Microbial and clinical factors are related to recurrence of symptoms after childhood lower respiratory tract infection

Childhood lower respiratory tract infections (LRTI) are associated with dysbiosis of the nasopharyngeal microbiota, and persistent dysbiosis following the LRTI may in turn be related to recurrent or chronic respiratory problems. Therefore, we aimed to investigate microbial and clinical predictors of early recurrence of respiratory symptoms as well as recovery of the microbial community following hospital admission for LRTI in children. To this end, we collected clinical data and characterised the nasopharyngeal microbiota of 154 children (4 weeks–5 years old) hospitalised for a LRTI (bronchiolitis, pneumonia, wheezing illness or mixed infection) at admission and 4–8 weeks later. Data were compared to 307 age-, sex- and time-matched healthy controls. During follow-up, 66% of cases experienced recurrence of (mild) respiratory symptoms. In cases with recurrence of symptoms during follow-up, we found distinct nasopharyngeal microbiota at hospital admission, with higher levels of Haemophilus influenzae/haemolyticus, Prevotella oris and other gram-negatives and lower levels of Corynebacterium pseudodiphtheriticum/propinquum and Dolosigranulum pigrum compared with healthy controls. Furthermore, in cases with recurrence of respiratory symptoms, recovery of the microbiota was also diminished. Especially in cases with wheezing illness, we observed a high rate of recurrence of respiratory symptoms, as well as diminished microbiota recovery at follow-up. Together, our results suggest a link between the nasopharyngeal microbiota composition during LRTI and early recurrence of respiratory symptoms, as well as diminished microbiota recovery after 4–8 weeks. Future studies should investigate whether (speed of) ecological recovery following childhood LRTI is associated with long-term respiratory problems

Substantial burden of non-medically attended RSV infection in healthy term infants – an international prospective birth cohort study

Background: During the first year of life, one in four infants develops a symptomatic respiratory syncytial virus (RSV) infection, yet only half seek medical attention. The current focus on medically attended RSV, therefore, underrepresents the true societal burden of RSV. We assessed the burden of non-medically attended RSV infections and compared them with medically attended RSV. Methods: We performed active RSV surveillance until the age of one year in a cohort (n=993) nested within RESCEU, a prospective birth cohort study enrolling healthy term-born infants in five European countries. Parent-reported daily symptoms, medication use, wheezing and impact on family life were analyzed. Results: For 97 of 120 (80.1%) non-medically attended RSV episodes sufficient data were available for analysis. In 50.5% (49/97), symptoms lasted ≥15 days. Parents reported impairment in usual daily activities in 59.8% (58/97), worries in 75.3% (73/97), anxiety in 34.0% (33/97), and work absenteeism in 10.8% (10/93) of episodes. Compared with medically attended RSV (n=102, 9 hospital admissions), ReSViNET severity scores were lower (3.5 vs. 4.6, p<0.001), whereas durations of respiratory symptoms and impairment of usual activities were comparable. Conclusion: Even when medical attendance is not required, RSV infection poses a substantial burden to infants, families and society at large. These findings are important for policymakers when considering the implementation of RSV immunization in national programs

Nasopharyngeal microbiota in children is associated with severe asthma exacerbations

Background: The respiratory microbiome has been associated with the etiology and disease course of asthma. Objective: We sought to assess the nasopharyngeal microbiota in children with a severe asthma exacerbation and their associations with medication, air quality, and viral infection. Methods: A cross-sectional study was performed among children aged 2 to 18 years admitted to the medium care unit (MCU; n = 84) or intensive care unit (ICU; n = 78) with an asthma exacerbation. For case-control analyses, we matched all cases aged 2 to 6 years (n = 87) to controls in a 1:2 ratio. Controls were participants of either a prospective case-control study or a longitudinal birth cohort (n = 182). The nasopharyngeal microbiota was characterized by 16S-rRNA-gene sequencing. Results: Cases showed higher Shannon diversity index (ICU and MCU combined; P = .002) and a distinct microbial community composition when compared with controls (permutational multivariate ANOVA R2 = 1.9%; P &lt; .001). We observed significantly higher abundance of Staphylococcus and “oral” taxa, including Neisseria, Veillonella, and Streptococcus spp. and a lower abundance of Dolosigranulum pigrum, Corynebacterium, and Moraxella spp. (MaAsLin2; q &lt; 0.25) in cases versus controls. Furthermore, Neisseria abundance was associated with more severe disease (ICU vs MCU MaAslin2, P = .03; q = 0.30). Neisseria spp. abundance was also related with fine particulate matter exposure, whereas Haemophilus and Streptococcus abundances were related with recent inhaled corticosteroid use. We observed no correlations with viral infection. Conclusions: Our results demonstrate that children admitted with asthma exacerbations harbor a microbiome characterized by overgrowth of Staphylococcus and “oral” microbes and an underrepresentation of beneficial niche-appropriate commensals. Several of these associations may be explained by (environmental or medical) exposures, although cause-consequence relationships remain unclear and require further investigations.</p

Nasopharyngeal microbiota in children is associated with severe asthma exacerbations

Background: The respiratory microbiome has been associated with the etiology and disease course of asthma. Objective: We sought to assess the nasopharyngeal microbiota in children with a severe asthma exacerbation and their associations with medication, air quality, and viral infection. Methods: A cross-sectional study was performed among children aged 2 to 18 years admitted to the medium care unit (MCU; n = 84) or intensive care unit (ICU; n = 78) with an asthma exacerbation. For case-control analyses, we matched all cases aged 2 to 6 years (n = 87) to controls in a 1:2 ratio. Controls were participants of either a prospective case-control study or a longitudinal birth cohort (n = 182). The nasopharyngeal microbiota was characterized by 16S-rRNA-gene sequencing. Results: Cases showed higher Shannon diversity index (ICU and MCU combined; P = .002) and a distinct microbial community composition when compared with controls (permutational multivariate ANOVA R2 = 1.9%; P &lt; .001). We observed significantly higher abundance of Staphylococcus and “oral” taxa, including Neisseria, Veillonella, and Streptococcus spp. and a lower abundance of Dolosigranulum pigrum, Corynebacterium, and Moraxella spp. (MaAsLin2; q &lt; 0.25) in cases versus controls. Furthermore, Neisseria abundance was associated with more severe disease (ICU vs MCU MaAslin2, P = .03; q = 0.30). Neisseria spp. abundance was also related with fine particulate matter exposure, whereas Haemophilus and Streptococcus abundances were related with recent inhaled corticosteroid use. We observed no correlations with viral infection. Conclusions: Our results demonstrate that children admitted with asthma exacerbations harbor a microbiome characterized by overgrowth of Staphylococcus and “oral” microbes and an underrepresentation of beneficial niche-appropriate commensals. Several of these associations may be explained by (environmental or medical) exposures, although cause-consequence relationships remain unclear and require further investigations.</p

Maturation of the infant respiratory microbiota, environmental drivers and health consequences: a prospective cohort study

Rationale: Perinatal and postnatal influences are presumed important drivers of the early-life respiratory microbiota composition. We hypothesized that the respiratory microbiota composition and development in infancy is affecting microbiota stability and thereby resistance against respiratory tract infections (RTIs) over time. Objectives: To investigate common environmental drivers, including birth mode, feeding type, antibiotic exposure, and crowding conditions, in relation to respiratory tract microbiota maturation and stability, and consecutive risk of RTIs over the first year of life. Methods: In a prospectively followed cohort of 112 infants, we characterized the nasopharyngeal microbiota longitudinally from birth on (11 consecutive sample moments and the maximum three RTI samples per subject; in total, n = 1,121 samples) by 16S-rRNA gene amplicon sequencing. Measurements and Main Results: Using a microbiota-based machine-learning algorithm, we found that children experiencing a higher number of RTIs in the first year of life already demonstrate an aberrant microbial developmental trajectory from the first month of life on as compared with the reference group (0-2 RTIs/yr). The altered microbiota maturation process coincided with decreased microbial community stability, prolonged reduction of Corynebacterium and Dolosigranulum, enrichment of Moraxella very early in life, followed by later enrichment of Neisseria and Prevotella spp. Independent drivers of these aberrant developmental trajectories of respiratory microbiota members were mode of delivery, infant feeding, crowding, and recent antibiotic use. Conclusions: Our results suggest that environmental drivers impact microbiota development and, consequently, resistance against development of RTIs. This supports the idea that microbiota form the mediator between early-life environmental risk factors for and susceptibility to RTIs over the first year of life