ALPHA(1)-PROTEINASE INHIBITOR, ELASTASE ACTIVITY, AND LUNG-DISEASE SEVERITY IN CYSTIC-FIBROSIS

The potential role of neutrophil elastase in exacerbating pulmonary in fection and tissue damage in cystic fibrosis (CF) has led to proposals for treatment of lung disease in CF with the elastase inhibitor, alph a(1)-proteinase inhibitor (alpha(1)PI). Reports that alpha(1)PI is ina ctivated in the CF lung suggest that the effectiveness of alpha(1)PI t herapy depends on the quantity of elastase present and the extent of a lpha(1)PI inactivation, both of which are expected to vary with diseas e severity. In this study we assessed the elastase-alpha(1)PI profile in sputum and plasma from CF patients with various degrees of pulmonar y involvement. Levels of active elastase in sputum samples increased w ith severity of pulmonary disease (F ratio = 5.63, p < 0.01), as did s putum levels of alpha(1)PI (F ratio = 4.88, p < 0.01). A positive corr elation was observed between sputum levels of active elastase and alph a(1)PI (r = 0.68, p < 0.005). Plasma alpha(1)PI levels were also eleva ted in CF patients compared with control subjects (p < 0.005), indicat ing a compensatory increase in plasma and sputum levels of alpha(1)PI in response to increased elastase load. Molar levels of total immunoge nic neutrophil elastase were, on average, 12 times higher than alpha(1 )PI in CF sputum. These results suggest that the major contributor to the elevated levels of active elastase observed in the CF lung is an i ncrease in elastase release rather than inactivation of alpha(1)PI.