Association of nasopharyngeal microbiota profiles with bronchiolitis severity in infants hospitalised for bronchiolitis

Abstract

Little is known about the relationship between specific composition of the airway microbiota and severity of bronchiolitis. We aimed to identify nasopharyngeal microbiota profiles and to link these profiles to acute severity in infants hospitalized for bronchiolitis. We conducted a multicenter prospective cohort study of 1005 infants (age <1 year) hospitalized for bronchiolitis over three winters, 2011-2014. By applying a 16S rRNA gene sequence and clustering approach to the nasopharyngeal aspirates collected within 24 hours of hospitalization, 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 distinct nasopharyngeal microbiota profiles – three profiles were dominated by either 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% vs 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 a Haemophilus-dominant profile (OR, 1.98; 95%CI, 1.08-3.62; P=0.03). These findings were externally validated in a separate cohort of 307 children hospitalized for bronchiolitis.

Respiratory microbiota and lower respiratory tract disease

“…In another large case-series published by the same author assessing the association of microbiota and bronchiolitis severity, Moraxella dominant profiles presented again the lowest risk of a negative outcome (defined as admission to the intensive care unit). 61 In this series, the profile with highest risk of negative outcome was the Haemophilus dominant one, consistent with most of the studies. Seasonal or geographical effects do not explain these discrepancies as most of the studies were conducted in the US in winter and merit further investigation.…”

Serum cathelicidin, nasopharyngeal microbiota, and disease severity among infants hospitalized with bronchiolitis

“…1 Although bronchiolitis has been considered virus-induced inflammation of small airways, 1 emerging evidence indicates that the pathogenesis involves a complex interplay among viral agents, airway microbiota, and the innate immune system. 2-4 …”

“…5 In prior studies, serum cathelicidin level was inversely associated with disease severity in children with bronchiolitis, 6 and administration of LL-37 (the main active form of human cathelicidin) altered the microbiota in animal models. 7 We have previously demonstrated that, in a cohort of infants with severe bronchiolitis (bronchiolitis requiring hospitalization), 4 infants with a Haemophilus -dominant nasopharyngeal microbiota profile had higher severity; however, host immune responses were not examined. In the present study, we sought to determine interactions between serum LL-37 levels and nasopharyngeal microbiota profiles with regard to disease severity by using the data from a prospective cohort of infants with severe bronchiolitis.…”

“…Briefly, this prospective cohort study, the 35th Multicenter Airway Research Collaboration (MARC-35), 4 enrolled infants (age <1 year) at 17 sites across 14 U.S. states (Table E1) during the 2011–2014 winter seasons. Bronchiolitis was defined per the American Academy of Pediatrics guidelines.…”

Bronquiolitis

“…Adicionalmente, aquellos pacientes con un perfil Dominante por Haemophilus y que tenían una infección concomitante por VSR tenían mayores probabilidades de quedar en cuidados intensivos (p=0.03). El estudio logró concluir, además, que pacientes con un perfil Dominante por Haemophilus tenían una mayor severidad de la bronquiolitis, al igual que mayor tiempo de estadía hospitalaria (12) .…”