Viral Respiratory Tract Infections in Cystic Fibrosis

Abstract

Cystic Fibrosis (CF) is the most commonly inherited potentially lethal disease amongst Caucasian children and young adults. In Europe, approximately 35,000 children and adults are affected by CF. The prevalence in the US and in Canada is approximately 30,000 and 3,000, respectively. CF is an autosomal recessive disorder and is caused by mutations in the Cystic Fibrosis Transmembrane Conductance Regulator gene (CFTR) (Riordan, Rommens et al. 1989). The main function of CFTR in many tissues is to regulate and participate in the transport of chloride ions across epithelial cell membranes. To date, more than 1,800 mutations have been described in this gene, but the most common mutation worldwide is caused by deletion of phenylalanine at position 508 (Delta F508) of the CFTR on chromosome 7. The dramatic improvement in survival from CF has taken great strides over the past 40 years with the introduction of specialist centre care, optimising nutritional status and preventing pulmonary inflammation. The median survival of children born in the 1990s is estimated to exceed 40 years of age with more than 85% of them achieving adulthood. CF is a multisystem disorder and is characterised by chronic suppurative lung disease and by exocrine pancreatic insufficiency which affects gastrointestinal function and causes restricted growth and maturation. CF also causes obstructive azoospermia and thus male infertility. However, in most individuals with CF the major burden is on the lungs. The absence of CFTR in airway epithelium leads to malfunction of chloride conductance and subsequent airway surface liquid (ASL) volume reduction, mucins are concentrated, the periciliary liquid depleted, and mucous clearance by ciliary and cough dependent mechanisms diminished, which leads to airflow obstruction and eventually bacterial colonisation. Bacteria implicated in the morbidity and mortality of CF include Pseudomonas aeruginosa, Burkholderia cepacia complex, Achromobacter xylosoxidans, Staphylococcus aureus, Haemophilus influenzae, Stenotrophomonas maltophilia and non-tuberculous mycobacteria. However despite the appropriate use of antibiotic therapy, chronic obstructive airway disease continues to develop in patients with CF and is the major cause of morbidity and mortality.