alpha-chymotrypsin and Lung-Diseases--Obstructive

In order to characterize the imbalance between proteinases and proteinase inhibitors in sputum sol phases, we studied 25 patients (mean age, 59 +/- 11 yr) with exacerbated chronic obstructive pulmonary disease (COPD). An aliquot of sputum was used for bacteriologic determinations, and the remainder was centrifuged in order to obtain gel and sol phases. On the basis of the bacteriologic data, patients were divided into colonized patients (14) and noncolonized patients (11). All of the major inhibitors were immunologically detectable in sol phases without a significant difference between colonized and noncolonized patients (alpha 1-proteinase inhibitor [alpha 1-PI], 2.56 microM +/- 0.53 microM and 2.39 microM +/- 0.72 microM; alpha 2-macroglobulin [alpha 2-MG], 0.21 microM +/- 0.07 microM and 0.16 microM +/- 0.05 microM; antileukoprotease (ALP), 1.78 microM +/- 0.57 microM and 1.53 microM +/- 0.6 microM, respectively [mean +/- SE]). With regard to proteinase activities, both free elastase-like and free chymotrypsin-like activities were detectable in the majority of patients (15/25) (0.59 microM +/- 0.15 microM and 0.74 microM +/- 0.15 microM for elastase-like activity [ELA], and 0.010 microM +/- 0.003 microM and 0.017 microM +/- 0.007 microM for chymotrypsin-like activity [CLA], respectively [mean +/- SE]). The inhibitory profile of proteinase activities, performed by means of a panel of inhibitors, allowed us to assign specific activities mainly to neutrophil elastase and cathepsin G (Cat G). Next we looked at the relationships between inhibitors and proteinase activities. We found a significant negative correlation between neutrophil elastase activity and ALP (r = -0.58; p < 0.01). In confirmation of this suggestion, sol phases were divided into samples (15) with detectable ELA (> 0.50 microM) and samples (10) with no detectable ELA (< 0.18 microM). Levels of alpha 1-PI and alpha 2-MG did not differ significantly between the two groups, whereas ALP values were higher in the group with no detectable ELA (3.12 microM +/- 0.69 microM) than in the other group (0.58 microM +/- 0.21 microM; p < 0.001). We conclude that most sputum sol phases from patients with exacerbated COPD have a high burden of free neutrophil elastase and Cat G. Antileukoprotease seems to be the major naturally occurring inhibitor effective in the modulation of proteinase activities in bronchial secretions under these conditions.

Topics: Adult; Aged; alpha-Macroglobulins; Chymotrypsin; Colony Count, Microbial; Endopeptidases; Female; Humans; Leukocyte Count; Leukocyte Elastase; Lung Diseases, Obstructive; Male; Middle Aged; Neutrophils; Pancreatic Elastase; Proteinase Inhibitory Proteins, Secretory; Proteins; Serine Proteinase Inhibitors; Sputum

The chymotrypsin activity of seven batches of Micropolyspora faeni and of five batches of Aspergillus fumigatus culture extracts, prepared for inhalation challenge in horses, was assayed and was found to range between 0.29 and 1.45 units/mg protein and 0.02 and 0.20 units/mg protein respectively. Horses affected with chronic obstructive pulmonary disease (COPD) were challenged with two batches of each antigen which had different chymotrypsin activities and no significant correlations were found between the degree of response to challenge and the chymotrypsin activity of the antigens. Inhalation of two doses of nebulised, purified chymotrypsin over 4 days did not induce signs of respiratory disease in COPD-affected horses. However, repeated chymotrypsin inhalations after an interval of 3 weeks caused an exacerbation of signs of COPD in one horse. These studies suggest that, although repeated inhalation of purified chymotrypsin may induce respiratory hypersensitivity in horses, the chymotrypsin-like enzymes of M. faeni and A. fumigatus do not play a major role in the precipitation of clinical signs of equine COPD.

Topics: Animals; Antigens, Bacterial; Antigens, Fungal; Aspergillus fumigatus; Bronchial Provocation Tests; Chymotrypsin; Dose-Response Relationship, Immunologic; Horse Diseases; Horses; Lung Diseases, Obstructive; Micromonosporaceae

The variability of sputum sol phase proteins was studied in 27 patients with stable chronic obstructive bronchitis. Within individual patients (n 1/2 11), variability over 5 consecutive days was similar for each of 4 proteins studied: average coefficient of variation (CV) for albumin was 39.8% for alpha 1-antitrypsin (alpha 1AT), 32.1%, for alpha 1-antichymotrypsin (alpha 1ACh), 26.6%, and for immunoglobulin A (IgA), 35.1%. The calculation of sputum-to-serum ratios did not affect this variability. Between patients (all patients studied on a single day) the variability of sputum sol phase proteins was greater (CV: albumin 1/2 84.5%, alpha 1AT 1/2 90.1%, alpha 1ACh 1/2 58.3%, and IgA 1/2 71.6%) and was also unaffected by the use of sputum-to-serum concentration ratios. "Standardization" for albumin reduced the average within-patient variability for sputum alpha 1AT (CV from 32.1 to 19.7%) but it had no effect on alpha 1ACh and IgA. However, although between-patient CV for sputum alpha 1AT was also reduced (from 90.1 to 53.4%, 2 p less than 0.01) it significantly increased for alpha 1ACh (from 58.3 to 86.0%, 2 p less than 0.05) and IgA (71.6 to 170.1%, 2 p less than 0.001), suggesting that such standardization may be inappropriate for these proteins.

Topics: Aged; Albumins; alpha 1-Antichymotrypsin; alpha 1-Antitrypsin; Blood Proteins; Bronchitis; Chronic Disease; Chymotrypsin; Colloids; Female; Humans; Immunoglobulin A, Secretory; Lung Diseases, Obstructive; Male; Middle Aged; Proteins; Reference Standards; Sputum; Trypsin Inhibitors

Topics: Chymotrypsin; Humans; Lung Diseases, Obstructive; Methods; Microbial Collagenase; Pancreatic Elastase; Sputum; Trypsin; Ultrasonics

A group of 163 patients with chronic obstructive pulmonary disease, from the pulmonary service of a large urban hospital, were evaluated for their protease inhibitor (Pi) type by starch gel and crossed immunoelectrophoresis, for serum concentrations of alpha1-antitrypsin and alpha1-antichymotrypsin, and for pulmonary function. Of the patients with emphysema, 17.8% were of Pi type Z; 50% of these were less than 45 years of age, compared to 13% of those of Pi type M. Of all patients with chronic obstructive pulmonary disease, 4.9% were of Pi type Z; 4.9% of patients were of Pi type MZ (heterozygotes) compared with 1.9% of the control population. There was an increased incidence of chronic obstructive pulmonary disease in persons of Pi type MZ, but no increase in persons of Pi type MS. Concentrations of both alpha1-antitrypsin and alpha1-antichymotrypsin were increased and were correlated. No patient had a deficiency of alpha1-antichymotrypsin.

Topics: Adult; Aged; alpha 1-Antitrypsin Deficiency; Chymotrypsin; Female; Heterozygote; Humans; Lung Diseases, Obstructive; Male; Middle Aged; Pulmonary Emphysema

Topics: Adult; Aged; Breast Neoplasms; Carcinoma; Cholecystitis; Chymotrypsin; Colorimetry; Duodenal Ulcer; Female; Hepatitis; Humans; Intestinal Diseases; Liver Cirrhosis; Lung Diseases; Lung Diseases, Obstructive; Male; Middle Aged; Neoplasm Metastasis; Pancreatitis; Pregnancy; Respiratory Tract Infections; Trypsin Inhibitors

Topics: Acetylcysteine; Acidosis, Respiratory; Anticoagulants; Bicarbonates; Bronchodilator Agents; Chymotrypsin; Ephedrine; Expectorants; Glucocorticoids; Guaiacol; Humans; Iodine Isotopes; Isoproterenol; Lung Diseases; Lung Diseases, Obstructive; Potassium Iodide; Sodium; Thyroid Gland; Tromethamine; Trypsin