Airway microbiome, host immune response and recurrent wheezing in infants with severe respiratory syncytial virus bronchiolitis

Abstract

Background: Early interactions between respiratory viruses and microbiota mightmodulate host immune responses and subsequently contribute to later development of recurrent wheezing and asthma in childhood. We aimed to study the possible association between respiratory microbiome, host immune response, and the development of recurrent wheezing in infants with severe respiratory syncytial virus (RSV) bronchiolitis.Methods: Seventy-four infants who were hospitalized at Beijing Children's Hospital during an initial episode of severe RSV bronchiolitis at 6 months of age or less were included and followed up until the age of 3 years. Sputum samples were collected, and their microbiota profiles, LPS, and cytokines were analyzed by 16S rRNA-based sequencing, ELISA, and multiplex immunoassay, respectively.Results: Twenty-six (35.1%) infants developed recurrent wheezing by the age of 3 years, and 48 (64.9%) did not. The relative abundance of Haemophilus, Moraxella, and Klebsiella was higher in infants who later developed recurrent wheezing than in those who did not (LDA score >3.5). Airway levels of LPS (P = .003), CXCL8 (P = .004), CCL5 (P = .029), IL-6 (P = .004), and IL-13 (P < .001) were significantly higher in infants who later developed recurrent wheezing than in those who did not. Moreover, high airway abundance of Haemophilus was associated with CXCL8 (r = 0.246, P = .037) level, and that of Moraxella was associated with IL-6 level (r = 0.236, P = .046) and IL-10 level (r = 0.266, P = .024). Conclusion:Our study suggests that higher abundance of Haemophilus and Moraxella in airway microbiome might modulate airway inflammation during severe RSV bronchiolitis in infancy, potentially contributing to the development of subsequent recurrent wheezing in later childhood. K E Y W O R D S airway inflammation, children, lipopolysaccharide, recurrent wheezing, respiratory microbiome, respiratory syncytial virus S U PP O RTI N G I N FO R M ATI O N Additional supporting information may be found online in the Supporting Information section. How to cite this article: Zhang X, Zhang X, Zhang N, et al. Airway microbiome, host immune response and recurrent wheezing in infants with severe respiratory syncytial virus bronchiolitis. Pediatr Allergy Immunol. 2020;31:281-289.

Nontypeable Haemophilus influenzae Responds to Virus-Infected Cells with a Significant Increase in Type IV Pilus Expression

“…Thereby, here we examined T4P expression specifically in the context of prior infection of respiratory tract epithelial cells with RSV, AV, or RV, as these viruses commonly predispose to NTHI disease (38,(47)(48)(49)(50)(51)(52). Coinfection with RSV and NTHI is associated with bronchiolitis and subsequent wheezing in children (49), and RV infection facilitates the development of both rhinosinusitis (33) and NTHI-induced exacerbations of COPD (59,60). Infection with RSV, AV, or RV is associated with increased risk of acute OM in children (32,47,61).…”

“…However, the effects of prior URT virus infection of respiratory tract epithelial cells on subsequent expression of T4P by NTHI have not been studied. Accordingly, here, we examined T4P expression by NTHI cultured with well-differentiated primary human airway epithelial cells (HAEs) with ongoing infection due to adenovirus (AV), respiratory syncytial virus (RSV), or rhinovirus (RV), three of the most common URT viruses associated with NTHI coinfections (38,(47)(48)(49)(50)(51)(52).…”

The use of β2-adrenoreceptor agonists in viral bronchiolitis: scientific rationale beyond evidence-based guidelines

“…In the same line, there is evidence showing that RSV and rhinovirus bronchiolitis are associated with significantly different nasopharyngeal metabolome, and bacterial metagenome [45,46]. For instance, STEWART et al [45] demonstrated that RSV and rhinovirus are associated with different metabolic pathways and that the associated bacterial functional capacity is derived primarily from Streptococcus pneumoniae in RSV bronchiolitis and from Haemophilus influenzae in rhinovirus bronchiolitis.…”

“…In the same line, there is evidence showing that RSV and rhinovirus bronchiolitis are associated with significantly different nasopharyngeal metabolome, and bacterial metagenome [ 45 , 46 ]. For instance, S tewart et al .…”

Risk factors for recurrent wheezing after bronchiolitis in infants: 2-year follow up in China

“…Follow up data from abroad showed that the incidence of post-bronchiolitis recurrent wheezing is as high as 31% [4] and about 48% of patients were diagnosed with asthma at the age of 7 years old following severe RSV bronchiolitis [5] . In a follow-up study in China [6] , 35.1% (26/74) of infants at 6 months of age or less with bronchiolitis had recurrent wheezing by the age of 3 years. However, the mechanism of recurrent wheezing after bronchiolitis has not been elucidated, and knowledge around risk factors is still controversial.…”