Bacterial colonisation is an important predictor of exacerbation in alpha-1 antitrypsin deficiency (AATD)-related chronic obstructive pulmonary disease (COPD) and could indicate the need for additional targeted therapy, a recent study has reported.
AATD predisposes individuals to lung damage, heightening their susceptibility to chronic bacterial colonisation and recurrent respiratory exacerbations.
This first-of-its-kind study aimed to determine the prevalence of potentially pathogenic microorganisms in the sputum of AATD-COPD patients – including those with bronchiectasis – and assess how colonisation affects exacerbation risk.
Sputum was collected from patients with AATD-related COPD during stable and exacerbation periods, then cultured for respiratory pathogens. Mild and severe deficiency genotypes were included to explore any differences in pathogen frequency related to AAT level or genotype.
Measuring bacterial lung colonisation
A total of 995 sputum samples from 91 patients were analysed and 29 (32%) had radiological bronchiectasis.
In stable AATD disease, sputum positivity for potentially pathogenic microorganisms was higher in those with bronchiectasis (72.8%) compared to those without (55.5%). A similar finding was observed during exacerbations at 87.9 % versus 66.4 %.
During exacerbations, the median total bacterial load increased in both groups, and Pseudomonas species predominated in bronchiectasis. Isolation of Pseudomonas, S. aureus, M. catarrhalis, or ‘other’ pathogens in the stable state were independently associated with increased odds of future exacerbation, whereas H. influenzae, S. pneumoniae, presence of bronchiectasis, or current smoking were not.
Targeted exacerbation management for AATD
Clinicians should be alert to these bacterial profiles in AATD-COPD patients, especially those with bronchiectasis, as repeated exacerbations can accelerate lung damage.
Indeed, the study authors advised that ‘identifying AATD subjects with bacterial colonisation may establish the need for additional treatment strategies’ and that such patients ‘could benefit from additional, targeted therapy’ to optimise their disease management.
The authors acknowledged a study limitation of a lack of recent antibiotic usage patient data and bacterial strain-level analysis, underscoring the need for deeper microbiological investigations. Clarifying these relationships could further guide infection management and ultimately enhance clinical outcomes for this high-risk population.
Considering future research to build on this study, the study authors suggested exploring the impact of bacterial colonisation on lung function, inflammation and quality of life, as well as using advanced molecular techniques to map the lung microbiome.
An ongoing investigation by this group is also examining how ‘triple therapy inhalers’ and azithromycin influence bacterial colonisation in this patient cohort.
Reference
Spittle DA et al. Bacterial colonisation doubles the risk of exacerbation in alpha-1 antitrypsin deficiency. Respir Med. 2025 Apr-May;240:108025.
