title: Inflammation in cystic fibrosis lung disease: Pathogenesis and therapy.
abstract: Lung disease is the major cause of morbidity and mortality in patients with cystic fibrosis (CF). Although CF lung disease is primarily an infectious disorder, the associated inflammation is both intense and ineffective at clearing pathogens. Persistent high-intensity inflammation leads to permanent structural damage of the CF airways and impaired lung function that eventually results in respiratory failure and death. Several defective inflammatory responses have been linked to cystic fibrosis transmembrane conductance regulator (CFTR) deficiency including innate and acquired immunity dysregulation, cell membrane lipid abnormalities, various transcription factor signaling defects, as well as altered kinase and toll-like receptor responses. The inflammation of the CF lung is dominated by neutrophils that release oxidants and proteases, particularly elastase. Neutrophil elastase in the CF airway secretions precedes the appearance of bronchiectasis, and correlates with lung function deterioration and respiratory exacerbations. Anti-inflammatory therapies are therefore of particular interest for CF lung disease but must be carefully studied to avoid suppressing critical elements of the inflammatory response and thus worsening infection. This review examines the role of inflammation in the pathogenesis of CF lung disease, summarizes the results of past clinical trials and explores promising new anti-inflammatory options.
authors: Pulmonary Division, University of Sherbrooke, 3001, 12th Avenue North, Sherbrooke, QC, Canada. Electronic address: Andre.Cantin@USherbrooke.ca.
authors: André M
authors: AM
authors: Cantin
authors: CF Center, Children's Hospital of the University of Tübingen, Tübingen, Germany.
authors: Dominik
authors: D
authors: Hartl
authors: Rainbow Babies and Children's Hospital, Case Western Reserve University School of Medicine, Cleveland, OH, USA.
authors: Michael W
authors: MW
authors: Konstan
authors: Rainbow Babies and Children's Hospital, Case Western Reserve University School of Medicine, Cleveland, OH, USA.
authors: James F
authors: JF
authors: Chmiel
mesh_terms: D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D003550:Cystic Fibrosis / Q000150:complications* / Q000473:pathology / Q000628:therapy; D006801:Humans; D011014:Pneumonia / Q000209:etiology* / Q000628:therapy*
chemical_list: D000900:Anti-Bacterial Agents; D000893:Anti-Inflammatory Agents
keywords: Anti-inflammatory therapies; Bronchiectasis; Cystic fibrosis; Lung inflammation; Mucosal immunity; Neutrophils