Nasopharyngeal Proteobacteria are associated with viral etiology and acute wheezing in children with severe bronchiolitis

摘要: To the editor: Bronchiolitis is leading cause of hospitalization for US infants1 and usually caused by respiratory syncytial virus (RSV) or human rhinovirus (HRV).2 These early-life viral infections are associated with development recurrent wheezing asthma.3 While primary focus research on asthma has been viruses, there increasing evidence that bacteria also play a role in pathogenesis.4 Bisgaard colleagues, prospective study 321 healthy neonates, found an increased risk infants who had hypopharyngeal bacterial colonization Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis.4 Moreover, Hilty colleagues pathogenic Proteobacteria phylum (e.g. species) was significantly more common children than controls. 5 It unknown, however, if specific colonizing tract (i.e. microbiome) contribute to severe bronchiolitis hospitalized bronchiolitis). Since at high later asthma,3 we examined these would have similar microbial perturbations as those observed older asthma..5 As part prospective, multicenter, multiyear >2,000 bronchiolitis, used 16S rRNA gene pyrosequencing analyze 100 nasopharyngeal aspirates (NPAs) from age <2 years one participating hospital. Since did not controls, hypothesized be etiology child's (RSV, HRV, both) acute status (present/absent). Detailed methods, including inclusion/ exclusion criteria patient demographics, may online supplement. Site teams gathered detailed clinical data, collected NPAs, performed short-term follow-up.2 described previously,2 every child this cohort NPA tested 16 viruses real-time RT-PCR.2 (n=100) whole genome shotgun (WGS, n=10) sequencing analysis were DNA isolated each sample (details supplement). Statistical analyses supervised machine learning (see supplement details) identify taxa status. Covariates but microbiome differences were: age, exposure cigarette smoke, antibiotic treatment, history breastfeeding (data shown). In addition, restricting following stringent definition <1 year no prior wheezing) materially change results shown). We increase H. influenzae M. catarrhalis discriminated between RSV/HRV co-infection single infection (Table 1). The finding interest given separate multivariable >2000 cohort, longer length-of-stay when compared RSV only infections.2 WGS analysis, detected most infected co-infected samples, samples HRV only. suggest context it possible promote presence species vice versa. Indeed, disturb epithelium, allowing greater adherence, possibly chances secondary infection.6 Interestingly, opposite predisposing disease) true since chance infection.7 Therefore, virus-only bacteria-only approach conditions too simplistic. And studies larger number needed confirm determine whether how interact or, alternatively, sign global susceptibility state. Table I Taxa discriminate bronchiolitis Another means confirming potential importance examine admission. Wheezing required diagnose bronchiolitis,8 wheeze certain times likely develop present study, wheezed admission insignificant mean relative abundance (15.6% vs. 10.2%, P=0.58) without (Figure Examining phyla genus level demonstrated upon (10.3% 3.64%, P=0.009, Table I Online II). Figure 1 Average abundances status Data regarding association seems accumulating. Directly building data Bisgaard 4 Hilty5, Marri higher proportions adults mild controls (37% 15%; P<0.001). Our support hypothesis illnesses. We believe first bronchiolitis. previously reported extend younger Of particular Proteobacteria, specifically catarrhalis, our show wheezing. However, until necessary fully understand relationship microbiome, causes developing illnesses. future conducted, researchers will need address challenges sampling lung both upper lower airway samples.9 Further area inform new therapeutic strategies, probiotics, prevent childhood asthma.