Viral Infections and Their Impact on the Respiratory Microbiome in Pediatric Patients with Cystic Fibrosis

Rationale:   Viruses are known to impact clinical status in patients with cystic fibrosis (CF); however their effects on the respiratory microbiome are unclear. The goal of our study is to assess changes in the lung microbiome of pediatric patients with CF during periods of wellness and exacerbation, with a focus on the impact of viral infection, using culture-dependent and independent techniques. Our hypothesis is that viruses impact the respiratory microbiome leading to worse clinical sequelae during exacerbation.

Methods:  In this prospective, longitudinal study we recruited 101 pediatric patients with CF, ages 0-22 years. We collected oropharyngeal swab, sputum, and BAL samples from subjects during their clinical baseline and exacerbation states. We used Illumina sequencing and standard culture for bacterial detection and quantitative RT-PCR techniques for viral detection. 

Results: We collected 380 samples from 102 subjects between March, 2013 and June, 2014. Seventy-three samples are virus positive and 307 are virus negative. The most prevalent viruses in our cohort are rhinovirus/enterovirus and coronavirus.  Virus (+) samples are associated with a greater prevalence of traditional CF pathogens (p = 0.0018).  We found no clear relationship between viral infections and clinical status or lung function.  Using deep-sequencing, we defined 1,772 OTUs rarified to 10,000 reads and found some changes in relative abundances of organisms in virus (+) compared to virus (-) samples, particularly prevotella species.

Conclusions: Detection of viruses in pediatric patients with CF may predict subsequent infection with traditional CF pathogens.  Viruses may also be associated with subtle changes in the microbiome but further analysis is needed.