When specific networks of bacteria are present in the upper airway microbiome during a respiratory illness, particularly during the fall, the risk for an exacerbation is increased in children with asthma, according to a study published in the Journal of Allergy and Clinical Immunology.

Susan V. Lynch, PhD, and colleagues also found that interactions between specific bacterial networks and host gene expression increased the risk for exacerbation. “Seasonal variation in asthma exacerbations, with a marked increase in incidence in the fall, is a well-described phenomenon,” Dr. Lynch says. “We reasoned that this may be due to seasonal dynamics in the upper airway microbiota. We further considered that season-specific interactions between discrete groups of upper airway microbes and epithelial gene expression could increase the risk for asthma exacerbation following a fall respiratory illness.”

The study assessed the nasal samples from children aged 6-17 with exacerbation-prone asthma who were enrolled in the Mechanisms Underlying Asthma Exacerbations Prevented and Persistent With Immune-based Therapy (MUPPITS-1)  trial. Samples were collected during a baseline visit and within 3 days of the onset of any symptoms of an upper respiratory illness. For the illness events, the patient was deemed to have an exacerbation if systemic corticosteroids or hospitalization were required. All samples underwent bacterial and fungal biomarker sequencing and virus detection via multiplex PCR.

Respiratory Illnesses & Asthma Exacerbations Showed Seasonal Trend

Among the 208 children with asthma enrolled in MUPPITS-1, there were 164 respiratory illnesses and 143 asthma exacerbations, both of which showed seasonal trends, with the highest incidence in the fall and winter. The bacterial composition of the nasal microbiota varied seasonally irrespective of whether children were relatively healthy or were experiencing respiratory illness. In the spring, an increase in Moraxella taxa was observed, whereas in the fall, there was an increase in Staphylococcus species. Seasonal variation in fungal species was found only in the illness samples, with enrichment for Malassezia in the spring and for Candida and Cladosporium in the fall.

Among the illness samples, season-specific links with nasal microbiota, virus detection, and exacerbations were observed. During the fall, respiratory illnesses and subsequent exacerbations were associated with members of the pathogenic bacteria Moraxella and Haemophilus, which were found to be enriched in patients who had virus positive respiratory illnesses and those who progressed to exacerbations. Similar associations were not observed for other seasons. Additionally, neither baseline nor illness fungal composition were linked with exacerbation risk.

“The airway microbiota is dynamic and exhibits seasonal dynamics,” Dr. Lynch explains. “It is only when this aspect is considered in statistical models that key microbial-host interactions are uncovered that relate to asthma exacerbation risk following a respiratory illness. More specifically, fall asthma exacerbations appear to be related to upper airway microbiota, while those experienced during other seasons appear to be due to other exposures (Figure).

Bacterial Microbiota Varied by Age of Children

When examining the baseline samples, the nasal bacterial microbiota composition differed by age. Older children were found to have nasal enrichment of several Staphylococcus and Corynebacterium members, whereas younger children exhibited enrichment for Moraxella, Haemophilus, and Alloiococcus taxa. Bacterial composition of the nasal microbiota at baseline did not correlate with time to respiratory illness but was correlated with time to exacerbation.

Similarly, fungal composition of the nasal microbiota varied by age. Malassezia taxon were associated with older children, whereas distinct members of Ascochyta, Malassezia, Cladosporium, and Verticillium were associated with younger children. Fungal communities at baseline were not associated with time to first illness; however, enrichment of Cladosporium was associated with a longer duration to respiratory illness.

Interactions Between Microbial Networks & Immune Transcriptional Modules

Two discrete bacterial networks exhibited opposing interactions with a group of genes expressed during exacerbation, including SMAD3. The first bacterial network was primarily made up of Streptococcus but also included Veillonella, Neisseria, and Haemophilus, whereas the second bacterial network was entirely made up of Staphylococcus members. An increased risk for exacerbation was observed in children with increased SMAD3 expression and a higher abundance of the Streptococcus network (OR, 14.71; 95% CI, 1.50-144.14; P=0.018). Children were also at increased risk for exacerbation if they exhibited increased SMAD3 expression and a reduced abundance of bacteria from the Staphylococcus network (OR, 39.17; 95% CI, 2.44-626.48; P=0.008), suggesting that the presence of this network of bacteria may be protective against asthma exacerbation. The bacterial  networks were not inversely related or mutually exclusive, and when they were considered outside of their relationship with SMAD3, the odds of exacerbation were significantly lower (OR, 3.22; 95% CI, 1.28-8.07; P=0.01), indicating that it is specifically the interaction of these groups of bacteria with the host that governs risk of subsequent exacerbation.

“Our study shows that the risk for asthma exacerbation following a respiratory illness is significantly increased in the fall when a specific network of co-associated bacteria, including Streptococcus and Haemophilus, colonizes the upper airways,” Dr. Lynch says. “It indicates that season-specific exposures may precipitate asthma exacerbations and that in the fall, bacterial colonization of the upper airways influences risk for post-respiratory illness exacerbation in school-aged children.”