Praxis Pharmaceutical
Cystic Fibrosis
Cystic fibrosis (CF) is the most common potentially fatal hereditary disease in Caucasians (1). CF is produced by the mutation of a single gene located on the long arm of chromosome 7, and which encodes for CFTR protein (cystic fibrosis transmembrane conductance regulator). This mutation affects the epithelial transport of water and ions, mainly in the cells of the respiratory, gastrointestinal, hepatobiliary and reproductive apparatuses. Within the airways, the decrease in chloride and water secretion leads to a viscous secretion and to alterations in mucociliary clearance.
A characteristic of patients with CF is chronic respiratory infection that may develop at a very early age (2), and which is responsible for most of the morbidity and mortality associated with the disease.Pseudomonas aeruginosa is the pathogen most commonly isolated from sputum and bronchoalveolar lavage (BAL) samples in CF patients of all ages. The lungs are colonised at about 5-10 years of age, and are unable to eliminate the bacterium.
In the early stages, P. aeruginosa colonisation is associated with a minor reduction in lung function (3). The bacterial density must increase, with chronification of the process, in order for respiratory function to show clear deterioration (4). It has been shown that change from the non-mucoid to the mucoid morphotype of the bacterium is accompanied by important changes in the respiratory parameters (5), and is associated with increased patient mortality. The persistence of P. aeruginosa, with high bacterial counts within the respiratory tract, is associated with increased respiratory impairment and a larger number of exacerbations.
In most CF patients colonised by mucoid P. aeruginosa, the infection induces faster impairment of lung function than in non-colonised patients. Lung function worsens over time, and chronic lung colonisation by P. aeruginosa accelerates pulmonary dysfunction (6) - ultimately leading to the death of the patient.