ena-STUDY-TEAGASC-11-09-2018-09:01:26:921-638
The lung microbiome in young children with cystic fibrosis: a longitudinal cohort study
Cystic fibrosis (CF) is an autosomal recessive condition with impaired mucociliary clearance and innate airway defences 1. Chronic airway infection and inflammation culminating in bronchiectasis are the main drivers of the morbidity and mortality of CF 1. There is good evidence these processes start early in life, with asymptomatic infants and pre-school children demonstrating clear associations between the presence of lower airway infection and inflammation and impaired lung function and structural airway changes 1,2.The use of 16S ribosomal RNA sequencing provides compelling evidence that CF airways are inhabited by diverse microbial communities 3-7. Perturbations in the CF airway microbiome are well described, however it is unclear what affect these have on the “infection-inflammation-structural damage” model of CF lung disease 3-12. Limited studies in young children with CF suggest microbial diversity is initially low but increases with age 3,7,9,11,12. In contrast, in older children and adults, diversity decreases with age and declining lung function 3,7,13,14. In adults, with advancing lung disease and repeated exposure to antibiotics over an extended period of time, dominant CF pathogens emerge in a relatively fixed microbiome with limited diversity 4,6,15,16.We aimed to describe the lower airway microbiome in clinically stable pre-school aged children with CF, and, using longitudinal data, explore how age influences its composition. Further analysis focused on comparing the CF microbiome with that of the non-CF lung and on examining the effect of airway inflammation and antibiotic use.
Cystic fibrosis (CF) is an autosomal recessive condition with impaired mucociliary clearance and innate airway defences 1. Chronic airway infection and inflammation culminating in bronchiectasis are the main drivers of the morbidity and mortality of CF 1. There is good evidence these processes start early in life, with asymptomatic infants and pre-school children demonstrating clear associations between the presence of lower airway infection and inflammation and impaired lung function and structural airway changes 1,2.The use of 16S ribosomal RNA sequencing provides compelling evidence that CF airways are inhabited by diverse microbial communities 3-7. Perturbations in the CF airway microbiome are well described, however it is unclear what affect these have on the “infection-inflammation-structural damage” model of CF lung disease 3-12. Limited studies in young children with CF suggest microbial diversity is initially low but increases with age 3,7,9,11,12. In contrast, in older children and adults, diversity decreases with age and declining lung function 3,7,13,14. In adults, with advancing lung disease and repeated exposure to antibiotics over an extended period of time, dominant CF pathogens emerge in a relatively fixed microbiome with limited diversity 4,6,15,16.We aimed to describe the lower airway microbiome in clinically stable pre-school aged children with CF, and, using longitudinal data, explore how age influences its composition. Further analysis focused on comparing the CF microbiome with that of the non-CF lung and on examining the effect of airway inflammation and antibiotic use.