Immunopathophysiologic mechanisms of cystic fibrosis lung disease

Abstract

Cystic fibrosis is a life-threatening autosomal recessive disorder with a highly variable clinical presentation. The pathophysiology is related to the mutant transmembrane conductance regulator (CFTR), a chloride channel that is encoded by the CF single gene located on chromosome 7. The variability of the clinical presentations, even among patients carrying the same mutation, is extensive enough to justify the hypothesis that other pathophysiologic mechanisms participate in the evolution of the disease phenotype. Presented here are recent lines of research on the contributing factors to respiratory tract morbidity, as well as the innate defense mechanisms in the CF lungs, the cytokines and chemokines that influence the inflammatory processes, the antioxidative system, and the composition of the airways surface fluid. These studies concluded that the clinical presentation is determined by pathology of the CFTR as well as by other mechanisms, some of which are related to the CFTR functions and others to the products of modifier genes as well as the influence of the environment.