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Allergen Skin Prick Testing in Early Childhood: Reproducibility and Prediction of Allergic Symptoms into Early Adulthood

Published:November 13, 2014DOI:https://doi.org/10.1016/j.jpeds.2014.10.009

      Objective

      To assess the predictive value of skin prick testing in early childhood on subsequent allergic symptoms up to adult age.

      Study design

      A cohort of 200 unselected healthy newborns was prospectively followed from birth to 20 years of age. Of them, 163 (82%) were reassessed at age 5 years, 150 (76%) at age 11 years, and 164 (83%) at age 20 years with a skin prick test that included 11 common allergens. On the basis of clinical examination and structured interview, the occurrence of atopic dermatitis, allergic rhinoconjunctivitis, recurrent wheezing, and symptoms of food hypersensitivity were recorded at each of the follow-up visits.

      Results

      The reproducibility of skin prick test positivity at age 5 years was 100% at ages 11 and 20 years, ie, none of the skin prick–positive subjects turned negative during the follow-up. Gaining of new sensitizations to aeroallergens was common. Skin prick test positivity at age 5 years predicted allergic symptoms at ages 11 (sensitivity 28%, specificity 94%) and 20 years (sensitivity 23%, specificity 91%) but not atopic dermatitis.

      Conclusions

      Skin prick test positivity at age 5 years strongly predicts later skin prick test positivity and is associated with respiratory symptoms, ie, allergic rhinoconjunctivitis and recurrent wheezing, at ages 11 and 20 years. However, skin prick test negativity at age 5 years does not exclude sensitization and allergic symptoms at a later age.
      PPV (Positive predictive value), SPT (Skin prick testing)
      Skin prick testing (SPT) is widely used for assessing specific immunoglobulin E–mediated sensitization
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      Practical guide to skin prick tests in allergy to aeroallergens.
      and as a screening method to detect atopic predisposition. The clinical relevance with regard to allergic symptoms has been documented
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      Respiratory disorders and allergy skin-test reactions.
      • Peat J.K.
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      Bronchial hyperresponsiveness in two populations of Australian schoolchildren. II. Relative importance of associated factors.
      • Bodtger U.
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      • Malling H.J.
      Long-term repeatability of the skin prick test is high when supported by history of allergen-sensitivity tests: a prospective clinical study.
      ; however, positivity on SPT may precede clinical symptoms of allergy,
      • Hagy G.W.
      • Settipane G.A.
      Risk factors for developing asthma and allergic rhinitis.
      but it may also persist without clinical relevance. The reproducibility of SPT results has been shown previously to be good in children and adults
      • Bodtger U.
      • Jacobsen C.R.
      • Poulsen L.K.
      • Malling H.J.
      Long-term repeatability of the skin prick test is high when supported by history of allergen-sensitivity tests: a prospective clinical study.
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      Longitudinal variability of skin prick test results.
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      despite variance in the size of the SPT reactions. The predictive value of SPT positivity on the occurrence of allergic symptoms has been assessed previously in children in studies with follow-up periods of 2-10 years.
      • Peat J.K.
      • Britton W.J.
      • Salome C.M.
      • Woolcock A.J.
      Bronchial hyperresponsiveness in two populations of Australian schoolchildren. II. Relative importance of associated factors.
      • Kuehr J.
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      • Frischer T.
      • Hendel-Kramer A.
      • Weiss K.
      • Moseler M.
      • et al.
      Longitudinal variability of skin prick test results.
      • Johnston S.L.
      • Clough J.B.
      • Pattemore P.K.
      • Smith S.
      • Holgate S.T.
      Longitudinal changes in skin-prick test reactivity over 2 years in a population of schoolchildren with respiratory symptoms.
      • Lodge C.J.
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      • Gurrin L.C.
      • Hill D.J.
      • Hosking C.S.
      • Khalafzai R.U.
      • et al.
      House dust mite sensitization in toddlers predicts current wheeze at age 12 years.
      • Codispoti C.D.
      • Levin L.
      • LeMasters G.K.
      • Ryan P.
      • Reponen T.
      • Villareal M.
      • et al.
      Breast-feeding, aeroallergen sensitization, and environmental exposures during infancy are determinants of childhood allergic rhinitis.
      Studies spanning from childhood to adult age are sparse. Recently, SPT positivity to aeroallergens at age 9-11 years was shown to be associated with the incidence and persistence of allergic rhinitis at age 15-18 years.
      • Kellberger J.
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      • Weinmayr G.
      • et al.
      Prediction of the incidence and persistence of allergic rhinitis in adolescence: a prospective cohort study.
      In the setting of a prospective follow-up study on healthy newborns followed from birth to 20 years of age, we had an opportunity to assess the long-term reproducibility of SPT and the predictive capacity of SPT performed at age 5 years on allergic symptoms later in childhood and adolescence.

      Methods

      SPT was performed at ages 5, 11, and 20 years with standardized allergen extracts (ALK, Copenhagen, Denmark) of birch, alder, timothy, Kentucky blue, mugwort, cat, dog, Dermatophagoides pteronyssinus, cow's milk, egg, and codfish on healthy skin on the forearm. Histamine hydrochloride (10 mg/mL) and a diluent control were included. A positive SPT was defined as a test reaction with a mean diameter ≥3 mm and equal to or greater than one-half of the diameter of the histamine wheal.
      • Meinert R.
      • Frischer T.
      • Karmaus W.
      • Kuehr J.
      Influence of skin prick test criteria on estimation of prevalence and incidence of allergic skin prick positivity in children.
      Atopic dermatitis was defined as a chronic or relapsing itchy dermatitis with characteristic morphology and distribution.
      • Hanifin J.M.
      • Rajka G.
      Diagnostic features of atopic dermatitis.
      Atopic dermatitis was recorded if it was present at a follow-up examination, or if it had been diagnosed by a physician and there was a history of relapsing eczema with typical features and localization during the preceding year.
      Allergic rhinoconjunctivitis was defined as recurrent noninfectious rhinitis and/or itching and watery discharge of the eyes at pollen seasons or on aeroallergen exposure. Recurrent wheezing was recorded if the subject had a diagnosis of bronchial asthma, or 2 or more separate episodes of respiratory distress and wheezing.
      Symptoms of food hypersensitivity were defined as a repeated history of itching or swelling of the lips, oral mucosa or throat, urticarial eruption, or severe vomiting after ingestion of a specific food. Because double-blind placebo-controlled food challenges were not feasible, we chose to rely on the history of food hypersensitivity, which was recorded in a personal interview by a physician and based on reports of typical symptoms appearing after ingestion of a specific food. At age 20 years, symptoms of food hypersensitivity were no longer taken into account. At ages 11 and 20 years, verified atopy was recorded if the subject had one or several allergic symptoms and a positive SPT to at least one of the common allergens tested.
      This investigation is based on a 20-year follow-up study of unselected full-term healthy newborns, which was initiated in 1981.
      • Siimes M.A.
      • Salmenperä L.
      • Perheentupa J.
      Exclusive breast-feeding for 9 months: risk of iron deficiency.
      • Pesonen M.
      • Kallio M.J.T.
      • Ranki A.
      • Siimes M.A.
      Prolonged exclusive breastfeeding is associated with increased atopic dermatitis. A prospective follow-up study of unselected healthy newborns from birth to age 20 years.
      The study was approved by the Ethical Review Board of the Hospital for Children and Adolescents and the Ethical Review Board for Internal Medicine of Helsinki University Hospital. Written informed consent was obtained from the parents at the beginning of the study and from the participants of the 20-year re-examination. Because this study was initiated in 1981, the trial was not registered.
      The inclusion criteria were a healthy full-term newborn with appropriate weight for gestational age, a 1-minute Apgar score of at least 8, and a healthy, nonsmoking mother with uncomplicated pregnancy and delivery. A total of 200 mothers fulfilled the criteria, agreed, and were encouraged to breast-feed exclusively for as long as possible. The mothers and the infants were seen monthly or bimonthly by a pediatrician. After the period of exclusive breastfeeding was considered terminated, the infant was gradually weaned to a cow's-milk-based formula (Tutteli; Valio, Finland) and to solid foods. Of the 200 newborns, 84 (42%) had a family history of allergy, defined as the presence of at least one first-grade relative with allergic symptoms.
      Of the 200 newborns, 163 (82%) were reassessed at age 5 years, 150 (75%) at age 11 years, and 164 (82%) at age 20 years with SPT, clinical examination, and parental (at ages 5 and 11) and personal (at age 20) structured interviews (Table I and Figure). At each of the 3 follow-up visits, all the subjects and their parents were personally interviewed by a single physician blinded to the early feeding history, laboratory measurements, and previous and current SPT results. The structured personal interview and the clinical examination were performed as previously described
      • Pesonen M.
      • Kallio M.J.T.
      • Ranki A.
      • Siimes M.A.
      Prolonged exclusive breastfeeding is associated with increased atopic dermatitis. A prospective follow-up study of unselected healthy newborns from birth to age 20 years.
      and the questions on allergic symptoms were similar at the three follow-up visits. On the basis of the interview and the clinical examination, the present allergic symptoms and those during the preceding year were recorded. We have previously published the prevalences of allergic symptoms at ages 5, 11, and 20 years in this follow-up cohort.
      • Pesonen M.
      • Kallio M.J.T.
      • Ranki A.
      • Siimes M.A.
      Prolonged exclusive breastfeeding is associated with increased atopic dermatitis. A prospective follow-up study of unselected healthy newborns from birth to age 20 years.
      Atopic dermatitis at age 5 years and food hypersensitivity at ages 5 and 11 years were overrepresented among the children who had received exclusive breastfeeding for ≥9 months.
      • Pesonen M.
      • Kallio M.J.T.
      • Ranki A.
      • Siimes M.A.
      Prolonged exclusive breastfeeding is associated with increased atopic dermatitis. A prospective follow-up study of unselected healthy newborns from birth to age 20 years.
      • Pesonen M.
      • Kallio M.J.
      • Siimes M.A.
      • Ranki A.
      Retinol concentrations after birth are inversely associated with atopic manifestations in children and young adults.
      • Pesonen M.
      • Ranki A.
      • Siimes M.A.
      • Kallio M.J.
      Serum cholesterol level in infancy is inversely associated with subsequent allergy in children and adolescents. A 20-year follow-up study.
      Smoking in the household during the infants' first year of life was reported in 17% of the participating families.
      • Pesonen M.
      • Kallio M.J.T.
      • Ranki A.
      • Siimes M.A.
      Prolonged exclusive breastfeeding is associated with increased atopic dermatitis. A prospective follow-up study of unselected healthy newborns from birth to age 20 years.
      None of the subjects received specific immunotherapy during the 20-year follow-up period.
      Table IDemographic data of the participants at the 3 follow-up visits at ages 5, 11, and 20 years
      Age at the follow-up visit5 years11 years20 years
      n163150164
      Female/male, n (% female)93/70 (57%)93/57 (62%)103/61 (63%)
      Family history of allergy, n (%)73 (45%)65 (43%)67 (40%)
      SPT positive, n (%)
      Positive SPT to one or more of the tested allergens.
      25 (15%)58 (39%)86 (52%)
      Allergic symptoms, n (%)40 (25%)69 (46%)85 (52%)
      Positive SPT to one or more of the tested allergens.
      Figure thumbnail gr1
      FigureSPT positivity at ages 5, 11, and 20 years. Number of SPT positive subjects is given above each bar. Number of participants was 163, 150, and 164 at ages 5, 11, and 20 years, respectively.

       Statistical Analyses

      Statistical analyses were performed with StatView 5.0 (SAS Institute, Cary, North Carolina). Sensitivity, specificity, and positive predictive value (PPV) were calculated according to standard procedures.
      • Hansen L.G.
      • Høst A.
      • Halken S.
      • Holmskov A.
      • Husby S.
      • Lassen L.B.
      • et al.
      Cord blood IgE. II. Prediction of atopic disease. A follow-up at the age of 18 months.
      Positive likelihood ratio was calculated as sensitivity/1 − specificity. The χ2 and Fisher exact tests were used to measure statistical significance, and P < .05 was considered indicative of statistical significance. Multivariate logistic regression analyses were performed to control for the effect of potential covariates. As potential covariates, sex, family history of allergy, sibship size, ie, the number of elder siblings (≥3), and duration of exclusive breastfeeding (<9 or ≥9 months) were taken into account. For the outcomes at age 20 years, personal smoking status of the subject was added.

      Results

       Reproducibility of SPT Results from Age 5 Years to Ages 11 and 20 Years

      The reproducibility of SPT was assessed by comparing the SPT results at age 5 years to those at ages 11 and 20 years, and the SPT results at age 11 years to those at age 20 years. Of the 163 children seen at age 5 years, 128 (79%) were seen at age 11 years, and 138 (85%) at age 20 years (Table II; available at www.jpeds.com). All the subjects with at least one positive SPT at age 5 years were SPT positive also at ages 11 and 20 years, ie, none of the subjects lost their SPT positivity during the follow-up of 15 years. Gaining of new sensitization was seen in 23% of subjects during the 6-year period between the follow-up visits at ages 5 and 11 years (Table III; available at www.jpeds.com). Typically, sensitization to animal and grass pollen allergens increased during this time. During the next decade, from 11 to 20 years of age, new sensitization occurred in 19% of subjects, most commonly to tree pollens and animals (Figure).
      During the follow-up from 5 to 11 years of age, loss of sensitization occurred only in 3 children with SPT positivity to foods (Table III). Therefore, the persistence of SPT positivity at age 5 years was 100% at ages 11 and 20 years, whereas the reproducibility of a negative SPT at age 5 years was 72% (78 of 108) at age 11 years and 53% (61 of 115) at age 20 years.
      Of the 84 subjects SPT negative at age 11 years, 19% turned SPT positive by age 20 years. Between ages 11 and 20 years, loss of sensitization to foods occurred in 7 of the 136 subjects available for comparison, to mugwort in 6 subjects, and even less infrequently to other aeroallergens, ie, tree and grass pollen and animals (Table III). Because most of the subjects experiencing loss of sensitization to individual allergens had developed new sensitivities to other allergens, a reversion from overall SPT positivity to SPT negativity during the follow-up from age 11 to 20 years of age was seen in 2 subjects only.
      In the long-term comparison of SPT results at 5 and 20 years of age, the reproducibility of a positive SPT was 100% (Table II). By age 20 years, 54 (39%) of the 115 children initially SPT negative had developed a new sensitization. Gaining of new sensitization to animals and tree and grass pollens occurred in 30%, 28%, and 27% of the subjects, respectively (Table III). Between ages 5 and 20 years, 3 subjects lost their sensitivity to food allergens (ie, milk, egg, or codfish) and 1 to tree pollen. Because these individuals had developed new sensitizations to other allergens, reversion from overall SPT positivity to SPT negativity did not occur during the follow-up period from 5 to 20 years of age.
      Of the 4 children SPT positive to foods at age 5 years, 2 were SPT positive to egg, 2 to cow's milk, and 1 child to both egg and milk. Three of these were reported as having symptoms of food hypersensitivity; 1 child with SPT positivity to milk was reported symptom-free. Of these 4 children, 3 turned SPT negative to egg and milk by age 11 years and remained so at age 20 years. One child with SPT positivity to both egg and milk at age 5 years turned SPT negative to egg at age 11 years but remained SPT positive to milk at ages 11 and 20 years and continued to have symptoms of food hypersensitivity when ingesting milk. At age 11 years, 5 children had SPT positivity to codfish. Two of them were reported to have had symptoms when ingesting fish. In addition, there were 2 children with SPT positivity to egg and 2 with SPT positivity to milk. All the children with SPT positivity to codfish at age 11 years turned SPT negative to codfish by age 20 years.

       Predictive Value of SPT at Age 5 Years on Allergic Symptoms at Ages 11 and 20 Years

      The proportion of children with allergic symptoms and those with a positive SPT approximately doubled between the visits at ages 5 and 11 years (Table I). Of the children with symptom-free SPT positivity at age 5 years, 7 (64%) had developed one or more allergic symptoms by age 11 years. SPT positivity at age 5 years was significantly associated with the presence of allergic symptoms and with verified atopy at age 11 years, which it predicted with a specificity of 94% (data not shown); however, the sensitivity of SPT at age 5 years in predicting allergic symptoms at age 11 years was limited (28% to 47%), reflecting the fact that a majority (72%) of the children with allergic symptoms at age 11 years had been SPT negative at age 5 years.
      SPT positivity at age 5 years was significantly associated with respiratory symptoms at age 20 years, whereas atopic dermatitis at age 20 years was not associated with SPT positivity at age 5 years (Table IV). The sensitivity of SPT at age 5 years in predicting any allergic symptom at age 20 years was relatively low, whereas the specificity was relatively high. Thus, a subject with positive SPT at age 5 years was likely to have one or more allergic symptoms at age 20 years; however, 77% of the subjects who had allergic symptoms at age 20 years had been SPT negative at age 5 years.
      Table IVSensitivity, specificity, positive likelihood ratio, PPV, and negative predictive value of SPT at age 5 years in predicting allergic symptoms at age 20 years
      SESPLR+PPVNPVP valueP adjusted,
      Logistic regression. P adjusted for sex, family history of allergy, sibship size (≥3), exclusive breastfeeding for 9 months or more, and personal smoking status at age 20 years.
      OR (95% CI)
      Symptoms at age 20 years
       Any allergic symptom (n = 74)23%91%2.674%50%.04.05, 2.8 (1.0-8.0)
       Respiratory symptoms (n = 63)27%92%3.481%50%.005.03, 3.4 (1.1-9.9)
       Atopic dermatitis (n = 31)23%91%2.654%71%NS (0.1)
       Verified atopy (n = 59)29%92%3.681%52%.008.03, 4.1 (1.2-14.1)
      SE, sensitivity; SP, specificity; LR+, positive likelihood ratio; NPV, negative predictive value; NS, not statistically signficant.
      In calculating SE, SP, LR+, PPV, and NPV, subjects symptom-free at age 20 years were used as healthy controls. P calculated for the association of SPT at age 5 years and occurrence of allergic symptoms at age 20 years. Unadjusted P calculated with Fisher exact. n (total) = 138. Respiratory symptoms, allergic rhinoconjunctivitis, and/or recurrent wheezing. Verified atopy, allergic symptoms and SPT positivity at age 20 years.
      Logistic regression. P adjusted for sex, family history of allergy, sibship size (≥3), exclusive breastfeeding for 9 months or more, and personal smoking status at age 20 years.
      Of the 13 subjects who were symptom-free but SPT positive at age 5 years, 12 were re-examined at age 20 years. Seven of them had developed an allergic symptom by age 20 years, whereas 5 remained symptom-free.

       Predictive Value of SPT at Age 11 Years on Allergic Symptoms at Age 20 Years

      SPT positivity in the 136 children seen both at ages 11 and 20 years was significantly associated with SPT positivity at age 11 years with the occurrence of respiratory symptoms (ie, allergic rhinoconjunctivitis and/or wheezing), atopic dermatitis, and verified atopy (ie, allergic symptoms and SPT positivity) at age 20 years (Table V); however, the sensitivity of SPT reactivity at 11 years of age in predicting later atopic dermatitis was lower than the sensitivities in predicting respiratory symptoms and verified atopy.
      Table VSE, SP, LR+, and PPV and NPV of SPT at age 11 years in predicting allergic symptoms at age 20 years
      SESPLR+PPVNPVP valueP adjusted,
      Logistic regression. P adjusted for sex, family history of allergy, sibship size (≥3), exclusive breastfeeding for 9 months or more, and personal smoking status at age 20 years.
      OR (95% CI)
      Symptoms at age 20 years
       Any allergic symptom (n = 72)61%86%4.483%66%<.0001<.0001, 9.9 (4.0-24.4)
       Respiratory symptoms (n = 62)68%86%4.982%73%<.0001<.0001, 13.5 (5.3-34.8)
       Atopic dermatitis (n = 32)47%86%3.463%76%.001.002, 5.5 (1.9-16.0)
       Verified atopy (n = 59)73%90%7.390%74%<.0001<.0001, 26.4 (8.1-87.0)
      Respiratory symptoms, allergic rhinoconjunctivitis, and/or recurrent wheezing. Verified atopy, allergic symptoms, and SPT positivity at age 20 years.
      P values calculated for the association of SPT at age 11 years and allergic symptoms at age 20 years. Unadjusted P calculated with Fisher exact, n (total) = 136.
      Logistic regression. P adjusted for sex, family history of allergy, sibship size (≥3), exclusive breastfeeding for 9 months or more, and personal smoking status at age 20 years.
      As potential confounders, the effect of environmental tobacco smoke exposure and pet exposure on SPT positivity and the occurrence of allergic symptoms were assessed. In the present cohort, smoking in the household during the infants' first year of life was reported in 17% of the participating families. It was not associated with the occurrence of allergic symptoms or SPT positivity at ages 5, 11, and 20 years. Smoking in the household was reported in 18% and in 28% of the families at the follow-up visits at ages 5 and 11 years, respectively. Reported smoking in the household was not associated with SPT positivity or occurrence of allergic symptoms in children seen at ages 5 and 11 years. At age 20 years, personal smoking was reported by 34% of the subjects. Smoking at age 20 years was not associated with SPT positivity or allergic symptoms at age 20 years.
      Pet exposure was recorded as the presence of any pet in the household. At age 5 years, 8% (n = 13) and at age 11 years, as many as 52% (n = 78) of the participating children were reported as having pets in the household. Pet exposure at ages 5 and 11 years was not associated with SPT positivity or occurrence of allergic symptoms. None of the children with pets at age 5 years were positive on SPT to cats or dogs. At age 20 years, 55% of the subjects reported having a pet in their household. At that age, subjects with current pet exposure were less likely to have allergic symptoms (P = .04) and to have SPT positivity to cats and dogs (P = .01) than those without pets.

      Discussion

      SPT is a well-established method for assessing immunoglobulin E–mediated sensitization and widely used in diagnosing allergic conditions; however, the long-term reproducibility and predictive value are limited. We assessed the predictive value of SPT in children, ie, at age 5 years, on subsequent allergic symptoms up to adult age.
      In the present follow-up cohort of healthy children, the reproducibility of SPT positivity detected at age 5 years was 100% at ages 11 and 20 years. Thus, none of the subjects with SPT positivity at age 5 years turned SPT negative by age 11 years or by age 20 years. Gaining of one or more new sensitizations was common; a total of 39% of the children SPT negative at age 5 years developed a new sensitization by age 20 years. The new sensitizations were mostly to aeroallergens; however, a few new sensitizations to foods (milk, egg, or codfish) also were seen during the follow-up from age 5 years to age 20 years. SPT positivity at age 5 years was associated with allergic symptoms, especially respiratory symptoms and verified atopy, at ages 11 and 20 years. However, SPT negativity at age 5 years does not exclude the possibility of developing SPT positivity and allergic symptoms at a later age.
      Conversion from SPT positive to SPT negative (reversion) has been reported to be very infrequent in previous follow-up studies on healthy children
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      but quite common in a more recent study on children in farming environment
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      Longitudinal changes in skin-prick test reactivity over 2 years in a population of schoolchildren with respiratory symptoms.
      In a longitudinal study on children 8-11 years of age with a follow-up period of 3 years, atopic children living on a farm lost their SPT positivity more frequently than children in nonfarming environments.
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      In our study, all the children lived in an urban environment.
      In one of the previous studies, SPT was performed on subjects aged from 3 to older than 75 years on 2 occasions with a mean of 8.1 years apart. An increase of SPT reactivity was observed in all age groups, and the greatest increase in prevalence occurred in children and adolescents.
      • Barbee R.A.
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      • Ranki A.
      • Siimes M.A.
      Prolonged exclusive breastfeeding is associated with increased atopic dermatitis. A prospective follow-up study of unselected healthy newborns from birth to age 20 years.
      Because all the children in our study cohort received some duration of exclusive breastfeeding, our results might not be directly applicable to the general population, which includes not only exclusively breast-fed but also bottle-fed and nonexclusively breast-fed subjects.
      In addition, because the participants of the present study cohort were derived from Finnish urban population, there might be limitations in the applicability of the results to other populations with very different ethnicity and living conditions. In this cohort, environmental tobacco smoke exposure and pet exposure in childhood were not significantly associated with SPT positivity or occurrence of allergic symptoms. Consequently, these were not included in the analyses as potential confounders. The negative association between pet exposure and allergic symptoms and SPT positivity to cat and dog observed at age 20 years probably reflects the allergic subjects' choice of not having pets.
      Sensitization to inhalant allergens (tree and grass pollen and domestic animals) has previously been shown to have little or no relevance to the occurrence of atopic dermatitis at age 6 years
      • Kjaer H.F.
      • Eller E.
      • Høst A.
      • Andersen K.E.
      • Bindslev-Jensen C.
      The prevalence of allergic diseases in an unselected group of 6-year-old children. The DARC birth cohort study.
      ; however, sensitized children, and especially those with persistent sensitization have been reported to have more severe atopic dermatitis than nonsensitized children.
      • Eller E.
      • Kjaer H.F.
      • Høst A.
      • Andersen K.E.
      • Bindslev-Jensen C.
      Development of atopic dermatitis in the DARC birth cohort.
      • Park J.H.
      • Choi Y.L.
      • Namkung J.H.
      • Kim W.S.
      • Lee J.H.
      • Park H.J.
      • et al.
      Characteristics of extrinsic vs. intrinsic atopic dermatitis in infancy: correlations with laboratory variables.
      • Illi S.
      • von Mutius E.
      • Lau S.
      • Nickel R.
      • Grüber C.
      • Niggemann B.
      • et al.
      The natural course of atopic dermatitis from birth to age 7 years and the association with asthma.
      In our study, SPT positivity at age 5 years was associated with atopic dermatitis at age 11 but not at ages 5 and 20 years.
      • Pesonen M.
      • Kallio M.J.T.
      • Ranki A.
      • Siimes M.A.
      Prolonged exclusive breastfeeding is associated with increased atopic dermatitis. A prospective follow-up study of unselected healthy newborns from birth to age 20 years.
      The PPV of SPT at age 5 years on atopic dermatitis at age 11 years was relatively low (26%) compared with the PPVs on respiratory symptoms or verified atopy.
      In conclusion, SPT positivity at age 5 years strongly predicts SPT positivity later in childhood and in adolescence. Gaining of new sensitivities between the ages of 5 and 20 years is common. Also, SPT positivity at age 5 years predicts the development of allergic symptoms, especially respiratory symptoms, by the ages 11 and 20 years. SPT negativity at age 5 years, however, does not exclude the possibility of developing SPT positivity and allergic symptoms at a later age.

      Appendix.

      Table IIPersistence of SPT positivity (%) from age 5 to 11 years, age 11 to 20 years, and age 5 to 20 years
      Age 5-11 yearsAge 11-20 yearsAge 5-20 years
      n128136138
      Allergen
       Tree pollen (birch, alder)1009791
       Grass pollen (timothy, Kentucky blue)10095100
       Mugwort pollen10071100
       Animals (cat, dog)10091100
       House dust mite (Dph pteron.)
      Percentage not calculated because of insufficient number of cases at age 5 years.
      100
      Percentage not calculated because of insufficient number of cases at age 5 years.
       Any aeroallergen10096100
       Foods (milk, egg, codfish)252025
      n, number of subjects available for each comparison.
      Percentage not calculated because of insufficient number of cases at age 5 years.
      Table IIILoss and gain of sensitization between ages 5 and 11 years (5-11), 11 and 20 years (11-20), and 5 and 20 years (5-20)
      Loss of sensitization, n (%)New sensitization, n (%)
      Follow-up period5-1111-205-205-1111-205-20
      n128136138128136138
      Allergen
       Tree pollen (birch, alder)01 (<1%)1 (<1%)18 (14%)20 (15%)38 (28%)
       Grass pollen (timothy, Kentucky blue)02 (1%)022 (17%)15 (11%)37 (27%)
       Mugwort pollen06 (5%)015 (12%)10 (8%)20 (14%)
       Animals (cat, dog)03 (2%)025 (20%)20 (15%)42 (30%)
       House dust mite (Dermatophagoides pteronyssinus)0004 (3%)6 (5%)13 (9%)
       Any aeroallergen02 (1%)031 (24%)20 (15%)48 (35%)
       Foods (milk, egg, codfish)3 (2%)7 (5%)3 (2%)7 (5%)6 (5%)6 (4%)
       Any allergen (total)02 (1%)030 (23%)26 (19%)54 (39%)

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