Unfolding treatable traits of obesity and Bronchiectasis as sub-phenotypes in severe asthma.

Bakgrund:

Severe asthma is a heterogeneous disease that accounts for a significant share of morbidity, mortality, and health care costs for asthma. Two less studied but well-known aggravating co-morbidities relate to obesity and Bronchiectasis, respectively, accepted as dominant treatable traits. At obesity-related asthma, observations are suggesting that metabolic disturbances associated with obesity may promote asthmatic airway inflammation by secretion from the adipose tissue of several cytokines or peptides, i.e. adipokines.

Adipokines also play a role in diabetes pathophysiology. Recent studies have suggested a strong relationship between insulin resistance and asthma that is, however, still unclear. Concerning Bronchiectasis, reports suggest that up to 40% of patients with severe asthma have Bronchiectasis.

These infections lead to increased severity and extent hospitalization. Macrophages the dominant cell in airways is affected in Bronkiektasis and is a valuable therapeutic target. Målsättning:

The goal of the project is to sequentially progress the knowledge about those two severe asthma treatable traits. The investigations of obesity-related severe asthma focus, in particular, on the hypothesis that diabetes is over-presented and adipokines are disease-driving. The investigations of bronchiectasis-related severe asthma investigate the probable role of macrophages in the underlying immunopathology.

Arbetsplan:

A novel multiplex assay for a panel of adipokines as biomarkers has been developed in-house and tested. New clinical investigations in parallel with the evaluation of adipokines are planned in patients with asthma and diabetes originating from the Stockholm Diabetes cohort. In Bronchiectasis, we will characterize airway macrophages and monocytes in patients with Bronchiectasis and asthma that undergoes clinical bronchoscopies.

Betydelse:

Gathering of such new knowledge about those important but still less studied severe asthma treatable traits we increase our future therapeutic options. In the case of obesity and diabetes, proof of a relationship will allow us to move to the next step and evaluate, optimization of diabetes as part of asthma treatment optimization. In the case of Bronchiectasis, confirmation of an inflammatory macrophage population will initiate a strengthened therapeutic approach with existence therapeutic options, i.e. the long-term macrolides.