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      Rhinovirus Type in Severe Bronchiolitis and the Development of Asthma

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          Abstract

          Background

          Respiratory syncytial virus (RSV)- and rhinovirus (RV)-induced bronchiolitis are associated with an increased risk of asthma, but more detailed information is needed on virus types.

          Objective

          To study whether RSV or RV types are differentially associated with the future use of asthma control medication.

          Methods

          Over 2 consecutive winter seasons (2008-2010), we enrolled 408 children hospitalized for bronchiolitis at age less than 24 months into a prospective, 3-center, 4-year follow-up study in Finland. Virus detection was performed by real-time reverse transcription PCR from nasal wash samples. Four years later, we examined current use of asthma control medication.

          Results

          A total of 349 (86%) children completed the 4-year follow-up. At study entry, the median age was 7.5 months, and 42% had RSV, 29% RV, 2% both RSV and RV, and 27% non-RSV/-RV etiology. The children with RV-A (adjusted hazard ratio, 2.3; P = .01), RV-C (adjusted hazard ratio, 3.5; P < .001), and non-RSV/-RV (adjusted hazard ratio, 2.0; P = .004) bronchiolitis started the asthma control medication earlier than did children with RSV bronchiolitis. Four years later, 27% of patients used asthma control medication; both RV-A (adjusted odds ratio, 3.0; P = .03) and RV-C (adjusted odds ratio, 3.7; P < .001) etiology were associated with the current use of asthma medication. The highest risk was found among patients with RV-C, atopic dermatitis, and fever (adjusted odds ratio, 5.0; P = .03).

          Conclusions

          Severe bronchiolitis caused by RV-A and RV-C was associated with earlier initiation and prolonged use of asthma control medication. The risk was especially high when bronchiolitis was associated with RV-C, atopic dermatitis, and fever.

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          Most cited references34

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          Viral Bronchiolitis in Children

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            A genome-wide association study identifies CDHR3 as a susceptibility locus for early childhood asthma with severe exacerbations.

            Asthma exacerbations are among the most frequent causes of hospitalization during childhood, but the underlying mechanisms are poorly understood. We performed a genome-wide association study of a specific asthma phenotype characterized by recurrent, severe exacerbations occurring between 2 and 6 years of age in a total of 1,173 cases and 2,522 controls. Cases were identified from national health registries of hospitalization, and DNA was obtained from the Danish Neonatal Screening Biobank. We identified five loci with genome-wide significant association. Four of these, GSDMB, IL33, RAD50 and IL1RL1, were previously reported as asthma susceptibility loci, but the effect sizes for these loci in our cohort were considerably larger than in the previous genome-wide association studies of asthma. We also obtained strong evidence for a new susceptibility gene, CDHR3 (encoding cadherin-related family member 3), which is highly expressed in airway epithelium. These results demonstrate the strength of applying specific phenotyping in the search for asthma susceptibility genes.
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              Rhinovirus wheezing illness and genetic risk of childhood-onset asthma.

              Both genetic variation at the 17q21 locus and virus-induced respiratory wheezing illnesses are associated with the development of asthma. Our aim was to determine the effects of these two factors on the risk of asthma in the Childhood Origins of Asthma (COAST) and the Copenhagen Prospective Study on Asthma in Childhood (COPSAC) birth cohorts. We tested genotypes at the 17q21 locus for associations with asthma and with human rhinovirus (HRV) and respiratory syncytial virus (RSV) wheezing illnesses and tested for interactions between 17q21 genotypes and HRV and RSV wheezing illnesses with respect to the risk of asthma. Finally, we examined genotype-specific expression of 17q21 genes in unstimulated and HRV-stimulated peripheral-blood mononuclear cells (PBMCs). The 17q21 variants were associated with HRV wheezing illnesses in early life, but not with RSV wheezing illnesses. The associations of 17q21 variants with asthma were restricted to children who had had HRV wheezing illnesses, resulting in a significant interaction effect with respect to the risk of asthma. Moreover, the expression levels of ORMDL3 and of GSDMB were significantly increased in HRV-stimulated PBMCs, as compared with unstimulated PBMCs. The expression of these genes was associated with 17q21 variants in both conditions, although the increase with exposure to HRV was not genotype-specific. Variants at the 17q21 locus were associated with asthma in children who had had HRV wheezing illnesses and with expression of two genes at this locus. The expression levels of both genes increased in response to HRV stimulation, although the relative increase was not associated with the 17q21 genotypes. (Funded by the National Institutes of Health.).
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                Author and article information

                Contributors
                Journal
                J Allergy Clin Immunol Pract
                J Allergy Clin Immunol Pract
                The Journal of Allergy and Clinical Immunology. in Practice
                Elsevier Inc
                2213-2198
                2213-2201
                11 September 2019
                February 2020
                11 September 2019
                : 8
                : 2
                : 588-595.e4
                Affiliations
                [a ]Department of Pediatrics, Kuopio University Hospital, Kuopio, Finland
                [b ]Department of Pediatrics, Central Hospital of Central Finland, Jyväskylä, Finland
                [c ]Department of Pediatrics and Adolescent Medicine, Turku University Hospital and University of Turku, Turku, Finland
                [d ]Center for Child Health Research, University of Tampere, Tampere, Finland
                [e ]Tampere University Hospital, Tampere, Finland
                [f ]Departments of Molecular Virology and Microbiology and Pediatrics, Baylor College of Medicine, Houston, Texas
                [g ]Departments of Pediatrics and Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wis
                [h ]Department of Emergency Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Mass
                Author notes
                []Corresponding author: Tuomas Jartti, MD, Department of Pediatrics and Adolescent Medicine, Turku University Hospital, PO Box 52, Turku FIN-20520, Finland. tuomas.jartti@ 123456utu.fi
                [∗]

                Equally contributing first authors.

                Article
                S2213-2198(19)30768-8
                10.1016/j.jaip.2019.08.043
                7012669
                31520837
                dabe3e02-a5e5-495e-928d-34fb64574bce
                © 2019 American Academy of Allergy, Asthma & Immunology.

                Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

                History
                : 22 March 2019
                : 11 August 2019
                : 28 August 2019
                Categories
                Article

                asthma development,bronchiolitis,respiratory syncytial virus,rhinovirus,wheeze,wheezing,ahr, adjusted hazard ratio,aor, adjusted odds ratio,hr, hazard ratio,or, odds ratio,rsv, respiratory syncytial virus,rv, rhinovirus

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