Deficient hydrophilic lung surfactant proteins A and D with normal surfactant phospholipid molecular species in cystic fibrosis

Chronic bacterial colonization of the lungs, with an excessive inflammatory response, is the major cause of morbidity and mortality in cystic fibrosis , Lung surfactant exhibits a spectrum of potential immunomodulatory propert ies: phospholipid components inhibit cellular inflammatory responses, where as the hydrophilic surfactant proteins A (SP-A) and D (SP-D) are integral c omponents of the innate host defense response of the lungs against bacteria l infection. Consequently, alteration to the relative proportions of lung s urfactant components may alter the susceptibility of the lungs to bacterial colonization. In this study, bronchoalveolar lavage (BAL) samples were col lected at diagnostic fiberoptic bronchoscopy from ii control children, 13 c hildren with cystic fibrosis, and 11 children with acute lung infection, El ectrospray ionization mass spectrometry analysis demonstrated negligible ch anges to the molecular species or total BAL concentrations of phosphatidylc holine, phosphatidylglycerol, or phosphatidylinositol among the three subje ct groups. In contrast, median SP-A concentration was decreased (P < 0.001) in the cystic fibrosis group (2.65 mu g/ml) compared with control (12.35 m u g/ml) and infection (9.76 mu g/ml) groups, Median SP-D was also decreased (P < 0.05) in the infection (12.17 ng/ml) compared with the control group (641 ng/ml), and was below assay limits for the majority of cystic fibrosis children (P < 0.001). This dramatic decrease of hydrophilic surfactant pro teins in the presence of normal surfactant phospholipid may be one mechanis m underlying the relative ineffectiveness of the cellular inflammatory resp onse in killing invading bacteria in the lungs of patients with cystic fibr osis.