No abstract

Background-Changes in T lymphocyte subsets have been observed in various forms of pulmonary disease. However, bronchoalveolar lymphocyte subsets have not been well characterised for healthy individuals diVering in age. A study was undertaken to investigate the bronchoalveolar lavage (BAL) and peripheral blood lymphocyte subsets in clinically normal volunteers of two diVerent age groups (19-36 and 64-83 years). Methods-Bronchoalveolar lavage was performed on all individuals in both age groups and peripheral venous blood was drawn just prior to BAL. Bronchoalveolar cell profiles were characterised by morphological criteria, and cell surface antigen expression of lymphocytes was determined by flow cytometry. Results-A significant increase in total BAL lymphocytes was observed for the oldest group compared with the youngest age group. Mean lymphocyte subset (CD4+/CD8+) ratios were significantly increased in BAL fluid from the older group compared with the younger group (mean (SE) 7.6 (1.5) vs 1.9 (0.2); p<0.0001). The increase in the BAL CD4+/ CD8+ T cell ratio was mostly due to an increase in relative numbers of CD4+ lymphocytes, and the BAL CD4/CD8 ratio was disproportionately increased compared with peripheral blood in the older group. Increased expression of HLA-DR and CD69 on CD4+ T lymphocytes was observed in the oldest age group. Relative numbers of natural killer (NK) cells did not vary with age, and T cells and CD5+ B cells were present in very low numbers in both age groups. Conclusions-CD4+ T cells accumulate in air spaces of the lower respiratory tract with age in healthy adults and express increased amounts of HLA-DR and CD69 on their surfaces, suggesting a relative degree of CD4+ T lymphocyte activation for healthy older individuals who have normal lung function.

Large numbers of neutrophils with unopposed neutrophil elastase (NE) proteolytic activity are found in lower respiratory tract secretions from most patients with advanced cystic fibrosis (CF). To determine whether antielastase defenses may be overwhelmed in epithelial lining fluid after lung transplantation, we measured NE activity (cleavage of the specific substrate, MeO-Suc-Ala-Ala-Pro-Val-pNA) in bronchoalveolar lavage fluids (BALF) obtained for surveillance or diagnostic purposes at various intervals (1 mo to 7 yr after transplantation) from 52 recipients who had undergone double or bilateral lung transplantation for end-stage CF. Unopposed NE activity was found in BALF from 14 recipients, most of whom also had >= 10(5) colony forming units (cfu) of Pseudomonas aeruginosa in BALF. Ten of the 14 recipients with unopposed NE in bronchoalveolar lavage (BAL) had developed obliterative bronchiolitis (OB), but only 8 of the 38 subjects without unopposed NE activity had OB (p = 0. 002; Fisher exact test). We conclude that antiprotease defenses in lower respiratory tract secretions of CF patients receiving lung allografts are sufficient in the majority of patients to prevent unopposed NE activity. However, the presence of unopposed NE activity in BAL from lung allografts of patients with CF is associated with progressive, irreversible OB and graft failure.