TGFß1 and POSTN as biomarkers of postinfectious bronchiolitis obliterans and asthma in children.

ABSTRACT

RATIONALE Asthma and postinfectious bronchiolitis obliterans (PIBO) are common chronic lung diseases in company with wheezing in children. However, it is not clear what is common and unique mechanisms between the two diseases. Thus, we used proteomic analysis to compare differences in biomarkers between children with asthma and PIBO. METHODS: Overall, 30 healthy children without respiratory underlying diseases, 18 children with asthma and 15 with PIBO were included for this study. Sequential window acquisition of all theoretical mass spectra (SWATH)-mass spectrometry (MS) was used to measure proteins in plasma samples. To identify specific pathways of each groups, we used the ingenuity pathway analysis (IPA) software. RESULTS: We identified and quantified 354 proteins across all 63 samples in the SWATH-MS analysis. Forty eight proteins were significantly different among 3 groups. The upstream analysis of IPA suggested that inhibitor of nuclear factor kappa B kinase subunit beta (IKBKB) was the upstream inhibitor of 4 differentially expressed proteins (DEPs) in asthma, while the upstream activator in PIBO subjects. Among 4 DEPs, TGF-ß1 in PIBO and periostin in asthma were negatively correlated with forced expiratory volume in 1 s (FEV1), FEV1/forced vital capacity, maximal med-expiratory flow, and PC20, respectively. CONCLUSION: These findings demonstrate that transforming growth factor ß1 and periostin were unique biomarkers of PIBO and asthma in children, respectively. The mechanism regulated by IKBKB may be therapeutically relevant for PIBO and asthma.