Molecular aspects of asthma in adults: allergen components and eosinophil-derived neurotoxin

Abstract

Identification of asthma phenotypes has become pivotal to providing better disease management, as it enables the implementation of precision medicine-based approaches. Biomarkers are essential in connecting asthma phenotypes to their underlying endotypes. As allergic asthma and eosinophilic asthma are two common asthma phenotypes, both molecular allergens and eosinophilic biomarkers can provide insights into disease characteristics at the individual level. This thesis characterized allergic and eosinophilic biomarkers in relation to asthma in adults within the ongoing population-based West Sweden Asthma Study. Paper I characterized the sensitization patterns to cat molecular allergens in cat-sensitized subjects. Individuals with asthma were more likely to be polysensitized (≥3 cat molecular allergens). Immunoglobulin E levels against cat molecular allergens (Fel d 1/2/4/7) were higher in subjects with asthma than in those without. Paper II investigated the association between dog molecular allergens, asthma, and clinical outcomes. Current asthma risk, lung function parameters, and inflammation markers differed in subjects based on their sensitization patterns to dog molecular allergens. Polysensitization was associated with higher odds of current asthma, worse lung function, and high blood eosinophil count. Paper III assessed the distribution of serum and nasal lavage fluid (NLF) eosinophil-derived neurotoxin (EDN). Then, risk factors for high EDN in various adult subsamples were evaluated. Current asthma, atopy, and male sex were related to high serum EDN. Sample type (nasal or serum) and study subpopulation also influenced the risk factors for high EDN. Paper IV defined levels of serum and NLF EDN in various clinically defined asthma phenotypes. Serum and NLF EDN were significantly higher in eosinophilic asthma compared to non-eosinophilic asthma. Serum, but not NLF EDN, yielded excellent discriminatory ability in differentiating eosinophilic asthma from non-eosinophilic asthma. Molecular allergens and eosinophilic biomarkers appear to potentially provide a more precise characterization of asthma in adults, which can advance precision medicine in asthma management.