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Background COPD is a leading cause of mortality. Research Question We hypothesized that applying machine learning to clinical and quantitative CT imaging features would improve mortality prediction in COPD. Study Design and Methods We selected 30 clinical, spirometric, and imaging features as inputs for a random survival forest. We used top features in a Cox regression to create a machine learning mortality prediction (MLMP) in COPD model and also assessed the performance of other statistical and machine learning models. We trained the models in subjects with moderate to severe COPD from a subset of subjects in Genetic Epidemiology of COPD (COPDGene) and tested prediction performance in the remainder of individuals with moderate to severe COPD in COPDGene and Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE). We compared our model with the BMI, airflow obstruction, dyspnea, exercise capacity (BODE) index; BODE modifications; and the age, dyspnea, and airflow obstruction index. Results We included 2,632 participants from COPDGene and 1,268 participants from ECLIPSE. The top predictors of mortality were 6-min walk distance, FEV1 % predicted, and age. The top imaging predictor was pulmonary artery-to-aorta ratio. The MLMP-COPD model resulted in a C index ≥ 0.7 in both COPDGene and ECLIPSE (6.4- and 7.2-year median follow-ups, respectively), significantly better than all tested mortality indexes (P Interpretation An MLMP-COPD model outperformed four existing models for predicting all-cause mortality across two COPD cohorts. Performance of machine learning was similar to that of traditional statistical methods. The model is available online at: https://cdnm.shinyapps.io/cgmortalityapp/.

BACKGROUND:Programs aimed at increasing physical activity in daily life (PADL) have generated growing interest to prevent the deleterious effects of physical inactivity. Recent literature has shown that a short-term protocol using pedometers increased PADL in smokers with normal lung function. However, the long-term effects of such a protocol were not yet studied. The objective of this study was to evaluate the results of 1-year follow-up after a program aimed at increasing PADL in smokers with normal lung function. METHODS:Twenty-four smokers were followed (15 men; mean [interquartile range (IQR)], 51 [41–57] years of age; BMI, 26 [22–29] kg/m2; 20 [20–30] cigarettes/d). Subjects were assessed at baseline, immediately after completion of the program, and 1 year later for PADL, lung function, 6-min walking distance (6MWD), smoking habits, quality of life, anxiety, and depression. The 5-month program used pedometers and informative booklets as interventions. RESULTS:The gains achieved after the program were maintained in the long term: steps/d (postprogram vs 1-year follow-up, mean [IQR]: 10,572 [9,804-12,237] vs 10,438 [9,151-12,862]); 6MWD (625 [530–694] m, 88 [81–97] % predicted vs 609 [539–694] m, 89 [81–96] % predicted), anxiety (34 [26–41] points vs 35 [36–47] points) and depression (6 [2–9] points vs 5 [2–11] points) (P> .05 for all). One year after the program, 20% of the subjects had quit smoking. CONCLUSIONS:In smokers with normal lung function, improvements in daily physical activity, exercise capacity, anxiety, and depression obtained through a 5-month program aimed at increasing physical activity are sustained 1 year after completion of the program. Furthermore, such a program can contribute to smoking cessation in this population.

Background: Midrange-proadrenomedullin (MR-proADM) has been shown to be elevated in patients hospitalized for an acute exacerbation of COPD (AECOPD) and in patients with communityacquired pneumonia. When measured during AECOPDs, MR-proADM has also been shown to be a predictor of mortality. We hypothesized that MR-proADM levels measured in a stable state could also predict mortality.Methods: We included 181 patients in whom we had paired plasma samples for MR-proADM determinations during a stable state and at hospitalization for an AECOPD when they also produced sputum. Time to death or censoring was compared between patients with MR-proADM above or below the median of 0.71 nmol/ L. The predictive value of MR-proADM for survival was determined by calculating the C statistic.Results: Patients with COPD and MR-proADM levels > 0.71 nmol/ L in the stable state had a threefold-higher risk of dying than did patients with MR-proADM levels Conclusions: MR-proADM measured in the stable state appeared to be a strong predictor of mortality in patients with COPD. MR-proADM is far easier to measure than other predictors of mortality in COPD, such as BMI, airfl ow obstruction, dyspnea, and exercise capacity score.

Background It is uncertain whether the effort and expense of performing a second walk for the 6-min walk test improves test performance. Hence, we attempted to quantify the improvement in 6-min walk distance if an additional walk were to be performed. Methods We studied patients consecutively enrolled into the National Emphysema Treatment Trial who prior to randomization and after 6 to 10 weeks of pulmonary rehabilitation performed two 6-min walks on consecutive days (N = 396). Patients also performed two 6-min walks at 6-month follow-up after randomization to lung volume reduction surgery (n = 74) or optimal medical therapy (n = 64). We compared change in the first walk distance to change in the second, average-of-two, and best-of-two walk distances. Results Compared with the change in the first walk distance, change in the average-of-two and best-of-two walk distances had better validity and precision. Specifically, 6 months after randomization to lung volume reduction surgery, changes in the average-of-two ( r = 0.66 vs r = 0.58, P = .01) and best-of-two walk distances ( r = 0.67 vs r = 0.58, P = .04) better correlated with the change in maximal exercise capacity (ie, better validity). Additionally, the variance of change was 14% to 25% less for the average-of-two walk distances and 14% to 33% less for the best-of-two walk distances than the variance of change in the single walk distance, indicating better precision. Conclusions Adding a second walk to the 6-min walk test significantly improves its performance in measuring response to a therapeutic intervention, improves the validity of COPD clinical trials, and would result in a 14% to 33% reduction in sample size requirements. Hence, it should be strongly considered by clinicians and researchers as an outcome measure for therapeutic interventions in patients with COPD.

Pulmonary rehabilitation (PR) is an evidence-based, multidisciplinary, comprehensive intervention that can be integrated into the management of individuals with chronic lung disease. It aims to reduce symptoms, optimize function, increase participation in daily life, and reduce health-care resource utilization. In this review, we summarize the new developments in PR over the past 5 years. Issues related to patient assessment include a comparison of cycle- and walking-based measures of exercise capacity, the emergence of multidimensional indices, the refinement of the minimal clinically important difference, and the importance of assessing physical activity. Issues related to exercise training focus on strategies to optimize the training load. We also comment on the acquisition of self-management skills, balance training, optimizing access, and maintaining gains following completion of PR.

Objective: Prognostic studies of mortality in patients with COPD have mostly focused on physiologic variables, with little attention to depressive symptoms. This stands in sharp contrast to the attention that depressive symptoms have been given in the outcomes of patients with other chronic health conditions. The present study investigated the independent association of depressive symptoms in stable patients with COPD with all-cause mortality.Methods: The baseline characteristics of 121 COPD patients (78 men and 43 women; mean [+/- SDI age, 61.5 +/- 9.1 years; and mean FEV(1), 36.9 +/- 15.5% predicted) were collected on hospital admission to a pulmonary rehabilitation center. The data included demographic variables, body mass index (BMI), post-bronchodilator therapy FEV(1), and Wpeak (peak workload [Wpeak]). Depressive symptoms were assessed using the Beck depression inventory. The vital status was ascertained using municipal registrations. In 8.5 years of follow-up, 76 deaths occurred (mortality rate, 63%). Survival time ranged from 88 days to 8.5 years (median survival time, 5.3 years). The Cox proportional hazard model was used to quantify the association of the baseline characteristics (ie, age, sex, marital status, smoking behavior, FEV(1), BMI, Wpeak, and depressive symptoms) with mortality.Results: Depressive symptoms (odds ratio [OR], 1.93; 95% confidence interval [CI], 1.12 to 3.33) were associated with mortality in patients with COPD, independent of other factors including male sex (OR, 1.73; 95% CI, 1.03 to 2.92), older age (OR, 1.05; 95% CI, 1.02 to 1.08), and lower Wpeak (OR, 0.98; 95% CI, 0.97 to 0.99).Conclusions: This study provides evidence that depressive symptoms assessed in stable patients with COPD are associated with their subsequent all-cause mortality.

Study objective To test the performance of a tool designed to estimate functional capacity in order to select a bicycle ramp protocol yielding a test duration from 8 to 12 min in healthy individuals, and to assess differences in exercise responses between bicycle and treadmill tests. Participants and measures Forty-one healthy and physically active volunteers (10 women; median age, 37 years; interquartile range [IQR], 29.5 to 41 years) performed an individualized ramp exercise protocol on a bicycle ergometer and a treadmill in random order. Prior to testing, the Veterans Specific Activity Questionnaire (VSAQ) combined with a modified variant of the VSAQ nomogram (metabolic equivalents [METs] derived from VSAQ and age with the modified nomogram, resulting in METs nomogram) was used to estimate exercise capacity and to select the treadmill protocol. The corresponding bicycle work capacity nomogram (in watts) was derived by the following equation: (METs nomogram − 1) × body weight/3.486. Results Using treadmill tests, all 41 participants (100%) achieved maximal exercise from 8 to 12 min, as compared to 33 participants (80%) for the bicycle tests (p = 0.003). Peak oxygen uptake ( V ˙ o 2 ) [bicycle: median, 49.7 mL/kg/min (IQR, 45.4 to 56.6 mL/kg/min); vs treadmill: median, 53.1 mL/kg/min (IQR, 47.3 to 57.7 mL/kg/min; p < 0.0001)] was lower using the bicycle compared to the treadmill. However, the difference in peak V ˙ o 2 values between the two exercise modes was lower (2.6 mL/kg/min; IQR, 1.1 to 4.3 mL/kg/min), corresponding to 4.6% (IQR, 2.4 to 8.5%) of the lower of both values than reported in previous studies, and seven participants (17%) even achieved a higher peak V ˙ o 2 using the bicycle. Conclusions A modified version of the VSAQ can be effectively used to select appropriate ramp rates for exercise testing using a bicycle ergometer in healthy individuals. Differences in maximal responses are less than those previously reported, suggesting that the bicycle ergometer is an appropriate alternative to the treadmill test in healthy volunteers.

Study objectives: The number of severely obese patients undergoing bariatric surgery is increasing. No incremental cycle ergometer data are available in this category of patients. The current study was undertaken to provide information and to compare outcomes between severely obese men and women during physical exercise.Design: Cross-sectional study. Participants: Twenty-two men and 34 women, all with a body mass index (BMI) of at least 40 kg/m(2), were selected from among persons participating in a dedicated weight management program that was carried out in the outpatient clinic of a large teaching hospital.Measurements and results: Body composition was estimated with bioelectrical impedance. Oxygen uptake (Vo(2)) was obtained by breath-by-breath minute ventilation (ventilated hood) and was measured under resting energy expenditure (REE) conditions. Endurance was measured with an incremental cycle ergometer test. Male and female groups were balanced for mean (+/- SD) age (42.7 +/- 7.6 vs 41.8 +/- 8.9 years, respectively), BMI (43.0 +/- 4.9 vs 41.3 +/- 5.2 kg/m(2), respectively), and fat weight (55.5 +/- 14.0 vs 56.8 +/- 2.2 kg, respectively). Fat-free mass (FFM), FFM index, fasting blood glucose level, insulin level, BEE, and VO2 at rest and during subjective maximal endurance were higher in the male group. However, maximal VO2 (women, 119 +/- 19% predicted; men, 92 +/- 16% predicted) and anaerobic threshold were higher in the female group (women, 64 +/- 12% predicted; men, 48 +/- 76% predicted, respectively; p = 0.0001).Conclusions: Severely obese men were more carbohydrate-intolerant and sustained less physical endurance than was predicted according to standards in comparison with obese women. The cycle ergometer data indicated that male gender was associated with less physical fitness.

One of the major goals of bronchodilator therapy in patients with COPD is to decrease airflow limitation in the airways and, as a consequence, improve dyspnea and exercise tolerance. The focus of this systematic review is to assess the effects of treatment with beta-agonists, anticholinergics, and theophyllines on dyspnea, and steady-state and incremental exercise capacity. Thirty-three, double-blind, randomized, placebo-controlled studies written in English were selected. This review shows that approximately half of the studies showed a significant effect of bronchodilator therapy on exercise capacity. Anticholinergic agents have significant beneficial effects in the majority of studies, especially when measured by steady-state exercise protocols. There is a trend toward a better effect of high-dose compared to low-dose anticholinergics. Short-acting beta(2)-mimetics have favorable effects on exercise capacity in more than two thirds of the studies; surprisingly, the situation is less clear for long-acting beta(2)-agents. The majority, of the results of the published reports on theophyllines and their effects on exercise are negative. Direct comparisons of different classes of bronchodilators have not been made in a sufficient number of studies for a rational preference. The addition of a second bronchodilator has no proven advantage for improving exercise test results, but this has not been studied extensively and not in sufficiently, large studies. The majority of studies reporting a measure of dyspnea found improvements, even in the absence of improvement in exercise capacity.

Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease with pulmonary vasculopathy.The purpose of this study was to determine whether sildenafil improves 6-min walk distance (6MWD) in subjects with IPF and right ventricular dysfunction.The IPFnet, a network of IPF research centers in the United States, conducted a randomized trial examining the effect of sildenafil on 6MWD in patients with advanced IPF, defined by carbon monoxide diffusing capacitylt; 35% predicted. A substudy examined 119 of 180 randomized subjects where echocardiograms were available for independent review by two cardiologists. Right ventricular (RV) hypertrophy (RVH), right ventricular systolic dysfunction (RVSD), and right ventricular systolic pressure (RVSP) were assessed. Multivariable linear regression models estimated the relationship between RV abnormality, sildenafil treatment, and changes in 6MWD, St. George's Respiratory Questionnaire (SGRQ), the EuroQol instrument, and SF-36 Health Survey (SF-36) from enrollment to 12 weeks.The prevalence of RVH and RVSD were 12.8% and 18.6%, respectively. RVSP was measurable in 71 of 119 (60%) subjects; mean RVSP was 42.5 mm Hg. In the subgroup of subjects with RVSD, subjects treated with sildenafil experienced less decrement in 6MWD (99.3 m; P = .01) and greater improvement in SGRQ (13.4 points; P = .005) and EuroQol visual analog scores (17.9 points; P = .04) than subjects receiving placebo. In the subgroup with RVH, sildenafil was not associated with change in 6MWD (P = .13), but was associated with greater relative improvement in SGRQ (14.8 points; P = .02) vs subjects receiving placebo. Sildenafil treatment in those with RVSD and RVH was not associated with change in SF-36.Sildenafil treatment in IPF with RVSD results in better preservation of exercise capacity as compared with placebo. Sildenafil also improves quality of life in subjects with RVH and RVSD.

Pulmonary rehabilitation has been shown to improve exercise capacity in patients with COPD. It has been suggested that this improvement applies to all age groups; however, to our knowledge, the effects of pulmonary rehabilitation on older elderly patients (or = 75 years of age) have not been studied. We compared changes in 12-min walking distance (12MD) and self-assessment scores in 47 older elderly patients with moderate to severe COPD who completed inpatient or outpatient pulmonary rehabilitation with those achieved by 87 younger patients who participated in the same programs from 1987 to 1992. There were 28 older elderly individuals (mean +/- SEM, 78 +/- 1 years) in the outpatient group and 56 younger patients (64 +/- 1 years). There were no differences between older and younger outpatients with respect to FEV1, FEV1/FVC, maximum inspiratory pressure (PImax), baseline 12MD, or baseline self-assessment score. After outpatient pulmonary rehabilitation, 12MD and self-assessment scores improved significantly in both groups. Inpatients included 19 older elderly individuals (81 +/- 1 years) who were also similar to the 31 younger inpatients (64 +/- 1 years) in FEV1, FEV1/FVC, PImax, and baseline self-assessment score, but they tended to be more limited in terms of baseline 12MD (p = 0.09). After inpatient pulmonary rehabilitation, significant improvements in 12MD and self-assessment were seen in both groups. We conclude that comprehensive outpatient and inpatient pulmonary rehabilitation programs are as beneficial in older elderly patients with COPD as they are in younger patients with similar lung function abnormalities. Patients 75 years of age or older should be considered for comprehensive pulmonary rehabilitation.

The weak relationship between left ventricular function and exercise capacity in heart failure has stimulated interest in neurohumoral mechanisms as possibly contributing to exercise intolerance. Although chronic activation of neuroendocrine systems is characteristic of heart failure and is accompanied by impaired reflex responsiveness to physiologic stimuli, data from clinical trials do not support the hypothesis that the abnormal neurohumoral state is directly related to exercise intolerance. Thus, these systems may play an important role in the natural history of the disease and its high mortality, but they may not be critical to the impaired exercise capacity.

Cold air may worsen asthmatic bronchoconstriction but can lessen breathlessness in normal individuals. Patients with COPD sometimes report improvement in their dyspnea in cold weather. We examined the effect of breathing cold air on exercise tolerance and the perception of breathlessness in 19 patients with stable COPD (age [+/- SD], 63 +/- 6 years; FEV1, 0.99 +/- 0.28 L) in a randomized open study. Patients exercised on a cycle ergometer breathing either room or cold air (-13 degrees C), breathlessness being assessed by Borg scaling. Peak exercise performance improved when breathing cold air (mean +/- SE), 46 +/- 6 W compared with 37 +/- 7 W (p0.05) while end-exercise breathlessness fell from 4.6 +/- 0.4 compared with 4.1 +/- 0.5 (p0.05) when breathing cold air. End-exercise ETCO2 was higher breathing cold air (6.1 +/- 0.3 kPa compared with 5.5 +/- 0.3 kPa) (p0.005). There was no difference in breathlessness at equivalent levels of ventilation. Cold air reduces breathlessness in COPD, probably by inducing relative hypoventilation.

A 13-year-old female patient with a pulmonary arteriovenous fistula (PAVF) of 24 percent shunt fraction (SF) underwent resection of segments 8 and 9 of the left lower lobe. Three months after the operation, the shunt became insignificant and PaO2 was normalized. In terms of the maximum work rate, maximum V ˙ o 2 and the V ˙ o 2 blood lactate relationship, this patient showed a remarkable postoperative improvement in the exercise capacity.