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- Papadopoulos, N G, et al.
(author)
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International consensus on (ICON) pediatric asthma.
- 2012
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In: Allergy. - : Wiley. - 1398-9995 .- 0105-4538. ; 67:8, s. 976-97
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Journal article (peer-reviewed)abstract
- Asthma is the most common chronic lower respiratory disease in childhood throughout the world. Several guidelines and/or consensus documents are available to support medical decisions on pediatric asthma. Although there is no doubt that the use of common systematic approaches for management can considerably improve outcomes, dissemination and implementation of these are still major challenges. Consequently, the International Collaboration in Asthma, Allergy and Immunology (iCAALL), recently formed by the EAACI, AAAAI, ACAAI, and WAO, has decided to propose an International Consensus on (ICON) Pediatric Asthma. The purpose of this document is to highlight the key messages that are common to many of the existing guidelines, while critically reviewing and commenting on any differences, thus providing a concise reference. The principles of pediatric asthma management are generally accepted. Overall, the treatment goal is disease control. To achieve this, patients and their parents should be educated to optimally manage the disease, in collaboration with healthcare professionals. Identification and avoidance of triggers is also of significant importance. Assessment and monitoring should be performed regularly to re-evaluate and fine-tune treatment. Pharmacotherapy is the cornerstone of treatment. The optimal use of medication can, in most cases, help patients control symptoms and reduce the risk for future morbidity. The management of exacerbations is a major consideration, independent of chronic treatment. There is a trend toward considering phenotype-specific treatment choices; however, this goal has not yet been achieved.
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- Skjerven, H. O., et al.
(author)
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Skin emollient and early complementary feeding to prevent infant atopic dermatitis (PreventADALL): a factorial, multicentre, cluster-randomised trial
- 2020
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In: The Lancet. - 0140-6736. ; 395:10228, s. 951-961
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Journal article (peer-reviewed)abstract
- Background: Skin emollients applied during early infancy could prevent atopic dermatitis, and early complementary food introduction might reduce food allergy in high-risk infants. The study aimed to determine if either regular skin emollients applied from 2 weeks of age, or early complementary feeding introduced between 12 and 16 weeks of age, reduced development of atopic dermatitis by age 12 months in the general infant population. Methods: This population-based 2×2 factorial, randomised clinical trial was done at Oslo University Hospital and Østfold Hospital Trust, Oslo, Norway; and Karolinska University Hospital, Stockholm, Sweden. Infants of women recruited antenatally at the routine ultrasound pregnancy screening at 18 weeks were cluster-randomised at birth from 2015 to 2017 to the following groups: (1) controls with no specific advice on skin care while advised to follow national guidelines on infant nutrition (no intervention group); (2) skin emollients (bath additives and facial cream; skin intervention group); (3) early complementary feeding of peanut, cow's milk, wheat, and egg (food intervention group); or (4) combined skin and food interventions (combined intervention group). Participants were randomly assigned (1:1:1:1) using computer- generated cluster randomisation based on 92 geographical living area blocks as well as eight 3-month time blocks. Carers were instructed to apply the interventions on at least 4 days per week. Atopic dermatitis by age 12 months was the primary outcome, based on clinical investigations at 3, 6 and 12 months by investigators masked to group allocation. Atopic dermatitis was assessed after completing the 12-month investigations and diagnosed if either of the UK Working Party and Hanifin and Rajka (12 months only) diagnostic criteria were fulfilled. The primary efficacy analyses was done by intention-to-treat analysis on all randomly assigned participants. Food allergy results will be reported once all investigations at age 3 years are completed in 2020. This was a study performed within ORAACLE (the Oslo Research Group of Asthma and Allergy in Childhood; the Lung and Environment). The study is registered at clinicaltrials.gov, NCT02449850. Findings: 2697 women were recruited between Dec 9, 2014, and Oct 31, 2016, from whom 2397 newborn infants were enrolled from April 14, 2015, to April 11, 2017. Atopic dermatitis was observed in 48 (8%) of 596 infants in the no intervention group, 64 (11%) of 575 in the skin intervention group, 58 (9%) of 642 in the food intervention group, and 31 (5%) of 583 in the combined intervention group. Neither skin emollients nor early complementary feeding reduced development of atopic dermatitis, with a risk difference of 3·1% (95% CI –0·3 to 6·5) for skin intervention and 1·0% (–2·1 to 4·1) for food intervention, in favour of control. No safety concerns with the interventions were identified. Reported skin symptoms and signs (including itching, oedema, exanthema, dry skin, and urticaria) were no more frequent in the skin, food, and combined intervention groups than in the no intervention group. Interpretation: Neither early skin emollients nor early complementary feeding reduced development of atopic dermatitis by age 12 months. Our study does not support the use of these interventions to prevent atopic dermatitis by 12 months of age in infants. Funding: The study was funded by several public and private funding bodies: The Regional Health Board South East, The Norwegian Research Council, Health and Rehabilitation Norway, The Foundation for Healthcare and Allergy Research in Sweden-Vårdalstiftelsen, Swedish Asthma and Allergy Association's Research Foundation, Swedish Research Council—the Initiative for Clinical Therapy Research, The Swedish Heart-Lung Foundation, SFO-V at the Karolinska Institute, Freemason Child House Foundation in Stockholm, Swedish Research Council for Health, Working Life and Welfare—FORTE, Oslo University Hospital, the University of Oslo, and Østfold Hospital Trust. © 2020 Elsevier Ltd
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| 5. |
- Östling, Jörgen, et al.
(author)
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IL-17-high asthma with features of a psoriasis immunophenotype
- 2019
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In: Journal of Allergy and Clinical Immunology. - : Elsevier. - 0091-6749 .- 1097-6825. ; 144:5, s. 1198-1213
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Journal article (peer-reviewed)abstract
- Background: The role of IL-17 immunity is well established in patients with inflammatory diseases, such as psoriasis and inflammatory bowel disease, but not in asthmatic patients, in whom further study is required.Objective: We sought to undertake a deep phenotyping study of asthmatic patients with upregulated IL-17 immunity.Methods: Whole-genome transcriptomic analysis was performed by using epithelial brushings, bronchial biopsy specimens (91 asthmatic patients and 46 healthy control subjects), and whole blood samples (n = 498) from the Unbiased Biomarkers for the Prediction of Respiratory Disease Outcomes (U-BIOPRED) cohort. Gene signatures induced in vitro by IL-17 and IL-13 in bronchial epithelial cells were used to identify patients with IL-17–high and IL-13–high asthma phenotypes.Results: Twenty-two of 91 patients were identified with IL-17, and 9 patients were identified with IL-13 gene signatures. The patients with IL-17–high asthma were characterized by risk of frequent exacerbations, airway (sputum and mucosal) neutrophilia, decreased lung microbiota diversity, and urinary biomarker evidence of activation of the thromboxane B2 pathway. In pathway analysis the differentially expressed genes in patients with IL-17-high asthma were shared with those reported as altered in psoriasis lesions and included genes regulating epithelial barrier function and defense mechanisms, such as IL1B, IL6, IL8, and β-defensin.Conclusion: The IL-17–high asthma phenotype, characterized by bronchial epithelial dysfunction and upregulated antimicrobial and inflammatory response, resembles the immunophenotype of psoriasis, including activation of the thromboxane B2 pathway, which should be considered a biomarker for this phenotype in further studies, including clinical trials targeting IL-17.
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- Khaleva, E, et al.
(author)
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Development of Core Outcome Measures sets for paediatric and adult Severe Asthma (COMSA)
- 2023
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In: The European respiratory journal. - : European Respiratory Society (ERS). - 1399-3003 .- 0903-1936. ; 61:4
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Journal article (peer-reviewed)abstract
- Effectiveness studies with biological therapies for asthma lack standardised outcome measures. The COMSA (Core Outcome Measures sets for paediatric and adult Severe Asthma) working group sought to develop Core Outcome Measures (COM) sets to facilitate better synthesis of data and appraisal of biologics in paediatric and adult asthma clinical studies.MethodsCOMSA utilised a multi-stakeholder consensus process among patients with severe asthma, adult, and paediatric clinicians, pharmaceutical representatives and health regulators from across Europe. Evidence included a systematic review of development, validity, and reliability of selected outcome measures plus a narrative review and a pan-European survey to better understand patients’ and carers’ views about outcome measures. It was discussed using a modified GRADE Evidence to Decision framework. Anonymous voting was conducted using predefined consensus criteria.ResultsBoth adult and paediatric COM sets include forced expiratory volume in 1 s (FEV1) as z scores, annual frequency of severe exacerbations and maintenance oral corticosteroid use. Additionally, the paediatric COM set includes the Paediatric Asthma Quality of Life Questionnaire, and Asthma Control Test (ACT) or Childhood-ACT while the adult COM includes the Severe Asthma Questionnaire and the Asthma Control Questionnaire-6 (symptoms and rescue medication use reported separately).ConclusionsThis patient-centred collaboration has produced two COM sets for paediatric and adult severe asthma. It is expected that they will inform the methodology of future clinical trials, enhance comparability of efficacy and effectiveness of biological therapies, and help assess their socioeconomic value. COMSA will inform definitions of non-response and response to biological therapy for severe asthma.
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| 13. |
- Khaleva, E, et al.
(author)
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Development of Core Outcome Measures sets for paediatric and adult Severe Asthma (COMSA)
- 2023
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In: The European respiratory journal. - : European Respiratory Society (ERS). - 1399-3003 .- 0903-1936. ; 61:4
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Journal article (peer-reviewed)abstract
- Effectiveness studies with biological therapies for asthma lack standardised outcome measures. The COMSA (Core Outcome Measures sets for paediatric and adult Severe Asthma) working group sought to develop Core Outcome Measures (COM) sets to facilitate better synthesis of data and appraisal of biologics in paediatric and adult asthma clinical studies.MethodsCOMSA utilised a multi-stakeholder consensus process among patients with severe asthma, adult, and paediatric clinicians, pharmaceutical representatives and health regulators from across Europe. Evidence included a systematic review of development, validity, and reliability of selected outcome measures plus a narrative review and a pan-European survey to better understand patients’ and carers’ views about outcome measures. It was discussed using a modified GRADE Evidence to Decision framework. Anonymous voting was conducted using predefined consensus criteria.ResultsBoth adult and paediatric COM sets include forced expiratory volume in 1 s (FEV1) as z scores, annual frequency of severe exacerbations and maintenance oral corticosteroid use. Additionally, the paediatric COM set includes the Paediatric Asthma Quality of Life Questionnaire, and Asthma Control Test (ACT) or Childhood-ACT while the adult COM includes the Severe Asthma Questionnaire and the Asthma Control Questionnaire-6 (symptoms and rescue medication use reported separately).ConclusionsThis patient-centred collaboration has produced two COM sets for paediatric and adult severe asthma. It is expected that they will inform the methodology of future clinical trials, enhance comparability of efficacy and effectiveness of biological therapies, and help assess their socioeconomic value. COMSA will inform definitions of non-response and response to biological therapy for severe asthma.
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| 19. |
- Mathioudakis, AG, et al.
(author)
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Management of asthma in childhood: study protocol of a systematic evidence update by the Paediatric Asthma in Real Life (PeARL) Think Tank
- 2021
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In: BMJ open. - : BMJ. - 2044-6055. ; 11:7, s. e048338-
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Journal article (peer-reviewed)abstract
- Clinical recommendations for childhood asthma are often based on data extrapolated from studies conducted in adults, despite significant differences in mechanisms and response to treatments. The Paediatric Asthma in Real Life (PeARL) Think Tank aspires to develop recommendations based on the best available evidence from studies in children. An overview of systematic reviews (SRs) on paediatric asthma maintenance management and an SR of treatments for acute asthma attacks in children, requiring an emergency presentation with/without hospital admission will be conducted.Methods and analysisStandard methodology recommended by Cochrane will be followed. Maintenance pharmacotherapy of childhood asthma will be evaluated in an overview of SRs published after 2005 and including clinical trials or real-life studies. For evaluating pharmacotherapy of acute asthma attacks leading to an emergency presentation with/without hospital admission, we opted to conduct de novo synthesis in the absence of adequate up-to-date published SRs. For the SR of acute asthma pharmacotherapy, we will consider eligible SRs, clinical trials or real-life studies without time restrictions. Our evidence updates will be based on broad searches of Pubmed/Medline and the Cochrane Library. We will use A MeaSurement Tool to Assess systematic Reviews, V.2, Cochrane risk of bias 2 and REal Life EVidence AssessmeNt Tool to evaluate the methodological quality of SRs, controlled clinical trials and real-life studies, respectively.Next, we will further assess interventions for acute severe asthma attacks with positive clinical results in meta-analyses. We will include both controlled clinical trials and observational studies and will assess their quality using the previously mentioned tools. We will employ random effect models for conducting meta-analyses, and Grading of Recommendations Assessment, Development and Evaluation methodology to assess certainty in the body of evidence.Ethics and disseminationEthics approval is not required for SRs. Our findings will be published in peer reviewed journals and will inform clinical recommendations being developed by the PeARL Think Tank.PROSPERO registration numbersCRD42020132990, CRD42020171624.
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| 20. |
- Nieto, A, et al.
(author)
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Allergy and asthma prevention 2014
- 2014
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In: Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology. - : Wiley. - 1399-3038. ; 25:6, s. 516-533
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Journal article (peer-reviewed)
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- Tedner, S. G., et al.
(author)
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Maternal sensitization during pregnancy
- 2018
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In: Allergy. European Journal of Allergy and Clinical Immunology. - : WILEY. - 0105-4538 .- 1398-9995. ; 73:Suppl. 105, s. 694-694
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Journal article (other academic/artistic)
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- Almqvist, C, et al.
(author)
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Direct and indirect exposure to pets : - risk of sensitization and asthma at 4 years in a birth cohort
- 2003
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In: Clinical and Experimental Allergy. - : Wiley-Blackwell. - 0954-7894 .- 1365-2222. ; 33, s. 1190-
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Journal article (peer-reviewed)abstract
- INTRODUCTION: There are conflicting data on the association between early exposure to pets and allergic diseases. Bias related to retrospective information on pet ownership has been addressed as a reason for distorted study results.OBJECTIVE: To elucidate how early exposure to cat and dog relates to IgE-sensitization and asthma in children at 2 and 4 years of age, in a prospective birth-cohort study.METHODS: Four thousand and eighty-nine families with children born 1994-1996 in predefined areas of Stockholm answered questionnaires on environmental factors and symptoms of allergic disease at birth, one, two and four years of age. Dust samples collected from the mothers' beds at birth were analysed for Fel d 1 and Can f 1 in a subgroup of the cohort. Blood samples taken at four years from 2614 children were analysed for allergen-specific IgE to common airborne allergens. Risk associations were calculated with a multiple logistic regression model, with adjustment for potential confounders.RESULTS: A correlation was seen between allergen levels and reported exposure to cat and dog. Exposure to cat seemed to increase the risk of cat sensitization, OR (odds ratio) 1.44 (95% confidence interval 1.03-2.01), whereas dog exposure did not have any effect on dog sensitization, OR 1.16 (0.79-1.72). Dog ownership was related to a reduced risk of sensitization to other airborne allergens, OR 0.36 (0.15-0.83), and a similar tendency was seen for cat ownership OR 0.63 (0.37-1.07). Early dog ownership seemed to be associated with a lower risk of asthma, OR 0.50 (0.24-1.03), with no corresponding effect after cat ownership, OR 0.88 (0.56-1.38).CONCLUSION: Early exposure to cat seems to increase the risk of sensitization to cat but not of asthma at 4 years of age. Dog ownership, on the other hand, appears to be associated with lowered risk of sensitization to airborne allergens and asthma. Both aetiological relationships and selection effects have to be considered in the interpretation of these findings.
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| 36. |
- Asarnoj, A., et al.
(author)
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IgE to peanut allergen components : relation to peanut symptoms and pollen sensitization in 8-year-olds
- 2010
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In: Allergy. European Journal of Allergy and Clinical Immunology. - : Wiley. - 0105-4538 .- 1398-9995. ; 65:9, s. 1189-1195
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Journal article (peer-reviewed)abstract
- Background: Allergen-specific IgE testing is often performed with crude peanut extract, but the results may be difficult to interpret because of cross-reactions between peanut and other plant allergens. The aim was to investigate IgE reactivity to peanut allergen components in children from a birch-rich region in relation to pollen sensitization and peanut symptoms. Methods: From a birth cohort, clinical parameters were obtained through questionnaires and IgE antibody levels to peanut and birch pollen were measured. Different peanut/birch sensitization phenotypes were defined among 200 selected children. IgE reactivity to peanut and pollen allergen components was analysed using microarray technique. Results: Peanut symptoms were reported in 87% of the children with IgE reactivity to any of the peanut allergens Ara h 1, 2 or 3 but not to Ara h 8 (n = 46) vs 17% of children with IgE reactivity to Ara h 8 but not to Ara h 1, 2 or 3 (n = 23), P < 0.001. Furthermore, symptoms were more severe in children with Ara h 1, 2 or 3 reactivity. Children with IgE reactivity both to Ara h 2 and to Ara h 1 or 3 more often reported peanut symptoms than children with IgE only to Ara h 2 (97% vs 70%, P = 0.016), particularly respiratory symptoms (50% vs 9%, P = 0.002). Conclusions: IgE analysis to peanut allergen components may be used to distinguish between peanut-sensitized individuals at risk of severe symptoms and those likely to have milder or no symptoms to peanut if sensitized to pollen allergens and their peanut homologue allergens.
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| 44. |
- Carlsen, O. C. L., et al.
(author)
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Physical activity in pregnancy: a Norwegian-Swedish mother-child birth cohort study
- 2021
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In: AJOG Global Reports. - : Elsevier BV. - 2666-5778. ; 1:1
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Journal article (peer-reviewed)abstract
- BACKGROUND: Physical activity during pregnancy is important for maternal and offspring health. Optimal conditions during pregnancy may help reduce the burden of noncommunicable diseases. National and international guidelines recommend at least 150 minutes of physical activity of at least moderate intensity per week. To optimize physical activity in pregnant women, it is important to identify factors associated with higher levels of physical activity. OBJECTIVE: This study aimed to explore types and levels of physical activity in midpregnancy in Norway and Sweden and to identify factors associated with higher levels of physical activity. MATERIALS AND METHODS: From the population-based mother-child cohort Preventing Atopic Dermatitis and Allergies in Children study recruiting 2697 women in Norway and Sweden from 2014 to 2016, we included 2349 women who answered an electronic questionnaire at enrollment in midpregnancy. Women were asked about regular physical activity in the last 2 weeks of pregnancy and afterward for types and levels of physical activity in pregnancy and before pregnancy and socioeconomic status, lifestyle, and maternal health. Logistic regression analyses were used to identify factors associated with higher levels of physical activity in pregnancy, defined as >30 minutes per session of ≥2 times per week of moderate- or high-intensity brisk walking, strength training, jogging, and bicycling. RESULTS: No regular physical activity during the last 2 weeks before answering the questionnaire at midpregnancy was reported by 689 women (29%). In this study, 1787 women (76%) reported weekly strolling during pregnancy. Regular physical activity at least twice weekly in the first half of pregnancy was reported as brisk walking by 839 women (36%), bicycling by 361 women (15%), strength training by 322 women (14%), and other activities by <10% of women. Among the 1430 women with regular moderate- or high-intensity physical activity, the estimated median duration per week was 120 minutes. Higher physical activity levels were achieved in 553 women (23.5%) by brisk walking, 287 women (12.2%) by strength training, 263 women (11.2%) by bicycling, and 114 women (4.9%) by jogging. Higher physical activity levels were positively associated with regular physical activity before pregnancy, dog ownership, and atopic dermatitis and negatively associated with higher body mass index, study location in Østfold, previous pregnancy or pregnancies, non-Nordic origin, suburban living, and sick leave. CONCLUSION: At midpregnancy, 29% of women were inactive, and less than 50% of women had at least 2 hours of moderate-intensity physical activity weekly. Awareness of physical activity in pregnancy should be discussed at pregnancy follow-up visits, particularly among women with higher body mass index, sick leave, previous pregnancy or pregnancies, and non-Nordic origin.
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| 49. |
- Fleming, L, et al.
(author)
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The burden of severe asthma in childhood and adolescence: results from the paediatric U-BIOPRED cohorts
- 2015
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In: The European respiratory journal. - : European Respiratory Society (ERS). - 1399-3003 .- 0903-1936. ; 46:5, s. 1322-1333
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Journal article (peer-reviewed)abstract
- U-BIOPRED aims to characterise paediatric and adult severe asthma using conventional and innovative systems biology approaches.A total of 99 school-age children with severe asthma and 81 preschoolers with severe wheeze were compared with 49 school-age children with mild/moderate asthma and 53 preschoolers with mild/moderate wheeze in a cross-sectional study.Despite high-dose treatment, the severe cohorts had more severe exacerbations compared with the mild/moderate ones (annual medians: school-aged 3.0 versus 1.1, preschool 3.9 versus 1.8; p<0.001). Exhaled tobacco exposure was common in the severe wheeze cohort. Almost all participants in each cohort were atopic and had a normal body mass index. Asthma-related quality of life, as assessed by the Paediatric Asthma Quality of Life Questionnaire (PAQLQ) and the Paediatric Asthma Caregiver's Quality of Life Questionnaire (PACQLQ), was worse in the severe cohorts (mean±se school-age PAQLQ: 4.77±0.15 versus 5.80±0.19; preschool PACQLQ: 4.27±0.18 versus 6.04±0.18; both p≤0.001); however, mild/moderate cohorts also had significant morbidity. Impaired quality of life was associated with poor control and airway obstruction. Otherwise, the severe and mild/moderate cohorts were clinically very similar.Children with severe preschool wheeze or severe asthma are usually atopic and have impaired quality of life that is associated with poor control and airflow limitation: a very different phenotype from adult severe asthma. In-depth phenotyping of these children, integrating clinical data with high-dimensional biomarkers, may help to improve and tailor their clinical management.
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