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Editorial

Chest. 2016;149(2):293-294. doi:10.1016/j.chest.2015.12.005
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Contemporary definitions of medical professionalism recognize that clinical practice “rests on the integrity of scientific standards grounded in research evidence and the translation of evidence into practice guidelines, which define the proper use and implementation of diagnostic testing and therapeutics.” Such calls for professionalism have become as much an administrative mandate as an aspirational goal now that guideline recommendations inform the development of physician performance measures created in response to society’s recognition that health care commonly diverges from best practices and too often wastes resources, thereby driving up costs and threatening our ability to deliver effective care., Clinical practice guidelines (CPGs), therefore, represent a critical resource for improving patient care and also helping physicians succeed within reimbursement schemas (eg, pay-for-performance).

Chest. 2016;149(2):295-297. doi:10.1016/j.chest.2015.08.024

The normal pulmonary circulation is a high-flow and low-pressure circuit, capable of handling exercise-associated increases in cardiac output and transmural pressures through distension and recruitment of pulmonary capillaries, which in turn leads to decreased pulmonary vascular resistance. The distensible properties of the pulmonary capillaries represent an important advantage for the right ventricle (RV) during exercise, allowing it to operate with maximal efficiency and at lower energy consumption. If the field of pulmonary hypertension (PH) could identify when this vascular response to exercise becomes abnormal, we may have an advantage for tracking those subclinical, at-risk patients before the development of overt resting PH. The epidemiologic impact of early identification is sizeable when considering that severe delays in PH diagnosis and referral remain a problem in modern clinical practice and for population-derived registries.,,

Chest. 2016;149(2):298-300. doi:10.1016/j.chest.2015.08.021

The effect of socioeconomic status (SES) on health is well established. People with higher incomes, better jobs, and more years of schooling tend to be healthier and live longer whereas lower SES is linked to a number of factors that influence health status, including access to health care, health behaviors, lifestyle factors, chronic stress, and environmental and neighborhood exposures. Health disparities can result from limited access to clinical care owing to lack of availability on a national or local level, to limited family resources that restrict access to specialized services or therapy (financial of physical), or to lack of knowledge or education regarding how the disease should be treated, resulting in poor adherence to therapy.

Chest. 2016;149(2):301-302. doi:10.1016/j.chest.2015.08.018

Atrial fibrillation (AF) and aging have several mutual relationships. As known from many epidemiological studies, both the prevalence and incidence of AF increase sharply after 65 years of age and more than 10% of patients aged at least 85 years (so-called “oldest-old” patients) have clinical AF., However, all of these epidemiological surveys underestimate the real prevalence and incidence of AF since a substantial proportion of elderly patients are asymptomatic, with AF often discovered at a routine check or only at the time of stroke, or even after stroke occurrence.,

Editorials: Point and Counterpoint

Chest. 2016;149(2):303-306. doi:10.1016/j.chest.2015.10.073

We argue that low-dose oxygen therapy (LDOT) does expose patients with COPD to more radiation-like risks than patients without COPD. Three considerations subtend our assertion: radiation and oxygen share oxidative stress mechanisms that constitute radiation-oxygen injury homology (ROIH); patients with COPD have higher, more problematic exposure rates to LDOT vs patients without COPD; and patients with COPD vs patients without COPD have disease burdens that amplify ROIH from LDOT. Thus, LDOT, independent of benefits, poses radiation-like risks with pernicious results that follow stochastic patterns.,

Chest. 2016;149(2):306-308. doi:10.1016/j.chest.2015.10.074

We interpret “radiation-like” risk to represent the potential for cellular toxicity caused by low-dose oxygen (LDO) exposure to result in a deleterious clinical outcome. The question asks whether or not patients with COPD exposed to LDO are at higher risk of cellular toxicity (oxygen toxicity) than patients without COPD who are receiving LDO. Because sufficient evidence of the benefit of LDO in normoxemic patients with COPD is lacking,, discussion will focus on hypoxemic patients with COPD.

Chest. 2016;149(2):308-309. doi:10.1016/j.chest.2015.10.072

We thank Drs Christopher and Repine. We rebut with three points and a reiterative call for a lowest oxygen level acceptable (LOLA) standard based on the “as low as reasonably achievable” standard used in radiology.

Topics: oxygen , toxic effect
Chest. 2016;149(2):309-310. doi:10.1016/j.chest.2015.10.075

We agree with our counterparts’ assertion that “…no ‘gold standard’ trials prove or disprove [their] position.”

Commentary

Chest. 2016;149(2):311-314. doi:10.1378/chest.15-1509

After a hemorrhagic stroke, it is uncertain whether this event scores one point (either for stroke or bleeding) or two points (one point each for stroke and bleeding) on the bleeding risk score termed HAS-BLED (hypertension, abnormal renal/liver function [one or two points], stroke, bleeding history or predisposition, labile international normalized ratio [INR], elderly [> 65 years], drugs/alcohol concomitantly [one or two points]). We investigated the value of a recalibration of the HAS-BLED score to account for two points from a hemorrhagic stroke. Data were analyzed from the Danish nationwide cohort of patients with incident atrial fibrillation (AF) from January 1999 to December 2013. The primary outcome in this observational study was major bleeding. The original and the recalibrated HAS-BLED scores were assessed, and the event rates of major bleeding were calculated. The predictive accuracy of major bleeding was compared by using C-statistics, the net reclassification index (NRI), and integrated discrimination improvement (IDI). An event rate for major bleeding of 4.3 per 100 person-years was recorded in the 210,299 patients with AF. The C-statistics for the two scores were modest: 0.613 (95% CI, 0.607-0.619) for the original score and 0.616 (95% CI, 0.610-0.622) for the recalibrated score. The NRI was 10.0% (95% CI, 7.6-12.4). The relative IDI was 23.6% (95% CI, 15.7-31.5), reflecting that the recalibrated HAS-BLED score more accurately predicted bleeding events. Recalibration of the “S” component in the HAS-BLED score (counting two points for a hemorrhagic stroke) resulted in an increase in the C-statistics, NRI, and IDI. This approach could potentially aid physicians in more accurate assessments of bleeding risk in patients with AF.

Evidence-Based Medicine

Chest. 2016;149(2):315-352. doi:10.1016/j.chest.2015.11.026
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Background  We update recommendations on 12 topics that were in the 9th edition of these guidelines, and address 3 new topics.

Methods  We generate strong (Grade 1) and weak (Grade 2) recommendations based on high- (Grade A), moderate- (Grade B), and low- (Grade C) quality evidence.

Results  For VTE and no cancer, as long-term anticoagulant therapy, we suggest dabigatran (Grade 2B), rivaroxaban (Grade 2B), apixaban (Grade 2B), or edoxaban (Grade 2B) over vitamin K antagonist (VKA) therapy, and suggest VKA therapy over low-molecular-weight heparin (LMWH; Grade 2C). For VTE and cancer, we suggest LMWH over VKA (Grade 2B), dabigatran (Grade 2C), rivaroxaban (Grade 2C), apixaban (Grade 2C), or edoxaban (Grade 2C). We have not changed recommendations for who should stop anticoagulation at 3 months or receive extended therapy. For VTE treated with anticoagulants, we recommend against an inferior vena cava filter (Grade 1B). For DVT, we suggest not using compression stockings routinely to prevent PTS (Grade 2B). For subsegmental pulmonary embolism and no proximal DVT, we suggest clinical surveillance over anticoagulation with a low risk of recurrent VTE (Grade 2C), and anticoagulation over clinical surveillance with a high risk (Grade 2C). We suggest thrombolytic therapy for pulmonary embolism with hypotension (Grade 2B), and systemic therapy over catheter-directed thrombolysis (Grade 2C). For recurrent VTE on a non-LMWH anticoagulant, we suggest LMWH (Grade 2C); for recurrent VTE on LMWH, we suggest increasing the LMWH dose (Grade 2C).

Conclusions  Of 54 recommendations included in the 30 statements, 20 were strong and none was based on high-quality evidence, highlighting the need for further research.

Original Research: Pulmonary Vascular Disease

Chest. 2016;149(2):353-361. doi:10.1378/chest.15-0125

Background  Exercise can distend the normally compliant, thin-walled pulmonary vessels. Loss of distensibility has been suggested as an early marker of pulmonary vascular remodeling. We hypothesized that in mild pulmonary vascular disease (PVD), a reduction in vascular distensibility during exercise occurs prior to the development of overt resting pulmonary hypertension (PH).

Methods  Distensibility α during exercise (percentage change in vessel diameter per mm Hg increase in transmural pressure) was estimated in 90 subjects using a model of the pulmonary circulation and invasive hemodynamic data. Distensible properties in mild PVD without resting PH (PVD-noPH) (n = 33) were compared with control subjects (n = 26) and PVD with overt resting PH (PVD-PH) (n = 31).

Results  Resting mean pulmonary artery pressure (mPpa) levels were 14 ± 4, 20 ± 3, and 34 ± 10 mm Hg with corresponding exercise mPpa-cardiac output slopes of 1.5 ± 0.6, 3.5 ± 0.9, and 5.7 ± 3.2 mm Hg/L/min for control subjects and the PVD-noPH and PVD-PH groups, respectively. The distensible model produced high accuracy and precision with no mean bias and 95% limits of agreement of −4.5 to 4.5 mm Hg between calculated and measured mPpa. Distensibility α was lowest in the PVD-PH group, intermediate in the PVD-noPH group, and highest in control subjects (0.25 ± 0.14%/mm Hg vs 0.45 ± 0.24%/mm Hg vs 1.40 ± 0.45%/mm Hg, P < .0001). Distensibility α discriminated PVD-noPH from control subjects with a sensitivity of 88% and a specificity of 100%. The discriminatory performance of α was similar for the subgroup of PVD-noPH, with a strictly normal resting mPpa ≤ 20 mm Hg.

Conclusions  Loss of pulmonary vascular distensibility during exercise occurs prior to resting PH in PVD. The usefulness of α as a novel vascular index for the early detection of PVD warrants further validation.

Chest. 2016;149(2):362-371. doi:10.1378/chest.15-0535

Background  A subset of patients with hereditary hemorrhagic telangiectasia (HHT) develops pulmonary hypertension (PH) by mechanisms including pulmonary arterial hypertension, high flow, and elevated pulmonary arterial wedge pressure (PAWP). We aimed to describe echocardiographic and hemodynamic characteristics of patients with coexisting HHT and PH.

Methods  We conducted a single-center cohort study of patients with confirmed HHT who underwent right-sided heart catheterization (RHC) and transthoracic two-dimensional echocardiography for suspected PH between June 1, 2003 and September 1, 2013 at Mayo Clinic Rochester, Minnesota.

Results  Of 38 patients with confirmed HHT who underwent RHC and echocardiography, 28 (74%) had a mean pulmonary artery pressure (MPAP) ≥ 25 mm Hg. Of those 28, 12 (43%) had pulmonary arterial hypertension. Two patients had normal PAWP and pulmonary vascular resistance (PVR), with PH secondary to either an atrial septal defect or high cardiac flow. Fourteen patients (50%) had elevated PAWP (≥ 15 mm Hg), nine with evidence of high flow. RHC in all 28 patients demonstrated a MPAP of 41 ± 11 mm Hg, PAWP of 17 ± 10 mm Hg, and PVR of 4.5 ± 4.2 Wood units. Echocardiography demonstrated moderate/severe right ventricular dysfunction in nine patients (32%). The presence of PH trended toward worse survival (P = .06).

Conclusions  PH in patients with HHT occurs by different mechanisms, and there is a trend toward worse survival in patients who develop PH despite the mechanism. The equal predilection toward all subtypes of PH illustrates the necessity of RHC to clarify the hemodynamics.

Chest. 2016;149(2):372-379. doi:10.1378/chest.14-2842

Background  Recent guidelines recommend assessing medical inpatients for bleeding risk prior to providing chemical prophylaxis for VTE. The International Medical Prevention Registry on Venous Thromboembolism (IMPROVE) bleeding risk score (BRS) was derived from a well-defined population of medical inpatients but it has not been validated externally. We sought to externally validate the IMPROVE BRS.

Methods  We prospectively collected characteristics on admission and VTE prophylaxis data each hospital day for all patients admitted for a medical illness to the Walter Reed Army Medical Center over an 18-month period. We calculated the IMPROVE BRS for each patient using admission data and reviewed medical records to identify bleeding events.

Results  From September 2009 through March 2011, 1,668 inpatients met the IMPROVE inclusion criteria. Bleeding events occurred during 45 separate admissions (2.7%); 31 events (1.9%) were major and 14 (0.8%) were nonmajor but clinically relevant. Two hundred fifty-six patients (20.7%) had an IMPROVE BRS ≥ 7.0. Kaplan-Meier curves showed a higher cumulative incidence of major (P = .02) and clinically important (major plus clinically relevant nonmajor) (P = .06) bleeding within 14 days in patients with an IMPROVE BRS ≥ 7.0. An IMPROVE BRS ≥ 7.0 was associated with major bleeding in Cox-regression analysis adjusted for administration of chemical prophylaxis (OR, 2.6; 95% CI, 1.1-5.9; P = .03); there was a trend toward a significant association with clinically important bleeding (OR, 1.9; 95% CI, 0.9-3.7; P = .07).

Conclusions  The IMPROVE BRS calculated at admission predicts major bleeding in medical inpatients. This model may help assess the relative risks of bleeding and VTE before chemoprophylaxis is administered.

Original Research: Genetic and Developmental Disorders

Chest. 2016;149(2):380-389. doi:10.1378/chest.14-2189

Background  Over the past 30 years, therapeutic advances have extended the median lifespan of patients with cystic fibrosis (CF). Hispanic patients are a vulnerable subpopulation with a high prevalence of risk factors for worse health outcomes. The consequences of these differences on health outcomes have not been well described. The objective of this study was to characterize the difference in health outcomes, including mortality rate, between Hispanic and non-Hispanic patients with CF.

Methods  This study is a retrospective analysis of CF Foundation Patient Registry data of California residents with CF, diagnosed during or after 1991, from 1991 to 2010. Ethnicity was self-reported. The primary outcome was mortality. Hazard ratios were estimated from a Cox regression model, stratified by sex, and adjusted for socioeconomic status, clinical risk factors, and year of diagnosis.

Results  Of 1,719 patients, 485 (28.2%) self-identified as Hispanic. Eighty-five deaths occurred, with an overall mortality rate of 4.9%. The unadjusted mortality rate was higher among Hispanic patients than among non-Hispanic patients (9.1% vs 3.3%, P < .0001). Compared with non-Hispanic patients, Hispanic patients had a lower survival rate 18 years after diagnosis (75.9% vs 91.5%, P < .0001). Adjusted for socioeconomic status and clinical risk factors, Hispanic patients had an increased rate of death compared with non-Hispanic patients (hazard ratio, 2.81; 95% CI, 1.70-4.63).

Conclusions  Hispanic patients with CF have a higher mortality rate than do non-Hispanic patients, even after adjusting for socioeconomic status and clinical severity. Further investigation into the mechanism for the measured difference in lung function will help inform interventions and improve the health of all patients with CF.

Chest. 2016;149(2):390-400. doi:10.1378/chest.15-0676

Background  Monitoring potential changes in the epidemiology of cystic fibrosis (CF) pathogens furthers our understanding of the potential impact of interventions.

Methods  We performed a retrospective analysis using data reported to the Cystic Fibrosis Foundation Patient Registry (CFFPR) from 2006 to 2012 to determine the annual percent changes in the prevalence and incidence of selected CF pathogens. Pathogens included Pseudomonas aeruginosa, methicillin-susceptible Staphylococcus aureus (MSSA), methicillin-resistant S aureus (MRSA), Haemophilus influenzae, Burkholderia cepacia complex, Stenotrophomonas maltophilia, and Achromobacter xylosoxidans. Changes in nontuberculous mycobacteria (NTM) prevalence were assessed from 2010 to 2012, when the CFFPR collected NTM species.

Results  In 2012, the pathogens of highest prevalence and incidence were MSSA and P aeruginosa, followed by MRSA. The prevalence of A xylosoxidans and B cepacia complex were relatively low. From 2006 to 2012, the annual percent change in overall (as well as in most age strata) prevalence and incidence significantly decreased for P aeruginosa and B cepacia complex, but significantly increased for MRSA. From 2010 to 2012, the annual percent change in overall prevalence of NTM and Mycobaterium avium complex increased.

Conclusions  The epidemiology of CF pathogens continues to change. The causes of these observations are most likely multifactorial and include improvements in clinical care and infection prevention and control. Data from this study will be useful to evaluate the impact of new therapies on CF microbiology.

Original Research: Cardiovascular Disease

Chest. 2016;149(2):401-412. doi:10.1378/chest.15-1095

Background  Atrial fibrillation (AF) is increasingly prevalent with age, and increasing age is an independent risk factor for ischemic stroke. Oral anticoagulant (OAC) therapy use in the extreme elderly (aged ≥ 85 years) is challenging.

Methods  The Fushimi AF Registry is a community-based prospective study of Japanese patients with AF (79 participating medical institutions in Fushimi-ku, Kyoto, Japan). Patient enrollment started in March 2011, and follow-up data were available for 3,304 patients as of July 2014. We compared clinical characteristics and outcomes between the extreme elderly group (n = 479 [14.5%]) and other age-groups.

Results  The extreme elderly group had a higher prevalence of major comorbidities and risk scores for stroke but received fewer OACs. After a mean follow-up of 2.0 years, end points in the extreme elderly group were as follows: all-cause death, 17.6; stroke/systemic embolism, 5.1; and major bleeding, 2.0 per 100 person-years. Extreme age was associated with a higher incidence of combined stroke/systemic embolism and all-cause death (hazard ratio [HR], 3.20; 95% CI, 2.66-3.84; P < .01) and higher incidences of stroke/systemic embolism (HR, 2.57; 95% CI, 1.77-3.65; P < .01) and mortality (HR, 3.48; 95% CI, 2.84-4.25; P < .01) compared with other patients (aged ≤ 84 years). The incidence of major bleeding was not significantly different (HR, 1.40; 95% CI, 0.78-2.36; P = .25).

Conclusions  In the present community-based prospective cohort, Japanese extreme elderly patients with AF had a higher incidence of stroke but similar major bleeding risks compared with the younger AF population.

Trial Registry  UMIN Clinical Trials Registry; No.: UMIN000005834; URL: http://www.umin.ac.jp/ctr/index.htm

Original Research: COPD

Chest. 2016;149(2):413-425. doi:10.1378/chest.15-1752

Background  The COPD Assessment Test (CAT) was developed as a simple instrument to assess health status in patients with COPD. This study aimed to systematically review the determinants of the CAT score, its ability to predict clinical outcomes, and the agreement between CAT (≥ 10) and the modified Medical Research Council scale (mMRC ≥ 2) to categorize patients into the new Global Initiative for Chronic Obstructive Lung Disease classification system.

Methods  From January 1, 2009, to June 30, 2015, databases were searched for studies using CAT in adults with COPD and in general populations aiming to detect COPD. Two investigators independently screened, selected, and extracted data by using a standardized form. Where appropriate, the results were combined in a random effects meta-analysis.

Results  Of 453 studies, 17 were included, and eight were used in the meta-analysis. The models to predict the CAT score were able to explain < 50% of its variance. CAT scores can indicate risk of exacerbation, depression, acute deterioration in health status, and mortality. All studies found a different proportion of patients in each Global Initiative for Chronic Obstructive Lung Disease category using CAT ≥ 10 or mMRC ≥ 2. On average, the distribution was 13% different according to the instrument used. The κ agreement between CAT and mMRC ranged from 0.13 to 0.77.

Conclusions  CAT may be used as a complementary tool in a patient's clinical assessment to predict COPD exacerbation, health status deterioration, depression, and mortality. The interpretation of this meta-analysis does not support the use of the recommended cutoff points of ≥10 for CAT and ≥2 for mMRC as equivalents for the purpose of assessing patient symptoms.

Chest. 2016;149(2):426-434. doi:10.1378/chest.15-0027

Background  Patients with COPD suffer from chronic dyspnea, which is commonly perceived as highly aversive and threatening. Moreover, COPD is often accompanied by disease-specific fears and avoidance of physical activity. However, little is known about structural brain changes in patients with COPD and respective relations with disease duration and disease-specific fears.

Methods  This study investigated structural brain changes in patients with COPD and their relation with disease duration, fear of dyspnea, and fear of physical activity. We used voxel-based morphometric analysis of MRI images to measure differences in generalized cortical degeneration and regional gray matter between 30 patients with moderate to severe COPD and 30 matched healthy control subjects. Disease-specific fears were assessed by the COPD anxiety questionnaire.

Results  Patients with COPD showed no generalized cortical degeneration, but decreased gray matter in posterior cingulate cortex (whole-brain analysis) as well as in anterior and midcingulate cortex, hippocampus, and amygdala (regions-of-interest analyses). Patients’ reductions in gray matter in anterior cingulate cortex were negatively correlated with disease duration, fear of dyspnea, and fear of physical activity. Mediation analysis revealed that the relation between disease duration and reduced gray matter of the anterior cingulate was mediated by fear of physical activity.

Conclusions  Patients with COPD demonstrated gray matter decreases in brain areas relevant for the processing of dyspnea, fear, and antinociception. These structural brain changes were partly related to longer disease duration and greater disease-specific fears, which might contribute to a less favorable course of the disease.

Chest. 2016;149(2):435-446. doi:10.1378/chest.15-0404

Background  The impact of bronchoscopic lung volume reduction (BLVR) on physiologic responses to exercise in patients with advanced emphysema remains incompletely understood. We hypothesized that effective BLVR (e-BLVR), defined as a reduction in residual volume > 350 mL, would improve cardiovascular responses to exercise and accelerate oxygen uptake (o2) kinetics.

Methods  Thirty-one patients (FEV1, 36% ± 9% predicted; residual volume, 219% ± 57% predicted) underwent a constant intensity exercise test at 70% peak work rate to the limit of tolerance before and after treatment bronchoscopy (n = 24) or sham bronchoscopy (n = 7). Physiologic responses in patients who had e-BLVR (n = 16) were compared with control subjects (ineffective BLVR or sham bronchoscopy; n = 15).

Results  e-BLVR reduced residual volume (−1.1 ± 0.5 L, P = .001), improved lung diffusing capacity by 12% ± 13% (P = .001), and increased exercise tolerance by 181 ± 214 s (P = .004). o2 kinetics were accelerated in the e-BLVR group but remained unchanged in control subjects (Δ mean response time, −20% ± 29% vs 1% ± 25%, P = .04). Acceleration of o2 kinetics was associated with reductions in heart rate and oxygen pulse response half-times by 8% (84 ± 14 to 76 ± 15 s, P = .04) and 20% (49 ± 16 to 34 ± 16 s, P = .01), respectively. There were also increases in heart rate and oxygen pulse amplitudes during the cardiodynamic phase post e-BLVR. Faster o2 kinetics in the e-BLVR group were significantly correlated with reductions in residual volume (r = 0.66, P = .005) and improvements in inspiratory reserve volume (r = 0.56, P = .024) and exercise tolerance (r = 0.63, P = .008).

Conclusions  Lung deflation induced by e-BLVR accelerated exercise o2 kinetics in patients with emphysema. This beneficial effect appears to be related mechanistically to an enhanced cardiovascular response to exercise, which may contribute to improved functional capacity.

Chest. 2016;149(2):447-458. doi:10.1378/chest.15-0513

Background  Many epidemiologic studies have documented variable relationships between ambient particulate matter (PM) and COPD hospitalizations and mortality in cities worldwide.

Methods  Comprehensive and systematic searches were performed in the electronic reference databases (PubMed, EMBASE, Google Scholar, Ovid, and Web of Science) with specific search terms and selection criteria for relevant studies. Summary ORs and 95% CIs were calculated to evaluate the relationship between short-term exposure to PM with aerodynamic diameters ≤ 2.5 μm (PM2.5) and COPD hospitalizations and mortality. The sources of heterogeneity and the effect of potential confounders were explored using subgroup analyses. Study findings were analyzed using a random effects model and a fixed effects model in COPD hospitalizations and mortality, respectively.

Results  The search yielded 12 studies suitable for meta-analysis of hospitalizations and six studies suitable for the mortality meta-analysis until April 15, 2015. A 10-μg/m3 increase in daily PM2.5 (lag days 0-7) was associated with a 3.1% (95% CI, 1.6%-4.6%) increase in COPD hospitalizations and a 2.5% (95% CI, 1.5%-3.5%) increase in COPD mortality. Significant publication bias was not found in studies focusing on the relationship between short-term PM2.5 exposure and COPD hospitalizations and mortality.

Conclusions  Our combined analysis indicated that short-term exposure to a 10-μg/m3 increment of ambient PM2.5 is associated with increased COPD hospitalizations and mortality. Further study is needed to elucidate to what extent this relationship is causal, together with other factors, and to elucidate the mechanism by which PM2.5 induces activation of cellular processes promoting COPD exacerbations.

Chest. 2016;149(2):459-466. doi:10.1378/chest.14-2554

Background  An estimated 700 million people suffer from mosquito-borne diseases worldwide. Various types of mosquito repellents are widely used to prevent mosquito bites. The objectives of this study were (1) to measure the indoor levels of particulate matter < 2.5 μm in mean aerodynamic diameter (PM2.5) and carbon monoxide (CO) during the burning of mosquito coils (MCs) and study the impact of indoor ventilation patterns; and (2) to study and compare the prevalence of respiratory ailments in homes using different types of mosquito repellents.

Methods  Indoor PM2.5 and CO levels were measured inside a bedroom during the burning of MCs keeping the window and/or door open/closed over a 6-h duration. A cross-sectional survey was conducted in three villages where 465 individuals were administered a questionnaire that captured demographic details, type and duration of mosquito repellents used, and prevalence of respiratory symptoms and diseases.

Results  Fifty-three percent of the subjects burned MCs on most days of the week, and 63% did so with their doors and windows closed. Burning of MCs produced very high levels of PM2.5 (1,031 μg/m3 mean, 1,613 μg/m3 peak) and CO (6.50 parts per million (ppm) mean, 10.27 ppm peak) when both the door and window were closed. These levels reduced by around 50% when the window was opened and > 95% when both the window and the door were opened. The prevalence rates of respiratory symptoms and diseases were higher in subjects using MCs, although not statistically significant. Those living in smaller homes and using MCs had significantly greater morbidity.

Conclusions  Burning of MCs produces indoor levels of PM2.5 and CO that are higher than those reported during the burning of biomass fuels for cooking purposes and may be associated with respiratory morbidity.

Chest. 2016;149(2):467-473. doi:10.1378/chest.15-0529

Background  COPD is a major cause of all-cause mortality. We examined predictors of 1-year mortality in patients with severe COPD and major depression after inpatient treatment in a rehabilitation hospital.

Methods  We screened 898 consecutively admitted patients. Of these, 138 patients received the diagnoses of COPD according to American Thoracic Society Guidelines and major depression by Diagnostic and Statistical Manual of Mental Disorders, 4th edition and signed consent; 67 were randomized to a treatment adherence enhancement intervention and 71 to usual care. We assessed history of falls, dyspnea-related disability, severity of depression, medical burden, and cognitive functioning. Following discharge from inpatient rehabilitation, participants were prospectively followed, and mortality was ascertained over 52 weeks from hospital notes and reports of primary care physicians and relatives.

Results  One-year, all-cause mortality was 22% (31 of 138). Multivariate Cox regression analysis showed that history of falls in the 6 months preceding hospital admission was the strongest predictor of mortality (OR, 3.05; 95% CI, 1.40-6.66; P < .005). Dyspnea during activities (Pulmonary Functional Status and Dyspnea Questionnaire-Modified domain) was also associated with mortality (OR, 1.05; 95% CI, 1.02-1.08; P < .002). Depression severity, medical burden, and cognitive impairment were not predictors of mortality.

Conclusions  Recent falls and dyspnea during activities identify subgroups of depressed patients with COPD at increased risk for all-cause mortality. These subgroups are in need of clinical attention and follow-up and can serve as targets for prevention research aiming to inform clinical strategies and public health planning.

Chest. 2016;149(2):474-482. doi:10.1378/chest.14-2309

Background  Cigarette smoking is a major environmental contributor to COPD, but understanding its epigenetic regulation of oxidative genes involved in the pathogenesis of COPD remains elusive.

Methods  We analyzed DNA methylation on glutamate-cysteine ligase catalytic subunit (GCLC), glutathione S-transferase M1 (GSTM1), glutathione S-transferase P1 (GSTP1), and superoxide dismutase 3 (SOD3) promoters in clinical samples from patients with COPD (current-smoker [CS-COPD]; ex-smoker [ES-COPD]) and subjects with normal pulmonary function (current-smoker [CS-NS]; ex-smoker [ES-NS]; never-smoker [NC]). Expression of GCLC messenger RNA (mRNA) and glutathione (GSH) synthesis in these clinical samples and human bronchial epithelial (BEAS-2B) cells stimulated by cigarette-smoke extract (CSE) was evaluated. GCLC mRNA and protein levels were measured to determine effects of demethylation and deacetylation agents on CSE-treated BEAS-2B cells.

Results  The DNA methylation level of the GCLC promoter was significantly increased in CS-COPD, CS-NS, and ES-COPD groups compared with ES-NS and NC groups. However, there were no significant differences in DNA methylation values of GSTM1, GSTP1, and SOD3 promoters among these groups. Expression of GCLC mRNA was downregulated in the lungs, and GSH levels decreased in plasma as a consequence of hypermethylation of the GCLC promoter. Similarly, CSE-treated BEAS-2B cells had hypermethylation of the GCLC gene, mRNA downregulation, and a decreased intracellular GSH level. GCLC expression in CSE-treated BEAS-2B cells was restored by the methylation inhibitor, 5-aza-2ʹ-deoxycytidine, but not by the deacetylation agent, trichostatin A.

Conclusions  Cigarette smoke-induced hypermethylation of the GCLC promoter is related to the initiation and progression of COPD. Our finding may provide a new strategy for COPD intervention by developing demethylation agents targeting GCLC hypermethylation.

Original Research: Sleep Disorders

Chest. 2016;149(2):483-490. doi:10.1378/chest.15-0693

Background  We sought to determine the impact of OSA syndrome (OSAS) on symptoms and quality of life (QoL) among patients with posttraumatic stress disorder (PTSD). In addition, we assessed adherence and response to positive airway pressure (PAP) therapy in this population.

Methods  This was a case-controlled observational cohort study at the Sleep Disorders Center of an academic military medical center. Two hundred consecutive patients with PTSD underwent sleep evaluations. Patients with PTSD with and without OSAS were compared with 50 consecutive age-matched patients with OSAS without PTSD and 50 age-matched normal control subjects. Polysomnographic data, sleep-related symptoms and QoL measures, and objective PAP usage were obtained.

Results  Among patients with PTSD, more than one-half (56.6%) received a diagnosis of OSAS. Patients with PTSD and OSAS had lower QoL and more somnolence compared with the other groups. Patients with PTSD demonstrated significantly lower adherence and response to PAP therapy. Resolution of sleepiness occurred in 82% of patients with OSAS alone, compared with 62.5% of PAP-adherent and 21.4% of nonadherent patients with PTSD and OSAS (P < .001). Similarly, posttreatment Functional Outcomes of Sleep Questionnaire ≥ 17.9 was achieved in 72% of patients with OSAS, compared with only 56.3% of patients with PTSD and OSA who were PAP adherent and 26.2% who were nonadherent (P < .03).

Conclusions  In patients with PTSD, comorbid OSAS is associated with worsened symptoms, QoL, and adherence and response to PAP. Given the negative impact on outcomes, the possibility of OSAS should be considered carefully in patients with PTSD. Close follow-up is needed to optimize PAP adherence and efficacy in this at-risk population.

Original Research: Diffuse Lung Disease

Chest. 2016;149(2):491-498. doi:10.1378/chest.15-0530

Background  Idiopathic pulmonary fibrosis is a progressive lung disease with variable course. The Gender-Age-Physiology (GAP) Index and staging system uses clinical variables to stage mortality risk. It is unknown whether clinical staging predicts future decline in pulmonary function. We assessed whether the GAP stage predicts future pulmonary function decline and whether interval pulmonary function change predicts mortality after accounting for stage.

Methods  Patients with idiopathic pulmonary fibrosis (N = 657) were identified retrospectively at three tertiary referral centers, and baseline GAP stages were assessed. Mixed models were used to describe average trajectories of FVC and diffusing capacity of the lung for carbon monoxide (Dlco). Multivariable Cox proportional hazards models were used to assess whether declines in pulmonary function ≥ 10% in 6 months predict mortality after accounting for GAP stage.

Results  Over a 2-year period, GAP stage was not associated with differences in yearly lung function decline. After accounting for stage, a 10% decrease in FVC or Dlco over 6 months independently predicted death or transplantation (FVC hazard ratio, 1.37; Dlco hazard ratio, 1.30; both, P ≤ .03). Patients with GAP stage 2 with declining pulmonary function experienced a survival profile similar to patients with GAP stage 3, with 1-year event-free survival of 59.3% (95% CI, 49.4-67.8) vs 56.9% (95% CI, 42.2-69.1).

Conclusions  Baseline GAP stage predicted death or lung transplantation but not the rate of future pulmonary function decline. After accounting for GAP stage, a decline of ≥ 10% over 6 months independently predicted death or lung transplantation.

Chest. 2016;149(2):499-507. doi:10.1378/chest.15-0615

Background  Pathologic features of end-stage pulmonary sarcoidosis (ESPS) are not well defined; anecdotal reports have suggested that ESPS may mimic usual interstitial pneumonia (UIP). We hypothesized that ESPS has distinct histologic features.

Methods  Twelve patients who received a diagnosis of pulmonary sarcoidosis and underwent lung transplantation were included. Control subjects were 10 age- and sex-matched lung transplant patients with UIP. Hematoxylin and eosin-stained tissue sections were examined for the following features: extent/pattern of fibrosis; presence and quantity (per 10 high-power fields) of fibroblast foci and granulomas; distribution and morphology of granulomas; and presence and extent of honeycomb change. Extent of fibrosis and honeycomb change in lung parenchyma was scored as follows: 1 = 1% to 25%; 2 = 26% to 50%; 3 = 51% to 75%; 4 = 76% to 100% of lung parenchyma.

Results  Eight of 12 cases demonstrated histologic findings typical of ESPS. All showed well-formed granulomas with associated fibrosis distributed in a distinct lymphangitic fashion. Granulomas were present in hilar or mediastinal lymph nodes from six of six patients with ESPS and none of eight control subjects. The extent of fibrosis, honeycomb change, and fibroblast foci was significantly lower in ESPS cases compared with control cases. Two patients with remote histories of sarcoidosis showed histologic features of diseases other than ESPS (UIP and emphysema) without granulomas. Two patients with atypical clinical findings demonstrated nonnecrotizing granulomas combined with either severe chronic venous hypertension or UIP.

Conclusions  ESPS and UIP have distinct histopathologic features in the lungs. Patients with a pretransplant diagnosis of sarcoidosis may develop other lung diseases that account for their end-stage fibrosis.

Original Research: Bronchiectasis

Chest. 2016;149(2):508-515. doi:10.1016/j.chest.2015.10.066

Background  Children with recurrent protracted bacterial bronchitis (PBB) and bronchiectasis share common features, and PBB is likely a forerunner to bronchiectasis. Both diseases are associated with neutrophilic inflammation and frequent isolation of potentially pathogenic microorganisms, including nontypeable Haemophilus influenzae (NTHi), from the lower airway. Defective alveolar macrophage phagocytosis of apoptotic bronchial epithelial cells (efferocytosis), as found in other chronic lung diseases, may also contribute to tissue damage and neutrophil persistence. Thus, in children with bronchiectasis or PBB and in control subjects, we quantified the phagocytosis of airway apoptotic cells and NTHi by alveolar macrophages and related the phagocytic capacity to clinical and airway inflammation.

Methods  Children with bronchiectasis (n = 55) or PBB (n = 13) and control subjects (n = 13) were recruited. Alveolar macrophage phagocytosis, efferocytosis, and expression of phagocytic scavenger receptors were assessed by flow cytometry. Bronchoalveolar lavage fluid interleukin (IL) 1β was measured by enzyme-linked immunosorbent assay.

Results  For children with PBB or bronchiectasis, macrophage phagocytic capacity was significantly lower than for control subjects (P = .003 and P < .001 for efferocytosis and P = .041 and P = .004 for phagocytosis of NTHi; PBB and bronchiectasis, respectively); median phagocytosis of NTHi for the groups was as follows: bronchiectasis, 13.7% (interquartile range [IQR], 11%-16%); PBB, 16% (IQR, 11%-16%); control subjects, 19.0% (IQR, 13%-21%); and median efferocytosis for the groups was as follows: bronchiectasis, 14.1% (IQR, 10%-16%); PBB, 16.2% (IQR, 14%-17%); control subjects, 18.1% (IQR, 16%-21%). Mannose receptor expression was significantly reduced in the bronchiectasis group (P = .019), and IL-1β increased in both bronchiectasis and PBB groups vs control subjects.

Conclusions  A reduced alveolar macrophage phagocytic host response to apoptotic cells or NTHi may contribute to neutrophilic inflammation and NTHi colonization in both PBB and bronchiectasis. Whether this mechanism also contributes to the progression of PBB to bronchiectasis remains unknown.

Original Research: Chest Infections

Chest. 2016;149(2):516-525. doi:10.1016/j.chest.2015.11.017

Background  It is often stated that the lifetime risk of developing active TB after an index infection is 5% to 10%, one-half of which accrues in the 2 to 5 years following infection. The goal of this study was to determine whether such estimates are consistent with local programmatic data.

Methods  This study included close contacts of individuals with active pulmonary TB notified in the Australian state of Victoria from January 1, 2005, to December 31, 2013, who we deemed to have been infected as a result of their exposure. Survival analysis was first performed on the assumption of complete follow-up through to the end of the study period. The analysis was then repeated with imputation of censorship for migration, death, and preventive treatment, using local mortality and migration data combined with programmatic data on the administration of preventive therapy.

Results  Of 613 infected close contacts, 67 (10.9%) developed active TB during the study period. Assuming complete follow-up, the 1,650-day cumulative hazard was 11.5% (95% CI, 8.9-14.1). With imputation of censorship for death, migration, and preventive therapy, the median 1,650-day cumulative hazard over 10,000 simulations was 14.5% (95% CI, 11.1-17.9). Most risk accrued in the first 5 months after infection, and risk was greatest in the group aged < 5 years, reaching 56.0% with imputation, but it was also elevated in older children (27.6% in the group aged 5-14 years).

Conclusions  The risk of active TB following infection is several-fold higher than traditionally accepted estimates, and it is particularly high immediately following infection and in children.

Chest. 2016;149(2):526-534. doi:10.1378/chest.14-2768

Background  In Japan, the routine use of early antiviral therapy for patients with influenza is standard.

Methods  This multicenter prospective cohort evaluation of hospitalized patients with laboratory-confirmed influenza identified prognostic factors among the patients receiving antiviral therapy.

Results  Of 1,345 patients with influenza (766 pediatric, 579 adult), excluding those aged < 1 year (who are not approved for antiviral therapy), 97.7% (1,224 of 1,253) received antiviral therapy. Among the adult patients, 24 (4.1%) died within 30 days, whereas none of the pediatric patients died. Five hundred twenty-eight (91.2%) adult patients had influenza A, 509 (87.9%) had a chronic underlying illness, and 211 (36.4%) had radiographically confirmed pneumonia. Twenty of the 24 patients who died had pneumonia of the following etiologies: Streptococcus pneumoniae (12.3%); Staphylococcus aureus (10.9%), including methicillin-resistant S aureus (MRSA) 3.3%; Enterobacteriaceae (8.1%); and Pseudomonas aeruginosa (3.3%). Of the adult patients, 151 were classified as having community-acquired pneumonia (CAP) and 60 as having health-care-associated pneumonia (HCAP). Inappropriate therapy was more common in HCAP than in CAP (15.2% vs 2%, P = .001). Potential multidrug-resistant (MDR) pathogens were more common (21.7% vs 2.6%, P < .001) in patients with HCAP, particularly MRSA (10% vs 0.7%, P = .002) and P aeruginosa (8.3% vs 1.3%, P = .021). Using Cox proportional hazards modeling with prescribed independent variables, male sex, severity score, serum albumin levels (malnutrition), and pneumonia were associated with survival 30 days from the onset of influenza.

Conclusions  Among the prognostic factors, malnutrition and pneumonia are amenable to medical intervention. An opportunity exists to improve empirical therapy for patients with HCAP and influenza.

Trial Registry  Japan Medical Association Center for Clinical Trials; No.: JMA-IIA00123; URL: http://www.jmacct.med.or.jp/en/

Original Research: Pulmonary Procedures

Chest. 2016;149(2):535-544. doi:10.1378/chest.15-0647

Background  Endobronchial ultrasound (EBUS)-guided biopsy is the mainstay for investigation of mediastinal lymphadenopathy for laboratory diagnosis of malignancy, sarcoidosis, or TB. However, improved methods for discriminating between TB and sarcoidosis and excluding malignancy are still needed. We sought to evaluate the role of genomewide transcriptional profiling to aid diagnostic processes in this setting.

Methods  Mediastinal lymph node samples from 88 individuals were obtained by EBUS-guided aspiration for investigation of mediastinal lymphadenopathy and subjected to transcriptional profiling in addition to conventional laboratory assessments. Computational strategies were used to evaluate the potential for using the transcriptome to distinguish between diagnostic categories.

Results  Molecular signatures associated with granulomas or neoplastic and metastatic processes were clearly discernible in granulomatous and malignant lymph node samples, respectively. Support vector machine (SVM) learning using differentially expressed genes showed excellent sensitivity and specificity profiles in receiver operating characteristic curve analysis with area under curve values > 0.9 for discriminating between granulomatous and nongranulomatous disease, TB and sarcoidosis, and between cancer and reactive lymphadenopathy. A two-step decision tree using SVM to distinguish granulomatous and nongranulomatous disease, then between TB and sarcoidosis in granulomatous cases, and between cancer and reactive lymphadenopathy in nongranulomatous cases, achieved > 90% specificity for each diagnosis and afforded greater sensitivity than existing tests to detect TB and cancer. In some diagnostically ambiguous cases, computational classification predicted granulomatous disease or cancer before pathologic abnormalities were evident.

Conclusions  Machine learning analysis of transcriptional profiling in mediastinal lymphadenopathy may significantly improve the clinical utility of EBUS-guided biopsies.

Translating Basic Research Into Clinical Practice

Chest. 2016;149(2):545-551. doi:10.1378/chest.15-1353

Respiratory infections are a major clinical problem, and treatment is increasingly complicated by the emergence of microbial antibiotic resistance. Development of new antibiotics is notoriously costly and slow; therefore, alternative strategies are needed. Antimicrobial peptides, central effector molecules of the immune system, are being considered as alternatives to conventional antibiotics. These peptides display a range of activities, including not only direct antimicrobial activity, but also immunomodulation and wound repair. In the lung, airway epithelial cells and neutrophils in particular contribute to their synthesis. The relevance of antimicrobial peptides for host defense against infection has been demonstrated in animal models and is supported by observations in patient studies, showing altered expression and/or unfavorable circumstances for their action in a variety of lung diseases. Importantly, antimicrobial peptides are active against microorganisms that are resistant against conventional antibiotics, including multidrug-resistant bacteria. Several strategies have been proposed to use these peptides in the treatment of infections, including direct administration of antimicrobial peptides, enhancement of their local production, and creation of more favorable circumstances for their action. In this review, recent developments in antimicrobial peptides research in the lung and clinical applications for novel therapies of lung diseases are discussed.

Recent Advances in Chest Medicine

Chest. 2016;149(2):552-561. doi:10.1378/chest.15-1858

Tobacco smoke and nicotine exposure during prenatal and postnatal life can impair lung development, alter the immune response to viral infections, and increase the prevalence of wheezing during childhood. The following review examines recent discoveries in the fields of lung development and tobacco and nicotine exposure, emphasizing studies published within the last 5 years. In utero tobacco and nicotine exposure remains common, occurring in approximately 10% of pregnancies within the United States. Exposed neonates are at increased risk for diminished lung function, altered central and peripheral respiratory chemoreception, and increased asthma symptoms throughout childhood. Recently, genomic and epigenetic risk factors, such as alterations in DNA methylation, have been identified that may influence the risk for long-term disease. This review examines the impact of prenatal tobacco and nicotine exposure on lung development with a particular focus on nicotinic acetylcholine receptors. In addition, this review examines the role of prenatal and postnatal tobacco smoke and nicotine exposure and its association with augmenting infection risk, skewing the immune response toward a T-helper type 2 bias and increasing risk for developing an allergic phenotype and asthmalike symptoms during childhood. Finally, this review outlines the respiratory morbidities associated with childhood secondhand smoke and nicotine exposure and examines genetic and epigenetic modifiers that may influence respiratory health in infants and children exposed to in utero or postnatal tobacco smoke.

Medical Ethics

Chest. 2016;149(2):562-567. doi:10.1378/chest.15-2209

There is little guidance on what clinicians should do when advance directives (or living wills, specifically) are challenged, particularly when surrogate decision-makers’ interpretations of patients’ wishes conflict with the living will. In our commentary, we make a controversial argument suggesting that overriding living wills can be ethically preferable to the alternative of strictly adhering to them. We propose four ethical considerations for determining whether it is ethically supportable to override living wills.

Topics in Practice Management

Chest. 2016;149(2):568-575. doi:10.1378/chest.15-0441

Balancing population-based efforts to modify the social and environmental factors that promote tobacco dependence with efforts to improve the delivery of case-based treatments is necessary for realizing maximum reductions in the cost and consequences of the disease. Public health antismoking campaigns following the 1964 Surgeon General's report on the health risks of smoking have changed social norms, prevented initiation among youth, and promoted abstinence among the addicted. However, the rate of progress enjoyed to date is unlikely to continue into the coming decades, given that current annual unassisted cessation rates among prevalent smokers remains fairly low. With more than 1 billion patient interactions annually, there is an enormous unrealized capacity for health-care systems to have an effect on this problem. Clinicians report a perceived lack of reimbursement as a significant barrier to full integration of tobacco dependence into health care. A more complete understanding of the coding and documentation requirements for successful practice in this critically important area is a prerequisite to increasing engagement. This paper presents several case-based scenarios illustrating important practice management issues related to the treatment of tobacco dependence in health care.

Contemporary Reviews in Critical Care Medicine

Chest. 2016;149(2):576-585. doi:10.1378/chest.15-1369

Capnography has made steady inroads in the ICU and is increasingly used for all patients who are mechanically ventilated. There is growing recognition that capnography is rich in information about lung and circulatory physiology and provides insight into many diseases and treatments. These include conditions of impaired matching of ventilation and perfusion, such as pulmonary embolism and obstructive lung diseases; circulatory questions, such as the adequacy of chest compressions during cardiac arrest or fluid responsiveness in patients in shock; and the safety of procedural sedation. In this review, we emphasize analysis of the entire capnographic waveform as a way to glean additional useful information. We also discuss important limitations of capnography, especially when it is considered to be a surrogate for Paco2.

Contemporary Reviews in Sleep Medicine

Chest. 2016;149(2):586-597. doi:10.1378/chest.15-1777

OSA is a commonly encountered comorbid condition in surgical patients. The risk of cardiopulmonary complications is increased by two to threefold with OSA. Among the different treatment options for OSA, CPAP is an efficacious modality. This review examines the evidence regarding the use of CPAP in the preoperative and postoperative periods in surgical patients with diagnosed and undiagnosed OSA.

Pectoriloquy

Chest. 2016;149(2):598. doi:10.1016/j.chest.2015.10.056
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It will be his knee that helps the bone manpay a bit of tuition,for his advance is full wince and waddle.Though on a wet day, a disc of some sort and the hipwill squeal as harshly.Such a frame is stuff for aspirin and descriptionenough to weary the nimble.His aches enjoy regard reserved for favored sons or baseball,and so he drinks his tea with them alone.Gone are the swell pals, new cleats, that college girl, thefirst good check, the tang of rye.All tucked into lifeboats and vanished horizons ago.These few companions, this final boat will waitand help him cross the rail and slip the davitsTo a dim and yielding sea.

Chest. 2016;149(2):599. doi:10.1016/j.chest.2015.10.057
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Percodanized with a double-dose Ativan kicker,the big shot’s head balloons into a watermelondense as a Grauman Chinese sidewalk staror Wilshire Boulevard manhole cover.Throw velvet linesto a drowning plastic vs. reconstructive surgeonwho is already on a tightrope, neck in a vice-- would have hung himself if only he could.No one can lift the cervical collar from its bed.Everyone reassures, Superhero, hang in there.Viable by a thread, when mistresses aren’t looking,imagininga human slinky,his six-pack abs and hair transplant backbendthen flop from king-sized mattress onto the red carpet.Determined not to slip that very last micro-millimeterof spinal canalwhich would pith our celebrity to death, pretzelwon’t untwist, losing consciousness, he hears the Dadhe never met urge from the grave,Son don’t you give up.While the departed’s being processed then possiblyaccepted into one or another tier of heaven, Godrequired a quiet tearful poem about the fragility of life…I observed my wife’s Medicare birthday from above.Our kids and their's played on the white sand, picnicked.First year unable to be there because of damned painthat kept me upstairs in traction,I took pride in howthe family carried on. Sons fondly helped their matriarchup the steps. One daughter-in-law packed the beach gear,the other clutched a baby. Back in the condominium,unconsoled grandchildrenasked if if if Grampa saw their waves from the seawhen they saw me perched at the picture windowin a tarnished chair wearing my new cervical halo.

Correspondence

Chest. 2016;149(2):600. doi:10.1016/j.chest.2015.10.076
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We read with interest the original research entitled “Thyroid Disease is Prevalent and Predicts Survival in Patients With Idiopathic Pulmonary Fibrosis” in CHEST (September 2015). In the study, the authors compared the prevalence of hypothyroidism among patients with idiopathic pulmonary fibrosis (IPF) and control subjects with COPD. They also compared survival among patients with IPF who did or did not have hypothyroidism. In the study, the authors recorded patients as having hypothyroid only when they reported the use of thyroid replacement therapy and did not report a history of thyroidectomy or radioactive iodine ablation. Hypothyroid status was not based on hormone levels. Consequently, some patients with subclinical hypothyroidism could have been missed. Subclinical hypothyroidism is much more prevalent than true hypothyroidism and the prevalence is still higher in the age group for IPF. Although the condition is called subclinical hypothyroidism, frequently patients have nonspecific symptoms such as fatigue. In case of coexisting IPF, such symptoms may be erroneously attributed to IPF and treatment may be denied.

Chest. 2016;149(2):600-601. doi:10.1016/j.chest.2015.11.014
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Dr Dutt and colleagues aptly call attention to the high probability of undiagnosed subclinical hypothyroidism (HT) being present among patients included in our article recently published in CHEST (September 2015) Because thyroid function tests (TFTs) were not performed for most patients with idiopathic pulmonary fibrosis (IPF), those who had subclinical HT, which is more prevalent than overt HT, may have been missed. On review of patients with IPF without known HT, for whom TFTs were available (n = 65), elevated thyroid-stimulating hormone (TSH) was observed in six. Two were subsequently diagnosed with overt HT, one with non-thyroidal illness syndrome, and three with subclinical HT, which supports the observation of these authors.

Chest. 2016;149(2):601-602. doi:10.1016/j.chest.2015.10.068
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We read with interest the physiologic article by Raman and colleagues in CHEST (February 2015). In the second in vivo experiment described in the article, five pigs were ventilated through a laryngeal mask airway and the pressure transmitted to the proximal esophagus was measured at increasing ventilatory pressures. The resulting pressure was negligible compared with that required to induce leakage at the anastomosis. The authors thus conclude that noninvasive ventilation (NIV) is a safe alternative to endotracheal intubation to treat respiratory distress after esophagectomy. However, this study has a relevant limitation.

Chest. 2016;149(2):602-603. doi:10.1016/j.chest.2015.11.006
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We thank Drs Giani and Beretta for their interest in our work recently published in CHEST.

Chest. 2016;149(2):603. doi:10.1016/j.chest.2015.10.064
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The article “Community-acquired pneumonia: pathogenesis of acute cardiac events and potential adjunctive therapies” by Feldman and Anderson was an excellent and clinically relevant review of the pathogenesis and therapeutic implications of acute cardiac events in pneumonia. An important addition to the otherwise comprehensive work might have been discussion of the role of cardiac biomarkers in the prediction of mortality in patients with community-acquired pneumonia (CAP). Several natriuretic peptides, neurohormones that are released in response to cardiac stress, have been associated with higher risk of poor outcomes in CAP. These include B-type natriuretic peptide,, N-terminal pro B-type natriuretic peptide, and midregional pro-atrial natriuretic peptide. A recent study found that the natriuretic peptides provided increased discrimination when added to the Pneumonia Severity Index compared with the Pneumonia Severity Index alone, and were especially useful in identifying patients at high risk for mortality. The predictive value of these cardiac biomarkers further illustrate the important interplay between cardiac stress and mortality in CAP.

Chest. 2016;149(2):603-604. doi:10.1016/j.chest.2015.11.002
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We thank Drs Taylor and Taylor for their interest in our recently published article and for their complimentary statements. We agree entirely with their comments about emerging evidence for using measurements of the concentrations of circulating natriuretic peptides in patients with community-acquired pneumonia as a strategy to identify those at highest risk for development of complications and death. Unfortunately, however, inclusion of this important topic was beyond the brief of our manuscript. In addition to the potential clinical utility of measurements of these peptides in identifying those patients with community-acquired pneumonia at high risk of mortality, it would be interesting to speculate that such measurements may also allow us to distinguish those patients who would benefit most from treatment with antiplatelet agents.

Chest. 2016;149(2):604. doi:10.1016/j.chest.2015.10.016
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Tranexamic acid (TA) is an antifibrinolytic agent (synthetic lysine analog), which reversibly binds to plasminogen. It has been used in major surgery for bleeding control, although systemic effects such as thrombosis require rigorous monitoring. To date, there is no general consensus regarding TA doses or routes of administration. Similarly, there is insufficient evidence on what antifibrinolytic agent should be used when hemoptysis takes place. We present a series of cases in which inhaled TA was a feasible alternative for hemoptysis secondary to lung cancer or bronchiectasis.

Chest. 2016;149(2):605. doi:10.1016/j.chest.2015.09.041
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Linares-Perdomo and colleagues describe significant differences among three predicted body weight (PBW) equations in both men and women. The PBW is widely used to determine tidal volume during mechanical ventilation, to deliver a lung-protective ventilation strategy. Linares-Perdomo and colleagues concluded that variation in calculated PBW as determined by these formulas might be an important confounder when comparing studies. This may well be true because even minor changes in the tidal volume may have significant clinical consequences. A retrospective study by Gajic and colleagues suggested that overventilation by even a small amount might be harmful. Patients admitted without acute lung injury had an OR of 1.3 (P < .01) of developing lung injury for every 1 mL/kg above 6 mL/kg tidal volume delivered.

Chest. 2016;149(2):605-606. doi:10.1016/j.chest.2015.11.023
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A critical care physician performs and interprets the examination, providing real-time diagnosis and therapeutic interventions; this is the world of point-of-care ultrasound (PCUS). It is a paradigm shift from traditional consultative imaging in which technologists and physicians not intimately involved in patient care are responsible for image acquisition and interpretation. The use of PCUS eliminates clinical and time dissociation in patient care, allows timely diagnosis without having to unnecessarily transport the patient, and can reduce radiation exposure. The critical care literature is replete with studies supporting the use of PCUS, and it is becoming the standard of care in many ICUs across the country., The expanding role of tele-medicine, as well as the shortage of critical care physicians, has led to a rapid growth of tele-ICUs across the country. As of 2013, tele-ICU monitoring and care delivery supported nearly 13% of all ICU beds in the United States.

Chest. 2016;149(2):606-607. doi:10.1016/j.chest.2015.10.079
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We congratulate Lunardi et al on their study in CHEST (October 2015) describing the efficacy of lung expansion techniques (LETs) on alterations in postoperative pulmonary complications (PPC) following upper abdominal surgery. However, we believe that the study’s significant flaws preclude drawing conclusions that might influence clinical practice.

Chest. 2016;149(2):607-608. doi:10.1016/j.chest.2015.09.040
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Luce described the case of Jahi McMath, a teenager whose family requested organ support be continued after she was declared brain dead, citing religious objection to death by neurologic criteria. Only four states (California, Illinois, New Jersey, New York) have laws about how to handle religious objection to brain death. Whereas New Jersey’s statute is very clear about how to manage situations like the McMath case, the laws in the other three states are vague (Table 1).,,, Thus, there is no concrete guidance for physicians in 98% of the country (49 states) about how to behave in situations like the McMath case.

Chest. 2016;149(2):608-609. doi:10.1016/j.chest.2015.10.078
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I read with interest the reply of the AIR2 trial authors entitled “Bronchial thermoplasty: ready for prime time—evidence is there!” One of the major findings in the AIR2 trial reported by Castro et al was the statistically significant difference in the rate of severe asthma exacerbations per subject per year between the bronchial thermoplasty arm and the sham arm. It is important to observe that the two groups were not matched in their baseline exacerbation rate per subject per year (see Table 1 in the AIR2 trial). Therefore, the difference in the asthma exacerbation rate could simply be a result of the fact that more patients with frequent baseline exacerbations (ie, frequent exacerbators) were included in the sham arm than in the bronchial thermoplasty arm. It remains unclear why important baseline characteristics such as number of exacerbations per subject per year, ED visits in the previous year, and work absenteeism were not considered in the baseline patient characteristics, while comparison between the two arms with regard to these outcomes was planned for and conducted. If there was an intention to measure these outcomes and compare them between the two groups, the two arms should have been matched in these characteristics as well.

Chest. 2016;149(2):609-610. doi:10.1016/j.chest.2015.10.077
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In their article in the July 2015 issue of CHEST, Andruska et al reported that pathogen-related pneumonia was associated with an increased hospital readmission rate. In the Discussion section, the authors noted that hospitalization readmission could be related, in that setting, to inappropriate antibiotic therapy. Approximately 46% of patients had culture-negative pneumonia, and these patients had a lower readmission rate. The data are interesting and highlight the difficulty in making an accurate diagnosis of pneumonia by using microbiological methods.

Selected Reports

Chest. 2016;149(2):e35-e38. doi:10.1016/j.chest.2015.10.040

Hepatopulmonary syndrome (HPS) is a liver-induced lung disorder defined as a triad of liver disease, pulmonary vascular dilatation, and a defect in oxygenation. It can complicate chronic liver disease of any etiology, but is most commonly associated with portal hypertension. Severe liver disease with portal hypertension is present in 2% to 8% of patients with cystic fibrosis (CF), but to date, to our knowledge, only one patient with CF has been reported to suffer from HPS. Here, we describe two patients with CF diagnosed with HPS, one subsequent to unresolved hypoxemia and the other following screening for HPS performed in our center. We speculate that HPS is underdiagnosed in patients with CF because of their coexisting respiratory morbidity, and we advocate routine screening for every patient with CF who has liver disease and portal hypertension.

Chest. 2016;149(2):e39-e40. doi:10.1016/j.chest.2015.08.003

Paroxysmal autonomic instability with dystonia (PAID) is a syndrome commonly related to traumatic brain injury (TBI) and rarely to anoxia associated with symptoms of dystonia, tachycardia, tachypnea, and diaphoresis. This is a case of a 20-year-old man who was stabbed in the heart. He underwent surgical repair of a ventricular septal defect and mitral valve replacement. Postoperatively, he developed dystonia with tachycardia and tachypnea consistent with PAID syndrome, secondary to prolonged hypoxia. Traditionally, this poorly understood syndrome is treated with morphine, clonazepam, and nonselective β-blockers. Second-line medications commonly used are baclofen, dantrolene, and gabapentin, which are aimed at the dystonia itself. In this case, both first- and second-line agents were ineffective. A 72-hour dexmedetomidine infusion resulted in complete resolution of symptoms. This is the first case of anoxia-induced PAID syndrome to be effectively treated with dexmedetomidine, which was previously used in a case induced by TBI.

Ultrasound Corner

Chest. 2016;149(2):e41-e43. doi:10.1016/j.chest.2015.12.009
Chest. 2016;149(2):e45-e47. doi:10.1016/j.chest.2015.08.025

A middle-aged woman with a medical history of COPD on 3 L of home oxygen, idiopathic thrombocytopenic purpura status postsplenectomy, and hypothyroidism presented to the ED with fever and change in mental status. On presentation, she was febrile (temperature 39.6°C), tachycardic (heart rate, 130-140 beats/min), and hypotensive (blood pressure, 89/57 mm Hg). Her respiratory rate was 24 to 26 breaths/min and oxygen saturation of 84% on room air, which improved to 95% on 40% Venti mask. Physical examination revealed a middle-aged woman who was unresponsive, moaning, and grunting. She had labored breathing with bilateral crackles. Cardiac examination revealed tachycardia with a collapsed jugular vein.

Chest Imaging and Pathology for Clinicians

Chest. 2016;149(2):e49-e55. doi:10.1016/j.chest.2015.10.070

An 82-year-old Japanese nonsmoking man presented with persistent dry cough and small left apical pneumothorax. High resolution CT scan of the chest demonstrated bilateral upper lobe pleuroparenchymal thickening and architectural distortion. Serial imaging revealed mild progression and development of small bilateral pneumothoraces, and pneumomediastinum. A surgical lung biopsy was required to confirm the diagnosis.

Pulmonary, Critical Care, and Sleep Pearls

Chest. 2016;149(2):e57-e60. doi:10.1016/j.chest.2015.06.010

A 49-year-old man with a history of cryptogenic cirrhosis was referred to pulmonary clinic for evaluation prior to liver transplantation. Chest imaging obtained as part of the transplant workup had shown evidence of interstitial abnormalities. The patient noted shortness of breath on moderate exertion that was worsening over the past 2 to 3 years and associated with a nonproductive cough. He denied chest pain, chills, or fevers. His past medical history was significant for hypothyroidism. He did not have a history of alcohol consumption, smoking, or occupational exposures. He noted a family history of lung disease in his father and evidence of prominent clubbing in his sister and nephew. Workup for liver failure included a liver biopsy, which showed cirrhosis without evidence of autoimmune hepatitis.

Chest. 2016;149(2):e61-e64. doi:10.1016/j.chest.2015.10.051

A 39-year-old white woman with a history of adult-onset asthma, chronic sinusitis, and nasal polyposis presented to the ED with dyspnea and left lower extremity weakness and pain. Three months prior to her presentation she had an uncomplicated delivery of her second child, but during her pregnancy she experienced increasing asthma symptoms and nasal congestion. These symptoms progressed after delivery despite treatment with albuterol inhalers and antibiotics.

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