Role of free radicals in the pathogenesis of cystic fibrosis.

In recent years great advances have been made in under-Genetically determined abnormalit standing the underlying genetic defect in cystic fibrosis, mucus secretion and airway electrc but the cause of the severe lung damage and pulmonary bacterial adhesion and impaire fibrosis, which are responsible for most of the deaths, mucociliary clearance remains unclear. The precise link between the cystic fibrosis gene, its biochemical consequences, and the increased susceptibility to pulmonary infection, particu- larly with Pseudomonas aeruginosa, has not been eluci- dated. It has proved to be extremely difficult to determine Bacterial colonisation what constitutes a primary abnormality and what is a secondary consequence of infection. However, irregulari- ties in ion transport leading to inspissation of mucous secretions, along with increased adherence of bacteria to Increased recruitment ofl epithelia and reduced mucociliary clearance, probably all polymorphonuclear f Bror contribute to the recurrent progressive pulmonary infec- leucocytes to the lungs Bro tion characteristic of the disease (fig The mechanism ne responsible for the damage to the lungs and the agents concerned have, however, been largely ignored in the pursuit of a genetic answer to the disease. The final Hy solution must inevitably have a genetic basis but, as this Free radicals, Pne may not be realised until the turn of the century at the proteases/elastases HaE earliest, investigation of the physiological damage may release Ate prove to be more beneficial to those already suffering from the disease. The role of free radicals in several diseases with pul- monary complications including hyperoxic lung injury in Pulmonary fibrosis and premature infants,' adult respiratory distress syndrome,2 bronchiectasis asthma,3 and the effect of environmental pollutants4 has recently attracted much attention. In all these cases it has been suggested that oxygen free radicals, produced in various ways, are implicated in the damage to the pulmon-Hypoxia and ary epithelium (table 1). Evidence is now accumulating pulmonary hypertension on August 2,