Study of biomarkers for improved diagnosis and therapy monitoring in young asthmatics

Background : Type-2 asthma is often related to atopy and is characterized by elevated type-2 biomarkers. However, less is known about the pathophysiology of non-type 2 asthma, factors associated therewith, and the stability of different asthma phenotypes over time. Aims : To identify an IgE antibody concentration and putative biomarkers that better separate non-type 2 from type-2 asthma. To study the association between longitudinal changes in inflammatory biomarkers and clinical outcomes. To investigate the pattern of IgE sensitization to different cat allergen components and its impact on type-2 biomarkers in young asthmatics. Methods : The present thesis is based on the MIDAS asthma cohort, which includes asthmatics (n = 408) and healthy controls (n = 118), aged 10–35 years at baseline, with a follow-up visit 43{23-65} months later. All the subjects were characterized with regard to IgE sensitization, inflammation was assessed based on fractional exhaled NO (FeNO), blood eosinophil count (B-Eos) and other biomarkers, both type-2 and non-type 2, and lung function was evaluated with spirometry. Results : FeNO and B-Eos maintained associations with clinical asthma outcomes in the IgE antibody concentration range 0.10–0.34 kU A /L, but not below 0.10 kU A /L. Non-atopic asthmatics with perceived cow’s milk hypersensitivity had poorer asthma-related quality of life than those with atopic asthma, and were characterized by clinically significant non-type 2 inflammation. Furthermore, longitudinal increase in height-adjusted FeNO associated independently with decline in lung function. IgE sensitization to cat lipocalins and/or cat serum albumin were independently associated with FeNO and B-Eos. Conclusions : Our findings demonstrated that a cut-off of 0.10 kU A /L for IgE antibodies appeared to be useful for ruling out type-2 asthma in young subjects. A subgroup of non-atopic asthmatics was characterized by perceived cow’s milk hypersensitivity and non-type 2 inflammation. Longitudinal changes in FeNO associated with lung function decline in asthmatics. IgE sensitization to minor cat allergen components may promote both local and systemic type 2 inflammation.