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Background: Asthma, rhinitis, and eczema are common. Considerable multimorbidity exists involving all three diseases, which cannot be explained by chance. Allergic sensitisation increases the risk of multimorbidity, though not much is known about other factors impacting their co-occurrence.

Aim: The overall aim of this thesis was to investigate factors associated with allergic multimorbidity. 

Methods and results: We have investigated allergic multimorbidity in terms of background and demographic factors, symptom burden, lung function, allergic sensitisation, and inflammatory markers: total immunoglobulin E (IgE), C-reactive protein (CRP), periostin, fractional exhaled nitric oxide (FENO), alveolar nitric oxide (CANO), blood eosinophil counts, eosinophil activation markers (eosinophil cationic protein (ECP), eosinophil-derived neurotoxin (EDN)).  

The study populations were mainly middle-aged adults, except for paper III, which comprised children and young adults. Paper I included 216 individuals from the European Community Respiratory Health Survey (ECRHS II). Paper II was based on 437 individuals from the Swedish part of the Global Allergy and Asthma European Network (GA2LEN). Paper III involved 411 participants from the Minimally Invasive Diagnostics for Asthma and Allergic Diseases Study (MIDAS). Paper IV was based on 255 individuals who were followed for 10 years from ECRHS II to ECRHS III. 

The main findings were that individuals with allergic multimorbidity were more likely to be polysensitised to allergens and had higher levels of total IgE compared with those with only one disease. Both factors, as well as higher FENO and ECP at baseline, were associated with persistent allergic disease over time. Multimorbidity was associated with higher levels of FENO in subjects with asthma aged under 18 years and EDN. Those with multimorbidity reported more asthma and allergy symptoms, had heredity, especially maternal heredity. We found both higher and lower lung function among those with more than one allergic disease, which underscores the heterogeneity of asthma as a disease. 

Conclusion: We found allergic multimorbidity to be associated with polysensitisation, higher levels of type 2 inflammation, and higher symptom burden compared with those with only one allergic disease. Highlighting the importance of multimodal management when striving to decrease the symptom burden and socioeconomic cost of allergic multimorbidity.

Background: Allergic disease is common. The aim of this study was to look at the change in asthma and rhinitis over time and to characterise factors contributing to remission and persistence of disease.

Methods: This cohort study included 255 individuals with or without asthma and or rhinitis that participated in a population survey and a follow-up 10 years later. The participants were tested for allergic sensitisation, total IgE, multiplex allergen component analysis and type-2 inflammatory markers: exhaled nitric oxide (FENO), eosinophil cationic protein (ECP) and eosinophil-derived neurotoxin (EDN).

Results: Of the 132 healthy individuals, 112 remained healthy, 16 developed rhinitis, 4 asthma and rhinitis over the 10 years. Out of 82 subjects with rhinitis, 26 went into remission, 53 remained unchanged and 3 developed asthma in addition to rhinitis. None of the 41 participants with asthma and rhinitis went into remission. Subjects with persistent rhinitis and asthma had higher levels of total IgE (odds ratio [OR] 95% confidence interval [CI]: 6.16 [3.05-12.5]) at baseline and after 10 years, and FENO and ECP at baseline (OR per log unit increase, 95% CI 5.21 [1.20-22.7] and 6.32 [1.52-26.4], respectively), compared with those that remained healthy. Subjects with persistent rhinitis were more likely to be sensitised to grass pollen and had higher total IgE levels than those that went into remission. Individuals with persistent asthma were more likely to be sensitised to tree pollen and furry animals than those with only persistent rhinitis (OR 95% CI: 3.50 [1.29-9.49] and 6.73 [2.00-22.6], respectively).

Conclusion: IgE sensitisation and total IgE levels are associated with the persistence of rhinitis and asthma. Participants with persistent allergic disease had higher levels of allergen sensitisation and type 2 inflammation markers at baseline than those who remained healthy.

BACKGROUND: Asthma is common worldwide and a large part of subjects with asthma have concomitant allergic multimorbidity in the form of rhinitis and/or eczema.

OBJECTIVE: The aim of this study is to investigate whether the presence of allergic multimorbidity in asthma relates to allergic sensitization, allergic and respiratory symptoms, quality of life, inflammatory markers, lung function, use of medication and background factors.

METHODS: A total of 437 asthmatics from the (GA² LEN) cross-sectional survey in Sweden were grouped depending on the presence of rhinitis and/or eczema. The impact of allergic multimorbidity was assessed in terms of allergic sensitization, allergic and respiratory symptoms, quality of life, type-2 inflammatory markers (exhaled nitric oxide, eosinophil activation markers, periostin), lung function, use of medication and background factors.

RESULTS: Subjects with asthma, rhinitis and eczema were more likely to be sensitized to seasonal allergens (67% vs 32%, P < .001), food allergens (54% vs 18%, P < .001) and to have a higher degree of sensitization than subjects with only asthma (23% vs 10%, P < .001). Subjects with allergic multimorbidity more often had allergic reactions to food (28% vs 10%, P = .002), more respiratory symptoms and anxiety/depression (40% vs, 14%, P < .001) than subjects with only asthma, despite having similar levels of type 2 inflammatory markers. Individuals with allergic multimorbidity were more likely to be diagnosed with asthma before the age of 12 (48% vs 27%, P = .016) and to have maternal heredity for allergy (53% vs 33%, P = .011) than subjects with only asthma.

CONCLUSION AND CLINICAL RELEVANCE: Asthmatics with allergic multimorbidity are more likely to be sensitized to seasonal aeroallergens, food allergens and they have a higher degree of sensitization compared with those with only asthma. Allergic multimorbidity is associated with respiratory and allergy symptoms, anxiety and/or depression.

Background Rhinitis is a common problem within the population. Many subjects with rhinitis also have atopic multimorbidity, such as asthma and eczema. The purpose of this investigation was to compare subjects with only rhinitis to those that have rhinitis, asthma and/or eczema in relation to immunoglobulin E (IgE) sensitization, inflammatory markers, family history, lung function and body mass index (BMI). Methods A total of 216 adult subjects with rhinitis from the European Community Respiratory Health Survey II were investigated with multiplex component allergen analysis (103 allergen components), total IgE, C-reactive protein, eosinophilic cationic protein, fractional exhaled nitric oxide and spirometry. Rhinitis, eczema, asthma and parental allergy were questionnaire-assessed. Results Of the 216 participants with rhinitis, 89 also had asthma and/or eczema. Participants with rhinitis that also had asthma or eczema were more likely to be IgE-sensitized (3.44, odds ratio, OR: 95% CI 1.62-7.30, adjusted for sex, age, mother's allergy, total IgE and forced expiratory volume (FEV1)). The number of IgE-positive components was independently associated with atopic multimorbidity (1.11, OR: 95% Cl 1.01-1.21) adjusted for sex, age, mother's allergy, total IgE and FEV1. When analysing different types of sensitization, the strongest association with atopic multimorbidity was found in participants that were IgE-sensitized both to perennial and seasonal allergens (4.50, OR: 95% CI 1.61-12.5). Maternal allergy (2.75, OR: 95% CI 1.15-4.46), high total IgE (2.38, OR: 95% CI 1.21-4.67) and lower FEV1 (0.73, OR: 95% CI 0.58-0.93) were also independently associated with atopic multimorbidity, while no association was found with any of the other inflammatory markers. Conclusion IgE polysensitization, to perennial and seasonal allergens, and levels of total IgE seem to be the main determinants of atopic multimorbidity in subjects with rhinitis. This indicates that disease-modifying treatment that targets IgE sensitization may be of value when decreasing the risk of developing atopic multimorbidity.