Inflammatory profiling in chronic lung disease

Chronic lung diseases (CLD), such as chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF) are increasing cause of death in the aging population. Symptoms include chronic dyspnoea, cough, fatigue and weight loss, which all contribute to a poor quality of life. CLD are often complicated by the presence of pulmonary hypertension (PH), where even a mild elevation of blood pressure in the pulmonary arteries is associated with an even poorer prognosis. Vascular remodelling underlies all forms of PH and directly contributes to the increased pulmonary pressure. Despite several therapeutic options being available for the idiopathic form of PH they only decrease the symptoms and delay clinical worsening and do not address the underlying causes. To date there are no medications available for the treatment of PH associated with CLD. Inflammation plays an important role in mediating vascular remodelling in idiopathic form of PH. Where the accumulation of inflammatory cells in and around the vascular wall correlates with the degree of vascular remodelling. These recruited cells release soluble mediators that directly induce vascular remodelling processes, and can induce a chronic inflammatory state by recruiting further inflammatory cells. Despite this knowledge, very little is known about the role of inflammation in PH associated with CLD. In this study, we will determine whether similarities exist in the inflammatory profile that could potentially underlie all forms of PH and determine its relationship to vascular remodelling. Furthermore, by examining isolated inflammatory cells, we determine how they can regulate vascular remodelling processes. This study will not only further our understanding of these deadly diseases, but also form the basis of strategies that can used for new immune-modulatory therapeutic approaches.

Chronic lung diseases such as chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF) are increasing cause of death in the aging population. Chronic lung diseases are often complicated by high blood pressure in the lung (pulmonary hypertension (PH)), which is associated with a worse prognosis. Our study investigated how the immune system is changed in how the lungs and pulmonary blood vessels of these patients. We found that the changes were strongest and most different in the COPD group compared to the healthy samples, while the fibrosis group was more mixed, some samples looked like COPD, while others were closer to healthy tissue. When we examined the composition of the immune cells more closely, we saw changes in several immune cell types, including T cells, granulocytes, macrophages and mast cells. Both COPD and fibrosis patients had more T cells, but people with pulmonary fibrosis had fewer natural killer T (NKT) cells - a cell type that helps control inflammation and infection. When comparing these diseases to another lung disease, called idiopathic pulmonary arterial hypertension, we observed the composition of the pulmonary arteries was different, which may be influenced by the differential immune cell abundance. When analysing within a patient group, we identified different disease subtypes, one COPD was characterised by severe pulmonary hypertension but less airspace remodelling (emphysema, and a second subtype with a very strong inflammatory signature, with worse emphysema and poorer gas exchange. These results are important as they show how immune cells and blood vessels are altered in these different lung diseases, in the future these results could help improve patient diagnosis, provide surrogates to monitor disease development and ultimately support the development of more targeted treatments.