Chest. 2012;142(4):815-816. doi:10.1378/chest.12-0979

In this issue of CHEST (see page 837), Trehel-Tursis and colleagues1 from France report their 6-year study (ending December 2010) of heparin-induced thrombocytopenia (HIT) occurring in a cardiothoracic surgery ICU. During this time, nearly 6,000 patients entered their ICU: 46% postcardiac surgery, 9% postcarotid endarterectomy, and 45% postthoracic surgery; 101 of 5,949 patients (1.7%) were suspected of possibly having HIT. All patients with suspected HIT were investigated by a polyspecific anti-PF4/heparin enzyme-linked immunosorbent assay (ELISA) that detects IgG, IgA, and IgM class antibodies. In about 90% of patients, additional testing was performed using a functional (platelet activation) assay, either a platelet aggregation test (PAT) or the serotonin release assay (SRA), or both. With few exceptions, patients were considered to have HIT if they tested positive in both the ELISA and one of the functional assays.

Chest. 2012;142(4):816-820. doi:10.1378/chest.12-0848

Pulmonary arterial hypertension (PAH) remains deadly despite some available treatment options.1 Diagnosis and therapeutic intervention tend to occur relatively late, particularly because symptoms are nonspecific and become evident when right ventricular (RV) dysfunction is already advanced. This, along with the fact that there are now groups of patients who are recognized as higher risk of developing the disease (ie, family members of inheritable PAH, patients with scleroderma or AIDS), makes the need for biomarkers pressing. Unfortunately, biomarkers with strong screening and prognostic value are lacking. Of the known circulating biomarkers, brain natriuretic peptide and troponin T are the most accepted,1 but both are derived from the right ventricle and, therefore, may only be relevant during RV failure, a relatively late stage of the disease. Moreover, both may also be released by the left ventricle, thereby lacking RV specificity, and are not involved in the pathogenesis of the PAH vascular remodeling. Thus, biomarkers that are relevant to disease pathogenesis and measurable at earlier stages and with some specificity for the pulmonary circulation are needed.

Chest. 2012;142(4):820-821. doi:10.1378/chest.12-1030

For many decades, COPD has been approached from a view of respiratory system involvement, and persistent and usually progressive airflow limitation associated with an enhanced chronic inflammatory response in the airways and the lung were characteristic findings. In the last decade, the definition of COPD has evolved to a disease with multicomponent involvement, and comorbidities, which are now assumed to contribute to the overall severity in individual patients.1 Instead of considering host-related factors to understand the heterogeneity of these comorbid conditions, the unifying concept of spillover of the local inflammation in the respiratory system was launched to understand the development and progression of this spectrum of comorbidities in COPD.

Chest. 2012;142(4):821-823. doi:10.1378/chest.12-0591

Sleep disordered breathing (SDB), in particular obstructive sleep apnea (OSA) and central sleep apnea-Cheyne-Stokes respiration (CSA-CSR), are prevalent in patients with heart failure and are associated with poor outcome.1 OSA is characterized by repeated pharyngeal airway collapse during sleep despite ongoing respiratory effort. CSA-CSR (or periodic breathing) describes a distinct respiratory pattern characterized by crescendo-decrescendo changes in tidal volume alternating with central apneas or central hypopneas. In both disorders, repetitive cortical arousals and oxyhemoglobin desaturation are of consequence during sleep. CSA-CSR in heart failure is thought to be secondary to instability of the ventilatory system due to increased chemo-responsiveness to Paco2. OSA in heart failure is thought to be due to a narrow upper airway, obesity, possibly pharyngeal wall edema, and ventilatory control instability.

Chest. 2012;142(4):823-825. doi:10.1378/chest.12-0933

The defining feature of chronic mountain sickness (CMS) (or Monge disease) is excessive erythrocytosis for the resident altitude, with hematocrit levels reported as high as 90% at 4,350 m.1 CMS is not only a public health problem in the Andes, but also in the Himalaya and Rocky Mountains. Many signs and symptoms stem from increased blood viscosity, greater hypoxemia, and pulmonary hypertension, which reduce cardiac output and effective tissue perfusion and oxygenation, ultimately leading to cor pulmonale and greater mortality.2 Fatigue with polycythemia is a typical finding and is a cardinal symptom in the international consensus definition of CMS.2 Although fatigue is a nonspecific symptom, it is often associated and equated with reduced exercise tolerance, and both are reported in CMS.1,2 Thus, the study by Groepenhoff et al3 in this issue of CHEST (see page 877) of maximal exercise in such patients, which found no evidence of decreased exercise capacity, is most intriguing. The surprising and novel findings of this first-rank cardiopulmonary physiologic investigation forces reconsideration of conventional wisdom.

Second Opinion

Chest. 2012;142(4):826. doi:10.1378/chest.142.4.826
Topics: burnout


Chest. 2012;142(4):827-836. doi:10.1378/chest.12-1060

Exacerbations of sarcoidosis are common. In particular, exacerbations of pulmonary sarcoidosis are reported in more than one-third of patients. Despite their frequent occurrence, there is little medical evidence concerning the definition, diagnosis, and treatment of pulmonary exacerbations of sarcoidosis. In this article, we propose a definition of acute pulmonary exacerbations of sarcoidosis (APES). We review the meager medical literature concerning the risk factors, diagnosis, and treatment of this condition. Given the limited information concerning APES, we acknowledge that this article is not a definitive resource but, rather, a position paper that will encourage greater consideration of the pathogenesis, diagnostic challenges, and treatment approaches to this condition. We believe that further focus on APES will improve the quality of care of patients with pulmonary sarcoidosis.

From the Pulmonary Department (Dr Panselinas), 411 General Army Hospital, Tripoli, Greece; and the Division of Pulmonary and Critical Care Medicine (Dr Judson), Albany Medical College, Albany, NY.

Correspondence to: Marc A. Judson, MD, FCCP, Division of Pulmonary and Critical Care Medicine, MC-91, Albany Medical College, Albany, NY 12208; e-mail: judsonm@mail.amc.edu

Financial/nonfinancial disclosures: The authors have reported to CHEST the following conflicts of interest: Dr Judson has been a consultant for Pulmonary Reviews; Janssen Biotech, Inc; and Celgene Corp. Dr Panselinas has reported that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

Other contributions: The authors acknowledge Sooyeon Kwon, PhD, for her outstanding assistance with the tables and figures in this manuscript. We also acknowledge Jared N. Kravitz, MD, who, to our knowledge, first coined the term, “APES.”

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.

Original Research: Critical Care

Chest. 2012;142(4):837-844. doi:10.1378/chest.11-3074

Background:  The diagnosis of heparin-induced thrombocytopenia (HIT) is problematic in the surgical ICU, as there are multiple potential explanations for thrombocytopenia. We conducted a study to assess the incidence, clinical presentation, and outcome of HIT in a cardiothoracic surgical ICU.

Methods:  From January 2005 to December 2010, all patients with suspicion of HIT were prospectively identified, and data were collected retrospectively. Detection of anti-PF4/heparin antibodies and functional assays were systematically performed.

Results:  During the study period, 5,949 patients were admitted to the ICU (2,751 after cardiac surgery and 3,198 after thoracic surgery), of whom 101 were suspected to have HIT (1.7% [95% CI, 1.4%-2.0%]). Suspicion of HIT occurred at a median of 5 (4-9) days after ICU admission. Diagnosis was confirmed in 28 of 5,949 patients (0.47% [95% CI, 0.33%-0.68%]). Thrombosis was detected in 14 patients with HIT (50%) and in 12 patients without HIT (16%) (P = .0006). After receiver operating characteristic analysis (area under curve = 0.78 ± 0.06), a 4Ts score ≥ 5 had a sensitivity of 86% and a specificity of 70%. Course of platelet count was similar between the two groups. Six patients (21%) with HIT and 20 (27%) without died (P = .77).

Conclusions:  Even with a prospective platelet monitoring protocol, suspicion for HIT arose in < 2% of patients in a cardiothoracic ICU. Most were found to have other causes of thrombocytopenia, with HIT confirmed in 28 of 101 suspected cases (0.47% of all patients in the ICU). The 4Ts score may have value by identifying patients who should have laboratory testing performed. The mortality of patients with HIT was not different from other very ill thrombocytopenic patients in the ICU.

Chest. 2012;142(4):845-850. doi:10.1378/chest.11-2103

Background:  A number of drugs have been reported as risk factors for acute lung injury (ALI) and ARDS. However, evidence is largely limited to case reports, and there is a paucity of data on the incidence and outcome of drug-associated ALI (DALI).

Methods:  Using a population-based retrospective cohort study design, critically ill patients with a diagnosis of ALI were studied. These patients were classified as having DALI or non-DALI, based on whether they were exposed to prespecified drugs prior to development of ALI. Outcomes were compared between the two groups and frequencies and incidences reported.

Results:  Among 514 patients with ALI, 49 (9.5%) had DALI with an estimated population-based incidence of 6.6 (95% CI, 4.8-8.5) per 100,000 person-years. Of the 49 patients with DALI, 36 received chemotherapeutic/antiinflammatory agents, and 14 received amiodarone. Twelve patients had no additional risk factors for ALI (probable DALI), whereas 37 had alternative risk factors (possible DALI). Patients with and without DALI had similar baseline characteristics. However, the APACHE (Acute Physiology and Chronic Health Evaluation) III scores (median, 83 vs 70, P = .03), ICU mortality (35% vs 20%, P = .03), and hospital mortality (63% vs 32%, P < .001) were significantly higher in the DALI group compared with those of the non-DALI group. Hospital mortality remained significantly higher after adjusting for APACHE III score on admission and the presence of malignancy in logistic regression analysis (OR, 2.8; 95% CI, 1.3-6.4; P = .009).

Conclusions:  Drugs are important risk factors for ALI, and recognizing them as such may have important implications for early identification of patients at risk, discontinuation of the offending agent, and prognosis.

Chest. 2012;142(4):851-858. doi:10.1378/chest.11-2164

Background:  There are few comparisons among the most recent versions of the major adult ICU prognostic systems (APACHE [Acute Physiology and Chronic Health Evaluation] IV, Simplified Acute Physiology Score [SAPS] 3, Mortality Probability Model [MPM]0III). Only MPM0III includes resuscitation status as a predictor.

Methods:  We assessed the discrimination, calibration, and overall performance of the models in 2,596 patients in three ICUs at our tertiary referral center in 2006. For APACHE and SAPS, the analyses were repeated with and without inclusion of resuscitation status as a predictor variable.

Results:  Of the 2,596 patients studied, 283 (10.9%) died before hospital discharge. The areas under the curve (95% CI) of the models for prediction of hospital mortality were 0.868 (0.854-0.880), 0.861 (0.847-0.874), 0.801 (0.785-0.816), and 0.721 (0.704-0.738) for APACHE III, APACHE IV, SAPS 3, and MPM0III, respectively. The Hosmer-Lemeshow statistics for the models were 33.7, 31.0, 36.6, and 21.8 for APACHE III, APACHE IV, SAPS 3, and MPM0III, respectively. Each of the Hosmer-Lemeshow statistics generated P values < .05, indicating poor calibration. Brier scores for the models were 0.0771, 0.0749, 0.0890, and 0.0932, respectively. There were no significant differences between the discriminative ability or the calibration of APACHE or SAPS with and without “do not resuscitate” status.

Conclusions:  APACHE III and IV had similar discriminatory capability and both were better than SAPS 3, which was better than MPM0III. The calibrations of the models studied were poor. Overall, models with more predictor variables performed better than those with fewer. The addition of resuscitation status did not improve APACHE III or IV or SAPS 3 prediction.

Chest. 2012;142(4):859-868. doi:10.1378/chest.12-0679

Background:  Ventilator-associated pneumonia (VAP) remains a common hazardous complication in patients who are mechanically ventilated and is associated with increased morbidity and mortality. We undertook a systematic review and meta-analysis of randomized controlled trials to evaluate the efficacy and safety of probiotics for the prevention of VAP.

Methods:  The PubMed and EMBASE databases were searched to identify randomized controlled trials comparing probiotics with control for VAP in adult patients undergoing mechanical ventilation. The primary outcome was the incidence of VAP. Secondary outcomes included ICU mortality, hospital mortality, urinary tract infection, catheter-related bloodstream infection, diarrhea, length of ICU stay, length of hospital stay, and duration of mechanical ventilation.

Results:  A total of 1,142 patients from seven trials were subjected to meta-analysis. Probiotics did not significantly decrease the incidence of VAP (OR, 0.82; 95% CI, 0.55-1.24; P = .35), with low heterogeneity among the studies (I2 = 36.5%, P = .15). Probiotics also did not appear to significantly alter any of the other meta-analysis end points.

Conclusions:  The limited evidence suggests that probiotics show no beneficial effect in patients who are mechanically ventilated; thus, probiotics should not be recommended for routine clinical application. However, the results of this meta-analysis should be interpreted with caution because of the heterogeneity among study designs. Future studies should focus on the safety of probiotics.

Original Research: Pulmonary Vascular Disease

Chest. 2012;142(4):869-876. doi:10.1378/chest.11-1267

Objectives:  Within the past decade, biochemical markers have emerged as attractive tools to assess pulmonary arterial hypertension (PAH) prognosis, being noninvasive and easily repeatable. The objective of this study was to determine whether biomarkers measured at initial diagnostic right-sided heart catheterization predict 3-year all-cause mortality for incident cases of PAH independently of clinical and hemodynamic parameters.

Methods:  Patients with incident PAH were enrolled between December 2003 and April 2006 in six centers from the French Network on Pulmonary Hypertension and followed for 3 years. Venous blood samples were taken during right-sided heart catheterization, and analyses were centralized.

Results:  Among 110 enrolled patients, 11 underwent lung or heart/lung transplantation, and 27 died during follow-up. The Kaplan-Meier estimates of survival were 91%, 78%, and 75% at 1, 2, and 3 years, respectively. Plasma big endothelin-1 (hazard ratio [HR] per 1-SD increase, 1.48; 95% CI, 1.14-1.92), serum troponin T > 0.01 mg/L (HR, 2.35; 95% CI, 1.05-5.29), and urinary F2-isoprostanes (15-F2t-isoprostane) (HR per 1-SD increase, 1.76; 95% CI, 1.31-2.36) were associated with increased unadjusted hazard of death. In multivariate analysis adjusting for patient characteristics, the level of urinary F2-isoprostanes was the only biomarker that remained independently associated with increased hazard of death (HR per 1-SD increase, 1.82; 95% CI, 1.28-2.60).

Conclusions:  This study shows that levels of urinary F2-isoprostane, a biomarker of lipid peroxidation, quantified at initial diagnostic right-sided heart catheterization are independently associated with mortality in a cohort of patients with incident PAH.

Chest. 2012;142(4):877-884. doi:10.1378/chest.11-2845

Background:  Chronic mountain sickness (CMS) is characterized by a combination of excessive erythrocytosis, severe hypoxemia, and pulmonary hypertension, all of which affect exercise capacity.

Methods:  Thirteen patients with CMS and 15 healthy highlander and 15 newcomer lowlander control subjects were investigated at an altitude of 4,350 m (Cerro de Pasco, Peru). All of them underwent measurements of diffusing capacity of lung for nitric oxide and carbon monoxide at rest, echocardiography for estimation of mean pulmonary arterial pressure and cardiac output at rest and at exercise, and an incremental cycle ergometer cardiopulmonary exercise test.

Results:  The patients with CMS, the healthy highlanders, and the newcomer lowlanders reached a similar maximal oxygen uptake at 32 ± 1, 32 ± 2, and 33 ± 2 mL/min/kg, respectively, mean ± SE (P = .8), with ventilatory equivalents for Co2 vs end-tidal Pco2, measured at the anaerobic threshold, of 0.9 ± 0.1, 1.2 ± 0.1, and 1.4 ± 0.1 mm Hg, respectively (P < .001); arterial oxygen content of 26 ± 1, 21 ± 2, and 16 ± 1 mL/dL, respectively (P < .001); diffusing capacity for carbon monoxide corrected for alveolar volume of 155% ± 4%, 150% ± 5%, and 120% ± 3% predicted, respectively (P < .001), with diffusing capacity for nitric oxide and carbon monoxide ratios of 4.7 ± 0.1 at sea level decreased to 3.6 ± 0.1, 3.7 ± 0.1, and 3.9 ± 0.1, respectively (P < .05) and a maximal exercise mean pulmonary arterial pressure at 56 ± 4, 42 ± 3, and 31 ± 2 mm Hg, respectively (P < .001).

Conclusions:  The aerobic exercise capacity of patients with CMS is preserved in spite of severe pulmonary hypertension and relative hypoventilation, probably by a combination of increased oxygen carrying capacity of the blood and lung diffusion, the latter being predominantly due to an increased capillary blood volume.

Chest. 2012;142(4):885-892. doi:10.1378/chest.11-2016

Background:  Limited data are available on the effects of air travel in patients with pulmonary hypertension (PH), despite their risk of physiologic compromise. We sought to quantify the incidence and severity of hypoxemia experienced by people with PH during commercial air travel.

Methods:  We recruited 34 participants for a prospective observational study during which cabin pressure, oxygen saturation (Spo2), heart rate, and symptoms were documented serially at multiple predefined time points throughout commercial flights. Oxygen desaturation was defined as Spo2 < 85%.

Results:  Median flight duration was 3.6 h (range, 1.0-7.3 h). Mean ± SD cabin pressure at cruising altitude was equivalent to the pressure 1,968 ± 371 m (6,456 ± 1,218 ft) above sea level (ASL) (maximum altitude = 2,621 m [8,600 ft] ASL). Median change in Spo2 from sea level to cruising altitude was −4.9% (range, 2.0% to −15.8%). Nine subjects (26% [95% CI, 12%-38%]) experienced oxygen desaturation during flight (minimum Spo2 = 74%). Thirteen subjects (38%) reported symptoms during flight, of whom five also experienced desaturations. Oxygen desaturation was associated with cabin pressures equivalent to > 1,829 m (6,000 ft) ASL, ambulation, and flight duration (all P values < .05).

Conclusions:  Hypoxemia is common among people with PH traveling by air, occurring in one in four people studied. Hypoxemia was associated with lower cabin pressures, ambulation during flight, and longer flight duration. Patients with PH who will be traveling on flights of longer duration or who have a history of oxygen use, including nocturnal use only, should be evaluated for supplemental in-flight oxygen.

Original Research: COPD

Chest. 2012;142(4):893-899. doi:10.1378/chest.11-2173

Background:  COPD is a chronic inflammatory disorder with high risk of cardiovascular morbidity and mortality. Adiponectin is a hormone that has antiinflammatory, antidiabetic, and antiatherogenic activities. We investigated the relationship of serum adiponectin to health outcomes in COPD.

Methods:  We measured adiponectin levels in serum samples from participants of the Lung Health Study, who were smokers with mild to moderate airflow limitation. We determined the relationship of serum adiponectin to hospitalization and mortality using a Cox proportional hazards model and to baseline lung function measurements and bronchial reactivity using multiple regression methods.

Results:  Serum adiponectin concentrations were inversely related to hospitalizations and mortality from coronary heart disease (hazard ratio [HR], 0.73; 95% CI, 0.62-0.86) and to cardiovascular disease (HR, 0.83; 95% CI, 0.73-0.94) and positively related to deaths from respiratory causes (HR, 2.09; 95% CI, 1.41-3.11). However, serum adiponectin concentrations were not significantly related to total mortality (HR, 1.10; 95% CI, 0.93-1.29) or cancer-related mortality (HR, 1.11; 95% CI, 0.92-1.34). Serum adiponectin concentrations were significantly related to increased bronchial reactivity and an accelerated decline in lung function (both P < .0001). Smoking status had no material influence on serum adiponectin concentrations.

Conclusions:  Adiponectin is a complex serum biomarker in COPD that is associated with decreased risk of cardiovascular events but increased risk of respiratory mortality. Because serum adiponectin is not significantly influenced by smoking status, it is a very promising biomarker of cardiovascular outcomes in COPD.

Chest. 2012;142(4):900-908. doi:10.1378/chest.11-2886

Background:  Intrabronchial valve placement for endoscopic lung volume reduction is used for patients with severe lung emphysema. Different treatment approaches are unilateral valve placement with the goal of complete occlusion and subsequent atelectasis leading to true volume reduction vs bilateral partial closure aiming for redistribution of ventilation but avoiding atelectasis. In this prospective pilot trial, we compared the efficacy of these treatment approaches.

Methods:  Patients with severe bilateral heterogeneous emphysema were randomized to two groups. In the first group, patients received unilateral valves aiming for total occlusion of one lobe. In the other group, valves were placed in two contralateral lobes with incomplete closure. In all cases, one-way valves were placed via a flexible bronchoscope. Patients were followed at 30 and 90 days, end points being change in pulmonary function tests (PFTs), 6-min walk distance (6MWD), and dyspnea score as measured by the modified Medical Research Council (mMRC) dyspnea score, as well as quality of life as measured by the St. George Respiratory Questionnaire (SGRQ).

Results:  Twenty-two patients were treated in this study, 11 patients in each arm. At 30 days and 90 days, significant differences were seen in PFT and 6MWD, as well as in mMRC and SGRQ scores, in favor of unilateral treatment. At 90 days, FEV1 was improved by 21.4% ± 10.7% in this group, but not in the bilateral group (−0.03% ± 13.9%, P = .002). One patient in the unilateral group experienced a pneumothorax, and two patients in the bilateral group were treated for transient respiratory failure.

Conclusions:  Unilateral intrabronchial valve placement with complete occlusion appears superior to bilateral partial occlusion.

Trial registry:  ClinicalTrials.gov; No.: NCT00995852; URL: www.clinicaltrials.gov

Chest. 2012;142(4):909-918. doi:10.1378/chest.11-2884

Background:  Prospective evidence on the association between secondhand smoke (SHS) and COPD and ischemic stroke is scarce.

Methods:  We prospectively examined the relationship between SHS and major tobacco-related deaths, particularly COPD and stroke, in 910 Chinese (439 men, 471 women) who never smoked from a 17-year follow-up study in Xi’an, China. SHS exposure was defined as exposure to another person’s tobacco smoke at home or in the workplace.

Results:  At baseline among the 910 subjects, 44.2% were exposed to SHS at home, 52.9% in the workplace, and 67.1% at home, work, or both. From March 1, 1994, to July 1, 2011, 249 (150 men, 99 women) died within 14,016 person-years. Those who were exposed to SHS had increased mortality due to coronary heart disease (adjusted relative risk [RR], 2.15; 95% CI, 1.00-4.61), ischemic stroke (RR, 2.88; 95% CI, 1.10-7.55), lung cancer (RR, 2.00; 95% CI, 0.62-6.40), COPD (RR, 2.30; 95% CI, 1.06-5.00), and all causes (RR, 1.72; 95% CI, 1.29-2.20), with significant dose-response relationships between cumulative SHS exposure at home and work and the increased risk of cause-specific and total mortality (P for linear trend ranged from .045 to <.001).

Conclusions:  This study shows dose-response relationships between SHS and major tobacco-related mortality and provides new evidence to support causation for COPD and ischemic stroke.

Chest. 2012;142(4):919-926. doi:10.1378/chest.11-2535

Background:  The use of inhaled corticosteroids in mild to moderate COPD is controversial. The aim of this study was to determine whether airway hyperresponsiveness to mannitol might identify patients who are likely to respond to add-on inhaled corticosteroids.

Methods:  Ninety subjects with mild to moderate COPD were recruited and 68 subsequently randomized in a double-blind manner to receive inhaled budesonide (1,600 μg/d, n = 31) or placebo (n = 37) for 3 months. Thirty-eight subjects had airway hyperresponsiveness to mannitol (17 received budesonide, 21 placebo). All subjects received tiotropium throughout the study, including 4 weeks before randomization. Spirometry, quality of life (St. George Respiratory Questionnaire), degree of dyspnea, airway responsiveness to mannitol, and exhaled nitric oxide were assessed at week 0 (recruitment), week 4 (baseline prior to randomization), and week 16 (posttreatment).

Results:  Compared with placebo, budesonide was associated with improved quality of life in subjects showing airway hyperresponsiveness to mannitol (difference of changes in quality of life score between randomization and study completion, −9.1; 95% CI, −15.8 to −2.3; P < .01). Treatment with inhaled budesonide also led to a reduction in airway responsiveness to mannitol compared with placebo (difference in log10 response-dose ratio, −0.3; 95% CI, −0.6 to −0.04; P < .01). However, postrandomization changes in FEV1 % predicted, quality of life, and exhaled nitric oxide showed no difference between budesonide and placebo.

Conclusions:  In subjects with mild to moderate COPD and airway hyperresponsiveness to mannitol, quality of life and airway responsiveness improved after treatment with inhaled corticosteroids added to long-acting bronchodilator therapy.

Trial registry:  ClinicalTrials.gov; No.: NCT00860938; URL: www.clinicaltrials.gov

Original Research: Sleep Disorders

Chest. 2012;142(4):927-934. doi:10.1378/chest.11-1899

Background:  Cheyne-Stokes respiration (CSR), which often occurs in patients with congestive heart failure (CHF), may be a predictor for poor outcome. Phrenic nerve stimulation (PNS) may interrupt CSR in patients with CHF. We report the clinical use of transvenous PNS in patients with CHF and CSR.

Methods:  Nineteen patients with CHF and CSR were enrolled. A single stimulation lead was placed at the junction between the superior vena cava and brachiocephalic vein or in the left-side pericardiophrenic vein. PNS stimulation was performed using Eupnea System device (RespiCardia Inc). Respiratory properties were assessed before and during PNS. PNS was assessed at a maximum of 10 mA.

Results:  Successful stimulation capture was achieved in 16 patients. Failure to capture occurred in three patients because of dislocation of leads. No adverse events were seen under maximum normal stimulation parameters for an overnight study. When PNS was applied following a series of central sleep apneic events, a trend toward stabilization of breathing and heart rate as well as improvement in oxygen saturation was seen. Compared with pre-PNS, during PNS there was a significant decrease in apnea-hypopnea index (33.8 ± 9.3 vs 8.1 ± 2.3, P = .00), an increase in mean and minimal oxygen saturation as measured by pulse oximetry (89.7% ± 1.6% vs 94.3% ± 0.9% and 80.3% ± 3.7% vs 88.5% ± 3.3%, respectively, all P = .00) and end-tidal CO2 (38.0 ± 4.3 mm Hg vs 40.3 ± 3.1 mm Hg, P = .02), but no significant difference in sleep efficiency (74.6% ± 4.1% vs 73.7% ± 5.4%, P = .36).

Conclusions:  The preliminary results showed that in a small group of patients with CHF and CSR, 1 night of unilateral transvenous PNS improved indices of CSR and was not associated with adverse events.

Trial registry:  ClinicalTrials.gov; No.: NCT00909259; URL: www.clinicaltrials.gov

Chest. 2012;142(4):935-942. doi:10.1378/chest.11-1844

Background:  It has been suggested that sleep-disordered breathing (SDB) is a risk factor for diabetes, but long-term follow-up studies are lacking. The aim of this community-based study was to analyze the influence of SDB on glucose metabolism after > 10 years.

Methods:  Men without diabetes (N = 141; mean age, 57.5 years) were investigated at baseline, including whole-night respiratory monitoring. After a mean period of 11 years and 4 months, they were followed up with an interview, anthropometric measurements, and blood sampling. Insulin resistance was quantified using the homeostasis model assessment of insulin resistance (HOMA-IR). ΔHOMA-IR was calculated as (HOMA-IR at follow-up − HOMA-IR at baseline). An oral glucose tolerance test was performed on 113 men to calculate the insulin sensitivity index.

Results:  The mean apnea-hypopnea index (AHI) and oxygen desaturation index (ODI) at baseline were 4.7 and 3.3, respectively. At follow-up, 23 men had diabetes. An ODI > 5 was a predictor of developing diabetes (OR, 4.4; 95% CI, 1.1-18.1, after adjusting for age, BMI, and hypertension at baseline and ΔBMI and years with CPAP during follow-up). The ODI was inversely related to the insulin sensitivity index at follow-up (r = −0.27, P = .003). A deterioration in HOMA-IR was significantly related to all variables of SDB (AHI, AHI > 5; ODI, ODI > 5; minimum arterial oxygen saturation), even when adjusting for confounders. When excluding the variable years with CPAP from the multivariate model, all associations weakened.

Conclusions:  SDB is independently related to the development of insulin resistance and, thereby, the risk of manifest diabetes mellitus.

Original Research: Signs and Symptoms of Chest Diseases

Chest. 2012;142(4):943-950. doi:10.1378/chest.11-2725

Background:  While the burden of chronic cough in children has been documented, etiologic factors across multiple settings and age have not been described. In children with chronic cough, we aimed (1) to evaluate the burden and etiologies using a standard management pathway in various settings, and (2) to determine the influence of age and setting on disease burden and etiologies and etiology on disease burden. We hypothesized that the etiology, but not the burden, of chronic cough in children is dependent on the clinical setting and age.

Methods:  From five major hospitals and three rural-remote clinics, 346 children (mean age 4.5 years) newly referred with chronic cough (> 4 weeks) were prospectively managed in accordance with an evidence-based cough algorithm. We used a priori definitions, timeframes, and validated outcome measures (parent-proxy cough-specific quality of life [PC-QOL], a generic QOL [pediatric quality of life (PedsQL)], and cough diary).

Results:  The burden of chronic cough (PC-QOL, cough duration) significantly differed between settings (P = .014, 0.021, respectively), but was not influenced by age or etiology. PC-QOL and PedsQL did not correlate with age. The frequency of etiologies was significantly different in dissimilar settings (P = .0001); 17.6% of children had a serious underlying diagnosis (bronchiectasis, aspiration, cystic fibrosis). Except for protracted bacterial bronchitis, the frequency of other common diagnoses (asthma, bronchiectasis, resolved without specific-diagnosis) was similar across age categories.

Conclusions:  The high burden of cough is independent of children’s age and etiology but dependent on clinical setting. Irrespective of setting and age, children with chronic cough should be carefully evaluated and child-specific evidence-based algorithms used.

Trial registry:  Australian New Zealand Clinical Trials registry; No.: ACTRN12607000526471; URL: www.anzctr.org.au

Topics: cough, chronic , cough
Chest. 2012;142(4):951-957. doi:10.1378/chest.12-0362

Background:  The urge to cough is a clinical symptom of respiratory disease that precedes the motor act of coughing. Although previous studies have shown that cough is particularly susceptible to placebo suppression, it is unclear whether the perception of an urge to cough is also modifiable by placebo. Therefore, we tested the hypothesis that capsaicin-evoked urge to cough could be suppressed by placebo conditioning.

Methods:  Eleven healthy participants were unknowingly conditioned to believe that an inert inhaler temporarily suppressed capsaicin-induced urge to cough by deceptively modifying the challenge concentration of capsaicin. In subsequent testing, capsaicin-evoked urge-to-cough subjective ratings were assessed in four challenges with a single dose of inhaled capsaicin following no treatment or the placebo metered-dose inhaler. An additional 10 participants were informed that the inhaler therapy was inert prior to receiving capsaicin challenges with and without inhaler treatment.

Results:  There was a significant decrease in mean urge-to-cough ratings to capsaicin challenge following placebo compared with no treatment followed by capsaicin challenge (P < .001), with a peak decrease of 45%. The placebo inhaler alone had no effect on urge-to-cough subjective ratings when participants were aware that it contained no active medication.

Conclusions:  These data confirm that the urge to cough is susceptible to placebo inhibition. This provides further evidence that higher brain networks are involved in the processing of respiratory sensations related to airway irritation.

Chest. 2012;142(4):958-964. doi:10.1378/chest.12-0044

Background:  Microaspiration is often considered a potential cause of cough. The aim of this study was to investigate the relationship between microaspiration, the degree and type of gastroesophageal reflux, and the frequency of coughing in patients with chronic cough.

Methods:  One hundred patients with chronic cough (mean [± SD] age, 55.8 years [± 11.0 years]; 65 women) and 32 healthy volunteers (median age, 43.5 years [interquartile range (IQR), 30-50.8 years]; 16 women) were recruited. Patients with chronic cough performed 24-h objective cough frequency with simultaneous esophageal impedance/pH monitoring and measurement of pepsin concentrations in sputum and BAL. Twelve healthy volunteers underwent bronchoscopy/BAL, and 20 underwent impedance/pH monitoring.

Results:  Patients with chronic cough had significantly more reflux episodes than healthy volunteers (median, 63.5 reflux episodes [IQR, 52.5-80.0] vs 59.0 [IQR, 41.8-66.0]; P = .03), although the absolute difference was small, and there was no difference in numbers of events extending into the proximal esophagus (median, 17.2% [IQR, 8.0%-26.0%] vs 20.3% [IQR, 5.1%-32.1%]; P = .36). BAL pepsin levels were also similar in chronic cough to control subjects (median, 18.2 ng/mL [range, 0-56.4 ng/mL] vs 9.25 ng/mL [range, 0-46.9 ng/mL]; P = .27). Sputum but not BAL pepsin weakly correlated with the number of proximally occurring reflux events (r = 0.33, P = .045) but was inversely related to cough frequency (r = −0.52, P = .04). Sputum pepsin was, therefore, best predicted by combining the opposing influences of cough and proximal reflux (r = 0.50, P = .004).

Conclusions:  Proximal gastroesophageal reflux and microaspiration into the airways have limited roles in provoking chronic cough. Indeed, coughing appears to be protective, reducing pepsin concentration in the larger airways of patients with chronic cough.

Trial registry:  ISRCTN Register; No.: ISRCTN62337037; URL: www.isrctn.org

Original Research: Chest Infections

Chest. 2012;142(4):965-972. doi:10.1378/chest.12-0364

Background:  The aim of this prospective, multicenter study was to define the accuracy of lung ultrasound (LUS) in the diagnosis of community-acquired pneumonia (CAP).

Methods:  Three hundred sixty-two patients with suspected CAP were enrolled in 14 European centers. At baseline, history, clinical examination, laboratory testing, and LUS were performed as well as the reference test, which was a radiograph in two planes or a low-dose CT scan in case of inconclusive or negative radiographic but positive LUS findings. In patients with CAP, follow-up between days 5 and 8 and 13 and 16 was scheduled.

Results:  CAP was confirmed in 229 patients (63.3%). LUS revealed a sensitivity of 93.4% (95% CI, 89.2%-96.3%), specificity of 97.7% (95% CI, 93.4%-99.6%), and likelihood ratios (LRs) of 40.5 (95% CI, 13.2-123.9) for positive and 0.07 (95% CI, 0.04-0.11) for negative results. A combination of auscultation and LUS increased the positive LR to 42.9 (95% CI, 10.8-170.0) and decreased the negative LR to 0.04 (95% CI, 0.02-0.09). We found 97.6% (205 of 211) of patients with CAP showed breath-dependent motion of infiltrates, 86.7% (183 of 211) an air bronchogram, 76.5% (156 of 204) blurred margins, and 54.4% (105 of 193) a basal pleural effusion. During follow-up, median C-reactive protein levels decreased from 137 mg/dL to 6.3 mg/dL at days 13 to 16 as did signs of CAP; median area of lesions decreased from 15.3 cm2 to 0.2 cm2 and pleural effusion from 50 mL to 0 mL.

Conclusions:  LUS is a noninvasive, usually available tool used for high-accuracy diagnosis of CAP. This is especially important if radiography is not available or applicable. About 8% of pneumonic lesions are not detectable by LUS; therefore, an inconspicuous LUS does not exclude pneumonia.

Trial registry:  ClinicalTrials.gov; No.: NCT00808457; URL: www.clinicaltrials.gov

Chest. 2012;142(4):973-981. doi:10.1378/chest.11-1160

Background:  Pneumonia is a frequent and serious illness in elderly people, with a significant impact on mortality and health-care costs. Lingering effects may influence clinical outcomes and medical service use beyond the acute hospitalization. This study describes the incidence and mortality of pneumonia in elderly Medicare beneficiaries based on treatment setting (outpatient, inpatient) and location of origin (health-care associated, community acquired) and estimates short- and long-term direct medical costs and mortality associated with an inpatient episode of pneumonia.

Methods:  Administrative claims from a 5% sample of fee-for-service Medicare beneficiaries aged ≥ 65 years from 2005 through 2007 were used. Total direct medical costs for patients during and after hospitalization for pneumonia compared with similar patients without pneumonia (the excess cost of pneumonia) were estimated using propensity score matching.

Results:  The age-adjusted annual cumulative incidence of any pneumonia was 47.4 per 1,000 beneficiaries (13.3 per 1,000 inpatient primary pneumonia), increasing with age; one-half of pneumonia cases were treated in the hospital. Thirty-day mortality was twice as high among beneficiaries with health-care-associated pneumonia than among those hospitalized with community-acquired pneumonia (13.4% vs 6.4%). Total medical costs for beneficiaries during and 1 year following a pneumonia hospitalization were $15,682 higher than matched control patients without pneumonia. The total annual excess cost of hospital-treated pneumonia as a primary diagnosis in the elderly fee-for-service Medicare population in 2010 is estimated conservatively at > $7 billion.

Conclusions:  Pneumonia in elderly people is associated with high acute-care costs and an overall impact on total direct medical costs and mortality during and after an acute episode.

Chest. 2012;142(4):982-987. doi:10.1378/chest.11-3183

Background:  Although marital status has been shown to affect the outcomes of many conditions, there are limited data on the relationships between marital status and the presentation and outcomes of pneumonia.

Methods:  We used Veterans Affairs administrative databases to identify a retrospective cohort of male veterans age ≥ 65 years hospitalized for pneumonia between 2002 and 2007. We assessed unadjusted and adjusted associations between marital status and mortality, hospital length of stay, and readmission to the hospital using generalized linear mixed-effect models with admitting hospital as a random effect and adjusted for baseline patient characteristics.

Results:  There were 48,635 patients (26,558 married and 22,077 unmarried) in the study. Married men had a slightly higher Charlson comorbidity score (3.0 vs 2.8, P < .0001) but were less likely to require ICU admission, ventilator support, and vasopressor treatment during the first 48 h of hospitalization. Married patients had significantly lower crude and adjusted in-hospital mortality (9.4% vs 10.6%; adjusted OR, 0.87; 95% CI, 0.81-0.93) and mortality during the 90 days after hospital discharge (14.7% vs 16.0%; adjusted OR, 0.92; 95% CI, 0.88-0.98). Their adjusted incidence rate ratio length of stay was also lower (0.92; 95% CI, 0.91-0.92).

Conclusions:  Unmarried elderly men admitted to the hospital with pneumonia have a higher risk of in-hospital and postdischarge mortality, despite having a lower degree of comorbidity. Although marital status may be a surrogate marker for other predictors, it is an easily identifiable one. These results should be considered by those responsible for care-transition decisions for patients hospitalized with pneumonia.

Chest. 2012;142(4):988-995. doi:10.1378/chest.11-1964

Background:  Pulmonary invasive fungal disease is a frequent complication in patients with hematologic malignancies. Surgical resection in addition to antifungal therapy is an option for selected cases but often feared because of immunosuppression.

Methods:  We analyzed the outcome of 71 patients undergoing lung resection for pulmonary invasive fungal disease. Most patients had leukemia, 44 underwent high-dose chemotherapy, and 18 underwent stem cell transplantation.

Results:  On the day of surgery, 44 patients were neutropenic, and 41 had a platelet count < 50 × 109/L. Forty-five nonanatomic (atypical) resections and 26 lobectomies were performed. Fungal infection was histologically proven in 53 patients. Reoperation was needed in four patients (bronchial stump dehiscence, persistent air leak, chylothorax, and seroma). Minor complications at the site of surgery occurred in 14 patients. In only two, there was an uncontrolled disseminated fungal infection. Overall, mortality at 30 days was 7% (five of 71). Long-term survival was mainly influenced by the underlying hematologic disease.

Conclusions:  Lung resection is a therapeutic option for hematologic patients with pulmonary fungal infection. Despite immunosuppression, the perioperative morbidity and mortality is acceptable, and, therefore, the prognosis is not determined by the surgical intervention.

Original Research: Cystic Fibrosis

Chest. 2012;142(4):996-1004. doi:10.1378/chest.11-2543

Background:  Previous studies report a high frequency of mutations in the cystic fibrosis (CF) transmembrane conductance regulator gene (CFTR) in patients with idiopathic bronchiectasis. However, most studies have based their findings on preselected patient groups or have performed limited testing for CF transmembrane conductance regulator (CFTR) dysfunction. The objective of our study was to evaluate the prevalence of CFTR gene mutations and/or CFTR-related ion channel abnormalities among subjects with idiopathic chronic sinopulmonary disease and the prevalence of CF or a CFTR-related disorder in this population.

Methods:  We evaluated 72 prospectively enrolled patients from 1995 to 2005 at the Hospital for Sick Children and St. Michael’s Hospital with idiopathic chronic sinopulmonary disease for evidence of CFTR-mediated abnormalities. We performed CFTR genotyping and assessed CFTR function using sweat testing and nasal potential difference testing. The results were compared with data from healthy control subjects, CF heterozygotes, and patients with CF.

Results:  The CFTR functional tests in idiopathic sinopulmonary patients showed a continuous spectrum, ranging from normal to values typically seen in individuals with CF. Forty-eight patients (66%) demonstrated CFTR mutations and/or abnormalities of CFTR function. Twenty-two (31%) fulfilled criteria for a diagnosis of CF and 26 (36%) for a CFTR-related disorder with a strong female preponderance. Functional tests, more than genotyping, were instrumental in establishing a CF diagnosis. Clinical features failed to distinguish subjects with CF from those with CFTR-related or idiopathic disease.

Conclusions:  The high prevalence of CF and CFTR dysfunction among patients with idiopathic chronic sinopulmonary disease underscores the need for extensive diagnostic evaluation for CF.

Original Research: Diffuse Lung Disease

Chest. 2012;142(4):1005-1010. doi:10.1378/chest.12-0298

Background:  The characteristics of long-term survivors with idiopathic pulmonary fibrosis (IPF) have never been fully elucidated. We sought to illustrate the attenuated mortality and describe the characteristics of patients with IPF who survived at least 5 years beyond their initial presentation.

Methods:  Patients with IPF evaluated between 1997 and 2006 were identified through the clinic database. Patients who survived beyond 5 years from the time of their evaluation were compared with those who died or underwent lung transplantation within 5 years. Survival analyses were performed from the time of initial evaluation and contingent on annualized survival thereafter.

Results:  Eighty-seven patients who survived at least 5 years formed the comparator group to whom other patients were contrasted. These patients had a higher BMI, FVC % predicted, FEV1 % predicted, total lung capacity % predicted, and diffusing capacity of lung for carbon monoxide % predicted, but a lower FEV1/FVC ratio and lower mean pulmonary artery pressures. More than one-half of these patients had moderate or severe disease at the time of presentation. Our annualized contingent survival analyses revealed a progressively increasing median survival dependent on the duration of the disease.

Conclusions:  Although we were able to demonstrate differences in our 5-year survivors, rather than being a distinct group, these patients appear to exist within a continuum of improving survival dependent on prior disease duration. This progressively improving time-dependent prognosis mandates the serial reevaluation of an individual patient’s projected outcomes. The implementation of dynamic counseling is an important concept in more accurately predicting life expectancy for patients with IPF who are frequently haunted by the prospects of a dismal survival.

Chest. 2012;142(4):1011-1019. doi:10.1378/chest.11-2879

Background:  Idiopathic pulmonary fibrosis (IPF) involves lung injury induced by reactive oxygen species (ROS), such as superoxide anion, and fibrosis. Superoxide dismutase (SOD) catalyses the dismutation of superoxide anion to hydrogen peroxide. We recently reported that inhalation of lecithinized SOD (PC-SOD) ameliorated bleomycin-induced pulmonary fibrosis. We here studied effects of PC-SOD on bleomycin-induced pulmonary fibrosis and lung dysfunction and compared the results to those obtained with pirfenidone, a newly developed drug for IPF.

Methods:  Lung mechanics (elastance) and respiratory function (FVC) were assessed using a computer-controlled ventilator. Respiratory function was evaluated by monitoring percutaneous arterial oxygen saturation (Spo2).

Results:  Both inhalation of PC-SOD and oral administration of pirfenidone ameliorated bleomycin-induced pulmonary fibrosis and changes in lung mechanics. Administration of bleomycin produced a decrease in both FVC and Spo2. PC-SOD treatment led to significant recovery of both parameters, whereas pirfenidone improved only Spo2. PC-SOD suppressed the bleomycin-induced pulmonary inflammatory response and production of superoxide anions in the lung more effectively than pirfenidone. Furthermore, both PC-SOD and pirfenidone produced a therapeutic effect even when the drug was administered after the development of fibrosis. PC-SOD and pirfenidone also produced a synergistic therapeutic effect.

Conclusions:  These results suggest that the superior activity of PC-SOD to pirfenidone against bleomycin-induced pulmonary fibrosis and lung dysfunction is due to its unique antioxidant activity. We propose that treatment of IPF with a combination of PC-SOD and pirfenidone could be therapeutically beneficial.

Original Research: Lung Cancer

Chest. 2012;142(4):1020-1026. doi:10.1378/chest.11-2943

Background:  We previously identified amplification of the fibroblast growth factor receptor 1 gene (FGFR1) as a potential therapeutic target for small-molecule inhibitor therapy in squamous cell lung cancer (L-SCC). Currently, clinical phase I trials are underway to examine whether patients with FGFR1-amplified L-SCC benefit from a targeted therapy approach using small-molecule inhibitors. Because most patients with lung cancer present with metastatic disease, we investigated whether lymph node metastases in L-SCC share the FGFR1 amplification status of their corresponding primary tumor.

Methods:  The study cohort consisted of 72 patients with L-SCC, 39 with regional lymph node metastases. Tissue microarrays were constructed from formalin-fixed, paraffin-embedded tissue of the primary tumors and, where present, of the corresponding lymph node metastasis. A biotin-labeled target probe spanning the FGFR1 locus (8p11.22-23) was used to determine the FGFR1 amplification status by fluorescence in situ hybridization.

Results:  FGFR1 amplification was detected in 16% (12 of 72) of all primary L-SCCs. In metastatic tumors, 18% (seven of 39) of the lymph node metastases displayed FGFR1 amplification with an exact correlation of FGFR1 amplification status between tumor and metastatic tissue.

Conclusions:  FGFR1 amplification is a common genetic event occurring at a frequency of 16% in L-SCCs. Moreover, lymph node metastases derived from FGFR1-amplified L-SCCs also exhibit FGFR1 amplification. Therefore, we suggest that the FGFR1 amplification is a clonal event in tumor progression. Beyond this biologically relevant observation, the findings carry potential therapeutic implications in that small-molecule inhibitors may be applicable to the treatment of a subset of patients with metastatic L-SCC.

Ahead of the Curve

Chest. 2012;142(4):1027-1034. doi:10.1378/chest.12-1540

Recent advances in the field of clinical biomarkers suggest that quantification of serum proteins could play an important role in the diagnosis, classification, prognosis, and treatment response of smoking-related parenchymal lung diseases. COPD and idiopathic pulmonary fibrosis (IPF), two common chronic progressive parenchymal lung diseases, share cigarette smoke exposure as a common dominant risk factor for their development. We have recently shown that COPD and interstitial lung disease may represent distinct outcomes of chronic tobacco use, whereas others have demonstrated that both diseases coexist in some individuals. In this perspective, we examine the potential role of peripheral blood biomarkers in predicting which individuals will develop COPD or IPF, as well as their usefulness in tracking disease progression and exacerbations. Additionally, given the current lack of sensitive and effective metrics to determine an individual’s response to treatment, we evaluate the potential role of biomarkers as surrogate markers of clinical outcomes. Finally, we examine the possibility that changes in levels of select protein biomarkers can provide mechanistic insight into the common origins and unique individual susceptibilities that lead to the development of smoking-related parenchymal lung diseases. This discussion is framed by a consideration of the properties of ideal biomarkers for different clinical and research purposes and the best uses for those biomarkers that have already been proposed and investigated.

Topics in Practice Management

Chest. 2012;142(4):1035-1038. doi:10.1378/chest.09-1283

Clinical documentation improvement is an important aspect to achieve top performance. Clinical documentation in a patient’s record includes any and all documentation that relates to the care of the patient during the patient’s stay or encounter at the hospital. Documentation is key to accurate clinical coding, validating length of stay, resource utilization, physician profiling, case management, severity of illness, risk of mortality, quality management, risk management, clinical outcomes, critical pathways, regulatory compliance, Joint Commission accreditation, managed care, and reimbursement. Good documentation minimizes coding errors, reduces claim denials, and optimizes reimbursement. Implementing quality improvement strategies that make documentation and coding an organizational priority can positively influence operations, services, and revenue. Other external and internal coding audits show that the cause of improper coding is due to lack of proper physician documentation to support reimbursement at the appropriate level. The purpose of this article is to provide tips for documenting pulmonary diagnoses that not only would ensure appropriate reimbursement but also would accurately represent the severity of a patient’s condition.

Selected Reports

Chest. 2012;142(4):1039-1041. doi:10.1378/chest.11-2732

Scimitar syndrome is one of the large congenital pulmonary venolobar syndromes and is defined as hypogenetic lung associated with partial anomalous pulmonary venous return. We report the case of a 25-year-old man with complex and exceptional variant scimitar syndrome. A chest CT scan with three-dimensional (3-D) reconstruction led us to identify hypoplastic right lung with homolateral hemidiaphragm agenesis and hypogenetic right pulmonary artery. There was a large and sinuous systemic arterial supply and anomalous venous return directed into the left atrium (venous return being usually directed into the right atrium or inferior vena cava in scimitar syndrome). Hyperoxia test showed no shunt. This variant scimitar syndrome has been previously reported and anomalous venous return called “meandering” pulmonary vein. Diagnosis and management of these patients with complex congenital anomalies are difficult because of their exceptional condition. Chest CT scan with 3-D reconstruction offers an accurate noninvasive diagnosis.

Postgraduate Education Corner: Contemporary Reviews in Critical Care Medicine

Chest. 2012;142(4):1042-1048. doi:10.1378/chest.12-1297

The availability of portable ultrasound devices is changing the approach to the diagnosis and management of shock by offering timely diagnosis and acting to guide therapy. Goal-directed echocardiography (GDE) can be performed well by noncardiologists and consists of a limited number of standard cardiac views: parasternal long axis, parasternal short axis, apical four chamber, subcostal long axis, and inferior vena cava long axis. GDE allows the intensivist to assess left and right ventricular pump function, pericardial effusion, septal dynamics, valvular morphology, major valve failure, and fluid responsiveness. Here, we review the questions involved in a systematic approach to the patient in shock, employing GDE: (1) Is there an imminently life-threatening cause for the shock? (2) Is the shock state likely to be fluid responsive? (3) Is there evidence of pump failure? (4) Is there more than one cause for the shock state? (5) Is the cause of the shock state other than cardiac in origin? In contrast to formal echocardiography, GDE is qualitative, can be performed in a few minutes, is interpreted immediately, can be repeated as often as needed, and is always integrated with other elements of the intensivist’s assessment to arrive at an understanding of the basis for the shock and a rational treatment plan. An important part of using GDE is recognizing its limitations and judging when to proceed to a comprehensive echocardiography examination. Competence in GDE has become an essential skill for the practicing intensivist.

Postgraduate Education Corner: Contemporary Reviews in Sleep Medicine

Chest. 2012;142(4):1049-1057. doi:10.1378/chest.11-3223

Complex sleep apnea syndrome (CompSAS) describes the coexistence or appearance and persistence of central apneas or hypopneas in patients with obstructive sleep apnea upon successful restoration of airway patency. We review data on treatment of CompSAS with CPAP, bilevel positive airway pressure, and adaptive servoventilation and discuss evidence for the addition of medications (analgesics, hypnotics, acetazolamide) and gases (oxygen, CO2) to positive airway pressure therapy. Future research should focus on defining outcomes in patients with CompSAS and allow for more accurate tailoring of therapy to the pathophysiology present in the individual patient.

Postgraduate Education Corner: Pulmonary and Critical Care Pearls

Chest. 2012;142(4):1058-1062. doi:10.1378/chest.12-0011

A 33-year-old man was referred to our institution for evaluation of multiple pulmonary nodules. The patient had been in his usual state of health until a week prior to admission, when he presented to an outside hospital with complaints of right-sided chest pain. An initial chest radiograph revealed multiple pulmonary nodules, and a CT scan of the chest confirmed the nodules. The CT scan of the chest also demonstrated a left upper lobe mass. The patient was referred to our institution. A review of systems revealed only the presence of right-sided chest pain for 1 week. The patient had no significant medical history. He had a 15-pack-year smoking history. He denied any travel history or contact with sick people or pets. His family history was significant for lung cancer and breast cancer in his paternal grandmother.

Chest. 2012;142(4):1063-1067. doi:10.1378/chest.11-2700

TaziA. Adult pulmonary Langerhans’ cell histiocytosis. Eur Respir J. 2006;27(6):1272-1285.HarocheJAmouraZWechslerBVeyssier-BelotCCharlotteFPietteJC. Erdheim-Chester disease [in French]. Presse Med. 2007;36(11 pt 2):1663-1668.HarocheJCluzelPToledanoD. Images in cardiovascular medicine. Cardiac involvement in Erdheim-Chester disease: magnetic resonance and computed tomographic scan imaging in a monocentric series of 37 patients. Circulation. 2009;119(25):e597-e598.ArnaudLPierreIBeigelman-AubryC. Pulmonary involvement in Erdheim-Chester disease: a single-center study of thirty-four patients and a review of the literature. Arthritis Rheum. 2010;62(11):3504-3512.BrunALTouitou-GottenbergDHarocheJ. Erdheim-Chester disease: CT findings of thoracic involvement. Eur Radiol. 2010;20(11):2579-2587.TsaiJWTsouJHHungLYWuHBChangKC. Combined Erdheim-Chester disease and Langerhans cell hisyiocytosis of skin are both monoclonal: a rare case with human androgen-receptor gene analysis. J Am Acad Dermatol. 2010;63(2):284-291.ArnaudLHervierBNéelA. CNS involvement and treatment with interferon-α are independent prognostic factors in Erdheim-Chester disease: a multicenter survival analysis of 53 patients. Blood. 2011;117(10):2778-2782.MasciPGZampaVBarisonALombardiM. Cardiovascular involvement in Erdheim-Chester disease. Int J Cardiol. 2012;154(2):e24-e26.


Chest. 2012;142(4):1068. doi:10.1378/chest.11-2854

I bore true blood in battle
though my breath came quick
and poorly; kept silent
while a needle’s sting
attacked my marrow
sorely. Suffered anonymity,
waiting for reports; then swore
upon my fainting heart
to take my name again:
to carry true blood singing,
secret and alone,
and release the captive
language tuning in the bone.

Chest. 2012;142(4):1068. doi:10.1378/chest.11-3055

February, after lunch. Every chief complaint
includes aches and sore throat. Nine
women. Two men. Deep lined faces seek
relief in this familiar space with blue
countertops. Three exam rooms, ordered
exactly, labels on drawers and doors.
I can’t find the correct swab I need
in this pile of white-tipped applicators:
compressed foam for viral cultures,
difficult-to-open rayon heads for strep,
and so on. I can’t catch a rhythm. It’s like
cooking dinner in someone else’s kitchen.
Between patients, one of the nurses tells
me about her trip to Mayo. She starts chemo
next week. Stethoscope thumps gawky against
my chest without breasts to damper the bumps.

Chest. 2012;142(4):1069. doi:10.1378/chest.11-2849

Mom says “I love you” on the telephone now. I only heard it once
before, as I walked out the door for school. She grabbed my arm,
demanded a kiss. I hesitated. Despite morning toothpaste, her
hangover and cigarette breath threatened. Her forehead furrowed—
What’s wrong? My friends say that I should kiss you before you outgrow it.
Too late for me. She wasn’t watching when I figured out that she filed
shoulds and oughts like three-by-five cards in a recipe box, crib notes
for sincerity. Joyless, I obeyed. Better this than another argument. Better
than looking like a bratty teenager. Better keep the peace. Better
that I allowed nature to follow its natural course when she forgot
friends’ advice and I returned to shutting the back door behind me
without a staged goodbye. In one week, surgeons will remove
most of her tongue, cutting out cancer that creeps along pink
tastebuds. This time, the words she speaks are not a demand. Her voice
trembles. Twenty-five years later, she still has an agenda. My mind substitutes
her real meaning: I’m scared. Fledglings both, I allow
her to practice on me. “I love you, too,” I reply, meaning,
I would never wish this on anyone.

Chest. 2012;142(4):1070. doi:10.1378/chest.11-2847

Ever since that day I posed from waist up
the image follows me like a child with a marker
trailing lines across walls
naked, first time
I glow on lightbox after lightbox
beneath radiologists’ gazes,
parse pathology reports—
moderately differentiated,
partly cloudy sky.
After summer’s rain leaves soft mists
rising from the lawn like steam
the image rises beneath my feet
colonies of twisted angleworms
oozing between blades of grass
absorbing oxygen through their flesh.
My screensaver is an unintended splash
of intraductal cribriform, coalescing left, center, right
rapid sequence Day-Glo lime on black.
I see calcium deposits in flocks of starlings
smattering the sky—
see how they disperse, regroup!
I prefer to see my cancer above, shout
to primed heavens, lift my chin, cheer
fireworks in the night, pupils constricted
exuberant burst fading to black
after-image etched in permanence.

Chest. 2012;142(4):1070. doi:10.1378/chest.11-3113

Whether to bring cotton pajamas
or flannel nightgown, white fluffy slippers
or purple flip-flops, these
were the questions consuming me.
The doctor plotted a minimal invasion
a detour around muscle and bone
with heavy artillery standing by
in the event of an unforeseen uprising.
The word “minimal” signaled No Big Deal
just a little valve job, a minor repair on a torn flap
letting blood leak into other chambers—like the atrium
which sounds better suited for cultivating plants.
Cut, stitch, secure with a tiny ring
to adorn my heart, a decorative piercing—
modern, trendy, sexy even,
while the heart-lung machine drained my blood
faster than Dracula’s kiss, as I lay swooning
wan and pale as Camille. I’d packed Moby Dick,
Anna Karenina, old New Yorkers, yarn to knit,
not anticipating two days in Recovery
tethered to the bed by a catheter, tubes,
besieged at all hours by beeps and bells,
the Ladies Home Journal sliding off the bed
as my eyes closed repeatedly, swathed for days
in stained hospital gowns, then graduated
to a room upstairs where I hauled behind me
the drainage tubes planted in my chest
like Jacob Marley dragging his chains.
Once home in my own bed
my worn comforter tucked under chin
pill bottles placed within easy reach
I wake at night and finally weep.


Chest. 2012;142(4):1071. doi:10.1378/chest.12-1078

1FyshETHWrightsonJMLeeYCGRahmanNM. Fractured indwelling pleural catheters. Chest. 2012;141(4):1090-1094.2Van MeterMEMMcKeeKYKohlwesRJ. Efficacy and safety of tunneled pleural catheters in adults with malignant pleural effusions: a systematic review. J Gen Intern Med. 2011;26(1):70-76.3PienGWGantMJWashamCLStermanDL. Use of an implantable pleural catheter for trapped lung syndrome in patients with malignant pleural effusion. Chest. 2001;119(6):1641-1646.4JanesSMRahmanNMDaviesRJOLeeG. Catheter-tract metastases associated with chronic indwelling pleural catheters. Chest. 2007;131(4):1232-1234.5CasalRFBashouraLOstD. Detecting medical device complications: lessons from an indwelling pleural catheter clinic. Am J Med Qual. In press.. .

Chest. 2012;142(4):1071-1072. doi:10.1378/chest.12-1357

1FyshETHWrightsonJMLeeYCGRahmanNM. Fractured indwelling pleural catheters. Chest. 2012;141(4):1090-1094.

Chest. 2012;142(4):1072. doi:10.1378/chest.12-1255

1GershonASVictorJCGuanJAaronSDToT. Pulmonary function testing in the diagnosis of asthma: a population study. Chest. 2012;141(5):1190-1196.2NarainRGeserAJambunathanMVSubramanianM. Some aspects of a tuberculosis prevalence survey in a south Indian district. Bull World Health Organ. 1963;29641-664.3HazaleusREColeJBerdischewskyM. Tuberculin skin test conversion from exposure to contaminated pulmonary function testing apparatus. Respir Care. 1981;26(1):53-55.

Chest. 2012;142(4):1072-1073. doi:10.1378/chest.12-1428

1GershonASVictorJCGuanJAaronSDToT. Pulmonary function testing in the diagnosis of asthma: a population study. Chest. 2012;141(5):1190-1196.

Chest. 2012;142(4):1073. doi:10.1378/chest.12-1262

1NanchalRKumarGTanejaA; from the Milwaukee Initiative in Critical Care Outcomes Research (MICCOR) Group of Investigators. Pulmonary embolism: the weekend effect. Chest. 2012;142(3):690-696.2DecoususHLeizoroviczAParentF. A clinical trial of vena caval filters in the prevention of pulmonary embolism in patients with proximal deep-vein thrombosis. Prévention du Risque d’Embolie Pulmonaire par Interruption Cave Study Group. N Engl J Med. 1998;338(7):409-415.3MonrealMFalgáCValdésM; RIETE Investigators. Fatal pulmonary embolism and fatal bleeding in cancer patients with venous thromboembolism: findings from the RIETE registry. J Thromb Haemost. 2006;4(9):1950-1956.4KearonCAklEAComerotaAJ. Antithrombotic therapy for VTE disease: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines2010;141(2):e419S-e494S.5SpencerFABatesSMGoldbergRJ. A population-based study of inferior vena cava filters in patients with acute venous thromboembolism. Arch Intern Med. 2010;170(16):1456-1462.

Chest. 2012;142(4):1074. doi:10.1378/chest.12-1408

1NanchalRKumarGTanejaA; from the Milwaukee Initiative in Critical Care Outcomes Research (MICCOR) Group of Investigators. Pulmonary embolism: the weekend effect. Chest. 2012;142(3):690-696.2SpencerFABatesSMGoldbergRJ. A population-based study of inferior vena cava filters in patients with acute venous thromboembolism. Arch Intern Med. 2010;170(16):1456-1462.

Chest. 2012;142(4):1074-1075. doi:10.1378/chest.12-1234

1KearonCAklEAComerotaAJ. Antithrombotic therapy for VTE disease: Antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2012;141(2):e419S-e494S.2GarciaDABaglinTPWeitzJISamamaMM. Parenteral anticoagulants: Antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2012;141(2):e24S-e43S.3Micromedex (Micromedex Drug Information) [mobile application]. Version 1.33.0b1180. New York, NY: Thompson Reuters (Healthcare) Inc. Accessed May 8, 2012.4MerliGSpiroTEOlssonCG; Enoxaparin Clinical Trial Group. Subcutaneous enoxaparin once or twice daily compared with intravenous unfractionated heparin for treatment of venous thromboembolic disease. Ann Intern Med. 2001;134(3):191-202.5IMS Health. The use of medicines in the United States: review of 2010. IMS Institute for Healthcare Informatics website.http://www.imshealth.com/ims/Global/Content/Insights/IMS%20Institute%20for%20Healthcare%20Informatics/IHII_UseOfMed_report1_.pdf. Accessed May 8, 2012.

Chest. 2012;142(4):1075-1076. doi:10.1378/chest.12-1303

1KearonCAklEAComerotaAJ. Antithrombotic therapy for VTE disease: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2012;141((2)):supple419S-e494S.2MerliGSpiroTEOlssonCG; Enoxaparin Clinical Trial Group. Subcutaneous enoxaparin once or twice daily compared with intravenous unfractionated heparin for treatment of venous thromboembolic disease. Ann Intern Med. 2001;134(3):191-202.3CharbonnierBAFiessingerJNBangaJDWenzelEd’AzemarPSagnardL. Comparison of a once daily with a twice daily subcutaneous low molecular weight heparin regimen in the treatment of deep vein thrombosis. FRAXODI group. Thromb Haemost. 1998;79(5):897-901.

Chest. 2012;142(4):1076. doi:10.1378/chest.12-1410

1NichollDDMAhmedSBLoewenAHS. Declining kidney function increases the prevalence of sleep apnea and nocturnal hypoxia. Chest. 2012;141(6):1422-1430.2FriedmanOBradleyTDChanCTParkesRLoganAG. Relationship between overnight rostral fluid shift and obstructive sleep apnea in drug-resistant hypertension. Hypertension. 2010;56(6):1077-1082.3YuminoDRedolfiSRuttanaumpawanP. Nocturnal rostral fluid shift: a unifying concept for the pathogenesis of obstructive and central sleep apnea in men with heart failure. Circulation. 2010;121(14):1598-1605.4DykenMEImKB. Obstructive sleep apnea and stroke. Chest. 2009;136(6):1668-1677.5MalhotraAOwensRL. What is central sleep apnea?. Respir Care. 2010;55(9):1168-1178.

Chest. 2012;142(4):1076-1077. doi:10.1378/chest.12-1482

1NichollDDMAhmedSBLoewenAHS. Declining kidney function increases the prevalence of sleep apnea and nocturnal hypoxia. Chest. 2012;141(6):1422-1430.2EliasRMBradleyTDKasaiTMotwaniSSChanCT. Rostral overnight fluid shift in end-stage renal disease: relationship with obstructive sleep apnea. Nephrol Dial Transplant. 2012;27(4):1569-1573.3AhmedSBRonksleyPEHemmelgarnBR. Nocturnal hypoxia and loss of kidney function. PLoS ONE. 2011;6(4):e19029.4JamesMTHemmelgarnBRTonelliM. Early recognition and prevention of chronic kidney disease. Lancet. 2010;375(9722):1296-1309.5CollopNAAndersonWMBoehleckeB. Portable Monitoring Task Force of the American Academy of Sleep Medicine. Clinical guidelines for the use of unattended portable monitors in the diagnosis of obstructive sleep apnea in adult patients. J Clin Sleep Med. 2007;3(7):737-747.

Chest. 2012;142(4):1077. doi:10.1378/chest.12-1433

1PearceMSSalottiJALittleMP. Radiation exposure from CT scans in childhood and subsequent risk of leukaemia and brain tumours: a retrospective cohort study. Lancet. In press.2O’ConnellOJMcWilliamsSMcGarrigleAM. Radiologic imaging in cystic fibrosis: cumulative effective dose and changing trends over 2 decades. Chest. 2012;141(6):1575-1583.3PapaioannouGYoungCOwensCM. Multidetector row CT for imaging the paediatric tracheobronchial tree. Pediatr Radiol. 2007;37(6):515-529.

Chest. 2012;142(4):1078. doi:10.1378/chest.12-1720

1O’ConnellOJMcWilliamsSMcGarrigleAM. Radiologic imaging in cystic fibrosis: cumulative effective dose and changing trends over 2 decades. Chest. 2012;141(6):1575-1583.2MettlerFAJrHudaWYoshizumiTTMaheshM. Effective doses in radiology and diagnostic nuclear medicine: a catalog. Radiology. 2008;248(1):254-263.3ImPACT’s ct dosimetry tool. ImPACT website. http://www.impactscan.org/ctdosimetry.htm. Accessed January 16, 2010.4PapaioannouGYoungCOwensCM. Multidetector row CT for imaging the paediatric tracheobronchial tree. Pediatr Radiol. 2007;37(6):515-529.5O’ConnorOJVandeleurMMcGarrigleAM. Development of low-dose protocols for thin-section CT assessment of cystic fibrosis in pediatric patients. Radiology. 2010;257(3):820-829.6CraigOO’NeillSO’NeillF. Diagnostic accuracy of computed tomography using lower doses of radiation for patients with Crohn’s disease. Clin Gastroenterol Hepatol. 2012;10(8):886-892.


Chest. 2012;142(4):1079. doi:10.1378/chest.12-1284

We would like to withdraw our abstract “Upregulated Oncogenic Pathways in Patients Exposed to Tobacco Smoke May Provide a Novel Approach to Lung Cancer Chemoprevention,” which appeared in CHEST2 and was presented as a poster on October 29, 2008.


Chest. 2012;142(4):1080. doi:10.1378/chest.12-2254

The title of the article “CaesarStone Silicosis: Disease Resurgence Among Artificial Stone Workers” published in the August 2012 issue of CHEST (2012;142[2]:419-424) has been changed to “Artificial Stone Silicosis: Disease Resurgence Among Artificial Stone Workers.”

Sign In to Access Full Content


Want Access?


Become a CHEST member and receive a FREE subscription as a benefit of membership.

Individuals can purchase this article on ScienceDirect.

Individuals can purchase a subscription to the journal.

Individuals can purchase a subscription to the journal or buy individual articles.

Learn more about membership or Purchase a Full Subscription.


Institutional access is now available through ScienceDirect and can be purchased at myelsevier.com.

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