Analisi genetica della broncopneumopatia cronica ostruttiva e nei casi di bronchiectasie disseminate

Chronic obstructive pulmonary diseases (COPD) and disseminated bronchiectases are classified among obstructive pulmonary diseases. Environmental factors are the major cause of COPD. Nevertheless, individual susceptibility to cigarette smoke and family aggregation of cases suggest that constitutional factors may also play a role in pathogenesis. Among these, the only definitely assessed risk factor is severe alpha1-antitrypsin deficiency, leading to juvanile liver disease and emphysema. Roughly 50% of disseminated bronchiectases are related to genetic disorders (Cystic Fibrosis, alpha1-antitrypsin deficiency, immunodeficiencies, primary ciliary diskinesia), suggesting that a non-identified constitutional factor may play a role also in apparently primary cases. Most studies on candidate genes were performed according to the case-control strategy. An obvious limitation is given by the fact that only mutation in known genes can be assessed for. A further problem is current poor knowledge of pathogenesis mechanisms. Anyway, linkage analysis is severely impaired by the impossibility of finding pedigrees of adequate size, due to the unequivocal definition of phenotype. Due to these reasons, studies in COPD analyzing proteases inhibitors, antioxidants, Cftr and cytokines genes have so far reported discordant data, with the mentioned exception of alpha1-antitrypsin deficiency. Since phenotype is better defined, studies on (apparently) primary disseminated bronchiectases showed that CFTR gene mutations are a sound risk factor. Much still has to be clarified on the genetically determined components of these multifactorial diseases and also on its relevance among other environmental risk factors.