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Altered Phospholipid Composition and Aggregate Structure of Lung Surfactant Is Associated with Impaired Lung Function in Young Children with Respiratory Infections

Child Health, Infection Inflammation and Repair Division, School of Medicine, Southampton General Hospital, Southampton; Department of Respiratory Medicine, Bristol Royal Hospital for Children, Bristol, United Kingdom; and Departments of Paediatric Pulmonology and Neonatology, Hannover Medical School, Hannover, Germany

Address correspondence to: A. D. Postle, Ph.D., Child Health, Level G (803), Centre Block, Southampton General Hospital, Tremona Road, Southampton SO16 6YD, UK. E-mail: adp{at}soton.ac.uk

Alterations to pulmonary surfactant structure, composition, and function contribute to the severity of respiratory infections. Analysis of bronchoalveolar lavage fluid (BALF) from children undergoing diagnostic bronchoscopy for structural abnormalities (control group, n = 24), asthma (n = 18), lung infection (n = 30), and cystic fibrosis (CF, n = 15) showed that BALF phospholipid concentration decreased with age for the control group and was elevated in all disease groups. The fractional concentration of the major surface active component, dipalmitoyl phosphatidylcholine (PC16:0/16:0), correlated (r² = 0.608, P < 0.01) with airway resistance (FEV_1% predicted), and decreased PC16:0/16:0 was accompanied by increased concentrations of phospholipid components characteristic of cell membranes (PC16:0/18:1 and PI18:0/20:4). Median minimal surface tension, measured by pulsating bubble surfactometer, was elevated (P < 0.01) in both infection (17.5 mN/m) and CF (17.1 mN/m) compared with the control group (1.5 mN/m). Centrifugation (60,000 x g, 40 min) of BALF indicated that infection was accompanied by accumulation of large aggregate forms of surfactant, in contrast to previous reports of increased conversion to inactive small aggregate surfactant particles in ventilated patients with respiratory failure. This accumulation of surface-inactive, large aggregate forms of surfactant, possibly due to mixing with membrane material from inflammatory cells, may contribute to severity of lung disease in children with respiratory infections.

Abbreviations: acute respiratory distress syndrome, ARDS • bronchoaveolar lavage fluid, BALF • cystic fibrosis, CF • dipalmitoylphosphatidylcholine, DPPC • electrospray ionization mass spectrometry, ESI-MS • large aggregate, LA • phosphatidylcholine, PC • phosphatidylglycerol, PG • phosphatidylinositol, PI • phospholipid, PL • small aggregate, SA •

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