SPUTUM PEROXIDASE-ACTIVITY CORRELATES WITH THE SEVERITY OF LUNG-DISEASE IN CYSTIC-FIBROSIS

Patients with cystic fibrosis (CF) of the same age differ significantl y in their degree of pulmonary disease. Based on preliminary observati ons,(1) we postulated that the activity of myeloperoxidase would be si gnificantly increased in patients with greater structural lung damage than in those with less lung damage. Acid extracts of weighed sputum s amples were assayed for lactoferrin concentrations by ELISA. Activitie s of peroxidase, cathepsin G, and elastase (with and without proteinas e 3) were determined by kinetic analysis using chromogenic substrates. The patients were divided into quartiles based on their Brasfield che st-radiograph score. Patients in the first quartile (least amount of s tructural lung abnormality) were compared to those in the fourth quart ile. The concentration of lactoferrin, a specific (secondary) granule protein of neutrophils, did not differ between the two patient groups. However, the activities of the neutrophil primary granule proteins, p eroxidase, elastase, and elastase plus proteinase 3, were significantl y elevated in the group with the most structural lung abnormality. Spu tum albumin concentration was used to estimate leakages of plasma prot eins into the airways. Peroxidase activity, but not the activity of ca thepsin G, of elastase, or of elastase plus proteinase 3, correlated s ignificantly with albumin/g sputum in both quartile groups. To confirm the association of sputum peroxidase activity with differences in lun g structure and to test its correlation with lung function, spirometry was performed in a second group of patients during the week prior to the time of sputum sampling. In this second group, increased sputum pe roxidase activity was associated with worse Brasfield scores and with decreased percent-predicted forced expiratory volume in 1 sec. Lactofe rrin concentration again did not differ between the groups. Bacterial factors also did not differ. The results indicate that the degree of l ung damage in patients with CF was more closely related to sputum pero xidase activity than to age, gender, CFTR genotype, or sputum bacteria l parameters. Further study is required to determine whether or not pe roxidase activity in the airway causes this lung damage. Pediatr Pulmo nol, 1995; 19:1-9. (C) 1995 Wiley-Liss, Inc.