| 1. |
- Ballardini, Natalia, et al.
(författare)
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Development and comorbidity of eczema, asthma and rhinitis to age 12 : data from the BAMSE birth cohort
- 2012
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Ingår i: Allergy. - Stockholm : Karolinska Institutet, Dept of Medical Epidemiology and Biostatistics. - 0105-4538 .- 1398-9995.
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Allergy-related diseases are a public health issue, but knowledge on development and comorbidity among children is scarce. The aim was to study the development of eczema, asthma and rhinitis in relation to sex and parental allergy, in a population-based cohort, during childhood. METHODS: At 1, 2, 4, 8 and 12 years, parental questionnaires were used to obtain data on allergy-related diseases. Complete data for all five follow-up occasions were available from 2916 children. Odds ratios for the risk of any allergy-related disease in relation to heredity and sex were calculated using generalized estimating equations. RESULTS: At 12 years, 58% of the children had had eczema, asthma and/or rhinitis at some time. Disease turnover was high for all three diseases throughout the study. Comorbidity increased with age, and at 12 years, 7.5% of all the children were affected by at least two allergy-related diseases. Parental allergy was associated with increased comorbidity and more persistent disease and increased the risk of having any allergy-related disease (adjusted OR 1.76; 95% CI 1.57-1.97) up to 12 years. Male sex was associated with an increased risk throughout childhood. Boys and girls did not differ in disease persistence, and for comorbidity, the differences were minor. CONCLUSIONS: Allergy-related diseases may affect a majority of children. Eczema, asthma and rhinitis develop dynamically throughout childhood, and allergic comorbidity is common. These findings indicate that allergy-related diseases should be neither seen nor studied as isolated entities.
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| 2. |
- Hedman, Anna M, et al.
(författare)
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Allergen-specific IgE over time in women before, during and after pregnancy
- 2018
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Ingår i: Allergy. - Stockholm : Karolinska Institutet, Dept of Medical Epidemiology and Biostatistics. - 0105-4538 .- 1398-9995.
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Tidskriftsartikel (refereegranskat)abstract
- The trajectory of IgE levels before, during and after pregnancy in sensitized individuals is characterized by significant increase in specific IgE to birch allergens but not to other allergens after multiple testing. This increase may warrant some surveillance in the antenatal care for those with clinical symptoms.
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| 3. |
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| 4. |
- Mogensen, N., et al.
(författare)
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Association between childhood asthma and ADHD symptoms in adolescence : a prospective population-based twin study
- 2011
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Ingår i: Allergy. European Journal of Allergy and Clinical Immunology. - Malden, USA : Wiley-Blackwell. - 0105-4538 .- 1398-9995. ; 66:9, s. 1224-1230
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Tidskriftsartikel (refereegranskat)abstract
- Background: Cross-sectional studies report a relationship between childhood asthma and attention-deficit hyperactivity disorder (ADHD) symptoms, but the mechanisms are yet unclear. Our objective was to investigate the longitudinal link between childhood asthma and the two dimensions of ADHD (hyperactivity-impulsivity, HI, and inattention, IN) in adolescence. We also aimed to explore the genetic and environmental contributions and the impact of asthma medication.Methods: Data on asthma, HI and IN, birth weight, socioeconomic status, zygosity, and medication were collected from the Swedish Medical Birth Register and through parental questionnaires at ages 8-9 and 13-14 years on 1480 Swedish twin pairs born 1985-1986. The association between asthma at age 8-9 and ADHD symptoms at age 13-14 was assessed with generalized estimating equations, and twin analyses to assess the genetic or environmental determinants were performed.Results: Children with asthma at age 8-9 had an almost twofold increased risk of having one or more symptom of HI (OR 1.88, 95% CI 1.18-3.00) and a more than twofold increased risk to have three symptoms or more of HI (OR 2.73, 95% CI 1.49-5.00) at age 13-14, independent of asthma medication. For IN, no significant relationship was seen. Results from twin modeling indicate that 68% of the phenotypic correlation between asthma and HI (r=0.23, 0.04-0.37) was because of genetic influences.Conclusions Our findings suggest that childhood asthma is associated with subsequent development of HI in early adolescence, which could be partly explained by genetic influences. Early strategies to identify children at risk may reduce burden of the disease in adolescence.
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| 5. |
- Ullemar, V., et al.
(författare)
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Heritability and confirmation of genetic association studies for childhood asthma in twins
- 2016
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Ingår i: Allergy. - Stockholm : Wiley. - 0105-4538 .- 1398-9995. ; 71:2, s. 230-238
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundAlthough the genetics of asthma has been extensively studied using both quantitative and molecular genetic analysis methods, both approaches lack studies specific to the childhood phenotype and including other allergic diseases. This study aimed to give specific estimates for the heritability of childhood asthma and other allergic diseases, to attempt to replicate findings from genomewide association studies (GWAS) for childhood asthma and to test the same variants against other allergic diseases. MethodsIn a cohort of 25 306 Swedish twins aged 9 or 12 years, data on asthma were available from parental interviews and population-based registers. The interviews also inquired about wheeze, hay fever, eczema, and food allergy. Through structural equation modeling, the heritability of all phenotypes was calculated. A subset of 10 075 twins was genotyped for 16 single nucleotide polymorphisms (SNPs) selected from previous GWAS; these were first tested for association with asthma and significant findings also against the other allergic diseases. ResultsThe heritability of any childhood asthma was 0.82 (95% CI 0.79-0.85). For the other allergic diseases, the range was approximately 0.60-0.80. Associations for six SNPs with asthma were replicated, including rs2305480 in the GSDMB gene (OR 0.80, 95% CI 0.74-0.86, P = 1.5*10(-8); other significant associations all below P = 3.5*10(-4)). Of these, only rs3771180 in IL1RL1 was associated with any other allergic disease (for hay fever, OR 0.64, 95% CI 0.53-0.77, P = 2.5*10(-6)). ConclusionAsthma and allergic diseases of childhood are highly heritable, and these high-risk genetic variants associated specifically with childhood asthma, except for one SNP shared with hay fever.
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| 6. |
- Johansson, SGO
(författare)
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Untitled
- 2002
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Ingår i: ALLERGY. - : Wiley. - 0105-4538. ; 57:9, s. 759-759
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 7. |
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| 8. |
- Aberg, N, et al.
(författare)
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Prevalence of allergic diseases in schoolchildren in relation to family history, upper respiratory infections, and residential characteristics.
- 1996
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Ingår i: Allergy. - : Wiley. - 0105-4538 .- 1398-9995. ; 51:4, s. 232-7
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Tidskriftsartikel (refereegranskat)abstract
- The prevalences of asthma, allergic rhinitis (AR), and eczema were analyzed in relation to retrospective risk factors from birth in a questionnaire study of schoolchildren in two areas covering the whole climatic span of Sweden: the Göteborg area on the southwestern coast (7-year-olds, n = 1649) and Kiruna, a mining town in the northernmost inland mountains (7-9-year-olds, n = 832). The strongest background factor, a family history of the diseases, was more common in children with another strong risk factor, particularly for asthma: high frequency of upper respiratory tract infection (URTI). Other significant risk factors related to high indoor humidity caused an increased prevalence of both allergic diseases and URTI. Active mechanical ventilation of the homes caused a slight reduction of the prevalence of allergic diseases, and repainting or new wallpaper in the bedroom of the child after birth caused a moderately increased risk of allergic disease. This study illustrates the interaction between genetic and environmental risk factors with special emphasis on factors related to an unventilated indoor climate, which may have substantially contributed to the current increase of the diseases in the country.
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| 9. |
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| 10. |
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| 11. |
- Accordini, S, et al.
(författare)
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The socio-economic burden of asthma is substantial in Europe
- 2008
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Ingår i: Allergy. European Journal of Allergy and Clinical Immunology. - : Wiley. - 0105-4538 .- 1398-9995. ; 63:1, s. 116-124
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- BACKGROUND: Few data are available on the asthma burden in the general population. We evaluated the level and the factors associated with the asthma burden in Europe. METHODS: In 1999-2002, 1152 adult asthmatics were identified in the European Community Respiratory Health Survey (ECRHS)-II and the socio-economic burden (reduced activity days and hospital services utilization in the past 12 months) was assessed. RESULTS: The asthmatics with a light burden (only a few reduced activity days) were 13.2% (95% CI: 11.4-15.3%), whereas those with a heavy burden (many reduced activity days and/or hospital services utilization) were 14.0% (95% CI: 12.1-16.1%). The burden was strongly associated with disease severity and a lower quality of life. Obese asthmatics had a significantly increased risk of a light [relative risk ratio (RRR) = 2.17; 95% CI: 1.18-4.00] or a heavy burden (RRR = 2.77; 95% CI: 1.52-5.05) compared with normal/underweight subjects. The asthmatics with frequent respiratory symptoms showed a threefold (RRR = 2.74; 95% CI: 1.63-4.61) and sixfold (RRR = 5.76; 95% CI: 3.25-10.20) increased risk of a light or a heavy burden compared with asymptomatic asthmatics, respectively. Moreover, the lower the forced expiratory volume in 1 s % predicted, the higher the risk of a heavy burden. The coexistence with chronic cough/phlegm only increased the risk of a heavy burden (RRR = 1.88; 95% CI: 1.16-3.06). An interaction was found between gender and IgE sensitization, with nonatopic asthmatic females showing the highest risk of a heavy burden (21.6%; 95% CI: 16.9-27.1%). CONCLUSIONS: The asthma burden is substantial in Europe. A heavy burden is more common in asthmatics with obesity, frequent respiratory symptoms, low lung function, chronic cough/phlegm and in nonatopic females.
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| 16. |
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| 17. |
- Admyre, C, et al.
(författare)
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Exosomes - nanovesicles with possible roles in allergic inflammation.
- 2008
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Ingår i: Allergy. - : Wiley. - 1398-9995 .- 0105-4538. ; 63:4, s. 404-8
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Forskningsöversikt (refereegranskat)abstract
- Exosomes are nano-sized membrane vesicles which are released extracellularly after fusion of multivesicular endosomes with the cell membrane. Despite their characteristic composition of proteins compared to the cell membrane, no exosome-specific molecule has so far been characterized. Exosomes are found in bronchoalveolar lavage (BAL), urine, serum and breast milk, and are released from several cells implicated in allergy including mast cells, dendritic cells (DC), T cells and epithelial cells. Antigen-loaded exosomes have been shown to be highly immunogenic and we propose that exosomes could be a modulating factor in allergic responses. Allergen-presenting exosomes could transport allergen and stimulate allergen-specific T cells, and possibly also biasing T cell responses depending on the molecules present on the exosome surface. Furthermore, exosomes from mast cells, highly active in allergic reactions, have been found to induce DC maturation and also to be able to transport functional RNA to recipient cells, suggesting a new pathway for cell communication. Reversely, tolerizing exosomes e.g. tolerosomes, from gut or breast milk, could block an allergic response or prevent allergy development. A better understanding of the role of exosomes in allergies could make us understand how allergy can be prevented or lead to the development of more efficient treatments.
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| 18. |
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| 19. |
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| 20. |
- Agache, Ioana, et al.
(författare)
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Prioritizing research challenges and funding for allergy and asthma and the need for translational research—The European Strategic Forum on Allergic Diseases
- 2019
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Ingår i: Allergy: European Journal of Allergy and Clinical Immunology. - : Wiley. - 0105-4538. ; 74:11, s. 2064-2076
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Tidskriftsartikel (refereegranskat)abstract
- The European Academy of Allergy and Clinical Immunology (EAACI) organized the first European Strategic Forum on Allergic Diseases and Asthma. The main aim was to bring together all relevant stakeholders and decision-makers in the field of allergy, asthma and clinical Immunology around an open debate on contemporary challenges and potential solutions for the next decade. The Strategic Forum was an upscaling of the EAACI White Paper aiming to integrate the Academy's output with the perspective offered by EAACI's partners. This collaboration is fundamental for adapting and integrating allergy and asthma care into the context of real-world problems. The Strategic Forum on Allergic Diseases brought together all partners who have the drive and the influence to make positive change: national and international societies, patients’ organizations, regulatory bodies and industry representatives. An open debate with a special focus on drug development and biomedical engineering, big data and information technology and allergic diseases and asthma in the context of environmental health concluded that connecting science with the transformation of care and a joint agreement between all partners on priorities and needs are essential to ensure a better management of allergic diseases and asthma in the advent of precision medicine together with global access to innovative and affordable diagnostics and therapeutics.
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| 21. |
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| 22. |
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| 23. |
- Ahlstedt, S, et al.
(författare)
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Immune stimulated regional inflammatory responses mediating lung reactivity in rats.
- 1985
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Ingår i: Allergy. - : Wiley. - 0105-4538 .- 1398-9995. ; 40:4, s. 282-8
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Tidskriftsartikel (refereegranskat)abstract
- Daily sensitization of SPF BNxWi/Fu rats with ovalbumin (OA) in aerosol during 2-week periods with a 4-week interval resulted after 7 weeks in IgE, IgA and IgG antibodies in serum and bronchial fluid. After cultivation of the regional, axillary, brachial and mediastinal (ABM) lymph node cells, IgE antibodies were found in the culture supernatant. Such antibodies were not found in culture supernatants of spleen and inguinal lymph nodes. Regional formation of IgE antibodies was also noted in the ABM lymph node cell culture supernatants after subcutaneous (s.c.) injections of 100 ng OA in the neck region. When the injections were given in the tail-root region, the inguinal but not the ABM lymph nodes produced the IgE antibodies. The s.c. sensitization induced inconsistent and rather low IgG and no IgA antibody responses. The aerosol but not the s.c. sensitization induced accumulations of mononuclear cells and mucous cells in the lungs. Clinically, the rats sensitized s.c. in the neck region reacted to aerosol and intravenous (i.v.) challenge as early as 1 week after sensitization had started, whereas the animals sensitized in the tail-root regions reacted 7 and 8 weeks after repeated sensitization. The animals sensitized by aerosol showed only weak clinical reactivity after i.v. challenge.
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| 24. |
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| 25. |
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| 26. |
- Akbarshahi, Hamid, et al.
(författare)
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House dust mite impairs antiviral response in asthma exacerbation models through its effects on TLR3
- 2018
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Ingår i: Allergy. - : Wiley. - 1398-9995 .- 0105-4538. ; 73:5, s. 1053-1063
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Impaired antiviral interferon expression may be involved in asthma exacerbations commonly caused by rhinovirus infections. Allergy is a known risk factor for viral-induced asthma exacerbation, but little is known whether allergens may affect interferon responses.OBJECTIVE: Our hypothesis is that house dust mite (HDM) impairs viral stimulus-induced antiviral signalling.METHODS: Experimental asthma exacerbations were produced in vitro in human bronchial epithelial cells (HBECs) and in mice by using sequential challenges with HDM and a viral infection mimic, Poly(I:C). We examined rhinovirus pattern recognition receptors (PRRs) signalling pathways and potential mechanisms of impaired interferon response.RESULTS: HBECs and mice exposed to HDM prior to Poly(I:C) exhibited a reduced antiviral response compared to Poly(I:C) alone, including reduced IFN-β, IFN-lambda, TLR3, RIG-I, MDA5, IRF-3 and IRF-7. Heat-inactivation of HDM partially restored the TLR3-induced interferon response in vitro and in vivo. Our HBEC-data further showed that HDM directly affects TLR3 signalling by targeting the receptor glycosylation level.CONCLUSIONS: Direct effects of allergens such as HDM on PRRs can present as potential mechanism for defective antiviral airway responses. Accordingly, therapeutic measures targeting inhibitory effects of allergens on antiviral PRRs may find use as a strategy to boost antiviral response and ameliorate exacerbations in asthmatic patients. This article is protected by copyright. All rights reserved.
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| 27. |
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| 28. |
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| 29. |
- Alenmyr, Lisa, et al.
(författare)
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TRPV1-mediated itch in seasonal allergic rhinitis.
- 2009
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Ingår i: Allergy. - : Wiley. - 1398-9995 .- 0105-4538. ; 64, s. 807-810
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Tidskriftsartikel (refereegranskat)abstract
- Background: Patients with allergic rhinitis may be abnormally sensitive to stimulation of the ion channel transient receptor potential vanilloid-1 (TRPV1). Aim of the study: To examine effects of various TRP ion channel activators on sensory symptoms in allergic rhinitis prior to and during seasonal allergen exposure. Methods: Nasal challenges were carried out with the TRPV1-activators capsaicin, anandamide and olvanil. Moreover, challenges were performed with mustard oil (allylisothiocyanate) and cinnamaldehyde as well as menthol, activators of TRPA1 and TRPM8, respectively. Nasal symptoms were monitored after each challenge and compared with symptoms reported following corresponding sham challenges. Symptoms recorded after challenge prior to pollen season were also compared with challenge-induced symptoms during pollen season. Results: The TRPV1, TRPA1 and TRPM8-activators produced sensory symptoms dominated by pain and smart. During seasonal allergen exposure, but not prior to season, TRPV1-activators also induced itch. Furthermore, the seasonal challenge to the TRPV1-activator olvanil was associated with rhinorrhoea. Conclusion: Patients with allergic rhinitis feature an increased itch response to TRPV1 stimulation at seasonal allergen exposure. We suggest that this reflects part of the hyperresponsiveness that characterizes on-going allergic rhinitis. Intervention with the TRPV1-signalling pathway may offer potential treatments of this condition.
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| 30. |
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| 31. |
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| 33. |
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| 34. |
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| 35. |
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| 36. |
- Alvarado-Vazquez, Perla Abigail, et al.
(författare)
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Circulating mast cell progenitors increase in frequency during natural birch pollen exposure in allergic asthma patients
- 2023
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Ingår i: Allergy. European Journal of Allergy and Clinical Immunology. - : John Wiley & Sons. - 0105-4538 .- 1398-9995. ; 78:11, s. 2959-2968
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Tidskriftsartikel (refereegranskat)abstract
- Background: Mast cells (MCs) develop from a rare population of peripheral blood circulating MC progenitors (MCps). Here, we investigated whether the frequency of circulating MCps is altered in asthma patients sensitized to birch pollen during pollen season, compared to out of season.Methods: Asthma patients were examined during birch pollen season in late April to early June (May), and out of season in November–January. Spirometry measurements, asthma and allergy-related symptoms, asthma control questionnaire (ACQ), and asthma control test (ACT) scores were assessed at both time points. The MCp frequency was determined by flow cytometry in ficoll-separated blood samples from patients with positive birch pollen-specific IgE, and analyzed in relation to basic and disease parameters.Results: The frequency of MCps per liter of blood was higher in May than in November (p = .004), particularly in women (p = .009). Patients that reported moderate to severe asthma symptoms (<.0001), nose or eye symptoms (p = .02; p = .01), or reduced asthma control (higher ACQ, p = .01) had higher MCp frequency in May than those that did not report this. These associations remained significant after adjusting for sex and BMI. The change in asthma control to a lower ACT score in May correlated with an increase in MCp frequency in May (p = .006, rho = 0.46).Conclusions: The data suggest that the frequency of MCps increases in symptomatic patients with allergic asthma. Our results unravel a link between asthma symptoms and circulating MCps, and bring new insight into the impact of natural allergen exposure on the expansion of MCs.
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| 37. |
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| 38. |
- Alvarado-Vazquez, Perla A., et al.
(författare)
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Use of spirometry-like measurements to monitor house dust mite-induced experimental asthma in mice
- 2021
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Ingår i: Allergy. European Journal of Allergy and Clinical Immunology. - : John Wiley & Sons. - 0105-4538 .- 1398-9995. ; 76:7, s. 2204-2207
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Tidskriftsartikel (refereegranskat)abstract
- Weight and age correlated positively with FEV 0.1 and PEF among other lung function parameters in naïve mice. Lung function parameters decline in a model of experimental asthma induced by intranasal HDM administrations. Systemic injections of dexamethasone improved lung function, decreased mast cell populations and BAL levels of mast cell protease-1 in the HDM model.
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| 39. |
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| 40. |
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| 41. |
- Amaral, A F S, et al.
(författare)
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The locus C11orf30 increases susceptibility to poly-sensitization
- 2015
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Ingår i: Allergy. European Journal of Allergy and Clinical Immunology. - : Wiley. - 0105-4538 .- 1398-9995. ; 70:3, s. 328-333
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Tidskriftsartikel (refereegranskat)abstract
- A number of genetic variants have been associated with allergic sensitization, but whether these are allergen specific or increase susceptibility to poly-sensitization is unknown. Using data from the large multicentre population-based European Community Respiratory Health Survey, we assessed the association between 10 loci and specific IgE and skin prick tests to individual allergens and poly-sensitization. We found that the 10 loci associate with sensitization to different allergens in a nonspecific manner and that one in particular, C11orf30-rs2155219, doubles the risk of poly-sensitization (specific IgE/4 allergens: OR = 1.81, 95% CI 0.80-4.24; skin prick test/4+ allergens: OR = 2.27, 95% CI 1.34-3.95). The association of rs2155219 with higher levels of expression of C11orf30, which may be involved in transcription repression of interferon-stimulated genes, and its association with sensitization to multiple allergens suggest that this locus is highly relevant for atopy.
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| 42. |
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| 43. |
- Amin, Kawa, et al.
(författare)
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The extracellular deposition of mast cell products is increased in hypertrophic airways smooth muscles in allergic asthma but not in nonallergic asthma
- 2005
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Ingår i: Allergy. European Journal of Allergy and Clinical Immunology. - : Wiley. - 0105-4538 .- 1398-9995. ; 60:10, s. 1241-1247
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Bronchial asthma is characterized by airways smooth muscle hypertrophy and infiltration of mast cells in the bronchial mucosa. The aim of this investigation was to study the distribution of mast cells in different compartments in the bronchial mucosa of allergic and nonallergic asthma in relation to airways remodeling. METHODS: Bronchial biopsies were obtained from 29 subjects with allergic and nonallergic asthma and healthy controls. The biopsies were stained for mast cells by means of the tryptase specific antibody AA1. Extracellular deposition of mast cell products were judged on a semi-quantitative scale. Mast cells per mm(2) were counted in epithelium, lamina propria and the smooth muscle compartment. Smooth muscle was visualized by actin antibodies and the proportion of staining of the biopsy estimated. Laminin and tenascin layers were visualized by their respective antibodies. RESULTS: Airways smooth muscle thickness was greater in allergic vs nonallergic asthma (P < 0.001). Mast cells were increased in all three compartments in both allergic and nonallergic asthma, with significantly higher numbers in smooth muscles in allergic asthma (P < 0.03). The extracellular deposition of mast cell products was more common in allergic than nonallergic asthma in lamina propria and smooth muscles (P = 0.025; P = 0.002, respectively). In patients with allergic asthma the numbers of mast cells with extracellular deposition of mast cell products were significantly correlated to the thickness of the laminin and tenascin layers. CONCLUSION: Our results suggest that there are large differences between allergic and nonallergic asthmatics as to mast cell activation and airways smooth muscle thickness. Our data implies that mast cells are causally involved in structural alterations in allergic asthma.
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| 44. |
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| 45. |
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| 46. |
- Andersson, Cecilia, et al.
(författare)
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Alveolar mast cells shift to an FcεRI-expressing phenotype in mild atopic asthma: a novel feature in allergic asthma pathology.
- 2011
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Ingår i: Allergy. - : Wiley. - 1398-9995 .- 0105-4538. ; 66:12, s. 1590-1597
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Tidskriftsartikel (refereegranskat)abstract
- Background: A unique feature of alveolar mast cells is their low high-affinity IgE receptor (FcεRI) expression. Recent discoveries in uncontrolled asthma suggest that the appearance of FcεRI-expressing alveolar mast cells may be a novel disease-specific feature of allergic asthma. This study investigates whether increased FcεRI-expressing alveolar mast cells are present in patients with mild allergic asthma or even in non-asthmatic allergic rhinitis patients (AR) who have developed bronchial hyperactivity (BHR). Methods: Bronchial and alveolar tissues were obtained from healthy controls, AR patients with or without BHR, and AR patients with concurrent asthma. Samples were processed for immunohistochemical identification of MC(T) and MC(TC) and expression of FcεRI and surface-bound IgE. Results: Bronchial mast cell expression of FcεRI was high in all groups. In contrast, in the alveolar tissue, the expression of FcεRI on mast cells was low in healthy controls and in the AR patient groups, whereas a high expression was present in AR patients with concurrent asthma (P = 0.006 compared to controls). The asthmatics had a 29-fold increase in numbers (P = 0.006) and a 19-fold increase in proportion (P = 0.007) of alveolar mast cells that expressed surface-bound IgE. Conclusions: The present data show that alveolar mast cells in patients with mild atopic asthma, but not atopic patients with AR, have turned into a highly FcεRI- and IgE-expressing phenotype. These data support the hypothesis that increased FcεRI expression on alveolar mast cells is a novel disease-specific feature of allergic asthma that is important for understanding asthma phenotypes and designing new therapeutic strategies.
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| 47. |
- Andersson, Cecilia K., et al.
(författare)
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Impaired airway epithelial cell wound-healing capacity is associated with airway remodelling following RSV infection in severe preschool wheeze
- 2020
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Ingår i: Allergy: European Journal of Allergy and Clinical Immunology. - : Wiley. - 0105-4538. ; 75:12, s. 3195-3207
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Tidskriftsartikel (refereegranskat)abstract
- Background: Respiratory syncytial virus (RSV) causes exacerbations of asthma and preschool wheeze (PSW). However, the anti-viral and repair responses of the bronchial epithelium in children with severe therapy-resistant asthma (STRA) and PSW are poorly understood. Methods: Children with STRA (age 12 [6-16] years), PSW (age 2 [1-5] years) and non-asthmatic controls (age 7 [2-14] years) underwent bronchoscopy with endobronchial brushings and biopsies. Anti-viral, wound injury responses were quantified in biopsies and primary bronchial epithelial cells (PBECs) in response to RSV, poly(I:C), house dust mite (HDM) or IL-33 using RT-qPCR, Luminex and live cell imaging. Collagen deposition and tissue expression of epithelial growth factor receptor (EGFR), IL-33 and receptor ST2 were investigated in bronchial biopsies. Results: PBECs from STRA and PSW had increased TLR3 gene expression and increased secretion of anti-viral and pro-inflammatory cytokines (IFN-γ, IL-6 and IL-13) in response to RSV compared to controls. Exposure of PBECs to concomitant TLR3 agonist poly(I:C) and HDM resulted in a significant reduction in epithelial cell proliferation in PSW compared to controls. Wound-healing was also impaired in PSW compared to controls at baseline and following IL-33 stimulation. In addition, tissue EGFR expression was significantly reduced in PSW and correlated with collagen deposition in endobronchial biopsies. Conclusions: Despite increased anti-viral responses, preschool children with severe wheeze had impaired airway epithelial proliferative responses following damage. This might be connected to the low expression of EGFR in PSW which may affect epithelial function and contribute to asthma pathogenesis.
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