Chronic obstructive pulmonary disease (COPD) stands as the third leading cause of both illness and mortality on a global scale. In COPD, persistent inflammation triggers a fixed airflow obstruction, characterized by a FEV1/FVC ratio below 70% on pulmonary function testing. While cigarette smoke exposure is the primary culprit, not all smokers experience physiological decline (an important question/priority identified by patient advocacy groups).
Another significant concern amongst patients, is the lack of pharmacological interventions capable of halting COPD progression or reducing mortality once the disease has taken hold. Thus, there is an urgent need to unravel the pathogenesis of early-stage COPD, offering a pathway to novel treatments. Recent advancements in technology have enabled researchers to delve into the lung microbiome and its impact on COPD. For instance, in advanced COPD, an increased abundance of potentially pathogenic microorganisms (PPMs) such as Streptococcus or Haemophilus has been linked to inflammatory exacerbations that worsen the disease. Additionally, our research group has demonstrated that lower airway colonization with oral anaerobes like Veillonella or Prevotella in early-stage COPD correlates with a pulmonary Th-17 response. In parallel, byproducts of bacterial metabolism, such as kynurenine and indole-3-derivatives, have been found to modulate pulmonary immunity in COPD.
Therefore, elucidating the functional capabilities and roles of these microorganisms in early COPD is paramount and now made feasible with cutting-edge technologies like metagenomics and metatranscriptomics. Our hypothesis posits that enhanced molecular and clinical profiling of COPD patients through next-generation sequencing can pave the way for precision medicine, ultimately reducing clinical risks for patients.
To achieve this, our objectives are threefold: 1) Identify microbial & host markers associated with early-stage COPD from non-invasive samples; 2) Identify microbial & host markers associated with early-stage COPD from invasive samples (bronchoscopy); and 3) Assess the impact of common COPD treatments on the lower airway micro-environment.