No abstract

We evaluated patients with cystic fibrosis (CF) and moderate obstructive lung disease in pulmonary exacerbation in a double-blind placebo-controlled trial to determine the contribution of antibiotic-mediated reduction in sputum bacterial density to clinical improvement. For the first 4 days of study, all patients received bronchodilating aerosols and chest physiotherapy but no antibiotics. During this time, the patients showed significant improvement in mean FVC, FEV1, and maximal midexpiratory flow rate (FEF25-75). In 12 of 13 trials, the patients showed no significant increases in the density of Pseudomonas aeruginosa during these first 4 days. In these 12 trials, the patients were stratified by their initial FVC and randomized to receive either parenteral tobramycin and ticarcillin (n = 7) or placebo (n = 5), in addition to continued aerosol and chest physiotherapy. In the remaining trial, the patient had a significant rise in the density of P. aeruginosa and was assigned to the antibiotic group. During the next 14 days of therapy, the antibiotic group showed significantly (p less than 0.01) greater reductions in log10 colony-forming units (cfu) of P. aeruginosa per gram of sputum and greater increases in FVC, FEV1, and FEF25-75 than did the placebo group. The degree of decrease in log10 cfu P. aeruginosa/g sputum correlated significantly (p less than 0.001) with the degree of improvement in FVC, FEV1, and FEF25-75.(ABSTRACT TRUNCATED AT 250 WORDS)

The antibacterial activity of phagocytic cells and opsonins in peritoneal dialysis effluents from 21 patients undergoing chronic peritoneal dialysis (CPD) was studied. Effluents contained an average of 12 x 10(6) cells per liter that were predominantly macrophages. Macrophages phagocytized and killed opsonized Staphylococcus epidermidis, Staphylococcus aureus, and Escherichia coli as efficiently as did polymorphonuclear neutrophils (PMNs) from healthy donors. Macrophage chemiluminescence was one-third of that observed with donor PMNs. In the absence of opsonins, macrophages efficiently phagocytized and killed S. aureus by binding S. aureus cell wall protein A to macrophage surface IgG. Nine (43%) of 21 effluents failed to opsonize S. epidermidis, and none opsonized E. coli. When present, titers of S. epidermidis opsonins were 50- to 100-fold lower than that of normal serum. IgG and C3 concentrations in effluent reflected its opsonic capacity. Macrophages from patients undergoing CPD thus have intact phagocytic and bactericidal functions. However, the low level of opsonic molecules and inadequate numbers of macrophages in the peritoneal cavity may predispose patients undergoing CPD to peritonitis.

No abstract

Patients with cystic fibrosis (CF) of the same age differ significantly in their degree of pulmonary disease. Based on preliminary observations, we postulated that the activity of myeloperoxidase would be significantly increased in patients with greater structural lung damage than in those with less lung damage. Acid extracts of weighed sputum samples were assayed for lactoferrin concentrations by ELISA. Activities of peroxidase, cathespsin G, and elastase (with and without proteinase 3) were determined by kinetic analysis using chromogenic substrates. The patients were divided into quartiles based on their Brasfield chest-radiograph score. Patients in the first quartile (least amount of structural lung abnormality) were compared to those in the fourth quartile. 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, peroxidase, elastase, and elastase plus proteinase 3, were significantly elevated in the group with the most structural lung abnormality. Sputum albumin concentration was used to estimate leakages of plasma proteins into the airways. Peroxidase activity, but not the activity of cathepsin G, of elastase, or of elastase plus proteinase 3, correlated significantly with albumin/g sputum in both quartile groups. To confirm the association of sputum peroxidase activity with differences in lung 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 peroxidase activity was associated with worse Brasfield scores and with decreased percent-predicted forced expiratory volume in 1 sec.(ABSTRACT TRUNCATED AT 250 WORDS)