Anushka Ruwanpathirana

Asthma has become more appreciated for its heterogeneity with studies identifying type 2 and non‐type 2 phenotypes/endotypes that ultimately lead to airflow obstruction, airway hyperresponsiveness, and remodeling. The pro‐inflammatory environment in asthma influences airway smooth muscle (ASM) structure and function. ASM has a vast repertoire of inflammatory receptors that, upon activation, contribute to prominent features in asthma, notably immune cell recruitment and activation, hypercontractility, proliferation, migration, and extracellular matrix protein deposition. These pro‐inflammatory responses in ASM can be mediated by both type 2 (e.g., IL‐4, IL‐13, and TSLP) and non‐type 2 (e.g., TNFα, IFNγ, IL‐17A, and TGFβ) cytokines, highlighting roles for ASM in type 2 and non‐type 2 asthma phenotypes/endotypes. In recent years, there has been considerable advances in understanding how pro‐inflammatory cytokines promote ASM dysfunction and impair responsiveness to asthma therapy, corticosteroids and long‐acting β2‐adrenergic receptor agonists (LABAs). Transcriptomic analyses on human ASM cells and tissues have expanded our knowledge in this area but have also raised new questions regarding ASM and its role in asthma. In this review, we discuss how pro‐inflammatory cytokines, corticosteroids, and LABAs affect ASM structure and function, with particular focus on changes in gene expression and transcriptional programs in type 2 and non‐type 2 asthma.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS□CoV□ 2) is a highly pathogenic corona virus which causes COVID-19 and resulted in millions of deaths and led to a global public health emergency. An effective and appropriate immune response is essential to control and eliminate viral infections, however, dysregulated immune responses may lead to immunopathology in viral infections. Clinical data showed that COVID-19 may promote the development of cardiovascular disorders (CVDs). However, exact mechanism associated with CVDs in COVID-19 patients is currently unknown. Monocytes are one of the major immune cell subsets that contribute to host defense against many infections but also associated with immunopathology and development of CVDs. Thus, in this study we investigated the role of monocyte subsets in COVID-19 associated CVDs. By using high dimensional flowcytometry, immune biomarker assays and multi variant data analysis in healthy donors (n=17), severe-COVID-19 patients (n=20) (ICU) and COVID-19 recovered individuals (n=30), we found elevated intermediate monocytes and Monocyte chemoattractant protein-1, one of the most important chemokines that regulates migration and infiltration of monocytes to the subendothelial space, where they may become foam cells. Spearman correlation network analysis showed that strong correlation between increase intermediate monocytes in the whole blood and plasma cardimetabolic biomarkers such as fatty acid binding protein 4, C-reactive protein, soluble CD14 and LPS binding protein in ICU patients. Our data show for the first time that the possible role of monocytes in the development of CVDs in ICU patients.