Emphysème pulmonaire : évolution des concepts

Abstract

La revolution dans les concepts physiopathologiques de l' emphyseme est survenue il y a pres de 30 ans avec la description, par des chercheurs suedois, du deficit en <alpha>1-anti-trypsine. Ces resultats ont abouti a la theorie du desequilibre de la balance protease-antiprotease, qui demeure encore aujourd' hui la cle de voute de la physiopathologie de cette maladie. Cependant, il n' y pas actuellement d' argument convaincant en faveur d' un deficit local en antiproteases dans l' emphyseme du fumeur non deficitaire en <alpha>1-antitrypsine et le role d' une inactivation de l' <alpha>1-antitrypsine par les oxydants contenus dans la fumee de tabac reste non demontre. Si l' on excepte les traitements medicaux pouvant etre proposes a toutes les formes de bronchopneumopathie chronique obstructive a l' etat stable, la prise en charge medicale propre a l' emphyseme pulmonaire se limite aux perfusions d' <alpha>-1-antitrypsine chez les patients deficitaires en cette proteine. La strategie chirurgicale repose quant a elle sur deux types d' intervention: la chirurgie de resection pulmonaire et la transplantation pulmonaire. Les progres des connaissances sur le plan physiopathologique et la progression de l' arsenal therapeutique ne doivent pas occulter le role causal fondamental du tabagisme dans la genese de l' emphyseme.

Pathophysiologic and therapeutic concepts concerning lung emphysema are evolving. The old pathophysiologic concept is based upon the hypothesis that emphysema is the consequence of an imbalance between the proteases released by neutrophils and the anti-proteases shield in the alveolar space that allows the destruction of elastin fibers. Recent data suggest (1) that proteases secreted by alveolar macrophages might be more relevant to the pathogenesis of the disease than that released by neutrophils (2) that collagenolytic enzymes might participate to the destruction process within the lung as well as elastolytic protease, (3) that the repair of elastin and collagen fibersoccurs in the lung simultaneously to their destruction, at least in animal models of emphysema, and (4) that repair is possible in a rat model of elastase-induced emphysema using all trans-retinoic acid. Therapeutic options in human emphysema are also evolving. Increasing the antiprotease alveolar shield through the intravenous or inhaled administration of alpha-1-antitrypsin in selected patients with genetical alpha-1-antitrypsin deficiency is used worldwide in selected patients despite the lack of scientific evidence of efficacy. Surgical treatments have been developed in the past 10 years and are currently under investigation. Lung transplantation is used in patients with severe airway obstruction on lung function tests and functionally disabled. Its beneficial effect in terms of survival is not prove but quality of life is improved with the technique. Lung volume reduction surgery improves dyspnea, lung function and gas exchange in most patients, but long term beneficial effects, selection criteria of the patients are currently unknown.