Allergen-Specific Immunoglobulin E Antibodies in Wheezing Infants: the Risk for Asthma in Later Childhood
Total Page:16
File Type:pdf, Size:1020Kb
Allergen-Specific Immunoglobulin E Antibodies in Wheezing Infants: The Risk for Asthma in Later Childhood Anne Kotaniemi-Syrja¨nen, MD*; Tiina M. Reijonen, MD*; Jarkko Romppanen, MD‡; Kaj Korhonen, MD*; Kari Savolainen, PhD‡; and Matti Korppi, MD* ABSTRACT. Objective. To evaluate whether the mea- predictive value; LRϩ, positive likelihood ratio; ROC, receiver surement of specific immunoglobulin E (IgE) antibodies operating characteristic. to food and/or inhalant allergens in infants who are hospitalized for wheezing can be used to predict later pproximately 20% of all children experience asthma. 1 Methods. Eighty-two children who were hospitalized wheezing in infancy, and these children are for wheezing at <2 years of age were followed prospec- Aat increased risk for asthma in later child- tively until early school age. The baseline data and the hood. On the basis of recent prospective follow-up characteristics of infancy had been collected at enroll- data, up to 40% of them experience asthma at school ment. At school age, the children were evaluated for age.2 The majority of children with asthma have asthma and allergic manifestations, including skin prick clinically evident atopic manifestations in later child- tests to common inhalant allergens. Frozen serum sam- hood, although allergies may not be apparent in ples obtained during the index episode of wheezing were infancy.2,3 Total serum immunoglobulin E (IgE),2 available for 80 children for determination of food and blood eosinophilia,2 and serum eosinophil cationic inhalant allergen-specific serum IgE antibodies by flu- 4 oroenzyme-immunometric assay, UniCAP, applying the protein (ECP) are markers that are often used to Phadiatop Combi allergen panel. determine subclinical atopy and susceptibility to Results. Asthma was present in 32 (40%) children at respiratory allergy. However, these markers are non- school age. Food-specific IgE antibodies of >0.35 kU/L specific, and to point out the allergen-specific re- were found in 37 (46%) wheezing infants, but only spe- sponses, skin prick tests (SPTs) or radioallergosor- cific IgE to wheat and to egg white at the level of >0.35 bent tests (RAST) thus far have had to be performed. kU/L were significantly associated with later asthma. In Both of these tests are qualitative, and for technical regard to specific IgE to the mixture of food allergens, the reasons, only a restricted number of allergens are cutoff level of >0.70 proved to be significant. Inhalant > applicable in SPTs in young children. These tests allergen-specific IgE of 0.35 kU/L was found only in 14 may also be susceptible to technical errors and vari- cases (18%), but when present, it was significantly pre- dictive of asthma. Elevated levels of specific IgE antibod- ations as a result of either nonstandardized or non- ies to food or inhalant allergens were significantly asso- automated methods. Consequently, new approaches ciated with allergic rhinitis and skin-test reactivity at are needed to screen those prone to atopy or aller- school age. gen-induced asthma among the large group of Conclusions. When present in wheezing infants, spe- wheezing infants. cific IgE of >0.35 kU/L to wheat, egg white, or inhalant We have followed up prospectively a group of allergens are predictive of later childhood asthma. Con- children who were hospitalized for wheezing at Ͻ2 sequently, detection of those specific IgE antibodies in years of age from 1992–1993 onward.5 In 1999–2000, wheezing infants may facilitate the early diagnosis of the children were examined for asthma, and the al- asthma, especially in cases with no clinically evident lergen-specific IgE antibodies were measured from atopic manifestations. Pediatrics 2003;111:e255–e261. URL: http://www.pediatrics.org/cgi/content/full/111/3/ frozen sera obtained during the hospitalization for e255; asthma, infant, follow-up study, sensitization, spe- wheezing in infancy. The aim of the present study cific IgE antibodies, wheezing. was to evaluate whether specific IgE antibodies to food and/or inhalant allergens in wheezing infants are predictive of later asthma. ABBREVIATIONS: IgE, immunoglobulin E; ECP, eosinophil cat- ionic protein; SPT, skin prick test; RAST, radioallergosorbent test; METHODS RSV, respiratory syncytial virus; FEV1, forced expiratory volume in 1 second; OR, odds ratio; CI, confidence interval; PVϩ, positive In 1992–1993, 100 children, aged 1 to 23 months, were recruited into this study. All of the children had infection-related wheezing resulting in hospital treatment in the Department of Pediatrics, From the Departments of *Pediatrics and ‡Clinical Chemistry, Kuopio Kuopio University Hospital. The baseline data were charted by University Hospital, Kuopio, Finland. using a structured questionnaire at enrollment, including the his- Presented in part at the International Paediatric Respiratory and Allergy tory of earlier episodes of wheezing, the history of atopic derma- Congress; April 1–4, 2001; Prague, Czech Republic. titis, pet contacts in infancy, and the family history of asthma and Received for publication Oct 2, 2001; accepted Oct 8, 2002. atopy.6 More details are presented in Table 1. In addition, total Reprint requests to (A.K.-S.) Department of Pediatrics, Kuopio University serum IgE and ECP concentrations and blood eosinophil counts Hospital, PO Box 1777, FIN-70211 Kuopio, Finland. E-mail: kotaniem@ were determined. The IgE concentration of Ն60 kU/L,7 the ECP hytti.uku.fi concentration of Ն16 g/L,8 and the eosinophil count of Ն0.45 ϫ PEDIATRICS (ISSN 0031 4005). Copyright © 2003 by the American Acad- 109 cells/L9 were considered as elevated. Seven common respira- emy of Pediatrics. tory viruses were studied by antibody and antigen assays; there http://www.pediatrics.org/cgi/content/full/111/3/Downloaded from www.aappublications.org/newse255 by guestPEDIATRICS on September Vol. 27, 2021 111 No. 3 March 2003 e255 TABLE 1. Baseline Data and Characteristics of Infants During control. Wheals with a mean diameter of at least 3 mm were the Index Episode of Wheezing regarded as positive,13 and no reactions were allowed in negative controls. Baseline Data Children ϭ In 2000, allergen-specific IgE antibodies (Phadiatop Combi) (n 80; %) were determined from frozen serum samples, which had been Boys 59 (74) obtained at enrollment into the study in 1992–1993, by the flu- Age Ն12 mo 31 (39) oroenzyme-immunometric assay, UniCAP (Pharmacia, Uppsala, 3 History of an earlier episode of wheezing 11 (14) Sweden). First, the presence of IgE antibodies to the mixtures of Atopic dermatitis* 23 (29) inhalant and food allergens was screened, the concentrations of Ն Family history of atopy† 45 (56) 0.35 kU/L being detectable in both assays. On occasions with Family history of asthma‡ 15 (19) detectable antibodies, additional determinations were performed Pet contacts in infancy§ 25 (31) to assess individual allergen-specific IgE antibody concentrations. Blood eosinophils of Ն0.45 ϫ 109 cells/L 26/78 (33) The detection limit was the same (0.35 kU/L) as for the allergen IgE of Ն60 kU/L 17/77 (22) mixtures. The other cutoff concentrations proposed by the manu- Ն Ն ECP of Ն16 g/L 15 (19) facturer ( 0.70 kU/L and 3.50 kU/L) were also explored in the RSV identification 20 (25) present analyses. Phadiatop Combi panel for food allergens in- cluded egg white, cow milk, fish, wheat, peanut, and soy bean and * Cases diagnosed by a physician. for inhalant allergens timothy grass pollen, birch pollen, mugwort † Allergic rhinitis or atopic dermatitis in parents or siblings, diag- pollen, cat dander, dog dander, horse dander, house dust mite D nosed by a physician. pteronyssinus, and spores of the mold C herbarum. ‡ Asthma in parents or siblings, diagnosed by a physician. The data were analyzed using SPSS/PC ϩ 9.0 software (SPSS § Furry pets at home or at day care. Inc, Chicago, IL). Statistical significances of the differences be- tween the groups were assessed by the 2 test for proportions. The Fisher exact test was used when the expected frequency for any were 25 respiratory syncytial virus (RSV) and 18 other viral iden- cell was Ͻ5. The logistic regression analysis was used to calculate tifications.10 the adjusted odds ratios (ORs) and the related 95% confidence The children were followed up prospectively, and in 1999, 82 intervals (CIs). Two-tailed tests were used in all analyses. P Ͻ .05 children, 61 boys and 21 girls, participated in the follow-up visit. was regarded as statistically significant. The statistics was ap- The age of the children varied from 5.6 to 8.8 years (median: 7.2 plied to compare agreement between allergen-specific IgE and years), and the time from enrollment (the index episode of wheez- other markers and characteristics of atopy. Ͼ 0.80 indicates good ing) ranged from 5.3 to 7.2 years (median: 6.3 years). Frozen serum agreement, 0.61 to 0.80 indicates substantial agreement, 0.41 to samples, which were obtained during the index episode of wheez- 0.60 indicates moderate agreement, 0.21 to 0.40 indicates fair ing at Ͻ2 years of age (median: 0.9 years), were available for agreement, and Յ0.20 indicates poor agreement.14 Sensitivity, allergen-specific IgE antibody determinations in 80 children, who specificity, positive predictive values (PVϩ), and positive likeli- form the subjects of the present study. hood ratios (LRϩ) were calculated by using routine equations. In the follow-up study from January to March 1999, a struc- LRϩ values of Ն3 are considered to have moderate effects on tured questionnaire was used to record the symptoms suggestive pretest probability, and LRϩ values of Ն10 (or of Ն5) significant of asthma associated with exercise, infections, or allergens. In effects.15 The receiver operating characteristic (ROC) curves were addition, physician-diagnosed allergic rhinitis and atopic derma- applied to evaluate the optimal cutoff concentrations for specific titis were recorded.