Effects of curative-intent lung cancer therapy on functional exercise capacity and patient-reported outcomes.

PURPOSE: Lung cancer treatment can lead to negative health consequences. We analyzed the effects of curative-intent lung cancer treatment on functional exercise capacity (EC) and patient-reported outcomes (PROs). METHODS: We performed a prospective, observational cohort study of consecutive patients with stage I-IIIA lung cancer undergoing curative-intent therapy and assessed functional EC (primary outcome, six-minute walk distance (6MWD)), cancer-specific quality of life (QoL) (secondary outcome, European Organization for Research and Treatment of Cancer QoL Questionnaire Core 30 (EORTC-QLQ-C30) summary score), and exploratory outcomes including dyspnea (University of California San Diego Shortness of Breath Questionnaire (UCSD SOBQ)) and fatigue Brief Fatigue Inventory (BFI)) symptoms before and at 1 to 3 months post-treatment. We analyzed the time effect of treatment on outcomes using multivariable generalized estimating equations. RESULTS: In 35 enrolled participants, treatment was associated with a clinically meaningful and borderline-significant decline in functional EC ((mean change, 95% CI) 6MWD = - 25.4 m (- 55.3, + 4.47), p = 0.10), clinically meaningful and statistically significant higher dyspnea (UCSD SOBQ = + 13.1 (+ 5.7, + 20.6), p = 0.001) and fatigue (BFI = + 10.0 (+ 2.9, + 17.0), p = 0.006), but no clinically meaningful or statistically significant change in cancer-specific QoL (EORTC-QLQ-C30 summary score = - 3.4 (- 9.8, + 3.0), p = 0.30). CONCLUSIONS: Among the first prospective analysis of the effect of curative-intent lung cancer treatment on functional EC and PROs, we observed worsening dyspnea and fatigue, and possibly a decline in functional EC but not cancer-specific QoL at 1 to 3 months post-treatment. Interventions to reduce treatment-related morbidities and improve lung cancer survivorship may need to focus on reducing dyspnea, fatigue, and/or improving functional EC.

Exercise capacity and cancer-specific quality of life following curative intent treatment of stage I-IIIA lung cancer.

PURPOSE: Lung cancer survivors are at risk for health impairments resulting from the effects and/or treatment of lung cancer and comorbidities. Practical exercise capacity (EC) assessments can help identify impairments that would otherwise remain undetected. In this study, we characterized and analyzed the association between functional EC and cancer-specific quality of life (QoL) in lung cancer survivors who previously completed curative intent treatment. METHODS: In a cross-sectional study of 62 lung cancer survivors who completed treatment ≥ 1 month previously, we assessed functional EC with the 6-min walk distance (6MWD) and cancer-specific QoL with the European Organization for Research and Treatment of Cancer QoL Questionnaire Core 30 (EORTC-QLQ-C30). Cancer-specific QoL was defined using a validated composite EORTC-QLQ-C30 summary score. Univariable (UVA) and multivariable linear regression analyses (MVA) were performed to assess the relationship between functional EC and cancer-specific QoL. RESULTS: Lung cancer survivors had reduced functional EC (mean 6MWD = 335 m, 65% predicted) and QoL (mean EORTC-QLQ-C30 summary score = 77, scale range 0-100). In UVA, 6MWD was significantly associated with cancer-specific QoL (R2 = 0.16, p = 0.001). In MVA, in a final model that also included heart failure, obstructive sleep apnea, and psychiatric illness, 6MWD was independently associated with cancer-specific QoL (partial R2 = 0.20, p = 0.001). CONCLUSIONS: Functional EC was independently associated with cancer-specific QoL in lung cancer patients postcurative intent treatment. Exercise-based interventions aimed at improving EC may improve cancer-specific QoL in these patients.

An Official American Thoracic Society/European Respiratory Society Policy Statement: Enhancing Implementation, Use, and Delivery of Pulmonary Rehabilitation.

RATIONALE: Pulmonary rehabilitation (PR) has demonstrated physiological, symptom-reducing, psychosocial, and health economic benefits for patients with chronic respiratory diseases, yet it is underutilized worldwide. Insufficient funding, resources, and reimbursement; lack of healthcare professional, payer, and patient awareness and knowledge; and additional patient-related barriers all contribute to the gap between the knowledge of the science and benefits of PR and the actual delivery of PR services to suitable patients. OBJECTIVES: The objectives of this document are to enhance implementation, use, and delivery of pulmonary rehabilitation to suitable individuals worldwide. METHODS: Members of the American Thoracic Society (ATS) Pulmonary Rehabilitation Assembly and the European Respiratory Society (ERS) Rehabilitation and Chronic Care Group established a Task Force and writing committee to develop a policy statement on PR. The document was modified based on feedback from expert peer reviewers. After cycles of review and revisions, the statement was reviewed and formally approved by the Board of Directors of the ATS and the Science Council and Executive Committee of the ERS. MAIN RESULTS: This document articulates policy recommendations for advancing healthcare professional, payer, and patient awareness and knowledge of PR, increasing patient access to PR, and ensuring quality of PR programs. It also recommends areas of future research to establish evidence to support the development of an updated funding and reimbursement policy regarding PR. CONCLUSIONS: The ATS and ERS commit to undertake actions that will improve access to and delivery of PR services for suitable patients. They call on their members and other health professional societies, payers, patients, and patient advocacy groups to join in this commitment.

An official American Thoracic Society/European Respiratory Society statement: key concepts and advances in pulmonary rehabilitation.

BACKGROUND: Pulmonary rehabilitation is recognized as a core component of the management of individuals with chronic respiratory disease. Since the 2006 American Thoracic Society (ATS)/European Respiratory Society (ERS) Statement on Pulmonary Rehabilitation, there has been considerable growth in our knowledge of its efficacy and scope. PURPOSE: The purpose of this Statement is to update the 2006 document, including a new definition of pulmonary rehabilitation and highlighting key concepts and major advances in the field. METHODS: A multidisciplinary committee of experts representing the ATS Pulmonary Rehabilitation Assembly and the ERS Scientific Group 01.02, "Rehabilitation and Chronic Care," determined the overall scope of this update through group consensus. Focused literature reviews in key topic areas were conducted by committee members with relevant clinical and scientific expertise. The final content of this Statement was agreed on by all members. RESULTS: An updated definition of pulmonary rehabilitation is proposed. New data are presented on the science and application of pulmonary rehabilitation, including its effectiveness in acutely ill individuals with chronic obstructive pulmonary disease, and in individuals with other chronic respiratory diseases. The important role of pulmonary rehabilitation in chronic disease management is highlighted. In addition, the role of health behavior change in optimizing and maintaining benefits is discussed. CONCLUSIONS: The considerable growth in the science and application of pulmonary rehabilitation since 2006 adds further support for its efficacy in a wide range of individuals with chronic respiratory disease.

Pulmonary rehabilitation improves sleep quality in chronic lung disease.

Sleep-related disorders are common in patients with chronic obstructive pulmonary disease (COPD) and, possibily, other lung disorders. Exercise has been shown to improve sleep disturbances. In patients with COPD, pulmonary rehabilitation (PR) produces important health benefits with improvement in symptoms, exercise tolerance, and quality of life. However, the effect of PR on sleep quality remains unknown. The aim of this observational study was to evaluate sleep quality in patients with chronic lung disease and the role of PR as a non-pharmacologic treatment to improve sleep. Sixty-four patients with chronic lung disease enrolled in an 8-week comprehensive PR program, and completed the study (48% male; obstructive [72%], restrictive [20%], mixed [8%]; 44% on supplemental oxygen). Baseline spirometry [mean (SD)]: FEV1% pred = 48.9 (17.4), FVC% pred = 72.5 (18.1), and FEV1/FVC% = 53.1 (18.9). Exercise tolerance and questionnaires related to symptoms, health-related quality of life (HRQL), and sleep quality using the Pittsburgh Sleep Quality Index (PSQI) were obtained before and after PR. 58% reported poor sleep quality (PSQI > 5) at baseline. Sleep quality improved by 19% (p = 0.017) after PR, along with significant improvements in dyspnea, exercise tolerance, self-efficacy, and HRQL. Sleep quality in patients with chronic lung disease was poor. In addition to expected improvements in symptoms, exercise tolerance, and HRQL after PR, the subgroup of patients with COPD had a significant improvement in sleep quality. These findings suggest that PR may be an effective, non-pharmacologic treatment option for sleep problems in patients with COPD.

Validation of the Brazilian Portuguese version of the University of California San Diego Shortness of Breath Questionnaire in patients with interstitial lung disease.

OBJECTIVE: To investigate the reliability, internal consistency and validity of the Brazilian Portuguese version of the University of California San Diego Shortness of Breath Questionnaire (UCSD SOBQ) in patients with interstitial lung disease (ILD). METHODS: Patients with ILD completed the questionnaire at three different time points, one week apart, with the assistance of two independent assessors. Intra- and inter-rater reliability were analysed via the intraclass correlation coefficient (ICC). Internal consistency was assessed with the Cronbach's alpha coefficient. For the validity analysis, associations between variables were assessed with Spearman's or Pearson's correlation coefficient. RESULTS: Thirty patients with ILD (idiopathic pulmonary fibrosis, connective tissue disease-associated pulmonary fibrosis, sarcoidosis, asbestosis or non-specific interstitial pneumonia) were included (15 men; mean age, 59 ± 10 years; DLCO: 46 [33-64] % predicted). UCSD SOBQ scores showed excellent agreement and internal consistency in the intra-rater analysis (ICC: 0.93 [0.85-0.97]; Cronbach alpha: 0.95) and in the inter-rater analysis (ICC: 0.95 [0.89-0.97]; Cronbach alpha: 0.95), as well as correlating significantly with dyspnoea (as assessed by the Medical Research Council scale; r = 0.56); Medical Outcomes Study 36-item Short-Form Health Survey domains bodily pain, general health, vitality and physical functioning (-0.40 ≤ r ≤ -0.74); six-minute walk distance (r = -0.38); and quadriceps muscle strength (r = -0.41). CONCLUSIONS: The Brazilian Portuguese version of the UCSD SOBQ is valid, is reliable and has internal consistency in patients with ILD in Brazil.

Characterization of Dyspnea in Veteran Lung Cancer Survivors Following Curative-Intent Therapy.

PURPOSE: Dyspnea is highly prevalent in lung cancer survivors following curative-intent therapy. We aimed to identify clinical predictors or determinants of dyspnea and characterize its relationship with functional exercise capacity (EC). METHODS: In an analysis of data from a cross-sectional study of lung cancer survivors at the VA San Diego Healthcare System who completed curative-intent therapy for stage I-IIIA disease ≥1 mo previously, we tested a thorough list of comorbidities, lung function, and lung cancer characteristics. We assessed dyspnea using the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer Module 13 (LC13) and functional EC using the 6-minute walk. We replicated results with the University of California San Diego Shortness of Breath Questionnaire. RESULTS: In 75 participants at a median of 12 mo since treatment completion, the mean ± SD LC13-Dyspnea score was 35.3 ± 26.2; 60% had abnormally high dyspnea. In multivariable linear regression analyses, significant clinical predictors or determinants of dyspnea were (ß [95% CI]) psychiatric illness (-20.8 [-32.4 to -9.09]), heart failure with reduced ejection fraction (-15.5 [-28.0 to -2.97]), and forced expiratory volume in the first second of expiration (-0.28 [-0.49 to -0.06]). Dyspnea was an independent predictor of functional EC (-1.54 [-2.43 to -0.64]). These results were similar with the University of California San Diego Shortness of Breath Questionnaire. CONCLUSION: We identified clinical predictors or determinants of dyspnea that have pathophysiological bases. Dyspnea was independently associated with functional EC. These results have implications in efforts to reduce dyspnea and improve exercise behavior and functional EC in lung cancer survivors following curative-intent therapy.

A Model-Based Cost-Effectiveness Analysis of an Exercise Program for Lung Cancer Survivors After Curative-Intent Treatment.

OBJECTIVE: The cost-effectiveness of exercise interventions in lung cancer survivors is unknown. We performed a model-based cost-effectiveness analysis of an exercise intervention in lung cancer survivors. DESIGN: We used Markov modeling to simulate the impact of the Lifestyle Interventions and Independence for Elders exercise intervention compared with usual care for stage I-IIIA lung cancer survivors after curative-intent treatment. We calculated and considered incremental cost-effectiveness ratios of less than US $100,000/quality-adjusted life-year as cost-effective and assessed model uncertainty using sensitivity analyses. RESULTS: The base-case model showed that the Lifestyle Interventions and Independence for Elders exercise program would increase overall cost by US $4740 and effectiveness by 0.06 quality-adjusted life-years compared with usual care and have an incremental cost-effectiveness ratio of US $79,504/quality-adjusted life-year. The model was most sensitive to the cost of the exercise program, probability of increasing exercise, and utility benefit related to exercise. At a willingness-to-pay threshold of US $100,000/quality-adjusted life-year, Lifestyle Interventions and Independence for Elders had a 71% probability of being cost-effective compared with 27% for usual care. When we included opportunity costs, Lifestyle Interventions and Independence for Elders had an incremental cost-effectiveness ratio of US $179,774/quality-adjusted life-year, exceeding the cost-effectiveness threshold. CONCLUSIONS: A simulation of the Lifestyle Interventions and Independence for Elders exercise intervention in lung cancer survivors demonstrates cost-effectiveness from an organization but not societal perspective. A similar exercise program for lung cancer survivors may be cost-effective.

Eosinophil and T cell markers predict functional decline in COPD patients.

BACKGROUND: The major marker utilized to monitor COPD patients is forced expiratory volume in one second (FEV1). However, a single measurement of FEV1 cannot reliably predict subsequent decline. Recent studies indicate that T lymphocytes and eosinophils are important determinants of disease stability in COPD. We therefore measured cytokine levels in the lung lavage fluid and plasma of COPD patients in order to determine if the levels of T cell or eosinophil related cytokines were predictive of the future course of the disease. METHODS: Baseline lung lavage and plasma samples were collected from COPD subjects with moderately severe airway obstruction and emphysematous changes on chest CT. The study participants were former smokers who had not had a disease exacerbation within the past six months or used steroids within the past two months. Those subjects who demonstrated stable disease over the following six months (DeltaFEV1 % predicted = 4.7 +/- 7.2; N = 34) were retrospectively compared with study participants who experienced a rapid decline in lung function (DeltaFEV1 % predicted = -16.0 +/- 6.0; N = 16) during the same time period and with normal controls (N = 11). Plasma and lung lavage cytokines were measured from clinical samples using the Luminex multiplex kit which enabled the simultaneous measurement of several T cell and eosinophil related cytokines. RESULTS AND DISCUSSION: Stable COPD participants had significantly higher plasma IL-2 levels compared to participants with rapidly progressive COPD (p = 0.04). In contrast, plasma eotaxin-1 levels were significantly lower in stable COPD subjects compared to normal controls (p < 0.03). In addition, lung lavage eotaxin-1 levels were significantly higher in rapidly progressive COPD participants compared to both normal controls (p < 0.02) and stable COPD participants (p < 0.05). CONCLUSION: These findings indicate that IL-2 and eotaxin-1 levels may be important markers of disease stability in advanced emphysema patients. Prospective studies will need to confirm whether measuring IL-2 or eotaxin-1 can identify patients at risk for rapid disease progression.

Longitudinal change in the BODE index predicts mortality in severe emphysema.

RATIONALE: The predictive value of longitudinal change in BODE (Body mass index, airflow Obstruction, Dyspnea, and Exercise capacity) index has received limited attention. We hypothesized that decrease in a modified BODE (mBODE) would predict survival in National Emphysema Treatment Trial (NETT) patients. OBJECTIVES: To determine how the mBODE score changes in patients with lung volume reduction surgery versus medical therapy and correlations with survival. METHODS: Clinical data were recorded using standardized instruments. The mBODE was calculated and patient-specific mBODE trajectories during 6, 12, and 24 months of follow-up were estimated using separate regressions for each patient. Patients were classified as having decreasing, stable, increasing, or missing mBODE based on their absolute change from baseline. The predictive ability of mBODE change on survival was assessed using multivariate Cox regression models. The index of concordance was used to directly compare the predictive ability of mBODE and its separate components. MEASUREMENTS AND MAIN RESULTS: The entire cohort (610 treated medically and 608 treated surgically) was characterized by severe airflow obstruction, moderate breathlessness, and increased mBODE at baseline. A wide distribution of change in mBODE was seen at follow-up. An increase in mBODE of more than 1 point was associated with increased mortality in surgically and medically treated patients. Surgically treated patients were less likely to experience death or an increase greater than 1 in mBODE. Indices of concordance showed that mBODE change predicted survival better than its separate components. CONCLUSIONS: The mBODE demonstrates short- and intermediate-term responsiveness to intervention in severe chronic obstructive pulmonary disease. Increase in mBODE of more than 1 point from baseline to 6, 12, and 24 months of follow-up was predictive of subsequent mortality. Change in mBODE may prove a good surrogate measure of survival in therapeutic trials in severe chronic obstructive pulmonary disease. Clinical trial registered with www.clinicaltrials.gov (NCT 00000606).

Heart rate variability and heart rate recovery in lung cancer survivors eligible for long-term cure.

Lung cancer survivors are at risk for physical fitness and autonomic function impairments. In a cross-sectional study of consecutive lung cancer survivors post-curative intent therapy, we assessed and identified predictors of resting heart rate variability (HRV) and heart rate recovery (HRR), defined as standard deviation of normal-to-normal-R-to-R intervals (SDNN) and root-mean-square-of-successive-differences (rMSSD) from routine outpatient single 10-s electrocardiographs (ECGs) and difference in heart rate (HR) at 1-minute following and the end of the six-minute-walk-test (6MWT), respectively. In 69 participants, the mean (SD) HRR was -10.6 (6.7) beats. Significant independent predictors of HRR were age and HR change associated with the 6MWT. In a subset of 41 participants with available ECGs, the mean (SD) SDNN and rMSSD were 19.1 (15.6) and rMSSD 18.2 (14.6) ms, respectively. Significant independent predictors of HRV were supine HR, HRR, and total lung capacity. HRV/HRR may be useful physiological measures in studies aimed at improving physical fitness and/or autonomic function in lung cancer survivors.

Pulmonary rehabilitation: summary of an evidence-based guideline.

Pulmonary rehabilitation has emerged as a standard of care for patients with chronic lung disease, based on a growing body of scientific evidence. Over recent decades, several organizations have championed pulmonary rehabilitation and developed comprehensive statements, practice guidelines, and evidence-based guidelines. Documenting the scientific evidence underlying clinical practice has been important in overcoming skepticism and convincing health professionals, health-care institutions, third-party payers, and regulatory agencies to support pulmonary rehabilitation programs. The literature on pulmonary rehabilitation has increased substantially and provided justification for including pulmonary rehabilitation in practice guidelines for chronic obstructive pulmonary disease and other chronic lung diseases. Therefore, the American College of Chest Physicians and the American Association of Cardiovascular and Pulmonary Rehabilitation decided to update their 1997 guidelines with a systematic, evidence-based review of the literature since the previous review. The panel updated prior topics and recommendations and reviewed new topics. Recommendations were given for outcomes of comprehensive pulmonary rehabilitation programs, including lower-extremity exercise training, dyspnea, health-related quality of life, health-care utilization, survival, psychosocial outcomes, and long-term benefits. Additional topics include the duration of pulmonary rehabilitation, post-rehabilitation maintenance strategies, intensity of aerobic exercise training, strength training, anabolic drugs, upper-extremity training, inspiratory-muscle training, education, psychological and behavioral components, oxygen supplementation, noninvasive ventilation, nutrition supplementation, rehabilitation for patients with disorders other than chronic obstructive pulmonary disease, and future pulmonary rehabilitation research. These guidelines provide an excellent summary of the recent literature and further strengthen the scientific basis of pulmonary rehabilitation.

Time to treatment and survival in veterans with lung cancer eligible for curative intent therapy.

BACKGROUND: The Institute of Medicine emphasizes care timeliness as an important quality metric. We assessed treatment timeliness in stage I-IIIA lung cancer patients deemed eligible for curative intent therapy and analyzed the relationship between time to treatment (TTT) and timely treatment (TT) with survival. METHODS: We retrospectively reviewed consecutive cases of stage I-IIIA lung cancer deemed eligible for curative intent therapy at the VA San Diego Healthcare System between 10/2010-4/2017. We defined TTT as days from chest tumor board to treatment initiation and TT using guideline recommendations. We used multivariable (MVA) Cox proportional hazards regressions for survival analyses. RESULTS: In 177 veterans, the median TTT was 35 days (29 days for chemoradiation, 36 for surgical resection, 42 for definitive radiation). TT occurred in 33% or 77% of patients when the most or least timely guideline recommendation was used, respectively. Patient characteristics associated with longer TTT included other cancer history, high simplified comorbidity score, stage I disease, and definitive radiation treatment. In MVA, TTT and TT [HR 0.53 (95% CI 0.27, 1.01) for least timely definition] were not associated with OS in stage I-IIIA patients, or disease-free survival in subgroup analyses of 122 stage I patients [HR 1.49 (0.62, 3.59) for least timely definition]. CONCLUSION: Treatment was timely in 33-77% of veterans with lung cancer deemed eligible for curative intent therapy. TTT and TT were not associated with survival. The time interval between diagnosis and treatment may offer an opportunity to deliver or improve other cancer care.

Pulmonary Rehabilitation: Joint ACCP/AACVPR Evidence-Based Clinical Practice Guidelines.

BACKGROUND: Pulmonary rehabilitation has become a standard of care for patients with chronic lung diseases. This document provides a systematic, evidence-based review of the pulmonary rehabilitation literature that updates the 1997 guidelines published by the American College of Chest Physicians (ACCP) and the American Association of Cardiovascular and Pulmonary Rehabilitation. METHODS: The guideline panel reviewed evidence tables, which were prepared by the ACCP Clinical Research Analyst, that were based on a systematic review of published literature from 1996 to 2004. This guideline updates the previous recommendations and also examines new areas of research relevant to pulmonary rehabilitation. Recommendations were developed by consensus and rated according to the ACCP guideline grading system. RESULTS: The new evidence strengthens the previous recommendations supporting the benefits of lower and upper extremity exercise training and improvements in dyspnea and health-related quality-of-life outcomes of pulmonary rehabilitation. Additional evidence supports improvements in health-care utilization and psychosocial outcomes. There are few additional data about survival. Some new evidence indicates that longer term rehabilitation, maintenance strategies following rehabilitation, and the incorporation of education and strength training in pulmonary rehabilitation are beneficial. Current evidence does not support the routine use of inspiratory muscle training, anabolic drugs, or nutritional supplementation in pulmonary rehabilitation. Evidence does support the use of supplemental oxygen therapy for patients with severe hypoxemia at rest or with exercise. Noninvasive ventilation may be helpful for selected patients with advanced COPD. Finally, pulmonary rehabilitation appears to benefit patients with chronic lung diseases other than COPD. CONCLUSIONS: There is substantial new evidence that pulmonary rehabilitation is beneficial for patients with COPD and other chronic lung diseases. Several areas of research provide opportunities for future research that can advance the field and make rehabilitative treatment available to many more eligible patients in need.

Age, gender, neck circumference, and Epworth sleepiness scale do not predict obstructive sleep apnea (OSA) in moderate to severe chronic obstructive pulmonary disease (COPD): The challenge to predict OSA in advanced COPD.

The combination of chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA) is associated with substantial morbidity and mortality. We hypothesized that predictors of OSA among patients with COPD may be distinct from OSA in the general population. Therefore, we investigated associations between traditional OSA risk factors (e.g. age), and sleep questionnaires [e.g. Epworth Sleepiness Scale] in 44 patients with advanced COPD. As a second aim we proposed a pilot, simplified screening test for OSA in patients with COPD. In a prospective, observational study of patients enrolled in the UCSD Pulmonary Rehabilitation Program we collected baseline characteristics, cardiovascular events (e.g. atrial fibrillation), and sleep questionnaires [e.g. Pittsburgh Sleep Quality Index (PSQI)]. For the pilot questionnaire, a BMI ≥25 kg/m2 and the presence of cardiovascular disease were used to construct the pilot screening test. Male: 59%; OSA 66%. FEV1 (mean ± SD) = 41.0±18.2% pred., FEV1/FVC = 41.5±12.7%]. Male gender, older age, and large neck circumference were not associated with OSA. Also, Epworth Sleepiness Scale and the STOP-Bang questionnaire were not associated with OSA in univariate logistic regression. In contrast, BMI ≥25 kg/m2 (OR = 3.94, p = 0.04) and diagnosis of cardiovascular disease (OR = 5.06, p = 0.03) were significantly associated with OSA [area under curve (AUC) = 0.74]. The pilot COPD-OSA test (OR = 5.28, p = 0.05) and STOP-Bang questionnaire (OR = 5.13, p = 0.03) were both associated with OSA in Receiver Operating Characteristics (ROC) analysis. The COPD-OSA test had the best AUC (0.74), sensitivity (92%), and specificity (83%). A ten-fold cross-validation validated our results. We found that traditional OSA predictors (e.g. gender, Epworth score) did not perform well in patients with more advanced COPD. Our pilot test may be an easy to implement instrument to screen for OSA. However, a larger validation study is necessary before further clinical implementation is warranted.

Association of systemic inflammation, adiposity, and metabolic dysregulation with asthma burden among Hispanic adults.

RATIONALE: Obesity-related asthma is associated with higher disease burden than normal-weight asthma among Hispanics. Adiposity, metabolic dysregulation, and inflammation are all implicated in pathogenesis of obesity-related asthma, but their independent contributions are poorly understood. OBJECTIVE: To examine the independent contributions of body fat distribution, metabolic abnormalities and inflammation on asthma symptoms and pulmonary function among Hispanics. METHODS: Participants of the Hispanic Community Health Study/Study of Latinos with doctor-diagnosed asthma who completed an asthma symptom questionnaire and performed a valid spirometry were included in the analysis (n = 1126). Multivariate analysis was used to examine the independent association of general adiposity (assessed using body mass index), truncal adiposity (assessed by waist circumference), metabolic dysregulation (presence of insulin resistance and low HDL) and inflammation (high-sensitivity C-Reactive Protein≥3 mg/L) with reported asthma symptoms or pulmonary function measures (FEV1, and FVC) while adjusting for demographic and clinical covariates. RESULTS: Of the 1126 participants, 334 (29.5%) were overweight, and 648 (57.8%) were obese. FEV1 and FVC were lower in obese compared to normal-weight asthmatics. In analyses controlling for metabolic and adiposity factors, high hs-CRP (>7 mg/L) was associated with more symptoms (prevalence-ratio 1.27 (95%CI 1.05, 1.54), and lower FVC (ß -138 ml (95%CI -27 ml, -249 ml)) and FEV1 (ß -155 ml (95% CI -38 ml, -272 ml). Low HDL was also associated with lower FVC (ß -111 ml (-22 ml, -201 ml) and FEV1 (ß -100 ml (-12 ml, -188 ml)). Results were similar in men and women. CONCLUSIONS: Our findings suggest that hs-CRP and low HDL, rather than general and truncal adiposity, are associated with asthma burden among overweight and obese Hispanic adults.

Feasibility of retinoids for the treatment of emphysema study.

BACKGROUND: Retinoids promote alveolar septation in the developing lung and stimulate alveolar repair in some animal models of emphysema. METHODS: One hundred forty-eight subjects with moderate-to-severe COPD and a primary component of emphysema, defined by diffusing capacity of the lung for carbon monoxide (Dlco) [37.1 +/- 12.0% of predicted] and CT density mask (38.5 +/- 12.8% of voxels <- 910 Hounsfield units) [mean +/- SD] were enrolled into a randomized, double-blind, feasibility study at five university hospitals. Participants received all-trans retinoic acid (ATRA) at either a low dose (LD) [1 mg/kg/d] or high dose (HD) [2 mg/kg/d], 13-cis retinoic acid (13-cRA) [1 mg/kg/d], or placebo for 6 months followed by a 3-month crossover period. RESULTS: No treatment was associated with an overall improvement in pulmonary function, CT density mask score, or health-related quality of life (QOL) at the end of 6 months. However, time-dependent changes in Dlco (initial decrease with delayed recovery) and St. George Respiratory Questionnaire (delayed improvement) were observed in the HD-ATRA cohort and correlated with plasma drug levels. In addition, 5 of 25 participants in the HD-ATRA group had delayed improvements in their CT scores that also related to ATRA levels. Retinoid-related side effects were common but generally mild. CONCLUSIONS: No definitive clinical benefits related to the administration of retinoids were observed in this feasibility study. However, time- and dose-dependent changes in Dlco, CT density mask score, and health-related QOL were observed in subjects treated with ATRA, suggesting the possibility of exposure-related biological activity that warrants further investigation.

The Utility of Exercise Testing in Patients with Lung Cancer.

The harm associated with lung cancer treatment include perioperative morbidity and mortality and therapy-induced toxicities in various organs, including the heart and lungs. Optimal treatment therefore entails a need for risk assessment to weigh the probabilities of benefits versus harm. Exercise testing offers an opportunity to evaluate a patient's physical fitness/exercise capacity objectively. In lung cancer, it is most often used to risk-stratify patients undergoing evaluation for lung cancer resection. In recent years, its use outside this context has been described, including in nonsurgical candidates and lung cancer survivors. In this article we review the physiology of exercise testing and lung cancer. Then, we assess the utility of exercise testing in patients with lung cancer in four contexts (preoperative evaluation for lung cancer resection, after lung cancer resection, lung cancer prognosis, and assessment of efficiency of exercise training programs) after systematically identifying original studies involving the most common forms of exercise tests in this patient population: laboratory cardiopulmonary exercise testing and simple field testing with the 6-minute walk test, shuttle walk test, and/or stair-climbing test. Lastly, we propose a conceptual framework for risk assessment of patients with lung cancer who are being considered for therapy and identify areas for further studies in this patient population.

The effects of pulmonary rehabilitation in the national emphysema treatment trial.

STUDY OBJECTIVES: Pulmonary rehabilitation is an established treatment in patients with chronic lung disease but is not widely utilized. Most trials have been conducted in single centers. The National Emphysema Treatment Trial (NETT) provided an opportunity to evaluate pulmonary rehabilitation in a large cohort of patients who were treated in centers throughout the United States. DESIGN: Prospective observational study of cohort prior to randomization in a multicenter clinical trial. SETTING: University-based clinical centers and community-based satellite pulmonary rehabilitation programs. PATIENTS AND INTERVENTION: A total of 1,218 patients with severe emphysema underwent pulmonary rehabilitation before and after randomization to lung volume reduction surgery (LVRS) or continued medical management. Rehabilitation was conducted at 17 NETT centers supplemented by 539 satellite centers. MEASUREMENTS AND RESULTS: Lung function, exercise tolerance, dyspnea, and quality of life were evaluated at regular intervals. Significant (p < 0.001) improvements were observed consistently in exercise (cycle ergometry, 3.1 W; 6-min walk test distance, 76 feet), dyspnea (University of California, San Diego Shortness of Breath Questionnaire score, -3.2; Borg breathlessness score: breathing cycle, -0.8; 6-min walk, -0.5) and quality of life (St. George Respiratory Questionnaire score, -3.5; Quality of Well-Being Scale score, +0.035; Medical Outcomes Study 36-item short form score: physical health summary, +1.3; mental health summary, + 2.0). Patients who had not undergone prior rehabilitation improved more than those who had. In multivariate models, only prior rehabilitation status predicted changes after rehabilitation. In 20% of patients, exercise level changed sufficiently after rehabilitation to alter the NETT subgroup predictive of outcome. Overall, changes after rehabilitation did not predict differential mortality or improvement in exercise (primary outcomes) by treatment group. CONCLUSIONS: The NETT experience demonstrates the effectiveness of pulmonary rehabilitation in patients with severe emphysema who were treated in a national cross-section of programs. Pulmonary rehabilitation plays an important role in preparing and selecting patients for surgical interventions such as LVRS.

Quality of well-being outcomes in the National Emphysema Treatment Trial.

BACKGROUND: Surgical and medical treatments for emphysema may affect both quality and quantity of life. The purpose of this article is to report outcomes from the National Emphysema Treatment Trial (NETT) using an index that combines quality and quantity of life. METHODS: This was a prospective randomized clinical trial. Following pulmonary rehabilitation, 1,218 patients with severe emphysema were randomly assigned to maximal medical therapy or to lung volume reduction surgery (LVRS). A generic quality-of-life measure, known as the Quality of Well-being Scale (QWB), was administered at baseline and again at 6, 12, 24, 36, 48, 60, and 72 months following treatment assignment. RESULTS: At baseline, QWB scores were comparable for the Medical and LVRS groups. For both groups, scores significantly improved following the rehabilitation program. The QWB scores before death for patients in the LVRS group improved up to the year 2 visit, whereas scores for the Medical group dropped significantly following the baseline visit. Imputing zeros (0) for death, QWB scores decreased significantly for both groups. With or without scoring death as 0, the LVRS group achieved better outcomes, and the significant differences were maintained until the sixth year. Over 6 years of follow-up, LVRS produced an average of 0.30 quality-adjusted life years (QALYs), or the equivalent of about 3.6 months of well life. CONCLUSIONS: Compared with maximal medical therapy alone, patients undergoing maximal medical therapy plus LVRS experienced improved health-related quality of life and gained more QALYs. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT00000606; URL: www.clinicaltrials.gov.