Monitoring Cystic Fibrosis Lung Disease

Abstract

Cystic Fibrosis (CF) is a severe, life-shortening genetic disease with a wide spectrum of clinical manifestations, affecting 70,000 patients in the EU and USA. The most prevalent clinical manifestation is structural lung disease. Structural lung disease is the main cause of morbidity in CF and accounts for 85% of the deaths in CF patients (1). Important for the pathogenesis of structural lung disease are genetic mutations on chromosome 7 encoding for the CF transmembrane conductance regulator (CFTR) (2-4). The most prevalent mutation is the dF508 deletion, but nowadays over 1926 mutations of the CFTR gene have been described not all resulting in CF and accounting for different disease severities (5). The wild type CFTR protein resides in the membrane of epithelial cells, and regulates the airway surface liquid by ion flux through the chloride channels at the epithelial surface (2,4). Due to CFTR gene mutations a dysfunctional CFTR protein is produced. Dysfunctional CFTR results in reduced or absent chloride secretion and increased sodium absorption, leading to an increase in mucus viscosity and impaired mucociliary clearance (6). As a result there is poor clearance of inhaled microorganisms. Chronic endobronchial infection by these microorganisms provokes an exaggerated inflammatory response leading eventually to structural lung damage (7,8). Despite extensive research many questions related to the pathophysiology of CF lung disease remain unanswered (7). It is well recognized that genetic and environmental modifiers can alter outcome. Importantly, prognosis is nowadays still primarily determined by the severity of CF lung disease (7). Therefore, in order to improve prognosis, CF lung disease should be prevented.