Chest. 2012;142(5):1081-1082. doi:10.1378/chest.12-1656

In the decade following the first successful lung transplant operation in 1963, the worldwide experience was characterized by limited survival because of allograft rejection and surgical complications. After an 8-year hiatus in lung transplantation (1973-1981), cyclosporine revolutionized solid organ transplantation, and there was steady growth in the number of lung transplant surgeries performed annually over the ensuing 30 years.1 Our collective experience has shown that although lung transplantation improves quality of life and prolongs survival for patients with end-stage lung disease, the incidence of rejection is higher than for other organ transplant recipients.2 Accordingly, long-term immunosuppression following lung transplantation mandates two- or three-drug regimens. Many of the agents used for the prevention of posttransplant rejection are increasingly used for patients with a variety of inflammatory lung diseases, including sarcoidosis, pulmonary vasculitides, and idiopathic interstitial pneumonitis.

Chest. 2012;142(5):1082-1085. doi:10.1378/chest.12-0981

The survival of patients with COPD is improving, albeit slowly, as a result of a series of modest enhancements in our management. In this issue of CHEST (see page 1104), Rodrigo and Neffen1 remind us of the latest of these incremental steps—the introduction of indacaterol, the first of the once-daily long-acting β2 agonists (LABAs) for the treatment of COPD.

Chest. 2012;142(5):1085-1087. doi:10.1378/chest.12-1115

Asthma self-management education has been an essential component of the National Asthma Education and Prevention Program guidelines since their initial publication in 1991.1 Although asthma self-management education made sense intuitively, there was limited evidence of benefit at first. Subsequent research has shown improved health outcomes and a reduction in asthma-related health-care costs with self-management programs in patients with chronic asthma.2 As a result, updated National Asthma Education and Prevention Program asthma guidelines in 1997 and 2007 gave this educational component greater emphasis.3,4 Recommended as part of such programs are (1) asthma information and self-management training, (2) self-monitoring with symptoms or peak expiratory flow measurements, (3) regular clinician assessment, and (4) a written action plan. Evidence-based assessment of these items individually has demonstrated the greatest benefit from asthma education and self-monitoring. A limited number of studies have assessed the effect of a written action plan separate from self-management programs in general. A Cochrane meta-analysis of these studies concluded they provided insufficient evidence that action plans as the sole intervention improve asthma outcomes.5

Chest. 2012;142(5):1087-1088. doi:10.1378/chest.12-1330

Out-of-proportion pulmonary hypertension (PH) is defined as an unjustified degree of PH that occurs in patients suffering from different types of parenchymal lung diseases (ie, COPD, idiopathic pulmonary fibrosis [IPF], and so forth). The concept of out-of-proportion PH was introduced quite recently in the field of PH. Until a few years ago, the term cor pulmonale was used to indicate the development of PH related to parenchymal diseases and exposure to chronic hypoxia, leading to chronic respiratory failure and, consequently, to right-sided heart failure. However, in recent years, a better understanding of the mechanisms underlying the structural remodeling of the pulmonary vascular bed has raised doubts as to whether everything can be explained by the presence of cor pulmonale. In fact, some patients may develop extremely high pulmonary artery pressure that cannot be explained solely by hypoxia and rearrangement of the pulmonary vascular bed. Due to a growing use of right-sided heart catheterization to select appropriate candidates for lung transplantation, a vast category of patients suffering from parenchymal lung diseases (often accompanied by minor pulmonary impairment on pulmonary function test and/or CT scan) with an unexplained severe degree of PH was brought to the attention of physicians. In these patients, the development of moderate to severe PH, which cannot be explained by the degree of parenchymal lung disease and hypoxia, has been termed “out-of-proportion” PH, and an arbitrary value of >35 mm Hg mean pulmonary artery pressure has been selected to identify this category of patients.

Editorials: Point/Counterpoint Editorials

Chest. 2012;142(5):1090-1092. doi:10.1378/chest.12-1995

Sedative and analgesic drugs are used routinely on patients in the ICU who are mechanically ven­tilated. These drugs can be administered either by continuous infusion or by intermittent IV bolus strategies. The theoretical benefit of a continuous infusion strategy is maintenance of a constant level of drug, leading to improved patient comfort. This strategy is also less taxing on the busy bedside nurse. The potential detriments include a tendency to use more drug(s), which may result in heavier levels of sedation. The theoretical benefit of an intermittent bolus strat­egy is a reduction in the drug amount used and a lesser tendency to oversedate patients; however, this approach may lead to a lower level of patient comfort and a greater burden on the bedside nursing staff. This editorial debate presents an evidence-based summary, highlighting the superiority of the continuous infusion strategy.

Chest. 2012;142(5):1092-1094. doi:10.1378/chest.12-1997

Sedative drug administration is considered part of the standard care of critically ill patients. Nowhere is this more evident than in the treatment of those requiring mechanical ventilation. The overarching concerns addressed by sedation include mitigating patient discomfort and facilitating ventilation, along with other parts of routine ICU care. Emphasizing the importance of these goals, a retrospective analysis of the 174 ICUs contributing data to Project IMPACT (Cerner Corp) showed that the use of IV infusions of sedative agents nearly doubled over the years 2001 to 2007, even when accounting for severity of illness.1

Chest. 2012;142(5):1095. doi:10.1378/chest.12-1996

Dr Vinayak1 offers important arguments regarding the minimization of sedation, a trend that has been present in the published literature for more than a decade. However, it is important to look at the practical options for this changing philosophy in sedation strategies. He cites the important study by Strøm et al,2 referred to as “no sedation.” A couple of aspects regarding this study deserve comment. First, patients in this trial who were randomized to the intervention group received morphine, rather than sedatives, as their foundational strategy. Morphine is an opiate analgesic drug. Although not in the category of pharmacologic sedatives, this drug certainly has a “calming” effect on patients who are mechanically ventilated. It is rare that a patient can be managed without any drug, at least not in the early stages of respiratory failure. Second, this study was performed in Denmark, where ICU nursing to patient ratios were universally 1:1. This luxury is very rare in the rest of the world and is certainly a practical limitation to the widespread institution of the “no sedation” strategy. Furthermore, a person who can be summoned to provide verbal reassurance in the event that a patient is agitated is not a reality in most busy ICUs around the world. Last, one of five patients in this study could not tolerate this “no sedation” strategy. Accordingly, this study, although impressive, has important practical limitations. Survival from critical illness is improving substantially. For these reasons, the reality is that sedatives will continue to be necessary for the foreseeable future for managing patients who are mechanically ventilated.

Chest. 2012;142(5):1095-1096. doi:10.1378/chest.12-1998

Dr Kress’s1 concluding comments regarding sedation management with continuous agents are irrefutable: (1) The evidence strongly supports a practice that interrupts sedation daily when continuous sedation is used. (2) As to choice of agent, the upcoming consensus sedative guideline revisions will significantly downsize the role of benzodiazepines compared with agents with more rapid offset pharmacology. Yet it remains unclear whether all ventilated patients need a continuous sedative drug as part of their management.

Second Opinion

Chest. 2012;142(5):1089. doi:10.1378/chest.142.5.1089
Topics: smoke

Commentary: Patient Safety Forum

Chest. 2012;142(5):1097-1103. doi:10.1378/chest.12-0148

Medical education research contributes to translational science (TS) when its outcomes not only impact educational settings, but also downstream results, including better patient-care practices and improved patient outcomes. Simulation-based medical education (SBME) has demonstrated its role in achieving such distal results. Effective TS also encompasses implementation science, the science of health-care delivery. Educational, clinical, quality, and safety goals can only be achieved by thematic, sustained, and cumulative research programs, not isolated studies. Components of an SBME TS research program include motivated learners, curriculum grounded in evidence-based learning theory, educational resources, evaluation of downstream results, a productive research team, rigorous research methods, research resources, and health-care system acceptance and implementation. National research priorities are served from translational educational research. National funding priorities should endorse the contribution and value of translational education research.

Topics: health care

Original Research: COPD

Chest. 2012;142(5):1104-1110. doi:10.1378/chest.11-2252

Background:  Bronchodilators are central to the symptomatic management of patients with COPD. Previous data have shown that inhaled indacaterol improved numerous clinical outcomes over placebo.

Methods:  This systematic review explored the efficacy and safety of indacaterol in comparison with tiotropium or bid long-acting β2-agonists (TD-LABAs) for treatment of moderate to severe COPD. Randomized controlled trials were identified after a search of different databases of published and unpublished trials.

Results:  Five trials (5,920 participants) were included. Compared with tiotropium, indacaterol showed statistically and clinically significant reductions in the use of rescue medication and dyspnea (43% greater likelihood of achieving a minimal clinically important difference [MCID] in the transitional dyspnea index [TDI]; number needed to treat for benefit [NNTB] = 10). Additionally, the MCID in health status was more likely to be achieved with indacaterol than with tiotropium (OR = 1.43; 95% CI, 1.22–1.68; P = .00001; NNTB = 10). Trough FEV1 was significantly higher at the end of treatment with indacaterol than with TD-LABAs (80 mL, P = .00001). Similarly, indacaterol significantly improved dyspnea (61% greater likelihood of achieving an MCID in TDI, P = .008) and health status (21% greater likelihood of achieving an MCID in St. George’s Respiratory Questionnaire, P = .04) than TD-LABA. Indacaterol showed similar levels of safety and tolerability to both comparators.

Conclusions:  Available evidence suggests that indacaterol may prove useful as an alternative to tiotropium or TD-LABA due to its effects on health status, dyspnea, and pulmonary function.CHEST 2012; 142(5):1104–1110

Chest. 2012;142(5):1111-1117. doi:10.1378/chest.12-0421

Background:  A clinical study was performed to assess the safety and efficacy of bilateral AeriSeal Emphysematous Lung Sealant System (ELS) treatment in patients with advanced emphysema out to 1 year.

Methods:  Twenty patients received treatment at four subsegments, two in each upper lobe. Ten had upper lobe disease, and 10 had homogeneous disease. Treatments were administered under moderate sedation. Efficacy was assessed at 3, 6, and 12 months.

Results:  Procedure times were short (15.2 ± 9.6 min), and hospital length of stay averaged 1.1 days. The study was successful in reaching its primary end point of a reduction at 3 months in upper lobe lung volume assessed by quantitative CT scan analysis (−895 ± 484 mL, P < .001). Treatment was associated with improvements in spirometry (ΔFEV1 at 6 months = 31.2% ± 36.6%, 12 months = 25.0% ± 33.4%), gas trapping (Δresidual volume/total lung capacity at 6 months = −7.2% ± 12.7%, 12 months = −10.9% ± 14.0%), diffusing capacity of lung for carbon monoxide (6 months = 12.7% ± 16.4%, 12 months = 12.3% ± 21.1%), symptom scores (ΔMedical Research Council dyspnea score at 6 months = median 0, range −2 to 1, 12 months = median −1, range −3 to 0), and health-related quality of life (ΔSt. George Respiratory Questionnaire at 6 months = −8.0 ± 17.2 U, 12 months = −7.0 ± 15.8 U). There was one serious procedural complication and seven all-cause significant respiratory adverse events over 17 patient-years of follow-up.

Conclusions:  Bilateral ELS treatment administered under conscious sedation in patients with advanced emphysema is associated with short procedure time and length of hospital stay and produces physiologic and functional improvement out to 1 year.

Trial registration:  ClinicalTrials.gov; No.: NCT01181466; URL: www.clinicaltrials.gov

Chest. 2012;142(5):1118-1125. doi:10.1378/chest.11-2421

Background:  COPD is associated with the risk of cardiovascular events (CVEs), but its impact on overall mortality has not been well quantified. We determined the impact of global CVE risk assessment on CVE and total mortality in subjects with COPD.

Methods:  We examined the severity of COPD in 6,266 US adult patients aged ≥ 40 years in relation to the estimated 10-year risk of CVEs. COPD was defined by spirometry, and severity was classified as mild (FEV1 ≥ 80%), moderate (50% ≤ FEV1 < 80%), or severe (FEV1 < 50%). Cox proportional hazards regression was used to evaluate the relationship of global CVE risk combined with COPD status to CVE and all-cause mortality over a mean follow-up of 98.8 ± 51.3 months.

Results:  The proportion of individuals at high risk for CVEs ranged from 25% (without COPD) to > 50% (with moderate to severe COPD) (P < .05). When global CVE risk scores were low, CVE mortality was also low (< 10/1,000 person-years) regardless of COPD severity, and CVE mortality was high when CVE global risk was high (> 40/1,000 person-years). Global CVE risk improved prediction for both CVEs and total mortality in patients with COPD (P < .0001), with a net reclassification improvement of 17.1% (P < .0001) and 13.0% (P < .0001), respectively, beyond lung function measures.

Conclusions:  The addition of global CVE risk scores to lung function data significantly improves risk stratification of patients with COPD for CVE and total mortality and, thus, adds to predicting long-term survival of these patients.

Chest. 2012;142(5):1126-1133. doi:10.1378/chest.11-2413

Background:  Comorbidities are frequent in patients hospitalized for COPD exacerbation, but little is known about their relation with short-term mortality and hospital readmissions. Our hypothesis is that the frequency and type of comorbidities impair the prognosis within 12 weeks after discharge.

Methods:  A longitudinal, observational, multicenter study of patients hospitalized for a COPD exacerbation with spirometric confirmation was performed. Comorbidity information was collected using the Charlson index and a questionnaire that included other common conditions not included in this index. Dyspnea, functional status, and previous hospitalization for COPD or other reasons among other variables were investigated. Information on mortality and readmissions for COPD or other causes was collected up to 3 months after discharge.

Results:  We studied 606 patients, 594 men (89.9%), with a mean (SD) age of 72.6 (9.9) years and a postbronchodilator FEV1 of 43.2% (21.2). The mean Charlson index score was 3.1 (2.0). On admission, 63.4% of patients had arterial hypertension, 35.8% diabetes mellitus, 32.8% chronic heart failure, 20.8% ischemic heart disease, 19.3% anemia, and 34% dyslipemia. Twenty-seven patients (4.5%) died within 3 months. The Charlson index was an independent predictor of mortality (P < .003; OR,1.23; 95% CI, 1.07-1.40), even after adjustment for age, FEV1, and functional status measured with the Katz index. Comorbidity was also related with the need for hospitalization from the ED, length of stay, and hospital readmissions for COPD or other causes.

Conclusions:  Comorbidities are common in patients hospitalized for a COPD exacerbation, and they are related to short-term prognosis.

Chest. 2012;142(5):1134-1142. doi:10.1378/chest.11-2144

Background:  Quadriceps dysfunction in COPD may be mediated by inflammatory mechanisms or impaired satellite cell function. Resistance training is of proven efficacy in these patients, but data on muscle inflammatory and satellite cell response to resistance exercise in COPD are lacking. We aimed to examine the inflammatory and satellite cell profile of the quadriceps in patients with COPD and healthy control subjects at rest and after acute and chronic resistance exercise.

Methods:  Seventeen patients with COPD and 10 healthy control subjects underwent 8 weeks of bilateral lower-limb, high-intensity resistance training, thrice weekly, on an isokinetic dynamometer. Quadriceps muscle biopsy specimens from the dominant thigh were obtained at baseline, 24 h following the first exercise bout, and after 8 weeks 24 h after the last exercise bout. Glycol methacrylate-embedded muscle biopsy specimens were analyzed using immunohistochemistry to identify neutrophils, macrophages, and satellite cells.

Results:  Neutrophils were significantly elevated in the quadriceps of patients with COPD at baseline compared with healthy control subjects (P = .03). Inflammatory cells were increased significantly at 24 h in both groups but were similar to baseline values at week 8, with no difference detectable between healthy control subjects and patients with COPD. Satellite cell numbers were comparable between patients and control subjects at baseline, tended to increase at 24 h, and remained elevated at week 8.

Conclusions:  Inflammatory cells are elevated in the resting quadriceps of patients with COPD. Acute resistance exercise leads to an inflammatory myositis, which is attenuated with regular training. Satellite cells in patients and control subjects are comparable and are increased in response to exercise.

Trial Registry:  ISRCTN Register; No.: ISRCTN22764439; URL: www.controlled-trials.com

Original Research: Asthma

Chest. 2012;142(5):1143-1149. doi:10.1378/chest.11-1700

Background:  Asthma action plans (AAPs) are a priority recommendation of the National Asthma Education and Prevention Program and have been shown to positively affect health outcomes. Patient satisfaction is an important clinical outcome, yet little is known about its association with receiving an AAP. This study examined the association between having an AAP and behaviors to keep asthma in control and patient satisfaction with care.

Methods:  The study design was a cross-sectional analysis of baseline data from a randomized trial evaluating a self-management program among 808 women with asthma. Participants reported demographic information, interactions with clinicians, whether they had an AAP and owned a peak flow meter, self-management behaviors, and symptoms.

Results:  The mean age of the participants was 48 ± 13.6 years, 84% (n = 670) were satisfied with their asthma care, and 48% (n = 383) had a written AAP from their physician. Women not having an AAP were less likely to take asthma medication as prescribed [χ2(1) = 13.68, P < .001], to initiate a discussion about asthma with their physicians [χ2(1) = 26.35, P < .001], and to own a peak flow meter [χ2(1) = 77.84, P < .001]. Adjusting for asthma control, income, and medical specialty, women who did not have an AAP were more likely to report dissatisfaction with their asthma care (OR, 2.07; 95% CI, 1.35-3.17; P < .001).

Conclusions:  Women without an AAP were less likely to initiate discussions with their physicians, take medications as prescribed, and own a peak flow meter to monitor asthma, all considered important self-management behaviors. They were also less satisfied with their care. Not having an AAP may affect interactions between patient and physician and clinical outcomes.

Original Research: Pulmonary Vascular Disease

Chest. 2012;142(5):1150-1157. doi:10.1378/chest.11-2490

Background:  Precapillary pulmonary hypertension (PH) is a complication of pulmonary Langerhans cell histiocytosis (PLCH) associated with increased mortality. However, outcomes and efficacy of pulmonary arterial hypertension (PAH) therapies in patients with PH complicating PLCH (PLCH-PH) remain unknown.

Methods:  Consecutive patients with PLCH with PH confirmed by right-sided heart catheterization were included in the study. Characteristics at baseline and during follow-up as well as survival were analyzed.

Results:  Twenty-nine patients were studied. Baseline characteristics of patients with PLCH-PH were as follows: 83% of patients in World Health Organization (WHO) functional class III to IV, mean 6-min walk distance of 355 ± 95 m, mean pulmonary arterial pressure (mPAP) of 45 ± 14 mm Hg, cardiac index of 3.2 ± 0.9 L/min/m2, and pulmonary vascular resistance (PVR) of 555 ± 253 dyne/s/cm5. Use of PAH therapy in 12 patients was followed by an improvement in mPAP (56 ± 14 mm Hg and 45 ± 12 mm Hg, P = .03) and PVR (701 ± 239 dyne/s/cm5 and 469 ± 210 dyne/s/cm5, P = .01) between baseline and follow-up evaluations. No significant oxygen worsening was observed in the treated group. The 1-, 3-, and 5-year survival estimates of the 29 patients were 96%, 92%, and 73%, respectively. Except a trend toward a better survival rate associated with the use of PAH therapy, WHO functional class was the only variable significantly associated with death.

Conclusions:  In this group of patients, PAH therapies improved hemodynamics without oxygen worsening or pulmonary edema. WHO functional class was the only prognostic factor identified. Prospective clinical trials focusing on this population of patients are warranted.

Chest. 2012;142(5):1158-1165. doi:10.1378/chest.12-0071

Background:  Exercise stress echocardiography has not been recommended in the diagnostic workup of pulmonary hypertension because of insufficient certainty about feasibility and limits of normal.

Methods:  Doppler echocardiography pulmonary hemodynamic measurements were performed at a progressively increased workload in 56 healthy male and 57 healthy female volunteers aged 19 to 63 years. Mean pulmonary artery pressure (mPAP) was estimated from the maximal tricuspid regurgitation jet velocity. Cardiac index was calculated from the left ventricular outflow velocity-time integral. Pulmonary vascular distensibility α index, the percentage change of vessel diameter per mm Hg of mPAP, was calculated from multipoint mPAP-cardiac output (CO) plots.

Results:  Peak exercise at 175 ± 50 W was associated with an mPAP of 33 ± 7 mm Hg and a CO of 18 ± 5 L/min. The slope of mPAP-CO relationships was 1.5 ± 0.5 mm Hg/L/min, and the distensibility coefficient (α) was 1.3% ± 1.0%/mm Hg. Maximal workload and cardiac index were higher in men than in women (P < .05), but mPAP-cardiac index relationships were not different. However, women had a higher α (1.6% ± 1.3%/mm Hg vs 1.1% ± 0.6%/mm Hg, P < .05). The average mPAP-cardiac index slope was higher and α lower in subjects ≥ 50 years old. Upper limits of normal of mPAP at exercise were 34 mm Hg at a CO < 10 L/min, 45 mm Hg at a CO < 20 L/min, and 52 mm Hg at a CO < 30 L/min. These values are in keeping with previously reported invasive measurements.

Conclusions:  Exercise stress echocardiography of the pulmonary circulation is feasible and allows for flow-corrected definition of upper limits of normal. Women have a more distensible pulmonary circulation.

Chest. 2012;142(5):1166-1174. doi:10.1378/chest.11-2798

Background:  Pulmonary hypertension (PH) is a well-recognized complication of COPD. The impact of PH on exercise tolerance is largely unknown. We evaluated and compared the circulatory and ventilatory profiles during exercise in patients with COPD without PH, with moderate PH, and with severe PH.

Methods:  Forty-seven patients, GOLD (Global Initiative for Chronic Obstructive Lung Disease) stages II to IV, underwent cardiopulmonary exercise testing and right-sided heart catheterization at rest and during exercise. Patients were divided into three groups based on mean pulmonary artery pressure (mPAP) at rest: no PH (mPAP, < 25 mm Hg), moderate PH (mPAP, 25-39 mm Hg), and severe PH (mPAP, ≥ 40 mm Hg). Mixed venous oxygen saturation (Svo2) was used for evaluating the circulatory reserve. Paco2 and the calculated breathing reserve were used for evaluation of the ventilatory reserve.

Results:  Patients without PH (n = 24) had an end-exercise Svo2 of 48% ± 9%, an increasing Paco2 with exercise, and a breathing reserve of 22% ± 20%. Patients with moderate PH (n = 14) had an exercise Svo2 of 40% ± 8%, an increasing Paco2, and a breathing reserve of 26% ± 15%. Patients with severe PH (n = 9) had a significantly lower end-exercise Svo2 (30% ± 6%), a breathing reserve of 37% ± 11%, and an absence of Paco2 accumulation.

Conclusion:  Patients with severe PH showed an exhausted circulatory reserve at the end of exercise. A profile of circulatory reserve in combination with ventilatory impairments was found in patients with COPD and moderate or no PH. The results suggest that pulmonary vasodilation might only improve exercise tolerance in patients with COPD and severe PH.

Chest. 2012;142(5):1175-1178. doi:10.1378/chest.11-2926

Background:  The increased exposure to heparin products for thromboprophylaxis against VTE in hospitalized patients raises concerns for an increase in the incidence of heparin-induced thrombocytopenia (HIT).

Methods:  We analyzed, among 90,875 patients exposed to heparin products between 2005 and 2009, the number of hematologic consultations for thrombocytopenia, requests for heparin-induced antibodies by enzyme-linked immunosorbent assay, and cases given a diagnosis of HIT by the hematology consult service.

Results:  We observed that despite a doubling in the number of patients receiving pharmacoprophylaxis with heparin, there was no significant increase in the number of consultations for thrombocytopenia, the number of requests for HIT tests, the number of positive HIT test results, or the number of HIT diagnoses. The number of cases of HIT was low and represented < 0.1% of patients exposed to heparin.

Conclusions:  We conclude that concerns about HIT should not be a limiting factor for the systematic implementation of heparin-based VTE prophylaxis.

Original Research: Critical Care

Chest. 2012;142(5):1179-1184. doi:10.1378/chest.11-2680

Background:  Early optimization of treatment is crucial when admitting patients to the ICU and could depend on the organization of the medical team. The aim of this retrospective observational study was to determine whether admissions during morning rounds are independently associated with hospital mortality in a medical ICU.

Methods:  The 3,540 patients admitted from May 2000 to April 2010 to the medical ICU of Sainte Marguerite Hospital in Marseille, France, were divided into two groups based on the time of admission. The non-morning rounds group was admitted between 1:00 pm and 7:59 am, and the morning rounds group was admitted between 8:00 am and 12:59 pm. Hospital mortality (crude and adjusted) was compared between the two groups.

Results:  The 583 patients (16.5%) admitted during morning rounds were older and sicker upon admission compared with those patients admitted during non-morning rounds. The crude hospital mortality was 35.2% (95% CI, 31.4-39.1) in the group of patients admitted during morning rounds and 28.0% (95% CI, 26.4-29.7) in the other group (P < .001). An admission during morning rounds was not independently associated with hospital death (adjusted hazard ratio, 1.10; 95% CI, 0.94-1.28; P = .24).

Conclusions:  Being admitted to the medical ICU during morning rounds is not associated with a poorer outcome than afternoon and night admissions. The conditions of the patients admitted during morning rounds were more severe, which underlines the importance of the ICU team’s availability during this time. Further studies are needed to evaluate if the presence of a specific medical team overnight in the wards would be able to improve patients’ outcome by preventing delayed ICU admission.

Chest. 2012;142(5):1185-1192. doi:10.1378/chest.11-3277

Background:  One in five deaths in the United States occurs in the ICU, and many of these deaths are experienced as less than optimal by families of dying people. The current study investigated the relationship between family satisfaction with ICU care and overall ratings of the quality of dying as a means of identifying targets for improving end-of-life experiences for patients and families.

Methods:  This multisite cross-sectional study surveyed families of patients who died in the ICU in one of 15 hospitals in western Washington State. Measures included the Family Satisfaction in the ICU (FS-ICU) and the Single-Item Quality of Dying (QOD-1) questionnaires. Associations between FS-ICU items and the QOD-1 were examined using multivariate linear regression controlling for patient and family demographics and hospital site.

Results:  Questionnaires were returned for 1,290 of 2,850 decedents (45%). Higher QOD-1 scores were significantly associated (all P < .05) with (1) perceived nursing skill and competence (β = 0.15), (2) support for family as decision-makers (β = 0.10), (3) family control over the patient’s care (β = 0.18), and (4) ICU atmosphere (β = 0.12). FS-ICU items that received low ratings and correlated with higher QOD-1 scores (ie, important items with room for improvement) were (1) support of family as decision-maker, (2) family control over patient’s care, and (3) ICU atmosphere.

Conclusions:  Increased support for families as decision-makers and for their desired level of control over patient care along with improvements in the ICU atmosphere were identified as aspects of the ICU experience that may be important targets for quality improvement.

Trial registry:  ClinicalTrials.gov; No.: NCT00685893; URL: www.clinicaltrials.gov.

Chest. 2012;142(5):1193-1199. doi:10.1378/chest.12-0576

Objective:  The purpose of our study was to examine in patients hospitalized with community-acquired pneumonia (CAP) the association between abnormal Paco2 and ICU admission and 30-day mortality.

Methods:  A retrospective cohort study was conducted at two tertiary teaching hospitals. Eligible subjects were admitted with a diagnosis of CAP. Arterial blood gas analyses were obtained with measurement of Paco2 on admission. Multivariate analyses were performed using 30-day mortality and ICU admission as the dependent measures.

Results:  Data were abstracted on 453 subjects with a documented arterial blood gas analysis. One hundred eighty-nine patients (41%) had normal Paco2 (35-45 mm Hg), 194 patients (42%) had a Paco2 < 35 mm Hg (hypocapnic), and 70 patients (15%) had a Paco2 > 45 mm Hg (hypercapnic). In the multivariate analysis, after adjusting for severity of illness, hypocapnic patients had greater 30-day mortality (OR = 2.84; 95% CI, 1.28-6.30) and a higher need for ICU admission (OR = 2.88; 95% CI, 1.68-4.95) compared with patients with normal Paco2. In addition, hypercapnic patients had a greater 30-day mortality (OR = 3.38; 95% CI, 1.38-8.30) and a higher need for ICU admission (OR = 5.35; 95% CI, 2.80-10.23). When patients with COPD were excluded from the analysis, the differences persisted between groups.

Conclusion:  In hospitalized patients with CAP, both hypocapnia and hypercapnia were associated with an increased need for ICU admission and higher 30-day mortality. These findings persisted after excluding patients with CAP and with COPD. Therefore, Paco2 should be considered for inclusion in future severity stratification criteria to appropriate identified patients who will require a higher level of care and are at risk for increased mortality.

Chest. 2012;142(5):1200-1210. doi:10.1378/chest.11-2614

Background:  Ventilated patients receiving intensive care are at significant risk of acquiring a ventilator-associated pneumonia that is associated with significant morbidity and mortality. Despite intensive research, it is still unclear why Pseudomonas aeruginosa, a microbe that rarely causes pneumonia outside of intensive care, is responsible for so many of these infections.

Methods:  We investigated whether medications frequently prescribed to patients in the ICU, the catecholamine inotropes, were affecting the growth and virulence of P aeruginosa. Effects of clinically attainable concentrations of inotropes on P aeruginosa pathogenicity were explored using in vitro growth and virulence assays and an ex vivo model of infection using ciliated human respiratory epithelium.

Results:  We found that inotropes were potent stimulators of P aeruginosa growth, producing up to 50-fold increases in bacterial numbers via a mechanism involving inotrope delivery of transferrin-iron, internalization of the inotrope, and upregulation of the key pseudomonal siderophore pyoverdine. Inotropes also markedly increased biofilm formation on endotracheal tubing and enhanced the biofilm production and toxicity of P aeruginosa in its interaction with respiratory epithelium. Importantly, catecholamine inotropes also facilitated the rapid recovery of P aeruginosa from tobramycin antibiotic challenge. We also tested out the effect of the inotropes vasopressin and phenylephrine on the growth and virulence of P aeruginosa and found that, in contrast to the catecholamines, these drugs had no stimulatory effect.

Conclusions:  Collectively, our results suggest that catecholamine inotrope-bacterial interactions may be an unexpected contributory factor to the development of P aeruginosa-ventilator-associated pneumonia.

Original Research: Sleep Disorders

Chest. 2012;142(5):1211-1221. doi:10.1378/chest.12-0815

Background:  Adaptive servoventilation (ASV) has demonstrated efficacy in treating sleep-disordered breathing (SDB) in patients with heart failure (HF), but large randomized trials are lacking. We, therefore, sought to perform a systematic review and meta-analysis of existing data.

Methods:  A systematic search of the PubMed database was undertaken in March 2012. Publications were independently assessed by two investigators to identify studies of ≥ 1-week duration that compared ASV to a control condition (ie, subtherapeutic ASV, continuous or bilevel pressure ventilation, oxygen therapy, or no treatment) in adult patients with SDB and HF. Mean, variability, and sample size data were extracted independently for the following outcomes: apnea-hypopnea index (AHI), left ventricular ejection fraction (LVEF), quality of life (SF-36 Health Survey; Medical Outcomes Trust), 6-min walk distance, peak oxygen consumption (V˙ o2) % predicted, and ventilatory equivalent ratio for CO2 (V˙ e/V˙ co2) slope measured during exercise. Random effects meta-analysis models were applied.

Results:  Fourteen studies were identified (N = 538). Comparing ASV to control conditions, the weighted mean difference in AHI (−14.64 events/h; 95% CI, −21.03 to −8.25) and LVEF (0.40; 95% CI, 0.08-0.71) both significantly favored ASV. ASV also improved the 6-min walk distance, but not peak V˙ o2 % predicted, V˙ e/V˙ co2 slope, or quality of life, compared with control conditions.

Conclusions:  In patients with HF and SDB, ASV was more effective than control conditions in reducing the AHI and improving cardiac function and exercise capacity. These data provide a compelling rationale for large-scale randomized controlled trials to assess the clinical impact of ASV on hard outcomes in these patients.

Chest. 2012;142(5):1222-1228. doi:10.1378/chest.11-2963

Background:  Patients with heart failure (HF) and obstructive sleep apnea (OSA) are less sleepy than patients with OSA but without HF. Furthermore, unlike the non-HF population, in the HF population, the degree of daytime sleepiness is not related to the apnea-hypopnea index (AHI). The sympathetic nervous system plays a critical role in alertness. HF and OSA both increase sympathetic nervous system activity (SNA) during wakefulness. We hypothesized that in patients with HF and OSA, the degree of subjective daytime sleepiness would be inversely related to SNA.

Methods:  Daytime muscle SNA (MSNA) was recorded in patients with HF and OSA. Subjective daytime sleepiness was assessed by the Epworth Sleepiness Scale (ESS).

Results:  We studied 27 patients with HF and OSA and divided them into two groups based on the median ESS score: a less sleepy group, with an ESS score < 6 (n = 13), and a sleepier group, with an ESS score ≥ 6 (n = 14). The less sleepy group had higher MSNA than did the sleepier group (82.5 ± 9.9 bursts/100 cardiac cycles vs 69.3 ± 18.6 bursts/100 cardiac cycles; P = .037) and a longer sleep-onset latency (33 ± 29 min vs 14 ± 13 min; P = .039). The ESS score was inversely related to MSNA (r = −0.63; P < .001) but not to the AHI, arousal index, or indices of oxygen desaturation.

Conclusions:  In patients with HF and OSA, the degree of subjective daytime sleepiness is inversely related to MSNA. This relationship is likely mediated via central adrenergic alerting mechanisms. These findings help to explain the previously reported lack of daytime hypersomnolence in patients with HF and OSA.

Original Research: Signs and Symptoms of Chest Disease

Chest. 2012;142(5):1229-1236. doi:10.1378/chest.12-0638

Background:  Vagal reflex initiated by esophageal stimulation and microaspiration can cause chronic cough in patients with gastroesophageal reflux disease (GERD). By raising intraabdominal pressure, cough can, in turn, predispose to GERD. The role of the upper esophageal sphincter (UES) in preventing esophagopharyngeal reflux during coughing is not well known. The aim of this study was to evaluate the UES response during coughing.

Methods:  We studied 20 healthy young (10 women; age, 27 ± 5 years) and 15 healthy elderly (nine women; age, 73 ± 4 years) subjects. Hard and soft cough-induced pressure changes in the UES, distal esophagus, lower esophageal sphincter, and stomach were determined simultaneously using high-resolution manometry and concurrent acoustic cough recordings.

Results:  Resting UES pressure was significantly higher in the young compared with the elderly subjects (42 ± 14 mm Hg vs 24 ± 9 mm Hg; P < .001). Cough induced a UES contractile response in all subjects. Despite lower UES resting pressures in the elderly subjects, the maximum UES pressure during cough was similar between the young and the elderly subjects (hard cough, 230 ± 107 mm Hg vs 278 ± 125 mm Hg, respectively; soft cough, 156 ± 85 mm Hg vs 164 ± 119 mm Hg, respectively; P not significant for both). The UES pressure increase over baseline during cough was significantly higher than that in the esophagus, lower esophageal sphincter, and stomach for both groups (P < .001).

Conclusions:  Cough induces a rise in UES pressure, and this response is preserved in elderly people. A cough-induced rise in UES pressure is significantly higher than that in the esophagus and stomach, thereby providing a barrier against retrograde entry of gastric contents into the pharynx.

Chest. 2012;142(5):1237-1243. doi:10.1378/chest.11-3309

Background:  The recent development of automated cough monitors has enabled objective assessment of cough frequency. A study was undertaken to determine whether short-duration recordings (< 6 h) accurately reflect 24-h cough frequency and to investigate their responsiveness.

Methods:  One hundred adults with chronic cough underwent 24-h cough frequency monitoring with the Leicester Cough Monitor and completed cough visual analog scales (VASs) and the Leicester Cough Questionnaire (LCQ). Cough recordings were analyzed using customized software to derive cough frequencies from 1 to 6 h and 24-h recordings. Responsiveness was assessed with repeat assessments following therapeutic trials.

Results:  The median (interquartile range) 24-h cough frequency was 11.5 (5.8-26.6) coughs/h. Four hours was considered the shortest recording duration that represented 24-h cough frequency (ρ = 0.9, P ≤ .001). Median 4-h cough frequency was 16.6 (7.3-36.8) coughs/h. Both 4-h and 24-h cough frequency correlated moderately with cough VAS (ρ = 0.49, P ≤ .01 and ρ = 0.44, P ≤ .01) and LCQ (ρ = −0.48, P ≤ .01; ρ = −0.50, P ≤ .01). Four-hour cough frequency was responsive to improvements in cough severity following trials of therapy.

Conclusions:  Four-hour cough frequency correlates highly with 24-h cough frequency recordings and relates equally well with subjective measures in chronic cough. Short-duration cough monitoring could be a practical tool to validate the presence of cough and assess response to trials of therapy in the clinic setting.

Topics: cough, chronic , cough

Original Research: Occupational and Environmental Lung Diseases

Chest. 2012;142(5):1244-1250. doi:10.1378/chest.11-2210

Background:  We examined the relationship between pulmonary function (FEV1) and confirmed recovery from three lower-respiratory symptoms (LRSs) (cough, dyspnea, and wheeze) up to 9 years after symptom onset.

Methods:  The study included white and black male World Trade Center (WTC)-exposed firefighters who reported at least one LRS on a medical monitoring examination during the first year after September 11, 2001. Confirmed recovery was defined as reporting no LRSs on two consecutive and all subsequent examinations. FEV1 was assessed at the first post-September 11, 2001, examination and at each examination where symptom information was ascertained. We used stratified Cox regression models to analyze FEV1, WTC exposure, and other variables in relation to confirmed symptom recovery.

Results:  A total of 4,368 firefighters met inclusion criteria and were symptomatic at year 1, of whom 1,592 (36.4%) experienced confirmed recovery. In univariable models, first post-September 11, 2001, concurrent, and difference between first post-September 11, 2001, and concurrent FEV1 values were all significantly associated with confirmed recovery. In adjusted analyses, both first post-September 11, 2001, FEV1 (hazard ratio [HR], 1.07 per 355-mL difference; 95% CI, 1.04-1.10) and FEV1 % predicted (HR, 1.08 per 10% predicted difference; 95% CI, 1.04-1.12) predicted confirmed recovery. WTC exposure had an inverse association with confirmed recovery in the model with FEV1, with the earliest arrival group less likely to recover than the latest arrival group (HR, 0.73; 95% CI, 0.58-0.92).

Conclusions:  Higher FEV1 and improvement in FEV1 after September 11, 2001, predicted confirmed LRS recovery, supporting a physiologic basis for recovery and highlighting consideration of spirometry as part of any postexposure respiratory health assessment.

Original Research: Lung Cancer

Chest. 2012;142(5):1251-1258. doi:10.1378/chest.12-0330

Background:  Disparities in lung cancer treatment and palliative care are well documented. However, the mechanisms underlying these disparities are not fully understood. In this study, we evaluated racial and ethnic differences in beliefs and attitudes about lung cancer treatment and palliative care among patients receiving a new diagnosis of lung cancer.

Methods:  Patients were recruited from four medical centers in New York City and surveyed about their beliefs regarding lung cancer care, including disease-directed treatments, palliative and end-of-life care, and fatalistic and spiritual beliefs. We used univariate and multiple regression analyses to compare the distribution of beliefs among minority (black and Hispanic) and nonminority patients.

Results:  Of the 335 patients, 21% were black, 20% were Hispanic, and 59% were nonminority. Beliefs about chemotherapy and radiotherapy were similar across the three groups (P > .05), whereas black patients were more likely to believe that surgery might cause lung cancer to spread (P = .008). Fatalistic beliefs potentially affecting cancer treatment were more common among both minority groups (P ≤ .02). No significant differences were found in attitudes toward clinician communication about cancer prognosis (P > .05). However, both blacks and Hispanics were more likely to have misconceptions about advance directives and hospice care (P ≤ .02).

Conclusions:  Similarities and differences in beliefs about disease-directed treatment were observed between minority and nonminority patients with lung cancer. Minority patients hold more fatalistic views about the disease and misperceptions about advance care planning and hospice care. Further research is needed to assess the impact of these beliefs on decisions about lung cancer care and patient outcomes.

Original Research: Cystic Fibrosis

Chest. 2012;142(5):1259-1266. doi:10.1378/chest.12-0628

Background:  While the mechanism of action by which azithromycin exerts positive effects in patients with cystic fibrosis remains unclear, evidence suggests that azithromycin may act as an immunomodulatory agent. We examined changes in systemic inflammatory markers in a double-blind, randomized, controlled trial of oral azithromycin in patients 6-18 years of age with cystic fibrosis who were uninfected with Pseudomonas aeruginosa.

Methods:  WBC counts and differential, serum myeloperoxidase (MPO), high-sensitivity C reactive protein (hsCRP), intracellular adhesion molecule 1, IL-6, calprotectin, serum amyloid A (SAA), and granulocyte colony-stimulating factor (G-CSF) were measured at baseline and after 28 and 168 days of treatment in patients receiving either oral azithromycin or placebo.

Results:  Inflammatory markers were similar in both groups at baseline. HsCRP, MPO, SAA, calprotectin, and the absolute neutrophil count (ANC) significantly decreased from baseline to day 28 in the azithromycin group compared with the placebo group (P < .05). This treatment effect was sustained at day 168 for ANC, calprotectin, and SAA (P < .05). Changes in hsCRP, calprotectin, and SAA at day 28 were negatively correlated with changes in FEV1 (L) and FEV1 (% predicted), as well as both absolute and relative changes in weight (P < .05). Except for weight (%), the associations remained significant for calprotectin; FEV1(L) and weight (%) remained significantly correlated with the 168-day change in hsCRP. The 168-day change in ANC was significantly correlated with changes in lung function, but not in weight; the change in G-CSF was significantly correlated with the change in weight (%) only.

Conclusions:  In patients not infected with P aeruginosa, oral azithromycin significantly reduced neutrophil counts and serum inflammatory markers within 28 days of initiating treatment.

Trial registry:  ClinicalTrials.gov; No.: NCT00431964; URL: www.clinicaltrials.gov

Original Research: Disorders of the Pleura

Chest. 2012;142(5):1267-1273. doi:10.1378/chest.11-3204

Background:  Malignant pleural mesothelioma (MPM) is an incurable cancer with a rising incidence. MPM is often perceived as a locally invasive cancer, and the exact cause of death is poorly understood. This two-center study describes the anatomic features of patients with MPM at postmortem.

Methods:  The Western Australia Mesothelioma Registry (Australia) and Coroner’s Office reports from the Avon region (England) were interrogated for the postmortem records of confirmed mesothelioma cases.

Results:  Postmortem records of 318 patients with pleural mesothelioma (169 from Western Australia and 149 from Avon) were identified. Most patients (91.5%) were men (mean age, 68.4 ± 11.5 years), and MPM was right-sided in 55.3%. Extrapleural dissemination of tumor was found in 87.7% of cases and lymph node involvement in 53.3%. Tumor dissemination in extrathoracic sites was common (55.4% of patients), and almost all organs were involved, including liver (31.9%), spleen (10.8%), thyroid (6.9%), and the brain (3.0%). Pulmonary emboli were found in 6% of cases and considered as directly contributing to death in 13 patients (4.1%). The precise cause of death could only be determined in 63 (19.8%) cases even after postmortem. The BMI was significantly lower in cases that had no identifiable anatomic cause of death at postmortem (18.8 ± 4.3 vs 21.0 ± 4.7, P = .034).

Conclusions:  In this largest, to our knowledge, postmortem series on MPM, extrathoracic dissemination of mesothelioma was common and often underrecognized. No anatomic cause of death was identified in the majority of patients even at autopsy, raising the possibility of physiologic and metabolic causes of death.

Original Research: Cardiovascular Disease

Chest. 2012;142(5):1274-1283. doi:10.1378/chest.11-1710

Background:  Cardiac asthma describes symptoms of airflow obstruction due to heart failure. Chronic heart failure is associated with decreased FEV1, and FEV1 improves after heart transplantation. Fibrotic remodeling of the heart and airways is mediated, in part, through transforming growth factor (TGF)-β. Blood TGF-β1 concentration correlates with ventricular remodeling in cardiac disease, and TGF-β decreases after repair.

Methods:  We established a coculture of normal human bronchial epithelial (NHBE) cells differentiated at air-liquid interface with submerged basal cardiomyoblasts. Airway cells were immunostained with cytokeratin, actin, and involucrin. TGF-β synthesis was assayed using enzyme-linked immunosorbent assay. Phosphorylation of Smad in NHBE cells was determined by Western blotting. Mice given doxorubicin developed cardiac failure, and their airways were histologically examined.

Results:  Coculture induced involucrin-positive squamous metaplasia of NHBE cells, and this was attenuated by TGF-β antibody. Total TGF-β1 was increased in coculture conditioned medium (P < .001). After 14 days of exposure to recombinant TGF-β1, there was squamous transformation of NHBE cells. One week after removing cardiomyoblasts from culture, squamous metaplasia resolved into normal ciliated epithelia. Smad was phosphorylated in NHBE cells with cardiomyoblasts or with recombinant TGF-β1 exposure. The airways of mice with heart failure also demonstrated involucrin-positive squamous transformation.

Conclusions:  TGF-β from cardiomyoblasts or from the failing heart can cause airway squamous metaplasia via Smad signaling, and this is blocked by anti-TGF-β antibody and reversed when cardiac cells are removed from culture. This appears to be an important mechanism for airflow obstruction with heart failure, sometimes described as cardiac asthma.

Evidence-Based Medicine

Chest. 2012;142(5):1284-1288. doi:10.1378/chest.12-1075

The use of nonsteroidal immunosuppressive drugs to treat systemic and pulmonary inflammatory disorders has increased considerably. These drugs are used to prevent and suppress posttransplant lung allograft rejection and to treat various forms of inflammatory lung disease, such as sarcoidosis, pulmonary vasculitis, and idiopathic interstitial pneumonias. Because these medications have become more widely used for a variety of indications, it has become increasingly common for these drugs to be administered and monitored by primary pulmonologists in community settings.

Chest. 2012;142(5):e1S-e111S. doi:10.1378/chest.12-1044

Objectives:  Immunosuppressive pharmacologic agents prescribed to patients with diffuse interstitial and inflammatory lung disease and lung transplant recipients are associated with potential risks for adverse reactions. Strategies for minimizing such risks include administering these drugs according to established, safe protocols; monitoring to detect manifestations of toxicity; and patient education. Hence, an evidence-based guideline for physicians can improve safety and optimize the likelihood of a successful outcome. To maximize the likelihood that these agents will be used safely, the American College of Chest Physicians established a committee to examine the clinical evidence for the administration and monitoring of immunosuppressive drugs (with the exception of corticosteroids) to identify associated toxicities associated with each drug and appropriate protocols for monitoring these agents.

Methods:  Committee members developed and refined a series of questions about toxicities of immunosuppressives and current approaches to administration and monitoring. A systematic review was carried out by the American College of Chest Physicians. Committee members were supplied with this information and created this evidence-based guideline.

Conclusions:  It is hoped that these guidelines will improve patient safety when immunosuppressive drugs are given to lung transplant recipients and to patients with diffuse interstitial lung disease.

Translating Basic Research into Clinical Practice

Chest. 2012;142(5):1289-1299. doi:10.1378/chest.12-0809

Important cellular processes such as inflammation, apoptosis, differentiation, and proliferation confer critical roles in the pathogenesis of human diseases. In the past decade, an emerging process named “autophagy” has generated intense interest in both biomedical research and clinical medicine. Autophagy is a regulated cellular pathway for the turnover of organelles and proteins by lysosomal-dependent processing. Although autophagy was once considered a bulk degradation event, research shows that autophagy selectively degrades specific proteins, organelles, and invading bacteria, a process termed “selective autophagy.” It is increasingly clear that autophagy is directly relevant to clinical disease, including pulmonary disease. This review outlines the principal components of the autophagic process and discusses the importance of autophagy and autophagic proteins in pulmonary diseases from COPD, α1-antitrypsin deficiency, pulmonary hypertension, acute lung injury, and cystic fibrosis to respiratory infection and sepsis. Finally, we examine the dual nature of autophagy in the lung, which has both protective and deleterious effects resulting from adaptive and maladaptive responses, and the challenge this duality poses for designing autophagy-based diagnostic and therapeutic targets in lung disease.

Recent Advances in Chest Medicine

Chest. 2012;142(5):1300-1307. doi:10.1378/chest.11-2766

The biologic nature of COPD inflammation is not well understood and agents that inhibit inflammation in COPD are a major unmet need. However, a variety of agents that have the potential to be inhibitors of COPD inflammation are in various stages of development. Agents that have been approved for a non-COPD indication but that have potential for inhibiting COPD inflammation include the statins, some phosphodiesterase inhibitors, some long-acting β agonists, tiotropium bromide, the peroxisome proliferator-activated receptor-γ agonist rosiglitazone, and various monoclonal antibodies. New molecular entities that are being developed specifically as antiinflammatory agents for COPD include a variety of chemokine receptor antagonists, inhibitors of matrix metalloproteinases, inhibitors of p38 mitogen-activated protein kinases, and stem cells. Some other novel agents that are in preclinical or early clinical stages are mentioned.

Ahead of the Curve

Chest. 2012;142(5):1308-1315. doi:10.1378/chest.12-1596

Household air pollution (HAP) from biomass fuels, coal, and kerosene burned in open fires, primitive stoves, and lamps causes at least 2 million deaths per year. Many of these deaths occur in children <5 years of age with pneumonia and in women with COPD, lung cancer, and cardiovascular disease. HAP is inextricably linked to poverty, with activities to obtain fuel consuming a large proportion of the time and financial resources of poor households. Thus, fewer resources used in this way means less is available for basic needs like food, education, and health care. The burden of work and the exposure to smoke, particularly during cooking, are predominantly borne by women and children. Although historically HAP has not received sufficient attention from the scientific, medical, public health, development, and policy-making communities, the tide has clearly changed with the broad-based support and launch of the Global Alliance for Clean Cookstoves in 2010. There is now considerable reason for optimism that this substantial cause of cardiorespiratory morbidity and mortality will be addressed comprehensively and definitively. Drawing on our experience from four continents, we provide background information on the problem of HAP, health impacts of HAP, opportunities for research, and the current best solutions.

Special Features

Chest. 2012;142(5):1316-1323. doi:10.1378/chest.11-3327

Immunohistochemistry has come to occupy a key position among the armamentarium of tools pathologists apply to the evaluation of lung and pleural neoplasms. This technique uses antibodies that bind to specific antigens, usually proteins, enabling microscopic detection of the antigens. Over the last several decades, an impressive array of antibodies has become commercially available, and many of these antibodies have become integrated into the routine practice of pathology. Evaluation of tissue or cytology samples with these antibodies can facilitate determination of tumor type and site of origin. Comments citing results of immunohistochemical staining with these antibodies frequently appear in pathology reports and may be difficult to translate for those less familiar with the technique. This review presents, in two parts, common diagnostic applications of immunohistochemistry, with information about strategies taken for frequently encountered differential diagnostic scenarios. This, the first of two parts, offers a basic overview of the technique and discusses its applications in the diagnosis of common primary lung carcinomas.

Chest. 2012;142(5):1324-1333. doi:10.1378/chest.12-0123

Immunohistochemistry has come to occupy a key position among the armamentarium of tools pathologists apply to the evaluation of lung and pleural neoplasms. This technique uses antibodies that bind to specific antigens, usually proteins, enabling microscopic detection of the antigens. Over the last several decades, an impressive array of antibodies has become commercially available, and many of these antibodies have become integrated into the routine practice of pathology. Evaluation of tissue or cytology samples with these antibodies can facilitate determination of tumor type and site of origin. Comments citing results of immunohistochemical staining with these antibodies frequently appear in pathology reports and may be difficult to translate for those less familiar with the technique. This review presents, in two parts, common diagnostic applications of immunohistochemistry with information about strategies taken for frequently encountered differential diagnostic scenarios. This article is the second of the two parts and focuses on immunohistochemical approaches to differentiating primary pulmonary from metastatic adenocarcinomas, mesotheliomas from carcinomas, and various types of spindle cell neoplasms. Potential future directions involving therapeutic and prognostic biomarkers are also discussed.

Selected Reports

Chest. 2012;142(5):1334-1336. doi:10.1378/chest.12-0181

A 51-year-old woman was given a diagnosis of primary retroperitoneal synovial sarcoma, which was surgically removed, and she was subsequently treated with chemotherapy and radiotherapy. Five years later, the patient was readmitted with a 1-month history of progressive dyspnea and was initially given a diagnosis of bilateral pulmonary embolism. Angiography performed some time later revealed progression of the previous filling defects and the appearance of two new nodular endovascular images. Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) was performed, and the cytologic analysis of the cell aspirate was compatible with endovascular metastatic sarcoma. In conclusion, EBUS-TBNA in the appropriate setting is an effective method for sampling endovascular lesions, adding pathologic information and allowing for early and accurate diagnosis.

Postgraduate Education Corner: Chest Imaging and Pathology for Clinicians

Chest. 2012;142(5):1338-1342. doi:10.1378/chest.11-2026

Postgraduate Education Corner: Pulmonary and Critical Care Pearls

Chest. 2012;142(5):1344-1347. doi:10.1378/chest.12-0594
Chest. 2012;142(5):1348-1351. doi:10.1378/chest.12-0482


Chest. 2012;142(5):1352. doi:10.1378/chest.11-3137

You don’t buy it,
the handshake,
the pleasantries,
the hmms and nods
from a short white coat.
You’ve been around
enough to know what you want:
just the prescription, thanks,
and to be left alone;
like you say,
you’re only allergic
to pain
and to doctors,
and sometimes
it’s hard
to tell
the difference.

Chest. 2012;142(5):1352. doi:10.1378/chest.11-3087

I should have known back then,
when I was piecing together
broken lines like this
in the margins of
organic chemistry textbooks,
that I wasn’t cut out for this.
I play the part, of course,
sometimes convincingly;
but who wants a mediocre doctor
who scribbles poetry
on the back of an ECG,
bemoaning the fact that
he missed his true calling,
if he ever had one?

Chest. 2012;142(5):1353. doi:10.1378/chest.11-2929

splendid uterus
four fetuses in cozy
quarters held, farewell.

Chest. 2012;142(5):1353. doi:10.1378/chest.11-3197

All night, trains squeal
down the tracks, kicking off
sparks that singe  the thin skin
of sleep.
  Pines, felled by his sawing
wheeze, thump  onto coiled springs,
scent the sheets with needles
  and bark. All night,
the orchestra tunes
  its instruments—cello and
kettle  drum, oboe and clarinet.
Finally, the conductor lifts his baton.
comes without


Chest. 2012;142(5):1354. doi:10.1378/chest.12-1642
Chest. 2012;142(5):1354-1355. doi:10.1378/chest.12-1853
Chest. 2012;142(5):1355-1356. doi:10.1378/chest.12-2328
Chest. 2012;142(5):1356-1357. doi:10.1378/chest.12-2024
Chest. 2012;142(5):1357-1358. doi:10.1378/chest.12-1595
Chest. 2012;142(5):1358. doi:10.1378/chest.12-1645
Chest. 2012;142(5):1358-1359. doi:10.1378/chest.12-1806
Chest. 2012;142(5):1359. doi:10.1378/chest.12-1927
Chest. 2012;142(5):1359-1361. doi:10.1378/chest.12-1797

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    Print ISSN: 0012-3692
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