The Impacts of COPD and Asthma on the Microbiome of the Airways

Historically it was believed that the airways were sterile, though recent studies have shown that although there is not a high number of microbes present, the respiratory tract does have a commensal microbial population. The microbiome of the airways is distributed throughout the respiratory tract, with 3 distinct populations in the oropharynx (which is more heavily colonized in healthy individuals), the bronchial tree and the lungs _[1,6]. The load in the lower respiratory tract is modulated by inhalation from the upper respiratory tract, mucociliary clearance and cellular innate immunity _[1].

COPD is characterized by largely irreversible airflow limitation, mucus hypersecretion, emphysema and small airway fibrosis. Patients experience acute exacerbations periods, where there is a worsening of respiratory symptoms _[6]. Frequently, these exacerbations result from bacterial infection and are therefore treated with antibiotics and inhaled corticosteroids that can alter the baseline respiratory microbiome _[1]. In COPD patients, the bronchial microbiome shows an increase in the abundance of Proteobacteria, which include a higher relative abundance of the genus Haemophilus, paralleled by a decrease in Bacteroidetes and Firmicutes; particularly Prevotella and Veillonella being the main genera affected _[1]. Maintaining a high diversity in the airway microbiome is hypothesised to aid in the management of COPD exacerbation symptoms within current research. Dicker et al reported both an increased exacerbation frequency and mortality in patients with low microbiome diversity and an increase of Haemophilus spp. in bronchial secretions _[2]. Similarly, Leitao et al reported that patients with higher microbial diversity in bronchial secretions when exacerbated had lower long-term mortality and Veillonella spp. were associated with a high one-year survival _[3].

Asthma is a chronic lung condition that encompasses a heterogeneous collection of disease entities. There are currently two classifications of asthma based on the immunopathogenesis, Type 2 (T2)-High Endotype and T2- Low Endotype _[4,5]. The T2- High classification is driven by the Type 2 immune response: a myriad of immune pathways including T helper 2 cell recruitment, the release of pro-inflammatory cytokines, eosinophil degranulation and mast cell activation _[5]. Adversely T2- Low endotype is based on clinical characteristics that include smoking, obesity and old age _[5]. A recent study isolated and cultivated bacteria from asthmatics and healthy controls via bronchoscopic brushings to study the characteristics of the airway microbiome _[6]. A Whitley Workstation was used to optimally grow anaerobic bacteria collected. The group found a of loss of diversity and pathobiont expansion within asthma patients and a significant difference in airway community species abundance _[6]. From this, further research into the role of microbial community instability in acute exacerbations of lung disease and how repairing dysbiotic airway microbial communities is needed and may help in asthma and COPD treatments.

Written by DWS Microbiologist, Charlotte Austin

References

1. L. Millares, E. Monso (2022) The Microbiome in COPD: Emerging Potential for Microbiome-Targeted Interventions. International Journal of Chronic Obstructive Pulmonary Disease 17, 1835-1845.
2. lison J. Dicker, Jeffrey T.J. Huang, Mike Lonergan, Holly R. Keir, Christopher J. Fong, Brandon Tan, Andrew J. Cassidy, Simon Finch, Hana Mullerova, Bruce E. Miller, Ruth Tal-Singer, James D. Chalmers (2021) The sputum microbiome, airway inflammation, and mortality in chronic obstructive pulmonary disease Journal of Allergy and Clinical Immunology 147, 158-167
3. F. Leitao, N. Alotaibi, D. Ngan, S. Tam, J. Yang, Z. Hollander, V. Chen, M. FitzGerald, C. Nislow, J. Leung, P. Man, D. Sin (2019) Sputum Microbiome Is Associated with 1-Year Mortality after Chronic Obstructive Pulmonary Disease Hospitalizations American Journal of Respiratory and Critical Care Medicine 199(10):1205–1213
4. Silpa T Taunk, Juan C. Cardet, Dennis K. Ledford (2022) Clinical implications of asthma endotypes and phenotypes Allergy and Asthma Proceedings 
5. M. Kuruvilla, F. Lee, and G. Lee (2019) Understanding Asthma Phenotypes, Endotypes, and Mechanisms of Disease Clinical reviews in allergy & immunology 56(2): 219–233
6. L. Cuthbertson, U. Löber, JS. Ish-Horowicz, C. McBrien, C. Churchward, J. Parker, M. Olanipekun, C. Burke, O. O’Carroll, J. Faul, G. Davies, K. Lewis, J. Hopkin, J. Creaser-Thomas, R. Goshal, K. Fan Chung, S. Piatek, S. Willis-Owen, T. Bartolomaeus, T. Birkner, S. Dwyer, N. Kumar, E. Turek, A. Musk, J. Hui, M. Hunter, A. James, M. Dumas, S. Filippi, M. Cox, T. Lawley, S. Forslund, M. Moffatt, W. Cookson (2022) Genomic and ecologic characteristics of the airway microbial- mucosal complex bioRxiv

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