ABSTRACT

I. Introduction Although cystic fibrosis (CF) impacts nearly every organ system, lung disease accounts for most of the morbidity and mortality (1). Epithelial cells, particularly those of exocrine glands, are the principal sites of expression of the cystic fibrosis transmembrane conductance regulator (CFTR) and therefore are most affected by its dysfunction. In the airway, abnormal CFTR leads to a vicious cycle of airway obstruction, chronic bacterial infection, and vigorous inflammation (2). The dysregulated inflammatory response eventually becomes more harmful than protective and actually encourages persistence of pathogens, promotes obstruction of the airway lumen, and causes destruction of airway wall architecture resulting in bronchiectasis (Fig. 1). Although the association between the basic defect in CFTR and the development and progression of the lung disease is not fully elucidated, understanding the pathophysiology of the process within the airways is vital to understanding current and emerging therapies.