Limits...
Surfactant lipidomics in healthy children and childhood interstitial lung disease.

Griese M, Kirmeier HG, Liebisch G, Rauch D, Stückler F, Schmitz G, Zarbock R, ILD-BAL working group of the Kids-Lung-Regist - PLoS ONE (2015)

Bottom Line: Two reference populations were compared to a broad range of children with ILD.Class 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatric Pulmonology, Hauner Children's Hospital, Ludwig Maximilians University, Member of the German Center for Lung Research (DZL), Lindwurmstr. 4a, D-80337 Munich, Germany.

ABSTRACT

Background: Lipids 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.

Methods: Comprehensive 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.

Results: Class 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.

Conclusions: Lipidomic 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.

Show MeSH

Related in: MedlinePlus

Display of results at the disease category level.A) Phosphatidylcholine, the major surfactant phospholipid class and B) its species dipalmitoylphosphatidylcholine (PC 32:0) are given as individual results of all patients included in the study according the disease category they belong to. The statistical comparisons were done by ANOVA and Dunn’s post hoc test; all significant results are displayed in each figure. To take multiple comparisons into consideration, an overall cut-off level of P<0.0182 was calculated. For A) 1-way ANOVA gave a P = 0.0020, for B) P < 0.0038; the significant results of Dunn’s post hoc tests are indicated as following: ____ = P < 0.05, _ _ _ = P < 0.01, and …. = P < 0.001. The species of the other phosphatidylcholines, the other phospholipid classes and their species composition are displayed in S3 Fig. Horizontal bar indicates median.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4333572&req=5

pone.0117985.g003: Display of results at the disease category level.A) Phosphatidylcholine, the major surfactant phospholipid class and B) its species dipalmitoylphosphatidylcholine (PC 32:0) are given as individual results of all patients included in the study according the disease category they belong to. The statistical comparisons were done by ANOVA and Dunn’s post hoc test; all significant results are displayed in each figure. To take multiple comparisons into consideration, an overall cut-off level of P<0.0182 was calculated. For A) 1-way ANOVA gave a P = 0.0020, for B) P < 0.0038; the significant results of Dunn’s post hoc tests are indicated as following: ____ = P < 0.05, _ _ _ = P < 0.01, and …. = P < 0.001. The species of the other phosphatidylcholines, the other phospholipid classes and their species composition are displayed in S3 Fig. Horizontal bar indicates median.

Mentions: For the first time extensive BAL lipidomics profile of children with a normal alveolar surfactant, i.e. healthy children and those with bronchitis and as such with no or very little impact on the alveolar space were determined comprehensively. We analyzed lavage for many of its lipids (Fig. 1) and found that total phospholipids constituted more than 85%; free cholesterol was about 10% and a small amount were cholesteryl esters (Table 2). Among the phospholipid species, phosphatidylcholine was by far the most abundant, as expected for pulmonary surfactant (Fig. 2A), with dipalmitoyl-phosphatiylcholine (32:0) as the main species (Fig. 2B). When compared to the healthy children, the children with bronchitis had a similar pattern with no differences in classes; however there were some difference in minor species of the non-surfactant lipid classes phosphatidylethanolamine, phosphatidylserine, plasmalogens and cholesteryl esters. This underscores the susceptibility of lipid species composition to influences from bronchial inflammatory processes (S2 Fig.), even if only few and not all cell lipids typical for cells are altered. To readily detect the extent, single values are displayed (Fig. 3, S3 Fig.).


Surfactant lipidomics in healthy children and childhood interstitial lung disease.

Griese M, Kirmeier HG, Liebisch G, Rauch D, Stückler F, Schmitz G, Zarbock R, ILD-BAL working group of the Kids-Lung-Regist - PLoS ONE (2015)

Display of results at the disease category level.A) Phosphatidylcholine, the major surfactant phospholipid class and B) its species dipalmitoylphosphatidylcholine (PC 32:0) are given as individual results of all patients included in the study according the disease category they belong to. The statistical comparisons were done by ANOVA and Dunn’s post hoc test; all significant results are displayed in each figure. To take multiple comparisons into consideration, an overall cut-off level of P<0.0182 was calculated. For A) 1-way ANOVA gave a P = 0.0020, for B) P < 0.0038; the significant results of Dunn’s post hoc tests are indicated as following: ____ = P < 0.05, _ _ _ = P < 0.01, and …. = P < 0.001. The species of the other phosphatidylcholines, the other phospholipid classes and their species composition are displayed in S3 Fig. Horizontal bar indicates median.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4333572&req=5

pone.0117985.g003: Display of results at the disease category level.A) Phosphatidylcholine, the major surfactant phospholipid class and B) its species dipalmitoylphosphatidylcholine (PC 32:0) are given as individual results of all patients included in the study according the disease category they belong to. The statistical comparisons were done by ANOVA and Dunn’s post hoc test; all significant results are displayed in each figure. To take multiple comparisons into consideration, an overall cut-off level of P<0.0182 was calculated. For A) 1-way ANOVA gave a P = 0.0020, for B) P < 0.0038; the significant results of Dunn’s post hoc tests are indicated as following: ____ = P < 0.05, _ _ _ = P < 0.01, and …. = P < 0.001. The species of the other phosphatidylcholines, the other phospholipid classes and their species composition are displayed in S3 Fig. Horizontal bar indicates median.
Mentions: For the first time extensive BAL lipidomics profile of children with a normal alveolar surfactant, i.e. healthy children and those with bronchitis and as such with no or very little impact on the alveolar space were determined comprehensively. We analyzed lavage for many of its lipids (Fig. 1) and found that total phospholipids constituted more than 85%; free cholesterol was about 10% and a small amount were cholesteryl esters (Table 2). Among the phospholipid species, phosphatidylcholine was by far the most abundant, as expected for pulmonary surfactant (Fig. 2A), with dipalmitoyl-phosphatiylcholine (32:0) as the main species (Fig. 2B). When compared to the healthy children, the children with bronchitis had a similar pattern with no differences in classes; however there were some difference in minor species of the non-surfactant lipid classes phosphatidylethanolamine, phosphatidylserine, plasmalogens and cholesteryl esters. This underscores the susceptibility of lipid species composition to influences from bronchial inflammatory processes (S2 Fig.), even if only few and not all cell lipids typical for cells are altered. To readily detect the extent, single values are displayed (Fig. 3, S3 Fig.).

Bottom Line: Two reference populations were compared to a broad range of children with ILD.Class 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatric Pulmonology, Hauner Children's Hospital, Ludwig Maximilians University, Member of the German Center for Lung Research (DZL), Lindwurmstr. 4a, D-80337 Munich, Germany.

ABSTRACT

Background: Lipids 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.

Methods: Comprehensive 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.

Results: Class 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.

Conclusions: Lipidomic 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.

Show MeSH
Related in: MedlinePlus