Presence of antibiotic resistance genes in the lower airways microbiome of patients with chronic lung disease and healthy controls

<bold>Background:</bold> Resistance against antibiotics is an increasing health crisis worldwide. With Whole genome sequencing (WGS) it is possible to map the cumulative presence of antibiotic resistance genes (ARGs) in a microbial community. We aimed to compare the presence of ARGs in healthy subjects compared to patients with chronic lung disease. <bold>Methods:</bold> 93 patients with COPD, 13 with asthma, 34 with sarcoidosis, 12 with idiopathic pulmonary fibrosis (IPF), and 100 healthy controls were examined with bronchoscopy in the MicroCOPD and MicroILD studies. Broncheoalveolar lavage (BAL) was sampled, and WGS performed on the BAL samples after DNA extraction, using the Illumina NovaSeq platform. The National Database of Antibiotic Resistant Organisms (NDARO) from the NCBI was used to map the ARGs. <bold>Results:</bold> 16% of the controls had any ARG present, compared with 28% of COPD patients, 8% of asthma patients, 38% of sarcoidosis patients and 50% of IPF patients (p=0.007). Overall, ARGs against tetracycline was the most common ARG class (18%), beta-lactam resistance second (16%). In a logistic regression analysis adjusted for sex, age, body composition and smoking, the OR (95% CI) for having any ARGs in the lower airways was 1.94 (0.92-4.08) in COPD, 0.44 (0.05-3.76) in asthma, 3.23 (1.18-8.84) in sarcoidosis, and 4.28 (1.15-15.85) in IPF, compared with controls. More men than women had ARGs, OR 1.8 (0.93-3.46). <bold>Conclusion:</bold> The prevalence of ARGs in the lower airways microbiome was markedly higher in patients with sarcoidosis and IPF than in controls. There was a trend towards higher prevalence of ARGs in COPD patients and men, but these results were not statistically significant.