Respiratory diseases such as chronic obstructive pulmonary disease (COPD), asthma, interstitial lung disease (ILD), bronchiectasis, and obstructive sleep apnoea (OSA) are common and often long-lasting. Many patients develop problems outside the lungs, including cardiovascular disease, diabetes and other metabolic disorders, liver and biliary disease, cognitive decline, mood disorders, neurodegenerative diseases, and related systemic complications. Non-malignant respiratory diseases contribute substantially to morbidity and mortality and are increasingly recognized as systemic disorders rather than lung-limited conditions. Proposed cross-organ mechanisms include chronic systemic inflammation, intermittent or chronic hypoxaemia, oxidative stress, immune dysregulation, endothelial dysfunction, autonomic imbalance, and metabolic remodeling. However, the biological mechanisms linking lung disease to damage in other organs remain insufficiently understood.
Using the UK Biobank resource, we will assess respiratory disease phenotypes and target-organ manifestations by integrating multi-organ, multi-omics data with symptom profiles, diagnostic information, lung function measures, imaging data, and relevant questionnaire responses, while accounting for indicators of disease severity and exacerbations. Using baseline and longitudinal follow-up data, we will examine associations with target-organ outcomes, including cardiovascular disease, metabolic/hepatobiliary disorders, cognitive function, and brain imaging phenotypes. We will then integrate these data to identify potential mediators and prioritize key mechanisms for laboratory validation, aiming to improve risk prediction and inform more effective prevention and treatment strategies.
