The Nasopharyngeal Microbiome is Perturbed During Respiratory Viral Infections and Asthmatic Exacerbations

Rationale: We employ a combination of next-generation sequencing methodologies to evaluate viral genomes and microbiomes of children with asthma exacerbations and controls with colds in order to compare clinical markers of... [ view full abstract ]

Rationale: We employ a combination of next-generation sequencing methodologies to evaluate viral genomes and microbiomes of children with asthma exacerbations and controls with colds in order to compare clinical markers of disease severity.

Methods:  Inpatient and children from emergency department visits, some with asthma exacerbations and children with colds without asthma are enrolled from two medical institutions in New Mexico and Arkansas.  We obtained nasal or nasopharyngeal swabs (NPS), Asthma Control Tests (ACT), and modified Jackson criteria (MJC). NPS were evaluated using the ResVir Panel, a hybridization-based genome sequencing method targeting 34 respiratory viruses. In addition, we sequenced the variable regions 4-6 of 16S ribosomal RNA gene.  The samples were sequenced in a high-throughput, multiplexed, rapid manner on the Illumina MiSeq. Clinical data was compared between viral induced asthma, asthma, viral induced colds, and colds.  Microbiome data was used to determine if specific bacteria or bacterial diversity were associated with viral infection, and viral-induced wheezing.

Results: ACT scores were lower in asthmatics with viruses compared to asthmatics without virus (med=17 (virus) vs. 20 (no virus); p<0.05).  Modified Jackson criteria scores for upper respiratory symptoms were similar between those subjects with viruses +/- asthma (med= 5 (virus asthma) and 6 (virus cold)).   Asthmatics with viruses had worse lower respiratory tract scores (med=8 (virus) and med=4 (no virus); p<0.05) than controls with virus.  We identified five microbiome profiles classified by dominant genus, Moraxella, Corynebacterium, Staphylococcus, Haemophilus, and Diverse. Controls were Moraxella-dominant in 52.9% and Diverse in 17.6%.  Asthmatics were 27.6% Moraxella-dominant and 37.9% Diverse. The microbiome of those subjects with RSV trended towards more species than the microbiome from subjects with other viruses (mean 362 (RSV) vs. 276 (Other viruses); p=0.055).

Conclusions:  Viral-induced asthma exacerbations are more likely to occur in children with less overall asthma control.  Lower respiratory symptoms are more pronounced in asthmatics with viruses than in their control counterparts. Asthmatics tend to have a more diverse nasopharyngeal microbiota.