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Laboratory and Animal Investigations |

Function and Composition of Pulmonary Surfactant and Surfactant-Derived Fatty Acid Profiles Are Altered in Young Adults With Cystic Fibrosis*

Keith C. Meyer, MD, FCCP; Anuja Sharma, MD; Raymond Brown, PhD; Mark Weatherly, MD; Fernando R. Moya, MD; June Lewandoski, BS; Jerry J. Zimmerman, MD, PhD
Author and Funding Information

*From the Department of Medicine, Section of Pulmonary and Critical Care Medicine (Drs. Meyer and Brown), University of Wisconsin Medical School, Madison, WI; Pulmonary & Critical Care Associates (Dr. Sharma), St. Paul, MN; Pulmonary Division (Dr. Weatherly), Nemours Children’s Clinic, Orlando, FL; Department of Pediatrics (Dr. Moya), UT Southwestern Medical Center, Dallas, TX; Department of Family Practice (Ms. Lewandoski), Franciscan Skemp Healthcare, La Crosse, WI; and Pediatric Critical Care Medicine (Dr. Zimmerman), Children’s Hospital Regional Medical Center, Seattle, WA.

Correspondence to: Keith Meyer, MD, FCCP, Section of Pulmonary and Critical Care Medicine, Department of Medicine, H6/380 Clinical Sciences Center, 600 Highland Ave, Madison, WI 53792-3240; e-mail: kcm@medicine.wisc.edu



Chest. 2000;118(1):164-174. doi:10.1378/chest.118.1.164
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Study objectives: To determine whether chronic lung inflammation in young adult 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 advertising and 15 CF patients recruited from the CF center.

Interventions: None.

Measurements and results: We performed BAL and measured surfactant-associated protein A (SP-A) via enzyme-linked immunosorbent assay in BAL fluid (BALF), and quantitated total phospholipid, phospholipid subclass, and fatty acid subclass content of extracted BALF. We also determined the protein and phospholipid content, SP-A content, and functional characteristics of surfactant isolated from BALF via high-speed centrifugation. The phospholipid-to-protein ratio (milligram/milligram) of surfactant isolated by centrifugation (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 all 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 decrease in SP-A for CF patients, compared to NV subjects. However, mean concentrations of SP-A in BALF that had not been subjected to high-speed centrifugation to isolate surfactant were not significantly different for CF patients (4.7 ± 0.8 μg/mL) vs NV subjects (4.6 ± 0.2 μg/mL). Additionally, 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 depressed (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 NV 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 nmol/mL; p < 0.01), and increased arachidonic 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 subclasses, altered surfactant-derived fatty acid profiles, high minimal surface tension, and decreased association of SP-A with lipid components of isolated surfactant indicate that surfactant components are considerably altered and dysfunctional in lower respiratory tract secretions of CF patients. Surfactant composition and function are altered in CF, and the pattern of phospholipid and surfactant-derived fatty acid subclass alterations in CF are characteristic of ongoing lung injury and may depress surfactant function.

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