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Rationale: Long-term antibiotic use for managing chronic respiratory disease is increasing; however, the role of the airway resistome and its relationship to host microbiomes remains unknown. Objectives: To evaluate airway resistomes and relate them to host and environmental microbiomes using ultradeep metagenomic shotgun sequencing. Methods: Airway specimens from 85 individuals with and without chronic respiratory disease (severe asthma, chronic obstructive pulmonary disease, and bronchiectasis) were subjected to metagenomic sequencing to an average depth exceeding 20 million reads. Respiratory and device-associated microbiomes were evaluated on the basis of taxonomical classification and functional annotation including the Comprehensive Antibiotic Resistance Database to determine airway resistomes. Co-occurrence networks of gene–microbe association were constructed to determine potential microbial sources of the airway resistome. Paired patient-inhaler metagenomes were compared (n = 31) to assess for the presence of airway–environment overlap in microbiomes and/or resistomes. Measurements and Main Results: Airway metagenomes exhibit taxonomic and metabolic diversity and distinct antimicrobial resistance patterns. A “core” airway resistome dominated by macrolide but with high prevalence of β-lactam, fluoroquinolone, and tetracycline resistance genes exists and is independent of disease status or antibiotic exposure. Streptococcus and Actinomyces are key potential microbial reservoirs of macrolide resistance including the ermX, ermF, and msrD genes. Significant patient-inhaler overlap in airway microbiomes and their resistomes is identified where the latter may be a proxy for airway microbiome assessment in chronic respiratory disease. Conclusions: Metagenomic analysis of the airway reveals a core macrolide resistome harbored by the host microbiome.

Patients admitted with acute exacerbations of bronchiectasis are a distinct population who has a significant morbidity and mortality. There are no known evidence based clinical pathways for the inpatient management of these patients. Aim: To evaluate the feasibility, safety and efficacy of an evidence based clinical pathway designed for in-hospital management of patients with acute exacerbations of bronchiectasis. Method: A retrospective analysis on all adult patients admitted with acute exacerbations of bronchiectasis between November 2013 and April 2014. Age, sex, length of hospital stay and co-morbidities were established. Patients were divided into 2 groups: 1) care pathway group (CP) and (2) non care pathway group (non-CP). The efficacy is defined as the event rate of recurrent hospitalization with acute bronchiectasis exacerbation within 30 days post discharge. The safety outcome is defined as the rate of mortality within 30 days post discharge. Results: A total of 125 patients were identified. 34 patients were in CP and 91 patients in non-CP group. There were no significant differences in age, gender and co-morbidities between the 2 groups. The median (IQR) length of hospital stay was significantly lower in the CP than the non-CP (4(3-6) vs 6(3-10) days; p=0.023). The readmission rate was 9% in the CP and 20% in non-CP (p=NS). The mortality was similar in both groups (9% vs 10%, p=NS). Conclusion: Our data suggests that managing patients with acute exacerbations of bronchiectasis using a clinical pathway specifically designed for this group of patients is feasible, safe and efficacious with the potential of reducing hospital length of stay.