The Role of the Lung Microbiome in Asthma

Abstract Rationale: Emerging evidence suggests that the lung microbiome plays a critical role in asthma, impacting pathophysiology, clinical presentation and treatment outcomes. This study investigates microbial profiles across asthma phenotypes and their association with treatment responses, aiming to inform personalized asthma therapies. Methods: This observational study enrolled patients from the Respiratory outpatient department at Beaumont Hospital between October 2023 and October 2024. Four in person visits were carried out over a three month period. The study population included non-asthma controls, those with Th2 inflammation without asthma and asthma (Th2 high/low). Blood, oral rinse, nasal swab and induced sputum were collected for microbiome analysis. Asthma control and comorbidity data were obtained through validated questionnaires. Spirometry and impulse oscillometry were used to assess respiratory function, while data on adherence, treatment changes, and exacerbation history were collected for comprehensive profiling. Results: Of the 58 participants, 15 were non-asthma controls, 7 were Th2 non-asthma, and 36 had asthma. Median age was 46 with a female predominance. Detailed demographic data for each subgroup available in Table 1 which outlines key characteristics such as age, gender distribution, BMI, and smoking history. There was a high prevalence of co-morbidities at enrolment specifically GERD and sino-nasal disease which are common among individuals with asthma and can significantly impact disease severity and treatment outcomes. Patients with asthma were phenotyped based on allergic status and the presence of Th2 inflammation. Comparative box plots show significant differences in respiratory function and microbial diversity across groups, highlighting potential microbiome-related drivers of asthma severity. Comparing diversity metrics there were significant microbial differences between the three groups. Conclusions: Asthma is a heterogenous condition that can present with variable and intermittent symptoms that make diagnosis challenging. A comprehensive diagnostic strategy that includes serial measurements is essential for accurate asthma diagnosis and effective management. Microbial signatures associated with three different groups of patients being referred for evaluation of asthma. These findings suggest that the microbial landscape may vary significantly based on asthma status and Th2 inflammation, potentially serving as important factors in the pathophysiology of asthma. Further research may establish the lung microbiome as a biomarker and therapeutic target in asthma, ultimately enhancing personalized treatment strategies. Table 1.