Characterizing complex host immune-microbiome relationships in chronic inflammatory lung diseases : insights into asthma and chronic obstructive pulmonary disease

Decades of research have shown that the microbiome plays a fundamental role in how the immune system develops and how inflammatory responses are shaped and regulated. The gut and airways are two microbiome sites that have been extensively studied in chronic obstructive lung diseases like asthma and chronic obstructive pulmonary disease (COPD). Dysbiosis of the gut microbiome is implicated in the development and progression of asthma and to some extent COPD. The field of COPD microbiome research is rapidly growing and with advances in sequencing techniques, people have been able to characterize various omes that when collectively analyzed may provide insights into the mechanisms that underlie COPD pathogenesis. Emerging studies highlight a novel biological cross-talk between the microbiome and host cells in the small airways of patients with COPD. While host-microbiome interactions have been previously investigated in COPD, the effects of specific steroid formulations on this complex cross-talk remain obscure. In this thesis, we examine host transcriptome and small airway microbiome changes in a randomized controlled cohort of COPD patients treated with salmeterol/fluticasone, formoterol/budesonide or formoterol-only. Our findings reveal that in COPD patients treated with salmeterol/fluticasone, the expression levels of host genes (mainly inflammatory genes) are significantly related to changes in both the alpha diversity and the relative abundance of Haemophilus in the small airways. Collectively, our data argue that ICS therapy, particularly salmeterol/fluticasone, is tightly linked to alterations in host transcriptome and shifts in the microbiome composition of the small airway microenvironment. These data may provide insights into why some COPD patients treated with inhaled corticosteroids are at an increased risk for airway infection, including pneumonia.Applied Science, Faculty ofBiomedical Engineering, School ofGraduat