Abstract
BackgroundUpper airway cultures guide the identification and treatment of lung pathogens in infants with cystic fibrosis (CF); however, this may not fully reflect the spectrum of bacteria present in the lower airway. Our objectives were to characterize the airway microbiota using bronchoalveolar lavage fluid (BALF) from asymptomatic CF infants during the first year of life and to investigate the relationship between BALF microbiota, standard culture and clinical characteristics.MethodsBALF, nasopharyngeal (NP) culture and infant pulmonary function testing data were collected at 6 months and one year of age during periods of clinical stability from infants diagnosed with CF by newborn screening. BALF was analyzed for total bacterial load by qPCR and for bacterial community composition by 16S ribosomal RNA sequencing. Clinical characteristics and standard BALF and NP culture results were recorded over five years of longitudinal follow-up.Results12 BALF samples were collected from 8 infants with CF. Streptococcus, Burkholderia, Prevotella, Haemophilus, Porphyromonas, and Veillonella had the highest median relative abundance in infant CF BALF. Two of the 3 infants with repeat BALF had changes in their microbial communities over six months (Morisita-Horn diversity index 0.36, 0.38). Although there was excellent percent agreement between standard NP and BALF cultures, these techniques did not routinely detect all bacteria identified by sequencing.ConclusionsBALF in asymptomatic CF infants contains complex microbiota, often missed by traditional culture of airway secretions. Anaerobic bacteria are commonly found in the lower airways of CF infants.
Highlights
Progressive, obstructive lung disease remains the biggest cause of morbidity and early mortality in cystic fibrosis (CF)
bronchoalveolar lavage fluid (BALF), nasopharyngeal (NP) culture and infant pulmonary function testing data were collected at 6 months and one year of age during periods of clinical stability from infants diagnosed with CF by newborn screening
BALF was analyzed for total bacterial load by Quantitative polymerase chain reaction (qPCR) and for bacterial community composition by 16S ribosomal RNA sequencing
Summary
Progressive, obstructive lung disease remains the biggest cause of morbidity and early mortality in cystic fibrosis (CF). Standard-of-care requires a quarterly airway culture from all CF patients, seeking to identify treatable bacteria that may alter the airway environment and lead to more aggressive lung disease. This targeted view of bacterial infection and CF lung disease does not reveal the full extent of polymicrobial communities in the airway, given traditional culture is limited in its scope. Culture-independent approaches using next-generation sequencing techniques in infants and children have revealed a more complex, polymicrobial community in the CF upper airway than previously identified using traditional culture, determining which microbiota residing in the upper airway are present in the lower airway has proved to be challenging [5,6]. Our objectives were to characterize the airway microbiota using bronchoalveolar lavage fluid (BALF) from asymptomatic CF infants during the first year of life and to investigate the relationship between BALF microbiota, standard culture and clinical characteristics
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