Pediatric Allergy and Immunology
ORIGINAL ARTICLE
Asthma
A population-based study of animal component sensitization, asthma, and rhinitis in schoolchildren Anders Bjerg1,2, Anna Winberg3, Malin Berthold4, Lars Mattsson4, Magnus P. Borres4,5 & € nmark1,2 Eva Ro €teborg, Sweden; Krefting Research Centre, Department of Internal Medicine and Clinical Nutrition, University of Gothenburg, Go Department of Public Health and Clinical Medicine, Occupational and Environmental, Medicine, the OLIN Unit, Ume a University, Ume a, Sweden; 3Department of Clinical Sciences, Pediatrics, the OLIN Unit, Ume a University, Ume a, Sweden; 4ThermoFisher Scientific, Uppsala, Sweden; 5Department of Women’s and Children’s Health, Uppsala University, Uppsala, Sweden 1 2
To cite this article: Bjerg A, Winberg A, Berthold M, Mattsson L, Borres MP, R€ onmark E. A population-based study of animal component sensitization, asthma, and rhinitis in schoolchildren. Pediatr Allergy Immunol 2015: 26: 557–563.
Keywords children; allergy; furry animals; allergen components; component-resolved diagnosis; asthma; rhinitis Correspondence Anders Bjerg, Krefting Research Centre, University of Gothenburg, P.O. Box 424, €teborg, Sweden SE-405 30 Go Tel. +46 070 760 4459 Fax: +46(0)31 7866730 E-mail: [email protected] Accepted for publication 4 June 2015 DOI:10.1111/pai.12422
Abstract Background: Animal sensitization is a major determinant of asthma in children. Component-resolved studies of unselected pediatric populations are lacking. The aim was to describe sensitization to animal components and the association with asthma and rhinitis in animal-sensitized schoolchildren. Methods: A random sample of 696 children (11–12 years) from a Swedish populationbased cohort was tested for sensitization to cat, dog, and horse dander using ImmunoCAP. Sera from animal-sensitized children were further analyzed by microarray including three allergen components from cat, four from dog, and two from horse. The parents completed an expanded ISAAC questionnaire. Results: Of 259 animal-sensitized children (≥0.1 kUA/l), 51% were sensitized to all three, 23% to two, and 25% to one species. Current asthma and asthma symptoms following contact with cats were associated with co-sensitization to Fel d 1 and Fel d 4. This association was seen already at moderate-level sensitization (1–15 ISU) to Fel d 4, at which level most children were sensitized to Fel d 1, as well. In dog-sensitized children, the majority was sensitized to more than one dog component, and cosensitization to Can f 5 and Can f 1/f 2 conferred the greatest risk for asthma. Sensitization to the highly cross-reactive serum albumins was uncommon and not associated with asthma. Conclusions: Among schoolchildren in northern Sweden, where mite allergy is uncommon, furry animals were the primary perennial sensitizers. Asthma was associated with higher levels of component sensitization, and sensitization to more than one component from the same animal conferred the greatest risk.
Allergic sensitization to cats, dogs, and other indoor animals is a well-known determinant of asthma and rhinitis (1, 2). The prevalence of sensitization to furry animals has increased in children (3), and apart from a few recent exceptions (4, 5) so has the prevalence of allergic diseases (6). The impact of animal sensitization on asthma is well described. Dog and cat are dominant sensitizers in young adults with asthma (7), and higher IgE titers to these animals Abbreviations IgE, Immunoglobulin E antibodies; kUA, Kilounits of allergen-specific IgE; ISU, ISAC standardized units for IgE; SPT, Skin prick test; OLIN, Obstructive Lung Disease In Northern Sweden Studies.
correlate with more severe disease (2). Further, animal sensitization predicts persistence of childhood asthma throughout the teen ages (8, 9). The prevalence of animal sensitization increases throughout childhood and adolescence and peaks in young adulthood (10–13), and it has been estimated between 10% and 20% in population-based samples of European schoolchildren (3, 14). Sensitization is traditionally determined by the measurement of specific IgE in serum or by skin prick test, using whole allergen extracts made from animal dander. These methods, however, cannot differentiate between primary sensitization and cross-reactivity between different sources (15–17). Newer molecular-based methods, i.e., component-resolved testing,
Pediatric Allergy and Immunology 26 (2015) 557–563 ª 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
557
IgE to animal components in children
have demonstrated cross-reactivity of serum albumins (18) and Equ c 1/Fel d 4/Can f 6 from the lipocalin protein families (19). Component-resolved IgE testing is an expanding area but the number of such studies in allergy to furry animals is still limited. In a population-based study of adults, IgE to any animal component was associated with markers of asthma, but the relevance of individual components was not explored (20). In children with asthma, multisensitization to secretoglobin, kallikrein, and lipocalin was associated with more severe disease and increased bronchial inflammation (21). A case– control study found higher levels of IgE to the major cat allergen Fel d 1, a secretoglobin, in children with asthma compared to children with rhinitis (22). Sensitization to animal components has, however, not been studied in representative pediatric populations. The Obstructive Lung Disease in Northern Sweden (OLIN) Studies have ongoing population studies in an area which has the advantage of being virtually mite-free and a very low prevalence of mite sensitization (3, 23). The aim of this study was to describe sensitization to animal allergen components in a population-based sample of schoolchildren and, furthermore, to investigate its relationship with asthma and rhinitis in animal-sensitized subjects.
Bjerg et al.
categorized into three levels: low-level sensitization (0.30–0.99 ISU), intermediate-level sensitization (1.00–14.99 ISU), and high-level sensitization (≥15 ISU). The detection limit of ImmunoCAPISAC was 0.30 ISU. Definitions Parental questionnaire: Physician-diagnosed asthma (rhinitis): Has your child been diagnosed by a physician as having asthma (rhinitis)? Current asthma: Physician-diagnosed asthma and either wheeze or use of asthma medications during the last 12 months. Current rhinitis: Physician-diagnosed rhinitis and either rhinitis symptoms or use of rhinitis medications during the last 12 months. Interview: Asthma (rhinoconjunctivitis) following exposure to cats (dogs): A report of symptoms from lower airways (asthma) or the eyes or nose (rhinoconjunctivitis) following contact with cats (dogs). Statistical analyses
Material and methods This study is based on the second pediatric cohort within the OLIN Studies, which has been previously described (3, 24). In brief, in 2006, all 2704 children in first and second grade, aged 7–8 years, in the three areas Kiruna, Lule a, and Pite a in northern Sweden were invited to a parental questionnaire study, and 96% participated. In the year 2010 follow-up, the parents of 2612 children (then 11–12 years) completed the questionnaire. In addition, all children in Kiruna and a 25% random sample from Lule a were invited to provide blood samples for analyses of allergen-specific IgE. In total, 696 children (73% of invited) participated. Immediately prior to the blood sampling, the child was interviewed regarding the presence of symptoms from eyes, nose, or lower airways following exposure to cat, dog, and horse. The study was approved by the regional ethics committee of Ume a. Written consent was obtained from the children’s parents.
Serum analyses Sera were collected between February and May 2010 and stored frozen before the analyses of specific IgE to cat, dog, horse, Cladosporium herbarum, timothy, birch, and mugwort using ImmunoCAP technology. A level of specific IgE antibodies ≥0.1 kUA/l was defined as positive, to include also children with low-level animal component sensitization. Sera positive for cat, dog, and/or horse (n = 259) was further analyzed for specific IgE to animal allergen components using ImmunoCAPISAC 112 (Phadia AB [now ThermoFisher Scientific], Uppsala, Sweden) according to the manufacturer’s instructions. Component sensitization was
558
Statistical analyses were performed using IBM SPSS Statistics v. 21.0 (IBM Corp. Armonk, NY, USA) and R v. 3.0 (R Foundation for Statistical Computing, Vienna, Austria). Bivariate comparisons used the chi-square test and Fisher’s exact test where appropriate. Quantitative comparisons were analyzed using Wilcoxon test including Bonferroni–Holm multiplicity adjustment. A p-value
ORIGINAL ARTICLE
Asthma
A population-based study of animal component sensitization, asthma, and rhinitis in schoolchildren Anders Bjerg1,2, Anna Winberg3, Malin Berthold4, Lars Mattsson4, Magnus P. Borres4,5 & € nmark1,2 Eva Ro €teborg, Sweden; Krefting Research Centre, Department of Internal Medicine and Clinical Nutrition, University of Gothenburg, Go Department of Public Health and Clinical Medicine, Occupational and Environmental, Medicine, the OLIN Unit, Ume a University, Ume a, Sweden; 3Department of Clinical Sciences, Pediatrics, the OLIN Unit, Ume a University, Ume a, Sweden; 4ThermoFisher Scientific, Uppsala, Sweden; 5Department of Women’s and Children’s Health, Uppsala University, Uppsala, Sweden 1 2
To cite this article: Bjerg A, Winberg A, Berthold M, Mattsson L, Borres MP, R€ onmark E. A population-based study of animal component sensitization, asthma, and rhinitis in schoolchildren. Pediatr Allergy Immunol 2015: 26: 557–563.
Keywords children; allergy; furry animals; allergen components; component-resolved diagnosis; asthma; rhinitis Correspondence Anders Bjerg, Krefting Research Centre, University of Gothenburg, P.O. Box 424, €teborg, Sweden SE-405 30 Go Tel. +46 070 760 4459 Fax: +46(0)31 7866730 E-mail: [email protected] Accepted for publication 4 June 2015 DOI:10.1111/pai.12422
Abstract Background: Animal sensitization is a major determinant of asthma in children. Component-resolved studies of unselected pediatric populations are lacking. The aim was to describe sensitization to animal components and the association with asthma and rhinitis in animal-sensitized schoolchildren. Methods: A random sample of 696 children (11–12 years) from a Swedish populationbased cohort was tested for sensitization to cat, dog, and horse dander using ImmunoCAP. Sera from animal-sensitized children were further analyzed by microarray including three allergen components from cat, four from dog, and two from horse. The parents completed an expanded ISAAC questionnaire. Results: Of 259 animal-sensitized children (≥0.1 kUA/l), 51% were sensitized to all three, 23% to two, and 25% to one species. Current asthma and asthma symptoms following contact with cats were associated with co-sensitization to Fel d 1 and Fel d 4. This association was seen already at moderate-level sensitization (1–15 ISU) to Fel d 4, at which level most children were sensitized to Fel d 1, as well. In dog-sensitized children, the majority was sensitized to more than one dog component, and cosensitization to Can f 5 and Can f 1/f 2 conferred the greatest risk for asthma. Sensitization to the highly cross-reactive serum albumins was uncommon and not associated with asthma. Conclusions: Among schoolchildren in northern Sweden, where mite allergy is uncommon, furry animals were the primary perennial sensitizers. Asthma was associated with higher levels of component sensitization, and sensitization to more than one component from the same animal conferred the greatest risk.
Allergic sensitization to cats, dogs, and other indoor animals is a well-known determinant of asthma and rhinitis (1, 2). The prevalence of sensitization to furry animals has increased in children (3), and apart from a few recent exceptions (4, 5) so has the prevalence of allergic diseases (6). The impact of animal sensitization on asthma is well described. Dog and cat are dominant sensitizers in young adults with asthma (7), and higher IgE titers to these animals Abbreviations IgE, Immunoglobulin E antibodies; kUA, Kilounits of allergen-specific IgE; ISU, ISAC standardized units for IgE; SPT, Skin prick test; OLIN, Obstructive Lung Disease In Northern Sweden Studies.
correlate with more severe disease (2). Further, animal sensitization predicts persistence of childhood asthma throughout the teen ages (8, 9). The prevalence of animal sensitization increases throughout childhood and adolescence and peaks in young adulthood (10–13), and it has been estimated between 10% and 20% in population-based samples of European schoolchildren (3, 14). Sensitization is traditionally determined by the measurement of specific IgE in serum or by skin prick test, using whole allergen extracts made from animal dander. These methods, however, cannot differentiate between primary sensitization and cross-reactivity between different sources (15–17). Newer molecular-based methods, i.e., component-resolved testing,
Pediatric Allergy and Immunology 26 (2015) 557–563 ª 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
557
IgE to animal components in children
have demonstrated cross-reactivity of serum albumins (18) and Equ c 1/Fel d 4/Can f 6 from the lipocalin protein families (19). Component-resolved IgE testing is an expanding area but the number of such studies in allergy to furry animals is still limited. In a population-based study of adults, IgE to any animal component was associated with markers of asthma, but the relevance of individual components was not explored (20). In children with asthma, multisensitization to secretoglobin, kallikrein, and lipocalin was associated with more severe disease and increased bronchial inflammation (21). A case– control study found higher levels of IgE to the major cat allergen Fel d 1, a secretoglobin, in children with asthma compared to children with rhinitis (22). Sensitization to animal components has, however, not been studied in representative pediatric populations. The Obstructive Lung Disease in Northern Sweden (OLIN) Studies have ongoing population studies in an area which has the advantage of being virtually mite-free and a very low prevalence of mite sensitization (3, 23). The aim of this study was to describe sensitization to animal allergen components in a population-based sample of schoolchildren and, furthermore, to investigate its relationship with asthma and rhinitis in animal-sensitized subjects.
Bjerg et al.
categorized into three levels: low-level sensitization (0.30–0.99 ISU), intermediate-level sensitization (1.00–14.99 ISU), and high-level sensitization (≥15 ISU). The detection limit of ImmunoCAPISAC was 0.30 ISU. Definitions Parental questionnaire: Physician-diagnosed asthma (rhinitis): Has your child been diagnosed by a physician as having asthma (rhinitis)? Current asthma: Physician-diagnosed asthma and either wheeze or use of asthma medications during the last 12 months. Current rhinitis: Physician-diagnosed rhinitis and either rhinitis symptoms or use of rhinitis medications during the last 12 months. Interview: Asthma (rhinoconjunctivitis) following exposure to cats (dogs): A report of symptoms from lower airways (asthma) or the eyes or nose (rhinoconjunctivitis) following contact with cats (dogs). Statistical analyses
Material and methods This study is based on the second pediatric cohort within the OLIN Studies, which has been previously described (3, 24). In brief, in 2006, all 2704 children in first and second grade, aged 7–8 years, in the three areas Kiruna, Lule a, and Pite a in northern Sweden were invited to a parental questionnaire study, and 96% participated. In the year 2010 follow-up, the parents of 2612 children (then 11–12 years) completed the questionnaire. In addition, all children in Kiruna and a 25% random sample from Lule a were invited to provide blood samples for analyses of allergen-specific IgE. In total, 696 children (73% of invited) participated. Immediately prior to the blood sampling, the child was interviewed regarding the presence of symptoms from eyes, nose, or lower airways following exposure to cat, dog, and horse. The study was approved by the regional ethics committee of Ume a. Written consent was obtained from the children’s parents.
Serum analyses Sera were collected between February and May 2010 and stored frozen before the analyses of specific IgE to cat, dog, horse, Cladosporium herbarum, timothy, birch, and mugwort using ImmunoCAP technology. A level of specific IgE antibodies ≥0.1 kUA/l was defined as positive, to include also children with low-level animal component sensitization. Sera positive for cat, dog, and/or horse (n = 259) was further analyzed for specific IgE to animal allergen components using ImmunoCAPISAC 112 (Phadia AB [now ThermoFisher Scientific], Uppsala, Sweden) according to the manufacturer’s instructions. Component sensitization was
558
Statistical analyses were performed using IBM SPSS Statistics v. 21.0 (IBM Corp. Armonk, NY, USA) and R v. 3.0 (R Foundation for Statistical Computing, Vienna, Austria). Bivariate comparisons used the chi-square test and Fisher’s exact test where appropriate. Quantitative comparisons were analyzed using Wilcoxon test including Bonferroni–Holm multiplicity adjustment. A p-value
