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There is little information about comorbidities and their risk factors in the preclinical stages of chronic obstructive pulmonary disease (COPD).This study aims to investigate the prevalence of premorbid risk factors and comorbid diseases and its association with daily physical activity in subjects detected with COPD by spirometry screening.Sixty subjects with preclinical COPD (63 ± 6 yr; 68% [n = 41] male) were compared with 60 smoking control subjects (62 ± 7 yr; 70% [n = 42] male) and 60 never-smoking control subjects (62 ± 6 yr; 57% [n = 34] male). Comorbidities (cardiovascular, metabolic, and musculoskeletal disease) and daily physical activity (by multisensor activity monitor) were measured objectively.The prevalence of premorbid risk factors and comorbid diseases was significantly higher in preclinical COPD compared with age-matched never-smoking control subjects, but was similar to smoking control subjects not suffering from COPD. In preclinical COPD and smoking control subjects, the combination of cardiovascular disease and musculoskeletal disease was the most prevalent (15% [n = 9] and 12% [n = 7], respectively). In a multivariate logistic regression analysis, physical inactivity and smoking were found to be independent risk factors for having greater than or equal to two comorbidities.Premorbid risk factors and comorbid diseases were more prevalent in the preclinical stages of COPD and smokers without COPD. Physical inactivity and smoking were more strongly associated with the presence of comorbidities compared with airflow obstruction. Clinical trial registered with www.clinicaltrials.gov (NCT 01314807).

Linda Nici, Claudio Donner, Emiel Wouters, Richard Zuwallack, Nicolino Ambrosino, Jean Bourbeau, Mauro Carone, Bartolome Celli, Marielle Engelen, Bonnie Fahy, Chris Garvey, Roger Goldstein, Rik Gosselink, Suzanne Lareau, Neil MacIntyre, Francois Maltais, Mike Morgan, Denis O’Donnell, Christian Prefault, Jane Reardon, Carolyn Rochester, Annemie Schols, Sally Singh, and Thierry Troosters, on behalf of the ATS/ERS Pulmonary Rehabilitation Writing Committee

The present study was undertaken to test whether endurance training in patients with COPD, along with enhancement of muscle bioenergetics, decreases muscle redox capacity as a result of recurrent episodes of cell hypoxia induced by high intensity exercise sessions. Seventeen patients with COPD (FEV 1 , 38 � 4% pred; Pa O2 , 69 � 2.7 mm Hg; Pa CO2 ,42 � 1.7 mm Hg) and five agematched control subjects (C) were studied pretraining and posttraining. Reduced (GSH) and oxidized (GSSG) glutathione, lipid peroxidation, and gamma-glutamyl cysteine synthase heavy subunit chain mRNA expression ( � GCS-HS mRNA) were measured in the vastus lateralis. Pretraining redox status at rest and after moderate (40% Wpeak) constant-work rate exercise were similar between groups. After training ( � Wpeak, 27 � 7% and 37 � 18%, COPD and C, respectively) (p � 0.05 each), GSSG levels increased only in patients with COPD (from 0.7 � 0.08 to 1.0 � 0.15 nmol/ mg protein, p � 0.05) with maintenance of GSH levels, whereas GSH markedly increased in C (from 4.6 � 1.03 to 8.7 � 0.41 nmol/

Recently, it was suggested that fatigue of peripheral muscles could contribute to exercise limitation in patients with chronic obstructive pulmonary disease (COPD). In order to quantify the role of peripheral muscle force, we restudied potential determinants of exercise capacity (6-min walking distance [6 MWD] and maximal oxygen consumption [V02max]) in 41 consecutive COPD patients (FEV1, 43 +/- 19% of predicted, TLCO, 56 +/- 25% of predicted) admitted to our pulmonary rehabilitation program. VO2max (incremental cycle ergometer test), 6 MWD (best of three), lung function (FEV1, FVC, TLC, FRC), diffusing capacity (TLCO), isometric quadriceps force (QF), hand grip force (HF), and maximal inspiratory (PImax) and expiratory (PEmax) pressures were measured. Patients had a poor 6 MWD (372 +/- 136 m) and VO2max (1.35 +/- 0.60 L, 71%), reduced respiratory (PImax 65 +/- 27%) and peripheral muscle force (QF 74 +/- 27%, HF 82 +/- 23%). In single regression analysis, significant correlations (r) were found for VO2max and TLCO (0.68), FEV1 (0.64), QF (0.55), HF (0.53), and body weight (0.49). Walking distance was significantly correlated with QF (0.63), HF (0.61), PImax (0.49), and TLCO (0.38). In stepwise multiple regression analysis, the variables significantly contributing to 6 MWD were QF and Plmax. For VO2max, variables significantly contributing were TLCO, QF, and FEV1. We conclude that lung function and peripheral muscle force are important determinants of exercise capacity in COPD.