CHEST publishes select peer-reviewed, accepted manuscripts Online First each week. The media embargo is lifted on the date of Online First publication. Final, edited versions will appear in a numbered issue of CHEST and may contain substantive changes. We encourage readers to check back for the final article. Online First papers are indexed in PubMed and by search engines, but the information, including the final title and author list, may be updated on final publication.

original research 
N. Gupta, MSc; L. Pinto, MD; A. Benedetti, PhD; P.Z. Li, MSc; W. Tan, MD; S. Aaron, MD; K.R. Chapman, MD; J.M. FitzGerald, MD; P. Hernandez, MD; D. Marciniuk, MD; F. Maltais, MD; D. O'Donnell, MD; D. Sin, MD; B. Walker, MD; J. Bourbeau, MD

Background  The COPD Assessment Test (CAT) is a valid disease specific questionnaire measuring health status. However, knowledge concerning its use regarding patient and disease characteristics remains limited. Our main objective was to assess the degree to which the CAT score varies and can discriminate between specific patient population groups.

Methods  The Canadian Cohort Obstructive Lung Disease (CanCOLD) is a random-sampled population-based, multicenter prospective cohort that includes subjects with COPD: GOLD 1 to 3. The CAT questionnaire was administered at three visits (baseline, 1.5 and 3 years). The CAT total score was determined for sex, age groups, smoking status, GOLD classification, exacerbations and comorbidities.

Results  716 subjects with COPD were included in the analysis. The majority of subjects (72.5%) were not previously diagnosed with COPD. The mean FEV1/FVC ratio was 61.1 ± 8.1% with a mean FEV1 % predicted of 82.3 ± 19.3%. The mean CAT scores were 5.8 ± 5.0, 9.6 ± 6.7 and 16.1 ± 10.0 for GOLD 1, 2, and 3 and higher, respectively. Higher CAT scores were observed in women, current smokers, ever-smokers and in subjects with previous diagnosis of COPD. The CAT was also able to distinguish between subjects who experience exacerbations versus no-exacerbations.

Conclusions  These results suggest that the CAT, originally designed for use in clinically symptomatic COPD patients, can also be used in individuals with mild airflow obstruction and newly diagnosed COPD. In addition, the CAT was able to discriminate between genders and subjects who experience frequent and infrequent exacerbations.

original research 
Thomas S. Valley, MD, MSc; Michael W. Sjoding, MD, MSc; Zachary D. Goldberger, MD, MS; Colin R. Cooke, MD, MSc, MS
Topics: , , ,

Background  Quality of care for acute myocardial infarction (AMI) and heart failure (HF) varies across hospitals, but factors driving variation are incompletely understood. We evaluated the relationship between a hospital’s intensive care unit (ICU) or coronary care unit (CCU) admission rate and quality of care provided to patients with AMI or HF.

Methods  A retrospective cohort study of Medicare beneficiaries hospitalized in 2010 with AMI or HF was performed. Hospitals were grouped into quintiles by their risk- and reliability-adjusted ICU admission rates for AMI or HF. We examined the rates that hospitals failed to deliver standard AMI or HF processes of care (process measure failure rates), 30-day mortality, 30-day readmissions, and Medicare spending after adjusting for patient and hospital characteristics.

Results  Hospitals in the lowest quintile had ICU admission rates < 29% for AMI or < 8% for HF. Hospitals in the top quintile had rates > 61% for AMI or > 24% for HF. Hospitals in the highest quintile had higher process measure failure rates for some but not all process measures. Hospitals in the top quintile had greater 30-day mortality (14.8% vs. 14.0%, p=0.002 for AMI; 11.4% vs. 10.6%, p<0.001 for HF), but no differences in 30-day readmissions or Medicare spending when compared to hospitals in the lowest quintile.

Conclusions  Hospitals with the highest rates of ICU admission for patients with AMI or HF delivered lower quality of care and had higher 30-day mortality for these conditions. High ICU use hospitals may be targets to improve care delivery.

ahead of the curve 
Xianglan Yao, M.D., Ph.D.; Elizabeth M. Gordon, Ph.D.; Amisha V. Barochia, M.B.B.S.; Alan T. Remaley, M.D., Ph.D.; Stewart J. Levine, M.D.
Topics: , ,

New treatments are needed for asthmatics who are refractory to standard therapies, such as individuals with a phenotype of “type 2 low” inflammation. This important clinical problem could potentially be addressed by the development of apolipoprotein A-I (apoA-I) mimetic peptides. Apolipoprotein A-I interacts with its cellular receptor, the ATP-binding cassette subfamily A, member 1 (ABCA1), to facilitate cholesterol efflux out of cells to form nascent HDL particles. The ability of the apoA-I/ABCA1 pathway to efflux cholesterol from cells that mediate adaptive immunity, such as antigen-presenting cells, can attenuate their function. Data from experimental murine models have demonstrated that the apoA-I/ABCA1 pathway can reduce neutrophilic airway inflammation primarily by suppressing the production of granulocyte-colony stimulating factor. Furthermore, administration of apoA-I mimetic peptides to experimental murine models of allergic asthma has decreased both neutrophilic and eosinophilic airway inflammation, as well as airway hyperresponsiveness and mucous cell metaplasia. Higher serum levels of apoA-I have also been associated with less severe airflow obstruction in asthmatics. Collectively, these results suggest that the apoA-I/ABCA1 pathway may have a protective effect in asthma and support the concept of advancing inhaled apoA-I mimetic peptides to clinical trials that can assess their safety and effectiveness. Thus, we propose that the development of inhaled apoA-I mimetic peptides as a new treatment could represent a clinical advance for severe asthmatics who are unresponsive to other therapies.

original research 
Sameer S. Kadri, MD, MS; Andrew C. Miller, MD; Samuel Hohmann, PhD; Stephanie Bonne, MD; Carrie Nielsen, MA; Carmen Wells, RN; Courtney Gruver, RN; Sadeq A. Quraishi, MD, MHA, MMSc; Junfeng Sun, PhD; Rongman Cai, PhD; Peter E. Morris, MD; Bradley D. Freeman, MD; James H. Holmes, MD; Bruce A. Cairns, MD; Anthony F. Suffredini, MD
Topics: , , ,

Background  Mortality after smoke inhalation-associated acute lung injury (SI-ALI) remains substantial. Age and burn surface area are risk factors of mortality, while the impact of patient and center-level variables and treatments on survival are unknown.

Methods  We performed a retrospective cohort study of burn and non-burn centers at 68 United States academic medical centers from 2011-2014. Adult SI-ALI inpatients were identified using an algorithm based on a billing code for respiratory conditions from smoke inhalation who were mechanically ventilated by hospital day 4, with either a length-of-stay ≥ 5-days or death within 4 days of hospitalization. Predictors of in-hospital mortality were identified using logistic regression. The primary outcome was the odds ratio for in-hospital mortality.

Results  769 patients (52.9 ± 18.1 years) with SI-ALI were analyzed. In-hospital mortality was 26% in the SI-ALI cohort and 50% in patients with ≥20% surface burns. In addition to age > 60 years (OR 5.1, 95%CI 2.53-10.26) and ≥20% burns (OR 8.7, 95%CI 4.55-16.75), additional risk factors of in-hospital mortality included initial vasopressor use (OR 5.0, 95%CI 3.16-7.91), higher DRG-based risk-of-mortality assignment and lower hospital bed capacity (OR 2.3, 95%CI 1.23-4.15). Initial empiric antibiotics (OR 0.93, 95%CI 0.58-1.49) did not impact survival. These new risk factors improved mortality prediction (ΔAUC) by 9.9%(p<0.001).

Conclusions  In addition to older age and major surface burns, mortality in SI-ALI is predicted by initial vasopressor use, higher DRG-based risk-of-mortality assignment and care at centers with <500 beds, but not by initial antibiotic therapy.

translating basic research in clinical practice 
Greer Arthur, PhD; Peter Bradding, DM, FRCP
No abstract is available for this article
original research 
Alejandro A. Diaz, MD, M.PH; Hans Petersen, MS; Paula Meek, PhD, RN; Akshay Sood, MD, MPH, FCCP; Bartolome Celli, MD, FCCP; Yohannes Tesfaigzi, PhD
Topics: , ,

Introduction  Smoking is associated with impaired health-related quality of life (HRQL) across all populations. Because decline in lung function and risk for COPD are lower in New Mexican Hispanic smokers compared to their non-Hispanic White (NHW) counterparts, we investigated whether HRQL differs between these two racial-ethnic groups and determined the factors that contribute to this difference.

Methods  We compared the score results of the Medical Outcomes Short-Form 36 Health Survey (SF-36) and St George’s Respiratory Questionnaire (SGRQ) in 378 Hispanics and 1,597 non-Hispanic whites (NHW) enrolled into the Lovelace Smokers’ Cohort (LSC) from New Mexico. The associations of race-ethnicity with SGRQ and SF-36 were assessed using multivariable regression.

Results  Physical functioning (difference -4.5, P=0.0008) but not mental health or role emotional domains of the SF-36 was worse in Hispanic smokers than their NWH counterparts in multivariable analysis. SGRQ total score and activity and impact subscores were worse in Hispanic (vs. NHW) smokers after adjustment for education level, current smoking, pack-years smoked, body mass index, number of comorbidities, and forced expiratory volume in one second % predicted (difference range, 2.9 to 5.0, all comparisons P≤0.001). While the difference in the SGRQ activity domain was above the clinically important difference of 4 units, the total score was not.

Conclusion  New Mexican Hispanic smokers have clinically relevant lower HRQL than their NHW counterparts. A perception of diminished physical functioning and impairment in daily-life activities contribute to the poorer HRQL among Hispanics.

original research 
Martha E. Billings, MD, MSc; Dayna Johnson, PhD, MPH, MS; Guido Simonelli, MD; Kari Moore, MS; Sanjay R. Patel, MD, MS; Ana V. Diez Roux, MD, PhD; Susan Redline, MD, MPH
Topics: , ,

Background  There has been growing interest in understanding how neighborhoods may relate to cardiovascular risk. Neighborhood effects on sleep apnea may be one contributing mechanism. We investigated whether neighborhood walking environment and personal activity levels are related to obstructive sleep apnea.

Methods  We analyzed data from a subpopulation of the Multi-Ethnic Study of Atherosclerosis (MESA), including subjects who participated in both MESA Sleep and Neighborhood studies (n=1,896). Perceived neighborhood walking environment and subjects’ objective activity were evaluated in multivariate, multi-level models for an association with sleep apnea severity as defined by the apnea hypopnea index. Sex, race/ethnicity and obesity were examined as moderators.

Results  Residing in the lowest quartile walking environment neighborhoods (score <3.75) was associated with more severe sleep apnea [mean 2.7 events/hr greater AHI, 95% CI (0.7, 4.6)], after adjusting for demographics, body mass index, co-morbidities, health behaviors, neighborhood socio-economic status and site. Associations were stronger among obese and male individuals. Approximately one standard deviation greater objective activity in men, was associated with a lower AHI [mean -2.4 95% CI (-3.5, -1.3) events/hr]. This association was partially mediated by body mass index (P<0.001).

Conclusions  Living in neighborhoods with a low walking environment score is associated with greater sleep apnea severity, especially in male and obese individuals. In men, greater activity level is associated with less severe sleep apnea, independent of body mass index, co-morbidities and socio-economics. Neighborhood-level interventions that increase walkability and enable increased physical activity may potentially reduce sleep apnea severity.

recent advances in chest medicine 
Hossein-Ardeschir Ghofrani, MD; Marc Humbert, MD; David Langleben, MD; Ralph Schermuly, MD; Johannes-Peter Stasch, PhD; Martin R. Wilkins, MD; James R. Klinger, MD
Topics: , ,

Pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) are progressive and debilitating diseases characterized by gradual obstruction of the pulmonary vasculature, leading to elevated pulmonary artery pressure and increased pulmonary vascular resistance. If untreated, they can result in death due to right heart failure. Riociguat is a novel soluble guanylate cyclase (sGC) stimulator that is approved for the treatment of PAH and CTEPH. Here we describe in detail the role of the nitric oxide–sGC–cyclic guanosine monophosphate (cGMP) signaling pathway in the pathogenesis of PAH and CTEPH, and the mode of action of riociguat. We also review the preclinical data associated with the development of riociguat, along with the efficacy and safety data of riociguat from initial clinical trials and the pivotal Phase III randomized clinical trials in PAH and CTEPH.

recent advances in chest medicine 
Kassem Harris, MD; Jonathan Puchalski, MD; Daniel Sterman
Topics: ,

The detection of peripheral lung nodules is increasing due to expanded use of computed tomography (CT) and implementation of lung cancer screening recommendations. Although surgical resection of malignant nodules remains the treatment modality of choice at present, many patients are not surgical candidates, thus prompting the need for other therapeutic options. Stereotactic body radiotherapy (SBRT) and percutaneous thermal ablation are emerging as viable alternatives to surgical resection. For safety, efficacy, and cost-effectiveness purposes, however, alternative bronchoscopic methods for treatment of peripheral lung cancer are currently under active exploration.

We searched the Cochrane Library and Medline from 1990 to 2015 to provide the most comprehensive review for bronchoscopic treatment of malignant lung nodules. We used the following search terms: bronchoscopy; lung nodule; peripheral lung lesion; and bronchoscopic treatment. We focused on peripheral pulmonary nodules that are confirmed or highly likely to be malignant. Seventy-one articles were included in this narrative review. We provide herein an overview of advanced bronchoscopic modalities that have been utilized or are under active investigation for definitive treatment of malignant pulmonary nodules. We concisely discuss the use of direct intratumoral chemotherapy or gene therapies, transbronchial brachytherapy, bronchoscopy-guided radiofrequency ablation, placement of markers to guide real time radiation and surgery, cryotherapy and photodynamic therapy. We also briefly report on emerging technologies such as vapor ablation of lung parenchyma for lung cancers. Advances in bronchoscopic therapy will bring additional treatment options to patients with peripheral lung malignancies, with putative advantages over other minimally invasive modalities.

medical ethics 
Gabriel T. Bosslet, MD, MA; Mary Baker, MD; Thaddeus M. Pope, JD, PhD
Topics: , , ,

Disputes regarding life-prolonging treatments are stressful for all parties involved. These disagreements are appropriately almost always resolved with intensive communication and negotiation. Those rare cases that are not that are not require a resolution process that ensures fairness and due process. We describe three recent cases from different countries (the United States, United Kingdom, and Ontario, Canada) to qualitatively contrast the legal responses to intractable, policy-level disputes regarding end of life care in each of these countries. In so doing, we define the continuum of clinical and social utility among different types of dispute resolution processes, and emphasize the importance of public reason-giving in the societal discussion regarding policy-level solutions to end-of-life treatment disputes. We argue that precedential, publicly available, written rulings for these decisions most effectively help to move the social debate forward in a way that is beneficial to clinicians, patients, and citizens. Our paper highlights the lack of such rulings within the United States.

original research 
Anna-Maija Tolppanen, PhD; Marjaana Koponen, MSc (Pharm); Antti Tanskanen, Phil Lic; Piia Lavikainen, MSc; Reijo Sund, DSocSc; Jari Tiihonen, MD, PhD; Sirpa Hartikainen, MD, PhD; Heidi Taipale, PhD (Pharm)
Topics: , , ,

Background  Antipsychotics have been associated with increased pneumonia risk, but although persons with dementia are particularly susceptible to pneumonia, only one small study assessed the risk of pneumonia in relation to antipsychotic use among persons with Alzheimer’s disease (AD).

Methods  We investigated whether incident antipsychotic use, or specific antipsychotics are related to higher risk of hospitalisation or death due to pneumonia in the MEDALZ cohort. The cohort includes all persons with AD who received a clinically verified AD diagnosis in Finland in 2005-2011 (N=60,584, n with incident pneumonia 12,225). A matched comparison cohort without AD (N=60,584, n with incident pneumonia 6,195) was used to compare the magnitude of risk. Results were adjusted for a propensity score derived from comorbidities, concomitant medications and sociodemographic characteristics. Sensitivity analyses with case-crossover design were conducted.

Results  Antipsychotic use was associated with higher pneumonia risk (adjusted hazard ratio, 95% confidence interval (CI) 2.01, 1.90-2.13) in the AD cohort and somewhat higher risk in the non-AD cohort (3.43, 2.99-3.93). Similar results were observed with case-crossover analyses (odds ratio 2.02, 95% CI 1.75-2.34 in the AD cohort, 2.59, 1.77-3.79 in the non-AD cohort). The three most commonly used antipsychotics (quetiapine, risperidone, haloperidol) had similar associations with pneumonia risk.

Conclusions  Regardless of applied study design, treatment duration, or the choice of drug, antipsychotic use was associated with higher risk of pneumonia. With observational data we cannot fully rule out a shared causality between pneumonia and antipsychotic use, but the risk-benefit balance should be considered when antipsychotics are prescribed.

original research 
Hye Yun Park, MD; Byeong-Ho Jeong, MD; Hae Ri Chon, MD; Kyeongman Jeon, MD; Charles L. Daley, MD; Won-Jung Koh, MD
Topics: , , ,

Background  There are few data regarding the impact of nontuberculous mycobacterial lung disease (NTM-LD) on lung function during the clinical course of disease. This study aimed to assess the impact of NTM-LD on lung function decline.

Methods  Treatment outcomes and spirometry data at diagnosis and at least three years later were obtained from 358 patients who were diagnosed as NTM-LD between January 1999 and November 2011 using the prospective NTM registry cohort. For analysis, patients were divided into three groups: observed without treatment, treatment success, and treatment failure.

Results  The treatment failure group (n = 68) had a significantly more rapid decline in forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) compared with the observation (n = 118) and treatment success (n = 172) groups (–52.2, –30.8, and –28.2 mL/yr, respectively, P = .023 for FEV1 decline; –50.4, –28.8, and –26.0 mL/yr, respectively, P = .002 for FVC decline). After adjusting for confounding factors, patients with treatment failure had greater FEV1 and FVC declines than those observed without treatment (adjusted P = .026 for FEV1 decline; adjusted P = .022 for FVC decline) or treated successfully (adjusted P = .004 for FEV1 decline; adjusted P = .002 for FVC decline). Patients treated successfully had similar declines in FEV1 and FVC to those in the observation group.

Conclusions  The change of lung function was variable over a median 5-year follow-up period. Treatment failure was associated with a substantial decline in lung function in NTM-LD.

topics in practice management 
Richard D. Zorowitz, M.D.
Topics: , ,

Intensive care unit acquired weakness (ICUAW) occurs with reported incidence rates from 25 to 100%. Risk factors include immobility, sepsis, persistent systemic inflammation, multi-organ system failure, hyperglycemia, glucocorticoids, and neuromuscular blocking agents. The pathophysiology remains unknown. Clinical features may be neuropathic, myopathic, or a combination of both. Although manual muscle testing is more practical in diagnosing ICUAW, the “gold standard” for the diagnosis of ICUAW remains electromyography (EMG) and nerve conduction studies. The only potential interventions known to date to prevent ICUAW include insulin therapy and early rehabilitation, but patients still may develop activity limitations in the acute care hospital. For these patients, rehabilitation may continue in long-term care hospitals (LTCH), inpatient rehabilitation facilities (IRF), or skilled nursing facilities (SNF). ICUAW is a catastrophic and debilitating condition that potentially leaves patients with permanent residual activity limitations and participation restrictions. Further research on ICUAW needs to better understand its pathophysiology such that more definitive preventative and therapeutic interventions may be developed.

original research 
Lucas Boeck, MD; Anna Gensmer, MD; Sylvia Nyilas, MD; Bram Stieltjes, MD, PhD; Thomas J. Re, MD, MSc; Michael Tamm, MD; Philipp Latzin, MD, PhD; Daiana Stolz, MD
Topics: ,

Background  Current functional assessments do not allow a reliable assessment of small airways, a major site of disease in COPD. Single-breath washout (SBW) tests are feasible and reproducible methods for evaluating small airway disease. Their relevance in COPD remains unknown.

Methods  We performed a cross-sectional study in 65 patients with moderate to severe COPD. Phase III slope of N2 (SIIIN2) and double tracer gas (SIIIDTG) SBW tests were used as a measure of ventilation inhomogeneity. The association of both markers with established physiological and clinical features of COPD was assessed.

Results  Ventilation inhomogeneity as measured by SIIIN2 and SIIIDTG was increased in COPD patients compared to healthy subjects (p < 0.001 and p < 0.001, respectively). SIIIN2 was associated with FEV1 predicted, RV/TLC and DLCO (all p < 0.001). Furthermore, SIIIN2 was related to dyspnea, exercise-induced desaturation and exercise capacity (p = 0.001, p < 0.001 and p = 0.047). SIIIDTG was associated with TLC, DLCO and cough (p < 0.001, p = 0.001 and p = 0.009). In multivariate regression models we demonstrate that these associations are largely independent of FEV1, and mostly stronger than associations with FEV1. In contrast, FEV1 was superior in predicting emphysema severity.

Conclusions  SIIIN2 and SIIIDTG, two fast and clinically applicable measures of small airway disease, reflect different physiological and clinical aspects of COPD, largely independent of spirometry.

original research 
Sandra S. Tøttenborg, MSc; Reimar W. Thomsen, DMSc; Søren P. Johnsen, DMSc; Henrik Nielsen, MSc; Peter Lange, DMSc
Topics: , , ,

Background  The beneficial effects of smoking cessation on progression of chronic obstructive pulmonary disease (COPD) are well established. Nevertheless, many COPD patients continue to smoke.

Methods  In this nationwide hospital-based prospective follow-up study, we examined rates of smoking cessation and clinical and socio-demographic determinants of smoking cessation in 3,233 COPD patients who smoked upon outpatient contact during 2008-2012. Using multivariate Cox regression we calculated hazard ratios (HR) of quitting.

Results  Within one and five years from first outpatient contact the probability of quitting was 19% and 45%, respectively. In adjusted analyses, patients were less likely to quit if they were younger, with a HR of 0.84 (95% CI 0.71-0.99) for patients aged 50-69 and 0.53 (95% CI 0.37-0.50) for patients aged 30-49 compared with those aged >70, had lower income (HR 0.79, 95% CI 0.67-0.94), lived alone (HR 0.75, 95% CI 0.64-0.88), were unemployed (HR 0.70, 95% CI 0.54-0.90), had milder COPD, with an HR of 0.67 (95% CI 0.53-0.84) for GOLD A and 0.61 (95% CI 0.47-0.80) for GOLD B compared with GOLD D, had MRC dyspnea scale <4 (HR 0.80, 95% CI 0.68-0.95), or no history of outpatient treated exacerbations (HR 0.80, 95% CI 0.68-0.93).

Conclusion  These findings reinforce that the young and socioeconomically disadvantaged patients have more difficulties achieving timely smoking cessation. A novel finding is that patients with milder COPD are less likely to quit. The findings suggest a need for intervention studies focusing on these subgroups to ensure abstinence in order to halt disease progression.

original research 
Marc Blondon, MD MS; Alessandro Casini, MD; Kara K. Hoppe, DO; Françoise Boehlen, MD; Marc Righini, MD; Nicholas L. Smith, PhD
Topics: ,

Background  Cesarean sections (CS) are believed to be associated with greater risks of postpartum venous thromboembolism (VTE). Our objective was to systematically review the evidence on this association and on the absolute risk of VTE after CS.

Methods  We searched Pubmed, Embase and conference proceedings from 1980 to 11/2015 for reports on the associations of delivery methods with postpartum VTE and on the incidence of VTE after CS. We excluded studies on thrombophilia or recurrent VTE and restricted to prospective studies when assessing the incidence of VTE. Pooled relative and absolute risks were estimated with random-effects models.

Results  Our search retrieved 28 mostly retrospective observational studies comparing risks of VTE after CS and after vaginal deliveries (VD) (n>53000 VTE events), and 32 prospective studies reporting risks of VTE after CS (n=218 VTE events). Compared with VD, the relative risk of VTE after CS ranged from 1-22, with a meta-analytic odds ratio (OR) of 3.7 (95%CI 3.0-4.6). Adjustment for age and BMI had a marginal influence on the estimated pooled OR. Associations were observed for both elective and emergency CS, with stronger estimates of associations for emergency CS. The pooled incidence was 2.6VTE/1000 CS (95%CI 1.7-3.5), and was greater in studies with a longer and better follow-up in the postpartum (4.3/1000 CS).

Conclusion  The risk of VTE is 4-fold greater after CS than VD, appears independent of other VTE risk factors, and is greater after emergency than elective CS. On average, 3 in 1000 women will develop a VTE after CS.

contemporary reviews in sleep medicine 
Emer Van Ryswyk, Dr; Nick Antic, Professor
Topics: ,

Opioid use for chronic pain analgesia, particularly chronic non-cancer pain (CNCP), has increased greatly since the late 1990s, resulting in an increase in opioid-associated morbidity and mortality. A clear link between opioid use and sleep disordered breathing (SDB) has been established, with the majority of chronic opioid users being affected by the condition, and dose dependent severity apparent for some opioids. More evidence is currently needed on how to effectively manage opioid-induced SDB. This review summarizes the current state of knowledge relating to management of patients on chronic opioid therapy who have SDB. Initial management of the patient on chronic opioid therapy with SDB requires thorough biopsychosocial assessment of their need for opioid therapy, consideration of reduction, or cessation of the opioid if possible and alternative therapies for treatment of their pain. If opioid therapy must be continued, then management of the associated SDB may be important. Several small-medium scale studies have examined the efficacy of non-invasive ventilation, particularly adaptive servo ventilation (ASV) for treatment of opioid-associated SDB. This is particularly because opioids predispose predominantly to central sleep apnoea (CSA), and also, to a lesser extent, to obstructive sleep apnoea (OSA). Generally, these studies have found positive results in treating opioid-associated SDB with ASV in terms of improving outcome measures such as central apnoea index and apnoea hypopnoea index. However, larger studies that measure longer term health outcomes, patient sleepiness and compliance are needed. Registries of health outcomes of ASV treated patients may assist with future treatment planning.

original research 
Philip S. Wells, MD; Martin H. Prins, MD, PhD; Bennett Levitan, MD, PhD; Jan Beyer-Westendorf, MD; Timothy A. Brighton, MD; Henri Bounameaux, MD; Alexander T. Cohen, MD, FRACP; Bruce L. Davidson, MD, MPH; Paolo Prandoni, MD, PhD; Gary E. Raskob, PhD; Zhong Yuan, MD, PhD; Eva G. Katz, PhD, MPH; Martin Gebel, PhD; Anthonie WA. Lensing, MD, PhD
Topics: , , , , ,

Background  Short-term anticoagulant treatment for acute deep-vein thrombosis (DVT) or pulmonary embolism (PE) effectively reduces the risk of recurrent disease during the first 6 to 12 months of therapy. Continued anticoagulation is often not instituted because of the perception among physicians that the risk of major bleeding will outweigh the risk of new venous thrombotic episodes.

Methods  Benefit-risk analysis using the randomized EINSTEIN-EXTENSION trial, which compared continued rivaroxaban versus placebo in 1197 patients with symptomatic DVT or PE who had completed 6-12 months of anticoagulation and in whom physicians had equipoise with respect to the need for continued anticoagulation. One-year Kaplan-Meier rates and rate differences of recurrent venous thromboembolism (VTE) and major bleeding were calculated. Benefits and risks were assessed using rate differences scaled to a population size of 10000 patients treated for 1 year.

Results  Recurrent VTE occurred in 8 (3.0%) rivaroxaban recipients and 42 (9.6%) placebo patients. In a population of 10000 patients treated for 1 year, rivaroxaban treatment would have resulted in 665 (95% CI 246-1084) fewer recurrent VTEs than placebo (number needed to treat=15). Major bleeding occurred in 4 (0.7%) and 0 patients, respectively. Rivaroxaban treatment would have resulted in 68 (95% CI 2-134) more major bleeding events than placebo (number needed to harm=147). Kaplan–Meier analysis showed early recurrent VTE reduction with rivaroxaban that continued to improve throughout treatment; major bleeding increased gradually, plateauing at ±100 days.

Conclusions  A clinically important benefit and a favorable benefit–risk profile of continued rivaroxaban anticoagulation was observed.

Renli Qiao, MD, PhD, FCCP; Darcy Marciniuk, MD, FRCPC, FCCP; Nicki Augustyn; Mark J. Rosen, MD, Master FCCP; Huaping Dai, MD; Rongchang Chen, MD, FCCP, FCCP; Sinan Wu, MD; Chen Wang, MD, PhD, FCCP
Topics: , , ,

This article provides an update on progress toward establishing pulmonary and critical care medicine (PCCM) fellowship training as one of the first four subspecialties to be recognized and supported by the Chinese government. Designed and implemented throughout 2013-2014 by a collaborative effort of the Chinese Thoracic Society (CTS) and the American College of CHEST Physicians (CHEST), 12 leading Chinese hospitals enrolled a total of 64 fellows into standardized PCCM training programs with common curricula, educational activities and assessment measures. Supplemental educational materials, online assessment tools and institutional site visits designed to evaluate and provide feedback on the programs’ progress are being provided by CHEST. As a result of this initial progress, the Chinese government, through the Chinese Medical Doctor’s Association, endorsed the concept of subspecialty fellowship training in China, with PCCM as one of the four pilot subspecialties to be operationalized nationwide in 2016, followed by implementation across other subspecialties by 2020. This article also reflects on the achievements of the training sites and the challenges they face, and outlines plans to enhance and expand PCCM training and practice in China.

original research 
Flávia B. Nerbass, PT, PhD; Vera M.C. Salemi, MD, PhD; Rodrigo P. Pedrosa, MD, PhD; Natanael de P. Portilho, MD; Julio C.A. Ferreira-Filho, MD, PhD; Henrique T. Moriya, PhD; Murillo O. Antunes, MD; Edmundo Arteaga-Fernández, MD, PhD; Luciano F. Drager, MD, PhD; Geraldo Lorenzi-Filho, MD, PhD
Topics: ,

Background  Hypertrophic cardiomyopathy (HCM) is a common genetic disease that may cause left ventricular outflow tract (LVOT) obstruction, heart failure, and sudden death. Recent studies have shown a high prevalence of obstructive sleep apnea among patients with HCM. Because the hemodynamics of patients with LVOT obstruction are unstable and depend on load conditions to the heart, we evaluated the acute effects of CPAP on hemodynamics and cardiac performance in patients with HCM.

Methods  We studied 26 stable patients with HCM divided into nonobstructive-HCM (n=12) and obstructive-HCM (n=14) groups (LVOT gradient pressure lower or higher than 30 mm Hg, respectively). Patients in the supine position while awake were continuously monitored by beat-to-beat blood pressure and electrocardiography. A 2-dimensional echocardiography was performed at rest (Baseline) and after 20 minutes of nasal CPAP at 1.5 cmH2O and 10 cmH2O, which was applied in a random order interposed by 10 minutes without CPAP.

Results  Blood pressure, cardiac output, stroke volume, heart rate, left ventricular ejection fraction and LVOT gradient did not change during the study period in either group. CPAP at 10 cmH2O decreased right atrial size and right ventricular relaxation in all patients. CPAP at 10 cmH2O decreased left atrial volume significantly and decreased right ventricular outflow acceleration time, suggesting an increase in pulmonary artery pressure in obstructive patients.

Conclusions  The acute application of CPAP is apparently safe in patients with HCM because CPAP does not lead to hemodynamic compromise. Long-term studies in HCM patients with sleep apnea and nocturnal CPAP are warranted.

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