Fiber atrophy, oxidative stress, and oxidative fiber reduction are the attributes of different phenotypes in chronic obstructive pulmonary disease patients.

Peripheral muscle dysfunction, associated with reductions in fiber cross-sectional area (CSA) and in type I fibers, is a key outcome in chronic obstructive pulmonary disease (COPD). However, COPD peripheral muscle function and structure show great heterogeneity, overlapping those in sedentary healthy subjects (SHS). While discrepancies in the link between muscle structure and phenotype remain unexplained, we tested whether the fiber CSA and the type I fiber reductions were the attributes of different phenotypes of the disease, using unsupervised clustering method and post hoc validation. Principal component analysis performed on functional and histomorphological parameters in 64 COPD patients {forced expiratory volume in 1 s (FEV1) = 42.0 [30.0-58.5]% predicted} and 27 SHS (FEV1 = 105.0 [95.0-114.0]% predicted) revealed two COPD clusters with distinct peripheral muscle dysfunctions. These two clusters had different type I fiber proportion (26.0 ± 14.0% vs. 39.8 ± 12.6%; P < 0.05), and fiber CSA (3,731 ± 1,233 vs. 5,657 ± 1,098 µm(2); P < 0.05). The "atrophic" cluster showed an increase in muscle protein carbonylation (131.5 [83.6-200.3] vs. 83.0 [68.3-105.1]; P < 0.05). Then, COPD patients underwent pulmonary rehabilitation. If the higher risk of exacerbations in the "atrophic" cluster did not reach statistical significance after adjustment for FEV1 (hazard ratio: 2.43; P = 0.11, n = 54), the improvement of VO2sl after training was greater than in the nonatrophic cluster (+24 ± 16% vs. +6 ± 13%; P < 0.01). Last, their age was similar (60.4 ± 8.8 vs. 60.8 ± 9.0 yr; P = 0.87), suggesting a different time course of the disease. We identified and validated two phenotypes of COPD patients showing different muscle histomorphology and level of oxidative stress. Thus our study demonstrates that the muscle heterogeneity is the translation of different phenotypes of the disease.

Blunted muscle angiogenic training-response in COPD patients versus sedentary controls.

The impaired skeletal muscle of chronic obstructive pulmonary disease (COPD) patients reduces exercise capacity. Similar to the oxidative muscle fibres, the angio-adaptation of muscle to training may be blunted in these patients, as in other chronic conditions. We therefore compared muscle functional responses and angio-adaptations after training in COPD patients and sedentary healthy subjects (SHS). 24 COPD patients (forced expiratory volume in 1 s 45.6 ± 17.5% predicted) and 23 SHS (<150 min · week(-1) of moderate-to-vigorous exercise) completed a 6-week rehabilitation programme based on individualised moderate-intensity endurance training. Histomorphological muscle analysis and measurements of pro-angiogenic vascular endothelial growth factor (VEGF)-A and anti-angiogenic thrombospondin (TSP)-1 were conducted before and after training. COPD patients and SHS showed improved symptom-limited oxygen consumption and muscle endurance, although improvements were lower in COPD patients (+0.96 ± 2.4 versus +2.9 ± 2.6 mL · kg(-1) · min(-1), p<0.05, and +65% versus +108%, p = 0.06, respectively). The capillary-to-fibre (C/F) ratio increased less in COPD patients than SHS (+16 ± 10% versus +37 ± 20%, p<0.05) and no fibre type switch occurred in COPD patients. The VEGF-A/TSP-1 ratio increased in COPD patients and SHS (+65% versus +35%, p<0.05). Changes in C/F and symptom-limited oxygen consumption were correlated (r = 0.51, p<0.05). In addition to a lack of fibre switch, COPD patients displayed a blunted angiogenic response to training.

Evidence of an early physical activity reduction in chronic obstructive pulmonary disease patients.

OBJECTIVE: To compare the lifetime pattern of physical activity (PA) in chronic obstructive pulmonary disease (COPD) patients and sedentary healthy subjects (SHS) using a PA questionnaire with a lifetime period of recall (Quantification de l'Activité Physique [QUANTAP] system), and to compare the pattern of PA reduction in COPD patients with the onset of breathlessness and other relevant clinical events in this disease (diagnosis, first rehabilitation, onset of smoking). DESIGN: Cross-sectional comparative study. SETTINGS: Outpatient university hospital and inpatient pulmonary rehabilitation center. PARTICIPANTS: COPD patients (n=129; mean age ± SD, 61±10y; forced expiratory volume in 1s, 57±23%) and SHS (n=29; mean age ± SD, 61±5y; <150min·wk(-1) of moderate-vigorous PA). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Lifetime PA was compared in COPD patients and SHS using the QUANTAP system. The patients with COPD and SHS underwent pulmonary function, exercise, and quadriceps endurance testing. The current PA level was assessed with a triaxial accelerometer and the Voorrips questionnaire. The age at the onset of breathlessness was also recorded. RESULTS: Accelerometry showed no significant difference between patients and SHS (in vector magnitude units, 136±56 vs 135±47; P=.95). Within the past 15 years, the cumulated PA level was not different for each 5-year period. Then, from the period of 16 to 40 years ago, it was systematically higher in patients compared with SHS (in metabolic equivalent/y(-1); median [interquartile range], 6973 [5400-12,207] vs 4248 [3545-5919]; P<.05). The COPD patients reduced their PA earlier than the SHS (45y vs 55y; P<.01), and the PA was dropped before the onset of breathlessness (45y vs 49y; P<.001). CONCLUSIONS: The observation of an early PA reduction, preceding the onset of breathlessness, suggests the implication of prior pathologic mechanisms in the PA reduction of COPD patients.