Bacterial colonization of the respiratory tract in patients with cystic fibrosis

Cystic fibrosis (CF) is the most common single gene disorder in The Netherlands and occurs approximately once in every 3600 children born alive. The heterozygous carrier frequency has been estimated to be approximately 1 :30. The defective gene was identified in 1989 and appeared to be located on chromosome. It codes for the cystic fibrosis transmembrane conductance regulator (CFTR), which acts as a transmembrane chloride channel. The most frequent mutation of this gene is the deletion of phenylalanine at position 508 ("F508). Almost 60% of the known CF patients in The Netherlands are homozygous for the "F508 mutation. More than 700 additional CFTR mutations related to CF have been identified as oflate May 1997 by the CF Genetic Analysis Consortium. The gene defect results in significant morbidity and affects mainly the respiratory tract and the pancreas. The CF lung presents an unique environment to microbial pathogens. The combination oflow or absent chloride secretion and an increased sodium absorption results in relative dehydration of the ainvays. Consequently, the disease is characterized by the production of abnonnally viscid secretions in epithelial tissues. Mucociliary clearance of bacteria from the lungs is impaired because of the viscid, dehydrated nature of the airway epithelia. Chronic ainvay inflammation leads to excessive secretion of purulent mucus and to obstmction of the airway which in turn causes bronchiectasis, pulmonary hypertension with cor pulmonale, haemoptysis, pneumothorax and, finally, respiratory failure. The exacerbation of puhnonary infections is the major cause of morbidity and mortality in patients with CF. Aggressive early treatment of respiratory infections is a critical success factor in the treatment ofCF patients. Thirty years ago, most patients died in infancy. Nowadays, patients born in the 1990's are likely to live up to a median age of 40 years.

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