Current Issue


Chest. 2015;148(2):297-298. doi:10.1378/chest.15-0786

In this issue of CHEST (see page 313), readers will find one of those increasingly rare essays on the principles of pathophysiology of chronic lung diseases, in this case, asthma and COPD.1 What is probably even more remarkable though is the fact that the article is largely based on a 1967 paper from the Journal of Applied Physiology2 whose senior author is also senior author of the current commentary—chapeau Prof Jay Nadel!

Chest. 2015;148(2):298-300. doi:10.1378/chest.14-2582

Hydraulic fracturing, or fracking, involves injecting large amounts of sand, water, and chemicals deep underground at high pressures to extract natural gas from rock formations. At the same time, fracking also generates by-products, such as dust, silica, and other gases. While some groups consider fracking to represent a health risk,1 others suggest that fracking poses little risk to the public.2 To date, most studies have measured emissions from the wells and estimated exposure and its health impact based on the distance from the wells,3,4 but none have addressed potential health effects associated with specific elements impacted by fracking.

Chest. 2015;148(2):300-301. doi:10.1378/chest.15-0506

The interactions among pepsin, acid, and mucosal injury have been a subject of interest since studies in the 1960s implicated pepsin as a major determinant of reflux injury at low pH.1 In its enzymatically active form, pepsin is the primary proteolytic enzyme of the digestive tract and key to the pathogenesis of “peptic” esophagitis in gastroesophageal reflux disease (GERD). Synthesized primarily by chief cells of the gastric fundus as the zymogen pepsinogen, pepsin requires an acidic environment before it can be converted to its active form. Its pH activity curve peaks at pH 2, falls off rapidly above pH 4.5, and is negligible above pH 5.5.2 As a biomarker for reflux, it is easily detected and uniformly found in gastric refluxate.3 Consequently, the presence of pepsin in the oropharynx or the tracheobronchial tree is indicative of regurgitation with or without aspiration. However, its presence in and of itself does not establish a causal relationship to epithelial damage and/or symptom generation from supraesophageal reflux. There must be a mechanism for activation as well. One such proposed mechanism in patients who are thought to have proton pump inhibitor-refractory supraesophageal GERD pathology is that inactive (but not denatured) pepsin is sufficiently reactivated by subsequent weakly acidic refluxate to cause laryngeal mucosal injury. Evidence substantiating that hypothesis is the demonstration of pepsin-induced depletion of laryngeal protective proteins (carbonic anhydrase isoenzyme III and squamous epithelial stress protein) in patients with laryngopharyngeal reflux.4-6

Chest. 2015;148(2):301-303. doi:10.1378/chest.15-0551

“See one, do one, teach one.” For many physicians, this was how we were expected to learn. Similar to no longer working unlimited hours, things have changed. Procedures are more complex now with the addition of more techniques, such as endobronchial ultrasound and other navigational tools, than were available even 5 years ago. In this issue of CHEST (see page 321), Ernst et al1 are tasked with a very difficult problem: How, or is it even possible, to determine competency of trainees in bronchoscopy?

Topics: bronchoscopes
Chest. 2015;148(2):303-305. doi:10.1378/chest.15-1269

Point and Counterpoint

Chest. 2015;148(2):306-308. doi:10.1378/chest.15-0477

One of the things that has challenged sleep medicine is the debate about which diagnostic study to use for the diagnosis of OSA. It is as if there was only one strategy possible that is appropriate for all patients. Diagnosis is, however, only one part, and indeed a relatively small part, of the total strategy for care.

Chest. 2015;148(2):308-310. doi:10.1378/chest.15-0479

It has been almost 7 years since the Centers for Medicare and Medicaid Services approved home sleep testing (HST) for the diagnosis of OSA in adults. Since the initial approval of HST, there have been several peer-reviewed studies validating many different portable diagnostic devices as well as numerous randomized controlled trials demonstrating similar outcomes when comparing an ambulatory approach that incorporates HST to a management strategy utilizing polysomnography (PSG) for diagnosis and determination of appropriate CPAP therapy.1-7 Yet, despite advancements in technology and a growing body of outcome data supporting the use of HST in appropriate patient populations, many clinicians have not willingly adopted HST as part of a standard strategy for the diagnosis and management of OSA.

Chest. 2015;148(2):310-311. doi:10.1378/chest.15-0478

Dr Freedman1 has accurately and effectively described the basis of the switch to use of home testing in the United States. I agree that for subjects with high pretest probabilities of OSA without other major issues, home testing is appropriate provided that subsequent management of therapy is by trained providers.

Chest. 2015;148(2):311-312. doi:10.1378/chest.15-0480

Dr Pack1 makes several excellent points, and unlike most pro-con debates, I tend to agree with most of his arguments. I would summarize and respond to his comments as follows.


Chest. 2015;148(2):313-320. doi:10.1378/chest.14-2483

Investigators believe most patients with asthma have reversible airflow obstruction with treatment, despite airway remodeling and hyperresponsiveness. There are smokers with chronic expiratory airflow obstruction despite treatment who have features of both asthma and COPD. Some investigators refer to this conundrum as the asthma-COPD overlap syndrome (ACOS). Furthermore, a subset of treated nonsmokers with moderate to severe asthma have persistent expiratory airflow limitation, despite partial reversibility. This residuum has been assumed to be due to large and especially small airway remodeling. Alternatively, we and others have described reversible loss of lung elastic recoil in acute and persistent loss in patients with moderate to severe chronic asthma who never smoked and its adverse effect on maximal expiratory airflow. The mechanism(s) responsible for loss of lung elastic recoil and persistent expiratory airflow limitation in nonsmokers with chronic asthma consistent with ACOS remain unknown in the absence of structure-function studies. Recently we reported a new pathophysiologic observation in 10 treated never smokers with asthma with persistent expiratory airflow obstruction, despite partial reversibility: All 10 patients with asthma had a significant decrease in lung elastic recoil, and unsuspected, microscopic mild centrilobular emphysema was noted in all three autopsies obtained although it was not easily identified on lung CT scan. These sentinel pathophysiologic observations need to be confirmed to further unravel the epiphenomenon of ACOS. The proinflammatory and proteolytic mechanism(s) leading to lung tissue breakdown need to be further investigated.

Evidence-Based Medicine

Chest. 2015;148(2):321-332. doi:10.1378/chest.14-0678

BACKGROUND:  The determination of competency of trainees in programs performing bronchoscopy is quite variable. Some programs provide didactic lectures with hands-on supervision, other programs incorporate advanced simulation centers, whereas others have a checklist approach. Although no single method has been proven best, the variability alone suggests that outcomes are variable. Program directors and certifying bodies need guidance to create standards for training programs. Little well-developed literature on the topic exists.

METHODS:  To provide credible and trustworthy guidance, rigorous methodology has been applied to create this bronchoscopy consensus training statement. All panelists were vetted and approved by the CHEST Guidelines Oversight Committee. Each topic group drafted questions in a PICO (population, intervention, comparator, outcome) format. MEDLINE data through PubMed and the Cochrane Library were systematically searched. Manual searches also supplemented the searches. All gathered references were screened for consideration based on inclusion criteria, and all statements were designated as an Ungraded Consensus-Based Statement.

RESULTS:  We suggest that professional societies move from a volume-based certification system to skill acquisition and knowledge-based competency assessment for trainees. Bronchoscopy training programs should incorporate multiple tools, including simulation. We suggest that ongoing quality and process improvement systems be introduced and that certifying agencies move from a volume-based certification system to skill acquisition and knowledge-based competency assessment for trainees. We also suggest that assessment of skill maintenance and improvement in practice be evaluated regularly with ongoing quality and process improvement systems after initial skill acquisition.

CONCLUSIONS:  The current methods used for bronchoscopy competency in training programs are variable. We suggest that professional societies and certifying agencies move from a volume- based certification system to a standardized skill acquisition and knowledge-based competency assessment for pulmonary and thoracic surgery trainees.

Original Research: Critical Care

Chest. 2015;148(2):333-339. doi:10.1378/chest.14-1967

BACKGROUND:  Gastroesophageal reflux (GER) and pulmonary aspiration are frequent in patients in the ICU. The presence of pepsin in airways seems to be the link between them. However, pepsin isoforms A (gastric specific) and C (pneumocyte potentially derived) need to be distinguished. This study aimed to evaluate GER patterns and to determine the presence of pepsin A and C in tracheal secretions of critically ill children receiving mechanical ventilation.

METHODS:  All patients underwent combined multichannel intraluminal impedance-pH (MII-pH) monitoring. Tracheal secretion samples were collected to determine the presence of pepsin. Pepsin A and C were evaluated by Western blot. MII-pH parameters analyzed were number of total GER episodes (NGER); acid, weakly acidic, and weakly alkaline GER episodes; and proximal and distal GER episodes.

RESULTS:  Thirty-four patients (median age, 4 months; range, 1-174 months) were included. MII-pH monitoring detected 2,172 GER episodes (77.0% were weakly acidic; 71.7% were proximal). The median NGER episodes per patient was 59.5 (25th-75th percentile, 20.3-85.3). Weakly acidic GER episodes per patient were significantly more frequent than acid GER episodes per patient (median [25th-75th percentile], 43.5 [20.3-68.3] vs 1.0 [0-13.8], respectively; P < .001). Only three patients had an altered acid reflux index (44.9%, 12.7%, and 13.6%) while not taking antacid drugs. Pepsin A was found in 100% of samples and pepsin C in 76.5%.

CONCLUSIONS:  The majority of GER episodes of children in the ICU were proximal and weakly acidic. All patients had aspiration of gastric contents as detected by pepsin A in tracheal fluid. A specific pepsin assay should be performed to establish gastropulmonary aspiration because pepsin C was found in > 70% of samples.

Chest. 2015;148(2):340-355. doi:10.1378/chest.14-3169

BACKGROUND:  Mechanical ventilation is a cornerstone in the management of acute respiratory failure. Both volume-targeted and pressure-targeted ventilations are used, the latter modes being increasingly used. We provide a narrative review of the physiologic principles of these two types of breath delivery, performed a literature search, and analyzed published comparisons between modes.

METHODS:  We performed a systematic review and meta-analysis to determine whether pressure control-continuous mandatory ventilation (PC-CMV) or pressure control-inverse ratio ventilation (PC-IRV) has demonstrated advantages over volume control-continuous mandatory ventilation (VC-CMV). The Cochrane tool for risk of bias was used for methodologic quality. We also introduced physiologic criteria as quality indicators for selecting the studies. Outcomes included compliance, gas exchange, hemodynamics, work of breathing, and clinical outcomes. Analyses were completed with RevMan5 using random effects models.

RESULTS:  Thirty-four studies met inclusion criteria, many being at high risk of bias. Comparisons of PC-CMV/PC-IRV and VC-CMV did not show any difference for compliance or gas exchange, even when looking at PC-IRV. Calculating the oxygenation index suggested a poorer effect for PC-IRV. There was no difference between modes in terms of hemodynamics, work of breathing, or clinical outcomes.

CONCLUSIONS:  The two modes have different working principles but clinical available data do not suggest any difference in the outcomes. We included all identified trials, enhancing generalizability, and attempted to include only sufficient quality physiologic studies. However, included trials were small and varied considerably in quality. These data should help to open the choice of ventilation of patients with acute respiratory failure.

Chest. 2015;148(2):356-364. doi:10.1378/chest.14-1139

BACKGROUND:  Surfactant has been shown to be dysfunctional in ARDS, and exogenous surfactant has proven effective in many forms of neonatal and pediatric acute lung injury (ALI). In view of the positive results of our studies in children along with evidence that surfactant-associated protein B containing pharmaceutical surfactants might be more effective, we designed a multiinstitutional, randomized, controlled, and masked trial of calfactant, a calf lung surfactant, in adults and children with ALI/ARDS due to direct lung injury.

METHODS:  Adult subjects within 48 h of initiation of mechanical ventilation for direct ARDS were randomized to receive up to three interventions with instilled calfactant vs air placebo. The primary outcome was 90-day all-cause mortality.

RESULTS:  Three hundred seventeen subjects were enrolled, 308 of whom could be evaluated. There were no significant baseline differences between groups. Calfactant administration was not associated with improved survival, lengths of stay, or oxygenation. Calfactant instillation was frequently associated with transient hypoxia and hypotension. The study was stopped at the first interim analysis at the sponsor’s request.

CONCLUSIONS:  Administration of calfactant was not associated with improved oxygenation or longer-term benefits relative to placebo in this randomized, controlled, and masked trial. At present, exogenous surfactant cannot be recommended for routine clinical use in ARDS.

TRIAL REGISTRY:  ClinicalTrials.gov; No.: NCT00682500; URL: www.clinicaltrials.gov.

Chest. 2015;148(2):365-374. doi:10.1378/chest.14-2476

BACKGROUND:  There are few data regarding mechanical ventilation and ARDS in the ED. This could be a vital arena for prevention and treatment.

METHODS:  This study was a multicenter, observational, prospective, cohort study aimed at analyzing ventilation practices in the ED. The primary outcome was the incidence of ARDS after admission. Multivariable logistic regression was used to determine the predictors of ARDS.

RESULTS:  We analyzed 219 patients receiving mechanical ventilation to assess ED ventilation practices. Median tidal volume was 7.6 mL/kg predicted body weight (PBW) (interquartile range, 6.9-8.9), with a range of 4.3 to 12.2 mL/kg PBW. Lung-protective ventilation was used in 122 patients (55.7%). The incidence of ARDS after admission from the ED was 14.7%, with a mean onset of 2.3 days. Progression to ARDS was associated with higher illness severity and intubation in the prehospital environment or transferring facility. Of the 15 patients with ARDS in the ED (6.8%), lung-protective ventilation was used in seven (46.7%). Patients who progressed to ARDS experienced greater duration in organ failure and ICU length of stay and higher mortality.

CONCLUSIONS:  Lung-protective ventilation is infrequent in patients receiving mechanical ventilation in the ED, regardless of ARDS status. Progression to ARDS is common after admission, occurs early, and worsens outcome. Patient- and treatment-related factors present in the ED are associated with ARDS. Given the limited treatment options for ARDS, and the early onset after admission from the ED, measures to prevent onset and to mitigate severity should be instituted in the ED.

TRIAL REGISTRY:  ClinicalTrials.gov; No.: NCT01628523; URL: www.clinicaltrials.gov

Original Research: COPD

Chest. 2015;148(2):375-381. doi:10.1378/chest.14-1453

BACKGROUND:  The high frequency of readmissions in patients with COPD remains a significant problem. The impact of a pulmonologist follow-up visit during the month after discharge from hospital because of COPD exacerbation on reducing readmissions was examined. A profile of patients who did not attend the follow-up visits was built.

METHODS:  Our population-based retrospective cohort study analyzed the data of all patients with COPD who were treated at a lung institute in an Israeli hospital and were hospitalized between January 1, 2004, and December 31, 2010. Multivariate logistic regression was used to characterize the patient who did not attend the follow-up visit and to examine the effect of lack of visit on rehospitalization within 90 days of discharge. Cox proportional hazards analysis was used to model the effect of lacking visit on additional hospitalization or death during the study period.

RESULTS:  Of the 195 patients enrolled in the study, 44.1% had follow-up visits with pulmonologists within 30 days of discharge. Not attending the follow-up visit was associated with distant residence, a higher number of hospitalizations in the previous year, a lack of a recommendation in the discharge letter for a follow-up visit, and a lower frequency of follow-up visits with pulmonologists in the previous year. Moreover, not attending the follow-up visit was associated with a significant increased risk of rehospitalization within 90 days of discharge (OR, 2.91; 95% CI, 1.06-8.01).

CONCLUSIONS:  Early follow-up visits with pulmonologists seem to reduce the exacerbation-related rehospitalization rates of patients with COPD. We recommend that patients have early postdischarge follow-up visits with pulmonologists.

Chest. 2015;148(2):382-388. doi:10.1378/chest.14-0520

BACKGROUND:  New markers of COPD and emphysema disease activity are urgently required since current measures of disease severity do not reflect the total disease burden nor predict disease progression. A recently described in vivo marker of neutrophil elastase activity (Aα-Val360) may be an effective marker of COPD and emphysema disease activity, and the current study explores its use in patients with α1-antitrypsin deficiency (AATD) across the disease severity spectrum with particular interest in whether it can be used as an early predictor of the need for intervention.

METHODS:  Cross-sectional and longitudinal relationships between Aα-Val360 and full lung-function tests, CT scan densitometry, and other biomarkers were explored in this study of a registry of untreated patients with PiZZ AATD.

RESULTS:  The Aα-Val360 related cross-sectionally to physiologic, radiologic, and symptomatic markers of disease severity though not disease progression. Similar cross-sectional relationships were observed in subjects with mild physiologic abnormalities; however, in this subgroup, baseline Aα-Val360 concentration did relate to subsequent disease progression.

CONCLUSIONS:  In cross-sectional studies, Aα-Val360 reflects disease severity in AATD and may be a useful marker of disease activity in patients with early disease in whom therapeutic intervention may be indicated.

Chest. 2015;148(2):389-396. doi:10.1378/chest.14-3091

BACKGROUND:  We previously observed that 30 months of inhaled corticosteroid (ICS) treatment can attenuate FEV1 decline in COPD, but it is unclear whether withdrawal induces a relapse. We hypothesized that FEV1 decline, airway hyperresponsiveness (AHR), and quality of life (QOL) deteriorate after ICS cessation even after prolonged use.

METHODS:  One hundred fourteen patients with moderate to severe COPD finished randomized 6-month or 30-month treatment with fluticasone (500 μg bid), 30-month treatment with fluticasone and salmeterol (500/50 μg bid), or placebo (first part of the Groningen and Leiden Universities Corticosteroids in Obstructive Lung Disease [GLUCOLD] study [GL1]). The subsequent 5 years, patients were prospectively followed annually, treated by their physician (GLUCOLD follow-up study [GL2]). Postbronchodilator FEV1, AHR, and QOL were initially recorded at baseline, at 30 months (GL1), and annually during GL2. Analysis was performed by linear mixed-effects models.

RESULTS:  Among 101 adherent patients during GL1, 79 patients started and 58 completed GL2. Patients using ICSs during GL1, but only using ICSs 0% to 50% of the time during GL2 (n = 56 of 79), had significantly accelerated annual FEV1 decline compared with GL1 (difference GL2-GL1 [95% CI]: 30-month treatment with fluticasone and salmeterol, −68 mL/y [−112 to −25], P = .002; 30-month treatment with fluticasone, −73 mL/y [−119 to −26], P = .002), accompanied by deterioration in AHR and QOL.

CONCLUSIONS:  ICS discontinuation after 30 months in COPD can worsen lung function decline, AHR, and QOL during 5-year follow-up. This suggests that ICS treatment lacks sustained disease-modifying effect after treatment cessation.

TRIAL REGISTRY:  ClinicalTrials.gov; No.: NCT00158847; URL: www.clinicaltrials.gov

Chest. 2015;148(2):397-407. doi:10.1378/chest.15-0084

BACKGROUND:  COPD guidelines recommend the combined use of inhaled long-acting β2-agonists (LABAs) and long-acting muscarinic antagonists (LAMAs) if symptoms are not improved by a single agent. This systematic review tested the hypothesis that the bronchodilator effect of the LABA/LAMA combination, umeclidinium (UMEC)/vilanterol (VIL), would translate into better outcomes without incurring increased adverse events (AEs).

METHODS:  This was a systematic review of randomized, placebo-controlled or crossover trials (> 4 weeks) involving UMEC/VIL compared with its monocomponents, tiotropium, or fluticasone/salmeterol. Primary outcomes were trough FEV1, serious adverse events (SAEs), and serious cardiovascular events (SCVEs).

RESULTS:  Eleven trials from 10 studies (9,609 patients) showed that UMEV/VIL provided superior improvements in lung function compared with UMEC, VIL, tiotropium, and fluticasone propionate/salmeterol (mean trough FEV1, 60, 110, 90, and 90 mL, respectively; P < .0001). Also, UMEC/VIL had a greater likelihood of demonstrating a minimal clinically important difference on the Transition Dyspnea Index compared with UMEC and VIL (number needed to treat for benefit [NNTB] = 14 and 10, respectively). UMEC/VIL therapy significantly reduced the risk of COPD exacerbations compared with UMEC and VIL (NNTB = 42 and 41, respectively). On the contrary, we noted no significant differences between UMEC/VIL and tiotropium with respect to dyspnea, health status, or risk of COPD exacerbation. Regarding safety issues, the incidence of AEs, SAEs, SCVEs, and mortality on treatment was similar across treatments, suggesting reduced safety concerns with the use of the UMEC/VIL combination.

CONCLUSIONS:  Once-daily inhaled UMEC/VIL showed superior efficacy compared with its monocomponents, tiotropium, and fluticasone/combination in patients with moderate to severe COPD.

Chest. 2015;148(2):408-416. doi:10.1378/chest.14-2240

BACKGROUND:  COPD includes the chronic bronchitis (CB) and emphysema phenotypes. Although it is generally assumed that emphysema or chronic airflow obstruction (CAO) is associated with worse quality of life (QOL) than is CB, this assumption has not been tested.

METHODS:  The current study’s analyses from the Lovelace Smokers’ Cohort (LSC) were validated in the COPD Gene Cohort (COPDGene). CB without CAO (CB only) was defined as self-reported cough productive of phlegm for ≥ 3 mo/y for 2 consecutive years and postbronchodilator FEV1/FVC ≥ 70%. CAO without CB (CAO only) was defined as a postbronchodilator FEV1/FVC < 70% with no evidence of CB. QOL outcomes were obtained from the St. George’s Respiratory Questionnaire (SGRQ) and the 36-Item Short Form Health Survey (SF-36) questionnaires. A priori covariates included age, sex, pack-years of smoking, current smoking, and FEV1.

RESULTS:  Smokers with CB without CAO (LSC = 341; COPDGene = 523) were younger and had a greater BMI and less smoking exposure than did those with CAO only (LSC = 302; COPDGene = 2,208). Compared with the latter group, QOL scores were worse for those with CB only. Despite similar SGRQ Activity and SF-36 Role Physical and Physical Functioning, SGRQ Symptoms and Impact scores and SF-36 emotional and social measures were worse in the CB-only group, in both cohorts. After adjustment for covariates, the CB-only group remained a significant predictor for “worse” symptoms and emotional and social measures.

CONCLUSIONS:  To our knowledge, this analysis is the first to suggest that among subjects with COPD, those with CB only present worse QOL symptoms and mental well-being than do those with CAO only.

Chest. 2015;148(2):417-429. doi:10.1378/chest.14-2168

BACKGROUND:  Music has been used as a distractive auditory stimulus (DAS) in patients with COPD, but its effects are unclear. This systematic review aimed to establish the effect of DAS on exercise capacity, symptoms, and health-related quality of life (HRQOL) under three conditions: (1) during exercise training, (2) during exercise testing, and (3) for symptom management at rest.

METHODS:  Randomized controlled or crossover trials as well as cohort studies of DAS during exercise training, during formal exercise testing, and for symptom management among individuals with COPD were identified from a search of seven databases. Two reviewers independently assessed study quality. Weighted mean differences (WMDs) with 95% CIs were calculated using a random-effects model.

RESULTS:  Thirteen studies (12 of which were randomized controlled or crossover trials) in 415 participants were included. DAS increased exercise capacity when applied over at least 2 months of exercise training (WMD, 98 m; 95% CI, 47-150 m). HRQOL improved only after a training duration of 3 months. Less dyspnea was noted with DAS during exercise training, but this was not consistently observed in short-term exercise testing or as a symptom management strategy at rest.

CONCLUSIONS:  DAS appears to reduce symptoms of dyspnea and fatigue when used during exercise training, with benefits observed in exercise capacity and HRQOL. When applied during exercise testing, the effects on exercise capacity and symptoms and as a strategy for symptom management at rest are inconsistent.

Chest. 2015;148(2):430-435. doi:10.1378/chest.14-2285

BACKGROUND:  Extracellular adenosine 5′-triphosphate (ATP) stimulates vagal C and Aδ fibers in the lung, resulting in pronounced bronchoconstriction and cough mediated by P2X2/3 receptors located on vagal sensory nerve terminals. We investigated the effects of nebulized ATP on cough and symptoms in control subjects, healthy smokers, and patients with COPD and compared these responses to the effects of inhaled adenosine, the metabolite of ATP.

METHODS:  We studied the effects of inhaled ATP and adenosine monophosphate (AMP) on airway caliber, perception of dyspnea assessed by the Borg score, cough sensitivity, and ATP in exhaled breath condensate in healthy nonsmokers (n = 10), healthy smokers (n = 14), and patients with COPD (n = 7).

RESULTS:  In comparison with healthy subjects, ATP induced more dyspnea, cough, and throat irritation in smokers and patients with COPD, and the effects of ATP were more pronounced than those of AMP. The concentration of ATP in the exhaled breath condensate of patients with COPD was elevated compared with that of healthy subjects.

CONCLUSIONS:  Smokers and patients with COPD manifest hypersensitivity to extracellular ATP, which may play a mechanistic role in COPD.

Original Research: Diffuse Lung Disease

Chest. 2015;148(2):436-443. doi:10.1378/chest.14-2746

BACKGROUND:  Acute exacerbation (AE) of idiopathic pulmonary fibrosis (IPF) presents as episodes of acute respiratory worsening closely associated with endothelial damage and disordered coagulopathy. Recombinant human soluble thrombomodulin (rhTM) regulates the coagulation pathway mainly by reducing thrombin-mediated clotting and enhancing protein C activation. We investigated the efficacy of rhTM for the treatment of patients with AE-IPF.

METHODS:  This historical control study comprised 40 patients with AE-IPF. Twenty patients treated with rhTM (0.06 mg/kg/d) for about 6 days (rhTM group) and 20 patients treated without rhTM (control group) were evaluated. The predictors of 3-month mortality (logistic regression model) were evaluated.

RESULTS:  There was no difference in baseline characteristics between the control group and the rhTM group. Three-month mortality of the rhTM group and control group was 30.0% and 65.0%, respectively. In univariate analysis, C-reactive protein and rhTM therapy were significant determinants for 3-month survival. In multivariate analysis, rhTM therapy (OR, 0.219; 95% CI, 0.049-0.978; P = 0.047) was an independent significant determinant for 3-month survival.

CONCLUSIONS:  We found that rhTM therapy improved 3-month survival of AE-IPF. The results observed here warrant further investigation of rhTM in randomized control trials.

Chest. 2015;148(2):444-449. doi:10.1378/chest.14-3095

BACKGROUND:  Lymphangioleiomyomatosis (LAM) is a manifestation of tuberous sclerosis complex (TSC) that causes destruction of the lung and chronic respiratory failure. Population-based estimates of demographics, clinical outcomes, and health-care utilization are lacking for TSC and LAM.

METHODS:  Data on demographics, clinical outcomes, and health-care utilization in the Quebec ministerial provincial health-care database were analyzed for their association with TSC and LAM.

RESULTS:  A total of 1,004 subjects with TSC were identified using International Classification of Diseases, Ninth and 10th Revisions, codes for a prevalence of one in 7,872 people. There were 38 subjects with LAM, nine of whom also had TSC. Mean ages as well as the mean age at death were lower in the LAM and TSC group than in the control group. Mortality rates were higher in subjects with LAM than in those with TSC or in control subjects. Subjects with LAM experienced more medical visits and hospitalizations than did those with TSC and control subjects; these were associated with higher health-care costs. Frequently prescribed drugs in TSC or LAM included anticonvulsants, antidepressants, and sedatives; the use of mammalian target of rapamycin inhibitors was uncommon.

CONCLUSIONS:  The prevalence of TSC in Quebec, Canada, is similar to estimates from previously published surveys. LAM is likely underreported, perhaps due to suboptimal case identification or referral. Health-care utilization and mortality for LAM are high, suggesting that timely diagnosis and therapy could be beneficial. Mental health disorders may be an unrecognized clinical feature of LAM. These results provide a population-based background for policymakers and researchers to better address the needs of patients with TSC and LAM.

Original Research: Pulmonary Procedures

Chest. 2015;148(2):450-471. doi:10.1378/chest.14-1530

BACKGROUND:  There are significant variations in how therapeutic bronchoscopy for malignant airway obstruction is performed. Relatively few studies have compared how these approaches affect the incidence of complications.

METHODS:  We used the American College of Chest Physicians (CHEST) Quality Improvement Registry, Evaluation, and Education (AQuIRE) program registry to conduct a multicenter study of patients undergoing therapeutic bronchoscopy for malignant central airway obstruction. The primary outcome was the incidence of complications. Secondary outcomes were incidence of bleeding, hypoxemia, respiratory failure, adverse events, escalation in level of care, and 30-day mortality.

RESULTS:  Fifteen centers performed 1,115 procedures on 947 patients. There were significant differences among centers in the type of anesthesia (moderate vs deep or general anesthesia, P < .001), use of rigid bronchoscopy (P < .001), type of ventilation (jet vs volume cycled, P < .001), and frequency of stent use (P < .001). The overall complication rate was 3.9%, but significant variation was found among centers (range, 0.9%-11.7%; P = .002). Risk factors for complications were urgent and emergent procedures, American Society of Anesthesiologists (ASA) score > 3, redo therapeutic bronchoscopy, and moderate sedation. The 30-day mortality was 14.8%; mortality varied among centers (range, 7.7%-20.2%, P = .02). Risk factors for 30-day mortality included Zubrod score > 1, ASA score > 3, intrinsic or mixed obstruction, and stent placement.

CONCLUSIONS:  Use of moderate sedation and stents varies significantly among centers. These factors are associated with increased complications and 30-day mortality, respectively.

Chest. 2015;148(2):472-480. doi:10.1378/chest.14-1907

BACKGROUND:  Specimens collected by CT scan-guided transthoracic core-needle biopsy (TTNB) are frequently used for the diagnosis of lung nodules, but the clinical value of negative results has not been sufficiently investigated. We sought to determine the negative predictive value (NPV) of TTNB specimens and investigate predictive factors of negative results.

METHODS:  All consecutive TTNBs performed in three centers between 2006 and 2012 were included. The medical charts of patients with nonmalignant TTNB specimens were reviewed and classified as true or false negatives. Binary logistic regression was used for multivariate analysis.

RESULTS:  Overall, findings from 980 TTNB specimens were included. Malignant disease was found in 79% (n = 777) of the cases, nonmalignant disease in 6% (n = 54), and “negative” results in 15% (n = 149). For the diagnosis of malignant disease, NPV was 51%. Estimated sensitivity, specificity, and accuracy were 89%, 99%, and 90%, respectively. The complication rate was 34% (life-threatening complication in 6%). In multivariate analysis, predictive factors for a false-negative result were radiologist experience (adjusted OR [AOR], 0.996; 95% CI, [0.994-0.998]), occurrence of a complication during the procedure (AOR, 1.958; 95% CI, [1.202-3.187]), and moderate to high maximum standardized uptake value on PET scan (AOR, 7.657; 95% CI, [1.737-33.763]). In 24 cases, a second TTNB was performed at the same target. The complication rate was 33%, and TTNB specimens provided diagnosis in 95% of cases with a 67% NPV.

CONCLUSIONS:  One-half of all “negative” TTNB specimen results were falsely negative for malignant diagnosis. Findings in tissue collected from a second TTNB at the same target provided a final diagnosis in most cases without increasing complication rates.

Original Research: Pulmonary Vascular Disease

Chest. 2015;148(2):481-490. doi:10.1378/chest.14-2169

BACKGROUND:  The dysregulation of microRNA (miRNA) is known to contribute to the pathobiology of pulmonary arterial hypertension (PAH). However, the relationships between changes in tissue and circulating miRNA levels associated with different animal models and human pulmonary hypertension (PH) have not been defined.

METHODS:  A set of miRNAs that have been causally implicated in PH, including miR-17, -21, -130b, -145, -204, -424, and -503, were measured by reverse transcription-quantitative polymerase chain reaction in the plasma, lung, and right ventricle of three of the most common rodent models of PH: the rat monocrotaline and SU5416 plus chronic hypoxia (SuHx) models and the mouse chronic hypoxia model. Plasma miRNA levels were also evaluated in a cohort of patients with PAH and healthy subjects.

RESULTS:  Several miRNA showed PH model-dependent perturbations in plasma and tissue levels; however, none of these were conserved across all three experimental models. Principle component analysis of miR expression changes in plasma revealed distinct clustering between rodent models, and SuHx-triggered PH showed the greatest similarity to human PAH. Changes in the plasma levels of several miRNA also correlated with changes in tissue expression. In particular, miR-424 was concordantly increased (1.3- to 1.5-fold, P < .05) in the plasma, lung, and right ventricle of hypoxic mice and in the plasma of patients with PAH.

CONCLUSIONS:  miRNAs with established etiologic roles in PH showed context-dependent changes in tissue and circulating levels, which were not consistent across rodent models and human PAH. This suggests different miRNA-dependent mechanisms may contribute to experimental and clinical PH, complicating potential diagnostic and therapeutic applications amenable to these miRNAs.

Original Research: Cardiovascular Disease

Chest. 2015;148(2):491-498. doi:10.1378/chest.14-3006

BACKGROUND:  Active smoking is associated with elevated thrombotic risk. Smoking status has recently been incorporated into the SAMe-TT2R2 (sex female, age < 60 years, medical history [more than two comorbidities], treatment [interacting drugs, eg, amiodarone for rhythm control], tobacco use [doubled], race [doubled]) score that can help predict poor international normalized ratio control in patients with atrial fibrillation (AF) treated with vitamin K antagonists (VKAs). The clinical benefit of antiplatelet therapy (APT) has been seen primarily in smokers. We hypothesized that active smoking may differently influence the risks of stroke and bleeding in patients with AF treated with VKAs or with APT.

METHODS:  We examined the clinical course of 7,809 consecutive patients with AF seen between 2000 and 2010. Outcomes in patients who were active smokers were compared with those in other patients.

RESULTS:  Among 7,809 patients with AF, 1,034 (13%) were active smokers. APT was prescribed on an individual basis for 2,761 patients (35%) and VKAs for 4,534 (57%). After a follow-up of 929 ± 1,082 days (median = 463 days, interquartile range = 1,564 days), smoking was not independently associated with a higher risk of stroke/thromboembolic event in patients with AF (hazard ratio [HR], 0.95; 95% CI, 0.78-1.22; P = .66). On multivariate analysis, smoking was independently associated with a worse prognosis for the risk of severe bleeding (HR, 1.23; 95% CI, 1.01-1.49; P = .04) and for the risk of major Bleeding Academic Research Consortium bleeding (HR, 1.40; 95% CI, 1.02-1.90; P = .03). Smoking was independently associated with a higher risk of bleeding in patients treated with VKAs (HR, 1.32; 95% CI, 1.04-1.67; P = .02), whereas the risk was nonsignificant in patients treated with APT (HR, 1.28; 95% CI, 0.94-1.74; P = .11).

CONCLUSIONS:  In AF, there was a higher risk of severe bleeding in smokers, mainly in those treated with VKAs.

Original Research: Chest Infections

Chest. 2015;148(2):499-506. doi:10.1378/chest.14-2764

BACKGROUND:  Bedaquiline is an oral antimycobacterial agent belonging to a new class of drugs called diarylquinolines. It has low equivalent minimal inhibitory concentrations for Mycobacterium tuberculosis and nontuberculous mycobacterial (NTM) lung disease, especially Mycobacterium avium complex (MAC) and Mycobacterium abscessus (Mab). Bedaquiline appears to be effective for the treatment of multidrug-resistant TB but has not been tested clinically for NTM disease.

METHODS:  We describe a case series of off-label use of bedaquiline for treatment failure lung disease caused by MAC or Mab. Only patients whose insurance would pay for the drug were included. Fifteen adult patients were selected, but only 10 (six MAC, four Mab) could obtain bedaquiline. The 10 patients had been treated for 1 to 8 years, and all were on treatment at the start of bedaquiline therapy. Eighty percent had macrolide-resistant isolates (eight of 10). The patients were treated with the same bedaquiline dosage as that used in TB trials and received the best available companion drugs (mean, 5.0 drugs). All patients completed 6 months of therapy and remain on bedaquiline.

RESULTS:  Common side effects included nausea (60%), arthralgias (40%), and anorexia and subjective fever (30%). No abnormal ECG findings were observed with a mean corrected QT interval lengthening of 2.4 milliseconds at 6 months. After 6 months of therapy, 60% of patients (six of 10) had a microbiologic response, with 50% (five of 10) having one or more negative cultures.

CONCLUSIONS:  This small preliminary report demonstrates potential clinical and microbiologic activity of bedaquiline in patients with advanced MAC or Mab lung disease but the findings require confirmation with larger studies.

Original Research: Genetic and Developmental Disorders

Chest. 2015;148(2):507-515. doi:10.1378/chest.14-1800

BACKGROUND:  Metabolomic evaluation of cystic fibrosis (CF) airway secretions could identify metabolites and metabolic pathways involved in neutrophilic airway inflammation that could serve as biomarkers and therapeutic targets.

METHODS:  Mass spectrometry (MS)-based metabolomics was performed on a discovery set of BAL fluid samples from 25 children with CF, and targeted MS methods were used to identify and quantify metabolites related to neutrophilic inflammation. A biomarker panel of these metabolites was then compared with neutrophil counts and clinical markers in independent validation sets of lavage from children with CF and adults with COPD compared with control subjects.

RESULTS:  Of the 7,791 individual peaks detected by positive-mode MS metabolomics discovery profiling, 338 were associated with neutrophilic inflammation. Targeted MS determined that many of these peaks were generated by metabolites from pathways related to the metabolism of purines, polyamines, proteins, and nicotinamide. Analysis of the independent validation sets verified that, in subjects with CF or COPD, several metabolites, particularly those from purine metabolism and protein catabolism pathways, were strongly correlated with neutrophil counts and were related to clinical markers, including airway infection and lung function.

CONCLUSIONS:  MS metabolomics identified multiple metabolic pathways associated with neutrophilic airway inflammation. These findings provide insight into disease pathophysiology and can serve as the basis for developing disease biomarkers and therapeutic interventions for airways diseases.

Original Research: Transplantation

Chest. 2015;148(2):516-522. doi:10.1378/chest.14-1948

BACKGROUND:  Limited data are available regarding the etiologic impact of health care-associated pneumonia (HCAP) in lung transplant recipients. Therefore, our aim was to evaluate the microbiologic differences between HCAP and hospital-acquired pneumonia (HAP)/ventilator-associated pneumonia (VAP) in lung transplant recipients with a radiographically confirmed diagnosis of pneumonia.

METHODS:  We performed a retrospective cohort study of lung transplant recipients with pneumonia at one transplant center over a 7-year period. Eligible patients included lung transplant recipients who developed a first episode of radiographically confirmed pneumonia ≥ 48 h following transplantation. HCAP, HAP, and VAP were classified according to the American Thoracic Society/Infectious Diseases Society of America 2005 guidelines. χ2 and Student t tests were used to compare categorical and continuous variables, respectively.

RESULTS:  Sixty-eight lung transplant recipients developed at least one episode of pneumonia. HCAP (n = 42; 62%) was most common, followed by HAP/VAP (n = 26; 38%) stratified in HAP (n = 20; 77%) and VAP (n = 6; 23%). Pseudomonas aeruginosa was the predominantly isolated organism (n = 22; 32%), whereas invasive aspergillosis was uncommon (< 10%). Multiple-drug resistant (MDR) pathogens were less frequently isolated in patients with HCAP compared with HAP/VAP (5% vs 27%; P = .009). Opportunistic pathogens were less frequently identified in lung transplant recipients with HCAP than in those with HAP/VAP (7% vs 27%; P = .02). Lung transplant recipients with HCAP had a similar mortality at 90 days (n = 9 [21%] vs n = 4 [15%]; P = .3) compared with patients with HAP/VAP.

CONCLUSIONS:  HCAP was the most frequent infection in lung transplant recipients. MDR pathogens and opportunistic pathogens were more frequently isolated in HAP/VAP. There were no differences in 30- and 90-day mortality between lung transplant recipients with HCAP and those with HAP/VAP.

Translating Basic Research Into Clinical Practice

Chest. 2015;148(2):523-532. doi:10.1378/chest.15-0484

Despite advances in antimicrobial chemotherapy and access to sophisticated intensive care facilities, bacterial community-acquired pneumonia (CAP) continues to carry an unacceptably high mortality rate of 10% to 15% in hospitalized cases. CAP, considered by many to be the most underestimated disease worldwide, poses a particular threat to the elderly whose numbers are steadily increasing in developed countries. Indeed, elderly patients with severe CAP, as well as those with other risk factors, are at significant risk for development of inflammation-mediated acute cardiac events that may undermine the success of antimicrobial therapy. Adjunctive antiinflammatory strategies are, therefore, of considerable potential benefit in this setting. Currently, the most promising of these are the macrolides, corticosteroids, and, more recently, statins, all of which target immune/inflammatory cells. In addition, recent insights into the immunopathogenesis of acute coronary events in patients with CAP have revealed a probable pivotal role of platelet activation, potentially modifiable by agents that possess antiinflammatory or platelet-targeted activities or both. Statins, which not only possess antiinflammatory activity but also appear to target several pathways involved in platelet activation, seem particularly well suited as adjuncts to antibiotic therapy in bacterial CAP. Following a brief consideration of the immunopathogenesis of bacterial CAP, this review is focused on mechanisms of platelet activation by CAP pathogens, as well as the pharmacologic control thereof, with emphasis on statins.

Recent Advances in Chest Medicine

Chest. 2015;148(2):533-542. doi:10.1378/chest.14-1997

Cystic fibrosis (CF) is the most common life-limiting inherited illness of whites. Most of the morbidity and mortality in CF stems from impaired mucociliary clearance leading to chronic, progressive airways obstruction and damage. Significant progress has been made in the care of patients with CF, with advances focused on improving mucociliary clearance, minimizing inflammatory damage, and managing infections; these advances include new antimicrobial therapies, mucolytic and osmotic agents, and antiinflammatory treatments. More recently, researchers have targeted disease-causing mutations using therapies to promote gene transcription and improve channel function, which has led to impressive physiologic changes in some patients. As we develop more advanced, allele-directed therapies for the management of CF, it will become increasingly important to understand the specific genetic and environmental interactions that cause the significant heterogeneity of lung disease seen in the CF population. This understanding of CF endotypes will allow for more targeted, personalized therapies for future patients. This article reviews the genetic and molecular basis of CF lung disease, the treatments currently available, and novel therapies that are in development.

Special Features

Chest. 2015;148(2):543-549. doi:10.1378/chest.15-0332

Blame has been thought to affect quality by decreasing error reporting. Very little is known about the incidence, characteristics, or consequences of the distress caused by being blamed. Blame-related distress (B-RD) may be related to moral distress, but may also be a factor in burnout, compassion fatigue, lateral violence, and second-victim syndrome. The purpose of this article is to explore these related concepts through a literature review applied to three index critical care clinician cases.

Contemporary Reviews in Critical Care Medicine

Chest. 2015;148(2):550-558. doi:10.1378/chest.14-1925

Renal dysfunction is common in patients with end-stage liver disease (ESLD); it takes on many forms from acute to chronic renal injury and may involve a variety of mechanisms. Hepatorenal syndrome (HRS) is a specific type of hepatorenal disorder (HRD) with a unique pathophysiology. HRS is characterized by splanchnic arterial vasodilatation and decreased effective intravascular volume that leads to renal vasoconstriction and decreased renal blood flow. The incidence of HRS in relation to other forms of HRD is unknown; however, it is estimated that 35% to 40% patients with ESLD and ascites eventually develop the condition. Two subtypes of HRS have been described. Type 1 HRS is rapidly progressive, whereas the renal function in type 2 HRS deteriorates slowly over weeks or months. Type 1 HRS may be precipitated by sepsis or acute alcoholic hepatitis and occasionally develops in patients who already have type 2 HRS. The diagnosis of HRS is based on the exclusion of other causes of renal dysfunction because no specific test is available. The definitive treatment of HRS is liver transplant. As a bridge to liver transplant, medical management with volume expansion and the use of vasoconstrictors is often implemented. A transjugular intrahepatic portosystemic shunt has been attempted in treating HRS, although there is little evidence of its efficacy compared with standard therapy. Renal replacement therapy is often used if the patient is a liver transplant candidate. Artificial liver assist devices are in the research phase.

Contemporary Reviews in Sleep Medicine

Chest. 2015;148(2):559-565. doi:10.1378/chest.14-3049

The overwhelming majority of surgical procedures performed in the United States are done on an outpatient basis. Patients with complicated medical problems are routinely scheduled for ambulatory procedures that have become progressively more complex. Appropriate patient selection is paramount to ensuring optimal perioperative outcomes, and the patient with known or suspected OSA presents unique challenges to the anesthesia care team regarding airway management, pain control, and postoperative monitoring requirements. Currently, a relative paucity of high-quality evidence exists on which to base guidelines or recommendations for the anesthetic care of these patients. It is generally agreed that early identification of those at risk for OSA allows for planning and implementation of strategies to help to reduce the risk of adverse perioperative events. Although various national societies have published consensus statements aimed at guiding the perioperative management of the patient at risk for OSA, more studies are needed to define the optimal approach to the perioperative care of this population.


Chest. 2015;148(2):566. doi:10.1378/chest.14-2801

Pain, blipping lines on a radar
saying here I come again
today, this morning, any time. Furrows
on your face sag again as you
write in your pain log. It's a red day, up
from orange, a long way from green.
Birds stand alert on wires outside our
kitchen window, their shapes
notes on sheet music but no songs
come that sound relief. Lines go
over our streets and sidewalks, tunnel
under ground, the very rooms we're in.
I'm about to speak, more words that
come narrow and squiggly, or may
erupt in volcanic spurts again and
again rising in spikes and arrows
across the equilibrium we try to keep,
that might keep days whole and sane
from the pain. Damn it. Angry at
this hour's lament, a roaring shoot
of flames up and down your spine,
lightning bolts igniting more tendrils
of frayed nerve endings through
flattened, degenerated discs,
snaking deeper and deeper ever
intent to throw off guard, keep us
fixated on a light emanating somewhere
in this maze of tunnels, no straight
tracts here. More banging for voices on
phone lines. Now. Somebody please listen
and help. Line up a new battery of
pills and prescriptions. Lay flat along a
line of yoga mats with a Buddha at the
end of the room and wonder where
the mercy has gone, how we got lost here.

Chest. 2015;148(2):567-568. doi:10.1378/chest.15-0463

  Certain ancient cultures in Southeast Asia placed their
  dead in coffins hung from the sides of cliffs. The
  inhabitants of those that fell the earliest were
  considered lucky.
All eventually plummet,
slip past the poles,
shed their exoskeletons of rotten wood,
cast the white rattling bones
like dice against the rocks.
And what awaits them
at the bottom?
For a while, I thought it might be
like Elysium.
Iced-over fields giving way to spring.
The first poppies raising
their necks above the snow.
Somehow, it made sense that a final
act of surrender,
this final prostration of the body
would lend you
a kind of heaven.
After her father’s funeral, my mother
didn’t balance at the edge of tragedy,
didn’t collapse. She folded a pair of pants
and placed it inside her suitcase,
cooked dinner with her sister.
Only much later,
in the solitude of her own house,
did she allow her body to swing
in the current of her grief,
let that grief steep in the rooms
until it became precious
as the remains of silk. But not then.
After she buried her father,
my mother ironed clothes,
packed luggage. She searched
for the plane ticket in the pockets
of our belongings, our shirts and dresses
flashes of color
against the inside of a box.

Chest. 2015;148(2):569-570. doi:10.1378/chest.15-0462

                    or, an ode to uncertainty
If only the medical school offered augury,
then maybe I’d know by now how to consult
the body for advice, write prescriptions
from the flight of an egret or Canadian goose.
I would unearth a falcon’s liver from its hill
of bone, stroll along the two lobes’ fissure,
take measure of the landscape with my hands.
I would call this strange red earth a map.
I would anoint it the captain of my ship,
because a map knows where it’s going, in theory,
not like the blood I’m called to interpret,
this stochastic traffic of proteins, antibodies,
and jetsam, nothing but a few laws of physics
to dictate what dark tunnels to go through next.
And what is there to guide us? Think about all
the choices you made on a whim, the language
you spoke to hurt or heal. Think of the doors
you closed to yourself because, that morning,
you chose the other one. Along the river,
red-winged blackbirds collect twigs from ground
frozen just two weeks ago, too busy to even
sing much. I like to believe, after the priests
exhumed the liver from its feathered tomb,
what happened next wasn’t just a ploy to appease
the king or to parade their intellect, but tell me,
would it matter? Not so bad, I think,
to draw maps out of nothing. Or to imagine priests
reclined against tree stumps, dazed over
the importance of so small a thing, a bird’s liver
in the living bird, tucked close to the ribs,
enshrined by bone to keep all its various
futures alive.

Chest. 2015;148(2):571. doi:10.1378/chest.15-0545

Those combed, articulated ridges
(visible texture of the clouds)
are never glimpsed by those of us
in bedlike chairs or chairlike beds;
we may recall, but cannot witness
moments of frozen transformation
(as when mountainside drizzle whitens
into snow). You can’t be present
– except as a spectator, aside
from fields of play – as winter springs
or summer falls. You cannot finish
your sentences – cannot watch
the monitors that spy on you.
What happened to make gravity
so heavy, time so undefined?
Why can’t you stand, have a razor,
see your face, or sleep unguarded?
You can neither disembody
nor incorporate the unknown
diagnosis you’ve been granted –
question marks to fill the blank.
The false and true alarms, sounds
of chirp or groan, obliterate
all calm. You cannot wander off
or dream for long that you are not
   here, inside the hospital.


Chest. 2015;148(2):572. doi:10.1378/chest.15-1273

The authors have reported to CHEST that an error appeared in Table 1 in “Poor Symptom Control Is Associated With Reduced CT Scan Segmental Airway Lumen Area in Smokers With Asthma” (Chest. 2015;147(3):735-744).

Selected Reports

Chest. 2015;148(2):e35-e37. doi:10.1378/chest.14-2529

We present the case of a 71-year-old woman with a long-standing history of refractory pulmonary sarcoidosis, who, upon commencement of treatment with lenalidomide for her newly diagnosed 5q-myelodysplastic syndrome, showed a remarkable, immediate, unexpected response and recovery of her sarcoidosis-related symptoms, improvement of her vital capacity, and complete clearance of her bibasal alveolor infiltrates. To our knowledge, this is the first case to report on the significant and immediate efficacy of lenalidomide in the management of pulmonary sarcoidosis. It provides a potential role for the use of lenalidomide as a novel therapeutic agent in patients with refractory pulmonary sarcoidosis.

Ultrasound Corner

Chest. 2015;148(2):e38-e41. doi:10.1378/chest.14-1621

A 73-year-old man presented to the ED with confusion. He had a history of atrial fibrillation complicated by ischemic stroke and a history of DVT with placement of an inferior vena caval filter. His primary care physician had discontinued anticoagulants because of repeated falls. On presentation, his admission chest radiograph revealed opacity of the left lower lobe. He received antibiotics for suspected community-acquired pneumonia.

Chest Imaging and Pathology for Clinicians

Chest. 2015;148(2):e42-e47. doi:10.1378/chest.14-2598

A 72-year-old female nonsmoker was admitted to our Thoracic Surgery Unit in 2013 because of a lesion detected on chest CT scan during oncologic follow-up. Her medical history was significant for the development of a single pulmonary metastasis discovered 1 year after sigmoidectomy for colic adenocarcinoma. At that time, the patient was treated with six cycles of neoadjuvant chemotherapy followed by left lower lobectomy. Histologic examination demonstrated a pulmonary metastasis of colic adenocarcinoma with diffuse necrotic areas. The patient underwent subsequent adjuvant chemotherapy with capecitabine and was followed annually with biohumoral oncologic screening (carcinoembryonic antigen, carbohydrate antigen 19-9), chest-abdomen CT scan, and colonoscopy.

Pulmonary, Critical Care, and Sleep Pearls

Chest. 2015;148(2):e48-e51. doi:10.1378/chest.14-3114

An 18-year-old woman with a history of refractory complex partial epilepsy presented for evaluation of snoring and episodes of gasping for air during sleep. She had uncontrolled epilepsy since the age of 8 years despite trial of multiple antiepileptic medications. She eventually underwent an implantation of a vagus nerve stimulator (VNS) device (model 103; Cyberonics Inc) with gradual adjustment of the VNS settings for better seizure control.

Chest. 2015;148(2):e52-e55. doi:10.1378/chest.14-1963

A previously healthy, immunocompetent 37-year-old man was hospitalized with a 3-month history of intermittent fevers and cough with mucopurulent sputum preceded by flu-like symptoms. Five episodes of similar symptoms had prompted two hospitalizations and three courses of outpatient antibiotics. The fever would subside with treatment but intermittent dry cough persisted. There was no history of weight loss, night sweats, wheezing, arthralgia, skin rash, hemoptysis, recent travel, sick contacts, or high-risk sexual behavior. He was a nonsmoker with no alcohol or recreational drug use. He was an accountant in the military with no history of significant organic or inorganic dust exposures.


Chest. 2015;148(2):e56. doi:10.1378/chest.15-0705
Chest. 2015;148(2):e57-e58. doi:10.1378/chest.15-0772
Chest. 2015;148(2):e59. doi:10.1378/chest.15-0716
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Chest. 2015;148(2):e63. doi:10.1378/chest.15-0956
Chest. 2015;148(2):e64-e65. doi:10.1378/chest.15-0818
Chest. 2015;148(2):e65. doi:10.1378/chest.15-0986
Chest. 2015;148(2):e66. doi:10.1378/chest.15-0520
Chest. 2015;148(2):e66-e67. doi:10.1378/chest.15-0936
Chest. 2015;148(2):e67-e68. doi:10.1378/chest.15-1097
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Chest. 2015;148(2):e69-e70. doi:10.1378/chest.15-1027
Chest. 2015;148(2):e70-e71. doi:10.1378/chest.15-1101

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