Apostolos Bossios

Bakgrund: Severe asthma includes a heterogeneous group of patients that accounts for a large share of the related morbidity, mortality, and healthcare costs. A new treatment approach focuses on identifying and addressing specific, treatable traits with targeted interventions. Bronchiectasis, a common comorbidity in severe asthma, shares symptoms like dyspnea, wheezing, chronic cough, and sputum production, making it difficult to distinguish between the two conditions when they coexist. The cellular immunopathology in severe asthma and bronchiectasis is comparable. For instance, both pathologies involve neutrophilic and eosinophilic chronic inflammation with a probable role of Th17 and Th2 signaling. Among T cells, T regulatory cells (Tregs) are crucial in downregulating this inflammation, and we, among others, have produced data suggesting an important role in asthmatic inflammation as well. Notably, Tregs and Th17 have a common origin. Tregs can resolve inflammation and prevent it from becoming chronic. We hypothesize that patients with severe asthma and bronchiectasis have a diminished and defective Treg population, where bacteria may also play a role, affecting the Treg /Th17 balance and their function. Aim: The project's overall goal is to characterize the role of Tregs in the underlying inflammation of patients with severe asthma with the comorbidity of bronchiectasis. Workplan: Patients with severe asthma, bronchiectasis, or both disorders will be recruited from a specialized outpatient clinic and undergo clinical characterization during stable disease and bacterial infections, as well as evaluation of their oral flora. Systemic and airway Treg phenotype and function will be evaluated using several approaches. Significance: The expected results will increase our understanding of the role of Tregs in the underlying airway inflammation in severe asthma and the comorbidity of bronchiectasis. This understanding may identify novel target mechanisms for diagnosis and therapies that involve Tregs that may help prevent the development of bronchiectasis.

Background: Severe asthma includes a heterogeneous group of patients that accounts for a large share of asthma-related morbidity, mortality, and healthcare costs. A new therapeutic approach recognizes clinically relevant, distinguishable, and treatable disease characteristics, followed by targeted and individualized treatment interventions to address treatable traits. For severe asthma, bronchiectasis represents a comorbidity and treatable treatable trait. This comorbidity is over-presented in patients with severe asthma

both these disorders share symptoms, including dyspnoea, wheezing, chronic cough, and sputum production. For these reasons, it is hard to distinguish each disorder when they exist in the same patient. Moreover, the cellular pathoimmunology is similar, leading to chronic inflammation involving both neutrophils and eosinophils. Because of this, the involvement of both Th17 and Th2 signaling seems likely. The latter underlines the possibility that regulatory T cells (Treg) play a critical role because this unique T cell population bears the capacity to downregulate inflammation mediated by Th17 and Th2 cells. As indicated in other settings, Treg may completely resolve this type of inflammation, thus preventing it from becoming chronic and severe. Given the refereed involvement of Th17 and Th2 in patients with severe asthma and bronchiectasis, we hypothesized that they have a diminished and defective population of Tregs, possibly due to the presence of airway bacteria that manipulate Tregs to promote their survival. Målsättning:The project's overall goal is to characterize the role of Treg in the underlying inflammation of patients with severe asthma and the comorbidity of bronchiectasis. Arbetsplan: Patients with severe asthma, bronchiectasis, or both disorders will be recruited from a specialized outpatient clinic and undergo clinical characterization during stable disease and bacterial infections. The involvement of the different subtypes of Treg and their function will be evaluated with several approaches. Bronchoscopy sampling will be utilized to determine the presence and function of local Treg. The role of oral dysbiosis on T regulatory cell function will also be evaluated. Betydelse:The expected results will increase our understanding of the role of Treg in the underlying airway inflammation in severe asthma and the comorbidity of bronchiectasis, resulting in identifying nove therapeutic target.

Biomass burning for cooking and heating produces a toxic cocktail of particulate matter (PM) and gaseous pollutants, resulting in chronic lung issues. Around 0.5-0.6 million deaths occur annually in India, mainly in the Indo-Gangetic Plains, from exposure to indoor air pollutants, indicating the multifaceted healthcare, economic and environmental burden in households, where biomass burning prevails. And yet, ground-based indoor exposure data are sparse, there is poor awareness about air pollution, and clean energy initiatives are lagging. We hypothesize that biomass combustion and PM exposure is related to specific pollutant classes (triggers) and their synergistic interactions, which trace early metabolic changes in plasma to diagnose asthma, lung aging, and chronic pulmonary obstructions. We aim to 1) conduct socioeconomic and health surveys and develop real-time indoor pollutant monitoring using automated sensor networks, 2) analyze organic compounds and oxidative metals that cause pulmonary stress, and 3) identify novel biomarkers in plasma and combine this with integrative transcriptomics, epidemiological and environmental chemical data. The proposed synergistic and integrated work packages on PM characteristics and metabolomics will establish causality with exposure posing a breakthrough for early clinical diagnosis. This strategy will help healthcare measures and mitigation plans advance the UN Sustainable Development Goals 3 and 7 for better air quality and health.