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      Human bocavirus 1 coinfection is associated with decreased cytokine expression in the rhinovirus‐induced first wheezing episode in children

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          Abstract

          Background

          Rhinovirus (RV)‐induced first wheezing episodes in children are associated with a markedly increased risk of asthma. Previous studies have suggested that human bocavirus 1 (HBoV1) may modify RV‐induced immune responses in young children. We investigated cytokine profiles of sole RV‐ and dual RV‐HBoV1‐induced first wheezing episodes, and their association with severity and prognosis.

          Methods

          Fifty‐two children infected with only RV and nine children infected with dual RV‐HBoV1, aged 3–23 months, with severe first wheezing episodes were recruited. At acute illness and 2 weeks later, peripheral blood mononuclear cells were isolated, and stimulated with anti‐CD3/anti‐CD28 in vitro. Multiplex ELISA was used to quantitatively identify 56 different cytokines at both study points. Patients were prospectively followed for 4 years.

          Results

          The mean age of the children was 14.3 months, and 30% were sensitized. During the acute illness, the adjusted analyses revealed a decrease in the expression of IL‐1b, MIP‐1b, Regulated upon activation, normal T cell expressed and presumably secreted (CCL5), TNF‐a, TARC, and ENA‐78 in the RV‐HBoV1 group compared with the RV group. In the convalescence phase, the RV‐HBoV1 group was characterized by decreased expression of Fractalkine, MCP‐3, and IL‐8 compared to the RV group. Furthermore, the hospitalization time was associated with the virus group and cytokine response (interaction p < 0.05), signifying that increased levels of epidermal growth factor and MIP‐1b were related with a shorter duration of hospitalization in the RV‐HBoV1 coinfection group but not in the RV group.

          Conclusions

          Different cytokine response profiles were detected between the RV and the RV‐HBoV1 groups. Our results show the idea that RV‐induced immune responses may be suppressed by HBoV1.

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          Most cited references52

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          Rhinovirus illnesses during infancy predict subsequent childhood wheezing.

          The contribution of viral respiratory infections during infancy to the development of subsequent wheezing and/or allergic diseases in early childhood is not established. To evaluate these relationships prospectively from birth to 3 years of age in 285 children genetically at high risk for developing allergic respiratory diseases. By using nasal lavage, the relationship of timing, severity, and etiology of viral respiratory infections during infancy to wheezing in the 3rd year of life was evaluated. In addition, genetic and environmental factors that could modify risk of infections and wheezing prevalence were analyzed. Risk factors for 3rd year wheezing were passive smoke exposure (odds ratio [OR]=2.1), older siblings (OR=2.5), allergic sensitization to foods at age 1 year (OR=2.0), any moderate to severe respiratory illness without wheezing during infancy (OR=3.6), and at least 1 wheezing illness with respiratory syncytial virus (RSV; OR=3.0), rhinovirus (OR=10) and/or non-rhinovirus/RSV pathogens (OR=3.9) during infancy. When viral etiology was considered, 1st-year wheezing illnesses caused by rhinovirus infection were the strongest predictor of subsequent 3rd year wheezing (OR=6.6; P < .0001). Moreover, 63% of infants who wheezed during rhinovirus seasons continued to wheeze in the 3rd year of life, compared with only 20% of all other infants (OR=6.6; P < .0001). In this population of children at increased risk of developing allergies and asthma, the most significant risk factor for the development of preschool childhood wheezing is the occurrence of symptomatic rhinovirus illnesses during infancy that are clinically and prognostically informative based on their seasonal nature.
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            Human Bocavirus and Acute Wheezing in Children

            Abstract Background . Human bocavirus is a newly discovered parvovirus. It has been detected primarily in children with acute lower respiratory tract infection, but its occurrence, clinical profile, and role as a causative agent of respiratory tract disease are not clear. Methods . We investigated the presence of human bocavirus by quantitative polymerase chain reaction of nasopharyngeal aspirate specimens and selected serum samples obtained from 259 children (median age, 1.6 years) who had been hospitalized for acute expiratory wheezing. The samples were analyzed for 16 respiratory viruses by polymerase chain reaction, virus culture, antigen detection, and serological assays. Results . At least 1 potential etiologic agent was detected in 95% of children, and >1 agent was detected in 34% of children. Human bocavirus was detected in 49 children (19%). A large proportion of the cases were mixed infections with other viruses, but human bocavirus was the only virus detected in 12 children (5%). High viral loads of human bocavirus were noted mainly in the absence of other viral agents, suggesting a causative role for acute wheezing. In addition, infections that had uncertain clinical relevance and low viral loads were prevalent. Human bocavirus DNA was frequently detected in serum specimens obtained from patients with acute wheezing, suggesting systemic infection. Conclusions . Human bocavirus is prevalent among children with acute wheezing and can cause systemic infection. Results suggest a model for bocavirus infection in which high viral loads are potentially associated with respiratory symptoms and low viral loads indicate asymptomatic shedding. Therefore, quantitative polymerase chain reaction analysis may be important for additional studies of human bocavirus.
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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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                Author and article information

                Contributors
                hurpek@utu.fi
                Journal
                Clin Transl Allergy
                Clin Transl Allergy
                10.1002/(ISSN)2045-7022
                CLT2
                Clinical and Translational Allergy
                John Wiley and Sons Inc. (Hoboken )
                2045-7022
                13 November 2023
                November 2023
                : 13
                : 11 ( doiID: 10.1002/clt2.v13.11 )
                : e12311
                Affiliations
                [ 1 ] Department of Pediatrics and Adolescent Medicine Turku University Hospital University of Turku Turku Finland
                [ 2 ] Swiss Institute of Allergy and Asthma Research (SIAF) University of Zürich Christine Kühne‐Center for Allergy Research and Education (CK‐CARE) Davos Switzerland
                [ 3 ] Department of Biostatistics University of Turku Turku Finland
                [ 4 ] New Children's Hospital Helsinki University Hospital University of Helsinki Helsinki Finland
                [ 5 ] Institute of Biomedicine University of Turku Turku Finland
                [ 6 ] Department of Clinical Microbiology Turku University Hospital Turku Finland
                [ 7 ] Department of Virology University of Helsinki Helsinki Finland
                [ 8 ] Research Unit of Clinical Medicine Medical Research Center University of Oulu Oulu Finland
                [ 9 ] Department of Pediatrics and Adolescent Medicine Oulu University Hospital Oulu Finland
                Author notes
                [*] [* ] Correspondence

                Pekka Hurme, Department of Paediatrics and Adolescent Medicine, Vinku Study Group, Turku University Hospital and Turku University, P.O. Box 52, Turku 20520, Finland.

                Email: hurpek@ 123456utu.fi

                Author information
                https://orcid.org/0000-0002-9748-2442
                Article
                CLT212311
                10.1002/clt2.12311
                10642552
                ecb59635-45a0-443f-9ddd-07ab722846b8
                © 2023 The Authors. Clinical and Translational Allergy published by John Wiley & Sons Ltd on behalf of European Academy of Allergy and Clinical Immunology.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 20 October 2023
                : 14 September 2023
                : 22 October 2023
                Page count
                Figures: 3, Tables: 3, Pages: 11, Words: 6902
                Funding
                Funded by: Lastentautien Tutkimussäätiö , doi 10.13039/501100005744;
                Funded by: Jalmari ja Rauha Ahokkaan Säätiö , doi 10.13039/100010125;
                Funded by: Suomen Kulttuurirahasto , doi 10.13039/501100003125;
                Funded by: Suomen Lääketieteen Säätiö , doi 10.13039/100008723;
                Funded by: Sigrid Juséliuksen Säätiö , doi 10.13039/501100006306;
                Funded by: Turun Yliopistosäätiö , doi 10.13039/501100022793;
                Funded by: Paulon Säätiö , doi 10.13039/501100007417;
                Funded by: The Life and Health Medical Support Association, Helsinki, Finland
                Funded by: Academy of Finland , doi 10.13039/501100002341;
                Award ID: 114034
                Award ID: 132595
                Funded by: Allergiasäätiö , doi 10.13039/501100013499;
                Categories
                Original Article
                Original Article
                Custom metadata
                2.0
                November 2023
                Converter:WILEY_ML3GV2_TO_JATSPMC version:6.3.4 mode:remove_FC converted:13.11.2023

                Immunology
                bocavirus,bronchiolitis,cytokine,rhinovirus,virus,wheeze,wheezing
                Immunology
                bocavirus, bronchiolitis, cytokine, rhinovirus, virus, wheeze, wheezing

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