Chest. 2017;151(5):951-952. doi:10.1016/j.chest.2016.12.015

Idiopathic pulmonary fibrosis (IPF) remains an inexorably progressive and fatal disorder, with an overall incidence of roughly 94 cases per 100,000 person-years in the United States. The disease is characterized by ongoing lung injury with insidious deposition of extracellular matrix material leading to progressive distortion of lung architecture and subsequent loss of respiratory function. Traditional antiinflammatory therapies are well documented as having no efficacy for treating this condition and may, in fact, be associated with worse outcomes., The disease manifests as a relentless reduction in respiratory function, with interspersed episodes of rapidly progressive deterioration known as acute exacerbations. Despite the recent availability of two US Food and Drug Administration-approved antifibrotic agents for treating this disorder, no current medical therapies are known to be curative., In this light, continued investigation is desperately needed to develop new therapies to address this extremely devastating illness. Cell-based therapies, including the use of human mesenchymal stem cells (hMSCs) have been postulated as one such novel approach to treat IPF. Stem cells are proposed to target sites of ongoing tissue injury, to foster tissue regeneration and modulate lung remodeling, and to regulate pulmonary inflammation. The desperate nature of IPF and the promise of cell-based therapies have driven patients to seek out such treatment approaches even outside the confines of carefully controlled clinical studies, at times resulting in unfavorable outcomes. Accordingly, it remains imperative that the application of cell-based therapies for IPF be conducted only in carefully controlled clinical trial settings.

Chest. 2017;151(5):953-954. doi:10.1016/j.chest.2016.12.026

In this issue of Chest, Aksamit and colleagues of the Bronchiectasis Research Registry (BRR) describe their national bronchiectasis cohort. The BRR is a large, U.S. consolidated database that exists under the umbrella of the COPD Foundation. It was created in 2007 at the recommendation of experts from the COPD Foundation in collaboration with the National Heart, Lung, and Blood Institute to better characterize non-CF patients with bronchiectasis and to serve as a reservoir from which to recruit patients for clinical trials and research. In 2011, a nontuberculous mycobacteria (NTM) component was added to the Registry in recognition of the link between the two diseases. At present, 13 clinical centers supply the centralized database with patient data. In essence, the BRR represents a unified, cohesive, national effort to take ownership of non-CF bronchiectasis, which has classically been referred to as an “orphan disease.”

Topics: bronchiectasis
Chest. 2017;151(5):955-957. doi:10.1016/j.chest.2017.01.011

Improving care and outcomes for patients with sepsis is an increasingly achievable goal. The United States Centers for Medicare and Medicaid Services (CMS) and the Joint Commission (JC) have joined forces to provide new publicly reported measures that aim to reduce preventable sepsis-related mortality. The Centers for Disease Control has long recognized the importance of expeditious and effective treatment of infections and has implemented creative programs that urge patient and family advocacy by having them ask their providers “Do you think this might be sepsis?” The SEP-1 sepsis core measure is supported by increasingly clear reproducible high-quality evidence from clinical trials that defines the timing of specific treatments and assessments for patients recognized as having sepsis. Translation of key clinical trial interventions into improved patient outcomes has been a major focus of professional society and philanthropic efforts.

Chest. 2017;151(5):958-959. doi:10.1016/j.chest.2016.11.025

Primary ciliary dyskinesia (PCD) is a genetically heterogeneous disorder of ciliary biogenesis, structure, and function. Diagnosis can be challenging. Several diagnostic tests have been used, including assessment of ciliary beat pattern by high-speed videomicroscopy, ciliary ultrastructure by transmission electron microscopy, nasal nitric oxide measurement, and, more recently, immunofluorescence testing using a panel of antibodies and genetic testing using a panel of PCD-associated genes. All of these tests require specialized equipment and expertise for interpretation and none of these tests has the accuracy needed for a “stand alone” diagnostic test.

Giants in Chest Medicine

Chest. 2017;151(5):960-961. doi:10.1016/j.chest.2016.11.060

Editorials: Point and Counterpoint

Chest. 2017;151(5):962-965. doi:10.1016/j.chest.2016.11.043

Spinal muscular atrophy (SMA) is an inherited disease of anterior horn cells. It varies in severity from type 1A (SMA1; or type 0), for which continuous noninvasive ventilatory support (CNVS) and enteral nutrition are required before 6 months of age (10% of cases); to typical, for which CNVS and enteral nutrition are needed by 18 months (75%) of age; to mild, when CNVS and enteral nutrition are subsequently needed (15%)., Without respiratory support, SMA1 has 50% mortality by 7 months of age and 90% by 1 year of age.

Chest. 2017;151(5):965-968. doi:10.1016/j.chest.2016.11.039

Among those physicians who offer ventilatory support to parents of children with SMA1, there seems to be a consensus that noninvasive ventilation (NIV) is the preferred method to provide that support.,, An SMA standard of care document advocates for the use of NIV whenever possible in those infants whose families choose to provide ventilatory support. Nevertheless, several groups advocate for the use of invasive ventilation via tracheostomy (IVTr) in a subset of their patients,,, and many practitioners express a willingness to consider offering mechanical ventilation via tracheostomy to families.

Chest. 2017;151(5):968-969. doi:10.1016/j.chest.2016.11.041

Dr Panitch’s thoughtful commentary deserves further consideration. The French and Italian users of NIV (ie, bilevel positive airway pressure [PAP]) who underwent tracheotomies included no CNVS users; thus, when needing more than sleep NIV or when intubated, they underwent tracheotomy. We routinely extubate “unweanable” patients with SMA1, including infants, to CNVS, thereby avoiding tracheotomies indefinitely provided that parents learn and administer CNVS and MIE. Infants capable of 50-mL tidal volumes (intermediate type) invariably wean postextubation from CNVS to sleep NVS, for one-half of them until after 10 years of age, and 80% develop functional speech. No patients with intermediate or severe SMA1 who undergo tracheotomy subsequently develop speech and few if any wean from continuous to sleep-only tracheostomy ventilatory support. Indeed, almost invariably in England and France, the infants with severe SMA1 who would require continuous support before 5 months of age die rather than receive CNVS or undergo tracheotomy. However, the medications and other treatments in the pipeline today can only benefit the living.

Chest. 2017;151(5):969-970. doi:10.1016/j.chest.2016.11.040

Dr Bach and I agree on the need for ventilatory support and airway clearance for infants with SMA1. He has demonstrated success with his noninvasive approach, although his recommendations for some of the applied pressures used for ventilation and cough clearance seem both arbitrary and excessive. The pressures applied at the airway opening to achieve adequate tidal volumes for ventilation or inspiratory capacities for cough clearance must overcome the elastance of the lungs and chest wall, as well as the resistance of the extrathoracic and intrathoracic airways. The chest wall of infants and young children with neuromuscular disease is more compliant (has a lower elastance) than the chest wall of age-matched children, whereas lung compliance is similar. Passive inflation of the respiratory system in healthy infants with 30 cm H2O pressure at the airway opening results in a lung volume that approximates total lung capacity. There is no reason to assume a priori that airways resistance should be elevated in infants and children with SMA compared with healthy children; thus, ample volumes and flows for airway clearance can be achieved at lower pressures than Dr Bach recommends, even when applied through pediatric tracheostomy tubes. When delivering ventilatory support through a bilevel generator with a passive expiratory valve, expiratory pressure of 3 to 4 cm H2O is required to guarantee expiratory flow to wash out circuit dead space and prevent CO2 rebreathing. Inspiratory pressure should be applied to achieve adequate chest rise and to eliminate thoraco-abdominal paradox. This outcome is usually achieved by creating a difference between inspiratory and expiratory pressure of at least 10 cm H2O. Limiting positive pressure to the amount necessary to achieve these goals enhances patient comfort and can limit untoward side effects of noninvasive ventilation and airway clearance therapies.

Original Research: Diffuse Lung Disease

Chest. 2017;151(5):971-981. doi:10.1016/j.chest.2016.10.061

Background  Despite Food and Drug Administration approval of 2 new drugs for idiopathic pulmonary fibrosis (IPF), curative therapies remain elusive and mortality remains high. Preclinical and clinical data support the safety of human mesenchymal stem cells as a potential novel therapy for this fatal condition. The Allogeneic Human Cells (hMSC) in patients with Idiopathic Pulmonary Fibrosis via Intravenous Delivery (AETHER) trial was the first study designed to evaluate the safety of a single infusion of bone marrow–derived mesenchymal stem cells in patients with idiopathic pulmonary fibrosis.

Methods  Nine patients with mild to moderate IPF were sequentially assigned to 1 of 3 cohorts and dosed with a single IV infusion of 20, 100, or 200 × 106 human bone marrow–derived mesenchymal stem cells per infusion from young, unrelated, men. All baseline patient data were reviewed by a multidisciplinary study team to ensure accurate diagnosis. The primary end point was the incidence (at week 4 postinfusion) of treatment-emergent serious adverse events, defined as the composite of death, nonfatal pulmonary embolism, stroke, hospitalization for worsening dyspnea, and clinically significant laboratory test abnormalities. Safety was assessed until week 60 and additionally 28 days thereafter. Secondary efficacy end points were exploratory and measured disease progression.

Results  No treatment-emergent serious adverse events were reported. Two nontreatment-related deaths occurred because of progression of IPF (disease worsening and/or acute exacerbation). By 60 weeks postinfusion, there was a 3.0% mean decline in % predicted FVC and 5.4% mean decline in % predicted diffusing capacity of the lungs for carbon monoxide.

Conclusions  Data from this trial support the safety of a single infusion of human mesenchymal stem cells in patients with mild-moderate IPF.

Trial Registry  ClinicalTrials.gov; No.: NCT02013700; URL: www.clinicaltrials.gov.

Original Research: Bronchiectasis

Chest. 2017;151(5):982-992. doi:10.1016/j.chest.2016.10.055

Objectives  We sought to describe the characteristics of adult patients with bronchiectasis enrolled in the US Bronchiectasis Research Registry (BRR).

Methods  The BRR is a database of patients with non-cystic-fibrosis bronchiectasis (NCFB) enrolled at 13 sites in the United States. Baseline demographic, spirometric, imaging, microbiological, and therapeutic data were entered into a central Internet-based database. Patients were subsequently analyzed by the presence of NTM.

Results  We enrolled 1,826 patients between 2008 and 2014. Patients were predominantly women (79%), white (89%), and never smokers (60%), with a mean age of 64 ± 14 years. Sixty-three percent of the patients had a history of NTM disease or NTM isolated at baseline evaluation for entry into the BRR. Patients with NTM were older, predominantly women, and had bronchiectasis diagnosed at a later age than those without NTM. Gastroesophageal reflux disease (GERD) was more common in those with NTM, whereas asthma, primary immunodeficiency, and primary ciliary dyskinesia were more common in those without NTM. Fifty-one percent of patients had spirometric evidence of airflow obstruction. Patients with NTM were more likely to have diffusely dilated airways and tree-in-bud abnormalities. Pseudomonas and Staphylococcus aureus isolates were cultured less commonly in patients with NTM. Bronchial hygiene measures were used more often in those with NTM, whereas antibiotics used for exacerbations, rotating oral antibiotics, steroid use, and inhaled bronchodilators were more commonly used in those without NTM.

Conclusions  Adult patients with bronchiectasis enrolled in the US BRR are described, with differences noted in demographic, radiographic, microbiological, and treatment variables based on stratification of the presence of NTM.

Topics: bronchiectasis
Chest. 2017;151(5):993-1001. doi:10.1016/j.chest.2016.09.015

Background  Digital high-speed video microscopy (DHSV) allows analysis of ciliary beat frequency (CBF) and ciliary beat pattern (CBP) of respiratory cilia in three planes. Normal reference data use a sideways edge to evaluate ciliary dyskinesia and calculate CBF using the time needed for a cilium to complete 10 beat cycles. Variability in CBF within the respiratory epithelium has been described, but data concerning variation of CBP is limited in healthy epithelium. This study aimed to document variability of CBP in normal samples, to compare ciliary function in three profiles, and to compare CBF calculated over five or 10 beat cycles.

Methods  Nasal brushing samples from 13 healthy subjects were recorded using DHSV in three profiles. CBP and CBF over a 10-beat cycle were evaluated in all profiles, and CBF was reevaluated over five-beat cycles in the sideways edges.

Results  A uniform CBP was seen in 82.1% of edges. In the sideways profile, uniformity within the edge was lower (uniform normal CBP, 69.1% [sideways profile]; 97.1% [toward the observer], 92.0% [from above]), and dyskinesia was higher. Interobserver agreement for dyskinesia was poor. CBF was not different between profiles (P = .8097) or between 10 and five beat cycles (P = .1126).

Conclusions  Our study demonstrates a lack of uniformity and consistency in manual CBP analysis of samples from healthy subjects, emphasizing the risk of automated CBP analysis in limited regions of interest and of single and limited manual CBP analysis. The toward the observer and from above profiles may be used to calculate CBF but may be less sensitive for evaluation of ciliary dyskinesia and CBP. CBF can be measured reliably by evaluation of only five-beat cycles.

Original Research: Critical Care

Chest. 2017;151(5):1002-1010. doi:10.1016/j.chest.2017.02.017

Background  Corticosteroid administration before elective extubation has been used to prevent postextubation stridor and reintubation. We updated a systematic review to identify which patients would benefit from prophylactic corticosteroid administration before elective extubation.

Methods  We searched PubMed, EMBASE, the Wanfang Database, the China Academic Journal Network Publishing Database, and the Cochrane Central Register of Controlled Trials for eligible trials from inception through February 29, 2016. All randomized controlled trials were eligible if they examined the efficacy and safety of systemic corticosteroids given prior to elective extubation in mechanically ventilated adults. We pooled data using the DerSimonian and Laird random-effects model.

Results  We identified 11 trials involving 2,472 participants for analysis. Use of prophylactic corticosteroids was associated with a reduced incidence of postextubation airway events (risk ratio [RR], 0.43; 95% CI, 0.29-0.66) and reintubation (RR, 0.42; 95% CI, 0.25-0.71) compared with placebo or no treatment. This association was prominent in participants at high risk for the development of postextubation airway complications, defined using the cuff-leak test, with a reduced incidence of postextubation airway events (RR, 0.34; 95% CI, 0.24-0.48) and reintubation (RR, 0.35; 95% CI, 0.20-0.64). This association was not found in trials with unselected participants. Adverse events were rare.

Conclusions  Administration of prophylactic corticosteroids before elective extubation was associated with significant reductions in the incidence of postextubation airway events and reintubation, with few adverse events. It is reasonable to select patients at high risk for airway obstruction who may benefit from prophylactic corticosteroids.

Chest. 2017;151(5):1011-1017. doi:10.1016/j.chest.2017.02.008

Background  The rates of central line-associated bloodstream infections (CLABSIs) in U.S. ICUs have decreased significantly, and a parallel reduction in the rates of total hospital-onset bacteremias in these units should also be expected. We report 10-year trends for total hospital-onset ICU-associated bacteremias at a tertiary-care academic medical center.

Methods  This was a retrospective analysis of all positive-result blood cultures among patients admitted to seven adult ICUs for fiscal year 2005 (FY2005) through FY2014 according to Centers for Disease Control and Prevention National Healthcare Safety Network definitions. The rate of change for primary and secondary hospital-onset BSIs was determined, as was the distribution of organisms responsible for these BSIs. Data from three medical, two general surgical, one combined neurosurgical/trauma, and one cardiac/cardiac surgery adult ICU were analyzed.

Results  Across all ICUs, the rates of primary BSIs progressively fell from 2.11/1,000 patient days in FY2005 to 0.32/1,000 patient days in FY2014; an 85.0% decrease (P < .0001). Secondary BSIs also progressively decreased from 3.56/1,000 to 0.66/1,000 patient days; an 81.4% decrease (P < .0001). The decrease in BSI rates remained significant after controlling for the number of blood cultures obtained and patient acuity.

Conclusions  An increased focus on reducing hospital-onset infections at the academic medical center since 2005, including multimodal multidisciplinary efforts to prevent central line-associated BSIs, pneumonia, Clostridium difficile disease, surgical site infections, and urinary tract infections, was associated with progressive and sustained decreases for both primary and secondary hospital-onset BSIs.

Original Research: COPD

Chest. 2017;151(5):1018-1027. doi:10.1016/j.chest.2016.12.006

Background  Sarcopenia and osteoporosis are systemic features of COPD. The present study investigated the association between sarcopenia and osteopenia/osteoporosis and the factors associated with low bone mineral density (BMD) in men with COPD.

Methods  Data from 777 men with COPD who underwent both pulmonary function test and dual-energy x-ray absorptiometry were extracted from the Korean National Health and Nutritional Examination Survey database between 2008 and 2011. Sarcopenia was assessed with the appendicular skeletal mass index (ASMI) and osteopenia/osteoporosis with the T-score.

Results  As the severity of airflow limitation increased, the prevalence of sarcopenia increased (Ptrend < .001). Additionally, as the degree of sarcopenia became severe, the prevalence of osteopenia/osteoporosis increased (Ptrend < .001), and a significant positive correlation was noted between appendicular skeletal muscle mass and BMD (ASMI/T-score: r = 0.408; P < .001). Sarcopenia was independently associated with an increased risk of low BMD in men with COPD (OR, 2.31; 95% CI, 1.53-3.46; P < .001). Old age and low fat mass were significantly associated with low BMD in both sarcopenic and non-sarcopenic participants. High serum hemoglobin and insulin levels were associated with a reduced risk of low BMD only in the sarcopenic participants, whereas exercise and dietary intake were associated with a reduced risk only in the non-sarcopenic participants.

Conclusions  Sarcopenia is closely correlated with osteopenia/osteoporosis in men with COPD. Moreover, different factors are associated with low BMD according to the presence/absence of sarcopenia in that population.

Chest. 2017;151(5):1028-1038. doi:10.1016/j.chest.2016.12.021

Background  Resident loved ones of patients with COPD can play an important role in helping these patients engage in physical activity. We aimed to compare activity levels and exercise motivation between patients with COPD and their resident loved ones; to compare the same outcome measures in patients after stratification for the physical activity level of the loved ones; and to predict the likelihood of being physically active in patients with a physically active resident loved one.

Methods  One hundred twenty-five patient/loved one dyads were cross-sectionally and simultaneously assessed. Sedentary behavior, light activities, and moderate to vigorous physical activity (MVPA) were measured with a triaxial accelerometer during free-living conditions for at least 5 days. Five exercise-motivation constructs were investigated: amotivation, external regulation, introjected regulation, identified regulation, and intrinsic regulation.

Results  Patients spent more time in sedentary behavior and less time in physical activity than their loved ones (P < .0001). More intrinsic regulation was observed in loved ones compared with patients (P = .003), with no differences in other constructs. Despite similar exercise motivation, patients with an active loved one spent more time in MVPA (mean 31 min/d; 95% CI, 24-38 min/d vs mean, 18 min/d; 95% CI, 14-22 min/d; P = .002) and had a higher likelihood of being active (OR, 4.36; 95% CI, 1.41-13.30; P = .01) than did patients with an inactive loved one after controlling for age, BMI, and degree of airflow limitation.

Conclusions  Patients with COPD are more physically inactive and sedentary than their loved ones, despite relatively similar exercise motivation. Nevertheless, patients with an active loved one are more active themselves and have a higher likelihood of being active.

Trial Registry  Dutch Trial Register (NTR3941).

Chest. 2017;151(5):1039-1050. doi:10.1016/j.chest.2016.11.033

Background  COPD is associated with reduced physical capacity. However, it is unclear whether pulmonary emphysema, which can occur without COPD, is associated with reduced physical activity in daily life, particularly among people without COPD and never smokers. We hypothesized that greater percentage of emphysema-like lung on CT scan is associated with reduced physical activity assessed by actigraphy and self-report.

Methods  The Multi-Ethnic Study of Atherosclerosis (MESA) enrolled participants free of clinical cardiovascular disease from the general population. Percent emphysema was defined as percentage of voxels < −950 Hounsfield units on full-lung CT scans. Physical activity was measured by wrist actigraphy over 7 days and a questionnaire. Multivariable linear regression was used to adjust for age, sex, race/ethnicity, height, weight, education, smoking, pack-years, and lung function.

Results  Among 1,435 participants with actigraphy and lung measures, 47% had never smoked, and 8% had COPD. Percent emphysema was associated with lower activity levels on actigraphy (P = .001), corresponding to 1.5 hour less per week of moderately paced walking for the average participant in quintile 2 vs 4 of percent emphysema. This association was significant among participants without COPD (P = .004) and among ever (P = .01) and never smokers (P = .03). It was also independent of coronary artery calcium and left ventricular ejection fraction. There was no evidence that percent emphysema was associated with self-reported activity levels.

Conclusions  Percent emphysema was associated with decreased physical activity in daily life objectively assessed by actigraphy in the general population, among participants without COPD, and nonsmokers.

Original Research: Tobacco Cessation and Prevention

Chest. 2017;151(5):1051-1057. doi:10.1016/j.chest.2017.02.006

Background  Despite accumulating evidence about its adverse health effects, water-pipe tobacco smoking has become very popular among youth. The aim of this study was to compare smoke exposure and the kinetics of exhaled carbon monoxide (eCO) between water-pipe and cigarette smokers under different conditions.

Methods  Using a cross-over study design, changes in eCO and urinary cotinine levels were measured in a cohort of 32 healthy university students after sessions of water-pipe smoking indoors and outdoors. An indoor cigarette smoking session with equal amounts of tobacco was conducted for reference purposes. Both active and passive smokers participated in all sessions.

Results  In indoor sessions, we found that among active participants, eCO levels were approximately 7.5-fold higher in water-pipe users than cigarette smokers. eCO levels remained significantly elevated even 10 h after discontinuing water-pipe smoking. Notably, eCO levels in passive water-pipe smokers were in the same range as in active cigarette smokers. Compared with indoor sessions, eCO levels in active water-pipe users were reduced in outdoor environments. Nonetheless, levels were still higher in these subjects than those in active cigarette smokers measured in indoor sessions. Urinary cotinine levels were comparable in active water-pipe and cigarette smokers.

Conclusions  Our results suggest that water-pipe smoking is associated with significantly higher toxicant exposure than cigarette smoking even in outdoor environments. Furthermore, even passive, indoor water-pipe smoke exposure may have significant health hazards compared with those of active cigarette smoking.

Original Research: Pulmonary Vascular Disease

Chest. 2017;151(5):1058-1068. doi:10.1016/j.chest.2016.11.030

Background  We aimed to determine the frequency and predictors of exercise limitation after pulmonary embolism (PE) and to assess its association with health-related quality of life (HRQoL) and dyspnea.

Methods  One hundred patients with acute PE were recruited at five Canadian hospitals from 2010 to 2013. Cardiopulmonary exercise testing (CPET) was performed at 1 and 12 months. Quality of life (QoL), dyspnea, 6-min walk distance (6MWD), residual clot burden (perfusion scan, CT pulmonary angiography), cardiac function (echocardiography), and pulmonary function tests (PFTs) were measured during follow-up. The prespecified primary outcome was percent predicted peak oxygen uptake (Vo2 peak) < 80% at 1-year CPET.

Results  At 1 year, 40 of 86 patients (46.5%) had percent predicted Vo2 peak < 80% on CPET, which was associated with significantly worse generic health-related QoL (HRQoL), PE-specific HRQoL and dyspnea scores, and significantly reduced 6MWD at 1 year. Predictors of the primary outcome included male sex (relative risk [RR], 3.2; 95% CI, 1.3-8.1), age (RR, 0.98; 95% CI, 0.96-0.99 per 1-year age increase), BMI (RR 1.1; 95% CI, 1.01-1.2 per 1 kg/m2 BMI increase), and smoking history (RR, 1.8; 95% CI, 1.1-2.9), as well as percent predicted Vo2 peak < 80% on CPET at 1 month (RR, 3.8; 95% CI,1.9-7.2), and 6MWD at 1 month (RR, 0.82; 95% CI, 0.7-0.9 per 30-m increased walking distance). Baseline or residual clot burden was not associated with the primary outcome. Mean PFT and echocardiographic results (pulmonary artery pressure, right and left ventricular systolic function) at 1 year were similarly within normal limits in both patients with exercise limitations and those without such limitations.

Conclusions  Almost half of patients with PE have exercise limitation at 1 year that adversely influences HRQoL, dyspnea, and walking distance. CPET or 6MWD testing at 1 month may help to identify patients with a higher risk of exercise limitation at 1 year after PE. Based on our results, we believe that the deconditioning that occurs after acute PE could underlie this exercise limitation, but we cannot exclude the fact that this may have been present before PE.

Trial Registry  ClinicalTrials.gov; No.: NCT01174628; URL: www.clinicaltrials.gov.

Original Research: Chest Infections

Chest. 2017;151(5):1069-1080. doi:10.1016/j.chest.2016.11.012

Background  Influenza causes excessive hospitalizations and deaths. The study assessed the efficacy and safety of a clarithromycin-naproxen-oseltamivir combination for treatment of serious influenza.

Methods  From February to April 2015, we conducted a prospective open-label, randomized, controlled trial. Adult patients hospitalized for A(H3N2) influenza were randomly assigned to a 2-day combination of clarithromycin 500 mg, naproxen 200 mg, and oseltamivir 75 mg twice daily, followed by 3 days of oseltamivir or to oseltamivir 75 mg twice daily without placebo for 5 days as a control method (1:1). The primary end point was 30-day mortality. The secondary end points were 90-day mortality, serial nasopharyngeal aspirate (NPA) virus titer, percentage of neuraminidase-inhibitor-resistant A(H3N2) virus (NIRV) quasispecies, pneumonia severity index (PSI), and duration of hospital stay.

Results  Among the 217 patients with influenza A(H3N2) enrolled, 107 were randomly assigned to the combination treatment. The median age was 80 years, and 53.5% were men. Adverse events were uncommon. Ten patients died during the 30-day follow-up. The combination treatment was associated with lower 30-day mortality (P = .01), less frequent high dependency unit admission (P = .009), and shorter hospital stay (P < .0001). The virus titer and PSI (days 1-3; P < .01) and the NPA specimens with NIRV quasispecies ≥ 5% (days 1-2; P < .01) were significantly lower in the combination treatment group. Multivariate analysis showed that combination treatment was the only independent factor associated with lower 30-day mortality (OR, 0.06; 95% CI, 0.004-0.94; P = .04).

Conclusions  Combination treatment reduced both 30- and 90-day mortality and length of hospital stay. Further study of the antiviral and immunomodulatory effects of this combination treatment of severe influenza is warranted.

Trial Registry  BioMed Central; No.: ISRCTN11273879 DOI 10.1186/ISRCTN11273879; URL: www.isrctn.com/ISRCTN11273879

Original Research: Palliative Care and End of Life/Ethics

Chest. 2017;151(5):1081-1087. doi:10.1016/j.chest.2016.12.003

Background  For optimal end-of-life decision-making, it is important to understand the stability of patients’ treatment preferences. The aim of this paper is to examine the stability of willingness to accept life-sustaining treatments during 1-year follow-up in Dutch patients with advanced chronic organ failure. In addition, we want to explore the association between willingness to accept high-burden treatment and preferences for CPR and mechanical ventilation (MV).

Methods  In this multicenter longitudinal study, 265 clinically stable outpatients with advanced COPD (Global Initiative for Chronic Obstructive Lung Disease stage III/IV [n = 105]), chronic heart failure (New York Heart Association class III/IV [n = 80]), or chronic renal failure (requiring dialysis [n = 80) were visited at baseline and at 4, 8, and 12 months to assess the stability of life-sustaining treatment preferences using the Willingness to Accept Life-sustaining Treatment instrument.

Results  Two hundred six patients completed 1-year follow-up (mean age, 67.2 years [SD, 13.1 years]; 64.1% men). Overall, proportions of patients who were willing to accept life-sustaining treatment during 1 year did not change over time. However, individual trajectories showed that about two-thirds of patients changed their preferences at least once during a year. Moreover, there was no association found between the stability of willingness to undergo high-burden therapy and the stability of preferences for CPR and MV.

Conclusions  The current findings show the complexity of preferences for end-of-life care and indicate once again that advance care planning is a continuous process between patients and physicians, in which preferences for specific situations are discussed and that needs to be regularly reevaluated to deliver high-quality end-of-life care.

Clinical Trial registration  Netherlands National Trial Register (NTR 1552).

Original Research: Pulmonary Physiology

Chest. 2017;151(5):1088-1098. doi:10.1016/j.chest.2016.12.017

Background  Recommendations on interpreting tests of bronchodilator responsiveness (BDR) are conflicting. We investigated the dependence of BDR criteria on sex, age, height, ethnicity, and severity of respiratory impairment.

Methods  BDR test data were available from clinical patients in the Netherlands, New Zealand, and the United States (n = 15,278; female subjects, 51.7%) and from surveys in Canada, Norway, and five Latin-American countries (n = 16,250; female subjects, 54.7%). BDR calculated according to FEV1, FVC, and FEV1/FVC was expressed as absolute change, a percentage of the baseline level (% baseline), a percentage of the predicted value (% predicted), and z score.

Results  Change (Δ) in FEV1 and FVC, in milliliters, was unrelated to the baseline value but was biased toward age, height, sex, and level of airways obstruction; ΔFEV1 was significantly lower in African Americans. In 1,106 subjects with low FEV1 (200-1,621 mL) the FEV1 increased by 12% to 44.7% relative to baseline but < 200 mL. Expressing BDR as a percentage of the predicted value or as a z score attenuated the bias and made the 200-mL criterion redundant, but reduced positive responses by half. ΔFEV1 % baseline increased with the level of airflow obstruction but decreased with severe obstruction when expressed as z scores or % predicted; ΔFVC, however expressed, increased with the level of airflow obstruction.

Conclusions  Expressing FEV1 responsiveness as % baseline spuriously suggests that responsiveness increases with the severity of respiratory impairment. Expressing change in FEV1 or FVC as % predicted or as z scores eliminates this artifact and renders the required 200-mL minimum increase redundant. In severe airways obstruction ΔFVC should be critically evaluated as an index of clinically important relief of hyperinflation, with implications for bronchodilator drug trials.

Original Research: Disorders of the Pleura

Chest. 2017;151(5):1099-1105. doi:10.1016/j.chest.2016.12.014

Background  Pleural effusion secondary to a nonmalignant cause can represent significant morbidity and mortality. Nonmalignant pleural effusion (NMPE) is common, with congestive heart failure representing the leading cause. Despite this, there are limited data on mortality risk and associated prognostic factors.

Methods  We recruited 782 consecutive patients presenting to a pleural service between March 2008 and March 2015 with an undiagnosed pleural effusion. Further analysis was conducted in 356 patients with NMPE. Pleural biochemical analysis, cytologic analysis, thoracic ultrasonography, and chest radiography were performed. Echocardiography, CT imaging, radiologically guided biopsy, and medical thoracoscopy were undertaken as clinically indicated. Patients were followed for a minimum duration of 12 months, with the final diagnosis decided through independent review by two respiratory consultants.

Results  Of the 782 patients, 356 were diagnosed with NMPE (46%). These patients had a mean age of 68 years (SD, 17 years) with 69% of them being men. Patients with cardiac, renal, and hepatic failure had 1-year mortality rates of 50%, 46%, and 25%, respectively. Bilateral effusions (hazard ratio [HR], 3.55; 95% CI, 2.22-5.68) and transudative effusions (HR, 2.78; 95% CI, 1.81-4.28) were associated with a worse prognosis in patients with NMPE, with a 57% and 43% 1-year mortality rate, respectively.

Conclusions  This is the largest prospectively collected series in patients with NMPE, demonstrating that cases secondary to organ dysfunction have extremely high 1-year mortality. In addition, the presence of bilateral and transudative effusions is an indicator of increased mortality. Clinicians should be aware of these poor prognostic features and guide management accordingly.

Original Research: Practice Management and Administration

Chest. 2017;151(5):1106-1113. doi:10.1016/j.chest.2016.11.035

Background  Capillary refill time (CRT) is a clinical test used to evaluate the circulatory status of patients; various methods are available to assess CRT. Conventional clinical research often demands large numbers of patients, making it costly, labor-intensive, and time-consuming. We studied the interobserver agreement on CRT in a nationwide study by using a novel method of research called flash mob research (FMR).

Methods  Physicians in the Netherlands were recruited by using word-of-mouth referrals, conventional media, and social media to participate in a nationwide, single-day, “nine-to-five,” multicenter, cross-sectional, observational study to evaluate CRT. Patients aged ≥ 18 years presenting to the ED or who were hospitalized were eligible for inclusion. CRT was measured independently (by two investigators) at the patient’s sternum and distal phalanx after application of pressure for 5 s (5s) and 15 s (15s).

Results  On October 29, 2014, a total of 458 investigators in 38 Dutch hospitals enrolled 1,734 patients. The mean CRT measured at the distal phalanx were 2.3 s (5s, SD 1.1) and 2.4 s (15s, SD 1.3). The mean CRT measured at the sternum was 2.6 s (5s, SD 1.1) and 2.7 s (15s, SD 1.1). Interobserver agreement was higher for the distal phalanx (κ value, 0.40) than for the sternum (κ value, 0.30).

Conclusions  Interobserver agreement on CRT is, at best, moderate. CRT measured at the distal phalanx yielded higher interobserver agreement compared with sternal CRT measurements. FMR proved a valuable instrument to investigate a relatively simple clinical question in an inexpensive, quick, and reliable manner.

Evidence-Based Medicine

Chest. 2017;151(5):1114-1121. doi:10.1016/j.chest.2017.01.024

Interventional pulmonology (IP) is a rapidly evolving subspecialty of pulmonary medicine. In the last 10 years, formal IP fellowships have increased substantially in number from five to now > 30. The vast majority of IP fellowship trainees are selected through the National Resident Matching Program, and validated in-service and certification examinations for IP exist. Practice standards and training guidelines for IP fellowship programs have been published; however, considerable variability in the environment, curriculum, and experience offered by the various fellowship programs remains, and there is currently no formal accreditation process in place to standardize IP fellowship training. Recognizing the need for more uniform training across the various fellowship programs, a multisociety accreditation committee was formed with the intent to establish common accreditation standards for all IP fellowship programs in the United States. This article provides a summary of those standards and can serve as an accreditation template for training programs and their offices of graduate medical education as they move through the accreditation process.

Translating Basic Research Into Clinical Practice

Chest. 2017;151(5):1122-1130. doi:10.1016/j.chest.2016.10.038

Inflammation is a hallmark of many airway diseases. Improved understanding of the cellular and molecular mechanisms of airway disease will facilitate the transition in our understanding from phenotypes to endotypes, thereby improving our ability to target treatments based on pathophysiologic characteristics. For example, allergic asthma has long been considered to be driven by an allergen-specific T helper 2 response. However, clinical and mechanistic studies have begun to shed light on the role of other cell subsets in the pathogenesis and regulation of lung inflammation. In this review, we discuss the importance of different lymphocyte subsets to asthma and other airway diseases, while highlighting the growing evidence that asthma is a syndrome that incorporates many immune phenotypes.

Recent Advances in Chest Medicine

Chest. 2017;151(5):1131-1140. doi:10.1016/j.chest.2016.06.019

This review addresses common questions regarding the role of surgical lung biopsy (SLB) in the diagnosis and treatment of interstitial lung disease (ILD). We specifically address when a SLB can be diagnostic as well as when it may be avoided; for example, when the combination of the clinical context and the imaging pattern seen on high-resolution CT (HRCT) chest scans can provide a confident diagnosis. Existing studies on the diagnostic utility as well as the complications associated with SLB are reviewed; also reviewed are the performance characteristics and reliability of HRCT scans of the chest in predicting the underlying histopathologic findings of the lung. The review is formatted in the form of answers to questions that clinicians regularly ask when considering an SLB in a patient with ILD.

Chest. 2017;151(5):1141-1146. doi:10.1016/j.chest.2016.06.018

Neuroendocrine tumors (NETs) are a rare, heterogeneous group of malignancies that arise from neuroendocrine cells throughout the body, with the lungs and GI tract being the most common sites of origin. Despite increasing incidence, awareness of lung NETs remains low among thoracic specialists who are often involved in the assessment and early treatment of these patients. Successful treatment requires accurate and timely diagnosis; however, classification can be challenging, particularly for well-differentiated and intermediate-differentiated lung NET types (typical carcinoids [TC] and atypical carcinoids [AC]). Diagnosis and management of lung NETs are further complicated by the nonspecificity of symptoms, variable natural history, and lack of high-level clinical evidence; a multidisciplinary approach is required, which has been shown to improve prognosis. Currently, surgery remains the only curative option for TC/AC. Inconsistencies between guideline recommendations for systemic therapies, especially for chemotherapy, result in a lack of consensus on a standardized treatment for unresectable disease. Recent data from the Phase III RAD001 in Advanced Neuroendocrine Tumors, Fourth Trial (RADIANT-4), which contained a large population of patients with advanced, well-differentiated, nonfunctional lung NETs in addition to those with GI NETs, found a reduced risk of disease progression and death with everolimus compared with placebo, leading to US approval of everolimus in these patient populations. This study is the first high-level therapeutic evidence in patients with TC/AC, and everolimus is currently the only agent approved for treatment of TC/AC. Increased awareness, prompt diagnosis, and additional adequately powered controlled clinical trials of patients with well-differentiated and intermediate-differentiated lung NETs are needed to further improve evidence-based care.

Special Features

Chest. 2017;151(5):1147-1155. doi:10.1016/j.chest.2016.11.009

Cystic fibrosis (CF) is a life-shortening autosomal recessive disorder caused by mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR). CFTR is an anion channel that conducts bicarbonate and chloride across cell membranes. Although defective anion transport across epithelial cells is accepted as the basic defect in CF, many of the features observed in people with CF and organs affected by CF are modulated by the nervous system. This is of interest because CFTR expression has been reported in both the peripheral and central nervous systems, and it is well known that the transport of anions, such as chloride, greatly modulates neuronal excitability. Thus it is predicted that in CF, lack of CFTR in the nervous system affects neuronal function. Consistent with this prediction, several nervous system abnormalities and nervous system disorders have been described in people with CF and in animal models of CF. The goal of this special feature article is to highlight the expression and function of CFTR in the nervous system. Special emphasis is placed on nervous system abnormalities described in people with CF and in animal models of CF. Finally, features of CF that may be modulated by or attributed to faulty nervous system function are discussed.

Contemporary Reviews in Sleep Medicine

Chest. 2017;151(5):1156-1172. doi:10.1016/j.chest.2016.12.007

Throughout the industrialized world, nearly one in five employees works some form of nontraditional shift. Such shift work is associated with numerous negative health consequences, ranging from cognitive complaints to cancer, as well as diminished quality of life. Furthermore, a substantial percentage of shift workers develop shift work disorder, a circadian rhythm sleep disorder characterized by excessive sleepiness, insomnia, or both as a result of shift work. In addition to adverse health consequences and diminished quality of life at the individual level, shift work disorder incurs significant costs to employers through diminished workplace performance and increased accidents and errors. Nonetheless, shift work will remain a vital component of the modern economy. This article reviews seminal and recent literature regarding shift work, with an eye toward real-world application in clinical and organizational settings.

CME Resource Center

Chest. 2017;151(5):1173-1174. doi:10.1016/j.chest.2017.03.017

As seen in this CME online activity (available at http://courses.elseviercme.com/chest16/647e), idiopathic pulmonary fibrosis (IPF) is a specific form of chronic progressive fibrotic lung disease of unknown cause. It is the most common form of idiopathic interstitial pneumonia in adults. Its prevalence among US Medicare beneficiaries has more than doubled in the past 14 years. With the approval of two agents that reduce functional decline and disease progression, and the 2015 update of the American Thoracic Society guidelines on the treatment of IPF, the options for appropriate clinical management of the disease have become well defined. Early diagnosis and early initiation of treatment are of critical importance for long-term clinical outcomes. The diagnostic process, which may require a multidisciplinary team of experts, is centered on excluding systemic diseases and exposures and identifying a pattern of usual interstitial pneumonia on high-resolution CT or surgical lung biopsy results. Familiarity with the 2015 American Thoracic Society guidelines is critical with respect to both the treatments that the guidelines recommend and those that they advise against. Standard immunosuppressive therapy is no longer indicated, whereas pirfenidone, nintedanib, and antacid therapy are all conditionally recommended for use. Individualizing treatment is important in light of potential improved adherence to both drug therapy and health behaviors. An early referral to an interstitial lung disease center offers the advantages of comprehensive diagnostic and disease-management expertise, potential enrollment in a clinical trial, and evaluation for transplantation.


Chest. 2017;151(5):1175. doi:10.1016/j.chest.2016.11.008

    Worse than the nose-pinching dose
    of cod-liver oil, it smelled
    of horse sweat, hot and rank.

    I hear my mother's dance,
    to keep its heat from the oven,
    down the long chilly hall.

    Her high heels on polished wood
    tapped all the way to the back room
    where I shook under extra skins of wool.

    She opened my pink pajamas
    for the yellowy paste
    wrapped in my brother's diaper.

    Watching the clock, I burned,
    yelling at the end, my chest cooked
    scarlet as a chop.

    The phlegm easing from my lungs,
    my mother began to hum
    a music I still hear

    standing over her uneasy bed.

Chest. 2017;151(5):1176. doi:10.1016/j.chest.2016.12.018

    I rest my hand on
    brown grooves
    painted by the rays of sunlight
    upon your own

    I assure you that we will
    scroll sideways and up and down through
    the silvery shades of your chest,
    divine the reason why you are
    walking less and less and
    breathing as though you no longer trust
    the strength of your broad weathered shoulders

    The next morning flecks of golden dawn
    dance and climb through
    half-shut hospital doors and
    yellowed windows

    Your chart is gone,
    no heart rates and blood pressures
    scribbled across perfect boxes
    that help us believe that we
    mold the contours of
    the day, the night

    They tell me
    your lungs were filled with
    cells so deadly
    they had lost their identity, and
    your heart stopped
    beating its mythical beat

    The memory of you,
    the first patient I (dare I say) loved
    and lost
    rests in a space that I have created
    for only you,
    and someone like you,
    a face, a slight gesture
    is revisited in the quiet
    by every healer
    who was disarmed
    by their first encounter with
    a new type of loss.


Chest. 2017;151(5):1177-1178. doi:10.1016/j.chest.2016.12.035

We read with great interest the review about ICU care before and after lung transplantation (LTx) by Fuehner et al. The authors suggest irreversible extrapulmonary organ failure, septic shock, severe arterial occlusive disease, and not being previously listed as specific contraindications for bridge to transplantation (BTT) with extracorporeal life support (ECLS).

Chest. 2017;151(5):1178-1179. doi:10.1016/j.chest.2017.02.026

We thank Dr Trudzinski and colleagues for their comments regarding extracorporeal life support (ECLS) in lung transplantation (LTx) and their interest in our review recently published in CHEST (August 2016). Contrasting the opinion that ECLS need alone will strengthen the argument for transplantation, we strongly urge clear appraisal of the facts.

Chest. 2017;151(5):1179-1180. doi:10.1016/j.chest.2017.01.039

The new American College of Chest Physicians/American Thoracic Society guidelines on ventilator weaning/extubation,, fail to take into account well-proven principles of diagnostic testing and basic pulmonary physiology. I invite the committee's response to four points.

  • 1.

    The committee states “weaning predictors…lack sufficient positive and negative predictive value to make them routinely useful.” The assertion is unreferenced. The previous guidelines reached the same conclusion based on a meta-analysis that contained 15 major methodological errors. No error has been defended. Members of the previous committee were contacted repeatedly by the Editor in Chief of Critical Care Medicine but refused to respond. The committee chair merely repeated assertions. On what data does the committee base its assertion?

Chest. 2017;151(5):1180-1181. doi:10.1016/j.chest.2017.02.027

Regarding Dr Tobin’s first point, he correctly notes that we did not reference our statement “Moreover, weaning predictors such as maximal inspiratory pressure, static respiratory system compliance, and rapid/shallow breathing index lack sufficient positive and negative predictive value to make them routinely useful for judging patients’ ability to wean.” We do so now in the work by Meade et al. In support of our statement, we also reference a study in which Conti et al evaluated nine weaning parameters prospectively. Likelihood ratios for all weaning parameters ranged from 0.61 to 1.87, indicating only small, clinically unimportant changes in the posttest probability of success or failure. The authors applied Bayes’ theorem and concluded that all indexes were of little use in discriminating those who could be successfully weaned and those who would fail extubation. Consistent with our guideline, they concluded “…the systematic use of these weaning predictors is thus of little use clinically.”

Chest. 2017;151(5):1181-1182. doi:10.1016/j.chest.2016.12.031

I read with extreme interest the recent article by Houben et al entitled, “Instability of Willingness to Accept Life-Sustaining Treatments of Patients With Advanced Chronic Organ Failure During 1 Year” published in this issue of CHEST (May 2017). The authors’ findings certainly echo the complexity of end-of-life (EOL) preferences but also raise a less obvious but equally important factor that affects EOL preferences—and that is race.

Chest. 2017;151(5):1182-1183. doi:10.1016/j.chest.2017.01.014

We thank Dr Chertoff for his letter to the editor in response to our manuscript entitled “Instability of Willingness to Accept Life-Sustaining Treatments of Patients with Advanced Chronic Organ Failure During 1 Year.” Chertoff’s main worry is about the racial breakdown of our study. More specifically, he wants to know how this racial breakdown affected our results and whether our findings are applicable to larger countries with significant racial diversity.

Chest. 2017;151(5):1183-1184. doi:10.1016/j.chest.2017.02.030

We read with interest the article by Rush et al published in the January issue of CHEST. In an analysis of the National Inpatient Sample, the authors showed that palliative care (PC) referrals in patients with COPD who are receiving home oxygen increased from 0.45% in 2006 to 2.56% in 2012. The authors also note that there were significant racial disparities, with whites more likely to be referred for PC. We commend the authors on a well-performed analysis on this important topic.

Chest. 2017;151(5):1184. doi:10.1016/j.chest.2017.02.029

We read the letter by Yaqoob et al with great interest and found their confirmatory analysis to be enlightening. We applaud them for this important confirmatory work demonstrating an increase in hospice deaths for end-stage COPD. The higher rates of hospice use for white patients compared with African Americans also confirms our findings of differential access rates to palliative care (PC) for minorities. Our hope is that this combined work will increase awareness of the benefits that PC can have on this patient population. Future studies need to be undertaken to demonstrate the benefit of PC referral in reducing hospitalizations and improving patient quality of life.

Chest. 2017;151(5):1184-1185. doi:10.1016/j.chest.2017.02.023

We read with interest the article “Treatment of ARDS With Prone Positioning” wherein the authors summarize the physiological principles, clinical evidence, and practical application of prone position ventilation in ARDS. Prone positioning entails an increased risk of complications, including pressure sores, endotracheal tube displacement, loss of venous access, and others. Girard et al compared the incidence and severity of pressure ulcers in the participants of the Proning Severe ARDS Patients (PROSEVA) trial and highlighted the need for active prevention of pressure sores in patients who are put in a prone position. At the time of placing a patient with ARDS in the prone position, a few important precautions should be taken, which are essential to minimize the hazards of prone positioning.

Chest. 2017;151(5):1185-1186. doi:10.1016/j.chest.2017.02.022

We thank Dr Baldi et al for their correspondence regarding our clinical overview of prone positioning in ARDS. Experienced centers treating ARDS with prone positioning and complementary lung-protective strategies can achieve significant reductions in mortality., However, in the modern era, prone positioning is likely still underused in patients with severe ARDS. Baldi et al’s practical and helpful safety mnemonic, in addition to online video resources, will be helpful for lower-volume centers looking to increase implementation of prone positioning.

Chest. 2017;151(5):1186. doi:10.1016/j.chest.2016.10.032

A substantial body of research suggests that the development of cancer is also influenced by the host immune system, underlying the importance of immunologic biomarkers in predicting prognosis and response to therapy.,, Thus, incorporating the immune score as a prognostic factor and introducing it into routine diagnostic assessment is indicated. The urgent need to agree to a standard laboratory protocol is underlined by the inherent complexity of quantitative immunohistochemistry, in conjunction with other variable factors—for example, the types of immune cells analyzed, regional selection criteria, and differences in quantifying immune infiltration. We read with great interest the paper by Wolin, in which the author highlights a marked correlation between tumor prognosis, histologic grade, and disease stage. In strict compliance with World Health Organization criteria, we analyzed 45 surgical specimens (29 lung, 12 midgut, four pancreas) of well-differentiated (grade 1) neuroendocrine carcinoid tumors. We found that a “brisk” tumor lymphocytic infiltrate correlates with a good prognosis, being the expression of an immunologic reaction to the neoplastic cells. Conversely, a “nonbrisk” or absent infiltrate represents a form of immune tolerance to the tumor, favoring its metastatic spread., The quantitative immune score can thus be considered a prognostic indicator to complement histologic grade in cases of carcinoid tumors. Everolimus is currently the only agent approved for their treatment. We would strongly advocate in the not to distant future the adoption of a modulated therapeutic approach in which the immune score is an integral part of the diagnostic protocol.

Chest. 2017;151(5):1187-1188. doi:10.1016/j.chest.2016.12.016

We applaud the recent updates to the ninth edition of the American College of Chest Physicians on antithrombotic therapy. Their 2012 recommendation to use weight-based unfractionated heparin (UFH) was a remarkable advance in tailored heparin therapy. Because of the lack of definitive evidence, the ninth edition and the recent update are silent on how to address weight-based UFH in the presence of obesity. We published our limited experience with the use of average-weight methodology in patients with acute coronary syndrome previously. In this brief report, we add to that body of knowledge our experience with patients undergoing catheter ablation for atrial fibrillation (AF).

Chest. 2017;151(5):1188-1189. doi:10.1016/j.chest.2016.12.019

Diffusing capacity of the lung for carbon monoxide (Dlco) is an important test for diagnosis, monitoring of disease progression, and response to therapy. The 2005 American Thoracic Society/European Respiratory Society Standardization of Lung Function Testing Task Force recommended that Dlco adjustments for hemoglobin and carboxyhemoglobin (COHb) “should always be made to ensure appropriate interpretation.” We conducted a study to examine the impact of Dlco adjustment on the interpretation of individual Dlco test results in a general population.

Chest. 2017;151(5):1189-1192. doi:10.1016/j.chest.2017.01.043

Parenteral prostacyclin analogues (PPAs) are potent medications for the treatment of advanced forms of pulmonary arterial hypertension.,, The Food and Drug Administration approved PPAs, including IV epoprostenol and IV or subcutaneous treprostinil, which are both dosed based on weight (ng/kg/min). Given the narrow therapeutic range of PPAs, variations in weight may have important consequences on the adjusted dose of these medications. Current guidelines do not elaborate on how to manage the dosing of PPAs in the setting of pronounced weight variations. We hypothesize that weight changes after the initiation of PPAs may be pronounced in certain patients with pulmonary hypertension (PH), resulting in prominent differences in PPA dosing.

Chest. 2017;151(5):1192-1194. doi:10.1016/j.chest.2017.01.028

Acute exacerbations of COPD (AECOPD) are of major importance with respect to prolonged detrimental effects on patients, accelerated disease progression, and high health-care costs., Among patients hospitalized for AECOPD, 20% and 35% require rehospitalization within 30 and 90 days, respectively., These hospitalizations increase patient mortality and morbidity and the economic burden of COPD., Although reduction of early readmissions has become a policy target in many developed countries, little is known regarding standards that can be applied to the timing and nature of discharge.

Chest. 2017;151(5):1194-1196. doi:10.1016/j.chest.2017.02.014

Intubation ultrasonography is used to localize an endotracheal tube in the trachea or esophagus.,,, We have developed phantoms that simulate the ultrasound appearance of esophageal and tracheal intubations.


Chest. 2017;151(5):1197. doi:10.1016/j.chest.2017.03.025

The author has reported to CHEST that there was an oversight in not addressing potential conflict of interest in “POINT: Should Radiation Dose From CT Scans Be a Factor in Patient Care? Yes.” (Chest. 2015;147(4):872-874.) Although the author did not receive any compensation for any of his academic work on his publications, he served as a consultant for attorneys in litigation and testified a year after the publications were released. (Donovan v. Philip Morris (PM) Civil Action No. 06-12234-DJC).

Chest. 2017;151(5):1197. doi:10.1016/j.chest.2017.03.026

The author has reported to CHEST that there was an oversight in not addressing potential conflict of interest in “Rebuttal From Dr McCunney.” (Chest. 2015;147(4):877-878.) Although the author did not receive any compensation for any of his academic work on his publications, he served as a consultant for attorneys in litigation and testified a year after the publications were released. (Donovan v. Philip Morris (PM) Civil Action No. 06-12234-DJC).

Chest. 2017;151(5):1197. doi:10.1016/j.chest.2017.03.027

The author Dr McCunney has reported to CHEST that there was an oversight in not addressing potential conflict of interest in Radiation Risks in Lung Cancer Screening Programs: A Comparison With Nuclear Industry Workers and Atomic Bomb Surviviors.” (Chest. 2014;145(3):618-624.) Although the author did not receive any compensation for any of his academic work on his publications, he served as a consultant for attorneys in litigation and testified a year after the publications were released. (Donovan v. Philip Morris (PM) Civil Action No. 06-12234-DJC).

Ultrasound Corner

Chest. 2017;151(5):e99-e102. doi:10.1016/j.chest.2016.09.049

A 76-year-old man with a 75 pack-year history of smoking presented to the pulmonary clinic for evaluation of a right upper lobe 1.4-cm spiculated peripheral pulmonary nodule that was incidentally detected on CT of the chest (Fig 1). PET-CT of the nodule prior to presentation showed avidity at the nodule with a standardized uptake value of 1.55 but no evidence of other metastatic foci.

Chest. 2017;151(5):e103-e105. doi:10.1016/j.chest.2016.11.062

A man in his 60s presented to an outside hospital with worsening shortness of breath over the preceding 6 months. He was hospitalized with atrial fibrillation with rapid ventricular response, and he experienced cardiac arrest requiring defibrillation and multiple doses of epinephrine. His vital signs on transfer to our ICU were temperature, 36.3°C; heart rate, 50 beats per minute; and BP, 90/50 mm Hg on 20 μg/min on norepinephrine. His ventilator settings were volume control rate of 16; tidal volume of 360 mL, positive end-expiratory pressure of 5, and Fio2 of 1.0. On physical examination he was sedated, with a 2/6 systolic murmur and decreased S1/S2 heart sounds. Pitting edema was present in all extremities, and his skin was cool to the touch. His laboratory examinations were remarkable for a WBC count of 14.7 × 103/μL, creatine level of 2.8 mg/dL, aspartate aminotransferase level of 7,000 units/L, international normalized ratio of 5.7, and lactate level of 8 mmol/L. His chest radiograph demonstrated multifocal opacities and bilateral pleural effusions. CT of the chest and abdomen showed abdominal ascites. Multiorgan failure quickly developed, including anuric renal failure, severe hypoxemia with Pao2/Fio2 ratio of 125, coagulopathy, worsening hyperlactatemia, and refractory hypotension despite maximal doses of norepinephrine and vasopressin. Broad-spectrum antibiotics and steroids were given empirically.

Chest Imaging and Pathology for Clinicians

Chest. 2017;151(5):e107-e113. doi:10.1016/j.chest.2017.01.029

A 61-year-old woman presented for outpatient evaluation of a 1-week history of fever and upper respiratory symptoms. She denied tobacco use, weight loss, hemoptysis, chronic cough, or recent travel and was in otherwise good health. Her medical history was insignificant except for her chronic hoarseness from a prior laryngeal disease. She denied any worsening hoarseness or any other vocal changes. She did report a positive family history of squamous cell lung cancer in her father.

Pulmonary, Critical Care, and Sleep Pearls

Chest. 2017;151(5):e115-e118. doi:10.1016/j.chest.2016.10.048

A woman in her 30s presented to the ED with a 3-month history of shortness of breath on exertion, dry cough, and pleuritic chest pain. A month ago, the patient was seen at an internal medicine clinic and was found to have a right pleural effusion. A thoracentesis revealed straw-colored fluid, a total nucleated cell count of 1,260 × 106/L, and a differential with neutrophils of 0.15, lymphocytes of 0.55, macrophages/monocytes of 0.19, and eosinophils of 0.10. Fluid cytology and culture were negative. The patient was presumed to have a parapneumonic effusion and treated empirically with antibiotics. However, she continued to have progressive symptoms, prompting her current visit to the ED. The patient was diagnosed with stage IIIB invasive cervical squamous cell carcinoma (SCC) approximately 7 months ago. MRI of the pelvis demonstrated a cervical mass with invasion of the right parametrial fat, but there was no evidence of uterine, vaginal, or lymph node involvement. A CT scan of the chest, abdomen, and pelvis was negative for distant metastases. The patient completed treatment with external beam radiation therapy and cisplatin chemotherapy 6 months ago. Three weeks prior to presentation to the ED, a repeat MRI pelvis showed no evidence of tumor progression and features consistent with posttreatment fibrotic changes.

Chest. 2017;151(5):e119-e122. doi:10.1016/j.chest.2016.10.049

A 33-year-old woman of Latin American origin was referred to our department by her primary care physician for a left lower lobe mass, which was incidentally found on a CT scan of her abdomen. The patient had complaints of abdominal pain for which she underwent imaging of her abdomen. Review of systems was negative for any respiratory complaints, and she denied any history of cigarette smoking or recreational drug use.

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    Print ISSN: 0012-3692
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