Update on Pathogenesis of Cystic Fibrosis Lung Disease
Update on Pathogenesis of Cystic Fibrosis Lung Disease
Purpose of review: It has been an ongoing challenge to translate knowledge pertaining to the molecular basis of cystic fibrosis (CF) into a clear understanding of the development of CF lung disease. Various hypotheses have attempted to explain the apparent breach of innate defenses in CF, although a definitive explanation has been elusive.
Recent findings: Recent data suggest that altered ion transport functions-namely sodium hyperabsorption and reduced chloride secretion-lead to a depletion of airway surface liquid. As a result, the overlying mucus layer may encroach upon cell surfaces and become adherent, thus interfering with cilia-dependent and cough clearance. These static, and ultimately anaerobic, niches provide a favorable environment for the development of bacterial biofilms and persistent infection with Pseudomonas aeruginosa.
Summary: With a better understanding of pathogenic steps leading to CF lung disease, we may now be able to direct the development of therapies that will substantially improve disease outcomes.
A clear understanding of the pathway linking cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations to cystic fibrosis (CF) lung disease has been aggressively sought and widely debated by the CF research community. Despite ongoing controversies, all agree on two points. First, CF lung disease reflects a failure of the innate defense system of the airway region. Second, knowledge of the pathogenetic sequence that leads to failure of innate defense is critical if we are to intervene on behalf of CF patients early in life, prior to the establishment of persistent bacterial infection and irreversible lung damage that ensues. In this review, we will touch on various hypotheses that have been advanced to describe the early pathogenesis of CF lung disease while emphasizing recent developments in the field. The role that altered airway surface liquid (ASL) volume plays in the disruption of airway host defenses will be highlighted.
Purpose of review: It has been an ongoing challenge to translate knowledge pertaining to the molecular basis of cystic fibrosis (CF) into a clear understanding of the development of CF lung disease. Various hypotheses have attempted to explain the apparent breach of innate defenses in CF, although a definitive explanation has been elusive.
Recent findings: Recent data suggest that altered ion transport functions-namely sodium hyperabsorption and reduced chloride secretion-lead to a depletion of airway surface liquid. As a result, the overlying mucus layer may encroach upon cell surfaces and become adherent, thus interfering with cilia-dependent and cough clearance. These static, and ultimately anaerobic, niches provide a favorable environment for the development of bacterial biofilms and persistent infection with Pseudomonas aeruginosa.
Summary: With a better understanding of pathogenic steps leading to CF lung disease, we may now be able to direct the development of therapies that will substantially improve disease outcomes.
A clear understanding of the pathway linking cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations to cystic fibrosis (CF) lung disease has been aggressively sought and widely debated by the CF research community. Despite ongoing controversies, all agree on two points. First, CF lung disease reflects a failure of the innate defense system of the airway region. Second, knowledge of the pathogenetic sequence that leads to failure of innate defense is critical if we are to intervene on behalf of CF patients early in life, prior to the establishment of persistent bacterial infection and irreversible lung damage that ensues. In this review, we will touch on various hypotheses that have been advanced to describe the early pathogenesis of CF lung disease while emphasizing recent developments in the field. The role that altered airway surface liquid (ASL) volume plays in the disruption of airway host defenses will be highlighted.
Source...