Surfactant Lipidomics in Healthy Children and Childhood Interstitial Lung Disease

Abstract

BackgroundLipids account for the majority of pulmonary surfactant, which is essential for normal breathing. We asked if interstitial lung diseases (ILD) in children may disrupt alveolar surfactant and give clues for disease categorization.MethodsComprehensive lipidomics profiles of broncho-alveolar lavage fluid were generated in 115 children by electrospray ionization tandem mass spectrometry (ESI-MS/MS). Two reference populations were compared to a broad range of children with ILD.ResultsClass and species composition in healthy children did not differ from that in children with ILD related to diffuse developmental disorders, chronic tachypnoe of infancy, ILD related to lung vessels and the heart, and ILD related to reactive lymphoid lesions. As groups, ILDs related to the alveolar surfactant region, ILD related to unclear respiratory distress syndrome in the mature neonate, or in part ILD related to growth abnormalities reflecting deficient alveolarisation, had significant alterations of some surfactant specific phospholipids. Additionally, lipids derived from inflammatory processes were identified and differentiated. In children with ABCA3-deficiency from two ILD causing mutations saturated and monounsaturated phosphatidylcholine species with 30 and 32 carbons and almost all phosphatidylglycerol species were severely reduced. In other alveolar disorders lipidomic profiles may be of less diagnostic value, but nevertheless may substantiate lack of significant involvement of mechanisms related to surfactant lipid metabolism.ConclusionsLipidomic profiling may identify specific forms of ILD in children with surfactant alterations and characterized the molecular species pattern likely to be transported by ABCA3 in vivo.

Increased Risk of Interstitial Lung Disease in Children with a Single R288K Variant of ABCA3

“…content in bronchoalveolar lavage of infants and raised surface tension compared with control group (19,20). Molecular species patterns of phosphatidylcholine, that is, dipalmitoylphosphatidylcholine (PC 32:0), were also decreased in lavage of affected children (20).…”

“…Molecular species patterns of phosphatidylcholine, that is, dipalmitoylphosphatidylcholine (PC 32:0), were also decreased in lavage of affected children (20). In this study we investigated the hypothesis that the ABCA3 variant R288K may be permissive for children's interstitial lung disease.…”

“…After protein level determination, lipids of bronchoalveolar lavages (BALs) obtained from the patients were analyzed by ESI-MS/MS in positive ion mode as described in (20).…”

Tools to explore ABCA3 mutations causing interstitial lung disease

“…Mutations affecting protein function in any way were termed “other.” From a cellular perspective mutations were previously distinguished between those with abnormal localization of the ABCA3 protein in the cells and those with ATP hydrolysis defects . The major role of ABCA3 in LB biogenesis and surfactant lipid synthesis, that is, dipalmitoyl‐phosphatidylcholine (PC 32:0) content of the cells, must also be considered …”

Update on Diffuse Lung Disease in Children

“…5 A recent study also suggests that lipidomic analysis of bronchoalveolar lavage fluid could aid in case identification. 44 Treatment options for surfactant production disorders continue to be limited, although there have been some reports of clinical improvement with systemic corticosteroids and/or hydroxychloroquine. deficiency and categorized their mutations as null-null, null-other, and other-other.…”