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Current Issue

Editorial

Chest. 2016;149(6):1355-1356. doi:10.1016/j.chest.2016.03.033
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Intensivists ubiquitously administer sedatives to palliate their patients’ discomfort. However, sedative-associated unresponsiveness confers significant risk and worsens outcomes., Sedative-associated morbid consequences are more likely to occur, given critically ill patients’ unique pharmacokinetics. Protocols mandating sedative titration benefit patients, but the persistence of oversedation,, despite these protocols, suggest that drug–drug interaction and metabolite accumulation may contribute to this iatrogenic complication., Some class-specific pharmacologic characteristics explain the association described between sedative exposure and untoward effects. Overall, the incidence, severity, and cost of sedation-associated problems appear to be rising.

Chest. 2016;149(6):1357-1359. doi:10.1016/j.chest.2016.01.032
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Dr Huang et al performed a systematic review of adjuvant epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in resected lung cancer. The studies largely comprised patients unselected for sensitive tyrosine kinase mutations (exon 19 deletions and point mutations replacing leucine for arginine at codon 858 in exon 21 [L858R]), and the trials had significant heterogeneity that limited conclusions. Patients receiving adjuvant TKIs (erlotinib or gefitinib) had a disease-free survival (DFS) benefit of 3% at 3 years, and benefits were greater for those receiving ≥ 18 months of TKI therapy. Overall survival was not improved. In the subset with sensitizing EGFR mutations, there was a DFS benefit of 9.5% at 3 years, with evidence of reduced distant relapse (hazard ratio, 0.71 [95% CI, 0.56-0.92]).

Chest. 2016;149(6):1360-1361. doi:10.1016/j.chest.2016.01.005
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OSA may affect as many as 50% of patients with established cardiovascular diseases referred to tertiary cardiology centers. However, OSA remains largely underrecognized in this group of patients in clinical practice. Why is that? One possible explanation is that many nonsleep specialists are not familiarized with OSA diagnosis and treatment. There may also be a perception that the causal link between OSA and cardiovascular diseases remains to be clearly established. Perhaps this is related to the fact that the field lacks large clinical trials showing benefits of OSA treatment on cardiovascular outcomes. On the other hand, it is also possible that sleep specialists have taken for granted that OSA is harmful to the cardiovascular system long before the link was fully established because of the observation that patients with severe OSA experience dramatic episodes of recurrent suffocation during sleep, causing large intrathoracic pressure swings and progressive hypoxia that must putatively harm the cardiovascular system.

Chest. 2016;149(6):1362-1364. doi:10.1016/j.chest.2016.03.056
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On September 11, 2001, the twin towers of the World Trade Center (WTC) in New York City were attacked by two hijacked commercial airplanes and subsequently collapsed. This heinous act of terrorism resulted in the deaths of 2,753 individuals, including 343 New York City firefighters who responded to the disaster., In this issue of CHEST, Aldrich et al report the results of a 13-year longitudinal study of spirometry results among 10,641 surviving firefighters with known smoking and body weight histories who were exposed to aerosolized dust following the collapse of the twin towers. This dust contained a highly toxic combination of pulverized building materials and chemical by-products of combustion and pyrolysis. The report published in this issue is a follow-up to two previous reports on lung function among firefighters at 1 year and 7 years following exposure to WTC dust., As such, it is the longest and most comprehensive study of longitudinal spirometry data among rescue and recovery workers who were exposed to toxic material during the response to a major environmental disaster. The results of this study are therefore extremely important for understanding the long-term effects of inhaling toxic aerosolized dust on lung function. Just as importantly, it is also the first study to report the effects of smoking and smoking cessation on longitudinal lung function decline caused by toxic exposures during a major environmental disaster.

Editorials: Point and Counterpoint

Chest. 2016;149(6):1365-1367. doi:10.1016/j.chest.2016.03.048
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The controversial debate on the IV use of albumin-containing solutions in patients with severe sepsis or septic shock and, more generally, in critically ill patients, dates back to 1998, when the first high-quality meta-analysis investigating this issue reported a potential increased risk of death associated with the administration of human albumin. After several years of lively debate and suboptimal clinical evidence, the first large, randomized controlled trial (RCT) conducted in critically ill patients showed no effect on 28-day survival as associated with IV administration of 4% albumin, compared with 0.9% sodium chloride, for volume resuscitation. Despite the overall equipoise of the two strategies in the entire study population, the trial suggested, for the first time, a potential benefit of human albumin in the predefined subgroup of patients with severe sepsis. To test such a hypothesis, in 2014, we concluded the first large RCT (ie, the Albumin Italian Outcome Sepsis [ALBIOS] study) comparing an albumin replacement strategy (including albumin and crystalloid administration) vs the use of crystalloids alone, for the first 28 days of treatment in patients with severe sepsis or septic shock. The trial reported no advantages of albumin administration on 28- or 90-day survival. Nonetheless, in a post hoc and not predefined subgroup analysis, patients with septic shock randomized to the albumin group reported a significant 6.3% absolute reduction in 90-day mortality compared with the crystalloid group.

Chest. 2016;149(6):1368-1370. doi:10.1016/j.chest.2016.03.050
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Hypoalbuminemia is common in patients with severe sepsis and septic shock and is associated with poor outcomes. The use of albumin for resuscitation in this population remains controversial. Despite theoretical benefits to the use of albumin, multiple clinical trials and systematic reviews have failed to demonstrate an outcome benefit. We believe that the use of albumin in the resuscitation of patients with severe sepsis and septic shock is not warranted, given the lack of evidence of outcome benefits and its high cost. We present a few important questions.

Chest. 2016;149(6):1370-1371. doi:10.1016/j.chest.2016.03.049
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I read with interest the arguments of my opponents. The questions posed are undoubtedly crucial. As I have originally foreseen, in my rebuttal, I will have to discuss the available data in more details.

Chest. 2016;149(6):1371-1372. doi:10.1016/j.chest.2016.03.051
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We agree with Dr Caironi that hypoalbuminemia, epiphenomenon or not, is associated with increased morbidity and mortality in critically ill patients. However, no study has shown that correcting hypoalbuminemia or using albumin in resuscitation alters these outcomes.

Original Research: Critical Care

Chest. 2016;149(6):1373-1379. doi:10.1378/chest.15-1389

Background  Current sedation guidelines recommend avoiding benzodiazepines but express no preference for propofol vs dexmedetomidine. In addition, few data exist on whether randomized controlled trials of sedatives can be successfully generalized to routine practice, in which conditions tend to be more varied and complex.

Methods  Data regarding daily sedative exposure were gathered from all patients undergoing mechanical ventilation for ≥ 3 days over a 7-year period in a large academic medical center. Hazard ratios (HRs) were compared for ventilator-associated events (VAEs), extubation, hospital discharge, and hospital death among patients receiving benzodiazepines, propofol, and dexmedetomidine. Proportional subdistribution hazard models with competing risks were used for analysis. All analyses were adjusted for ICU type, demographic characteristics, comorbidities, procedures, severity of illness, hypotension, oxygenation, renal function, opioids, neuroleptic agents, neuromuscular blockers, awakening and breathing trials, and calendar year.

Results  A total of 9,603 consecutive episodes of mechanical ventilation were evaluated. Benzodiazepines and propofol were associated with increased VAE risk, whereas dexmedetomidine was not. Propofol was associated with less time to extubation compared with benzodiazepines (HR, 1.4; 95% CI, 1.3-1.5). Dexmedetomidine was associated with less time to extubation compared with benzodiazepines (HR, 2.3; 95% CI, 2.0-2.7) and propofol (HR, 1.7; 95% CI, 1.4-2.0), but relatively few dexmedetomidine exposures were available for analysis. There were no differences between any two agents in HRs for hospital discharge or mortality.

Conclusions  In this large, real-world cohort, propofol and dexmedetomidine were associated with less time to extubation compared with benzodiazepines, but dexmedetomidine was also associated with less time to extubation vs propofol. These possible differences merit further study.

Chest. 2016;149(6):1380-1383. doi:10.1016/j.chest.2016.02.657

Background  We describe the feasibility, utility, and safety of oral midodrine to replace IV vasopressors during recovery from septic shock.

Methods  This was a retrospective study performed in a medical ICU. All study subjects had a diagnosis of septic shock requiring at least 24 hours of IV vasopressors and demonstrated clinical stability with stable or decreasing doses of IV vasopressors. The two groups compared were those who received IV vasopressors only and those who received IV vasopressors with adjunctive midodrine.

Results  Of the 275 study patients, 140 received an IV vasopressor only and 135 received midodrine in addition to an IV vasopressor. There was no difference between the groups’ demographics (age, sex, Acute Physiology and Chronic Health Evaluation 4 score). Mean IV vasopressor duration was 3.8 days in the IV vasopressor only group and 2.9 days in the IV vasopressor with midodrine group (P < .001). An IV vasopressor was reinstituted after discontinuation in 21 of 140 (15%) patients in the IV vasopressor only group and in 7 of 135 (5.2%) patients in the IV vasopressor with midodrine group (P = .007). ICU length of stay was 9.4 days in the IV vasopressor only group and 7.5 days in the IV vasopressor with midodrine group (P = .017). There were no complications associated with midodrine use except transient bradycardia in one patient, which resolved upon discontinuation of midodrine.

Conclusions  Midodrine may reduce the duration of IV vasopressors during recovery phase from septic shock and may be associated with a reduction in length of stay in the ICU.

Original Research: Lung Cancer

Chest. 2016;149(6):1384-1392. doi:10.1016/j.chest.2015.12.017

Background  The role of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in the adjuvant treatment of non-small cell lung cancer (NSCLC) has not been well-established. Our meta-analysis aimed to determine whether the administration of EGFR-TKIs could improve the outcomes of patients with NSCLC undergoing complete resection.

Methods  We comprehensively searched databases and extracted data from eligible studies. Disease-free survival (DFS) and overall survival (OS) with hazard ratios (HRs) as well as disease relapse with odds ratios (OR) were calculated using random and/or fixed-effects models. Meta-regression analysis and test for interaction between subgroups were also carried out.

Results  A total of 1,960 patients in five studies were included. Adjuvant EGFR-TKI treatment was associated with a significant benefit on DFS (HR, 0.63; 95% CI, 0.41-0.99), corresponding to an absolute benefit of 3.1% at 3 years, yet with significant heterogeneity (I2 = 83.4%, P < .001). The survival benefit was superior (Pinteraction = .03) in studies with more than an 18-month median treatment duration. EGFR mutation rate was also identified as a source of heterogeneity (P = .017). In the population with EGFR mutations, HR for DFS was 0.48 (95% CI, 0.36-0.65), corresponding to an absolute benefit of 9.5% at 3 years, with a reduced risk of distant metastasis (OR, 0.71; 95% CI, 0.56-0.92). Adjuvant EGFR-TKI treatment resulted in a marginally statistically significant benefit on OS (HR, 0.72; 95% CI, 0.49-1.06). The rate of overall grade 3 or greater adverse events was 42.3% (95% CI, 39.1-45.6).

Conclusions  Adjuvant EGFR-TKI treatment may enhance disease-free survival and reduce the risk of distant metastasis in patients with EGFR-mutant NSCLC undergoing complete resection.

Chest. 2016;149(6):1393-1399. doi:10.1016/j.chest.2016.01.015

Objective  The aim of this study was to analyze the spectral features of the radiofrequency of lymph nodes during endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) and to determine its diagnostic value for detecting metastatic nodes in patients with lung cancer.

Methods  Ultrasound spectrums of lymph nodes during EBUS-TBNA were retrospectively analyzed. A linear regression of frequency spectrum and the ultrasonic spectral parameters midband-fit, slope, and intercept were calculated. Mean values for these parameters within lymph nodes were computed. The cutoff values for each parameter for distinguishing metastatic vs benign lymph nodes were first determined within the training set; these cutoff values were then applied to the testing set for validation.

Results  Overall, 362 lymph nodes (112 metastatic, 250 benign) were analyzed as the training set, and 284 lymph nodes (74 metastatic, 210 benign) were evaluated as the testing set. In the training set, all of the parameters showed a significant difference between metastatic and benign lymph nodes (P < .001). The metastatic nodes tended to show low midband-fit, high slope, and low intercept. When midband-fit and intercept were combined, the diagnostic accuracy was maximized in the training set. In the testing set, the combination of intercept and slope produced the highest diagnostic accuracy, with the following outcomes: sensitivity, 79.7%; specificity, 84.3%; diagnostic accuracy, 83.1%; positive predictive value, 64.1%; and negative predictive value, 92.2%.

Conclusions  Metastatic lymph nodes possess unique ultrasonic spectrum features, and spectrum analysis can be used as a novel diagnostic tool for differentiating between benign and malignant nodes in patients with lung cancer.

Original Research: Sleep Disorders

Chest. 2016;149(6):1400-1408. doi:10.1016/j.chest.2015.11.010

Background  Intermittent hypoxia (IH) is the principal injurious factor involved in the cardiovascular morbidity and mortality associated with OSA. The gold standard for treatment is CPAP, which eliminates IH and appears to reduce cardiovascular risk. There is no experimental evidence on the reversibility of cardiovascular remodeling after IH withdrawal. The objective of the present study is to assess the reversibility of early cardiovascular structural remodeling induced by IH after resumption of normoxic breathing in a novel recovery animal model mimicking OSA treatment.

Methods  We investigated cardiovascular remodeling in C57BL/6 mice exposed to IH for 6 weeks vs the normoxia group and its spontaneous recovery after 6 subsequent weeks under normoxia.

Results  Aortic expansive remodeling was induced by IH, with intima-media thickening and without lumen perimeter changes. Elastic fiber network disorganization, fragmentation, and estrangement between the end points of disrupted fibers were increased by IH. Extracellular matrix turnover was altered, as visualized by collagen and mucoid interlaminar accumulation. Furthermore, left ventricular perivascular fibrosis was increased by IH, whereas cardiomyocytes size was unaffected. These cardiovascular remodeling events induced by IH were normalized after recovery in normoxia, mimicking CPAP treatment.

Conclusions  The early structural cardiovascular remodeling induced by IH was normalized after IH removal, revealing a novel recovery model for studying the effects of OSA treatment. Our findings suggest the clinical relevance of early detection and effective treatment of OSA in patients to prevent the natural course of cardiovascular diseases.

Chest. 2016;149(6):1409-1418. doi:10.1016/j.chest.2016.01.013

Objective  We developed and validated the first-ever sleep apnea (SA) risk calculator in a large population-based cohort of Hispanic/Latino subjects.

Methods  Cross-sectional data on adults from the Hispanic Community Health Study/Study of Latinos (2008-2011) were analyzed. Subjective and objective sleep measurements were obtained. Clinically significant SA was defined as an apnea-hypopnea index ≥ 15 events per hour. Using logistic regression, four prediction models were created: three sex-specific models (female-only, male-only, and a sex × covariate interaction model to allow differential predictor effects), and one overall model with sex included as a main effect only. Models underwent 10-fold cross-validation and were assessed by using the C statistic. SA and its predictive variables; a total of 17 variables were considered.

Results  A total of 12,158 participants had complete sleep data available; 7,363 (61%) were women. The population-weighted prevalence of SA (apnea-hypopnea index ≥ 15 events per hour) was 6.1% in female subjects and 13.5% in male subjects. Male-only (C statistic, 0.808) and female-only (C statistic, 0.836) prediction models had the same predictor variables (ie, age, BMI, self-reported snoring). The sex-interaction model (C statistic, 0.836) contained sex, age, age × sex, BMI, BMI × sex, and self-reported snoring. The final overall model (C statistic, 0.832) contained age, BMI, snoring, and sex. We developed two websites for our SA risk calculator: one in English (https://www.montefiore.org/sleepapneariskcalc.html) and another in Spanish (http://www.montefiore.org/sleepapneariskcalc-es.html).

Conclusions  We created an internally validated, highly discriminating, well-calibrated, and parsimonious prediction model for SA. Contrary to the study hypothesis, the variables did not have different predictive magnitudes in male and female subjects.

Original Research: Occupational and Environmental Lung Disease

Chest. 2016;149(6):1419-1427. doi:10.1016/j.chest.2015.10.067

Background  World Trade Center (WTC)-exposed Fire Department of the City of New York firefighters lost, on average, 10% of lung function after September 11, 2011, and >10% developed new obstructive airways disease. There was little recovery (on average) over the first 6 years. Follow-up into the next decade allowed us to determine the longer-term exposure effects and the roles of cigarette smoking and cessation on lung function trajectories.

Methods  We examined serial measurements of FEV1 from March 11, 2000, to September 10, 2014, among 10,641 WTC-exposed Fire Department of the City of New York firefighters with known smoking and body weight histories.

Results  The median number of FEV1 measurements during follow-up was 9; 15% of firefighters arrived at the WTC during the morning of September 11, 2001; and 65% never smoked. Firefighters arriving the morning of September 11, 2001 averaged lower lung function than did lesser exposed firefighters; this difference remained significant during most of follow-up (P < .05). Never smokers had significantly better lung function than current smokers; former smokers fell in between, depending upon their cessation date. Those arriving the morning of September 11, 2001 were more likely to have an FEV1 < lower limits of normal compared with those arriving between September 13, 2001, and September 24, 2001 (OR = 1.70, P < .01). Current smokers were more likely to have an FEV1 < lower limits of normal compared with never smokers (OR = 2.06, P < .01), former smokers who quit before September 11, 2001 (OR = 1.96, P < .01), or those who quit between September 11, 2001 and March 10, 2008 (OR = 1.49, P < .01).

Conclusions  Thirteen years after September 11, 2001, most firefighters continued to show a lack of lung function recovery, with the trajectory of decline differing by WTC exposure and smoking status. Unlike the immutable effect of WTC exposure, we demonstrated the benefit on lung function of smoking cessation in this unique occupational/environmental cohort.

Chest. 2016;149(6):1428-1435. doi:10.1016/j.chest.2015.12.033

Background  The medical and recreational use of marijuana is now legal in some parts of the United States; the health effects are unknown. We aimed to evaluate associations between recent marijuana use and exhaled nitric oxide (eNO) and pulmonary function.

Methods  We performed a cross-sectional study of 10,327 US adults participating in the National Health and Nutrition Examination Survey in the years 2007 to 2012. We examined associations between marijuana use and eNO, FEV1, FVC, the FEV1/FVC ratio, and forced expiratory flow (midexpiratory phase) (FEF25%-75%) by weighted linear regression.

Results  In the study population, there were 4,797 never users, 4,084 past marijuana users, 555 participants who used marijuana 5 to 30 days before the examination, and 891 participants who used marijuana 0 to 4 days before the examination. Current marijuana use in the past 4 days was associated with 13% lower eNO (95% CI, –18% to 8%). FVC was higher in past users (75 mL; 95% CI, 38-112) and current users in the past 5 to 30 days (159 mL; 95% CI, 80-237) and in users within 0 to 4 days of the examination (204 mL; 95% CI, 139-270) compared with never users. All associations remained unchanged and statistically significant in sensitivity analyses excluding current and past tobacco users.

Conclusions  Current marijuana use was associated with lower levels of eNO and higher FVC. The lower eNO in marijuana smokers suggests that short-term exposure to marijuana may, like tobacco, acutely affect the pulmonary vascular endothelium and impair airflow through the small airways.

Original Research: Asthma

Chest. 2016;149(6):1436-1444. doi:10.1016/j.chest.2016.02.639

Background  Exposure to gun violence and African ancestry have been separately associated with increased risk of asthma in Puerto Rican children.

Objective  The objective of this study was to examine whether African ancestry and gun violence interact on asthma and total IgE in school-aged Puerto Rican children.

Methods  This is a case-control study of 747 Puerto Rican children aged 9 to 14 years living in San Juan, Puerto Rico (n = 472), and Hartford, Connecticut (n = 275). Exposure to gun violence was defined as the child’s report of hearing gunshots more than once, and the percentage of African ancestry was estimated using genome-wide genotypic data. Asthma was defined as parental report of physician-diagnosed asthma and wheeze in the previous year. Serum total IgE (IU/mL) was measured in study participants. Multivariate logistic and linear regressions were used for the analysis of asthma and total IgE, respectively.

Results  In multivariate analyses, there was a significant interaction between exposure to gun violence and African ancestry on asthma (P = .001) and serum total IgE (P = .04). Among children exposed to gun violence, each quartile increase in the percentage of African ancestry was associated with approximately 45% higher odds of asthma (95% CI, 1.15-1.84; P = .002) and an approximately 19% increment in total IgE (95% , 0.60-40.65, P = .04). In contrast, there was no significant association between African ancestry and asthma or total IgE in children not exposed to gun violence.

Conclusions  Our results suggest that exposure to gun violence modifies the estimated effect of African ancestry on asthma and atopy in Puerto Rican children.

Chest. 2016;149(6):1445-1459. doi:10.1016/j.chest.2016.01.024

Background  Bronchial epithelial ciliary dysfunction is an important feature of asthma. We sought to determine the role in asthma of neutrophilic inflammation and nicotinamide adenine dinucleotide phosphate (NADPH) oxidases in ciliary dysfunction.

Methods  Bronchial epithelial ciliary function was assessed by using video microscopy in fresh ex vivo epithelial strips from patients with asthma stratified according to their sputum cell differentials and in culture specimens from healthy control subjects and patients with asthma. Bronchial epithelial oxidative damage was determined by 8-oxo-dG expression. Nicotinamide adenine dinucleotide phosphate oxidase (NOX)/dual oxidase (DUOX) expression was assessed in bronchial epithelial cells by using microarrays, with NOX4 and DUOX1/2 expression assessed in bronchial biopsy specimens. Ciliary dysfunction following NADPH oxidase inhibition, using GKT137831, was evaluated in fresh epithelial strips from patients with asthma and a murine model of ovalbumin sensitization and challenge.

Results  Ciliary beat frequency was impaired in patients with asthma with sputum neutrophilia (n = 11) vs those without (n = 10) (5.8 [0.6] Hz vs 8.8 [0.5] Hz; P = .003) and was correlated with sputum neutrophil count (r = –0.70; P < .001). Primary bronchial epithelial cells expressed DUOX1/2 and NOX4. Levels of 8-oxo-dG and NOX4 were elevated in patients with neutrophilic vs nonneutrophilic asthma, DUOX1 was elevated in both, and DUOX2 was elevated in nonneutrophilic asthma in vivo. In primary epithelial cultures, ciliary dysfunction did not persist, although NOX4 expression and reactive oxygen species generation was increased from patients with neutrophilic asthma. GKT137831 both improved ciliary function in ex vivo epithelial strips (n = 13), relative to the intensity of neutrophilic inflammation, and abolished ciliary dysfunction in the murine asthma model with no reduction in inflammation.

Conclusions  Ciliary dysfunction is increased in neutrophilic asthma associated with increased NOX4 expression and is attenuated by NADPH oxidase inhibition.

Original Research: Signs and Symptoms of Chest Disease

Chest. 2016;149(6):1460-1466. doi:10.1016/j.chest.2016.02.676

Background  Cough is recognized as an important troublesome symptom in the diagnosis and monitoring of asthma. Asthma control is thought to be determined by the degree of airway inflammation and hyperresponsiveness but how these factors relate to cough frequency is unclear. The goal of this study was to investigate the relationships between objective cough frequency, disease control, airflow obstruction, and airway inflammation in asthma.

Methods  Participants with asthma underwent 24-h ambulatory cough monitoring and assessment of exhaled nitric oxide, spirometry, methacholine challenge, and sputum induction (cell counts and inflammatory mediator levels). Asthma control was assessed by using the Global Initiative for Asthma (GINA) classification and the Asthma Control Questionnaire (ACQ). The number of cough sounds was manually counted and expressed as coughs per hour (c/h).

Results  Eighty-nine subjects with asthma (mean ± SD age, 57 ± 12 years; 57% female) were recruited. According to GINA criteria, 18 (20.2%) patients were classified as controlled, 39 (43.8%) partly controlled, and 32 (36%) uncontrolled; the median ACQ score was 1 (range, 0.0-4.4). The 6-item ACQ correlated with 24-h cough frequency (r = 0.40; P < .001), and patients with uncontrolled asthma (per GINA criteria) had higher median 24-h cough frequency (4.2 c/h; range, 0.3-27.6) compared with partially controlled asthma (1.8 c/h; range, 0.2-25.3; P = .01) and controlled asthma (1.7 c/h; range, 0.3-6.7; P = .002). Measures of airway inflammation were not significantly different between GINA categories and were not correlated with ACQ. In multivariate analyses, increasing cough frequency and worsening FEV1 independently predicted measures of asthma control.

Conclusions  Ambulatory cough frequency monitoring provides an objective assessment of asthma symptoms that correlates with standard measures of asthma control but not airflow obstruction or airway inflammation. Moreover, cough frequency and airflow obstruction represent independent dimensions of asthma control.

Chest. 2016;149(6):1467-1472. doi:10.1016/j.chest.2016.01.008

Background  Patients with deflation cough (DC), the cough-like expulsive effort(s) evoked by maximal lung emptying during a slow vital capacity maneuver, also present symptoms of gastroesophageal reflux. DC can be inhibited by prior intake of antacids. We wished to assess DC prevalence and association between DC and chemical characteristics of refluxate in patients with gastroesophageal reflux symptoms.

Methods  A total of 157 consecutive outpatients underwent DC assessment and 24-h multichannel intraluminal impedance pH (MII-pH) monitoring; 93/157 also had chronic cough. Patients performed two to four slow vital capacity maneuvers and DC was detected aurally. Subsequently, they underwent 24-h MII-pH monitoring, the outcomes of which were defined as abnormal when acid or non-acid reflux events were > 73.

Results  DC occurred in 46/157 patients, 18 of whom had abnormal MII-pH outcomes; 28 of the remaining 111 patients without DC also had abnormal MII-pH findings. Thus, in the patients as a group, there was no association between DC and MII-pH outcomes. DC occurred in 40/93 of the chronic coughers; 15 of whom had acid reflux. All but 2 of the 53 patients without DC had normal MII-pH outcomes (P < .001), and the negative predictive value of DC for excluding acid reflux was 96.2%. At follow-up, 65% of coughers showed significant improvement after treatment.

Conclusions  The overall prevalence of DC was 29%, increasing to 43% in chronic coughers in whom the absence of DC virtually excludes acid reflux. Therefore, DC assessment may represent a useful screening test for excluding acid reflux in chronic coughers with reflux symptoms.

Original Research: Diffuse Lung Disease

Chest. 2016;149(6):1473-1481. doi:10.1016/j.chest.2015.12.030

Background  Hypersensitivity pneumonitis (HP) is an interstitial lung disease caused by the inhalation of environmental antigens. The relationship between clinical, radiologic, and histopathologic findings of chronic HP remains unclear.

Methods  Sixteen patients with proven chronic bird-related HP with a usual interstitial pneumonia-like pattern were analyzed retrospectively. Histopathologic findings were semiquantitatively assessed and compared with clinical and radiologic findings. We also evaluated the histopathologic findings affecting prognosis.

Results  The extent of centrilobular fibrosis was negatively correlated with Pao2 (r = –0.55, P = .03). The extent of bridging fibrosis was positively correlated with the ratio of maximal expiratory flow at 50% of forced vital capacity to that at 25% (r = 0.60, P = .02). Patients with a greater extent of fibroblastic foci (FF) had more radiologic reticulation (P = .01), honeycombing (P = .01), and traction bronchiectasis (P = .02), and had significantly shorter survival time (P = .01) than patients with a lesser extent of FF. Multivariate analysis showed that the extent of FF was a significant prognostic factor (hazard ratio, 2.36; 95% confidence interval, 1.02-5.48; P = .04).

Conclusions  Our findings demonstrated that the extent of FF was significantly associated with reticulation, honeycombing, and traction bronchiectasis on high-resolution CT scanning. Moreover, the extent of FF could be a useful predictor of mortality in chronic HP with a usual interstitial pneumonia-like pattern.

Original Research: Pulmonary Vascular Disease

Chest. 2016;149(6):1482-1493. doi:10.1016/j.chest.2016.01.004

Background  Pulmonary arterial hypertension (PAH) encompasses a group of conditions with distinct causes. Immunologic disorders are common features of all forms of PAH and contributes to both disease susceptibility and progression. Regulatory T lymphocytes (Treg) are dysfunctional in patients with idiopathic PAH (iPAH) in a leptin-dependent manner. However, it is not known whether these abnormalities are specific to iPAH. Hence, we hypothesized that (1) Treg dysfunction is also present in heritable (hPAH) and connective tissue disease-associated PAH (CTD-PAH); (2) defective leptin-dependent signaling is present in hPAH and CTD-PAH and could contribute to Treg dysfunction; (3) modulating the leptin axis in vivo could protect against Treg dysfunction; and (4) restoration of Treg activity could limit or reverse experimental chronic hypoxia-induced pulmonary hypertension in vivo.

Methods  We analyzed 62 patients with PAH (30 with iPAH, 18 with hPAH, and 14 with CTD-PAH), 7 patients with CTD without PAH, and 20 healthy control subjects.

Results  Our results indicate that Treg are dysfunctional in all PAH forms tested, as well as in patients with CTD without PAH. Importantly, the leptin axis is crucial in Treg dysfunction in patients with iPAH and those with CTD (with or without PAH), whereas in patients with hPAH, Treg are altered in a leptin-independent manner. We found that leptin receptor-deficient rats, which develop less severe hypoxia-induced pulmonary hypertension, are protected against decreased Treg function after hypoxic exposure.

Conclusions  Taken together, our results suggest that Treg dysfunction is common to all forms of PAH and may contribute to the development and the progression of the disease.

Original Research: Diseases of the Pleura

Chest. 2016;149(6):1494-1500. doi:10.1016/j.chest.2016.01.001

Background  Malignant pleural effusion (MPE) is common. Existing literature on pleural fluid compositions is restricted to cross-sectional sampling with little information on longitudinal changes of fluid biochemistry and cytokines with disease progression. Indwelling pleural catheters provide the unique opportunity for repeated sampling and longitudinal evaluation of MPE, which may provide insight into tumor pathobiology.

Methods  We collected 638 MPE samples from 103 patients managed with indwelling pleural catheters over 95 days (median, range 0-735 days) and analyzed them for protein, pH, lactate dehydrogenase, and glucose levels. Peripheral blood was quantified for hematocrit, platelets, leukocytes, protein, and albumin. Cytokine levels (monocyte chemotactic protein [MCP]-1; vascular endothelial growth factor; interleukin-6, -8, and -10; tumor necrosis factor-α; and interferon-gamma) were determined in 298 samples from 35 patients with mesothelioma. Longitudinal changes of all parameters were analyzed using a linear mixed model.

Results  Significant decreases were observed over time in pleural fluid protein by 8 g/L per 100 days (SE, 1.32; P < .0001) and pH (0.04/100 days; SE, 0.02; P = .0203), accompanied by a nonsignificant rise in lactate dehydrogenase. The ratio of pleural fluid to serum protein decreased by 0.06/100 days (SE, 0.02; P = .04). MPEs from mesothelioma (n = 63) had lower pleural fluid glucose (P = .0104) at baseline and a faster rate of decline in glucose (P = .0423) when compared with non-mesothelioma effusions (n = 38). A progressive rise in mesothelioma pleural fluid concentration of [log] MCP-1 ([log] 0.37 pg/mL per 100 days; SE, 0.13; P = .0046), but not of other cytokines, was observed.

Conclusions  MPE fluids become less exudative and more acidic over the disease course. The rise in MCP-1 levels suggests a pathobiological role in MPE.

Original Research: Chest Infections

Chest. 2016;149(6):1501-1508. doi:10.1016/j.chest.2016.02.675

Background  Previous studies reported an association of diabetes mellitus (DM) with TB susceptibility. Many studies were retrospective, had weak diagnostic criteria for DM, and did not assess other comorbidities. The Effects of Diabetes on Tuberculosis Severity (EDOTS) study is addressing these limitations with a longitudinal comparison of patients with TB who are classified as diabetic or normoglycemic according to World Health Organization criteria. We report interim findings after enrolling 159 of a planned 300 subjects.

Methods  A cohort study of patients with TB in South India with DM or normoglycemia defined by oral glucose tolerance test (OGTT) and fasting glucose. Glycohemoglobin (HbA1c), serum creatinine, lipids, and 25-hydroxyvitamin D were measured at enrollment. Patients were monitored monthly during TB treatment, and HbA1c measurement was repeated after 3 months.

Results  Of 209 eligible patients, 113 (54.1%) were classified as diabetic, 44 (21.0%) with impaired glucose tolerance, and 52 (24.9%) as normoglycemic. More patients with diabetes were detected by OGTT than by HbA1c. Diabetes was a newly received diagnosis for 37 (32.7%) in the DM group, and their median HbA1c (6.8%) was significantly lower than in those with previously diagnosed DM (HbA1c, 10.4%). Among 129 patients monitored for 3 months, HbA1c declined in all groups, with the greatest difference in patients with a newly received diagnosis of DM.

Conclusions  Early EDOTS study results reveal a strikingly high prevalence of glycemic disorders in South Indian patients with pulmonary TB and unexpected heterogeneity within the patient population with diabetes and TB. This glycemic control heterogeneity has implications for the TB-DM interaction and the interpretation of TB studies relying exclusively on HbA1c to define diabetic status.

Chest. 2016;149(6):1509-1515. doi:10.1016/j.chest.2015.12.027

Background  Pleural effusions are present in 15% to 44% of hospitalized patients with pneumonia. It is unknown whether effusions at first presentation to the ED influence outcomes or should be managed differently.

Methods  We studied patients in seven hospital EDs with International Statistical Classification of Disease and Health Related Problems-Version 9 codes for pneumonia, or empyema, sepsis, or respiratory failure with secondary pneumonia. Patients with no confirmatory findings on chest imaging were excluded. Pleural effusions were identified with the use of radiographic imaging.

Results  Over 24 months, 4,771 of 458,837 adult ED patients fulfilled entry criteria. Among the 690 (14.5%) patients with pleural effusions, their median age was 68 years, and 46% were male. Patients with higher Elixhauser comorbidity scores (OR, 1.13 [95% CI, 1.09-1.18]; P < .001), brain natriuretic peptide levels (OR, 1.20 [95% CI, 1.12-1.28]; P < .001), bilirubin levels (OR, 1.07 [95% CI, 1.00-1.15]; P = .04), and age (OR, 1.15 [95% CI, 1.09-1.21]; P < .001) were more likely to have parapneumonic effusions. In patients without effusion, electronic version of CURB-65 (confusion, uremia, respiratory rate, BP, age ≥ 65 years accurately predicted mortality (4.7% predicted vs 5.0% actual). However, eCURB underestimated mortality in those with effusions (predicted 7.0% vs actual 14.0%; P < .001). Patients with effusions were more likely to be admitted (77% vs 57%; P < .001) and had a longer hospital stay (median, 2.8 vs 1.3 days; P < .001). After severity adjustment, the likelihood of 30-day mortality was greater among patients with effusions (OR, 2.6 [CI, 2.0-3.5]; P < .001), and hospital stay was disproportionately longer (coefficient, 0.22 [CI, 0.14-0.29]; P < .001).

Conclusions  Patients with pneumonia and pleural effusions at ED presentation in this study were more likely to die, be admitted, and had longer hospital stays. Why parapneumonic effusions are associated with adverse outcomes, and whether different management of these patients might improve outcome, needs urgent investigation.

Original Research: Antithrombotic Therapy

Chest. 2016;149(6):1516-1524. doi:10.1016/j.chest.2015.12.029

Background  Direct oral anticoagulants (DOACs) are used as an alternative for traditional antithrombotic therapy. However, the safety profile of DOACs in patients with renal failure (RF) has not been determined.

Methods  A systematic review was performed assessing the reported safety of DOACs compared with vitamin K antagonists (VKAs) in patients with RF and estimated creatinine clearance (eCrCL) < 50 mL/min and eCrCL 50 to 80 mL/min. MEDLINE, EMBASE, Cochrane, and the Clinical Trials Registry (ClinicalTrials.gov) were searched for randomized clinical trials up to November 2015. The data were pooled by using both traditional frequentist and Bayesian random effects models.

Results  Nine trials met the inclusion criteria. Among 94,897 participants, 54,667 (58%) had RF. Compared with VKAs, DOACs were associated with a significantly decreased risk for major bleeding in patients with eCrCL 50 to 80 mL/min (risk ratio, 0.87 [95% CI, 0.81-0.93]) and a nonsignificant decrease in the risk for major bleeding in patients with eCrCL < 50 mL/min (risk ratio, 0.83 [95% CI, 0.68-1.02]); there was evidence of significant heterogeneity. Indirect comparisons, using Bayesian network analysis, indicated that apixaban was associated with a decreased rate of major bleeding compared with other DOACs in patients with eCrCL < 50 mL/min. DOACs were associated with a significant decrease in the risk for hemorrhagic stroke compared with VKAs in patients with eCrCL < 50 mL/min and 50 to 80 mL/min.

Conclusions  As a class, DOACs are associated with a reduced risk for hemorrhagic stroke compared with VKAs in patients with RF. However, DOACs may differ from each other in their relative risk for major bleeding in patients with eCrCL < 50 mL/min.

Trial Registry  PROSPERO registry; No.: CRD42014013730; URL: http://www.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD42014013730

Recent Advances in Chest Medicine

Chest. 2016;149(6):1525-1534. doi:10.1016/j.chest.2015.12.034

A link between metabolic syndrome (MetS) and lung diseases has been observed in several cross-sectional and longitudinal studies. This syndrome has been identified as an independent risk factor for worsening respiratory symptoms, greater lung function impairment, pulmonary hypertension, and asthma. This review will discuss several potential mechanisms to explain these associations, including dietary factors and the effect of adiposity and fat-induced inflammation on the lungs, and the role of other comorbidities that frequently coexist with MetS, such as OSA and obesity. In contrast to the well-known association between asthma and obesity, the recognition that MetS affects the lung is relatively new. Although some controversy remains as to whether MetS is a unique disease entity, its individual components have independently been associated with changes in pulmonary function or lung disease. There is, however, uncertainty as to the relative contribution that each metabolic factor has in adversely affecting the respiratory system; also, it is unclear how much of the MetS-related lung effects occur independently of obesity. In spite of these epidemiological limitations, the proposed mechanistic pathways strongly suggest that this association is likely to be causal. Given the wide prevalence of MetS in the general population, it is imperative that we continue to further understand how this metabolic disorder impacts the lung and how to prevent its complications.

Special Features

Chest. 2016;149(6):1535-1545. doi:10.1016/j.chest.2015.12.019

Lung transplantation is now an established treatment for a broad spectrum of end-stage pulmonary diseases. According to the International Society for Heart and Lung Transplantation Registry, more than 50,000 lung transplants have been performed worldwide, with nearly 11,000 lung transplant recipients alive in the United States. With the increasing application of lung transplantation, pulmonologists must be cognizant of common complications unique to the postlung transplant period and the associated radiologic findings. The aim of this review is to describe clinical manifestations and prototypical radiographic features of both common and rare complications encountered in lung transplant recipients.

Contemporary Reviews in Critical Care Medicine

Chest. 2016;149(6):1546-1555. doi:10.1016/j.chest.2016.01.002

Kidney transplantation is the most common solid organ transplantation performed worldwide. Up to 6% of kidney transplant recipients experience a life-threatening complication that requires ICU admission, chiefly in the late posttransplantation period (≥ 6 months). Acute respiratory failure and septic shock are the main reasons for ICU admission. Cardiac pulmonary edema, bacterial pneumonia, acute graft pyelonephritis, and bloodstream infections account for the vast majority of diagnoses in the ICU. Pneumocystis jirovecii pneumonia is the most common opportunistic infection, and one-half of the patients so infected require mechanical ventilation. The incidence of cytomegalovirus visceral infections in the era of preemptive therapy has dramatically decreased. Drug-related neutropenia, sirolimus-related pneumonitis, and posterior reversible encephalopathy syndrome are among the most common immunosuppression-associated toxic effects. Importantly, the impact of critical illness on graft function is worrisome. Throughout the ICU stay, acute kidney injury is common, and about 40% of the recipients require renal replacement therapy. One-half of the patients are discharged alive and free from dialysis. Hospital mortality can reach 30% and correlates with acute illness severity and reason for ICU admission. Transplant characteristics are not predictors of short-term survival. Graft survival depends on pre-ICU graft function, disease severity, and renal toxicity of ICU investigations and treatments.

Contemporary Reviews in Sleep Medicine

Chest. 2016;149(6):1556-1565. doi:10.1016/j.chest.2016.02.670

There is a widening gap between sleep provider access and patient demand for it. An American Academy of Sleep Medicine position paper recently recognized sleep telemedicine as one tool to narrow that divide. We define the term sleep telemedicine as the use of sleep-related medical information exchanged from one site to another via electronic communications to improve a patient’s health. Applicable data transfer methods include telephone, video, smartphone applications, and the Internet. Their usefulness for the treatment of insomnia and sleep-disordered breathing is highlighted. Sleep telemedicine programs range in complexity from telephone-based patient feedback systems to comprehensive treatment pathways incorporating real-time video, telephone, and the Internet. While large, randomized trials are lacking, smaller studies comparing telemedicine with in-person care suggest noninferiority in terms of patient satisfaction, adherence to treatment, and symptomatic improvement. Sleep telemedicine is feasible from a technological and quality-driven perspective, but cost uncertainties, complex reimbursement structures, and variable licensing rules remain significant challenges to its feasibility on a larger scale. As legislative reform pends, larger randomized trials are needed to elucidate impact on patient outcomes, cost, and health-care system accessibility.

Topics in Practice Management

Chest. 2016;149(6):1566-1570. doi:10.1016/j.chest.2016.02.637

Auditors in Medicare overpayment or False Claims Act (FCA) cases often use statistical extrapolation to estimate a health-care provider’s total liability from a small sample of audited claims. Courts treat statistical extrapolation differently depending on the context. They generally afford the government substantial discretion in using statistical extrapolation in overpayment cases. By contrast, courts typically more closely scrutinize the use of extrapolation in FCA cases involving multiple damages and civil penalties to ensure that the sample truly reflects the entire universe of claims and that the extrapolation rests on a sound methodological foundation. In recent cases, however, multiple courts have allowed the use of extrapolation in FCA cases. When auditors attempt to use statistical extrapolation, providers should closely inspect the sample and challenge the extrapolation when any reasonable argument exists that the sample does not constitute a reliable or accurate representation of all the provider’s claims.

Pectoriloquy

Chest. 2016;149(6):1571. doi:10.1016/j.chest.2015.10.010
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    You have extremely dense breasts.
    Snow-capped peaks in a furious blizzard

    on display in this dimly-lit room.
    Flurry of connective tissue appears

    like a whiteout on the Buffalo thruway.
    How I dread driving in zero visibility

    when a semi can easily jackknife,
    send us on an unknown detour.

    Who could find a snow owl in these squalls?
    Every soft feather concealed.

    It looks normal, but I can’t see anything.
    Next time get an ultrasound or 3D image.

    Gripping the steering wheel tighter,
    I hope for blind luck.

Chest. 2016;149(6):1572. doi:10.1016/j.chest.2015.12.004
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    Please return my dignity.
    It’s quite the proper thing to do.
    It was only a temporary loan-
    When I disrobed.
    When I trusted you with my secrets.
    So, before you say ‘goodbye’
    (If you remember to do so),
    Before you pass your responsibilities
    On to the nurse, the receptionist…
    Please make good your oath.
    Leave me at least as well as you found me;
    As proud as I felt or feigned
    Before you pulled back the curtain.
    Cobble me together.
    Palliate me, cloak me,
    Wrap me up again.

Chest. 2016;149(6):1573-1574. doi:10.1016/j.chest.2015.12.006
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July 2, 2015: The U.S. Food and Drug Administration today approved the first drug for cystic fibrosis directed at treating the cause of the disease in people who have two copies of a specific mutation.

    Prologue
    Tilt my head up and to the right,
    catch the eye of the moon and beg.
    For one day without it. One school day
    with no pain, no worry, no wheezing
    or crackling or coughing. Wish the moon
    would reach in with his moony fingers
    and pull out all the mucus like half-
    dried rubber cement, peel it away.

    My nurse asks where the congestion
    lurks. I dip into my chest, send
    a little mind-speck of light from
    the back of my eyes down the inside
    of my face, down my throat, let it sweep
    through my upper chest before dropping
    like a plumb bob to the cellar
    of my lungs. I point and she listens
    with the stethoscope. Her faraway
    look becomes a smile; she high-fives
    me. Or she shakes her head and says
    “An inch to the left.” I learn.

    Week One
    I.
    Fifteen minutes after commencement,
    a thin, clear film of saliva slips across
    my tongue, back to front. Spit. I have
    not had spit in fifteen years. Moisture
    layers my eyes--not tears, just the normal
    wetness of normal eyes. When the fan
    is on, my lids close over the cool.

    II.
    It is not the sensation I expected. The moon
    has not ravaged my body. Instead, a French
    Revolution has risen up. Creeks and rivulets
    are flooding the alveoli streets with pickaxes
    and battering rams. The rioters push
    against the old stone battlements that have
    been getting thicker and more impenetrable
    for four decades. Pain climbs until they bring
    the walls down and rebels and stones
    are coughed down the channels, up, and out.

    III.
    Sick, my chest once held a baby sock
    of air, but now the shapes change hourly.
    At first, a finger on the left. Above
    it, a playing card teaser that soon fleshes
    out to the fullness of a stretching hand.
    Then, a clementine-sized shock. A thin,
    grey veil of headrush every time
    I breathe in. I should be Julie Andrews,
    my arms flung out on top
    of the mountain. Instead I am Boo
    Radley behind a door.

    Week Two
    I.
    Two a.m., seized awake. A thousand
    steel balls on strings pulled
    through my left lung toward the center.
    A thousand knives. A thousand intruders.
    The front line ignites. Its contour edges
    to my midline, the pain a sharp angel,
    bringing ruin, bringing salvation.

    II.
    I gain a cannonball of lung in one day.
    The controlled explosion brings up
    years of my life. A breath,
    and my favorite red shirt in middle school,
    news stories long forgotten, an election
    I wore a badge for flash
    into mind. The memories were hiding,
    barricaded by dark green milestones. I am
    breathing as well as when I was thirteen.

    III.
    99.9 degrees. Skin sore, as if my back is
    some kind of spiny animal. I want
    to pull out the invisible hairs on my
    sacrum. A cleaner lung smell makes
    the sinus infection stand out
    as a lone, sad trumpet.

    IV.
    Energy level steadily increasing. Dizzy
    every afternoon to bedtime. Constant
    confusion like a camera changing focus.
    Sputum color and consistency, thin
    and light green. Fighting cautious optimism.

    Epilogue
    We go for a walk which turns to a bike
    ride when we see the rentals. Indian summer,
    and the crowds are out. A hundred
    pedal-turns in and I am waiting for the pain,
    the usual moment when my thighs,
    hamstrings, and calves fill with sand and glue.
    Instead, the clear, deep breaths reach my toes
    and the rubber-band muscles push without effort.
    The sun has found me.

Correspondence

Chest. 2016;149(6):1575. doi:10.1016/j.chest.2016.02.685
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We read with great attention the article by Liu et al in a recent issue of CHEST (May 2016) regarding ultrasound diagnostic criteria of transient tachypnea of the neonate (TTN). It is an unmasked, retrospective series by a single ultrasonographer that reaches conclusions different from what had been previously described.,,, Liu et al show that no ultrasound picture is unique to TTN and basically not distiguishable from respiratory distress syndrome (RDS). They also allude to a different ultrasound appearance between the acute vs the convalescent patient with TTN. Although some degree of overlapping is acknowledged, TTN and RDS are different diseases. The former results from delayed clearing of lung fluid, particularly frequent in late preterm infants. The latter is due to deficient surfactant production, a common feature of significant prematurity.

Chest. 2016;149(6):1575-1576. doi:10.1016/j.chest.2016.03.022
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We thank Raimondi et al for their attention and insightful comments in response to our recent publication describing how ultrasound is used to diagnose transient tachypnea of newborns (TTN). Raimondi et al have conducted a large amount of research in this field, and reviewing their publications has increased our knowledge.

Chest. 2016;149(6):1576-1577. doi:10.1016/j.chest.2016.02.678
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In a recent issue of CHEST (February 2016), Bruce et al describe decision-making when surrogates disagree with an advance directive and then lay out four considerations for overriding an advance directive. The authors may be comforted to know that there is empiric evidence showing that most patients would welcome having their advance directive ignored. In a study of 300 terminally ill patients who were asked whether they would want their advance directive followed should a loved one object, 54% said they would want their advance directive ignored. Reasons given were that surrogates made better decisions, or the patients were concerned that the surrogates’ best interest be paramount.

Chest. 2016;149(6):1577-1578. doi:10.1016/j.chest.2016.02.677
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Dr Terry has commented on our article in CHEST, where we provide a conceptual framework for how clinicians could approach situations when surrogate decision-makers interpret patients’ wishes differently than what is expressed through patients’ advance directives (ADs). We thank our colleague for his comments and for supporting our analyses. As clinical ethicists, we believe we cannot formulate ethically sound frameworks unless they are (1) practical frameworks, (2) tied to well-established ethical concepts, and (3) grounded in empirical evidence. Thus, we are aware of data suggesting that patients would welcome having their surrogates “override” patients’ ADs; some of these data have been published recently.,

Chest. 2016;149(6):1578-1579. doi:10.1016/j.chest.2016.02.683
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We read with interest the article titled “Update on Diffuse Lung Disease in Children” from Vece and Young in a recent issue of CHEST (March 2016). We particularly appreciated their clear approach and recommendations about this heterogeneous and complex group of rare conditions. The exhaustive description of diagnosis, evaluations, and treatments is helpful, as most institutions will only manage a few cases per year and can be confused when faced with childhood interstitial lung disease (chILD).

Chest. 2016;149(6):1579-1580. doi:10.1016/j.chest.2016.03.020
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We thank Dr Berteloot and colleagues for their interest in our review article recently published in CHEST. The authors present two interesting cases as a platform to discuss a 2010 report of chest CT scan findings in neuroendocrine cell hyperplasia of infancy (NEHI). Berteloot et al raise concerns about the specificity of chest CT scans by proposing that their cases had imaging findings suggestive of NEHI but did not ultimately have NEHI based on the histologic findings and the clinical response to corticosteroid therapy.

Chest. 2016;149(6):1580-1581. doi:10.1016/j.chest.2016.03.052
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We read with interest the article by Zaidi and Koenig in a recent issue of CHEST (February 2016). The intersection of tele-medicine with point-of-care ultrasound (PCUS) in clinical decision-making represents an exciting frontier that can improve access to dynamic diagnostic modalities. Remote mentorship by a tele-medicine specialist allows physicians and nonphysicians alike to obtain high-quality, clinically useful images with PCUS.

Chest. 2016;149(6):1581-1582. doi:10.1016/j.chest.2016.03.053
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We thank Dr Levine and colleagues for their interest in our letter to the editor and pilot study regarding the use of point-of-care ultrasound (PCUS) through the tele-ICU. Our small pilot study serves as a proof of concept and provides evidence that PCUS images obtained at the bedside can be accurately interpreted by a tele-intensivist.

Chest. 2016;149(6):1582-1583. doi:10.1016/j.chest.2016.03.054
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We read the study by Whitson et al in this issue of CHEST (June 2016) with great interest. We applaud their creativity regarding the replacement of IV vasopressors with midodrine in the recovery phase of septic shock, which may have financial benefits without compromising patient care. The investigators suggest that adding midodrine reduced the duration of vasopressor use and ICU length of stay, a finding different from that of Poveromo et al. These disparate findings may be due to different patient populations and midodrine dosing schemes.

Chest. 2016;149(6):1583-1584. doi:10.1016/j.chest.2016.03.058
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We appreciate the correspondence of Drs Hammond, Smith, and Meena and their interest in our study examining the use of midodrine during resolution of septic shock. In response to their comments regarding the findings of our study compared with a recent retrospective study by Poveromo et al, we agree that the populations in the two studies were markedly different. In the study by Poveromo et al, < 15% of patients received a diagnosis of septic shock, and “providers elected to use midodrine in a patient population inherently different from those who did not receive midodrine.” In their study, midodrine was used predominantly in patients who had already failed IV vasopressor weaning. In addition, the midodrine doses observed in our study were twice those observed by Poveromo et al. Midodrine has been shown to reduce the dosage of IV vasopressors, and our findings of a shortened ICU length of stay may be secondary to our unique patient population experiencing vasoplegia in septic shock and the early institution of higher doses of midodrine prior to failed or difficult weaning of IV vasopressors.

Chest. 2016;149(6):1584-1586. doi:10.1016/j.chest.2016.03.025
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Transbronchial lung biopsy (TBLB) is a common bronchoscopic procedure used in the diagnosis of sarcoidosis. Whether use of alligator forceps would increase the diagnostic yield of TBLB remains unknown. In this prospective, randomized controlled trial, consecutive subjects with clinicoradiologic suspicion of sarcoidosis were randomized 1:1 to undergo TBLB with either cup or alligator forceps. The primary end point was the diagnostic yield of TBLB, defined as demonstration of granulomas in subjects with a final diagnosis of sarcoidosis. The study protocol (e-Table 1) was approved by the Institute Ethics Committee (reference number NK/1995/Res/310), and written informed consent was obtained from all subjects. The trial was registered at ClinicalTrials.gov.

Chest. 2016;149(6):1586-1587. doi:10.1016/j.chest.2016.03.062
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We read with interest the article by Bak et al in CHEST (January 2016) on quantitative CT scanning analysis of pure ground-glass opacity nodules to predict further CT change. We would like to hear the authors’ comments regarding the following three points. First, why did the authors include three different histological tumor types in this study, namely adenocarcinoma in situ, minimally invasive adenocarcinoma, and invasive adenocarcinoma. Does this mean “ground-glass opacity nodules” were classified into these three pathological types upon examination of resected tumors? Second, although the authors provided a definition for a “central fibrotic lesion” in the Materials and Methods section, a lesion’s “solid component” was not defined anywhere in the article. We are unclear as to the confirmed pathology of the “solid component.” Were there other pathological changes such as intratumor lymphatic, vascular, or pleural alterations that were also considered a “solid component”? Finally, was the “fibrous area” always located at the “central” part of the lesion”? How was its position evaluated?

Chest. 2016;149(6):1587-1588. doi:10.1016/j.chest.2016.04.005
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We would like to thank to Drs Tamura and Satoh for their interest regarding our study on quantitative CT analysis of pure ground-glass opacity nodules to predict further CT change. We are grateful for their questions, for which our responses are listed as follows.

Chest. 2016;149(6):1588. doi:10.1016/j.chest.2016.03.061
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Anatomical imbalance in OSA can be assessed with upper airway imaging taking into account the amount of soft tissues within a bony enclosure; such imbalance has been shown to increase the collapsibility of the passive pharyngeal airway. The study by Schorr et al examined the relationship between tongue/mandibular volume ratio and passive critical closing pressure in white and Japanese-Brazilian subjects. It showed that this anatomical imbalance only influenced passive critical closing pressure in the white subjects. An important methodological consideration in this study is that the bony compartment was a measurement of the mandibular bone, rather than the mandibular bony “enclosure” volume. The shorter mandible length in the Japanese/Brazilian subjects is also inconsistent with the larger mandibular bony volume reported, suggesting that the bony measurement used was not demonstrative of the degree of craniofacial bony restriction. Imaging studies examining upper airway anatomical imbalance should apply methods to measure the bony enclosure.,

Chest. 2016;149(6):1588-1589. doi:10.1016/j.chest.2016.04.003
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Our recent publication in CHEST (March 2016) on the craniofacial predictors of passive critical closing pressure (Pcrit) among Japanese-Brazilians and whites was commented upon by Dr Lee. We performed Pcrit measurements and upper airway CT in 78 Japanese-Brazilians and whites and showed that Pcrit is influenced by different predictors among Japanese-Brazilians and whites.

Chest. 2016;149(6):1589-1590. doi:10.1016/j.chest.2016.03.055
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We have read with great interest the article entitled “Recalibration of the HAS-BLED Score: Should Hemorrhagic Stroke Account for One or Two Points?” in a recent issue of CHEST (February 2016). The authors noted that after a hemorrhagic stroke, it is unclear whether it should count 1 point (either for stroke or bleeding) or 2 points (1 point each for stroke and bleeding) on the bleeding risk score HAS-BLED (hypertension, abnormal renal/liver function [1 or 2 points], stroke, bleeding history or predisposition, labile international normalized ratio, elderly [> 65 years], drugs/alcohol concomitantly [1 or 2 points]). About 2 years ago, we emphasized this issue, in addition to other criteria used in HAS-BLED scoring, in our article entitled “Should HAS-BLED scoring be revised for better risk estimation in patients with intracerebral hemorrhage?” In this article, we suggested that the type of stroke should be evaluated separately (as ischemic or hemorrhagic) for a better evaluation and estimation of recurrent intracerebral hemorrhage. In the study of Nielsen et al, recalibration of the HAS-BLED score (counting 2 points for a hemorrhagic stroke) resulted in improved accuracy of predicting major bleeding events, which supports our article and suggestions. Such an approach would result in a more accurate assessment of bleeding risk in patients with atrial fibrillation.

Chest. 2016;149(6):1590-1591. doi:10.1016/j.chest.2016.03.057
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We thank Ince and Senel for their interest in our research. The objective of our commentary article was to clarify an opacity incorporated into the bleeding risk score HAS-BLED (hypertension, abnormal renal/liver function [1 or 2 points], stroke, bleeding history or predisposition, labile international normalized ratio, elderly [> 65 years], drugs/alcohol concomitantly [1 or 2 points]). This question is encountered in everyday clinical practice: does a hemorrhagic stroke count as a bleeding event in addition to the stroke event? Using the well-validated nationwide Danish registries, we found that the recalibrated HAS-BLED score more accurately predicted major bleeding in patients sustaining an intracranial hemorrhage (ICH).

Selected Reports

Chest. 2016;149(6):e157-e160. doi:10.1016/j.chest.2015.12.022

Myiasis refers to a parasitic infestation of vertebrate mammals by dipterous larvae (maggots) of higher flies. Infections in humans typically occur in tropical and subtropical regions, regions with limited medical access, and areas with poor hygiene and living conditions. Infestations in humans have been described in subcutaneous, nasal, ocular, oropharyngeal, and orotracheal cases; however, reports of pulmonary myiasis in humans in the United States and other developed countries are extremely rare. We describe a patient with recently diagnosed primary pleural angiosarcoma who presented to our clinic for the management of a thoracostomy tube and was diagnosed with pleural myiasis.

Chest. 2016;149(6):e161-e167. doi:10.1016/j.chest.2015.12.032

In emphysema airway resistance can exceed collateral airflow resistance, causing air to flow preferentially through collateral pathways. In severe emphysema ventilation through openings directly through the chest wall into the parenchyma (spiracles) could bypass airway obstruction and increase alveolar ventilation via transpleural expiration. During lung transplant operations, spiracles occasionally can occur inadvertently. We observed transpleural expiration via spiracles in three subjects undergoing lung transplant for emphysema. During transpleural spiracle ventilation, inspiratory tidal volumes (TV) were unchanged; however, expiration was entirely transpleural in two patients whereas the expired TV to the ventilator circuit was reduced to 25% of the inspired TV in one. At baseline, mean PCO2 was 61 ± 5 mm Hg, which decreased to a mean PCO2 of 49 ± 5 mm Hg (P = .05) within minutes after transpleural spiracle ventilation and further decreased at 1 to 2 h (36 ± 4 mm Hg; P = .002 compared with baseline) on unchanged ventilator settings. This observation of increased alveolar ventilation supports further studies of spiracles as a possible therapy for advanced emphysema.

Ultrasound Corner

Chest. 2016;149(6):e169-e171. doi:10.1016/j.chest.2016.01.035
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A 21-year-old man presented to the ED with a 2-month history of chest pain. During the preceding several days, he described hearing “sloshes” in his chest with positional changes, which ultimately prompted his visit. He has a history of epilepsy and was compliant with his phenytoin therapy.

Chest. 2016;149(6):e173-e175. doi:10.1016/j.chest.2015.12.044
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A 33-year-old woman presents with febrile neutropenia after initiating treatment with deferiprone, an iron chelating agent. She has a history of beta-thalassemia requiring monthly blood transfusions, complicated by iron overload and significant myocardial iron deposition. Before her hospitalization, she was asymptomatic from a cardiac perspective and had normal left and right ventricular systolic function. On admission, the patient was treated for a retropharyngeal abscess with piperacillin-tazobactam.

Chest Imaging and Pathology for Clinicians

Chest. 2016;149(6):e177-e182. doi:10.1016/j.chest.2016.02.665
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A woman in her 30s presented with recurrent low-grade fever and cough (onset, 1 week). She reported occasional night sweats and weight loss of approximately 20 pounds over the past 4 months. She denied nausea, vomiting, diarrhea, or any urinary complaints. Her past medical history was significant for chronic hepatitis C and HIV infection, the latter diagnosed in 2001. She was noncompliant with highly active antiretroviral therapy for more than 4 years and had pneumocystis pneumonia 2 years prior to this presentation. She had a 10-pack per year smoking history and reported active use of cocaine and heroin. The patient denied any occupational exposures.

Chest. 2016;149(6):e183-e190. doi:10.1016/j.chest.2016.02.652
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A 27-year-old female patient was referred to our outpatient clinic with a 1-year history of shortness of breath when walking fast on level ground or when climbing stairs. Symptoms worsened after a second episode of spontaneous left pneumothorax, when a chest tube was placed in another hospital for complete lung expansion. During this hospitalization, an open lung biopsy was performed. There was no history of rhinorrhea, nasal congestion, cough, hemoptysis, wheezing, or expectoration.

Topics: lung , cyst

Pulmonary, Critical Care, and Sleep Pearls

Chest. 2016;149(6):e191-e194. doi:10.1016/j.chest.2015.12.035
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A 65-year-old man with treated latent tuberculous infection presented with 1 week of fevers (up to 39.6°C), chills, headache, lightheadedness, and malaise. He reported a chronic, nonproductive cough without hemoptysis but denied other localizing symptoms, sick contacts, or recent travel. He lived in an urban area in eastern Colorado and owned one healthy dog but otherwise denied known animal exposures. He was a retired oil driller who had worked in southern Arizona, New Mexico, and northern Mexico (Sonora region). Other travel included 3 years in the early 1970s working as a military aircraft mechanic in Vietnam, Laos, and Thailand. Six weeks prior to admission, he began work as a groundskeeper on a golf course that had experienced recent flooding, using a riding mower and exposing himself to airborne dust and organic debris. He smoked a pipe daily for 30 years but quit 2 months prior to presentation, although he continued to smoke marijuana weekly. He denied intravenous drug use.

Chest. 2016;149(6):e195-e199. doi:10.1016/j.chest.2015.12.037
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A 61-year-old man presented with an 18-month history of progressive shortness of breath on exertion, fatigue, worsening bilateral lower extremity edema, abdominal swelling, and increased assistance with activities of daily living. Pertinent past medical history included right-sided pneumonia secondary to Streptococcus pneumoniae that was complicated by empyema, requiring right-sided video-assisted thoracoscopic surgery with decortication 2 years earlier. He had a negative cardiac history, no recent travel in the last 3 years, and no known exposure to tuberculosis. His medications included aspirin and daily furosemide. His symptoms appeared to be refractory to diuretic therapy. Previous workup 6 months earlier included an echocardiography (ECHO) showing enlarged left and right atria with a normal ejection fraction, and a catheterization of the left side of the heart with reported normal left ventricular function and unobstructed coronary arteries.

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