Chest. 2012;141(6):1371-1372. doi:10.1378/chest.12-0205

As practitioners of pulmonary and cardiac medicine, many of us have no doubt been asked by our patients who smoke about so-called “electronic cigarettes” (e-cigarettes). These devices, termed electronic nicotine delivery systems (ENDS) by the World Health Organization, have been available in the US market since 2007. Our patients have likely heard far more about these devices through marketing, chat rooms, and word of mouth, than we as physicians have through the medical literature. Because ENDS are not currently regulated by the US Food and Drug Administration (FDA) as medical devices— recent court decisions, denied the agency the right to such oversight—manufacturers of ENDS have not been required to establish either safety or efficacy, and we have had few data with which to answer our patients’ queries about these products. Are e-cigarettes a smoking cessation tool? Are they a harmless alternative to cigarettes, as manufacturers claim?

Topics: cigarettes
Chest. 2012;141(6):1372-1375. doi:10.1378/chest.11-2989

In this issue of CHEST (see page 1407), Yamashiro and Kryger1 report the results from a consecutive series of patients with obstructive sleep apnea (OSA) who underwent CT scans. The authors observed important associations between pharyngeal airway length and various risk factors for OSA (including age and sex) and postulated that “laryngeal descent,” perhaps having evolved for speech, may have consequences from the standpoint of pharyngeal mechanics. The article helps to corroborate existing literature and provides an opportunity to consider the mechanical basis underlying pharyngeal airway collapse in humans.

Chest. 2012;141(6):1375-1376. doi:10.1378/chest.11-2780

In acute coronary syndromes (ACSs), current guidelines recommend early risk stratification in order to plan appropriate treatment.1-3 This can be achieved using an established risk scoring system that predicts mortality. The National Institute for Clinical Health and Clinical Excellence, the American College of Cardiology Foundation/American Heart Association (ACC/AHA), and the European Society of Cardiology (ESC) all advocate the Global Registry of Acute Cardiac Events (GRACE),4 even though others exist.5-7

Chest. 2012;141(6):1377-1378. doi:10.1378/chest.11-2662

In this issue of CHEST (see page 1466), Zhu et al1 describe an interesting and informative relationship between a germ-line genotypic characteristic (intronic polymorphism rs430397 in the glucose-regulated protein 78 [GRP78] gene) and outcome in non-small cell lung cancer treated with platinum-based therapy. GRP78 is a heat-shock protein that has long been known to play an important role in the cellular response to endoplasmic reticulum (ER) stress. In the setting of cellular stress due to inadequate nutrients, hypoxia, and other unfavorable conditions in the microenvironment, GRP78 ER-associated activity promotes tumor cell survival. Recent data indicate that GRP78-mediated actions outside of the ER may have an even more prominent effect on tumor progression. GRP78 localized to non-ER cytoplasm and cytoplasmic membranes appears to be associated with many protumorigenic activities. Although some cell-surface GRP78-ligand interactions can induce apoptosis, interactions with T-cadherin, α2-macroglobulin, and Cripto have been demonstrated to induce proliferation and cell survival.2 In addition, cytosolic interaction with p58IPK also promotes cell survival.3 Finally, when GRP78 expression is found on the cell surface of tumor cells, it is generally absent in associated normal tissues, suggesting that therapeutic interventions targeting cell-surface GRP78 hold significant promise.


Chest. 2012;141(6):1379-1382. doi:10.1378/chest.12-0155

Positive end-expiratory pressure (PEEP) is externally applied through the ventilator circuit during mechanical ventilation. In injured regions with airless alveoli capable of being opened (recruitable alveoli), PEEP may diminish ventilator-induced lung injury by decreasing cyclic collapse and reopening. Alveolar recruitment may improve ventilation-perfusion matching and reduce exposure to oxygen (a cellular toxin). In less injured or healthy lung regions, PEEP may cause overdistention injury. Balancing recruitment and overdistention effects of PEEP is an important clinical challenge. We know little about the interactions between PEEP and Fio2, between circulatory status and PEEP/Fio2 used to increase arterial oxygenation, and between PEEP and lung injury etiology. Thus, the best strategy for adjusting PEEP remains uncertain. Two strategies are common: (1) titration of PEEP based on static or dynamic respiratory system pressure-volume (PV) relationships and (2) pairing of PEEP and Fio2 into a PEEP/Fio2 table.

Chest. 2012;141(6):1382-1384. doi:10.1378/chest.12-0157

Nearly 40 years ago, novel animal studies laid the foundation for lung-protective ventilation. Both lung overdistention and the absence of positive end-expiratory pressure (PEEP) were linked to gross and histologic lung injury.1 Tidal volume was shown subsequently to be clinically important: 6 mL/kg compared with 12 mL/kg predicted body weight reduced absolute mortality by 9% in patients with acute lung injury (ALI) or ARDS.2 PEEP is biologically relevant, too: Limiting tidal recruitment and derecruitment reduces lung inflammation.3,4,5,6 Yet PEEP may provoke deleterious effects, so that choosing the appropriate level requires balancing benefits and costs. In addition, PEEP should be individualized—in the right amount, to those most likely to benefit.

Chest. 2012;141(6):1384-1386. doi:10.1378/chest.12-0156

Application of positive end-expiratory pressure (PEEP) in ARDS is evolving. Higher PEEP may prove beneficial in some patients with ARDS.1 We propose combining PEEP and Fio2 using a table. Dr Schmidt2 has appropriately pointed out several limitations of this method and suggested alternative strategies to management of PEEP. However, we remain unconvinced that these have been tested sufficiently to prove their reliability, safety, or overall clinical effectiveness.

Chest. 2012;141(6):1386-1387. doi:10.1378/chest.12-0158

There is little question that positive end-expiratory pressure (PEEP) has both beneficial and harmful consequences in ARDS, perhaps even simultaneously in the same patient.1 Teasing out the effects of PEEP from those due to tidal volume, ventilator mode, fractional inspired oxygen, sedative regimen, and fluid therapy challenges clinicians and investigators alike. Even our vocabulary—“best PEEP,” “least PEEP,” “open-lung PEEP,” “optimal PEEP”—testifies to the continued debate about how PEEP should be set. The stakes have risen lately with the demonstration that higher PEEP may improve survival for some patients.2,3


Chest. 2012;141(6):1388. doi:10.1378/chest.141.6.13
Topics: health care


Chest. 2012;141(6):1389-1392. doi:10.1378/chest.12-0955

Before the oral arguments in late March, the vast majority of legal scholars felt confident that the Supreme Court of the United States would uphold the individual mandate against the constitutional challenge that 26 states have levied against it. Since the oral arguments, that confidence has been severely shaken. This article asks why legal scholars were so confident before the argument and what has made us so concerned since the argument. The article posits that certain fundamental characteristics of health insurance, particularly its unusual role in steering health-care consumption decisions, which distinguishes health insurance from standard kinds of indemnity insurance, should make the constitutional question easy, but the Obama Administration’s legal team was understandably hesitant to highlight those unique characteristics in its arguments. Because the Supreme Court justices seemed not to understand the uniqueness of health insurance without the government’s help and because the justices seemed unusually willing to adopt a new constitutional constraint in this case, the individual mandate appears to be in far greater jeopardy than we legal scholars anticipated.

Chest. 2012;141(6):1393-1399. doi:10.1378/chest.11-2819

Large differences exist in the provision of ICU beds worldwide, with a complicated mix of risks and benefits to the population of having either too few or too many beds. Having too few beds can result in delayed admission of patients to the ICU or no admission at all, with either scenario potentially increasing mortality. Potential societal benefits of having few beds include lower costs for health care and less futile intensive care at the end of life. With added ICU beds for a population, mortality benefit should accrue, but there is still the question of whether the addition of beds always means that more lives will be saved or whether there is a point at which no additional mortality benefit is gained. With an abundance of ICU beds may come the possibility of increasing harm in the forms of unnecessary costs, poor quality of deaths (ie, excessively intensive), and iatrogenic complications. The possibility of harm may be likened to the concept of falling off a Starling curve, which is traditionally used to describe worsening heart function when overfilling occurs. This commentary examines the possible implications of having too few or too many ICU beds and proposes the concept of a family of Starling curves as a way to conceptualize the balance of societal benefits and harms associated with different availability of ICU beds for a population.


Chest. 2012;141(6):1400-1406. doi:10.1378/chest.11-2443

Background:  Debate exists over the scientific evidence for claims that electronic cigarettes (e-cigarettes) have no health-related ramifications. This study aimed to assess whether using an e-cigarette for 5 min has an impact on the pulmonary function tests and fraction of exhaled nitric oxide (Feno) of healthy adult smokers.

Methods:  Thirty healthy smokers (aged 19-56 years, 14 men) participated in this laboratory-based experimental vs control group study. Ab lib use of an e-cigarette for 5 min with the cartridge included (experimental group, n = 30) or removed from the device (control group, n = 10) was assessed.

Results:  Using an e-cigarette for 5 min led to an immediate decrease in Feno within the experimental group by 2.14 ppb (P = .005) but not in the control group (P = .859). Total respiratory impedance at 5 Hz in the experimental group was found to also increase by 0.033 kPa/(L/s) (P < .001), and flow respiratory resistance at 5 Hz, 10 Hz, and 20 Hz also statistically increased. Regression analyses controlling for baseline measurements indicated a statistically significant decrease in Feno and an increase in impedance by 0.04 kPa/(L/s) (P = .003), respiratory resistance at 5 Hz by 0.04 kPa/(L/s) (P = .003), at 10 Hz by 0.034 kPa/(L/s) (P = .008), at 20 Hz by 0.043 kPa/(L/s) (P = .007), and overall peripheral airway resistance (β, 0.042 kPa/[L/s]; P = .024), after using an e-cigarette.

Conclusions:  e-Cigarettes assessed in the context of this study were found to have immediate adverse physiologic effects after short-term use that are similar to some of the effects seen with tobacco smoking; however, the long-term health effects of e-cigarette use are unknown but potentially adverse and worthy of further investigation.

Original Research: SLEEP DISORDERS

Chest. 2012;141(6):1407-1413. doi:10.1378/chest.10-3238

Background:  A lower (more caudal) position of the larynx may result in a longer collapsible segment of the upper airway. One could thus hypothesize that the lower the larynx the greater the risk for obstructive sleep apnea (OSA). To test this hypothesis, we measured the upper airway length to the level of the vocal cord and the horizontal and vertical segments of the supralaryngeal vocal cord tract (SVT) using multislice CT scan in Japanese patients with OSA.

Methods:  We recruited 249 consecutive patients who had polysomnography for suspected OSA (age, 47.8 ± 14.8 years; BMI, 24.8 ± 4.3 kg/m2). Using CT images, we measured airway length (AL), airway length to vocal cord (ALVC), ALVC-AL, horizontal segment of SVT (SVTH), and vertical segment of SVT (SVTV). The ratio SVTR (SVTH to SVTV) was calculated. The correlation between these measurements and age, BMI, and AHI were evaluated.

Results:  Men had a longer ALVC than women. AL, ALVC, and SVTR were significantly correlated with age and AHI in all patients. Logistic regression analysis showed that ALVC > 0.24 (OR, 4.2; CI, 2.3-7.6) and BMI > 25 (OR, 4.8; CI, 2.7-8.5) were significant variables predicting AHI > 30. Even after controlling for BMI, the effect of ALVC was still significant.

Conclusions:  The laryngeal position is lower in men than women. Aging is associated with a lower laryngeal position, and a longer ALVC is independently associated with OSA severity in Japanese patients. We conclude that both laryngeal descent and BMI may be risk factors for OSA.

Chest. 2012;141(6):1414-1421. doi:10.1378/chest.11-1945

Background:  Although up to 90% of patients with type 2 diabetes mellitus (T2DM) have obstructive sleep apnea (OSA), the rate at which primary care providers diagnose OSA in patients with diabetes has not been assessed.

Methods:  A retrospective, population-based, multiclinic study was performed to determine the proportion of patients with T2DM managed in primary care clinics who were given a diagnosis of OSA and to identify factors associated with an OSA diagnosis. Electronic health records of adult patients with a diagnosis of T2DM were reviewed for a coexisting diagnosis of OSA, and the diagnostic prevalence of OSA was compared with the expected prevalence.

Results:  A total of 16,066 patients with diabetes with one or more primary care office visits in 27 primary care ambulatory practices during an 18-month period from 2009 to 2010 were identified. Analysis revealed that 18% of the study population received an OSA diagnosis, which is less than the 54% to 94% prevalence reported previously. The 23% prevalence of OSA among obese study patients was lower than the expected 87% prevalence. In a logistic model, male sex, BMI, several chronic conditions, and lower low-density lipoprotein levels and hemoglobin A1c identified patients more likely to carry an OSA diagnosis (likelihood ratio, χ2 = 1,713; P < .0001).

Conclusions:  Primary care providers underdiagnose OSA in patients with T2DM. Obese men with comorbid chronic health conditions are more likely to receive a diagnosis of OSA. Efforts to improve awareness of the association of OSA with T2DM and to implement OSA screening tools should target primary care physicians.

Chest. 2012;141(6):1422-1430. doi:10.1378/chest.11-1809

Background:  Sleep apnea is an important comorbidity in patients with chronic kidney disease (CKD) and end-stage renal disease (ESRD). Although the increased prevalence of sleep apnea in patients with ESRD is well established, few studies have investigated the prevalence of sleep apnea in patients with nondialysis-dependent kidney disease, and no single study, to our knowledge, has examined the full spectrum of kidney function. We sought to determine the prevalence of sleep apnea and associated nocturnal hypoxia in patients with CKD and ESRD. We hypothesized that the prevalence of sleep apnea would increase progressively as kidney function declines.

Methods:  Two hundred fifty-four patients were recruited from outpatient nephrology clinics and hemodialysis units. All patients completed an overnight cardiopulmonary monitoring test to determine the prevalence of sleep apnea (respiratory disturbance index ≥ 15) and nocturnal hypoxia (oxygen saturation < 90% for ≥ 12% of monitoring). Patients were stratified into three groups based on estimated glomerular filtration rate (eGFR) as follows: eGFR ≥ 60 mL/min/1.73 m2 (n = 55), CKD (eGFR < 60 mL/min/1.73 m2 not on dialysis, n = 124), and ESRD (on hemodialysis, n = 75).

Results:  The prevalence of sleep apnea increased as eGFR declined (eGFR ≥ 60 mL/min/1.73 m2, 27%; CKD, 41%; ESRD, 57%; P = .002). The prevalence of nocturnal hypoxia was higher in patients with CKD and ESRD (eGFR ≥ 60 mL/min/1.73 m2, 16%; CKD, 47%; ESRD, 48%; P < .001).

Conclusions:  Sleep apnea is common in patients with CKD and increases as kidney function declines. Almost 50% of patients with CKD and ESRD experience nocturnal hypoxia, which may contribute to loss of kidney function and increased cardiovascular risk.


Chest. 2012;141(6):1431-1440. doi:10.1378/chest.11-0435

Background:  Atrial fibrillation (AF) is common in patients with acute coronary syndromes (ACS). We aimed to describe the value of the CHADS2 (congestive heart failure, hypertension, age ≥ 75 years, diabetes, prior stroke or transient ischemic attack) score as a risk assessment tool for mortality and stroke in patients with ACS, irrespective of the presence or absence of AF.

Methods:  Consecutive patients with ACS admitted to the coronary care unit were prospectively included in a risk stratification study. We calculated the CHADS2 scores from the data collected at admission, and all patients were followed until January 1, 2007, or death.

Results:  Of 2,335 patients with ACS in this study, 442 (age 71 ± 8 years, 142 women) had AF. Their mean CHADS2 score was 1.6 ± 1.4 vs 1.0 ± 1.1 in patients without AF (P < .0001). The all-cause mortality at 10 years was strongly associated with the CHADS2 score in patients with AF (hazard ratio [HR] and 95% CI per unit increase in the six-grade CHADS2 score, 1.21 [1.07-1.36]; P = .002), but the same association was also present in patients without AF (HR 1.38 [1.28-1.48], P < .0001), after adjustment for potential confounders. The more complicated GRACE (Global Registry of Acute Coronary Events) risk score provided a better prediction for short- and long-term mortality than the simpler CHADS2 score (P < .0001). Hospitalization for stroke was significantly associated with the CHADS2 score in patients without AF (but not in those with AF) after adjustment (HR 1.46 [1.27-1.68], P < .0001).

Conclusions:  In patients with ACS, AF is associated with poor prognosis. The CHADS2 score developed for AF has even greater prognostic value in patients who do not have AF, and it may help to identify patients with high risk for subsequent stroke or death and a need for optimization of risk-reducing treatment.

Chest. 2012;141(6):1441-1448. doi:10.1378/chest.11-2032

Background:  There are limited data describing contemporary trends in the management and outcomes of patients with COPD who develop acute myocardial infarction (AMI).

Methods:  The study population consisted of patients hospitalized with AMI at all greater Worcester, Massachusetts, medical centers between 1997 and 2007.

Results:  Of the 6,290 patients hospitalized with AMI, 17% had a history of COPD. Patients with COPD were less likely to be treated with β-blockers or lipid-lowering therapy or to have undergone interventional procedures during their index hospitalization than patients without COPD. Patients with COPD were at higher risk for dying during hospitalization (13.5% vs 10.1%) and at 30 days after discharge (18.7% vs 13.2%), and their outcomes did not improve during the decade-long period under study. After multivariable adjustment, the adverse effects of COPD remained on both in-hospital (OR, 1.25; 95% CI, 0.99-1.50) and 30-day all-cause mortality (OR, 1.31; 95% CI, 1.10-1.58). The use of evidence-based therapies for all patients with AMI increased between 1997 and 2007, with a particularly marked increase for patients with COPD.

Conclusions:  Our results suggest that the gap in medical care between patients with and without COPD hospitalized with AMI narrowed substantially between 1997 and 2007. Patients with COPD, however, remain less aggressively treated and are at increased risk for hospital adverse outcomes than patients without COPD in the setting of AMI. Careful consideration is necessary to ensure that these high-risk complex patients are not denied the benefits of effective cardiac therapies.

Chest. 2012;141(6):1449-1456. doi:10.1378/chest.11-1724

Background:  Excess sudden death due to ventricular tachyarrhythmias remains a major mode of mortality in patients with systolic heart failure. The aim of this study was to determine the association of nocturnal ventricular arrhythmias in patients with low ejection fraction heart failure. We incorporated a large number of known pathophysiologic triggers to identify potential targets for therapy to reduce the persistently high incidence of sudden death in this population despite contemporary treatment.

Methods:  Eighty-six ambulatory male patients with stable low (≤ 45%) ejection fraction heart failure underwent full-night attendant polysomnography and simultaneous Holter recordings. Patients were divided into groups according to the presence or absence of couplets (paired premature ventricular excitations) and ventricular tachycardia (VT) (at least three consecutive premature ventricular excitations) during sleep.

Results:  In multiple regression analysis, four variables (current smoking status, increased number of arousals, plasma alkalinity, and old age) were associated with VT and two variables (apnea-hypopnea index and low right ventricular ejection fraction) were associated with couplets during sleep.

Conclusions:  We speculate that cessation of smoking, effective treatment of sleep apnea, and plasma alkalosis could collectively decrease the incidence of nocturnal ventricular tachyarrhythmias and the consequent risk of sudden death, which remains high despite the use of β blockades.

Chest. 2012;141(6):1457-1465. doi:10.1378/chest.11-1903

Background:  Little is known about the association between left ventricular (LV) diastolic dysfunction and outcomes in patients with idiopathic or heritable pulmonary arterial hypertension (PAH). Our rationale was to investigate the prevalence of LV diastolic dysfunction, and its association with disease severity and outcomes, in patients with idiopathic or heritable PAH.

Methods:  Using the Cleveland Clinic Pulmonary Hypertension Registry, we identified subjects with heritable or idiopathic PAH who underwent Doppler echocardiography and right-sided heart catheterization. Echocardiographic diastolic parameters were assessed in each patient.

Results:  A total of 61 patients met the inclusion criteria (idiopathic 85%, heritable 15%). The age at the time of echocardiography was 48.3 ± 18 years, 84% of the subjects were women, and 48% were on PAH-targeted therapies. Normal LV diastolic function, impaired relaxation, and pseudonormalization were seen in 10%, 88%, and 2% of the patients, respectively. Peak early diastolic (peak E) velocity was directly associated with LV end-diastolic volume and cardiac index and inversely associated with the degree of right ventricular dilation, right atrial pressure, and pulmonary vascular resistance. Peak E velocity was associated with mortality adjusted for age and sex (hazard ratio [HR], 1.5; 95% CI, 1.1-2 per 10 cm/s decrease; P = .015) and age, sex, 6-min walk distance, and cardiac output (HR, 1.8; 95% CI, 1.2-2.9 per 10 cm/s decrease; P = .01).

Conclusions:  LV diastolic dysfunction of the impaired relaxation type is observed in the majority of patients with advanced idiopathic or heritable PAH. A decrease in transmitral flow peak E velocity is associated with worse hemodynamics and outcome.

Original Research: CANCER

Chest. 2012;141(6):1466-1472. doi:10.1378/chest.11-0469

Background:  Glucose-regulated protein 78 (GRP78) is involved in not only the progression of non-small cell lung cancer (NSCLC) but also chemotherapeutic effects. We hypothesized that an intronic polymorphism (rs430397G>A) in GRP78 affects survival among patients with NSCLC treated with platinum-based chemotherapy.

Methods:  Blood samples of patients with advanced NSCLC (IIIB/IV) were maintained in our specimen bank between 2001 and 2006. Genomic DNA was genotyped for rs430397. Associations between rs430397 and platinum-based treatment response, overall survival (OS), NSCLC-related survival, progression-free survival (PFS), and relapses were evaluated. GRP78 RNA and protein in NSCLC tissues were tested by real-time polymerase chain reaction and immunohistochemistry.

Results:  The AA genotype is significantly associated with platinum-based chemoresistance (P = .019) and NSCLC-related death (P = .022). OS, NSCLC-related survival, and PFS of the AA genotype group are decreased compared with the GG and AG genotype groups (log-rank P < .05, respectively). The AA group showed a higher prevalence of early NSCLC relapses than the AG and GG group (P = .030). In addition, the AA genotype showed a significantly increased risk for OS (hazard ratio, 1.95) and PFS (hazard ratio, 1.80) compared with the GG group. Functional analysis showed that NSCLC tissues with genotype AA have higher GRP78 RNA and protein expression compared with those carrying GG at rs430397.

Conclusions:  The rs430397 AA genotype of GRP78 is associated with reduced survival and higher prevalence of early relapses in patients with advanced NSCLC treated with platinum-based chemotherapy.

Chest. 2012;141(6):1473-1481. doi:10.1378/chest.11-2005

Background:  The most serious complications of airway stenting are long term, including infection and granulation tissue formation. However, to our knowledge, no studies have quantified the incidence rate of long-term complications for different stents.

Methods:  To compare the incidence of complications of different airway stents, we conducted a retrospective cohort study of all patients at our institution who had airway stenting for malignant airway obstruction from January 2005 to August 2010. Patients were excluded if more than one type of stent was in place at the same time. Complications recorded were lower respiratory tract infections, stent migration, granulation tissue, mucus plugging requiring intervention, tumor overgrowth, and stent fracture.

Results:  One hundred seventy-two patients with 195 stent procedures were included. Aero stents were associated with an increased risk of infection (hazard ratio [HR] = 1.98; 95% CI, 1.03-3.81; P = .041). Dumon silicone tube stents had an increased risk of migration (HR = 3.52; 95% CI, 1.41-8.82; P = .007). Silicone stents (HR = 3.32; 95% CI, 1.59-6.93; P = .001) and lower respiratory tract infections (HR = 5.69; 95% CI, 2.60-12.42; P < .001) increased the risk of granulation tissue. Lower respiratory tract infections were associated with decreased survival (HR = 1.57; 95% CI, 1.11-2.21; P = .011).

Conclusions:  Significant differences exist among airway stents in terms of infection, migration, and granulation tissue formation. These complications, in turn, are associated with significant morbidity and mortality. Granulation tissue formation develops because of repetitive motion trauma and infection.

Chest. 2012;141(6):1482-1489. doi:10.1378/chest.11-1566

Background:  Pulmonary metastasectomy with lung-sparing local excisions is a widely accepted method of treating stage IV malignancies in selected cases. The ability to predict postoperative lung function is an unresolved issue, especially when multiple wedge resections are planned. To help develop a method to predict postoperative lung function after wedge resections, we present this prospective observational study.

Methods:  A total of 77 patients who underwent one or more wedge resections to remove lung metastases completed the study protocol. Spirometry results, diffusion capacity of lung for carbon monoxide (Dlco), and blood gases and potential confounding factors were measured prior to, immediately following, and 3 months after the procedure and were analyzed.

Results:  Seventy-seven patients with a median age of 61.3 years underwent up to 22 wedge resections. The mean lung function losses were FVC (−7.5%), total lung capacity (TLC) (−7.9%), FEV1 (−9.2%), and Dlco (−8.8%), and all were statistically significant (P < .001). The lung function losses also differed significantly between those having a single and those with more than eight wedge resections. Using regression analysis, we found that for every additional wedge resection, there was a reduction in FVC of 30 mL (0.7%), in TLC of 44 mL (0.65%), and in FEV1 of 23 mL (0.58%).

Conclusions:  Metastasectomy by wedge resection significantly reduces lung function parameters. As a benchmark, we can predict a 0.6% decrease in spirometry values and Dlco for every additional wedge resection, and a decrease of approximately 5% that may be attributed to thoracotomy.

Original Research: CRITICAL CARE

Chest. 2012;141(6):1490-1495. doi:10.1378/chest.11-2860

Background:  Changes in platelet reactivity during 2009 influenza A(H1N1) (A[H1N1]) have not been characterized.

Methods:  We prospectively examined platelet activation and cytokine responses in patients with A(H1N1) (n = 20), matched patients with bacterial pneumonia (n = 15), and nonhospitalized, healthy control subjects (n = 10).

Results:  Platelet-monocyte aggregation was higher in patients with A(H1N1) (21.4% ± 4.7%) compared with patients with pneumonia (10.9% ± 3.7%) and control subjects (8.1% ± 4.5%, P < .05). Similarly, PAC-1 (antibody that binds to the active conformation of integrin αIIbβ3) binding to platelets is increased in patients with A(H1N1) (9.5% ± 4.7%) compared with patients with pneumonia (1.0% ± 0.7%) and healthy subjects (0.61% ± 0.15%, P < .10). PAC-1 binding was twofold higher in patients with A(H1N1) with shock vs those without shock. IL-6 levels were elevated in patients with A(H1N1), indicating systemic inflammation consistent with activation of circulating platelets.

Conclusions:  These findings, derived from a small but documented cohort of patients, demonstrate that platelet activation responses during A(H1N1) are enhanced—exceeding responses in patients with bacterial pneumonia—and provide new evidence that platelets may contribute to inflammatory responses during A(H1N1).

Original Research: COPD

Chest. 2012;141(6):1496-1503. doi:10.1378/chest.11-1708

Background:  Although balance deficits are increasingly recognized in COPD, little is known regarding the disordered subcomponents underlying the control of balance. We aimed to determine the specific components of balance that are impaired in COPD and to investigate the association among balance, peripheral muscle strength, and physical activity.

Methods:  Balance, physical activity, and lower extremity muscle strength were assessed in 37 patients with COPD and 20 age-matched healthy control subjects using the Balance Evaluation Systems Test (BESTest), the Physical Activity Scale for the Elderly, and an isokinetic dynamometer, respectively. A subset of subjects (20 patients with COPD and 20 control subjects) underwent a second testing session in which postural perturbations were delivered using a lean-and-release system.

Results:  Subjects with COPD (age, 71 ± 7 years; FEV1, 39% ± 16% predicted) exhibited significantly lower scores than did control subjects (age, 67 ± 9 years) on all of the BESTest subscales (all P < .001). In response to anterior perturbations, subjects with COPD showed a longer time to foot-off (P = .027) and foot contact (P = .018), and a longer duration anticipatory phase (P = .008) compared with control subjects. Muscle strength (P = .008) and self-reported physical activity (P = .033) explained 35% of the variance in balance in subjects with COPD.

Conclusions:  Individuals with COPD exhibit impairments in all balance subcomponents and demonstrate slower reaction times in response to perturbations. Deficits in balance are associated with reduced physical activity levels and skeletal muscle weakness.

Original Research: ASTHMA

Chest. 2012;141(6):1504-1511. doi:10.1378/chest.11-0232

Background:  The clinical manifestations of bronchial remodeling in asthma and the potential impact of this process on lung function remain unclear. We aimed to determine whether the presence of pathologic features of airway remodeling in patients with asthma was associated with steroid responsiveness in the short term.

Methods:  Sixty-three consecutive patients with severe asthma with chronic airflow impairment (post-bronchodilator FEV1 < 80% predicted values) were recruited, clinically characterized, and had an initial bronchoscopy where endobronchial biopsy and BAL were performed. BAL cellular content was reported and reticular basement membrane (RBM) thickness was measured by validated repeated measures. Patients were then treated with 1 mg/kg/d of methyl prednisone, directly administered IV, for 10 days. A threshold of 15% FEV1 improvement was used to discriminate responsive (group 1) and refractory patients (group 2).

Results:  Thirty-eight patients had a steroid responsiveness > 15% (group 1) and a thinner RBM at the biopsy level (5.78 ± 2.0 μm vs 7.60 ± 2.2 μm; P = .001) compared with nonsteroid responsive group 2 patients as defined. The best predictors for being unresponsive were no long-term treatment with oral steroids and increased RBM thickness. The associated receiver operating characteristic curve indicated that RBM thickness could predict steroid responsiveness below 15% with an area under the curve of 0.747 (P = .0002) at a threshold of 7 μm.

Conclusions:  Features of airway remodeling are associated with limited short-term steroid responsiveness in severe asthma.


Chest. 2012;141(6):1512-1521. doi:10.1378/chest.11-1880

Background:  Reports of pulmonary fibrosis, emphysema, and, more recently, pulmonary alveolar proteinosis (PAP) in indium workers suggested that workplace exposure to indium compounds caused several different lung diseases.

Methods:  To better understand the pathogenesis and natural history of indium lung disease, a detailed, systematic, multidisciplinary analysis of clinical, histopathologic, radiologic, and epidemiologic data for all reported cases and workplaces was undertaken.

Results:  Ten men (median age, 35 years) who produced, used, or reclaimed indium compounds were diagnosed with interstitial lung disease 4-13 years after first exposure (n = 7) or PAP 1-2 years after first exposure (n = 3). Common pulmonary histopathologic features in these patients included intraalveolar exudate typical of alveolar proteinosis (n = 9), cholesterol clefts and granulomas (n = 10), and fibrosis (n = 9). Two patients with interstitial lung disease had pneumothoraces. Lung disease progressed following cessation of exposure in most patients and was fatal in two. Radiographic data revealed that two patients with PAP subsequently developed fibrosis and one also developed emphysematous changes. Epidemiologic investigations demonstrated the potential for exposure to respirable particles and an excess of lung abnormalities among coworkers.

Conclusions:  Occupational exposure to indium compounds was associated with PAP, cholesterol ester crystals and granulomas, pulmonary fibrosis, emphysema, and pneumothoraces. The available evidence suggests exposure to indium compounds causes a novel lung disease that may begin with PAP and progress to include fibrosis and emphysema, and, in some cases, premature death. Prospective studies are needed to better define the natural history and prognosis of this emerging lung disease and identify effective prevention strategies.

Topics: lung diseases , indium
Chest. 2012;141(6):1522-1527. doi:10.1378/chest.11-1134

Background:  Airway inflammatory responses to specific inhalation challenges (SICs) with low-molecular-weight (LMW) and high-molecular-weight (HMW) agents have not been studied thoroughly. We assessed the changes in airway inflammatory cells following SIC in sensitized workers, and looked at the influence of various factors on the pattern of inflammatory responses to SIC.

Methods:  Induced sputum analysis was performed in workers sensitized to LMW (n = 41) or HMW agents (n = 41) after a control day and after a positive SIC. Cell counts were compared with lung function and various clinical parameters.

Results:  In the LMW group, eosinophils were increased following late asthmatic responses (median [interquartile range], 0.02 [0.04] × 106 cells/g vs 0.30 [0.80] × 106 cells/g and 1.0% [3.5] vs 8.9% [8.0], P < .05), as were neutrophil numbers (0.8 [1.3] × 106 cells/g vs 2.3 [5.4] × 106 cells/g, P = .04). In the HMW group, eosinophil percentages increased both after early (1.0% [2.2] vs 5.5% [14.5], P = .003) and dual asthmatic responses (4.5% [3.7] vs 15.0% [13.7], P = .02). In the LMW group, the increases in neutrophils were higher in current smokers than in ex-smokers or nonsmokers. The length of exposure to the agent, tobacco use, and baseline percentage of eosinophils were independent predictors of the change in eosinophils, whereas age and baseline neutrophil percentage were predictors of the change in neutrophils.

Conclusions:  This study confirms that eosinophils and neutrophils are increased after SIC, whatever the causal agent. The type of agent is not predictive of the inflammatory response to SIC. Smoking is associated with a more neutrophilic response after SIC with an LMW agent.

Original Research: CHEST INFECTIONS

Chest. 2012;141(6):1528-1536. doi:10.1378/chest.11-1547

Background:  Pneumonia is the leading infectious cause of death. Early deterioration and death commonly result from progressive sepsis, shock, respiratory failure, and cardiac complications. Recent data suggest that cardiac arrest may also be common, yet few previous studies have addressed this. Accordingly, we sought to characterize early cardiac arrest in patients who are hospitalized with coexisting pneumonia.

Methods:  We performed a retrospective analysis of a multicenter cardiac arrest database, with data from > 500 North American hospitals. We included in-hospital cardiac arrest events that occurred in community-dwelling adults with pneumonia within the first 72 h after hospital admission. We compared patient and event characteristics for patients with and without pneumonia. For patients with pneumonia, we also compared events according to event location.

Results:  We identified 4,453 episodes of early cardiac arrest in patients who were hospitalized with pneumonia. Among patients with preexisting pneumonia, only 36.5% were receiving mechanical ventilation and only 33.3% were receiving infusions of vasoactive drugs prior to cardiac arrest. Only 52.3% of patients on the ward were receiving ECG monitoring prior to cardiac arrest. Shockable rhythms were uncommon in all patients with pneumonia (ventricular tachycardia or fibrillation, 14.8%). Patients on the ward were significantly older than patients in the ICU.

Conclusions:  In patients with preexisting pneumonia, cardiac arrest may occur in the absence of preceding shock or respiratory failure. Physicians should be alert to the possibility of abrupt cardiopulmonary collapse, and future studies should address this possibility. The mechanism may involve myocardial ischemia, a maladaptive response to hypoxia, sepsis-related cardiomyopathy, or other phenomena.

Chest. 2012;141(6):1537-1545. doi:10.1378/chest.11-1446

Background:  The inflammatory response in community-acquired pneumonia (CAP) depends on the host and on the challenge of the causal microorganism. Here, we analyze the patterns of inflammatory cytokines, procalcitonin (PCT), and C-reactive protein (CRP) in order to determine their diagnostic value.

Methods:  This was a prospective study of 658 patients admitted with CAP. PCT and CRP were analyzed by immunoluminometric and immunoturbidimetric assays. Cytokines (tumor necrosis factor-α [TNF-α], IL-1β, IL-6, IL-8, and IL-10) were measured using enzyme immunoassay.

Results:  The lowest medians of CRP, PCT, TNF-α, and IL-6 were found in CAP of unknown cause, and the highest were found in patients with positive blood cultures. Different cytokine profiles and biomarkers were found depending on cause: atypical bacteria (lower PCT and IL-6), viruses (lower PCT and higher IL-10), Enterobacteriaceae (higher IL-8), Streptococcus pneumoniae (high PCT), and Legionella pneumophila (higher CRP and TNF-α). PCT ≥ 0.36 mg/dL to predict positive blood cultures showed sensitivity of 85%, specificity of 42%, and negative predictive value (NPV) of 98%, whereas a cutoff of ≤ 0.5 mg/dL to predict viruses or atypicals vs bacteria showed sensitivity of 89%/81%, specificity of 68%/68%, positive predictive value of 12%/22%, and NPV of 99%/97%. In a multivariate Euclidean distance model, the lowest inflammatory expression was found in unknown cause and the highest was found in L pneumophila, S pneumoniae, and Enterobacteriaceae. Atypical bacteria exhibit an inflammatory pattern closer to that of viruses.

Conclusions:  Different inflammatory patterns elicited by different microorganisms may provide a useful tool for diagnosis. Recognizing these patterns provides additional information that may facilitate a broader understanding of host inflammatory response to microorganisms.


Chest. 2012;141(6):1546-1553. doi:10.1378/chest.11-1087

Background:  Most measures of dyspnea assess a single aspect (intensity or distress) of the symptom. We developed the Multidimensional Dyspnea Profile (MDP) to measure qualities and intensities of the sensory dimension and components of the affective dimension. The MDP is not indexed to a particular activity and can be applied at rest, during exertion, or during clinical care. We report on the development and testing of the MDP in patients with a variety of acute and chronic cardiopulmonary conditions.

Methods:  One hundred fifty-one adults admitted to the ED with breathing symptoms completed the MDP three times in the ED, twice at least 1 h apart (T1, T2), and near discharge from the ED (T3). Measures were repeated in 68 patients twice in a follow-up session 4 to 6 weeks later (T4-T5). The ED sample was 56% men with a mean age of 53 ± 15 years; the follow-up sample was similar.

Results:  Factor analysis resulted in a two-factor solution with a total explained variance of 63%, 74%, and 72% at T1, T2, and T3, respectively. One domain related to primary sensory qualities and immediate unpleasantness, and the second encompassed emotional response. For the two domains, Cronbach α ranged from 0.82 to 0.95, and the intraclass correlation coefficient ranged from 0.91 to 0.98. Repeated-measures analysis was significant for change (T1, T3, T4), showing responsiveness to change in MDP domains with treatment (F[2,66] = 19.67, P > .001).

Conclusions:  These analyses support the reliability, validity, and responsiveness to clinical change of the MDP with two domains in an acute care and follow-up setting.

Topics: dyspnea

Original Research: PEDIATRICS

Chest. 2012;141(6):1554-1567. doi:10.1378/chest.11-1306

Background:  The purpose of this systematic literature review was to examine current empirical research on general and respiratory health outcomes in adult survivors of bronchopulmonary dysplasia (BPD).

Methods:  We searched seven databases up to the end of November 2010 (MEDLINE, PubMed, EMBASE, PsycINFO, Maternity and Infant Care, Cumulative Index of Nursing and Allied Health Literature, and Web of Knowledge). We independently screened and included only those studies concerning the assessment of outcome measures in adult survivors of BPD. Data on methodologic design and findings were extracted from each included study; in addition, the methodologic quality of each study was assessed using the Critical Appraisal Skills Programme checklist.

Results:  Fourteen cohort studies met the review criteria. Of those, a total of eight studies were considered to be of high quality (score 9-12), five of moderate quality (score 5-8), and only one was of low quality (score 0-4). In all studies of adult survivors of BPD, differences were found between the index and control groups, suggesting that many adults survivors of BPD who were born preterm or with very low birth weight had more respiratory symptoms and pulmonary function abnormalities compared with their peers. Five studies concerning radiologic findings reported structural changes persisting into adulthood. Findings from three studies suggested impairment in exercise capacity, although firm conclusions were limited by the small sample size in the studies reviewed.

Conclusions:  Compared with adults born at term, adult survivors of BPD have more impairment in general and respiratory health, which does not seem to diminish over time.

Original Research: CYSTIC FIBROSIS

Chest. 2012;141(6):1568-1574. doi:10.1378/chest.11-1573

Background:  Up to 80% of patients with cystic fibrosis (CF) may have increased gastroesophageal reflux and aspiration of duodenogastric contents into the lungs. We aimed to assess aspiration in patients with CF by measuring duodenogastric components in induced sputum and to investigate whether the presence of bile acids (BAs) in sputum was correlated with disease severity and markers of inflammation.

Methods:  In 41 patients with CF, 15 healthy volunteers, 29 patients with asthma, and 28 patients with chronic cough, sputum was obtained after inhalation of hypertonic saline. Sputum supernatant was tested for BA and neutrophil elastase. Spirometry and BMI were assessed on the day of sputum collection.

Results:  Two of 15 healthy patients (13%), eight of 29 patients (28%) with asthma, four of 28 patients (14%) with chronic cough, and 23 of 41 patients (56%) with CF had BA in sputum. BA concentrations were similar in patients who are positive for BA with genotype F508del homozygote, F508del heterozygote, and other CF mutations and were not related with BMI and age. Patients with CF with BA in sputum had a higher concentration of neutrophil elastase compared with patients without BA in sputum (31.25 [20.33-54.78] μg/mL vs 14.45 [7.11-27.88] μg/mL, P < .05). There was a significant correlation between BA concentrations and dynamic lung volumes (FEV1 % predicted [r = −0.53, P < .01], FVC% [r = −0.59, P < .01]) as well as with number of days of antibiotic IV treatment (r = 0.58, P < .01).

Conclusions:  BAs are present in the sputum of more than one-half of patients with CF, suggesting aspiration of duodenogastric contents. Aspiration of BA was associated with increased airway inflammation. In patients with BA aspiration, the levels of BA were clearly associated with the degree of lung function impairment as well as the need for IV antibiotic treatment.

Chest. 2012;141(6):1575-1583. doi:10.1378/chest.11-1972

Objective:  With the increasing life expectancy for patients with cystic fibrosis (CF), and a known predisposition to certain cancers, cumulative radiation exposure from radiologic imaging is of increasing significance. This study explores the estimated cumulative effective radiation dose over a 17-year period from radiologic procedures and changing trends of imaging modalities over this period.

Methods:  Estimated cumulative effective dose (CED) from all thoracic and extrathoracic imaging modalities and interventional radiology procedures for both adult and pediatric patients with CF, exclusively attending a nationally designated CF center between 1992-2009 for > 1 year, was determined. The study period was divided into three equal tertiles, and estimated CED attributable to all radiologic procedures was estimated for each tertile.

Results:  Two hundred thirty patients met inclusion criteria (2,240 person-years of follow-up; 5,596 radiologic procedures). CED was > 75 mSv for one patient (0.43%), 36 patients (15.6%) had a CED between 20 and 75 mSv, 56 patients (24.3%) had a CED between 5 and 20 mSv, and in 138 patients (60%) the CED was estimated to be between 0 and 5 mSv over the study period. The mean annual CED per patient increased consecutively from 0.39 mSv/y to 0.47 mSv/y to 1.67 mSv/y over the tertiles one to three of the study period, respectively (P < .001). Thoracic imaging accounted for 46.9% of the total CED and abdominopelvic imaging accounted for 42.9% of the CED, respectively. There was an associated 5.9-fold increase in the use of all CT scanning per patient (P < .001).

Conclusions:  This study highlights the increasing exposure to ionizing radiation to patients with CF as a result of diagnostic imaging, primarily attributable to CT scanning. Increased awareness of CED and strategies to reduce this exposure are needed.

Recent Advances in Chest Medicine

Chest. 2012;141(6):1584-1594. doi:10.1378/chest.11-1513

Identifying patients with impaired renal function is crucial in the setting of critical illness. Serum creatinine serves as the gold standard for assessing steady-state renal function, helping to define those with chronic kidney disease (CKD). Although these baseline creatinine values are often not available in the setting of critical illness, CKD, whether defined by serum creatinine or proteinuria, increases the risk of developing acute kidney injury (AKI). Despite delays in elevations following renal insults, serum creatinine remains the standard for assessing acute changes in renal function. Standardized definitions of AKI, using changes in serum creatinine and urine output, have informed the epidemiology of ICU-acquired AKI and have helped define the long-term outcomes in patients who experience AKI. A complex cyclical interplay exists between AKI and CKD, in which CKD predisposes patients to an increased risk of AKI, whereas those with AKI, regardless of baseline renal function, are more likely to suffer from post-AKI CKD. The clarification of the AKI-CKD dynamic remains a work in progress and will be aided by the implementation of novel measures of renal function. Several novel biomarkers of renal function have been proposed to augment serum creatinine in the diagnosis of AKI and CKD. These biomarkers, taken with recent clinical investigations, have laid the groundwork for the impending paradigm shift in risk stratifying and in diagnosing changes in renal function in the ICU.

Selected Reports

Chest. 2012;141(6):1595-1598. doi:10.1378/chest.11-1812

We report the case of a man with a history of intermittent fever and arthritis who presented with a dry cough and associated lung involvement, who was eventually given the diagnosis of Whipple disease. The pulmonary symptoms preceded the development of GI manifestations. Five years later, periodic acid-Schiff (PAS)-positive macrophages were identified in duodenal biopsy specimens and polymerase chain reaction for Tropheryma whipplei was positive in the duodenum, stools, saliva, and cerebrospinal fluid. Pulmonary T whipplei was retrospectively confirmed by positive PAS staining and immunoreactivity to specific antibodies in endobronchial biopsy specimens. Antibiotic treatment was followed by remission. A literature review identified eight other cases of Whipple disease presenting with lung parenchymal involvement, predominantly interstitial lung disease (ILD), and without initial GI symptoms. In the absence of GI symptoms, a diagnosis of Whipple disease should be considered in middle-aged men presenting with ILD or lung nodules, if the patient has a history of unexplained arthralgia and/or fever. The association of mediastinal adenopathy or pleural effusion offers additional concern. Whipple disease may be fatal in the absence of treatment, but prolonged antibiotic treatment often leads to complete remission.

Chest. 2012;141(6):1598-1600. doi:10.1378/chest.11-1402

Pulmonary arterial hypertension (PAH) is a rare complication of hereditary hemorrhagic telangiectasia (HHT). The triggers that promote the development of PAH in HHT remain poorly understood. We present the case of a 45-year-old woman with decompensated right-sided heart failure secondary to newly diagnosed PAH. The clinical diagnosis of HHT was confirmed on the basis of recurrent spontaneous epistaxis, multiple typical mucocutaneous telangiectasia, and the presence of pulmonary arteriovenous malformation. There was also a suggestive family history. The patient was discovered to have active and extensive stimulant abuse in addition to HHT. We concluded that there may be a temporal relationship between exposure to stimulants and development of PAH in a host with underlying gene mutation. This case highlights the paradigm of PAH development after environmental exposure in a genetically susceptible host.

Postgraduate Education Corner

Chest. 2012;141(6):1626-1632. doi:10.1378/chest.11-1800

In scientific publications, laboratory and clinical images are part of the evidence on which authors base the interpretation and conclusions of their research. However, variability in biology, image acquisition and quality, standards for interpretation, training and experience of evaluators, and presence of artifacts can markedly reduce interrater and intrarater reliability. This variability in interpretation suggests that authors should support their claims with complete information about the image on which those claims are based. Yet, without appropriate guidelines, the documentation of these published images almost certainly will be incomplete and inconsistent. Here, we propose six principles for documenting clinical and laboratory images in publications: the clinical and laboratory images in publications (CLIP) principles. The principles were inspired by the CONSORT (Consolidated Standards of Reporting Trials) and related initiatives that are intended to improve the documentation of research through the use of guidelines. However, the CLIP principles are not formal guidelines, standards, or requirements but, rather, reminders about the information that may be needed to support interpretations and conclusions based on images. These principles organize the self-evident factors related to the nature, acquisition, reporting, and presentation of clinical and laboratory images. As imaging technologies become more complex, however, so too does the specific information needed to document how specific types of images are acquired. Thus, in addition to general direction for all authors, the CLIP principles give journals and professional societies a foundation, a direction, and some models to assist them in developing technology-specific guidelines for reporting the images common in their area of practice.


Chest. 2012;141(6):1601-1610. doi:10.1378/chest.11-2214

Obstructive sleep apnea syndrome (OSAS) is a common disorder with far-reaching health implications. One of the major consequences of OSAS is an impact on neurocognitive functioning. Several studies have shown that OSAS has an adverse effect on inductive and deductive reasoning, attention, vigilance, learning, and memory. Neurocognitive impairment can be measured objectively with tests such as the Wechsler Adult Intelligence Scale-Revised, the Psychomotor Vigilance Task, the Steer Clear Performance Test, and tests of repetitive finger tapping. In children, OSAS may cause attention-deficit hyperactivity disorder in addition to behavioral problems and learning disabilities. Risk factors for cognitive impairment include increasing age, male sex, apolipoprotein E ε4 allele positivity, current cigarette smoking, obesity, hypertension, diabetes mellitus, metabolic syndrome, Down syndrome, hypothyroidism, significant alcohol consumption, stroke, and the use of psychoactive medications. At a cellular level, OSAS likely causes cognitive impairment through intermittent hypoxia, hormonal imbalance, and/or systemic inflammation, either independently or via the resultant endothelial dysfunction that occurs. Excessive daytime sleepiness should be measured and minimized in all studies of neurocognitive impairment. Recent studies have used functional and structural neuroimaging to delineate the brain areas affected in patients with OSAS with neurocognitive dysfunction. A common finding in several of these studies is decreased hippocampal volume. Other affected brain areas include the frontal and parietal lobes of the brain, which show focal reductions in gray matter. These changes can be reversed at least partially with the use of CPAP, which highlights the importance of early recognition and treatment of OSAS. The currently available data in this field are quite limited, and more research is needed.


Chest. 2012;141(6):1611-1617. doi:10.1378/chest.11-1100

A 40-year-old black man was referred to pulmonary clinic for evaluation of pulmonary nodules. He reported a recent one time incident of right lower quadrant abdominal pain for which he was seen in the ED where an abdominal CT scan and a chest radiograph revealed a right lower lobe lung nodular opacity. On further review of systems, he reported occasional right-sided pleuritic chest pain, mild malaise, mild exertional dyspnea, and extensive nonpruritic skin rash on his left shin that had developed about 3 months before his current presentation. The rash had worsened despite the efforts of his primary care providers to treat it. He denied cough, fever, chills, night sweats, hemoptysis, arthralgias, or weight loss. Additional medical problems included poorly controlled hypertension. His family history was significant for diabetes in his mother and two siblings, chronic anemia in his sister, and lung cancer in his uncle. He lived in northwest Louisiana and worked as a roofer most of his adult life but had recently worked in landscaping. No significant environmental exposure to chemicals, dust, or asbestos was indicated. He reported a 15 pack-year smoking history, but no alcohol or illicit drugs. Six years before his current presentation, he was incarcerated for a period of 8 months. He also reported sexual activity with a male partner in the past but no recent sexual activity.


Chest. 2012;141(6):1618-1621. doi:10.1378/chest.11-2085

DubeyJPMillerNLFrenkelJKThe Toxoplasma gondii oocyst from cat fecesJ Exp Med19701324636662FrenkelJKHammondDMLongPLToxoplasmosis: parasite life cycle pathology and immunologyThe Coccidia1973Baltimore, MDUniversity Park Press343410DecGWJrWaldmanHSouthernJFallonJTHutterAMJrPalaciosIViral myocarditis mimicking acute myocardial infarctionJ Am Coll Cardiol19922018589PorterSBSandeMAToxoplasmosis of the central nervous system in the acquired immunodeficiency syndromeN Engl J Med19923272316431648LuftBJHafnerRKorzunAHToxoplasmic encephalitis in patients with the acquired immunodeficiency syndrome. Members of the ACTG 077p/ANRS 009 Study TeamN Engl J Med1993329149951000Gorgievski-HrisohoMGermannDMatterLDiagnostic implications of kinetics of immunoglobulin M and A antibody responses to Toxoplasma gondiiJ Clin Microbiol199634615061511LauerBNiederauCKühlUCardiac troponin T in patients with clinically suspected myocarditisJ Am Coll Cardiol199730513541359CookAJCGilbertREBuffolanoWEuropean Research Network on Congenital ToxoplasmosisSources of toxoplasma infection in pregnant women: European multicentre case-control studyBMJ20003217254142147DubeyJPHillDEJonesJLPrevalence of viable Toxoplasma gondii in beef, chicken, and pork from retail meat stores in the United States: risk assessment to consumersJ Parasitol200591510821093EzaDELucasSBFulminant toxoplasmosis causing fatal pneumonitis and myocarditisHIV Med200676415420PergolaGCasconeARussoMAcute pericarditis and myocarditis by Toxoplasma gondii in an immunocompetent young man: a case reportInfez Med20101814852

Topics: chest pain , fever
Chest. 2012;141(6):1622-1625. doi:10.1378/chest.11-2136

1ThotathilZLongJErlotinib effective against refractory bronchorrhea from advanced non-small cell lung cancerJ Thorac Oncol2007298818822FalcozPEHoanNTLe Pimpec-BarthesFRiquetMSevere hypoxemia due to intrapulmonary shunting requiring surgery for bronchioloalveolar carcinomaAnn Thorac Surg20098812872883ArenbergDBronchioloalveolar carcinomaSemin Respir Crit Care Med201132152614TravisWDBrambillaENoguchiMInternational Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society international multidisciplinary classification of lung adenocarcinomaJ Thorac Oncol201162244285


Chest. 2012;141(6):1633. doi:10.1378/chest.11-2115

Having been given permission to die,
he died.
An order written, duly noted:
He set about his task without delay,
accompanied at times
by a practical nurse
and, twice a day,
the woman who scrubs floors,
who pays attention to work of all kinds.
He was not coded.
Called to certify
that the job was done, that he
had done it well, I
heard only the last of a life of breaths,
was for him
but a waver
in the dim light of endtime.
I said “It’s over”,
and closed the door.
Dreams waver
in the dim light.
I nod to the dimness.
It walks beside me down the hall,
an old friend.
I go back to bed.
Cold, it climbs in.

Chest. 2012;141(6):1633. doi:10.1378/chest.11-2143

You never charged me for your time
when I was suicidal
but came to my studio apartment
sometimes after midnight.
There, away from your office
where you were forever in a hurry
with prescriptions and the next patient
you squashed me
underneath your alcoholic belly
with what I thought was love.
You pretended to be a mind-reader
and talked to me about my dead father
as if you could be a substitute for him.
I opened my thighs to you
and let all of Purgatory in;
you said you liked religion in stirrups.
I wasn’t protected
and couldn’t stay Catholic
as fur goes where it’s hunted.
You ended our affair
and changed my diagnosis
to a delusional disorder
so your peers wouldn’t set off
bombs of disapproval and blame.
Now I go to chapel every day
because it’s the only place I can carry
my scarecrow silence.
I’m spooky as an old woman
looking through a window
with a face that doesn’t
have teeth anymore.

Chest. 2012;141(6):1634. doi:10.1378/chest.11-2211

     You never put a camera in my head.
           –from The Truman Show
You put a camera right into my heart.
Unseemly route through my groin.
I wonder what you expect to find
that you can’t see from the outside,
considering it’s housed within open gates,
flapping like an overused hospital gown.
All the signs of a lifetime posted
along the hallway as I am driven by:
Blood Areas, Waiting, Cardio with an arrow—
I think I saw Dr. Kildare pass by winking.
But ask the right questions, and I’ll tell you no lies;
hold my hand, mark my history, dear.
There are few secrets when the world watches
through some critical lens or other,
except the ones we truly guard, the ones
that won’t go near a heart in the first place,
in an area where no camera should be allowed.
One room I’ll never, ever let you enter.

Chest. 2012;141(6):1634. doi:10.1378/chest.11-2402

I’ve been in and out of stores
shopping for a metaphor
but can’t find what I’m looking for.
You say: My joints hurt.
I say: You need a new roof.
You say: I can’t swallow.
I say: You’re behind on your payments.
You say: I’m out of breath.
I say: the Bank wants it back.
You say: I can’t feel my toes.
I say: Let’s fill the john
with cement mix
and storm out to the applause
of the half-hinged screen door.
It turns out foreclosure
wasn’t what I wanted.
The customer is always.
With a credit to my account
I’m driving on an eight-lane highway,
faster than the speed limit,
semi’s like linebackers on either side.
You say: My joints hurt.
I say: None of the stations are coming in.
You say: I can’t swallow.
I say: Adjust the sun visor.
You say: I’m out of breath.
I say: We’ll look for a rest stop.
You say: I can’t feel my toes.
I say: Something’s trying to pass us.
We both can sense it:
how it will overtake us
once it leaves the blind spot.


Chest. 2012;141(6):1635-1636. doi:10.1378/chest.11-3099

1PrigersonHGHorowitzMJJacobsSCProlonged grief disorder: psychometric validation of criteria proposed for DSM-V and ICD-11PLoS Med200968e10001212BoelenPAPrigersonHGThe influence of symptoms of prolonged grief disorder, depression, and anxiety on quality of life among bereaved adults: a prospective studyEur Arch Psychiatry Clin Neurosci200725784444523ChenJHBierhalsAJPrigersonHGKaslSVMazureCMJacobsSGender differences in the effects of bereavement-related psychological distress in health outcomesPsychol Med19992923673804PochardFDarmonMFassierTFrench FAMIREA study groupSymptoms of anxiety and depression in family members of intensive care unit patients before discharge or death. A prospective multicenter studyJ Crit Care200520190965PrigersonHGMaciejewskiPKA call for sound empirical testing and evaluation of criteria for complicated grief proposed for the DSM-V. Symposium on Complicated GriefOmega2005521166PrigersonHGMaciejewskiPKReynoldsCFIIIInventory of Complicated Grief: a scale to measure maladaptive symptoms of lossPsychiatry Res1995591-26579

Chest. 2012;141(6):1636-1637. doi:10.1378/chest.11-3248

1SchwartzsteinRMParkerMJRising Paco2 in the ICU: using a physiologic approach to avoid cognitive biasesChest20111406163816422CroskerryPThe importance of cognitive errors in diagnosis and strategies to minimize themAcad Med20037887757803CroskerryPAchieving quality in clinical decision making: cognitive strategies and detection of biasAcad Emerg Med2002911118412044TverskyAKahnemanDJudgment under uncertainty: heuristics and biasesScience19741854157112411315AbereggSKO’BrienJMLucarelliMTerryPBThe search-inference framework: a proposed strategy for novice clinical problem solvingMed Educ20084243893956BaronJThinking and Deciding2008New York, NYCambridge University Press7KahnemanDThinking, Fast and Slow2011New York, NYFarrar, Straus and Giroux

Chest. 2012;141(6):1637. doi:10.1378/chest.12-0182

1SchwartzsteinRMParkerMJRising Paco2 in the ICU: using a physiologic approach to avoid cognitive biasesChest20111406163816422TverskyAKahnemanDJudgment under uncertainty: heuristics and biasesScience19741854157112411313CroskerryPAchieving quality in clinical decision making: cognitive strategies and detection of biasAcad Emerg Med2002911118412044KahnemanDThinking Fast and Slow2011New York, NYFarrar, Strauss, and Giroux5AbereggSKO’BrienJMLucarelliMTerryPBThe search-inference framework: a proposed strategy for novice clinical problem solvingMed Educ20084243893956SchwartzsteinRMParkerMJInteractive physiology grand rounds: introduction to the seriesChest2009135168

Chest. 2012;141(6):1637-1638. doi:10.1378/chest.11-3302

1MartinoJLStapletonRDWangMExtreme obesity and outcomes in critically ill patientsChest20111405119812062Garrouste-OrgeasMTrochéGAzoulayEBody mass index. An additional prognostic factor in ICU patientsIntensive Care Med20043034374433RutkowskiPKlassenASebekovaKBahnerUHeidlandARenal disease in obesity: the need for greater attentionJ Ren Nutr20061632162234HernánMAClaytonDKeidingNThe Simpson’s paradox unraveledInt J Epidemiol20114037807855TopeliALaghiFTobinMJEffect of closed unit policy and appointing an intensivist in a developing countryCrit Care Med2005332299306

Chest. 2012;141(6):1638-1639. doi:10.1378/chest.12-0420

1MartinoJLStapletonRDWangMExtreme obesity and outcomes in critically ill patientsChest2011140511981206

Chest. 2012;141(6):1639. doi:10.1378/chest.12-0144

1AdesPASavagePDLischkeSThe effect of weight loss and exercise training on flow-mediated dilatation in coronary heart disease: a randomized trialChest20111406142014272KraicziHCaidahlKSamuelssonAPekerYHednerJImpairment of vascular endothelial function and left ventricular filling: association with the severity of apnea-induced hypoxemia during sleepChest20011194108510913AltinROzdemirHMahmutyazicioğluKEvaluation of carotid artery wall thickness with high-resolution sonography in obstructive sleep apnea syndromeJ Clin Ultrasound200533280864ChungSYoonIYLeeCHKimJWThe association of nocturnal hypoxemia with arterial stiffness and endothelial dysfunction in male patients with obstructive sleep apnea syndromeRespiration20107953633695AtkesonAJelicSMechanisms of endothelial dysfunction in obstructive sleep apneaVasc Health Risk Manag200846132713356CicconeMMFavaleSScicchitanoPReversibility of the endothelial dysfunction after CPAP therapy in OSAS patients [published online ahead of print February 24, 2011]Int J Cardioldoi:10.1016/j.ijcard.2011.01.0657AkinnusiMELaportaREl-SolhAALectin-like oxidized low-density lipoprotein receptor-1 modulates endothelial apoptosis in obstructive sleep apneaChest20111406150315108JohanssonKNeoviusMLagerrosYTEffect of a very low energy diet on moderate and severe obstructive sleep apnoea in obese men: a randomised controlled trialBMJ2009339b4609

Chest. 2012;141(6):1640. doi:10.1378/chest.12-0517

1AdesPASavagePDLischkeSThe effect of weight loss and exercise training on flow-mediated dilatation in coronary heart disease: a randomized trialChest20111406142014272SharmaSParkerATPrevalence of obstructive sleep apnea in a patient population undergoing cardiac rehabilitationJ Cardiopulm Rehabil Prev20113131881923SharmaSKAgrawalSDamodaranDCPAP for the metabolic syndrome in patients with obstructive sleep apneaN Engl J Med201136524227722864Theorell-HaglöwJBerneCJansonCLindbergEThe role of obstructive sleep apnea in metabolic syndrome: a population-based study in womenSleep Med2011124329334

Chest. 2012;141(6):1640-1641. doi:10.1378/chest.12-0153

1WahidiMMJainPJantzMAmerican College of Chest Physicians consensus statement on the use of topical anesthesia, analgesia, and sedation during flexible bronchoscopy in adult patientsChest20111405134213502CredleWFJrSmiddyJFElliottRCComplications of fiberoptic bronchoscopyAm Rev Respir Dis1974109167723SurattPMSmiddyJFGruberBDeaths and complications associated with fiberoptic bronchoscopyChest19766967477514FeinsilverSHFeinAMTextbook of Bronchoscopy1995Baltimore, MDWilkins and Williams5ColtHGMatsuoTHospital charges attributable to bronchoscopy-related complications in outpatientsRespiration200168167726DavisKLChannickCLSafety of topical tetracaine in patients undergoing flexible bronchoscopyJ Bronch Intervent Pulmonol200916295987GuayJMethemoglobinemia related to local anesthetics: a summary of 242 episodesAnesth Analg20091083837845

Chest. 2012;141(6):1641. doi:10.1378/chest.12-0754

1WahidiMMJainPJantzMAmerican College of Chest Physicians consensus statement on the use of topical anesthesia, analgesia, and sedation during flexible bronchoscopy in adult patientsChest20111405134213502GuayJMethemoglobinemia related to local anesthetics: a summary of 242 episodesAnesth Analg200910838378453US Department of Health and Human ServicesFDA’s information for healthcare professionalsUS Food and Drug Administration website. http://www.fda.gov/downloads/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/UCM274557.pdf. Accessed March 21, 20124ByrneMFMitchellRMGerkeHThe need for caution with topical anesthesia during endoscopic procedures, as liberal use may result in methemoglobinemiaJ Clin Gastroenterol20043832252295GregoryPJMatsudaKCetacaine spray-induced methemoglobinemia after transesophageal echocardiographyAnn Pharmacother200034910776KhanNAKruseJAMethemoglobinemia induced by topical anesthesia: a case report and reviewAm J Med Sci199931864154187BaumannMHGuttermanDDAmerican College of Chest Physicians evidence-based guidelines—the next generation: considering resource use and evolution to a single grading systemChest200612911012

Chest. 2012;141(6):1641-1642. doi:10.1378/chest.12-0296

1SchweickertWDKressJPImplementing early mobilization interventions in mechanically ventilated patients in the ICUChest20111406161216172CramerSCSurMDobkinBHHarnessing neuroplasticity for clinical applicationsBrain2011134pt 6159116093BernhardtJDeweyHThriftACollierJDonnanGA very early rehabilitation trial for stroke (AVERT): phase II safety and feasibilityStroke20083923903964Tay-TeoKMoodieMBernhardtJEconomic evaluation alongside a phase II, multi-centre, randomised controlled trial of very early rehabilitation after stroke (AVERT)Cerebrovasc Dis20082654754815CummingTBThriftAGCollierJMVery early mobilization after stroke fast-tracks return to walking: further results from the phase II AVERT randomized controlled trialStroke2011421153158

Chest. 2012;141(6):1642-1643. doi:10.1378/chest.12-0827

1SchweickertWDKressJPImplementing early mobilization interventions in mechanically ventilated patients in the ICUChest20111406161216172BienvenuOJColantuoniEMendez-TellezPADinglasVDShanholtzCHusainNDepressive symptoms and impaired physical function after acute lung injury: a 2-year longitudinal studyAm J Respir Crit Care Med201218555175243DesaiSVLawTJNeedhamDMLong-term complications of critical careCrit Care Med20113923713794MorrisPEGriffinLBerryMThompsonCHiteRDWinkelmanCReceiving early mobility during an intensive care unit admission is a predictor of improved outcomes in acute respiratory failureAm J Med Sci201134153733775JacksonJCMitchellNHopkinsROCognitive functioning, mental health, and quality of life in ICU survivors: an overviewAnesthesiol Clin2011294751764

Chest. 2012;141(6):1643. doi:10.1378/chest.12-0317

1Fernández-VillarALeiro-FernándezVBotana-RialMRepresas-RepresasCNúñez-DelgadoMThe endobronchial ultrasound-guided transbronchial needle biopsy learning curve for mediastinal and hilar lymph node diagnosisChest201214112782792Du RandIABarberPVGoldringJBritish Thoracic Society Interventional Bronchoscopy Guideline GroupBritish Thoracic Society guideline for advanced diagnostic and therapeutic flexible bronchoscopy in adultsThorax201166suppl 3iii1iii21

Chest. 2012;141(6):1643-1644. doi:10.1378/chest.12-0684

1Fernández-VillarALeiro-FernándezVBotana-RialMRepresas-RepresasCNúñez-DelgadoMThe endobronchial ultrasound-guided transbronchial needle biopsy learning curve for mediastinal and hilar lymph node diagnosisChest201214112782792Du RandIABarberPVGoldringJBritish Thoracic Society Interventional Bronchoscopy Guideline GroupBritish Thoracic Society guideline for advanced diagnostic and therapeutic flexible bronchoscopy in adultsThorax201166suppl 3iii1iii213KennedyMPJimenezCMhatreADMoriceRCEapenGAFactors influencing the diagnosis yield of endobronchial ultrasound-guided transbronchial needle aspirationJournal of Bronchology and Interventional Pulmonology20101732022084NavaniNNankivellMNadarajanPPereiraSPKocjanGJanesSMThe learning curve for EBUS-TBNAThorax20116643523535HoltyJEKuschnerWGGouldMKAccuracy of transbronchial needle aspiration for mediastinal staging of non-small cell lung cancer: a meta-analysisThorax200560119499556GrothSSWhitsonBAD’CunhaJMaddausMAAlsharifMAndradeRSEndobronchial ultrasound-guided fine-needle aspiration of mediastinal lymph nodes: a single institution’s early learning curveAnn Thorac Surg200886411041109


Chest. 2012;141(6):1645. doi:10.1378/chest.141.6.1645

We regret that the article “Perioperative Management of Antithrombotic Therapy: Prevention of VTE in Nonsurgical Patients: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines” published in the February 2012 supplement of CHEST (2012;141[2][Suppl]:e195S-e226S) contained several errors:

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