Association of alpha(1)-antichymotrypsin deficiency with milder lung disease in patients with cystic fibrosis.

BACKGROUND Cystic fibrosis (CF) is characterised by an excess of free proteinases that destroy lung tissue. Despite this, previous studies have shown that patients with CF with a mild deficiency variant of the proteinase inhibitor α 1 -antitrypsin have less, rather than more, severe pulmonary disease. Alpha 1 -antichymotrypsin is another important serine proteinase inhibitor that protects the lung against proteolytic attack, and point mutations in the α 1 -antichymotrypsin gene that result in plasma deficiency are associated with chronic obstructive pulmonary disease. METHODS The effect of α 1 -antichymotrypsin deficiency and the –15 α 1 -antichymotrypsin signal peptide genotype on lung function was assessed in patients with CF. RESULTS One hundred and fifty seven patients with CF were screened and 10 were identified with a plasma deficiency of α 1 -antichymotrypsin (plasma concentration 1 -antichymotrypsin: forced expiratory volume in one second (FEV 1 ) 69.9% predicted versus 53.2% predicted (p=0.04) and chest radiographic score of 7.2 versus 9.7 (p=0.03) for those with and without α 1 -antichymotrypsin deficiency, respectively. The –15 signal peptide genotype did not affect plasma levels, but the –15 Ala/Ala signal peptide genotype was over-represented in individuals with CF compared with healthy blood donor controls. CONCLUSION These data indicate that deficiency of α 1 -antichymotrypsin is associated with less severe pulmonary disease in patients with CF, and support our previous observations that mild genetic deficiency of a proteinase inhibitor is associated with an improved outcome.