Clinical and pathophysiological significance of neutrophil elastase in sputum and the effect of erythromycin in chronic respiratory diseases

Abstract

The concentration and activity of neutrophil elastase (NE) in sputa were measured in 24 patients with chronic respiratory diseases such as diffuse pan-bronchiolitis, bronchiectasis and and chronic bronchitis. The results were compared to the clinico-pathophysiological parameters such as clinical impairment score, concentration of albumin and ciliary transport velocity of the sputum. Furthermore, the relationship between the post-therapeutic change of NE in sputum and clinical effect of erythromycin (EM) was investigated in the same cases. Physico-chemical properties of the sputum, including rheological characteristics, mucus transport velocity, phospholipid composition, concentration of albumin and fucose were also analyzed before and after EM therapy. There was a significant positive correlation between NE in sputum and the clinical impairment score, which suggested that the concentration and activity of NE in sputum reflected the clinical severity in such diseases. The concentration and activity of NE also had significant positive and negative correlation to the concentration of albumin and ciliary transport velocity, respectively. Therefore, it was considered that NE in airway could bring the leakage of albumin from serum and interfere with mucociliary transport. The patients were divided into responders (n = 12) and non-responders (n = 12) after EM therapy based on the change of the clinical impairment score. The clinical effect of EM in chronic respiratory diseases was not associated with its bacteriostatic action, but with the quantitative and qualitative suppression of sputum NE. The decrease of the adhesive properties of the sputum, which was observed in responders after administration of EM, was considered to depend on the reduction of the concentration of albumin in sputum. Concerning the phospholipid composition of sputum, sphingomyelin and phosphatidyl-ethanolamine, which had been suggested to be components of serum and cellular membrane, had a tendency to decrease in responders. The proportion of phosphatidylcholine increased in responders. The improvement of ciliary transport velocity of the sputum, which was noted in responders, was probably due to the results mentioned above. In non-responders, these findings were not observed after EM therapy. EM had no influence on the production, release and activity of NE as a result of in vitro experiments using human peripheral neutrophils. Neutrophil chemotaxis was however suppressed after incubation with EM. These results suggest that the mechanisms of the effect of EM is not direct action on NE but through suppression of neutrophil chemotaxis.