Interrelationships between neutrophil elastase, serum alpha, -antitrypsin, lung function and chest radiography in patients with chronic airflow obstruction

Abstract

We assayed protease and elastase activity of lysosomal granules of purified neutrophil suspensions in 58 patients with chronic irreversible airflow obstruction and compared them to 26 healthy control subjects. Denatured hemoglobin and tritiated elastin were used as substrates for protease and elastase assays. Forty-two patients had M antitrypsin phemotype, five had MS, and 11 had Z variant (five were homozygotes and six were heterozygotes). We did not find significant differences in mean lysosomal elastase or protease activity between patients with normal antitrypsin and control subjects; however, a few patients had concentrations of neutrophil elastase that exceeded the range among control subjects. There was no significant correlation between neutrophil protease or elastase activity and age, smoking, degree of airway obstruction, diffusing capacity, lung elastic recoil, or radiologic presence of emphysema in patients with M and MS antitrypsin. In patients with Z variant antitrypsin, protease and elastase concentrations per unit of lysosomal protein were not significantly different from those in control subjects or M patients; however, both elastase and protease content per 108 neurtophils was significantly higher in homozygous and heterozygous Z patients as compared to normalsubjects and M patients, which suggest an increase in the neutrophil content of protease and elastase in patients with Z antitrypsin deficiency. These results suggest that hte concentrations of protease and elastase in neutrophils do not appear to interact as additive risk factors in the pulmonary impairment of most patients with chronic airflow obstruction, but may be of importance as risk factors in patients with Z or MZ phenotype and in a few patients with M phenotype.