic completion, increased inflammatory markers correlated with treatment failure. Failure rates decreased with increasing number of active antimicrobial agents used based on in vitro susceptibility (zero, 28/65 [43%]; one, 38/140 [27%]; two, 59/245 [24%]; three, 0/2 [0%]; P = .02).

Conclusions:  One-fourth of PEx fail to respond adequately to initial management. Patient demographic and episode-specific clinical information can be used to identify individuals at increased risk of initial management failure.

Translating Basic Research Into Clinical Practice

Chest. 2012;141(2):494-499. doi:10.1378/chest.11-1730

The OX40 receptor is preferentially expressed by T cells, and its cognate ligand OX40L is primarily expressed by antigen-presenting cells such as dendritic cells following activation by thymic stromal lymphopoietin (TSLP). TSLP is released by the bronchial epithelium, airway smooth muscle, and some inflammatory cells in response to numerous insults such as allergens, viruses, and physical damage. OX40L is a costimulatory molecule that plays a sentinel role in the adaptive immune response by promoting T helper (Th) 2 polarization of naive T cells within the lymph node. These polarized T cells produce Th2 cytokines such as IL-4, IL-5, and IL-13, which have been implicated particularly in allergic eosinophilic asthma. Animal models have positioned both TSLP and OX40/OX40L as critical in the development of airway inflammation and hyperreactivity. In human disease, there is good evidence that TSLP is upregulated in asthma, but there are limited data to demonstrate overexpression of OX40 or OX40L in disease. Targeting the OX40/OX40L axis or TSLP presents a novel therapeutic strategy that has the potential of modifying the disease process and, therefore, impacting on its natural history. Whether this approach can demonstrate efficacy in established disease rather than at disease onset is unknown. Biologic therapies directed toward OX40/OX40L are in early phases of development, and results from these studies are eagerly awaited.

Ahead of the Curve

Chest. 2012;141(2):500-505. doi:10.1378/chest.11-2521

Over the past 50 years, we have seen dramatic changes in cardiovascular science and clinical care, accompanied by marked declines in the morbidity and mortality. Nonetheless, cardiovascular disease remains the leading cause of death and disability in the world, and its nature is changing as Americans become older, fatter, and ethnically more diverse. Instead of young or middle-aged men with ST-segment elevation myocardial infarction, the “typical” cardiac patient now presents with acute coronary syndrome or with complications related to chronic hypertension or ischemic heart disease, including heart failure, sudden death, and atrial fibrillation. Analogously, structural heart disease is now dominated by degenerative valve or congenital disease, far more common than rheumatic disease. The changing clinical scene presents cardiovascular scientists with a number of opportunities and challenges, including taking advantage of high-throughput technologies to elucidate complex disease mechanisms, accelerating development and implementation of evidence-based strategies, assessing evolving technologies of unclear value, addressing a global epidemic of cardiovascular disease, and maintaining high levels of innovation in a time of budgetary constraint and economic turmoil.

Topics in Practice Management

Chest. 2012;141(2):506-512. doi:10.1378/chest.11-0254

Over the last decade, endobronchial ultrasound (EBUS) evolved into a validated and powerful diagnostic tool. Although it is integral to medical care in some health-care systems, others struggle to justify its purchase based on diminishing reimbursement. In analyzing its value to a health-care system, looking at procedural reimbursement alone will grossly underestimate its economic impact. Downstream revenue has been defined by administrators as revenue captured after patients use one hospital service and then use others. By analyzing consecutive EBUS cases and taking downstream revenue into account, $2.4 million in collections was attributed to 97 patients who were newly referred for this procedure.

Selected Reports

Chest. 2012;141(2):513-514. doi:10.1378/chest.11-0956

Mucinous bronchioloalveolar carcinoma (BAC) can be associated with significant bronchorrhea. A 46-year-old man presented with BAC with 2,000 mL of sputum production on a daily basis, which prevented him from being extubated. As this condition is rare, there are only case reports outlining the therapy for the associated bronchorrhea. We used azithromycin, scopolamine, and inhaled fluticasone with moderate success. The initiation of an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, gefitinib, resulted in dramatic improvement in the volume of pulmonary secretions produced. The patient’s EGFR mutation status was subsequently found to be negative, which supports the hypothesis that the mechanism of reduction of bronchorrhea is independent of the antiproliferative effect of the drug.

Chest. 2012;141(2):515-517. doi:10.1378/chest.11-1483

The polymyxins (polymyxin B and E) are bactericidal polypeptide antibiotics first discovered in 1947 and used for the treatment of gram-negative bacterial infections. Renal and neurologic toxicities coupled with the increasing availability of effective alternatives led to declining use in the 1960s. The emergence of multidrug-resistant organisms in the past decade has resulted in a resurgence in the use of polymyxins in critically ill patients, yet the side effects are not well known. We report two cases of respiratory arrest likely due to polymyxin B infusions in the context of a 10-fold increase in the use of polymyxin B in our institution over the past 10 years.

Postgraduate Education Corner

Chest. 2012;141(2):545-558. doi:10.1378/chest.10-1302

Plain chest roentgenogram remains the most commonly ordered screening test for pulmonary disorders. Its lower sensitivity demands greater accuracy in interpretation. This greater accuracy can be achieved by adhering to an optimal and organized approach to interpretation. It is important for clinicians not to misread an abnormal chest radiograph (CXR) as normal. Clinicians can only acquire the confidence in making this determination if they read hundreds of normal CXRs. An individual should follow the same systematic approach to reading CXRs each time. All clinicians must make a concerted effort to read plain CXRs themselves first without reading the radiologist report and then discuss the findings with their radiology colleagues. Looking at the lateral CXR may shed light on 15% of the lung that is hidden from view on the posteroanterior film. Comparing prior films with the recent films is mandatory, when available, to confirm and/or extend differential diagnosis. This article outlines one of the many systematic approaches to interpreting CXRs and highlights the lesions that are commonly missed. A brief description of the limitations of CXR is also included.

From the Division of Pulmonary and Critical Care Medicine (Drs Suhail Raoof and Irugulpati), New York Methodist Hospital, Brooklyn, NY; the Department of Radiology (Dr Feigin), The Johns Hopkins University, Baltimore, MD; the Division of Pulmonary and Critical Care Medicine (Dr Sung), Beth Israel Medical Center, New York, NY; the Department of Radiology (Dr Sabiha Raoof), Jamaica Hospital Medical Center, Jamaica, NY; and the Department of Pulmonary and Critical Care Medicine (Dr Rosenow), Mayo Clinic, Rochester, MN.

Correspondence to: Suhail Raoof, MD, FCCP, Division of Pulmonary and Critical Care Medicine, New York Methodist Hospital, 506 Sixth St, Brooklyn, NY 11215; e-mail: sur9016@nyp.org

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (http://www.chestpubs.org/site/misc/reprints.xhtml).

Financial/nonfinancial disclosures: The authors have reported to CHEST the following conflicts of interest: Dr Sung was the principal investigator for Broncus Technologies 2007 to 2009. Drs Suhail Raoof, Feigin, Sabiha Raoof, Irugulpati, and Rosenow have reported that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.


Chest. 2012;141(2):518-527. doi:10.1378/chest.11-0331

Part 2 of this review of ICU scoring systems examines how scoring system data should be used to assess ICU performance. There often are two different consumers of these data: lCU clinicians and quality leaders who seek to identify opportunities to improve quality of care and operational efficiency, and regulators, payors, and consumers who want to compare performance across facilities. The former need to know how to garner maximal insight into their care practices; this includes understanding how length of stay (LOS) relates to quality, analyzing the behavior of different subpopulations, and following trends over time. Segregating patients into low-, medium-, and high-risk populations is especially helpful, because care issues and outcomes may differ across this severity continuum. Also, LOS behaves paradoxically in high-risk patients (survivors often have longer LOS than nonsurvivors); failure to examine this subgroup separately can penalize ICUs with superior outcomes. Consumers of benchmarking data often focus on a single score, the standardized mortality ratio (SMR). However, simple SMRs are disproportionately affected by outcomes in high-risk patients, and differences in population composition, even when performance is otherwise identical, can result in different SMRs. Future benchmarking must incorporate strategies to adjust for differences in population composition and report performance separately for low-, medium- and high-acuity patients. Moreover, because many ICUs lack the resources to care for high-acuity patients (predicted mortality >50%), decisions about where patients should receive care must consider both ICU performance scores and their capacity to care for different types of patients.


Chest. 2012;141(2):528-544. doi:10.1378/chest.11-0773

There is a strong association between sleep-related problems and neurologic diseases. Neurologic diseases of the CNS can directly cause sleep problems when sleep-wake mechanisms associated with the ascending reticular activating system are involved. The major sleep disorders associated with neurologic problems are outlined in the International Classification of Sleep Disorders, 2nd edition, as hypersomnias of central origin, sleep-related breathing disorders, the insomnias, circadian rhythm sleep disorders, sleep-related movement disorders, parasomnias, and sleep-related epilepsy. In a patient with CNS disease and excessive sleepiness, sleep-related breathing disorders should be a first concern, given the known association between obstructive sleep apnea (OSA) and cerebrovascular disease and the potential confounding effects that OSA might have on an otherwise compromised ischemic CNS penumbra. A basic knowledge of the anatomy and physiology of the sleep-wake mechanisms provides a rationale for pharmacologic intervention. Nonpharmacologic treatments are also important, especially when sleep-related breathing disorders are a concern. In addition, as patients with neurologic diseases are often prone to the adverse effects of many medications, the specific treatment regimen for any given individual should always include good sleep hygiene practices that use cognitive behavioral therapy.


Chest. 2012;141(2):560-563. doi:10.1378/chest.11-1493

LightRWBallWCJr.Glucose and amylase in pleural effusionsJAMA19732253257260CameronJLKiefferRSAndersonWJZuidemaGDInternal pancreatic fistulas: pancreatic ascites and pleural effusionsAnn Surg19761845587593MetzgerJBGaragusiVFKerwinDMPulmonary oxalosis caused by Aspergillus nigerAm Rev Respir Dis19841293501502PottmeyerEWIIIFreyCFMatsunoSPancreaticopleural fistulasArch Surg19871226648654RockeyDCCelloJPPancreaticopleural fistula. Report of 7 patients and review of the literatureMedicine (Baltimore)1990696332344BurgessNAMooreHEWilliamsJOLewisMHA review of pancreatico-pleural fistula in pancreatitis and its managementHPB Surg1992527986LaiCCLiawSJHsiaoYCEmpyema thoracis due to Rhizopus oryzae in an allogenic bone marrow transplant recipientMed Mycol20064417578SahnSAPleural effusions of extravascular originClin Chest Med2006272285308Rojas-SolanoJRLightRWBrenes-DittelABlack pleural fluid [in Spanish]Arch Bronconeumol2009452103104LiaoWCChenCHTuCYBlack pleural effusion in melanomaCMAJ20101828E314


Chest. 2012;141(2):564. doi:10.1378/chest.11-0326

Now I know it all.
Now I know your heart’s
imperfections: left anterior
descending coronary artery
fifty percent occluded,
right one nearly as bad.
Aorta: distal, mild.
Those petechial hemorrhages
on the small and large intestines,
they can’t hide from me now.
I know about that benign
cortical cyst on your right kidney,
the bilateral pulmonary edema.
The M.E. noted that your body
was “well-developed, well-nourished,
consistent with the recorded age
of 48,” yet your intestine
was digesting itself: autolysis.
He and I, we know
your secrets. Even though I was
no longer your wife, he told me
on the phone precisely how you died,
before the toxicology reports
were in. O secretive one,
now I know exactly how much
your heart weighed.

Chest. 2012;141(2):565. doi:10.1378/chest.11-1151

i carry your heart with me(i carry it in my heart)…
      E. E. Cummings
A heart of wisdom,
I said that day
beside the lake,
knowing even then
about the narrowing
that stood between us
patiently whispering
its own story.
Always the unseen
universe of shadows
has its demands, its
plans to hurry us along,
the tall tree circle of ifs and
thens moving in a little closer.
(What I want is time
and time and time and no
cutting of his sweet skin and
no slicing through his
good bones and no
hurt, no pain, and my
arms wrapping protection
around him
as if things ever
worked that way.)
Almost painful that
sapphire, that magenta:
impatiens, morning glories
pouring out their last
into the burnished air.
No pale new shoots,
tame blossoms now but this
bright frenzied overgrowth
grabbing for our throats
and hanging on, this
wringing out of drops,
savoring of crumbs, sharp
metal taste on tongue,
this dazzling ache of
petals littering the ground.

Chest. 2012;141(2):566. doi:10.1378/chest.11-1354

Not wanting to show favoritism
I deposit my uterus, ovaries and meningioma
at Yale-New Haven Hospital
and my gall bladder and appendix
at St. Raphael’s
and stay at each hospital
for $1300 a night.
TV extra, no HBO, cold toast, no hot towels,
no fresh flowers, no iMac computer,
no gold-foiled chocolates
on my pillow at night.
Today I e-mailed my HMO.
Sirs: If I should need a tonsilectomy,
(the only thing I’ve left to part with)
for the same rates
I will recuperate in
the Waldorf Towers,
the Ritz in Paris,
or Gritti Palace in Venice
with a view of the gondeliers.

Chest. 2012;141(2):566. doi:10.1378/chest.11-1372

How many times have I peered
into black pupils of blue eyes
through windows of cornea
past blooming iris
beyond vitreous chambers
and protein oceans
until my light reached
the yellow flush of macula
optic disc
bright as a harvest moon
where nerves and vessels
weave and converge
knitting a synaptic web
where I imagine
all the beautiful
images are stored.


Chest. 2012;141(2):567. doi:10.1378/chest.11-1965

1GounantVNinaneVJansonXRelease of metal particles from needles used for transbronchial needle aspirationChest201113911381432CasoniGLGurioliCRavagliaCGurioliCPolettiVEndobronchial ultrasound-guided transbronchial needle aspiration: one defect away from perfectChest20111401265

Chest. 2012;141(2):568. doi:10.1378/chest.11-2316

1GounantVNinaneVJansonXRelease of metal particles from needles used for transbronchial needle aspirationChest20111391138143

Chest. 2012;141(2):568-569. doi:10.1378/chest.11-2056

1O’DonnellDEDeesomchokALamYMEffects of BMI on static lung volumes in patients with airway obstructionChest201114024614682van den BemtLvan WayenburgCASmeeleIJSchermerTRObesity in patients with COPD, an undervalued problem?Thorax20096476406413SchermerTRSmeeleIJThoonenBPCurrent clinical guideline definitions of airflow obstruction and COPD overdiagnosis in primary careEur Respir J20083249459524HoSFO’MahonyMSStewardJABreayPBuchalterMBurrMLDyspnoea and quality of life in older people at homeAge Ageing20013021551595LandboCPrescottELangePVestboJAlmdalTPPrognostic value of nutritional status in chronic obstructive pulmonary diseaseAm J Respir Crit Care Med1999160618561861

Chest. 2012;141(2):569. doi:10.1378/chest.11-2904

1O’DonnellDEDeesomchokALamY-MEffects of BMI on static lung volumes in patients with airway obstructionChest201114024614682SchermerTRSmeeleIJThoonenBPCurrent clinical guideline definitions of airflow obstruction and COPD overdiagnosis in primary careEur Respir J20083249459523HansenJESunXGWassermanKSpirometric criteria for airway obstruction: use percentage of FEV1/FVC ratio below the fifth percentile, not <70%Chest200713123493554JonesRLNzekwuMMUThe effects of body mass index on lung volumesChest200613038278335OraJLavenezianaPOfirDDeesomchokAWebbKAO’DonnellDECombined effects of obesity and chronic obstructive pulmonary disease on dyspnea and exercise toleranceAm J Respir Crit Care Med200918010964971

Chest. 2012;141(2):569-570. doi:10.1378/chest.11-2364

1PetersJSinghHBrooksEGPersistence of community-acquired respiratory distress syndrome toxin-producing Mycoplasma pneumoniae in refractory asthmaChest201114024014072SutherlandERMartinRJAsthma and atypical bacterial infectionChest20071326196219663MagantiKOnyemereKJonesMPOral erythromycin and symptomatic relief of gastroparesis: a systematic reviewAm J Gastroenterol20039822592634FriedlanderALAlbertRKChronic macrolide therapy in inflammatory airways diseasesChest2010138512021212

Chest. 2012;141(2):570. doi:10.1378/chest.11-2909

1PetersJSinghHBrooksEGPersistence of community-acquired respiratory distress syndrome toxin-producing Mycoplasma pneumoniae in refractory asthmaChest201114024014072HardyRDCoalsonJJPetersJAnalysis of pulmonary inflammation and function in the mouse and baboon after exposure to Mycoplasma pneumoniae CARDS toxinPLoS ONE2009410e75623WuQMartinRJLafastoSToll-like receptor 2 down-regulation in established mouse allergic lungs contributes to decreased mycoplasma clearanceAm J Respir Crit Care Med200817777207294FriedlanderALAlbertRKChronic macrolide therapy in inflammatory airways diseasesChest2010138512021212

Chest. 2012;141(2):570-571. doi:10.1378/chest.11-2409

1HanMKCurran-EverettDDransfieldMTand the COPD Gene InvestigatorsRacial differences in quality of life in patients with COPDChest20111405116911762LohLCTehPNSethKDRamanSVijayasinghamPThayaparanTEthnicity as a determinant of asthma-related quality of life in a multiracial countryAsia Pac J Public Health200618149553KuykenWOrleyJHudelsonPSartoriusNQuality of life assessment across culturesInt J Ment Health1994235274StåhlEPostmaDSJuniperEFSvenssonKMearILöfdahlCGHealth-related quality of life in asthma studies. Can we combine data from different countries?Pulm Pharmacol Ther200316153595NgTPLimLCJinAShinfukuNEthnic differences in quality of life in adolescents among Chinese, Malay and Indians in SingaporeQual Life Res2005147175517686OlsonLMLaraMPat FrintnerMMeasuring health status and quality of life for US children: relationship to race, ethnicity, and income statusAmbul Pediatr20044suppl 4377386

Chest. 2012;141(2):571. doi:10.1378/chest.11-2539

1HanMKCurran-EverettDDransfieldMTand the COPD Gene InvestigatorsRacial differences in quality of life in patients with COPDChest20111405116911762JonesPWAndersonJACalverleyPMTORCH investigatorsHealth status in the TORCH study of COPD: treatment efficacy and other determinants of changeRespir Res20111271

Chest. 2012;141(2):571-572. doi:10.1378/chest.11-2414

1EnriquezJRParikhSVSelzerFIncreased adverse events after percutaneous coronary intervention in patients with COPD: insights from the National Heart, Lung, and Blood Institute dynamic registryChest201114036046102BergerJSSanbornTAShermanWBrownDLEffect of chronic obstructive pulmonary disease on survival of patients with coronary heart disease having percutaneous coronary interventionAm J Cardiol20049456496513KonecnyTSomersKOrbanMInteractions between COPD and outcomes after percutaneous coronary interventionChest201013836216274SorianoJBRigoFGuerreroDHigh prevalence of undiagnosed airflow limitation in patients with cardiovascular diseaseChest20101372333340

Chest. 2012;141(2):572-573. doi:10.1378/chest.11-2564

1EnriquezJRParikhSVSelzerFIncreased adverse events after percutaneous coronary intervention in patients with COPD: insights from the National Heart, Lung and Blood Institute Dynamic RegistryChest201114036046102National Heart, Lung and Blood Institute. Morbidity & Mortality: 2009 Chart Book on Cardiovascular, Lung, and Blood DiseasesNational Heart, Lung and Blood Institute Web site .http://www.nhlbi.nih.gov/resources/docs/2009_ChartBook.pdf. Accessed December 19, 20113RabeKFHurdSAnzuetoAGlobal Initiative for Chronic Obstructive Lung DiseaseGlobal strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summaryAm J Respir Crit Care Med200717665325554QaseemAWiltTJWeinbergerSEAmerican College of PhysiciansAmerican College of Chest PhysiciansAmerican Thoracic SocietyEuropean Respiratory SocietyDiagnosis and management of stable chronic obstructive pulmonary disease: a clinical practice guideline update from the American College of Physicians, American College of Chest Physicians, American Thoracic Society, and European Respiratory SocietyAnn Intern Med201115531791915HananiaNAMarciniukDDA unified front against COPD: clinical practice guidelines from the American College of Physicians, the American College of Chest Physicians, the American Thoracic Society, and the European Respiratory SocietyChest20111403565566

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