Serum cathelicidin, nasopharyngeal microbiota, and disease severity among infants hospitalized with bronchiolitis.
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ABSTRACT:
SUBMITTER: Hasegawa K
PROVIDER: S-EPMC5385272 | biostudies-literature | 2017 Apr
REPOSITORIES: biostudies-literature
Publications
Serum cathelicidin, nasopharyngeal microbiota, and disease severity among infants hospitalized with bronchiolitis.
Hasegawa Kohei K Mansbach Jonathan M JM Ajami Nadim J NJ Petrosino Joseph F JF Freishtat Robert J RJ Teach Stephen J SJ Piedra Pedro A PA Camargo Carlos A CA
The Journal of allergy and clinical immunology 20161112 4
Similar Datasets
Project description:BackgroundEmerging evidence suggests relationships between the nasopharyngeal metabolome and both the microbiota and severity of bronchiolitis. However, the influence of host systemic metabolism on disease pathobiology remains unclear. We aimed to examine metabolome profiles and their association with more-severe disease, defined by use of positive pressure ventilation (PPV), in infants hospitalized for bronchiolitis.MethodsIn 140 infants with bronchiolitis, metabolomic profiling was performed on serum; samples from 70 were in a training data set, and samples from 70 were in an independent test data set. We also profiled the nasopharyngeal airway microbiota and examined its association with the serum metabolites.ResultsSerum metabolome profiles differed by bronchiolitis severity (P < .001). In total, 20 metabolites in the training data set were significantly associated with the risk of PPV, of which 18 remained significant following adjustment for confounders (false-discovery rate [FDR], < 0.10). Phosphatidylcholine metabolites were associated with higher risks of PPV use, while metabolites from the plasmalogen subpathway were associated with lower risks. The test data set validated these findings (FDR < 0.05). Streptococcus abundance was positively associated with metabolites that are associated with higher risks of PPV.ConclusionsSerum metabolomic signatures were associated with both the nasopharyngeal microbiota and the severity of bronchiolitis. Our findings advance research into the complex interrelations between the airway microbiome, host systemic response, and pathobiology of bronchiolitis.
| S-EPMC6534192 | biostudies-literature
Project description:Little is known about the relationship between the specific airway microbiota composition and severity of bronchiolitis. We aimed to identify nasopharyngeal microbiota profiles and link these profiles to acute severity in infants hospitalised for bronchiolitis.We conducted a multicentre prospective cohort study of 1005 infants (age <1?year) hospitalised for bronchiolitis over three winters, 2011-2014. By applying a 16S rRNA gene sequence and clustering approach to the nasopharyngeal aspirates collected within 24?h of hospitalisation, we determined nasopharyngeal microbiota profiles and their association with bronchiolitis severity. The primary outcome was intensive care use, i.e. admission to an intensive care unit or use of mechanical ventilation.We identified four nasopharyngeal microbiota profiles: three profiles were dominated by one of Haemophilus, Moraxella or Streptococcus, while the fourth profile had the highest bacterial richness. The rate of intensive care use was highest in infants with a Haemophilus-dominant profile and lowest in those with a Moraxella-dominant profile (20.2% versus 12.3%; unadjusted OR 1.81, 95% CI 1.07-3.11, p=0.03). After adjusting for 11 patient-level confounders, the rate remained significantly higher in infants with Haemophilus-dominant profiles (OR 1.98, 95% CI 1.08-3.62, p=0.03). These findings were externally validated in a separate cohort of 307 children hospitalised for bronchiolitis.
| S-EPMC5459592 | biostudies-literature
Project description:Emerging evidence suggests that the airway microbiota plays an important role in viral bronchiolitis pathobiology. However, little is known about the combined role of airway microbiota and CCL5 in infants with bronchiolitis. In this multicenter prospective cohort study of 1005 infants (age <1 year) hospitalized for bronchiolitis during 2011-2014, we observed statistically significant interactions between nasopharyngeal airway CCL5 levels and microbiota profiles with regard to the risk of both intensive care use (Pinteraction =.02) and hospital length-of-stay ≥3 days (Pinteraction =.03). Among infants with lower CCL5 levels, the Haemophilus-dominant microbiota profile was associated with a higher risk of intensive care use (OR, 3.20; 95%CI, 1.18-8.68; P=.02) and hospital length-of-stay ≥3 days (OR, 4.14; 95%CI, 2.08-8.24; P<.001) compared to the Moraxella-dominant profile. Conversely, among those with higher CCL5 levels, there were no significant associations between the microbiota profiles and these severity outcomes (all P≥.10).
| S-EPMC5601014 | biostudies-literature
Project description:ObjectiveTo investigate the relationship between socioeconomic factors and bronchiolitis severity among hospitalized infants.MethodsWe performed a 17-center, prospective cohort study from 2011 to 2014. Children <1 year old hospitalized with bronchiolitis were enrolled. Socioeconomic factors included estimated median household income (MHI) per home ZIP code, parent-reported household income, number of adults and children in household, and insurance type. We defined higher bronchiolitis severity as receipt of intensive care treatment. Multivariable logistic regression was used to analyze the association between socioeconomic factors and bronchiolitis severity, with the final model adjusted for potential clustering by site.ResultsIn multivariable models adjusted for demographic and clinical characteristics, estimated MHI was the socioeconomic factor most strongly associated with severity. Compared to infants with an intermediate MHI ($40,000-$79,999), odds of receiving intensive care treatment were significantly higher for those with MHI of ≥$80,000 (aOR 2.05, 95% CI 1.19-3.53). No significant associations were found for the other socioeconomic factors (all P > .30). While there were no significant differences in clinical presentation between income groups (all P > .25) or in receipt of mechanical ventilation alone (P = .98), infants with estimated MHI ≥$80,000 were significantly more likely to specifically have been admitted to the intensive care unit (P = .01).ConclusionsIn this multicenter study of infants hospitalized with bronchiolitis, we identified higher median household income as a risk factor for intensive care treatment. This work may yield important biological or nonbiological insights for the future management of infants with bronchiolitis.
| S-EPMC6930979 | biostudies-literature
Project description:The relation of nasopharyngeal microbiota to the clearance of respiratory syncytial virus (RSV) in infants hospitalized for bronchiolitis is not known. In a multicenter cohort, we found that 106 of 557 infants (19%) hospitalized with RSV bronchiolitis had the same RSV subtype 3 weeks later (ie, delayed clearance of RSV). Using 16S ribosomal RNA gene sequencing and a clustering approach, infants with a Haemophilus-dominant microbiota profile at hospitalization were more likely than those with a mixed profile to have delayed clearance, after adjustment for 11 factors, including viral load. Nasopharyngeal microbiota composition is associated with delayed RSV clearance.
| S-EPMC6500556 | biostudies-literature
Project description:IntroductionRespiratory syncytial virus (RSV) is the most common cause of bronchiolitis and hospitalization in infants worldwide. The nasopharyngeal microbiota has been suggested to play a role in influencing the clinical course of RSV bronchiolitis, and some evidence has been provided regarding oral and gut microbiota. However, most studies have focused on a single timepoint, and none has investigated all three ecosystems at once.MethodsHere, we simultaneously reconstructed the gut, oral and nasopharyngeal microbiota dynamics of 19 infants with RSV bronchiolitis in relation to the duration of hospitalization (more or less than 5 days). Fecal samples, oral swabs, and nasopharyngeal aspirates were collected at three timepoints (emergency room admission, discharge and six-month follow-up) and profiled by 16S rRNA amplicon sequencing.ResultsInterestingly, all ecosystems underwent rearrangements over time but with distinct configurations depending on the clinical course of bronchiolitis. In particular, infants hospitalized for longer showed early and persistent signatures of unhealthy microbiota in all ecosystems, i.e., an increased representation of pathobionts and a depletion of typical age-predicted commensals.DiscussionMonitoring infant microbiota during RSV bronchiolitis and promptly reversing any dysbiotic features could be important for prognosis and long-term health.
| S-EPMC10482328 | biostudies-literature
Project description:Background: There is limited data on how different RSV genotypes and associated viral loads influence disease phenotypes. We characterized the genetic variability of RSV strains during five non-consecutive respiratory seasons, and evaluated the role of RSV subtypes, genotypes and viral loads on clinical disease severity. Methods: Healthy infants hospitalized with RSV bronchiolitis were prospectively enrolled and nasopharyngeal samples obtained within 24h of hospitalization for RSV load quantitation by PCR, typing and genotyping. Parameters of disease severity were assessed, and multivariate models constructed to identify virologic and clinical factors predictive of clinical outcomes. Results: From March 2004 to April 2011, we enrolled 253 patients (56.5 % males; median age 2.1 (1.1-4.0) months). RSV A infections predominated over RSV B (69% vs. 31%; p<0.001) and showed greater genotype variability. The most common genotypes were RSV A/GA2, A/GA5 and RSV B/BA. Infants infected with RSV GA5 had higher viral loads compared with GA2 or BA infection (p<0.01), independent of duration of symptoms. After adjusting for other covariates, RSV A/GA5 infections were associated with longer hospital stay. Conclusions: RSV A infections were more frequent than RSV B infections and displayed greater genetic variability. Infections with GA5 were independently associated with clinical disease severity.
2018-03-21 | GSE103842 | GEO
Project description:BackgroundBronchiolitis is a leading cause of infant hospitalization. Recent research suggests the heterogeneity within bronchiolitis and the relationship of airway viruses and bacteria with bronchiolitis severity. However, little is known about the pathobiological role of fungi. We aimed to identify bronchiolitis mycotypes by integrating fungus and virus data, and determine their association with bronchiolitis severity and biological characteristics.MethodsIn a multicentre prospective cohort study of 398 infants (age <1 year, male 59%) hospitalized for bronchiolitis, we applied clustering approaches to identify mycotypes by integrating nasopharyngeal fungus (detected in RNA-sequencing data) and virus data (respiratory syncytial virus [RSV], rhinovirus [RV]) at hospitalization. We examined their association with bronchiolitis severity-defined by positive pressure ventilation (PPV) use and biological characteristics by nasopharyngeal metatranscriptome and transcriptome data.ResultsIn infants hospitalized for bronchiolitis, we identified four mycotypes: A) fungiM.restrictavirusRSV/RV, B) fungiM.restrictavirusRSV, C) fungiM.globosavirusRSV/RV, D) funginot-detectedvirusRSV/RV mycotypes. Compared to mycotype A infants (the largest subtype, n = 211), mycotype C infants (n = 85) had a significantly lower risk of PPV use (7% vs. 1%, adjOR, 0.21; 95% CI, 0.02-0.90; p = 0.033), while the risk of PPV use was not significantly different in mycotype B or D. In the metatranscriptome and transcriptome data, mycotype C had similar bacterial composition and microbial functions yet dysregulated pathways (e.g., Fc γ receptor-mediated phagocytosis pathway and chemokine signaling pathway; FDR <0.05).InterpretationIn this multicentre cohort, fungus-virus clustering identified distinct mycotypes of infant bronchiolitis with differential severity risks and unique biological characteristics.FundingThis study was supported by the National Institutes of Health.
| S-EPMC10415709 | biostudies-literature
Project description:RationaleBronchiolitis is the most common lower respiratory infection in infants; however, it remains unclear which infants with bronchiolitis will develop severe illness. In addition, although emerging evidence indicates associations of the upper-airway microbiome with bronchiolitis severity, little is known about the mechanisms linking airway microbes and host response to disease severity.ObjectivesTo determine the relations among the nasopharyngeal airway metabolome profiles, microbiome profiles, and severity in infants with bronchiolitis.MethodsWe conducted a multicenter prospective cohort study of infants (age <1 yr) hospitalized with bronchiolitis. By applying metabolomic and metagenomic (16S ribosomal RNA gene and whole-genome shotgun sequencing) approaches to 144 nasopharyngeal airway samples collected within 24 hours of hospitalization, we determined metabolome and microbiome profiles and their association with higher severity, defined by the use of positive pressure ventilation (i.e., continuous positive airway pressure and/or intubation).Measurements and main resultsNasopharyngeal airway metabolome profiles significantly differed by bronchiolitis severity (P < 0.001). Among 254 metabolites identified, a panel of 25 metabolites showed high sensitivity (84%) and specificity (86%) in predicting the use of positive pressure ventilation. The intensity of these metabolites was correlated with relative abundance of Streptococcus pneumoniae. In the pathway analysis, sphingolipid metabolism was the most significantly enriched subpathway in infants with positive pressure ventilation use compared with those without (P < 0.001). Enrichment of sphingolipid metabolites was positively correlated with the relative abundance of S. pneumoniae.ConclusionsAlthough further validation is needed, our multiomic analyses demonstrate the potential of metabolomics to predict bronchiolitis severity and better understand microbe-host interaction.
| S-EPMC5649976 | biostudies-literature
Project description: Not available
| S-EPMC5992049 | biostudies-literature