Patients with chronic lung disease may have a higher prevalence of antimicrobial resistance genes in the lower airway microbiome compared with healthy controls, with the largest differences observed among patients with sarcoidosis and idiopathic pulmonary fibrosis, according to a recent study.
Researchers collected and analyzed the bronchoalveolar lavage samples from 263 participants drawn from the MicroCOPD and MicroILD cohorts in Western Norway between 2012 and 2016. Among them were 100 healthy controls as well as 93 participants with chronic obstructive pulmonary disease (COPD), 34 with sarcoidosis, 13 with asthma, 12 with idiopathic pulmonary fibrosis (IPF), and 11 with unclassifiable interstitial lung disease (ILD). The participants hadn't used antibiotics in the 14 days prior to their bronchoscopy.
The researchers used bronchoscopy with protected, sterile sampling with catheters designed to minimize contamination from the upper airway to obtain samples from the middle lobe followed by shotgun metagenomic sequencing to characterize the airway resistome. DNA was extracted and sequenced using an Illumina NovaSeq 6000 in paired-end 150 bp mode, and antimicrobial resistance genes were identified through alignment with the National Database of Antibiotic-Resistant Organisms. Read counts were normalized to counts per million.
Across all study groups, tetracycline resistance genes were detected in 33% of the samples followed by beta-lactam (26%) and macrolide resistance genes (26%). Additionally, the researchers detected antimicrobial resistance genes in 38% of healthy controls compared with 39% of the patients with asthma, 51% of those with COPD, 65% of those with sarcoidosis, and 83% of those with IPF.
Multivariable regression analyses adjusting for age, sex, body composition, smoking status, and antibiotic exposure showed that patients with sarcoidosis and IPF had a respective 3.5 and 6.4 higher odds of harboring antimicrobial resistance genes compared with controls. The risk of carrying antibiotic-resistance genes was statistically insignificant between the participants with COPD and asthma and controls.
Differences also emerged in the relative abundance of resistance genes. The patients with sarcoidosis and IPF had higher normalized counts across multiple antibiotic resistance genes
Recent antibiotic exposure was associated with higher resistome burden. Participants who reported antibiotic use within 3 months prior to bronchoscopy had mean resistance gene counts of 404 counts per million compared with 198 counts per million among those without recent exposure. Antibiotic use within the previous 3 or 12 months increased the likelihood of detecting resistance genes in several analyses.
Among patients with COPD, subgroup analyses showed that those with two or more exacerbations in the previous year had an increased risk of tetracycline resistance genes, even following adjustment for antibiotic exposure within the last 1 year. Lung function and inhaled steroid use weren't associated with the presence of antibiotic resistance genes.
The study had several limitations. The cross-sectional design prevented causal interpretation, and small sample sizes in the asthma, IPF, and unclassifiable ILD groups limited subgroup analyses. Antibiotic exposure was self-reported and didn't include details on specific antibiotics taken. Sampling from a single lung lobe may not represent the full pulmonary microbiome, and metagenomic analyses depend on evolving resistance gene databases.
The findings underscored that "antibiotic use impacts the presence of antibiotic resistance mechanisms in [the] microbiome,” wrote lead study author Guri D. Kringeland, of the Department of Clinical Science in the Faculty of Medicine at the University of Bergen as well as of the Department of Thoracic Medicine at the Haukeland University Hospital in Norway, and colleagues.
Lead study author Guri D. Kringeland declared lecture fees from Boehringer Ingelheim, co–study author Kristel S. Knudsen declared lecture fees from AstraZeneca, co–study author Rune Nielsen declared grants from Sanofi and AstraZeneca, and co–study author Tomas M. L. Eagan declared grant from GSK and lecture fees from Boehringer Ingelheim and AstraZeneca. The study authors reported no other competing interests.
Source: BMJ Open Respiratory Research