毛细支气管炎分型不同，患哮喘的风险存在差异 | 热心肠日报
11-13, Article
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Background: Young children with rhinovirus (RV) infection—particularly bronchiolitis—are at high risk for developing childhood asthma. Emerging evidence suggests clinical heterogeneity within RV bronchiolitis. However, little is known about these biologically-distinct subgroups (endotypes) and their relations with asthma risk.
Objective: We aimed to identify RV bronchiolitis endotypes and examine their longitudinal relations with asthma risk.
Methods: As part of multicenter prospective cohort study of infants (age <12 months) hospitalized for bronchiolitis, we integrated clinical, RV species, nasopharyngeal microbiome (16S rRNA gene sequencing), cytokine, and metabolome (liquid chromatography–tandem mass spectrometry) data collected at hospitalization. We then applied network and clustering approaches to identify bronchiolitis endotypes. We also examined their longitudinal association with risks of developing recurrent wheeze by age 3 years and asthma by age 5 years.
Results: Of 122 infants hospitalized for RV bronchiolitis (median age, 4 months), we identified four distinct endotypes—mainly characterized by RV species, microbiome, and type 2 cytokine (T2) response: A) virus RV-Cmicrobiome mixedT2 low, B) virus RV-Amicrobiome HaemophilusT2 low, C) virus RSV/RVmicrobiome StreptococcusT2 low, and D) virus RV-Cmicrobiome MoraxellaT2 high. Compared with endotype A infants, endotype D infants had a significantly higher rate of recurrent wheeze (33% vs. 64%; HR, 2.23; 95%CI, 1.00-4.96; P=0.049) and higher risk for developing asthma (28% vs. 59%; OR, 3.74: 95%CI, 1.21-12.6; P=0.03)
Conclusion: Integrated-omics analysis identified biologically-meaningful RV bronchiolitis endotypes in infants, such as one characterized by RV-C infection, Moraxella-dominant microbiota, and high T2 cytokine response, at higher risk for developing recurrent wheeze and asthma. This study should facilitate further research to validating our inferences.
First Authors:
Yoshihiko Raita
Correspondence Authors:
Yoshihiko Raita
All Authors:
Yoshihiko Raita,Carlos A Camargo Jr,Yury A Bochkov,Juan C Celedón,James E Gern,Jonathan M Mansbach,Eugene P Rhee,Robert J Freishtat,Kohei Hasegawa