Keywords:
Cystic Fibrosis, lung disease, early detection
Abstract:
Cystic fibrosis (CF) lung disease is characterized by neutrophilic inflammation and progressive structural lung disease that commences soon after birth. Neither the genesis of the early inflammatory response nor the mechanistic links between deficient cystic fibrosis transmembrane regulator function, inflammation, and aberrant responses to pathogens is understood. A range of pathobiological factors has been proposed that includes a primary role for dysregulated early innate immune responses to bacterial and viral pathogens and alternative causative pathways that are initially independent of infection, including airway obstruction with excess and abnormal mucin that can, for example, stimulate airway neutrophils and a vicious cycle of neutrophilic inflammation or trigger inflammatory pathways via local hypoxia. Others have proposed intrinsic abnormalities of neutrophils and macrophages that contribute to the early and exaggerated neutrophilic response that has been consistently observed in young children. The critical issues that need to be resolved are the factors that initiate the early, progressive, neutrophil dominant airway inflammation and the mechanisms that underpin the heterogeneity of structural lung disease both within and between individuals.