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Altered phospholipid composition and aggregate structure of lung surfactant is associated with impaired lung function
Ann Mander1, Simon Langton-Hewer, Wolfgang Bernhard
1Child Health, Infection Inflammation and Repair Division, School of Medicine, Southampton General Hospital, Southampton, UK.
Insights
Pulmonary surfactant alterations worsen respiratory infections. In children, decreased surfactant phospholipids and increased surface tension in bronchoalveolar lavage fluid (BALF) correlate with lung disease severity, particularly in infections.
Area of Science:
- Pulmonary Medicine
- Biochemistry
- Pediatric Respiratory Health
Background:
- Pulmonary surfactant alterations impact respiratory infection severity.
- Surfactant dysfunction is implicated in various pediatric lung diseases.
Purpose of the Study:
- To investigate pulmonary surfactant composition and function in children with respiratory infections, asthma, and cystic fibrosis (CF).
- To correlate surfactant alterations with disease severity and airway resistance.
Main Methods:
- Analysis of bronchoalveolar lavage fluid (BALF) phospholipid concentration and composition.
- Measurement of minimal surface tension using a pulsating bubble surfactometer.
- Assessment of surfactant aggregate forms via centrifugation.
Main Results:
- BALF phospholipid concentration was elevated in all disease groups compared to controls.
- Decreased dipalmitoyl phosphatidylcholine (PC16:0/16:0) correlated with increased airway resistance.
- Elevated minimal surface tension was observed in infection and CF groups.
- Infection was associated with accumulation of large aggregate surfactant forms.
Conclusions:
- Altered surfactant composition and function contribute to pediatric respiratory disease severity.
- Accumulation of surface-inactive surfactant aggregates in infections may exacerbate lung disease.
- Surfactant analysis offers insights into disease mechanisms and potential therapeutic targets.
Abstract:
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 (r(2) = 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.
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