Function and composition of pulmonary surfactant and surfactant-derived fatty acid profiles are altered in young adults with cystic fibrosis

Study objectives: To determine whether chronic lung inflammation in young a dult patients with cystic fibrosis (CF) alters the composition and function of surfactant and surfactant components in bronchoalveolar secretions. Design: A prospective, descriptive study. Setting: An adult CF center in a tertiary health-care center. Participants: Thirteen normal volunteer (NV) subjects recruited via local a dvertising and 15 CF patients recruited from the CF center. Interventions: None. Measurements and results: We performed BAL and measured surfactant-associat ed protein A (SP-A) via enzyme-linked immunosorbent assay in BAL fluid (BAL F), and quantitated total phospholipid, phospholipid subclass, and fatty ac id subclass content of extracted BALF. We also determined the protein and p hospholipid content, SP-A content, and functional characteristics of surfac tant isolated from BALF via high-speed centrifugation. The phospholipid-to- protein ratio (milligram/milligram) of surfactant isolated by centrifugatio n (mean +/- SEM) was 1.01 +/- 0.07 for NV subjects and 2.62 +/- 0.42 for CF patients (p = 0.0001). Minimal surface tension was < 1 dyne.s.cm(-5) in al l samples from NV subjects, but 21.9 +/- 0.73 dyne.s.cm(-5) for surfactant from CF patients. Immunoblotting of isolated surfactant revealed a marked d ecrease in SP-A for CF patients, compared to NV subjects. However, mean con centrations of SP-A in BALF that had not been subjected to high-speed centr ifugation to isolate surfactant were not significantly different for CF pat ients (4.7 +/- 0.8 mu g/mL) vs NV subjects (4.6 +/- 0.2 mu g/mL). Additiona lly, phospholipid-to-protein ratios (0.32 +/- 0.04 for NV subjects vs 0.10 +/- 0.02 for CF patients; p < 0.0001) in extracted uncentrifuged BALF, and SP-A-to-protein ratios (microgram/milligram) in BALF were significantly dep ressed (74 +/- 8 for NV subjects vs 16 +/- 3 for CF patients; p < 0.0001). The phospholipid and fatty acid subclass profiles of extracted CF BALF vs N V BALF revealed a decreased mean phosphatidylcholine-to-sphingomyelin ratio (20.7 +/- 10.0 vs 55.2 +/- 8.7; p = 0.002), increased oleic acid content ( 12.1 +/- 2.3 nmol/mL, vs 3.2 +/- 0.9 mmol/mL; p < 0.01), and increased arac hidonic acid content (2.2 +/- 0.5 nmol/mL vs 0.6 +/- 0.3 nmol/mL; p < 0.05) for CF patients. Conclusions: Altered phospholipid-to-protein ratios and phospholipid subcla sses, altered surfactant-derived fatty acid profiles, high minimal surface tension, and decreased association of SP-A with lipid components of isolate d surfactant indicate that surfactant components are considerably altered a nd dysfunctional in lower respiratory tract secretions of CF patients. Surf actant composition and function are altered in CF, and the pattern of phosp holipid and surfactant-derived fatty acid subclass alterations in CF are ch aracteristic of ongoing lung injury and may depress surfactant function.