Longitudinal investigation of the airway microbiota in children with chronic suppurative lung disease
Recurrent airway infection and its complications are the leading cause of death in Cystic Fibrosis (CF) but remain poorly understood. Molecular microbiology demonstrates that the CF airways are more polymicrobial than previously thought. The role of the microbiota in disease prognosis is unclear. There have been few longitudinal studies of the airway microbiota in children, partly because sampling the lower airways is difficult as many children cannot expectorate. Part one of this thesis
... this thesis determined whether upper airway samples could act as surrogates for the lower airway microbiota in children. Cough swabs [CS], throat swabs [TS] and lower airway samples (bronchoalveolar lavage and bronchial brushings) were collected for 16S rRNA gene sequencing. There was good correlation between TS and the lower airways at a community but not an individual level; TS distinguished disease differences, suggesting that they could be used in longitudinal studies of the airway microbiota in children. CS sequenced poorly, thus precluding their use for molecular microbiology. The longitudinal study had two arms; infants with CF diagnosed on newborn screening (NBS), in whom molecular microbiology revealed a small increase in diversity of the airway microbiota until 2 years of age; Streptococcus spp. and Haemophilus spp. were the most common organisms and showed an inverse relationship in their relative abundances over time. The second compared older children with CF with Primary Ciliary Dyskinesia (PCD), which shares a similar pathology to CF but rarely the same rate of disease progression. This revealed similar trends to those seen in NBS in the relative abundance of Streptococcus spp. and Haemophilus spp. in PCD but not in CF. This suggests that early changes in CF mirror those seen in later childhood in PCD and a switch occurs in CF during childhood from a milder to a more pathological community composition.