Rational Chronic Obstructive Pulmonary Disease (COPD) is a major cause of healthcare system use and related cost. While pulmonary rehabilitation (PR) is efficient, maintenance programs (PR-MA) can maintain the benefits over time. Yet, the long-term impact (>36 months) of PR-MA on healthcare resource and cost has never been assessed. Recently, a PR-MA program based on self-help associations has shown a clinical efficacy beyond 36 months, Thus, we aimed to assess the effect of this PR-MA program on long-term hospitalizations and costs versus usual care (PR-UC). Methods We performed an ancillary analysis of the post-rehabilitation LTAir+R cohort study, which compared a PR-MA group (n=144) to a matched PR-UC group (n=137) of COPD patients. Data were collected in 82 PR-MA and 93 PR-UC patients, from the Montpellier University Hospital database and patient records over 60 months, including hospitalizations, consultations, emergency visits, and associated costs. Results In PR-AM vs. PR-UC group, the hospitalization probability reduction almost reached significance (hazard ratio: 1.68; p=0.05). The costs of each hospitalization day (867±116 vs. 1213±138 euros/day; p<0.05), emergency visits (8±5 euros/year vs. 12±3 euros/year) and medical consultations (110±3 vs. 174±3 euros/year; p<0.01) were significantly lower in the PR-AM vs. PR-UC group. Last, PR-MA mitigated the increase in total hospitalizations (p<0.001) associated with the follow-up duration. Conclusion In addition to its long-term clinical efficacy, this PR-MA program showed a positive impact on hospitalization and healthcare use costs. The effect on hospitalization number and costs could be larger in patients with the longest PR-MA adherence.

Chronic obstructive pulmonary disease (COPD) is frequently associated with skeletal muscle dysfunction, having a considerable impact on exercise tolerance and patient prognosis. Mitochondria play a role in skeletal muscle weakness and exercise intolerance in COPD, but the majority of studies on mitochondrial function are biased by the fact that physical activity is greater in healthy subjects than in patients. Furthermore, exercise training (ET) has been proposed as a therapeutic strategy to prevent skeletal muscle dysfunction in COPD, but very few results are available on mitochondrial adaptation in response to ET. Skeletal muscle mitochondrial function and the potential efficacy of ET on this function were compared between 12 patients with COPD and 21 healthy subjects with similar low levels of physical activity. Various markers of mitochondrial respiration, oxidative stress, biogenesis, and dynamics were assessed. Lower oxidative phosphorylation (OxPhos; p < 0.001) and increased nonphosphorylating respiration (p = 0.025) and mitochondrial oxidative damage (lipid peroxidation (p = 0.014) and protein carbonylation (p = 0.020)) were observed in patients. While ET increased OxPhos efficiency (p = 0.011) and reduced nonphosphorylating respiration (p < 0.001) and lipid peroxidation (p < 0.001) in patients' muscle mitochondria, it fails to improve maximal respiration (p = 0.835) and expression of the antioxidant enzyme MnSOD (p = 0.606), mitochondrial transcription factor TFAM (p = 0.246), and mitochondrial complexes I, III, and IV (p = 0.816, p = 0.664, p = 0.888, respectively) as observed in healthy subjects. The mitochondrial dysfunction and the defects in mitochondrial adaptation to ET that we observe in the muscle of patients with COPD are intrinsic to the disease and do not arise from muscle disuse.

Pulmonary rehabilitation (PR) is a core component for the management of obstructive lung disease (OLD), but the benefits decline within 6 to 12 months without maintenance strategies (Spruit et al, 2013 AJRCCM). Pragmatic and effective long-term PR maintenance programs are therefore crucial. This study evaluated the effectiveness of a PR maintenance program to stabilize the benefits of PR over 7 years in patients with OLD. Data were prospectively collected from 289 OLD patients (age: 66.5±8.7 years, FEV1: 64.0±24.8%predic.) who followed a PR maintenance program lasting from 1 to 7 years. The program was carried out in self-help associations within a healthcare network and consisted in 1 session/week of supervised exercise training and 8 sessions/year of therapeutic education. Changes in 6-minute walk distance (6MWD), quality of life score (VQ11), dyspnea (MRC) and lung function (FEV1) were assessed using mixed effect linear models. Over the 7 years of follow-up, no significant deterioration in the VQ11 score (time effect: β=0.61, p=0.52), dyspnea (time effect: β=0.28, p=0.10) or FEV1 (%predic.; time effect: β=0.35, p=0.16) was observed. Conversely, 6MWD declined (%predic.; time effect: p<0.01) but this decline was statistically significant only from the 60th month (p<0.05). This study demonstrated that PR gains in exercise tolerance were maintained for 5 years and that the PR effect on dyspnea and quality of life remained stabilized for 7 years. These findings suggest that pragmatic PR maintenance programs can conserve a long term efficiency.

Le maintien de la tolérance à l’effort ainsi que la stabilisation des symptômes et de la qualité de vie constituent le « Graal » de la réhabilitation des malades respiratoires chroniques. Les programmes de post-réhabilitation (PR) permettent d’éviter le déclin de la dyspnée, de la tolérance à l’effort et de la qualité de vie à court terme [1]. À ce jour, seule une étude a évalué l’impact de la PR au-delà d’un an, mais non applicable en France [2]. L’objectif était de déterminer l’effet d’un programme de post-réhabilitation sur l’évolution annuelle des patients sur 24 mois et d’évaluer la contribution de déterminants cliniques et fonctionnels à cette évolution. Après une réhabilitation en centre, les patients ont intégré le réseau de PR Air + R Occitanie, pour des sessions de réentraînement (REE) : 2 h/semaine et d’éducation thérapeutique (ETP) : 8 h/an. Les évaluations annuelles des patients de 2013 à 2018 ont été analysées : Dyspnée (MRC), distance au test de marche de 6 minutes (TDM6) et questionnaire de qualité de vie (VQ-11). Chez 151 patients (VEMS : 68 ± 29 % théo. ; BODE index : 1,88 ± 2,02), la dyspnée, la distance au TDM6, et le VQ-11 sont restés stables à 12 et 24 mois (2,2 ± 1,2 à 2,2 ± 1,3, p = 0,42 ; 466 ± 101 m à 456 ± 111 m, p = 0,31 ; 23,9 ± 8,3 à 24,3 ± 8,8, p = 0,69, respectivement), de même que le VEMS (69 ± 29 à 67 ± 27 % théorique ; p = 0,95). Nous n’avons pas observé de corrélation significative entre les caractéristiques des patients et les changements de dyspnée, TDM6, et VQ-11 à 24 mois. Si les patients améliorant leur TDM6 (+30 m : 20 %) étaient moins sévères que ceux le détériorant (−30 m : 34 %) sur le plan de la dyspnée MRC (1,0 [1,0–2,0] vs 2,0 [1,0–3,3] ; p < 0,05) et du TDM6 (505 ± 89 m vs 400 ± 110 m ; p < 0,001), l’évolution du VEMS (−0,5 [−8,8–0,0] % vs +1,0 [−1,0–8,0] % ; p < 0,05 et l’observance du REE (56 ± 21 % vs 60 ± 25 % vs p = 0,24) n’était pas supérieurs chez ces patients qui amélioraient le tolérance à l’effort à 2 ans. Les bénéfices de la réhabilitation respiratoire se maintiennent au moins 24 mois chez les patients intégrant un programme de post-réhabilitation, avec même gains de tolérance à l’effort chez 20 % des patients, les moins sévères.

In COPD patients oxidative stress (OS) is a limiting factor of exercise training effects on muscle impairment during pulmonary rehabilitation (PR). Antioxidant supplementation used during PR appeared inappropriate to cope with COPD-related antioxidant deficits. We therefore investigated whether exercise training PR, combined with non-pharmacological antioxidant supplementation (vitamins C and E, zinc, selenium), would have beneficial effects on muscle impairment and exercise capacity. 58 stable COPD patients (61 years; FEV1: 59%predicted) referred for a 4-week PR program, were recruited in a double-blind randomized, placebo-controlled clinical trial. Primary outcome was change in quadriceps endurance (Qend). Secondary outcomes were: quadriceps maximal voluntary contraction (QMVC), exercise capacity (maximal oxygen uptake (Vo2sl), systemic OS markers and muscle fiber cross sectional area (CSA). Qend was significantly increased in both COPD patient groups. QMVC and VO2sl were improved (+9 and +16%, respectively) exclusively in “PR+antioxidant” group (p=0.01 and p<0.05). The “PR+antioxidant” group showed a significant increase in vitamin E and selenium compared to “PR+placebo” group (p=0.05 and p<0.001, respectively) without differences in vitamin C and lipid peroxidation. Muscle fiber CSA was significantly increased in “PR+antioxidant” group compared to “PR+placebo” group (+17% vs -6% respectively, p<0.05). In conclusion, this study showed that antioxidant supplementation combining vitamin C, E, zinc and selenium, improves the PR effects on QMVC, Vo2sl and muscle fiber CSA by enhancing antioxidant capacity of COPD patients.

To determine and/or adjust exercise training intensity for patients when the cardiopulmonary exercise test is not accessible, the determination of dyspnoea threshold (defined as the onset of self-perceived breathing discomfort) during the 6-min walk test (6MWT) could be a good alternative. The aim of this study was to evaluate the feasibility and reproducibility of self-perceived dyspnoea threshold and to determine whether a useful equation to estimate ventilatory threshold from self-perceived dyspnoea threshold could be derived. A total of 82 patients were included and performed two 6MWTs, during which they raised a hand to signal self-perceived dyspnoea threshold. The reproducibility in terms of heart rate (HR) was analysed. On a subsample of patients (n=27), a stepwise regression analysis was carried out to obtain a predictive equation of HR at ventilatory threshold measured during a cardiopulmonary exercise test estimated from HR at self-perceived dyspnoea threshold, age and forced expiratory volume in 1 s. Overall, 80% of patients could identify self-perceived dyspnoea threshold during the 6MWT. Self-perceived dyspnoea threshold was reproducibly expressed in HR (coefficient of variation=2.8%). A stepwise regression analysis enabled estimation of HR at ventilatory threshold from HR at self-perceived dyspnoea threshold, age and forced expiratory volume in 1 s (adjusted r=0.79, r 2=0.63, and relative standard deviation=9.8 bpm). This study shows that a majority of patients with chronic obstructive pulmonary disease can identify a self-perceived dyspnoea threshold during the 6MWT. This HR at the dyspnoea threshold is highly reproducible and enable estimation of the HR at the ventilatory threshold.

INTRODUCTION:The aim of our study was to investigate whether exclusive home-based training was feasible and effective in COPD patients and if patients have a persistent improvement in their level of physical activity after this intervention. METHODS:One hundred COPD patients (FEV1=42.6% predicted) first underwent 25 weekly sessions of supervised cycle ergometry training, followed by one year of monthly supervised follow-up. Six minutes walking test, endurance test, BODE index and activity monitoring were performed before, after and one year after inclusion. RESULTS:About 80% of the patients completed the program. They improved their exercise tolerance and their daily physical activity level, even one year after inclusion. However, more severe patients did not maintain these benefits. Daily physical activity quantity was also decreased in these patients one year after inclusion. CONCLUSION:This home-based exercise training program is feasible and effective. Improvements are sustainable for the majority of patients. However, severe patients were not able to maintain these benefits. Other exercise training strategies may have to be considered in these patients.

Letter to the EditorReference values for vastus lateralis fiber type proportion and fiber sizeFares Gouzi, Jonathan Maury, Nicolas Molinari, Pascal Pomiès, Jacques Mercier, Christian Préfaut, and Maurice HayotFares GouziINSERM U-1046, CHRU Montpellier, Department of Clinical Physiology, University of Montpellier I and II, Montpellier, France; Pulmonary Rehabilitation Center “La Solane”, Fontalvie Group, Osséja, France; and , Jonathan MauryINSERM U-1046, CHRU Montpellier, Department of Clinical Physiology, University of Montpellier I and II, Montpellier, France; Pulmonary Rehabilitation Center “La Solane”, Fontalvie Group, Osséja, France; and , Nicolas MolinariUMR 729 MISTEA, CHRU Montpellier, Department of Medical Information, University of Montpellier I, Montpellier, France, Pascal PomièsINSERM U-1046, CHRU Montpellier, Department of Clinical Physiology, University of Montpellier I and II, Montpellier, France; , Jacques MercierINSERM U-1046, CHRU Montpellier, Department of Clinical Physiology, University of Montpellier I and II, Montpellier, France; , Christian PréfautINSERM U-1046, CHRU Montpellier, Department of Clinical Physiology, University of Montpellier I and II, Montpellier, France; , and Maurice HayotINSERM U-1046, CHRU Montpellier, Department of Clinical Physiology, University of Montpellier I and II, Montpellier, France; Published Online:15 Jan 2014https://doi.org/10.1152/japplphysiol.01332.2013MoreSectionsPDF (32 KB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations to the editor: In a previous issue of the Journal of Applied Physiology, Gosker and Schols (1) commented on the reference values for fiber CSA of the vastus lateralis of the quadriceps in healthy subjects >40 years old.First, we are pleased to read that the fiber CSA values provided by our meta-analysis are significantly correlated with the Maastricht team's data from healthy subjects. This reinforces our findings, because data from a healthy population were not included in our systematic review. Moreover, the data on type I fiber proportions published by Gosker et al. agree with data obtained using a systematic approach (2). Altogether, the data provided by Gosker and Schols validate our publication.However, the authors contest the statement that the reference values for type I fiber proportion in our study are more valid than those published previously by their group (1). This statement in no way diminishes the merit of the paper from Gosker et al. because they systematically reviewed only studies of COPD patients and provided results similar to those found in our study. Yet the systematic review process was not performed in the same way for healthy subjects, as stated in their methods section: “For control values of quadriceps femoris fibre type proportions we used age-matched healthy control groups of the COPD related papers described above” (2). Therefore, nine studies matching the inclusion criteria for the systematic review in healthy subjects included in our meta-analysis were missed.Conversely, we do not contest the limited usefulness of our reference values for fiber CSA in the context of a drastic fiber type switch. In under 33% of type I fiber, the lower limits of the normal (LLNs) are 1,255 μm2 and 826 μm2, respectively, in men and women, which is low. In our cohort of 39 COPD patients, we found that, using our published LLNs, 2/39 (5%) COPD patients had fiber atrophy. This is discrepant with the 20% recently reported (4) using a different methodology. However, given the variability inherent to sampling from a small group (n = 30), the LLNs in this latter study should have been considered as random variables with their own mean and SD. Thus the real LLNs should have taken this variability into account and must, in fact, have been much lower.As explained in our discussion section, the low LLNs obtained in our meta-analysis are the consequence of the remaining variability of the fiber CSA. Yet, the fiber CSA coefficients of variation (CVs) are lower than the CVs in studies with small sample sizes (3, 4) and in agreement with the CV obtained in a study (5) with a similarly large sample (n = 418). The variability of fiber CSA can be explained by several factors and may indicate its potential sensitivity to external factors, which is mandatory for a potential biomarker.Altogether, our conclusion that “ongoing work with inclusions of new studies of well-characterized populations of healthy subjects will further optimize these reference values by reducing the present variability in fiber CSA and proportions” is consistent with the limitation reported in the letter from Gosker and Schols. Therefore, we invite the Maastricht team to join us in the multicentric study that we are now designing to improve the accuracy of the current reference values in healthy subjects.DISCLOSURESNo conflicts of interest, financial or otherwise, are declared by the author(s).AUTHOR CONTRIBUTIONSAuthor contributions: F.G., J. Maury, and N.M. drafted manuscript; F.G., C.-G.P., and M.H. edited and revised manuscript; F.G., J. Maury, N.M., P.P., J. Mercier, C.-G.P., and M.H. approved final version of manuscript.REFERENCES1. Gosker HR, Schols AM. Reference values for vastus lateralis fiber type proportions and fiber size. J Appl Physiol 115: 771, 2013.Link | ISI | Google Scholar2. Gosker HR, Zeegers MP, Wouters EF, Schols AM. Muscle fibre type shifting in the vastus lateralis of patients with COPD is associated with disease severity: a systematic review and meta-analysis. Thorax 62: 944–949, 2007.Crossref | PubMed | ISI | Google Scholar3. Gouzi F, Prefaut C, Abdellaoui A, Roudier E, de Rigal P, Molinari N, Laoudj-Chenivesse D, Mercier J, Birot O, Hayot M. Blunted muscle angiogenic training-response in COPD patients versus sedentary controls. Eur Respir J 41: 806–814, 2013.Crossref | PubMed | ISI | Google Scholar4. Natanek SA, Gosker HR, Slot IG, Marsh GS, Hopkinson NS, Man WD, Tal-Singer R, Moxham J, Kemp PR, Schols NM, Polkey MI. Heterogeneity of quadriceps muscle phenotype in chronic obstructive pulmonary disease (COPD); implications for stratified medicine? Muscle Nerve 48: 488–497, 2013.Crossref | ISI | Google Scholar5. Simoneau JA, Bouchard C. Human variation in skeletal muscle fiber-type proportion and enzyme activities. Am J Physiol Endocrinol Metab 257: E567–E572, 1989.Link | ISI | Google ScholarAUTHOR NOTESAddress for reprint requests and other correspondence: F. Gouzi, INSERM U-1046, Univ. Montpellier I, Univ. Montpellier II, Dept. of Clinical Physiology, CHRU Montpellier, 34295 Montpellier cedex 5, France (e-mail: [email protected]fr). Download PDF Previous Back to Top Next FiguresReferencesRelatedInformation More from this issue > Volume 116Issue 2January 2014Pages 228-228 Copyright & PermissionsCopyright © 2014 the American Physiological Societyhttps://doi.org/10.1152/japplphysiol.01332.2013PubMed24429104History Published online 15 January 2014 Published in print 15 January 2014 Metrics

Background: Exercise training may improve components of metabolic syndrome and obstructive sleep apnea syndrome (OSAS). The objective of our pilot randomized controlled study was to determine the benefits of a short intensive inpatient individualized exercise training (IET) program in sedentary untreated OSAS patients.Methods: Twenty-two sedentary patients with moderate to severe OSAS were randomly assigned either to one-month education activity sessions (n = 11; control group) or to inpatient rehabilitation program (n = 11), including IET, education activities sessions, and dietary management. Full polysomnography (PSG), OSLER (Oxford Sleep Resistance test), body composition, anthropometric measurements, metabolic syndrome components, and questionnaires were performed at baseline and at study end point.Results: No changes occurred in the control group in all variables. Compared to controls, participants randomized to the IET group presented a significant decrease in apnea-hypopnea index (AHI) (40.6 +/- 19.4 vs 28.0 +/- 19.3; P < 0.001), oxygen desaturation index (ODI), and arousal index, which occurred in conjunction with significant decrease in body mass index (BMI), neck circumference, fat mass, fasting glucose, and diastolic blood pressure. Increased sleep latency was found in participants in the IET group with altered values at baseline.Conclusions: IET reduced OSAS severity with improvement of metabolic syndrome components with concomitant loss in body fat in sedentary adults. If confirmed on a larger scale, a comprehensive rehabilitation program could constitute an additional or alternative treatment for moderate to severe OSAS patients. (C) 2014 Published by Elsevier B.V.

La drépanocytose, maladie génétique la plus fréquente en France, est non seulement une maladie de l'hémoglobine, mais aussi une maladie vasculaire associée à des phénomènes inflammatoires. La douleur est au premier plan. Elle est devenue une maladie chronique émaillée de complications aiguës. Le dépistage néonatal a permis d'améliorer de manière très significative la mortalité et la morbidité grâce aux mesures préventives (antibioprophylaxie, vaccinations, dépistage de la vasculopathie cérébrale), à l'éducation thérapeutique et à la prise en charge psychologique débutées dès l'âge de 2 mois. Dès l'annonce, la prise en charge doit être multidisciplinaire et en réseau de soins. Dans les formes sévères, l'intensification thérapeutique par hydroxycarbamide, des transfusions régulières et/ou une greffe de moelle en ont transformé le pronostic. Les principales complications aiguës (crise vaso-occlusive, syndrome thoracique aigu, anémie brutale, infection sévère, accident vasculaire cérébral) peuvent survenir de manière imprévisible chez l'enfant et mettre en jeu le pronostic vital. Elles nécessitent un diagnostic et une prise en charge thérapeutique urgents. À l'avenir, un des challenges sera de repérer très précocement les patients à risque de développer une maladie sévère afin qu'ils puissent bénéficier d'une intensification thérapeutique précoce, et de pouvoir prévenir l'apparition des complications organiques chroniques chez l'adulte.

La bronchopneumopathie chronique obstructive (BPCO) est une pathologie respiratoire à l’origine d’une mortalité et d’un handicap important. Les sujets âgés de plus de 65 ans sont plus fréquemment touchés par cette maladie que les patients plus jeunes. Les interventions non pharmacologiques prennent une place importante dans la prise en charge de la BPCO et présentent des spécificités chez la personne âgée. Le sevrage tabagique doit être proposé quel que soit l’âge compte tenu de l’amélioration de la qualité de vie et du risque d’hospitalisation. L’augmentation de l’activité physique est également source de réduction des symptômes de dyspnée. Des tests sous-maximaux comme le « Short Physical Performance Battery » sont à privilégier. L’utilisation du test de marche de 6 minutes est également incontournable. L’augmentation de l’activité physique doit se faire en association avec l’amélioration du statut nutritionnel. Un dépistage de la dénutrition par questionnaire, calcul de l’indice de masse corporelle et dosage de l’albuminémie est recommandé chez le sujet âgé. En cas de dénutrition, la supplémentation orale semble diminuer le risque de réhospitalisation. Toutes ces mesures doivent s’intégrer dans un programme d’éducation thérapeutique adapté aux difficultés présentées par les personnes âgées (surdité, isolement…).Chronic obstructive pulmonary disease (COPD) is a respiratory disorder responsible for a high mortality and disability. People older than 65 years are more commonly affected than younger people and tend to present with more symptoms and a greater level of disability. Non-pharmacological interventions play an important role in the management of all patients with COPD and this is particularly true in the elderly. Given the improvement in quality of life and risk of hospitalization, smoking cessation should be promoted to patients of all ages. Increased physical activity is associated with reduced respiratory symptoms. Tests such as the “Short Physical Performance Battery” can be useful in frailer older people with COPD, while walking tests such as the 6-minute walk test are used as an assessment before pulmonary rehabilitation. Increased physical activity should be combined with nutritional management. Screening for undernutrition by questionnaire, body mass index and albumin quantification is recommended in the elderly. In case of undernutrition, oral supplementation seems to reduce the risk of re-admission. All these measures must be included in an education program adapted to the elderly comorbidities (hearing loss, isolation…).

To study the exercise-induced arterial hypoxaemia (EIAH) kinetics in a world class Ironman triathlete at ventilatory threshold (THvent), the authors simulated the cycle-run succession (CR, 20 min + 20 min) and a 20-min isolated run (R). Although 'moderate EIAH' was noted during CR, the SpO2 kinetics of the isolated R reflected 'severe EIAH' from minutes 7 to 15 with a nadir of 85 % SpO2 that stabilised at 90 % SpO2 from minute 15 on. The physiological processes involved in these responses are discussed. These data indicate a systematic 'moderate EIAH' in a world class Ironman champion during CR and R at THvent and a temporary 'severe EIAH' during R, which was attenuated when running was successive to cycling. The physiological significance of this phenomenon remains unclear, however, and further experiments are needed.

Oxidative stress is involved in the skeletal muscle dysfunction of patients with COPD. Resting or exercise-induced imbalance between oxidants and antioxidants is common in COPD, but the precise systemic oxidative stress profile remains unclear. This could explain the limited effects reported following antioxidant supplementation. We therefore determined the systemic oxidative profile of stable COPD patients to identify the proportion with an abnormal profile. We measured the plasma levels of enzymatic and non-enzymatic antioxidants and of lipid peroxidation (LP) markers in 28 stable COPD patients at rest and after a quadriceps endurance test (Qend) at 30% of the maximal strength. Results were compared with the lower and upper limits of reference (LLR and ULR) of a healthy subject cohort. At rest, the Vitamin C/Vitamin E ratio was decreased in 54% of patients (0.58±0.27; LLR=0.59) and selenium level in 73% (91±14 μg/ml; LLN=94). The Cu/Zn ratio was increased in 79% (1.44±0.31; ULR=1.17). LP level was increased in 64% of patients and significantly correlated with the 6-min walking distance (r=0.60; p<0.005) and muscle mass (r=0.47; p<0.05). After the Qend, Vitamin E and Zn plasma levels decreased in 55% and 91% of patients respectively, without changes in LP level. Altogether, our findings indicate that in 92% of stable COPD patients, the systemic oxidative stress profile is imbalanced, particularly the concentration of dietary vitamins and trace elements, and is associated with the skeletal muscle dysfunction. This imbalanced profile can be modified by local quadriceps exercise. More patients are needed to identify specific phenotypes of antioxidant deficits.

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.

AIM:To assess whether the severity of obstructive sleep apnoea syndrome (OSAS) is associated with altered fat oxidation (FO) during physical exercise in men with type 2 diabetes (T2DM) and/or the metabolic syndrome (MetS). METHODS:A total of 105 consecutive overweight or/and T2DM male patients were hospitalized for metabolic check-ups including bioimpedancemetry to measure lean body mass (LBM), standardized exercise calorimetry to assess FO, maximum fat oxidation (MFO) and carbohydrate oxidation (CHO), and OSAS screening using respiratory polygraphy. Twenty patients were classified as having severe OSAS, according to the apnoea/hypopnoea index (AHI), with greater than 30 events/h (mean AHI: 45.2±14.3 events/h). They were group-matched for age, BMI, and the presence of T2DM and/or MetS with two other OSAS groups: mild (AHI<15 events/h [n=20]; mean AHI: 8.8±4.5 events/h); and moderate (AHI>15 events/h and<30 events/h [n=20]; mean AHI: 23.7±4.2 events/h). RESULTS:MFO adjusted for LBM was severely decreased in the severe OSAS group (1.6±1.0 mg.min(-1).kgLM(-1)) compared with the moderate (2.5±0.9 mg.min(-1).kgLM(-1); P=0.008) and mild (2.9±0.8 mg.min(-1).kgLM(-1); P=0.003) groups. All exercise-intensity levels (20%, 30%, 40% and 60% of the theoretical maximum aerobic power) showed reduced FO levels between the severe and mild-to-moderate OSAS groups. However, no differences in CHO were seen at any level of exercise between groups. Pearson's correlation analysis showed that AHI and the oxygen desaturation index were negatively associated with MFO corrected for LBM (r=0.41 and r=0.37, respectively; P<0.005). CONCLUSION:OSAS severity is associated with altered FO during exercise.

During exercise, healthy individuals are able to maintain arterial oxygenation, whereas highly-trained endurance athletes may exhibit an exercise-induced arterial hypoxaemia (EIAH) that seems to reflect a gas exchange abnormality. The effects of EIAH are currently debated, and different hypotheses have been proposed to explain its pathophysiology. For moderate exercise, it appears that a relative hypoventilation induced by endurance training is involved. For high-intensity exercise, ventilation/perfusion (V̇ A /Q̇) mismatching and/or diffusion limitation are thought to occur. The causes of this diffusion limitation are still under debate, with hypotheses being capillary blood volume changes and interstitial pulmonary oedema. Moreover, histamine is released during exercise in individuals exhibiting EIAH, and questions persist as to its relationship with EIAH and its contribution to interstitial pulmonary oedema. Further investigations are needed to better understand the mechanisms involved and to determine the long term consequences of repetitive hypoxaemia in highly trained endurance athletes.