Acquired Cystic Fibrosis Transmembrane Conductance Regulator Dysfunction in Chronic Bronchitis and Other Diseases of Mucus Clearance

Abstract

Chronic obstructive pulmonary disease (COPD) is a major public health problem. No therapies alter the natural history of the disease. Chronic bronchitis is perhaps the most clinically troublesome phenotype. Emerging data strongly suggest that cigarette smoke and its components can lead to acquired cystic fibrosis transmembrane conductance regulator (CFTR) dysfunction. Findings in vitro, in animal models, and in smokers with and without COPD also show acquired CFTR dysfunction, which is associated with chronic bronchitis. This abnormality is also present in extrapulmonary organs, suggesting that CFTR dysfunction may contribute to smoking-related systemic diseases.

Keywords: Chronic bronchitis; Chronic obstructive pulmonary disease; Cystic fibrosis transmembrane conductance regulator; Mucociliary clearance.

Figure 1. Acquired CFTR Dysfunction in smokers and COPD patients

A: Reduced CFTR activity in smokers with and without COPD as measured by nasal potential difference (change Cl⁻-free plus isoproterenol). See reference. B: Reduced CFTR activity in smokers with and without COPD measured by lower airway potential difference (change Cl⁻-free plus isoproterenol). See reference. C: Elevated sweat chloride, a measure of CFTR activity, in smokers and COPD patients. See reference. D: Normalized CFTR activity estimated using sweat chloride values and corrected for the non-linear relationship between sweat chloride and CFTR function. See reference. E: Reduced CFTR-dependent, beta-adrenergic stimulated sweat secretion measured by evaporative water loss (EWL) in patients with COPD. See reference. *P<0.05, **P<0.01, ***P<0.001, ****P<0.0001.