Académie royale de Médecine de Belgique

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Résumé de Charles Pilette (Séance du 3.09.2011)

 

ASTHMA : FROM OSLER’S NEVROSIS TO IMMUNOBIOLOGICAL TARGETS

par Ch. PILETTE (U.C.L.), invité.      

Asthma is one of the most common chronic disease, affecting up to 10% of the population in western countries. While the first written descriptions of this pathology come from Egyptians (3,500 BC) and Chinese, the first era of asthma pathophysiology described in Europe by medical pioneers (from Hippocrate to Osler) involved a disequilibrium between the body “humeurs”, causing bronchoconstriction. Asthma became a psychosomatic disorder, although the environment was recognized to play a critical role. The second era arose from immunological findings (~1970’s), first the identification of immunoglobulin E (IgE) as mediating “atopic” hypersensitivity to environmental antigens and second of eosinophilic inflammation of the asthmatic airways.  A T helper 2-type immune response was further discovered as driving IgE synthesis, mucus overproduction and hyperresponsiveness of the bronchial smooth muscle to non-specific stimuli such as cholinergic agonists. Inhaled corticosteroids become at this stage the mainstay of asthma treatment, on the top of b2-adrenergic agonists as rescue bronchodilators. The current third era is progressively highlighting cellular and molecular mechanisms integrating interactions between the environment and (>50) susceptibility genes operating during inception and exacerbations of asthma, in particular a synergy between allergen/IgE and viral pathways which involve cross-talks at the level of the airway epithelium and antigen-presenting cells. Concomitantly research leads to the development of several biological therapies targeting immune pathways, anti-IgE monoclonal antibody being the first of these to be approved as effective add-on treatment of severe allergic asthma.

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