Current Issue


Chest. 2015;147(4):867-868. doi:10.1378/chest.14-2661

In this issue of CHEST (see page 951), Kerlin and colleagues1 provide another layer of evidence that 24/7 intensivist staffing is not associated with significant mortality or length-of-stay benefits. The observation that high-intensity critical care specialist involvement is associated with lower mortality and costs for adults with severe illness and injuries2 led to the hypothesis that 24/7 on-site intensivist staffing would result in better outcomes than daytime-only on-site staffing.3,4 The role of 24/7 intensivist staffing models for improving outcomes is an important issue in an era when the supply of critical care specialists is insufficient to meet the demands of an aging population.5 Concentrating specialists in ICUs that provide 24/7 staffing is expensive for institutions that can retain enough intensivists and reduces access to specialist care for other ICUs who must compete for a smaller pool of qualified specialists.

Chest. 2015;147(4):868-869. doi:10.1378/chest.14-2979

In 1968, the Phillip Morris Company launched a memorable campaign to sell its cigarettes, Virginia Slims, using a catchy slogan: “You’ve come a long way, baby,” which led to a massive increase in sales of cigarettes, especially among women, and launched the modern epidemic of COPD in the United States. Today, there are > 12.7 million Americans with COPD, and nearly 140,000 Americans succumb to this disease every year.1 Over the past 2 decades, there has been a concerted effort to find new therapeutic solutions to address the growing burden of COPD. How have we done?

Chest. 2015;147(4):869-871. doi:10.1378/chest.14-2406

Medical thoracoscopy (or pleuroscopy) under local anesthesia is a technique known since the 18th century when the Swedish physician Christian Jackobeus treated his patients with TB by cutting the adhesions using a cystoscope.1 However, it is only in the last 20 years that the technique has been spread all over the world because of industrial development and more widespread access to sources of knowledge. The latter evidence was mainly attributed to pioneer physicians, educational courses launched from departments traditionally performing this technique, and, finally, the development of new tools, such as the mini-thoracoscope2 and the semirigid pleuroscope.3 Indeed, the semirigid thoracoscope, which was developed in the early 2000s,3,4 has revolutionized the application of the technique, since it resembles the fiber-optic bronchoscope, a device very familiar to respiratory physicians.5

Point and Counterpoint

Chest. 2015;147(4):872-874. doi:10.1378/chest.14-3020

How radiation from a CT scan should be considered in patient care depends upon the circumstances in which the test is conducted. Ionizing radiation, the adverse health effects from which are cumulative, should be minimized but used when appropriate.

Chest. 2015;147(4):874-877. doi:10.1378/chest.14-3022

There is considerable disagreement in the scientific community on the carcinogenicity of low-dose radiation (LDR). Since the 1950s, international advisory bodies have consistently recommended using the linear no-threshold (LNT) model to extrapolate the high-dose cancer risks to low doses as a conservative approach to radiation safety, implying that LDR would increase the cancer risk. Hence, it is generally considered prudent to try to reduce the radiation dose from CT scans to reduce patients’ cancer risk. The entire radiologic community has embarked on efforts to reduce the radiation dose from CT scans. Are these LDR carcinogenic concerns and CT scan dose-reduction efforts justified? The answer to the question depends on (1) whether LDR is indeed carcinogenic, and (2) whether the CT scan dose-reduction efforts are likely to result in improved patient health. These two questions will be examined in some detail now to answer the question “Should radiation dose from CT scans be a factor in patient care?”

Chest. 2015;147(4):877-878. doi:10.1378/chest.14-3021

Dr Doss raises interesting points about low-dose radiation and cancer risks, including a role for hormesis in reducing risk of cancer.1 Although a uniform definition of low-dose radiation appears lacking, we agree that radiation concerns are insignificant in therapeutic and diagnostic uses. In contrast, lung cancer screening programs, performed on healthy people without symptoms, are intended to last at least 25 years and involve radiation exposure in screening and diagnostic follow-up of nodules.2 Annual low-dose CT scans will be accompanied by the inevitable follow-up of suspicious nodules, > 96% of which were benign in the National Lung Screening Trial (NLST).3

Chest. 2015;147(4):878-879. doi:10.1378/chest.14-3023

I welcome the opportunity to respond to Dr McCunney.1 His statement in the opening paragraph of his Point editorial that the adverse health effects from ionizing radiation are cumulative does not take into consideration the important effect of the body’s defensive response to low-dose radiation (LDR) exposure. This response, known as adaptive protection, would reduce the endogenous damage that would have occurred in the absence of the LDR exposure, thereby resulting in less overall DNA damage and cancer.2 For example, in a study of 5,000 childhood cancer survivors who had undergone radiation therapy and were followed up for an average of 29 years, the number of second cancers per kg of tissue in the regions of body subjected to radiation dose of about 20 cGy was found to be less than that in the nonirradiated regions of body.3 This observation and additionally cited examples4 involving a variety of LDR exposures demonstrate the effectiveness of LDR given over an extended period of time in reducing the risk of cancers. Thus, his concern about the number of screening CT scans that may be done in the few decades of follow-up of smokers would not be justified.

Giants in Chest Medicine

Chest. 2015;147(4):880-882. doi:10.1378/chest.14-2901

I thank Richard S. Irwin, MD, Master FCCP, and Editor in Chief, CHEST, for offering me the opportunity to profile Jay A. Nadel, MD, a giant in chest medicine. Born in 1929 in Philadelphia, Pennsylvania, Dr Nadel received his MD degree from Jefferson Medical College in 1953. During his internship and residency in cardiology at Philadelphia General Hospital (1953-1956), Dr Nadel met Julius Comroe, MD, who headed the Graduate School at the University of Pennsylvania. Subsequently, Dr Nadel spent 2 years in the US Air Force (Travis Air Force Base) near San Francisco, California, and Dr Comroe was recruited to head the Cardiovascular Research Institute at the University of California, San Francisco (UCSF). In 1958, Dr Nadel was chosen to be Dr Comroe’s research fellow.

Topics: pulmonology

Evidence-Based Medicine

Chest. 2015;147(4):883-893. doi:10.1378/chest.14-1677

COPD is a common disease with substantial associated morbidity and mortality. Patients with COPD usually have a progression of airflow obstruction that is not fully reversible and can lead to a history of progressively worsening breathlessness, affecting daily activities and health-related quality of life.1-3 COPD is the fourth leading cause of death in Canada4 and the third leading cause of death in the United States where it claimed 133,965 lives in 2009.5 In 2011, 12.7 million US adults were estimated to have COPD.6 However, approximately 24 million US adults have evidence of impaired lung function, indicating an underdiagnosis of COPD.7 Although 4% of Canadians aged 35 to 79 years self-reported having been given a diagnosis of COPD, direct measurements of lung function from the Canadian Health Measures Survey indicate that 13% of Canadians have a lung function score indicative of COPD.4

Chest. 2015;147(4):894-942. doi:10.1378/chest.14-1676

BACKGROUND:  COPD is a major cause of morbidity and mortality in the United States as well as throughout the rest of the world. An exacerbation of COPD (periodic escalations of symptoms of cough, dyspnea, and sputum production) is a major contributor to worsening lung function, impairment in quality of life, need for urgent care or hospitalization, and cost of care in COPD. Research conducted over the past decade has contributed much to our current understanding of the pathogenesis and treatment of COPD. Additionally, an evolving literature has accumulated about the prevention of acute exacerbations.

METHODS:  In recognition of the importance of preventing exacerbations in patients with COPD, the American College of Chest Physicians (CHEST) and Canadian Thoracic Society (CTS) joint evidence-based guideline (AECOPD Guideline) was developed to provide a practical, clinically useful document to describe the current state of knowledge regarding the prevention of acute exacerbations according to major categories of prevention therapies. Three key clinical questions developed using the PICO (population, intervention, comparator, and outcome) format addressed the prevention of acute exacerbations of COPD: nonpharmacologic therapies, inhaled therapies, and oral therapies. We used recognized document evaluation tools to assess and choose the most appropriate studies and to extract meaningful data and grade the level of evidence to support the recommendations in each PICO question in a balanced and unbiased fashion.

RESULTS:  The AECOPD Guideline is unique not only for its topic, the prevention of acute exacerbations of COPD, but also for the first-in-kind partnership between two of the largest thoracic societies in North America. The CHEST Guidelines Oversight Committee in partnership with the CTS COPD Clinical Assembly launched this project with the objective that a systematic review and critical evaluation of the published literature by clinical experts and researchers in the field of COPD would lead to a series of recommendations to assist clinicians in their management of the patient with COPD.

CONCLUSIONS:  This guideline is unique because it provides an up-to-date, rigorous, evidence-based analysis of current randomized controlled trial data regarding the prevention of COPD exacerbations.


Chest. 2015;147(4):943-950. doi:10.1378/chest.14-1755

Pulmonary hypertension (PH) is a common complication of numerous diseases, including left-sided heart diseases and chronic lung diseases and/or hypoxia, where PH is associated with exercise limitation and a worse prognosis. Other forms of PH include pulmonary arterial hypertension (PAH), chronic thromboembolic PH (CTEPH), and PH with unclear multifactorial mechanisms. Over the past decade, it has been documented that systolic pulmonary artery pressure (sPAP) may help estimate mean pulmonary artery pressure (mPAP) in adults with high accuracy and reasonably good precision (mPAP = 0.61 sPAP + 2 mm Hg). This strong linear relationship between sPAP and mPAP was unexpected from a classic physiologic point of view. Consistent results have been obtained from independent teams using either high-fidelity micromanometer-tipped PA catheters or fluid-filled catheters. Overall, the strong link between sPAP and mPAP has been documented over a wide range of PAPs, heart rate, cardiac output, wedge pressure, and causes of PH, during changes in posture and activity, and irrespective of patient’s sex, age, and BMI. A review of available invasive data confirms that patients with CTEPH and idiopathic PAH matched for their mPAP exhibit essentially similar sPAP. Pressure redundancy may be explained by the dependence of PA compliance upon mPAP. The 25 mm Hg threshold used to define PH accurately corresponds to an sPAP of 38 mm Hg. Although the limits of the echocardiographic estimation of sPAP are widely documented, results from invasive studies may furnish an evidence-based sPAP-derived mPAP value, potentially useful in the multiparameter echocardiographic approach currently used to diagnose and follow patients with PH.

Original Research: Critical Care Medicine

Chest. 2015;147(4):951-958. doi:10.1378/chest.14-0501

BACKGROUND:  Evidence regarding nighttime physician staffing of ICUs is suboptimal. We aimed to determine how nighttime physician staffing models influence patient outcomes.

METHODS:  We performed a multicenter retrospective cohort study in a multicenter registry of US ICUs. The exposure variable was the ICU’s nighttime physician staffing model. The primary outcome was hospital mortality. Secondary outcomes included new limitations on life support, ICU length of stay, hospital length of stay, and duration of mechanical ventilation. Daytime physician staffing was studied as a potential effect modifier.

RESULTS:  The study included 270,742 patients in 143 ICUs. Compared with nighttime staffing with an attending intensivist, nighttime staffing without an attending intensivist was not associated with hospital mortality (OR, 1.03; 95% CI, 0.92-1.15; P = .65). This relationship was not modified by daytime physician staffing (interaction P = .19). When nighttime staffing was subcategorized, neither attending nonintensivist nor physician trainee staffing was associated with hospital mortality compared with attending intensivist staffing. However, nighttime staffing without any physician was associated with reduced odds of hospital mortality (OR, 0.79; 95% CI, 0.68-0.91; P = .002) and new limitations on life support (OR, 0.83; 95% CI, 0.75-0.93; P = .001). Nighttime staffing was not associated with ICU or hospital length of stay. Nighttime staffing with an attending nonintensivist was associated with a slightly longer duration of mechanical ventilation (hazard ratio, 1.05; 95% CI, 1.02-1.09; P < .001).

CONCLUSIONS:  We found little evidence that nighttime physician staffing models affect patient outcomes. ICUs without physicians at night may exhibit reduced hospital mortality that is possibly attributable to differences in end-of-life care practices.

Chest. 2015;147(4):959-968. doi:10.1378/chest.14-1216

BACKGROUND:  The use of noninvasive ventilation (NIV) in acute exacerbation of COPD has increased over time. However, little is known about patient factors influencing its use in routine clinical practice.

METHODS:  This was a retrospective cohort study of 723,560 hospitalizations for exacerbation of COPD at 475 hospitals between 2001 and 2011. The primary study outcome was the initial form of ventilation (NIV or invasive mechanical ventilation [IMV]). Hierarchical generalized linear models were used to examine the trends in ventilation and patient characteristics associated with receipt of NIV.

RESULTS:  After adjusting for patient and hospital characteristics, initial NIV increased by 15.1% yearly (from 5.9% to 14.8%), and initial IMV declined by 3.2% yearly (from 8.7% to 5.9%); annual exposure to any form of mechanical ventilation increased by 4.4% (from 14.1% to 20.3%). Among case subjects treated with ventilation, those aged ≥ 85 years had a 22% higher odds of receiving NIV compared with those aged < 65 years, while blacks (OR, 0.86) and Hispanics (OR, 0.91) were less likely to be treated with NIV than were whites. Cases with a high burden of comorbidities and those with concomitant pneumonia had high rates of NIV failure and were more likely to receive initial IMV. Use of NIV increased at a faster rate among the admissions of the oldest patients relative to the youngest.

CONCLUSIONS:  The use of NIV for COPD exacerbations has increased steadily, whereas IMV use has declined. Several patient factors, including age, race, and comorbidities, influenced the receipt of NIV. Further research is needed to identify the factors driving these patterns.

Chest. 2015;147(4):969-978. doi:10.1378/chest.14-1426

BACKGROUND:  Although the mechanisms and pathways mediating ARDS have been studied extensively, less attention has been given to the mechanisms and pathways that counteract injury responses. This study found that the apelin-APJ pathway is an endogenous counterinjury mechanism that protects against ARDS.

METHODS:  Using a rat model of oleic acid (OA)-induced ARDS, the effects of ARDS on apelin and APJ receptor expressions and on APJ receptor binding capacity were examined. The protective effect of activating the apelin-APJ pathway against OA- or lipopolysaccharide (LPS)-induced ARDS was evaluated.

RESULTS:  ARDS was coupled to upregulations of the apelin and APJ receptor. Rats with OA-induced ARDS had higher lung tissue levels of apelin proprotein and APJ receptor expressions; elevated plasma, BAL fluid (BALF), and lung tissue levels of apelin-36 and apelin-12/13; and an increased apelin-APJ receptor binding capacity. Upregulation of the apelin-APJ system has important pathophysiologic function. Stimulation of the apelin-APJ signaling using receptor agonist apelin-13 alleviated, whereas inhibition of the apelin-APJ signaling using receptor antagonist [Ala]-apelin-13 exacerbated, OA-induced lung pathologies, extravascular lung water accumulation, capillary-alveolar leakage, and hypoxemia. The APJ receptor agonist inhibited, and the APJ receptor antagonist augmented, OA-induced lung tissue and BALF levels of tumor necrosis factor-α and monocyte chemoattractant protein-1, and plasma and lung tissue levels of malondialdehyde. Postinjury treatment with apelin-13 alleviated lung inflammation and injury and improved oxygenation in OA- and LPS-induced lung injury.

CONCLUSIONS:  The apelin-APJ signaling pathway is an endogenous anti-injury and organ-protective mechanism that is activated during ARDS to counteract the injury response and to prevent uncontrolled lung injury.

Chest. 2015;147(4):979-988. doi:10.1378/chest.14-0797

BACKGROUND:  Collection of genetic biospecimens as part of critical illness investigations is increasingly commonplace. Oversight bodies vary in restrictions imposed on genetic research, introducing inconsistencies in study design, potential for sampling bias, and the possibility of being overly prohibitive of this type of research altogether. We undertook this study to better understand whether restrictions on genetic data collection beyond those governing research on cognitively intact subjects reflect the concerns of surrogates for critically ill patients.

METHODS:  We analyzed survey data collected from 1,176 patients in nonurgent settings and 437 surrogates representing critically ill adults. Attitudes pertaining to genetic data (familiarity, perceptions, interest in participation, concerns) and demographic information were examined using univariate and multivariate techniques.

RESULTS:  We explored differences among respondents who were receptive (1,333) and nonreceptive (280) to genetic sample collection. Whereas factors positively associated with receptivity to research participation were “complete trust” in health-care providers (OR, 2.091; 95% CI, 1.544-2.833), upper income strata (OR, 2.319; 95% CI, 1.308-4.114), viewing genetic research “very positively” (OR, 3.524; 95% CI, 2.122-5.852), and expressing “no worry at all” regarding disclosure of results (OR, 2.505; 95% CI, 1.436-4.369), black race was negatively associated with research participation (OR, 0.410; 95% CI, 0.288-0.585). We could detect no difference in receptivity to genetic sample collection comparing ambulatory patients and surrogates (OR, 0.738; 95% CI, 0.511-1.066).

CONCLUSIONS:  Expressing trust in health-care providers and viewing genetic research favorably were associated with increased willingness for study enrollment, while concern regarding breach of confidentiality and black race had the opposite effect. Study setting had no bearing on willingness to participate.

Original Research: COPD

Chest. 2015;147(4):989-998. doi:10.1378/chest.14-2146

BACKGROUND:  Numbers and rates of hospitalizations and ED visits by patients with COPD are important metrics for surveillance purposes. The objective of this study was to examine trends in these rates from 2001 to 2012 among adults aged ≥ 18 years in the United States.

METHODS:  Data from the Nationwide Inpatient Sample (NIS) and Nationwide Emergency Department Sample (NEDS) were examined for temporal trends in the numbers and rates of hospitalizations by patients with COPD or bronchiectasis, mean length of stay, in-hospital case-fatality rate, 30-day readmission rate, and numbers and rates of ED visits.

RESULTS:  The national number of discharges with COPD or bronchiectasis as the principal diagnosis was about 88,000 higher in 2012 than in 2001, but the age-adjusted rate of discharges did not change significantly (range, 242.7-286.0 per 100,000 population, P trend = .554). In contrast, hospitalization rates for common cardiovascular disorders, pneumonia, and lung cancer decreased significantly by 27% to 68%, whereas the mean charge doubled and mean cost increased by 40%. From 2006 to 2011, the numbers of ED visits increased from 1,480,363 to 1,787,612. The age-adjusted rate increased nonsignificantly from 654 to 725 per 100,000 population (P trend = .072).

CONCLUSIONS:  Despite many local and national efforts to reduce the burden of COPD, total hospitalizations and ED visits over the past decade have increased for COPD, and the age-adjusted rates of hospitalizations and ED visits for COPD or bronchiectasis have not changed significantly in the United States.

Chest. 2015;147(4):999-1007. doi:10.1378/chest.14-0655

OBJECTIVE:  Exacerbations of COPD requiring hospital admission have important clinical and societal implications. We sought to investigate the incidence, recurrence, risk factors, and mortality of patients with COPD exacerbations requiring hospital admission compared with those without hospital admission during 3-year follow-up. Patients with COPD (N = 2,138) were identified from the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) observational cohort.

METHODS:  An analysis of time to first event of hospital admission was performed using Kaplan-Meier curves and Cox proportional hazard regression adjusting for possible confounders.

RESULTS:  Of the 2,138 patients, 670 (31%) reported a total of 1,452 COPD exacerbations requiring hospital admission during the study period; 313 patients (15%) reported multiple events. A prior history of exacerbation of COPD requiring hospital admission was the factor associated with the highest risk of a new hospitalization for exacerbation (hazard ratio, 2.71; 95% CI, 2.24-3.29; P < .001). Other risk factors included more severe airflow limitation, poorer health status, older age, radiologic evidence of emphysema, and higher WBC count. Having been hospitalized for exacerbation significantly increased the risk of mortality (P < .001).

CONCLUSIONS:  Exacerbations of COPD requiring hospital admission occur across all stages of airflow limitation and are a significant prognostic factor of reduced survival across all COPD stages. Patients with COPD at a high risk for hospitalization can be identified by their past history for similar events, and other factors, including the severity of airflow limitation, poor health status, age, presence of emphysema, and leukocytosis.

TRIAL REGISTRY:  ClinicalTrials.gov; No.: NCT00292552; URL: www.clinicaltrials.gov

Original Research: Pulmonary Procedures

Chest. 2015;147(4):1008-1012. doi:10.1378/chest.14-0637

BACKGROUND:  Medical thoracoscopy (MT) is a diagnostic and therapeutic procedure that permits the study of the pleural space. The presence of pleural adhesions is the most important contraindication to performing MT. Lesions of the pleura in absence of pleural effusion are usually studied in video-assisted thoracoscopic surgery (VATS) with preoperative ultrasound evaluation. No data are available about ultrasound-guided MT in the absence of pleural effusion.

METHODS:  From January 2007 to June 2013, 622 consecutive MTs were performed under ultrasound guidance without inducing a pneumothorax. A retrospective cohort of 29 patients affected by pleural diseases without fluid was reviewed. The fifth or sixth intercostal spaces along the midaxillary line with a good echographic “sliding sign” and normal appearance of the pleural line were chosen as the entry site. The pleural cavity was explored, and biopsies were performed.

RESULTS:  The mean age of the patient cohort was 62.8 years; there were 20 male patients and nine female patients. Pleural adherences were avoided, and adequate number of pleural biopsies were performed. No parenchymal lung injuries, bleeding, or hematoma occurred. Seventeen patients had a completely free pleural cavity, four patients had a single pleural adhesion, and eight had multiple pleural adhesions; in all cases, however, endoscopic exploration was possible and biopsy specimens were adequate. The most frequent histopathologic diagnosis was malignant pleural mesothelioma.

CONCLUSIONS:  We have shown that thoracic ultrasound accurately identifies intrathoracic adhesions and, in experienced hands, can guide MT access, replacing the VATS approach, even in the complete absence of pleural effusion.

Chest. 2015;147(4):1013-1019. doi:10.1378/chest.14-1306

BACKGROUND:  Ultrasonography has been used for the diagnosis of many kinds of lung conditions, but few studies have investigated ultrasound for the diagnosis of neonatal pulmonary atelectasis (NAP). In this study, we evaluated the usefulness of lung ultrasonography for the diagnosis of NPA.

METHODS:  From May 2012 to December 2013, 80 neonates with NPA and 50 neonates without lung disease were enrolled in this study. Each lung of every infant was divided into the anterior, lateral, and posterior regions by the anterior and posterior axillary lines. Each region was scanned carefully with the probe perpendicular or parallel to the ribs. The ultrasound findings were confirmed by chest radiograph (CXR) or CT scan.

RESULTS:  Sixty of the 80 patients with signs of NPA on lung ultrasound also had signs of NPA on CXR (termed focal-type atelectasis), and the other 20 patients had signs of NPA on chest CT scan while there were no abnormal findings on CXR (termed occult lung atelectasis). In patients with NPA, the main ultrasound findings were large areas of lung consolidation with clearly demarcated borders, air bronchograms, pleural line abnormalities, and absence of A-lines, as well as the presence of lung pulse and absence of lung sliding on real-time ultrasound. The sensitivity of lung ultrasonography for the diagnosis of NPA was 100%, whereas the sensitivity of CXR was 75%. Large areas of lung consolidation with clearly demarcated borders were only observed in patients with NPA.

CONCLUSIONS:  Lung ultrasonography is an accurate and reliable method for diagnosing NPA; most importantly, it can find those occult lung atelectasis that could not be detected on CXR. Routine lung ultrasonography is a useful method of diagnosing or excluding NPA in neonates.

Original Research: Sleep Disorders

Chest. 2015;147(4):1020-1028. doi:10.1378/chest.14-1959

OBJECTIVE:  The objective of this study was to evaluate the diagnostic reliability of home respiratory polygraphy (HRP) in children with a clinical suspicion of OSA-hypopnea syndrome (OSAS).

METHODS:  A prospective blind evaluation was performed. Children between the ages of 2 to 14 years with clinical suspicion of OSAS who were referred to the Sleep Unit were included. An initial HRP followed by a later date, same night, in-laboratory overnight respiratory polygraphy and polysomnography (PSG) in the sleep laboratory were performed. The apnea-hypopnea index (AHI)-HRP was compared with AHI-PSG, and therapeutic decisions based on AHI-HRP and AHI-PSG were analyzed using intraclass correlation coefficients, Bland-Altman plots, and receiver operator curves (ROCs).

RESULTS:  Twenty-seven boys and 23 girls, with a mean age of 5.3 ± 2.5 years, were studied, and 66% were diagnosed with OSAS based on a PSG-defined obstructive respiratory disturbance index ≥ 3/h total sleep time. Based on the availability of concurrent HRP-PSG recordings, the optimal AHI-HRP corresponding to the PSG-defined OSAS criterion was established as ≥ 5.6/h The latter exhibited a sensitivity of 90.9% (95% CI, 79.6%-100%) and a specificity of 94.1% (95% CI, 80%-100%).

CONCLUSIONS:  HRP recordings emerge as a potentially useful and reliable approach for the diagnosis of OSAS in children. However, more research is required for the diagnosis of mild OSAS using HRP in children.

Chest. 2015;147(4):1029-1036. doi:10.1378/chest.14-1655

BACKGROUND:  Carotid arteriosclerosis and sleep apnea are considered as independent risk factors for stroke. Whether sleep apnea mediates severity of carotid stenosis remains unclear. Sleep apnea comprises two pathophysiologic conditions: OSA and central sleep apnea (CSA). Although OSA results from upper airway occlusion, CSA reflects enhanced ventilatory drive mainly due to carotid chemoreceptor dysfunction.

METHODS:  Ninety-six patients with asymptomatic extracranial carotid stenosis of ≥ 50% underwent polysomnography to (1) determine prevalence and severity of sleep apnea for different degrees of carotid stenosis and (2) analyze associations between OSA and CSA, carotid stenosis severity, and other arteriosclerotic risk factors.

RESULTS:  Sleep apnea was present in 68.8% of patients with carotid stenosis. Prevalence and severity of sleep apnea increased with degree of stenosis (P ≤ .05) because of a rise in CSA (P ≤ .01) but not in OSA. Sleep apnea (OR, 3.8; P ≤ .03) and arterial hypertension (OR, 4.1; P ≤ .05) were associated with stenosis severity, whereas diabetes, smoking, dyslipidemia, BMI, age, and sex were not. Stenosis severity was related to CSA (P ≤ .06) but not to OSA. In addition, CSA but not OSA showed a strong association with arterial hypertension (OR, 12.5; P ≤ .02) and diabetes (OR, 4.5; P ≤ .04).

CONCLUSIONS:  Sleep apnea is highly prevalent in asymptomatic carotid stenosis. Further, it is associated with arteriosclerotic disease severity as well as presence of hypertension and diabetes. This vascular risk constellation seems to be more strongly connected with CSA than with OSA, possibly attributable to carotid chemoreceptor dysfunction. Because sleep apnea is well treatable, screening should be embedded in stroke prevention strategies.

Original Research: Asthma

Chest. 2015;147(4):1037-1042. doi:10.1378/chest.14-1742

BACKGROUND:  We have previously shown that in patients with asthma a single dose of an inhaled glucocorticosteroid (ICS) acutely potentiates inhaled albuterol-induced airway vascular smooth muscle relaxation through a nongenomic action. An effect on airway smooth muscle was not seen, presumably because the patients had normal lung function. The purpose of the present study was to conduct a similar study in patients with asthma with airflow obstruction to determine if an ICS could acutely also potentiate albuterol-induced airway smooth muscle relaxation in them.

METHODS:  In 15 adult patients with asthma (mean ± SE baseline FEV1, 62% ± 3%), the response to inhaled albuterol (180 μg) was assessed by determining the change in FEV1 (ΔFEV1) for airway smooth muscle and in airway blood flow (ΔQaw) for airway vascular smooth muscle measured 15 min after drug inhalation. Using a double-blind design, the patients inhaled a single dose of the ICS mometasone (400 μg) or placebo simultaneously with or 30 min before albuterol inhalation.

RESULTS:  After simultaneous drug administration, mean ΔFEV1 was 0.20 ± 0.05 L (10%) after placebo and 0.32 ± 0.04 L (19%) after mometasone (P < .05); mean ΔQaw was −2% after placebo and 30% after mometasone (P < .005). When mometasone or placebo was administered 30 min before albuterol, there was a lesser and insignificant difference in ΔFEV1 between the two treatments, whereas the difference in ΔQaw remained significant.

CONCLUSIONS:  This pilot study showed that in adult patients with asthma with airflow obstruction, a single standard dose of an ICS can acutely increase the FEV1 response to a standard dose of inhaled albuterol administered simultaneously. The associated potentiation of albuterol-induced vasodilation in the airway was of greater magnitude and retained when the ICS was administered 30 min before albuterol. The clinical significance of this observation will have to be established by a study involving a larger patient cohort.

TRIAL REGISTRY:  ClinicalTrials.gov; No.: NCT01210170; URL: www.clinicaltrials.gov

Original Research: Pulmonary Vascular Disease

Chest. 2015;147(4):1043-1062. doi:10.1378/chest.14-1888

BACKGROUND:  Studies suggest outpatient treatment or early discharge of patients with acute pulmonary embolism (aPE) is reasonable for those deemed to be at low risk of early mortality. We sought to determine clinical prediction rule accuracy for identifying patients with aPE at low risk for mortality.

METHODS:  We performed a literature search of Medline and Embase from January 2000 to March 2014, along with a manual search of references. We included studies deriving/validating a clinical prediction rule for early post-aPE all-cause mortality and providing mortality data over at least the index aPE hospitalization but ≤ 90 days. A bivariate model was used to pool sensitivity and specificity estimates using a random-effects approach. Traditional random-effects meta-analysis was performed to estimate the weighted proportion of patients deemed at low risk for early mortality and their ORs for death compared with high-risk patients.

RESULTS:  Forty studies (52 cohort-clinical prediction rule analyses) reporting on 11 clinical prediction rules were included. The highest sensitivities were observed with the Global Registry of Acute Coronary Events (0.99, 95% CI = 0.89-1.00), Aujesky 2006 (0.97, 95% CI = 0.95-0.99), simplified Pulmonary Embolism Severity Index (0.92, 95% CI = 0.89-0.94), Pulmonary Embolism Severity Index (0.89, 95% CI = 0.87-0.90), and European Society of Cardiology (0.88, 95% CI = 0.77-0.94) tools, with remaining clinical prediction rule sensitivities ranging from 0.41 to 0.82. Of these five clinical prediction rules with the highest sensitivities, none had a specificity > 0.48. They suggested anywhere from 22% to 45% of patients with aPE were at low risk and that low-risk patients had a 77% to 97% lower odds of death compared with those at high risk.

CONCLUSIONS:  Numerous clinical prediction rules for prognosticating early mortality in patients with aPE are available, but not all demonstrate the high sensitivity needed to reassure clinicians.

Chest. 2015;147(4):1063-1071. doi:10.1378/chest.14-0701

BACKGROUND:  Even after years of stable response to therapy, patients with idiopathic pulmonary arterial hypertension (IPAH) may show an unexpected clinical deterioration due to progressive right ventricular (RV) failure. Therefore, the aim of this study was to assess in 5-year clinically stable patients with IPAH whether initial differences or subsequent changes in RV volumes precede late clinical progression.

METHODS:  Included were 22 clinically stable patients with IPAH as reflected by stable or improving New York Heart Association functional class II-III and exercise capacity during 5 years of follow-up. Twelve patients subsequently remained stable during a total follow-up of 10 years, whereas 10 other patients showed late progression leading to death or lung transplantation after a follow-up of 8 years. All patients underwent right-sided heart catheterization and cardiac MRI at baseline and at 1½, 3½, 6½, and, if still alive, 10 years follow-up.

RESULTS:  Baseline hemodynamics were comparable in both groups and remained unchanged during the entire follow-up period. Baseline RV end-systolic volume (RVESV) was higher and RV ejection fraction (RVEF) was lower in late-progressive patients. Late-progressive patients demonstrated a gradually increased RV end-diastolic volume and RVESV and a decline in RVEF, whereas long-term stable patients did not show any RV changes.

CONCLUSIONS:  In patients with stable IPAH for 5 years, subsequent late disease progression is preceded by changes in RV volumes. The results indicate that monitoring RV volumes anticipates clinical worsening, even at a time of apparent clinical stability.

Chest. 2015;147(4):1072-1079. doi:10.1378/chest.14-1353

BACKGROUND:  There is considerable interindividual variability in pulmonary artery pressure among high-altitude (HA) dwellers, but the underlying mechanism is not known. At low altitude, a patent foramen ovale (PFO) is present in about 25% of the general population. Its prevalence is increased in clinical conditions associated with pulmonary hypertension and arterial hypoxemia, and it is thought to aggravate these problems.

METHODS:  We searched for a PFO (transesophageal echocardiography) in healthy HA dwellers (n = 22) and patients with chronic mountain sickness (n = 35) at 3,600 m above sea level and studied its effects (transthoracic echocardiography) on right ventricular (RV) function, pulmonary artery pressure, and vascular resistance at rest and during mild exercise (50 W), an intervention designed to further increase pulmonary artery pressure.

RESULTS:  The prevalence of PFO (32%) was similar to that reported in low-altitude populations and was not different in participants with and without chronic mountain sickness. Its presence was associated with RV enlargement at rest and an exaggerated increase in right-ventricular-to-right-atrial pressure gradient (25 ± 7 mm Hg vs 15 ± 9 mm Hg, P < .001) and a blunted increase in fractional area change of the right ventricle (3% [−1%, 5%] vs 7% [3%, 16%], P = .008) during mild exercise.

CONCLUSIONS:  These findings show, we believe for the first time, that although the prevalence of PFO is not increased in HA dwellers, its presence appears to facilitate pulmonary vasoconstriction and RV dysfunction during a mild physical effort frequently associated with daily activity.

TRIAL REGISTRY:  ClinicalTrials.gov; No.: NCT01182792; URL: www.clinicaltrials.gov

Chest. 2015;147(4):1080-1085. doi:10.1378/chest.14-1461

BACKGROUND:  Pulmonary vascular capacitance (PVC) is reduced in pulmonary arterial hypertension (PAH). In normal lung, PVC is largely a function of vascular compliance. In PAH, increased pulmonary vascular resistance (PVR) arises from the arterioles. PVR and PVC share pressure and volume variables. The dependency between the two qualities of the vascular bed is unclear in a state of intense vasoconstriction.

METHODS:  We compared PVC and PVR before and during nitric oxide (NO) inhalation during right-sided heart catheterization in eight NO-responsive patients with PAH. NO only directly affects tone in parenchymal vessels.

RESULTS:  During NO inhalation, pulmonary arterial systolic pressure decreased, 80 ± 20 SD to 48 ± 20 mm Hg, and stroke volume increased, 62 ± 19 mL to 86 ± 24 mL (P < .01). PVR dropped from 10 ± 4.4 Wood units to 4.7 ± 2.2 Wood units (P < .012), and PVC increased from 1.4 ± 1.1 mL/mm Hg to 3.2 ± 1.8 mL/mm Hg (P < .018). The magnitude of PVR drop was 57% ± 6% and the decrease in 1/PVC was 54% ± 14% (P = not significant).

CONCLUSIONS:  In vasoresponsive PAH, PVC is a function of the pressure response of the vasoconstricted arterioles to stroke volume. Immediately upon vasodilation, the capacitance increases markedly. The compliance vessels are, thus, the same as the resistance vessels. The immediate reduction in pulmonary arterial pressure during NO inhalation suggests that large vessel remodeling is not a major contributor to systolic pressure in these patients.

Original Research: Diffuse Lung Disease

Chest. 2015;147(4):1086-1093. doi:10.1378/chest.14-1099

BACKGROUND:  Sarcoidosis, a systemic disorder characterized by chronic granulomatous inflammation, occurs more frequently among US black women, as do overweight and obesity. Little is known about the relation of overweight and obesity, which induce chronic inflammation, to incidence of sarcoidosis.

METHODS:  We assessed the relation of obesity and weight gain to the incidence of sarcoidosis in the Black Women’s Health Study, a follow-up study of 59,000 US black women aged 21 to 69 years at baseline in 1995. Information on weight at age 18 years, height, current weight, incident sarcoidosis, and covariates was collected at baseline and on biennial follow-up questionnaires. Cox regression models adjusted for age, education, geographic region, smoking, alcohol consumption, and physical activity were used to estimate incidence rate ratios (IRRs) and 95% CIs.

RESULTS:  From 1995 through 2011, 454 incident cases of sarcoidosis occurred during 707,557 person-years of follow-up. The incidence of sarcoidosis increased with increasing BMI and weight gain. The IRR was 1.40 (95% CI, 0.88-2.25) for BMI ≥ 30 kg/m2 at age 18 years relative to 20 to 24 kg/m2 (P trend = .18), 1.42 (95% CI, 1.07-1.89) for BMI ≥ 35 kg/m2 at baseline relative to 20 to 24 kg/m2 (P trend = .01), and 1.47 (95% CI, 1.10-1.97) for a weight gain between age 18 years and baseline of ≥ 30 kg relative to 0 to 9 kg (P trend = .16). In stratified analyses, there were significant trends of sarcoidosis incidence with increasing BMI and weight gain in women aged ≥ 45 years and ever smokers.

CONCLUSIONS:  The present study provides evidence that weight gain and obesity during adulthood are associated with increased sarcoidosis incidence.

Original Research: Chest Infections

Chest. 2015;147(4):1094-1102. doi:10.1378/chest.14-0960

BACKGROUND:  The potential role of environmental Mycobacterium tuberculosis in the epidemiology of TB remains unknown. We investigated the transmission of M tuberculosis from humans to the environment and the possible transmission of M tuberculosis from the environment to humans.

METHODS:  A total of 1,500 samples were collected from three counties of the Tehran, Iran metropolitan area from February 2012 to January 2014. A total of 700 water samples (47%) and 800 soil samples (53%) were collected. Spoligotyping and the mycobacterial interspersed repetitive units-variable number of tandem repeats typing method were performed on DNA extracted from single colonies. Genotypes of M tuberculosis strains isolated from the environment were compared with the genotypes obtained from 55 patients with confirmed pulmonary TB diagnosed during the study period in the same three counties.

RESULTS:  M tuberculosis was isolated from 11 of 800 soil samples (1%) and 71 of 700 water samples (10%). T family (56 of 82, 68%) followed by Delhi/CAS (11 of 82, 13.4%) were the most frequent M tuberculosis superfamilies in both water and soil samples. Overall, 27.7% of isolates in clusters were related. No related typing patterns were detected between soil, water, and clinical isolates. The most frequent superfamily of M tuberculosis in clinical isolates was Delhi/CAS (142, 30.3%) followed by NEW-1 (127, 27%). The bacilli in contaminated soil (36%) and damp water (8.4%) remained reculturable in some samples up to 9 months.

CONCLUSIONS:  Although the dominant M tuberculosis superfamilies in soil and water did not correspond to the dominant M tuberculosis family in patients, the presence of circulating genotypes of M tuberculosis in soil and water highlight the risk of transmission.

Original Research: Cardiovascular Disease

Chest. 2015;147(4):1103-1110. doi:10.1378/chest.14-2096

BACKGROUND:  Diabetes mellitus is recognized as a stroke risk factor in atrial fibrillation (AF). Patients with diabetes with retinopathy have an increased risk for systemic cardiovascular complications, and severe diabetic retinopathy predisposes to ocular bleeding. We hypothesized that patients with diabetes, retinopathy, and AF have increased stroke/thromboembolism (TE) and severe bleeding risks when compared with patients with diabetes and AF who do not have retinopathy or to patients with AF and without diabetes.

METHODS:  We tested our hypothesis in a large “real-world” cohort of individuals with AF from the Loire Valley Atrial Fibrillation project.

RESULTS:  Of 8,962 patients with AF in our dataset, 1,409 (16%) had documented diabetes mellitus. Of these, 163 (1.8% of the whole cohort) were patients with diabetic retinopathy. After a follow-up of 31 ± 36 months, when compared with patients without diabetes, the risk of stroke/TE in patients with diabetes with no retinopathy increased 1.3-fold (relative risk [RR], 1.30; 95% CI, 1.07-1.59; P = .01); in patients with diabetes with retinopathy, the risk of stroke/TE was increased 1.58-fold (RR, 1.58; 95% CI, 1.07-2.32; P = .02). There was no significant difference when patients with diabetes with no retinopathy were compared with patients with diabetes with retinopathy (RR, 1.21; 95% CI, 0.80-1.84; P = .37). A similar pattern was seen for mortality and severe bleeding. On multivariate analysis, the presence of diabetic retinopathy did not emerge as an independent predictor for stroke/TE or severe bleeding.

CONCLUSIONS:  Crude rates of stroke/TE increased in a stepwise fashion when patients without diabetes and with AF were compared with patients with diabetes with no retinopathy and patients with diabetes with retinopathy. However, we have shown for the first time, to our knowledge, that the presence of diabetic retinopathy did not emerge as an independent predictor for stroke/TE or severe bleeding on multivariate analysis.

Original Research: Lung Cancer

Chest. 2015;147(4):1111-1117. doi:10.1378/chest.14-1960

BACKGROUND:  The natural history of typical pulmonary carcinoid tumors has not been described and has important implications for counseling elderly patients or patients with high operative-risk about surgical resection.

METHODS:  Data from the Surveillance, Epidemiology, and End Results Program were used to identify 4,111 patients with biopsy specimen-proven lymph node-negative typical carcinoid tumor of the lung between 1988 and 2010; 306 had no resection, 929 underwent sublobar resection, and 2,876 underwent lobectomy. Overall survival and disease-specific survival (DSS) were analyzed using Kaplan-Meier plots. Multivariate analysis was used to determine predictors of survival.

RESULTS:  Five-year overall survival in patients who underwent lobectomy, sublobar resection, or no surgery was 93%, 92%, and 69%, respectively (P < .0001); 5-year DSS was 97%, 98%, and 88%, respectively (P < .0001). Among T1 tumors, DSS was 98% for patients who underwent lobectomy and sublobar resection and 92% for no surgery; among T2 tumors, DSS was 97%, 100%, and 87%, respectively, and among T3 and T4 tumors, it was 96%, 100%, and 75%, respectively. On multivariate analysis, nonoperative management was associated with an increased risk for disease-specific mortality compared with lobectomy (hazard ratio, 2.14; 95% CI, 1.35-3.40; P = .0013).

CONCLUSIONS:  In this population-based cohort, surgical resection of lymph node-negative carcinoid tumors is associated with a survival advantage over nonoperative treatment. However, the DSS at 5 years was still high without any treatment, suggesting that observation of asymptomatic peripheral typical carcinoid tumors or endoscopic management of symptomatic central carcinoid tumors may be considered in patients at high risk for surgical resection.

Original Research: Pulmonary Physiology

Chest. 2015;147(4):1118-1126. doi:10.1378/chest.14-0698

BACKGROUND:  Poor fetal growth rate is associated with lower respiratory function; however, there is limited understanding of the impact of growth trends and BMI during childhood on adult respiratory function.

METHODS:  The current study data are from the Mater-University of Queensland Study of Pregnancy birth cohort. Prospective data were available from 1,740 young adults who performed standard spirometry at 21 years of age and whose birth weight and weight, height, and BMI at 5, 14, and 21 years of age were available. Catch-up growth was defined as an increase of 0.67 Z score in weight between measurements. The impact of catch-up growth on adult lung function and the relationship between childhood BMI trends and adult lung function were assessed using regression analyses.

RESULTS:  Lung function was higher at 21 years in those demonstrating catch-up growth from birth to 5 years (FVC, men: 5.33 L vs 5.54 L; women: 3.78 L vs 4.03 L; and FEV1, men: 4.52 L/s vs 4.64 L/s; women: 3.31 L/s vs 3.45 L/s). Subjects in the lowest quintile of birth (intrauterine growth retardation) also showed improved lung function if they had catch-up growth in the first 5 years of life. There was a positive correlation between increasing BMI and lung function at 5 years of age. However, in the later measurements when BMI increased into the obese category, a drop in lung function was observed.

CONCLUSIONS:  These data show evidence for a positive contribution of catch-up growth in early life to adult lung function. However, if weight gain or onset of obesity occurs after 5 years of age, an adverse impact on adult lung function is noted.

Chest. 2015;147(4):1127-1134. doi:10.1378/chest.14-1749

BACKGROUND:  Obesity is a global and growing public health problem. Bariatric surgery (BS) is indicated in patients with morbid obesity. To our knowledge, the effects of morbid obesity and BS on ventilation/perfusion (V. a/Q. ) ratio distributions using the multiple inert gas elimination technique have never before been explored.

METHODS:  We compared respiratory and inert gas (V. a/Q.  ratio distributions) pulmonary gas exchange, breathing both ambient air and 100% oxygen, in 19 morbidly obese women (BMI, 45 kg/m2), both before and 1 year after BS, and in eight normal-weight, never smoker, age-matched, healthy women.

RESULTS:  Before BS, morbidly obese individuals had reduced arterial Po2 (76 ± 2 mm Hg) and an increased alveolar-arterial Po2 difference (27 ± 2 mm Hg) caused by small amounts of shunt (4.3% ± 1.1% of cardiac output), along with abnormally broadly unimodal blood flow dispersion (0.83 ± 0.06). During 100% oxygen breathing, shunt increased twofold in parallel with a reduction of blood flow to low V. a/Q.  units, suggesting the development of reabsorption atelectasis without reversion of hypoxic pulmonary vasoconstriction. After BS, body weight was reduced significantly (BMI, 31 kg/m2), and pulmonary gas exchange abnormalities were decreased.

CONCLUSIONS:  Morbid obesity is associated with mild to moderate shunt and V. a/Q.  imbalance. These abnormalities are reduced after BS.

Translating Basic Research into Clinical Practice

Chest. 2015;147(4):1135-1143. doi:10.1378/chest.14-1286

Physicians are more and more often challenged by difficult-to-treat cases of TB. They include patients infected by strains of Mycobacterium tuberculosis that are resistant to at least isoniazid and rifampicin (multidrug-resistant TB) or to at least one fluoroquinolone (FQ) and one injectable, second-line anti-TB drug in addition to isoniazid and rifampicin (extensively drug-resistant TB). The drug treatment of these cases is very long, toxic, and expensive, and, unfortunately, the proportion of unsatisfactory outcomes is still considerably high. Although FQs and pyrazinamide (PZA) are backbone drugs in the available anti-TB regimens, several uncertainties remain about their mechanisms of action and even more remain about the mechanisms leading to drug resistance. From a clinical point of view, a better understanding of the genetic basis of drug resistance will aid (1) clinicians to provide quality clinical management to both drug-susceptible and drug-resistant TB cases (while preventing emergence of further resistance), and (2) developers of new molecular-based diagnostic assays to better direct their research efforts toward a new generation of sensitive, specific, cheap, and easy-to-use point-of-care diagnostics. In this review we provide an update on the molecular mechanisms leading to FQ- and PZA-resistance in M tuberculosis.

Medical Ethics

Chest. 2015;147(4):1144-1151. doi:10.1378/chest.14-2227

A 13-year-old patient named Jahi McMath was determined to be dead by neurologic criteria following cardiopulmonary arrest and resuscitation at a hospital in Oakland, California. Her family did not agree that she was dead and refused to allow her ventilator to be removed. The family’s attorney stated in the media that families, rather than physicians, should decide whether patients are dead and argued in the courts that the families’ constitutional rights of religion and privacy would be violated otherwise. Ultimately, a judge agreed that the patient was dead in keeping with California law, but the constitutional issue was undecided. The patient was then transferred to a hospital in New Jersey, a state whose laws allow families to require on religious grounds that death be determined by cardiopulmonary criteria. Although cases such as this are uncommon, they demonstrate public confusion about the concept of neurologic death and the rejection of this concept by some families. The confusion may be caused in part by a lack of uniformity in state laws regarding the legal basis of death, as reflected in the differences between New Jersey and California statutes. Families who reject the determination of death by neurologic criteria on religious grounds should be given reasonable accommodation in all states, but society should not pay for costly treatments for patients who meet these criteria unless the state requires it, as only New Jersey does. Laws that give physicians the right to determine death by neurologic criteria in other states probably can survive a constitutional challenge. Physicians and hospitals faced with similar cases in the future should follow state laws and work through the courts if necessary.

Topics in Practice Management

Chest. 2015;147(4):1152-1160. doi:10.1378/chest.14-1471

Electronic health records (EHRs) have the potential to improve health-care quality by allowing providers to make better decisions at the point of care based on electronically aggregated data and by facilitating clinical research. These goals are easier to achieve when key, disease-specific clinical information is documented as structured data elements (SDEs) that computers can understand and process, rather than as free-text/natural-language narrative. This article reviews the benefits of capturing disease-specific SDEs. It highlights several design and implementation considerations, including the impact on efficiency and expressivity of clinical documentation and the importance of adhering to data standards when available. Pulmonary disease-specific examples of collection instruments are provided from two commonly used commercial EHRs. Future developments that can leverage SDEs to improve clinical quality and research are discussed.

Recent Advances in Chest Medicine

Chest. 2015;147(4):1161-1167. doi:10.1378/chest.14-1299

Air pollution exposure is a well-established risk factor for several adverse respiratory outcomes, including airways diseases and lung cancer. Few studies have investigated the relationship between air pollution and interstitial lung disease (ILD) despite many forms of ILD arising from environmental exposures. There are potential mechanisms by which air pollution could cause, exacerbate, or accelerate the progression of certain forms of ILD via pulmonary and systemic inflammation as well as oxidative stress. This article will review the current epidemiologic and translational data supporting the plausibility of this relationship and propose a new conceptual framework for characterizing novel environmental risk factors for these forms of lung disease.

Contemporary Reviews in Critical Care Medicine

Chest. 2015;147(4):1168-1178. doi:10.1378/chest.14-1567

Improving value within critical care remains a priority because it represents a significant portion of health-care spending, faces high rates of adverse events, and inconsistently delivers evidence-based practices. ICU directors are increasingly required to understand all aspects of the value provided by their units to inform local improvement efforts and relate effectively to external parties. A clear understanding of the overall process of measuring quality and value as well as the strengths, limitations, and potential application of individual metrics is critical to supporting this charge. In this review, we provide a conceptual framework for understanding value metrics, describe an approach to developing a value measurement program, and summarize common metrics to characterize ICU value. We first summarize how ICU value can be represented as a function of outcomes and costs. We expand this equation and relate it to both the classic structure-process-outcome framework for quality assessment and the Institute of Medicine’s six aims of health care. We then describe how ICU leaders can develop their own value measurement process by identifying target areas, selecting appropriate measures, acquiring the necessary data, analyzing the data, and disseminating the findings. Within this measurement process, we summarize common metrics that can be used to characterize ICU value. As health care, in general, and critical care, in particular, changes and data become more available, it is increasingly important for ICU leaders to understand how to effectively acquire, evaluate, and apply data to improve the value of care provided to patients.

Contemporary Reviews in Sleep Medicine

Chest. 2015;147(4):1179-1192. doi:10.1378/chest.14-1617

Insomnia disorder is characterized by chronic dissatisfaction with sleep quantity or quality that is associated with difficulty falling asleep, frequent nighttime awakenings with difficulty returning to sleep, and/or awakening earlier in the morning than desired. Although progress has been made in our understanding of the nature, etiology, and pathophysiology of insomnia, there is still no universally accepted model. Greater understanding of the pathophysiology of insomnia may provide important information regarding how, and under what conditions, the disorder develops and is maintained as well as potential targets for prevention and treatment. The aims of this report are (1) to summarize current knowledge on the pathophysiology of insomnia and (2) to present a model of the pathophysiology of insomnia that considers evidence from various domains of research. Working within several models of insomnia, evidence for the pathophysiology of the disorder is presented across levels of analysis, from genetic to molecular and cellular mechanisms, neural circuitry, physiologic mechanisms, sleep behavior, and self-report. We discuss the role of hyperarousal as an overarching theme that guides our conceptualization of insomnia. Finally, we propose a model of the pathophysiology of insomnia that integrates the various types of evidence presented.

Topics: sleep , insomnia


Chest. 2015;147(4):1193. doi:10.1378/chest.14-2216

I am defeated by an eyelash that holds its position by static to her
eyeglasses [Leslie, my wife] and by the little red scabs of polish on her nails.
I am defeated as she ties a perfect bow at the waist of her hospital Johnny.
I am defeated when she says, Tell me I’ll be OK.
On the third night her fever reaches its apex again. I lie beside her in the bed.
We watch the order of news—first war, then weather. We watch a documentary.
A grizzly glares at the cameraman from a distance. It takes two slow steps in his
direction. Good grizzly, says the cameraman.
Someone comes to scrub out the shower stall, Windex the mirror over the sink,
take away the garbage. Someone else wearing a blue mask and purple
latex gloves comes to take away the hazmat. Someone calls. No more
flowers, Leslie yells into her cell.
We’ve got to get out of this room, I think, so I help my wife into the wheel chair,
unhook her oxygen tank, roll her out the door and down the hall,
past the day-shift nurses, saying they won’t drink hospital tap water, debating
which bottled water’s best.
Leslie says to me: you are my anchor, hold me. Oh, shit, I think, we’re both going
to drown. Oh shit, and allow myself five minutes of self-pity, while the woman
next door calls out in the darkness. Is anybody there? Calls out through the beeping
monitors: Is anybody there?
They bring us breakfast: very quiet scrambled eggs. I walk to the window
that overlooks the Charles. Wind is whipping whitecaps. A runner is struggling
headstrong into that wind. There’s a gull above him, like a guardian angel,
maintaining stasis.

Chest. 2015;147(4):1194. doi:10.1378/chest.14-2428

Not one word
in the name of this crazy pounding
that starts boom
just like that
  in the  middle of my chest
in the middle of the night
   or at 2 p.m. and
 flies up through my neck to
my jaws and has me thinking
  I will drop  dead
not one word
in its name
that even a person who went to college
would know. They talk about
the upper chamber and all I can remember
is the porcelain potty Grandma
used in the upstairs bedroom
when she was  85 and couldn’t
  make it  down the steps, the one
 mama emptied  every morning. They
   talk about fluttering
and it makes me think of the chicken bodies
jumping all over the back yard
after papa cut off their heads. And why
can’t they just say “every now and then”?
They say don’t worry,  the
 rat poison  ( they call it warfarin
) will keep  the blood from  clotting
  and the diltiazem will stop the heart
But when they call something
a name like this
it must be bad.

Chest. 2015;147(4):1195. doi:10.1378/chest.14-2489

Wind sharpens itself
on the edges
of worn brick walls.
This is personal
space. You
no longer have a say.
Thick sky presses you
above the asphalt
valley to freedom
a hundred feet below
your bed.
The last thing you want to see coming:
     Aide Bearing Plastic Trays.
The number of feet allotted you here:
   Twenty, including your cage.
Unless you cough
or seize.
Doors open for those in crisis.
Through the bars
pale sunlight forms
a branded Y
from skull
to eye
and back.
wrapped in sheets,
staring at nothing.
Black is the new 40.

Chest. 2015;147(4):1196. doi:10.1378/chest.14-2490

You need to have a head on hand
greens, raw and shredded. You
carry a diagnosis. You carry your iPad
to the funeral, watch YouTube
while the casket runs down the aisle.
When today is tomorrow you know
you are in Japan. The body
is uninhabited. You carry a diagnosis
a gift to you. Half portion.
Holes are insatiable, do not feed.
The corpse needs to be fresh, lightly
salted. Standard equipment on all models.
Flesh removed, fat marbled.
Do not let the brain
loll in its cerebral hammock.
You carry a diagnosis. Your bed
a small boat lost
in a weird, frothy sea,
soup-chunky with regret.
Watch the show, serve the tail
last. Do not stew. Do not forget:
you carry a diagnosis. Write it down
on index cards. Pass the recipe
to your children.
Serve chilled.


Chest. 2015;147(4):1197. doi:10.1378/chest.15-0170

An addition was made to the abstract in “The Association of Direct Thrombin Inhibitor Anticoagulants With Cardiac Thromboses” published in the January 2015 issue of CHEST (Chest 2015;147(1):21-24). The first line of the abstract was changed to include examples of anticoagulant drugs.

Selected Reports

Chest. 2015;147(4):e131-e133. doi:10.1378/chest.14-1849

Dronedarone is an amiodarone-like antiarrhythmic with a modified structure. The addition of a methyl sulfonyl group theoretically reduces the toxicity of amiodarone, specifically, adverse thyroid and pulmonary effects. Although animal studies have implicated dronedarone as a cause of lung injury, to date controlled trials in humans have not demonstrated an association. A 68-year-old woman developed a dry cough and worsening respiratory distress after receiving dronedarone for 6 months. Discontinuation of dronedarone therapy and subsequent steroid therapy led to a dramatic improvement of symptoms. Dronedarone may be associated with interstitial lung disease. We believe that patients receiving dronedarone should have their diffusing capacity of lung for carbon monoxide and lung volumes monitored prior to initiation of therapy and frequently thereafter.

Chest. 2015;147(4):e134-e136. doi:10.1378/chest.14-1884

Diffuse alveolar hemorrhage (DAH) is a syndrome caused by different mechanisms, including capillary stress failure, diffuse alveolar damage, and capillaritis. Capillaritis is the most common cause and is often associated with systemic autoimmune disorders, most commonly antineutrophilic cytoplasmic antibody-associated vasculitis. The occurrence of DAH with underlying pulmonary capillaritis but without clinical or serologic findings of an associated underlying systemic disorder is known as isolated pauciimmune pulmonary capillaritis (IPPC), and only eight cases have been described in the literature. The mainstay of treatment of this rare condition has been cyclophosphamide and glucocorticoids. When cases are unresponsive to cyclophosphamide, there is no known alternative treatment. Herein, we describe a case of IPPC that failed cyclophosphamide treatment with recurrent DAH. Rituximab therapy was then initiated with no further evidence of recurrence. This case report suggests that rituximab could be considered an alternative therapy to induce remission in patients with IPPC.

Ultrasound Corner

Chest. 2015;147(4):e137-e139. doi:10.1378/chest.14-1101

A 39-year-old woman presented to the ED with sudden onset of dyspnea after developing palpitations. On further questioning, she had noted swollen legs and had been on a flight from Utah to Massachusetts 10 days prior to admission. Her past medical history included obesity, and she had started taking oral contraceptive agents 2 months prior to her presentation.

Chest Imaging and Pathology for Clinicians

Chest. 2015;147(4):e140-e147. doi:10.1378/chest.14-1858

A 66-year-old woman presented with acute onset of fever, chills, and productive cough associated with right-sided chest pain. During a recent hospitalization for dyspnea, she had been diagnosed with Coombs-positive autoimmune hemolytic anemia and had been taking a tapering dose of prednisone starting approximately 6 weeks prior to admission. In the interim, her dyspnea had resolved on treatment with steroids. At the time of presentation, her prednisone dose was 40 mg. Additional medical history included VTE, for which the patient was receiving anticoagulation therapy, and steroid-induced diabetes mellitus. Many years earlier, she had been treated for TB in her home country. The patient had immigrated to Queens, New York, from a Nepalese village 8 years prior. While still in Nepal, she had worked on a farm and had been in close proximity to cows. In Queens, she lived with her family in a house with a small garden but had no pets. Recent travel included a visit to Nepal 9 months ago and a trip to Syracuse, New York, one month prior to presentation. She was a never smoker and did not consume alcohol.

Pulmonary, Critical Care, and Sleep Pearls

Chest. 2015;147(4):e148-e151. doi:10.1378/chest.14-1971

A 15-year-old boy presented for evaluation of snoring and sleep-disordered breathing. The parents noted that the patient snored every night and that he had episodes when he stopped breathing, ending with gasping for air. He had no history of sleep walking, night terrors, tongue biting, or seizures. The patient had two healthy siblings, but he had a history of intellectual disability and developmental delay. The patient had a history of adenotonsillectomy.

Topics: snoring , molar tooth
Chest. 2015;147(4):e152-e155. doi:10.1378/chest.14-1595

A 3-month-old infant was brought to clinic for evaluation of recurrent apparent life-threatening events (ALTEs). Two ALTE episodes occurred while the infant was sleeping in a safety car seat. The first one occurred when he was 4 weeks old. His mother noticed that he was not breathing; he appeared limp with full body cyanosis. His mother picked him up from the car seat, and he started breathing spontaneously and without any sign of distress. His skin color returned to normal. He was evaluated at the ED where the physical examination was normal. He was hospitalized 1 day for observation. During this time, workup, including ECG and chest radiograph, was normal. The parents were instructed on cardiorespiratory resuscitation and recommended to change car seats. The infant was discharged with an apnea monitor. He wore the apnea monitor while in the car seat. A second similar episode occurred at 10 weeks of age for which he was seen at the ED and referred to our clinic for further evaluation. Neither episode was related to feeding.


Chest. 2015;147(4):e156. doi:10.1378/chest.14-2909
Chest. 2015;147(4):e156-e157. doi:10.1378/chest.14-3088
Chest. 2015;147(4):e158. doi:10.1378/chest.14-3111
Chest. 2015;147(4):e158-e159. doi:10.1378/chest.14-3235
Chest. 2015;147(4):e160-e163. doi:10.1378/chest.14-2919
Chest. 2015;147(4):e164-e165. doi:10.1378/chest.14-3051

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