| 1. |
- Kalm-Stephens, Pia, 1959-
(författare)
-
Development of allergic and respiratory symptoms in adolescence and early adulthood : Risk factors and gender differences
- 2020
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Asthma and allergic diseases have increased in prevalence for several decades and affect a substantial number of individuals in everyday life, as well as their families and public healthcare resources. Subjects with asthma report impaired self-rated health. Fractional exhaled nitric oxide (FeNO) is a marker of type 2 inflammation in the airways and higher levels may precede the development of allergic and respiratory disease.Aims: To investigate the development of allergic and respiratory symptoms in adolescence and early adulthood, and related baseline risk factors. Further, to study self-rated health in young adults with reported asthma.Methods: A total of 959 schoolchildren completed a standardized respiratory questionnaire and underwent lung function and FeNO measurements at baseline (12–15 years; early adolescence). Four (late adolescence) and sixteen (early adulthood) years later, 921 (96%) and 502 (52%) of these individuals completed a similar questionnaire. A total of 491 subjects participated in all three examinations. Nineteen clinically assessed non-asthmatic subjects with elevated FeNO and 28 control subjects with low FeNO and without symptoms of asthma or allergy in early adolescence were identified. Their FeNO, IgE sensitization, airway responsiveness, and inflammatory markers in blood and sputum were measured.Results: The main finding was that higher FeNO in early adolescence was associated with an increased risk of developing allergic symptoms to cat and dog, but not pollen allergens, during adolescence. Gender-stratified data showed that obesity at baseline in girls and an atopic constitution in boys were associated with increased risk of developing wheeze during adolescence. The prevalence of asthma and wheeze had increased in early adulthood, but the increase was significant only in females. Reduced lung function at baseline in females and higher FeNO in males were associated with an increased risk of incident asthma sixteen years later. The increase in allergic symptoms during this period was significant but without sex differences. Asthmatic females rated their health worse than non-asthmatic females, a difference not observed in males. Non-asthmatic adolescents with higher FeNO at baseline were to a higher extent sensitized, had more reactive airways, higher blood eosinophil counts, and lower systemic activation of neutrophils, compared with controls.Conclusions: It is important to detect risk factors for the development of allergic and respiratory diseases at an early stage to optimize health and wellbeing. Gender differences in respiratory development, associated risk factors, and treatment of respiratory symptoms must be taken into account.
|
|
| 2. |
- Nyström, Niklas
(författare)
-
Metabolomic features and viral infections in paediatric inflammatory bowel disease
- 2024
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Up to 25% of patients with inflammatory bowel disease have a paediatric onset (PIBD). The pathophysiological processes underlying PIBD are complex and largely unknown. Aims: To investigate a hypothesized role for human enterovirus B (HEV-B) in Crohn’s disease (CD) (I). To map and compare the mucosal and plasma metabolomes in new-onset PIBD patients and controls (II). To search for a new blood-based diagnostic biomarker for PIBD (III). To investigate the effect of exclusive enteral nutrition (EEN) treatment on the mucosal and plasma metabolomes in CD patients (IV). Methods: Immunohistochemistry and chromogen in situ hybridisation were used to search for HEV-B in surgical specimens from patients who had undergone surgery for stricturing ileocecal CD, and from volvulus patients as controls. Ultra-high-performance liquid chromatography mass spectrometry were used on biopsies and plasma from patients in the Uppsala PIBD inception cohort for metabolomic (II and IV) and lipidomic analyses (III). Patients were stratified by phenotypic subtypes and treatment responses. Symptomatic patients without PIBD were used as non-IBD controls. In Study III, two other independent PIBD inception cohorts were used for validation and confirmation. Results: I: HEV-B was detected in epithelial cells and neuronal ganglia of the enteric nervous system, and the specific cellular Coxsackie and adenovirus receptor (CAR) was expressed in both the intestinal epithelium and the enteric nervous system. II: Alterations in two metabolic compound classes were seen: decreased levels of lysophospholipids in inflamed ileum of CD patients and altered levels of sphingolipids in inflamed ileum and colon in both CD and ulcerative colitis, as compared with non-IBD controls. III: Discovery, validation and confirmation in three independent PIBD inception cohorts of a blood-based diagnostic two-lipid signature of PIBD. IV: A generalised downregulation of the non-inflamed ileal lipid metabolism after successful remission induction with EEN, as compared with baseline, and also as compared with non-IBD controls. Reduction of several lysophospholipids was a characteristic feature of the post-EEN ileal metabolome.Conclusions: The demonstrated presence of HEV-B supports, but does not confirm, its hypothesised role in CD. The CD-associated downregulation of mucosal metabolism both at disease onset and after successful EEN-induced inflammation resolution indicates a central role for the ileal mucosal lipid metabolism in CD, including lysophospholipids. The blood-based two-lipid signature has the potential of becoming a diagnostic tool in the clinical work-up of suspected PIBD.
|
|
| 3. |
- Öman, Anders, 1975-
(författare)
-
Studies of the Role of the Gastrointestinal Tract in Children with Juvenile Idiopathic Arthritis (JIA)
- 2021
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease in children, but its cause is not fully established. Changes in the intestinal canal and an unfavourable composition of gut bacteria have been suggested as factors that can increase the risk of developing JIA and influence the disease course.This thesis investigated the possible association between JIA and changes in the intestinal canal.In a population-based study, 213 children diagnosed with JIA were screened for coeliac disease using immunoglobulin antibodies against tissue transglutaminase 2. Three children had a diagnosis of coeliac disease prior to screening and three previously undiagnosed cases were found through screening. The point prevalence for coeliac disease among children with JIA was 2.8%.In order to investigate if the composition of gut microbiotas in children with JIA differed from in healthy children and healthy siblings, 75 children with JIA were compared with 24 healthy controls, and eight children with JIA were compared pairwise with healthy siblings. Comparisons of microbiotas revealed trends towards altered relative abundances of taxa in children with JIA, but these were not significant when corrected for multiple comparisons.To examine the effects on gut microbiotas of treatment with methotrexate (MTX) or etanercept (ETN), faecal samples from 46 treatment-naïve children with JIA were compared with samples from children during treatment with MTX (n=29) or ETN (n=12). Paired comparisons were also made of children sampled both as treatment-naïve and during treatment with MTX (n=15) or ETN (n=7), including analyses of levels of faecal short-chain fatty acids. No significant differences were found after correction for multiple analyses.A pilot study investigated if improved clinical symptoms after interventions with exclusive enteral nutrition (EEN; n=6) or specific carbohydrate diet (SCD; n=10) in children with JIA were linked to changes in the gut microbiota. Faecal samples collected before the interventions were compared pairwise with samples collected after 3–5 weeks on the interventions. Both interventions altered microbiota composition, with a significant decrease in alpha-diversity and relative abundance of Actinobacteria during SCD.In conclusion, children with JIA most likely have an increased risk of coeliac disease and screening should be recommended. Faecal microbiota in children with JIA do not seem to differ compared with in healthy children or siblings. Treatment with MTX or ETN has no, or very limited, effect on the microbiota in faecal samples, but dietary interventions with EEN or SCD showed some changes in a pilot study.
|
|
| 4. |
- Krantz, Christina
(författare)
-
Nitric oxide within the concept of united airway disease : Exhaled and nasal nitric oxide in cystic fibrosis, asthma and upper airway inflammatory diseases
- 2021
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Within the concept of united airway disease, it is postulated that inflammatory disorders in the upper and lower airways are interrelated and influence each other. Fractional exhaled nitric oxide (FeNO) is an established biomarker of type-2 inflammation in the lower airways and is elevated in patients with asthma. However, the relation between nasal nitric oxide (nNO) and upper airway inflammation is less clear. Although cystic fibrosis (CF) is associated with increased airway inflammation, nitric oxide is not elevated in patients with CF.Aims: To study nNO and FeNO as biomarkers of type-2 inflammation in the upper and lower airways, respectively, in relation to symptoms, disease control and treatment of both upper and lower airway diseases, and in relation to systemic inflammation.Methods: This thesis is based on the MIDAS cohort of children and young adults with asthma (n=411) with a follow-up after 2-5 years (n=258), as well as one cohort of children and adults with CF (n=38) and one multicentre population-based cohort of middle-aged adults (n=5,824). Cross-sectional (Paper I-IV) and longitudinal (Paper III) analyses were performed. The main outcomes were nNO (Paper I-III) and FeNO (Paper II and IV) and their relations to IgE sensitisation, upper and lower airway symptoms and treatment, and systemic inflammation.Results: In subjects with asthma, nNO was associated with FeNO and increased bronchial responsiveness and nNO was higher in subjects with perennial sensitisation. In non-asthmatic middle-aged subjects with perennial sensitisation, rhinitis and rhinoconjunctivitis were associated with higher FeNO. There was also a positive interaction with perennial sensitisation for the relation between upper airway inflammatory disorders and FeNO. Treatment with nasal or inhaled corticosteroids was associated with lower nNO levels in subjects with asthma. In middle-aged subjects with asthma and perennial sensitisation, use of nasal corticosteroids related to lower FeNO, whereas use of inhaled corticosteroids related to higher FeNO levels. Patients with CF had lower levels of nNO and FeNO than controls. Moreover, lower FeNO levels were associated with lower lung function and higher blood neutrophil counts in CF.Conclusion: Within the concept of united airway disease, nNO is related to lower airway inflammation, responsiveness and treatment, and FeNO is related to upper airway inflammatory disorders, with a significant interaction with perennial sensitisation. In CF, lower FeNO is related to more severe disease with lower lung function and more systemic inflammation.
|
|
| 5. |
- Heldin, Johanna, et al.
(författare)
-
Clinical remission of asthma and allergic rhinitis : in a longitudinal population study
- 2022
-
Ingår i: Journal of Asthma and Allergy. - : Dove press. - 1178-6965. ; 15, s. 1569-1578
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Although asthma and allergic rhinitis are chronic diseases, some patients experience periods of remission. Information on prognostic factors associated with the remission of asthma and allergic rhinitis is valuable in resource prioritization. This study investigated factors associated with the clinical remission of asthma and allergic rhinitis.Methods: In the Respiratory Health In Northern Europe (RHINE) study, data was collected with questionnaires in stage one (RHINE I, 1989–1992) and two follow-ups (RHINE II, 1999–2001 and RHINE III, 2010–2012) from Sweden, Norway, Denmark, Iceland and Estonia. Clinical remission was defined as having reported asthma or allergic rhinitis in RHINE I or RHINE II but not in RHINE III.Results: Of 13,052 participants, 975 (7.5%) reported asthma in RHINE I or RHINE II, and 3379 (25.9%) allergic rhinitis. Clinical remission of asthma and allergic rhinitis was found in 46.4% and 31.8%, respectively. Living in Estonia (OR (95% CI) 2.44 (1.22– 4.85)) and living in an apartment (1.45 (1.06–1.98)) were related to remission of asthma, while subjects reporting allergic rhinitis (0.68 (0.51–0.90)), asthma onset ≤ 12 years of age (0.49 (0.35–0.68)), receiving treatment with antibiotics for respiratory illness (0.64 (0.47– 0.87)) were less likely to have asthma remission. Factors related to a higher likelihood of remission of allergic rhinitis were no asthma at baseline, age ≥ 58 years in RHINE III, allergic rhinitis onset after 12 years of age, living in rural areas as a child, having only a primary school education and not being pregnant.Conclusion: Clinical remission was found in almost one-half of those with asthma and one-third of persons with allergic rhinitis. Coexisting allergic symptoms were associated with less clinical asthma remission. Age, asthma symptoms and environmental factors in childhood, such as living in a rural area, were found to influence the clinical remission of allergic rhinitis.
|
|
| 6. |
- Krantz, Christina, et al.
(författare)
-
Cross-sectional study on exhaled nitric oxide in relation to upper airway inflammatory disorders with regard to asthma and perennial sensitization
- 2022
-
Ingår i: Clinical and Experimental Allergy. - : Wiley. - 0954-7894 .- 1365-2222. ; 52:2, s. 297-311
-
Tidskriftsartikel (refereegranskat)abstract
- Background Fractional exhaled nitric oxide (FeNO) is a well-known marker of type-2 inflammation. FeNO is elevated in asthma and allergic rhinitis, with IgE sensitization as a major determinant. Objective We aimed to see whether there was an independent association between upper airway inflammatory disorders (UAID) and FeNO, after adjustment for asthma and sensitization, in a multi-centre population-based study. Methods A total of 741 subjects with current asthma and 4155 non-asthmatic subjects participating in the second follow-up of the European Community Respiratory Health Survey (ECRHS III) underwent FeNO measurements. Sensitization status was based on measurement of IgE against airborne allergens; information on asthma, UAID and medication was collected through interview-led questionnaires. Independent associations between UAID and FeNO were assessed in adjusted multivariate regression models and test for interaction with perennial sensitization and asthma on the relation between UAID and FeNO were made. Results UAID were associated with higher FeNO after adjusting for perennial sensitization, asthma and other confounders: with 4.4 (0.9-7.9) % higher FeNO in relation to current rhinitis and 4.8 (0.7-9.2) % higher FeNO in relation to rhinoconjunctivitis. A significant interaction with perennial sensitization was found in the relationship between current rhinitis and FeNO (p = .03) and between rhinoconjunctivitis and FeNO (p = .03). After stratification by asthma and perennial sensitization, the association between current rhinitis and FeNO remained in non-asthmatic subjects with perennial sensitization, with 12.1 (0.2-25.5) % higher FeNO in subjects with current rhinitis than in those without. Conclusions & Clinical Relevance Current rhinitis and rhinoconjunctivitis was associated with higher FeNO, with an interaction with perennial sensitization. This further highlights the concept of united airway disease, with correlations between symptoms and inflammation in the upper and lower airways and that sensitization needs to be accounted for in the relation between FeNO and rhinitis.
|
|
