Paradoxical role of proteinase inhibitors in cystic fibrosis

While free proteinases destroy lung tissue in cystic fibrosis, logic predicts that proteinase inhibitors should offer protection. However, for some time doctors have observed that a mild genetic deficiency in an inhibitor is actually associated with a better, rather than worse, outcome. In January's issue of Thorax, Dr Mahadeva and colleagues from the University of Cambridge support this observation with their new findings (Thorax 2001 56:53-58).

They screened 157 patients with cystic fibrosis and identified 10 with a plasma deficiency of α₁-antichymotrypsin (plasma concentration <0.2 g/l). In a multivariate analysis these individuals had significantly less severe lung disease than those who had normal or raised levels of α₁-antichymotrypsin. They concluded, paradoxical though it may be, that a deficiency of the inhibitor α₁-antichymotrypsin is associated with less severe pulmonary disease in patients with cystic fibrosis.