[COLIBRI: Improving clinical practice and producing relevant scientific data]. / COLIBRI : optimiser la pratique clinique et produire des données scientifiques pertinentes.

COLIBRI-COPD is a francophone consultation web portal accessible to pulmonologists in the hospital and in the community. We present this observation which describes the phenotype of COPD patients entered (anthropometry, exposures, addictions, functional impairments, questionnaires: MRC, DIRECT, CAT, HAD, Epworth, co-morbidities, incidence of exacerbations, drug treatment or other treatments). The results of the first 1079 patients show a high level of completeness for the main data items. A comparison of patients seen in outpatient consultations shows significant variability between patients with the same GOLD stage, regarding the incidence of exacerbations, signs of anxiety-depression, of diabetes mellitus, or the prescriptions of anticholinergics and inhaled corticosteroids. These initial results suggest that data collection in real life gives a reliable database to obtain longitudinal data on various aspects of COPD. The data quality (completeness, reliability) is partly related to the usability of the web tool and to the possibility of doing self-assessment of practitioners' own recorded data.

[Cardiopulmonary exercise testing and dyspnea in patients with chronic respiratory diseases]. / Exploration fonctionnelle à l'exercice (EFX) et dyspnée au cours de maladies respiratoires chroniques.

Cardiopulmonary exercise testing (CPET) is the most comprehensive investigation for understanding the mechanisms responsible for dyspnea in patients with chronic respiratory disease. The two observations presented here illustrate how CPET can contribute to the management of patients with interstitial lung diseases. A 60-year-old woman had been followed for 20 years for non-progressive pulmonary sarcoidosis, untreated for many years. CPET led to the diagnosis of an atrial septal defect. A 76-year-old man was treated for idiopathic pulmonary fibrosis. Before pulmonary rehabilitation, CPET was performed which revealed significant aortic valve stenosis, which had been to that point asymptomatic. In these two observations, CPET determined the presence of an associated disease, distinct from the interstitial lung disease.

Breathing patterns during eccentric exercise.

Eccentric (ECC) work is interesting for rehabilitation purposes because it is more efficient than concentric (CON). This study assessed respiratory patterns and electromyographic activity (EMG) during ECC and CON cycling, both at similar power outputs and VO2 in eight healthy male subjects. Measurements include ventilation (VE), tidal volume (Vt), breathing frequency (Fb), arterial blood gases, and vastus lateralis (VL) and biceps brachii (BB) EMG. At the same mechanical power, VO2 and VE were fivefold lower in ECC as was VL EMG while BB EMG, Vd/Vt, PaO2 and PaCO2, were not different between modalities. At the same VO2, there was no difference in VE but Vt was lower and Fb higher in ECC. VL EMG was not different between modalities while BB EMG was higher in ECC. The latter observation suggests that ECC cycling may result in arm bracing and restricted chest expansion. Since hyperpnea is a known trigger of exaggerated dynamic hyperinflation, the prescription of ECC cycling for patient rehabilitation requires further assessment.

[Physiological significance and interpretation of plasma lactate concentration and pH in clinical exercise testing]. / Signification physiologique et interprétation clinique de la lactatémie et du pH au cours de l'EFX incrémentale.

According to a widely accepted model, based on the theory of the anaerobic threshold (AT), the increase in plasma lactate concentration which develops after the first ventilatory threshold (VT1, considered as an AT) is due to compensation for insufficient aerobic metabolism by anaerobic glycolysis, with accumulation of lactic acid resulting in a decrease in pH. Bicarbonate is the main buffer of protons (>90%) producing non-metabolic CO2 in muscle and thus increasing the CO2 flux to the lungs. This phenomenon, along with the low pH, triggers hyperventilation. Because of this model, great importance has been placed on plasma lactate and pH. We argue that this importance is excessive and these variables should be used with caution in the interpretation of clinical exercise testing, because the model based on AT is not valid: there is no aerobic failure above VT1 and, thus, there is no evidence of an AT; the increase in plasma lactate does not reflect anaerobiosis but is the marker of the increase in the error signal needed for the stimulation of mitochondrial respiration; bicarbonate is not the main buffer during exercise (these are proteins and phosphocreatine breakdown in the muscle; hemoglobin in the blood); non-metabolic CO2 is not produced in the muscle but in the lung because of the low pH and hyperventilation (the control of which remains unknown); and the flux of CO2 to the lung does not increase at faster rate after than before VT1.

[Cardiopulmonary exercise testing and unexpected dyspnea]. / Exploration fonctionnelle à l'exercice (EFX) et dyspnée inattendue.

Cardiopulmonary exercise testing (CPET) is the examination of choice to understand mechanisms responsible for dyspnea in patients without significant medical history. The three observations illustrate the major interest of the CPET in this frequent situation in clinical practice. A 68-year-old man who has severe dyspnea in her leisure time hiking in the mountains, a 25-year cyclist presenting disabling dyspnea follow competitors racing neo-professional cyclists, and a 37-year woman who developed a persistent dyspnea, 6 months after delivery. In these three situations, CPET determined the disorder responsible for the symptoms without increasing the diagnostic tests.

[From interpretation of cardiopulmonary exercise testing to medical decision]. / De l'interprétation de l'exploration fonctionnelle d'exercice (EFX) à la décision médicale.

Exercise is a situation that involves cardiovascular, respiratory and metabolic responses simultaneously. Thus, interpretating the results of the cardiopulmonary exercise testing (CPET) requires an integrated understanding of the pathophysiology of exercise intolerance which may result from lung, heart, pulmonary or peripheral circulation, muscles disturbances, or a combination of these functional disorders. In this paper, we offer a systematic method to assist clinicians in developing a pathophysiological reasoning from the functional competency of each component measured during incremental exercise. We propose to go through four steps: descriptive analysis, prioritization of the functional disorders, mechanistic proposals and diagnostic and/or therapeutic suggestions. The descriptive analysis step should answer seven key physiological questions, the prioritization step is based on the magnitude of the functional disorders and their relevance to the primary symptoms causing exercise intolerance, the mechanistic proposals step aims at suggesting different mechanisms and etiologies compatible with the scale of observed functional abnormalities, which will finally be tested by exploring specific diagnostic or therapeutic suggestions.

[Widening of the alveolar-arterial oxygen gradient during incremental exercise]. / Le parcours de l'oxygène au cours de l'exercice incrémental.

Excessive widening of the alveolar-arterial gradient for oxygen, with respect to the subject's age and oxygen uptake, is the most sensitive signal of a disturbance in pulmonary gas exchange, whether it is due to ventilation, circulation or diffusion. During incremental exercise, simultaneous measurements of metabolic power, ventilation and dead space may suggest a possible aetiological diagnosis without confirming the causal nature of the impairment. The magnitude and the kinetic of P(Ai-a)O(2) can suggest explanations of the mechanisms involved and lead to complementary functional or morphological investigations (CT, ultrasound, DLCO, etc.) in relation to the clinical setting. The purpose of this text is to review the physiology of the pathway of oxygen from the alveolar air to pulmonary capillary blood during incremental exercise, with emphasis on the predominant role of the dimensions of diffusion and pulmonary capillary capacity in relation to oxygen uptake and the functional responses (alveolar ventilation and cardiac output).

[Pulmonary and alveolar ventilation, gas exchanges and arterial blood gases during ramp exercise]. / Ventilation pulmonaire et alvéolaire, échanges gazeux et gaz du sang à l'exercice en rampe.

In response to ramp exercise, changes in ventilation, gas exchange and arterial blood gases, which are closely interrelated, reflect the two roles of ventilation: 1) providing O(2) and eliminating metabolic CO(2) (from rest to maximal exercise); and 2) contributing to acid-base balance by eliminating non metabolic CO(2) from the alkaline reserve (from the first ventilatory threshold [VT(1)] to maximal exercise). Hyperpnea before VT(1) increases gas exchanges as needed for aerobic metabolism without large changes in ventilatory equivalent of O(2) and CO(2) (VE/V(O2) or VE/V(CO2)), in P(O2) and P(CO2) in alveoli or arterial blood (except for a small widening of alveolo-arterial P(O2) gradient), and in bicarbonate concentration. In contrast, above VT(1), CO(2) is washed-out from the alkaline reserve due to the combined effect of the fall in PA(CO2) (because of hyperventilation) and in pH, and this helps maintaining acid-base balance. Pa(CO2) and bicarbonate concentration decrease while PA(O2) and VE/V(O2) increase, and V(CO2), which follows VE, becomes higher than V(O2). In healthy young subjects, but very seldom in patients, the end of exercise can occur after a second ventilatory threshold (VT(2)), which is the zone where the increase in V(CO2) fails to follow that in VE in spite of hyperventilation and acidosis because of the progressive depletion of the alkaline reserve.

[Prevention of COPD exacerbation: a fundamental challenge]. / Prévention des exacerbations de BPCO : un enjeu fondamental.

INTRODUCTION: Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are a cause of suffering for patients and a burden for healthcare systems and society. Their prevention represents individual and collective challenge. The present article is based on the work of a group of experts who met on 5th and 6th May 2011 and seeks to highlight the importance of AECOPD. STATE OF THE ART: In the absence of easily quantifiable criteria, the definition of AECOPD varies in the literature, making identification difficult and affecting interpretation of study results. Exacerbations increase mortality and risk of cardiovascular disease. They also increase the risk of developing further exacerbations, accelerate the decline in lung function and contribute to reduction in muscle mass. By limiting physical activity and affecting mental state (anxiety, depression), AECOPD are disabling and impair quality of life. They increase work absenteeism and are responsible for about 60% of the global cost of COPD. PERSPECTIVES: Earlier identification with simple criteria, possibly associated to patient phenotyping, could be helpful in preventing hospitalization. CONCLUSIONS: Given their immediate and delayed impact, AECOPD should not be trivialized or neglected. Their prevention is a fundamental issue.

Effects of training at mild exercise intensities on quadriceps muscle energy metabolism in patients with chronic obstructive pulmonary disease.

AIM: To study the effects of physical training at mild intensities on skeletal muscle energy metabolism in eight patients with chronic obstructive pulmonary disease (COPD) and eight paired healthy sedentary subjects. METHODS: Energy metabolism of patients and controls vastus lateralis muscle was studied before and after 3 months of cycling training at mild exercises intensities. RESULTS: The total amount of work accomplished was about 4059 ± 336 kJ in patients with COPD and 7531 ± 1693 kJ in control subjects. This work corresponds to a mechanical power set at 65.2 ± 7.5% of the maximum power for patients with COPD and 52 ± 3.3% of the maximum power in control group. Despite this low level of exercise intensities, we observed an improvement in mitochondrial oxidative phosphorylation through the creatine kinase system revealed by the increased apparent K(m) for ADP (from 105.5 ± 16.1 to 176.9 ± 26.5 µm, P < 0.05 in the COPD group and from 126.9 ± 16.8 to 177.7 ± 17.0, P > 0.05 in the control group). Meanwhile, maximal mechanical and metabolic power increased significantly from 83.1 ± 7.1 to 91.3 ± 7.4 Watts (P < 0.05) and from 16 ± 0.8 to 18.7 ± 0.98 mL O(2) kg(-1) min(-1) (P < 0.05) only in the COPD group. CONCLUSION: This study shows that physical training at mild intensity is able to induce comparable changes in skeletal muscles oxidative energy metabolism in patients with COPD and sedentary healthy subjects, but different changes of maximal mechanical and metabolic power.

Beyond corticosteroids: future prospects in the management of inflammation in COPD.

Inflammation plays a central role in the pathophysiology of chronic obstructive pulmonary disease (COPD). Exposure to cigarette smoke induces the recruitment of inflammatory cells in the airways and stimulates innate and adaptive immune mechanisms. Airway inflammation is involved in increased bronchial wall thickness, increased bronchial smooth muscle tone, mucus hypersecretion and loss of parenchymal elastic structures. Oxidative stress impairs tissue integrity, accelerates lung ageing and reduces the efficacy of corticosteroids by decreasing levels of histone deacetylase-2. Protease-antiprotease imbalance impairs tissues and is involved in inflammatory processes. Inflammation is also present in the pulmonary artery wall and at the systemic level in COPD patients, and may be involved in COPD-associated comorbidities. Proximal airways inflammation contributes to symptoms of chronic bronchitis while distal and parenchymal inflammation relates to airflow obstruction, emphysema and hyperinflation. Basal levels of airways and systemic inflammation are increased in frequent exacerbators. Inhaled corticosteroids are much less effective in COPD than in asthma, which relates to the intrinsically poor reversibility of COPD-related airflow obstruction and to molecular mechanisms of resistance relating to oxidative stress. Ongoing research aims at developing new drugs targeting more intimately COPD-specific mechanisms of inflammation, hypersecretion and tissue destruction and repair. Among new anti-inflammatory agents, phosphodiesterase-4 inhibitors have been the first to emerge.