<p>Background: Asthma is a major health problem in children and most troublesome during severe or persistent symptoms. Children with problematic severe asthma have a disproportionate consumption of health care, despite high-dose treatment with inhaled corticosteroids (ICS). Little is known about children with impaired asthma control or problematic severe asthma in regards to prevalence in a normal population, characterisation and classification, and health effects measured as health-related quality of life (HR-QoL).</p><p>Aim: The overall aim of this doctoral thesis was to evaluate the burden of symptoms and factors associated with impaired asthma control in schoolchildren.</p><p>Materials and Methods: The study population consisted of 3 015 children up to 12 years of age from the prospective birth cohort BAMSE, and children from the Severe asthma study with problematic severe asthma (n = 56) and, for comparison, controlled asthma (n = 39). Parental questionnaires collected data on environmental exposures, asthma symptoms and treatments. In the BAMSE study, asthma control was classified based on parental reports and according to a modified GINA classification. The prevalence of severe asthma with dispensed high-dose ICS was estimated through the Swedish drug register. Evaluations with component-resolved allergy diagnostics, exhaled nitric oxide (FeNO), bronchial hyperresponsiveness to methacholine (BHR), blood count of eosinophils and HR-QoL were applied in the Severe asthma study.</p><p>Results: In the BAMSE cohort, a high proportion of children with asthma were classified as impaired in their asthma control (partly or uncontrolled) at 8 years, 84% of 323, and at 12 years, 53% of 329, (p < 0.001). Parental report of symptoms varied in these children, with more activity limitation (66% vs. 48%, p < 0.001) and wheeze > 4 times in last year (52% vs. 38%, p = 0.002) at 12 years compared with at 8 years, but fewer with nocturnal symptoms (36% vs. 82%, p < 0.001) and less acute healthcare utilization (15% vs. 34%, p < 0.001) at 12 years. Severe asthma was prevalent in 0.4% of children in a normal urban population at age 12, or 4% among children with asthma. Children with impaired asthma control at both 8 and 12 years in the BAMSE cohort (n = 91) and children with problematic severe asthma had more often a family history of allergic disease and comorbidity of rhinitis than children with controlled asthma. Multi-sensitization to animal-derived components was more pronounced in problematic severe asthma than in controlled asthma, 25% vs. 8% (p = 0.03), and was associated with increased eosinophil inflammation as compared with children sensitized to fewer animal-derived components, FeNO 38 ppb vs. 25 ppb (p = 0.002), blood eosinophils 0.65 vs. 0.39 (p = 0.021), and BHR 112 vs. 28 (p = 0.002). Children with problematic severe asthma were more impaired in HR-QoL than children with controlled asthma 5.4 vs. 6.7 (p < 0.001).</p><p>Conclusion: A high proportion of schoolchildren reported impaired asthma control. Children with problematic severe asthma have impaired HR-QoL, with effects of limitations in daily activities and reduced emotional well-being. Common factors associated with children having impaired asthma control at both 8 and 12 years and problematic severe asthma were family history of allergic disease and comorbidity of rhinitis.</p><h3>List of scientific papers</h3><p>I. Nordlund B, Melén E, Schultz E, Grönlund H, Hedlin G, Kull I. Severe asthma and asthma control among schoolchildren: study from the BAMSE birth cohort. [Submitted]</p><p>II. Konradsen JR, Nordlund B, Lidegran M, Pedroletti C, Grönlund H, van Hage M, Dahlen B, Hedlin G; In cooperation with the Swedish Network of Pediatric Allergists, Severe Asthma Network. Problematic severe asthma: A proposed approach to identifying children who are severely resistant to therapy. Pediatr Allergy Immunol. 2011 Feb;22(1 Pt 1):9-18. <br><a href="https://doi.org/10.1111/j.1399-3038.2010.01098.x">https://doi.org/10.1111/j.1399-3038.2010.01098.x</a><br><br> </p><p>III. Nordlund B, Konradsen JR, Kull I, Borres MP, Önell A, Hedlin G, Grönlund H. IgE antibodies to animal-derived lipocalin, kallikrein and secretoglobin are markers of bronchial inflammation in severe childhood asthma. Allergy. 2012 May;67(5):661-9. <br><a href="https://doi.org/10.1111/j.1398-9995.2012.02797.x">https://doi.org/10.1111/j.1398-9995.2012.02797.x</a><br><br> </p><p>IV. Nordlund B, Konradsen JR, Pedroletti C, Kull I, Hedlin G. The clinical benefit of evaluating health-related quality of life in children with problematic severe asthma. Acta Paediatr. 2011 Nov;100(11):1454-60. <br><a href="https://doi.org/10.1111/j.1651-2227.2011.02359.x">https://doi.org/10.1111/j.1651-2227.2011.02359.x</a><br><br> </p>