2Bronchiectasis is accompanied by chronic bronchial infection that may drive disease progression.3 However, the evidence base for antibiotic therapy is limited. DNA based methods offer better 4 identification and quantification of microbial constituents of sputum than standard clinical culture and 5 may help inform patient management strategies. Our study objective was to determine the longitudinal 6 variability of the non-CF bronchiectasis microbiome in sputum with respect to clinical variables. 7 Eighty-five patients with non-cystic fibrosis (CF) bronchiectasis and daily sputum production were 8 recruited from outpatient clinics and followed for six months. Monthly sputum samples and clinical 9 measurements were taken, together with additional samples during exacerbations. 16S rRNA gene 1 0 sequencing of the sputum microbiota was successful for 381 samples from 76 patients and analysed 1 1 in conjunction with clinical data.

Chronic obstructive pulmonary disease (COPD) is a smoking-related illness affecting 64 million people worldwide. Airway infection drives recurrent exacerbations and lung function decline. Prophylactic antibiotics may prevent exacerbations but their use is a significant cause of population antimicrobial resistance.We characterised the sputum microbiome by 16S rRNA gene analysis using 138 samples collected during a randomised controlled trial of prophylactic antibiotics in 71 patients with stable COPD. On comparing the profile of the microbiome obtained by sequencing to the isolates grown from samples using standard culture, there were similarities overall, although with a much narrower spectrum of genera on culture with under-representation of certain genera including Veillonella and Prevotella. There was concordance in the most abundant genera within samples and the number of isolates cultured reflected the measured bacterial diversity.We found that at baseline the microbiota of 17 (24%) patients were dominated by Haemophilus influenzae, accompanied by narrowed microbial diversity and higher levels of sputum inflammatory cytokines. Different H. influenzae strains co-existed within individuals. Opportunistic whole genome sequencing of six H. influenzae isolates obtained during the study revealed that all were non-typeable H. influenzae (NTHI), with a range of different antibiotic resistance gene profiles, but an identical complement of virulence genes.Administration of 13 weeks prophylaxis with moxifloxacin, azithromycin or doxycycline revealed distinctive changes in microbial communities for each group. Haemophilus numbers reduced by 90% compared to placebo only after moxifloxacin, and significant reduction in sputum cytokines occurred in patients dominated by Haemophilus at baseline. Haemophilus influenzae dominance defines COPD patients with active disease who may particularly benefit from antibiotics or vaccination.