Abstract
BackgroundWith the continued advancement of CFTR modulator therapies there is likely to be a burgeoning population of adult cystic fibrosis (CF) patients unable to expectorate sputum. Consequently, the detection and surveillance of pulmonary colonisation, previously reliant on sputum culture, needs re-examining. We hypothesised that cough swabs analysed with culture-independent analysis of the 16S gene could serve as a surrogate for colonisation of the lower airways. MethodsCough swabs and sputum samples were prospectively collected from consecutive adults and children with CF across two sites at regular outpatient appointments. Conventional culture analysis and next generation sequencing were used to compare paired same day samples. ResultsTwenty-two adults and 8 paediatric patients provided 75 paired cough swabs and sputum samples. Alpha diversity measures showed increased bacterial richness in sputum, while evenness and Simpson's diveristy index were higher in cough swabs. Within each sampling technique, microbial composition showed greater similarity when considering intra-patient variation. Poor concordance was observed between culture independent cough swabs and culture dependent/independent sputum analysis for specific pathogens, with cough swabs unable to accurately identify commonly associated CF pathogens (AUROCC range: 0.51 to 0.64). ConclusionCulture independent analysis of cough swabs provides an inaccurate diagnosis of lower respiratory tract colonisation and should not be used as a diagnostic test in patients with CF.
Highlights
Cystic fibrosis (CF) is the result of a disorder in the cystic fibrosis transmembrane conductance regulator (CFTR) gene and is characterised by thick mucus formation in multiple organs
Thirty adult and 25 paediatric CF patients were recruited from outpatient clinics at Amsterdam University Medical Centres (UMC) and were eligible for inclusion if they had (i) CF diagnosis based on clinical symptoms in combination with an abnormal sweat test and/or identification of mutations in both alleles of the CFTR gene [14], (ii) stable respiratory disease for at least 6 weeks and (iii) ability to perform lung function testing
This study aimed to establish the validity of cough swab identification for the most clinically relevant bacterial species associated with pulmonary exacerbations in CF, along with bacterial species that have showed increasing prevalence [24,25,26,27]
Summary
Cystic fibrosis (CF) is the result of a disorder in the cystic fibrosis transmembrane conductance regulator (CFTR) gene and is characterised by thick mucus formation in multiple organs. Treatment of CF has been revolutionised in last decade by the introduction of CFTR modulator therapies and increased focus on eradication of colonising pathogens in children and young adults. With the continued advancement of CFTR modulator therapies there is likely to be a burgeoning population of adult cystic fibrosis (CF) patients unable to expectorate sputum. We hypothesised that cough swabs analysed with culture-independent analysis of the 16S gene could serve as a surrogate for colonisation of the lower airways. Results: Twenty-two adults and 8 paediatric patients provided 75 paired cough swabs and sputum samples.
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