D. W. Hide

The prevalence of and risk factors for atopy in early childhood : A whole population birth cohort study

OBJECTIVES A birth cohort was followed-up to age 4 years to record the development of allergic disorders and to study the influence of genetic and environmental factors. METHODS Information on family history and environmental factors was obtained at birth, and serum cord IgE was measured. At age 4 years, 1218 children were reviewed. RESULTS By age 4 years, 27% of the children had symptoms of allergic disease. Period prevalence of asthma increased from 8.7% in infancy to 14.9% at 4 years. Family history of atopy was the single most important risk factor for atopy in children. Sibling atopy was a stronger predictor of clinical disease than maternal or paternal atopy, whereas paternal atopy, male sex, and high cord IgE were significant for the development of allergen sensitization. Children of asthmatic mothers were three times more likely to have asthma (odds ratio [OR]: 3.0, 95% confidence interval [CI]: 1.6-5.8) and rhinitis (OR: 2.9, CI: 1.1-7.4). Formula feeding before 3 months of age predisposed to asthma at age 4 years (OR: 1.8, CI: 1.2-2.6). The effect of maternal smoking on childhood wheeze seen at 1 and 2 years was lost by age 4, except for a subgroup with negative skin test responses (nonatopic asthma). Less than half (46%) of the infantile wheezers were still wheezing at 4 years of age. CONCLUSION Family history of atopy remains the most important risk factor for atopy in children, but other markers can be identified with a potential for intervention at an early age.

Cohort study of peanut and tree nut sensitisation by age of 4 years.

Abstract Objective: To determine the prevalence of sensitisation to peanuts and tree nuts in all children born during one year in one geographical area. Design: Birth cohort study with structured review at ages 1, 2, and 4 years. Setting: All children born on the Isle of Wight between January 1989 and February 1990. Subjects: Of 1456 children originally included, 1218 were reviewed at age 4 years. Of these, 981 had skin prick tests. Main outcome measures: Positive skin test results, clinical atopic disease, and risk factors for the development of atopy. Results: 15 of 1218 (1.2%) children were sensitised to peanuts or tree nuts (13 to peanuts). Six had had allergic reactions to peanuts (0.5% of the population), one to hazelnuts, and one to cashew nuts; three had had anaphylactic reactions. Seven children had positive skin test results or detectable IgE to peanuts without clinical symptoms. Two children who reacted to peanut in infancy had lost their sensitivity by 4 years. Family history of atopy, allergy to egg (odds ratio 9.9, 95% confidence interval 2.1 to 47.9, and eczema (7.3, 2.1 to 26.1) were important predictors for peanut allergy. Conclusions: IgE mediated allergy to peanuts is common in early childhood. In many the allergy persists but a minority may develop tolerance. Key messages Key messages This study suggests that 1 in 200 children could have reactions to peanuts and tree nuts by the age of 4 years and a similar number could have asymp- tomatic sensitisation Children with allergy to peanuts invariably have another atopic disorder such as asthma, eczema, or rhinitis Sensitisation to peanuts and tree nuts may coexist

Allergen avoidance in infancy and allergy at 4 years of age.

In an attempt to prevent or reduce the manifestations of atopic disease, a group of infants considered to be genetically at high risk of atopy was entered in a prenatally randomized, controlled study. A prophylactic group (n= 58) was either breast‐fed with their mothers excluding foods regarded as highly antigenic from their diets, or given an extensively hydrolysed formula. In addition, strenuous efforts were made to reduce exposure to the house‐dust mite by application of acaricide to the bedroom and living room carpets and upholstered furniture. A control group (n= 62) was fed conventionally by breast or on formula, and no specific environmental measures were taken. The results (previously reported) after 1 year showed significantly less total allergy, asthma, and eczema in the prophylactic group. Similar results were obtained at 2 years although the reduction in asthma no longer achieved statistical significance. However, there was significantly less sensitization, as shown by a battery of skin prick tests (SPTs), to both dietary allergens and aeroallergens in the prophylactic group. A11 the children have now been reviewed at the age of 4 years, and SPTs to a wide range of dietary allergens and aeroallergens have been performed. The control group continues to show more total allergy (odds ratio [OR] 2.73, 95% confidence interval [CI] 1.21–6.13, P<0.02), definite allergy (allergic symptoms plus positive SPT) (OR 5.6, CI 1.8–17.9, P<0.005), and eczema (OR 3.4, CI 1.2–10.1, P<0.05). More control children have positive SPTs (OR 3.7, CI 1.3–10.0, P<0.02). A dual approach to the prevention of allergic disease, avoiding as far as possible sensitization to food and aeroallergens, significantly reduces the risk of atopic disease. This should be reserved for infants considered at very high risk of atopy, and close medical and dietetic supervision must be available.

The effect of genetic and environmental factors on the prevalence of allergic disorders at the age of two years

The effect of genetic and environmental factors on the prevalence of allergic disorders in early childhood was determined in a prospective follow‐up study. Information was available on 1174 children at the age of 2 years. Two‐hundred and seventy‐five were considered to have an allergic disorder. The prevalence varied from 3.2% for rhinitis to 10.9%, for asthma. At 2 years 60 children reacted positively on skin‐prick test (SPT). Multivariate logistic regression analysis was used to obtain adjusted odds ratios (95% confidence interval) for each factor. For asthma, positive family history, male sex, low birth‐weight, maternal smoking and season of birth were significant risk factors. For eczema, positive family history was the only significant risk factor. For rhinitis, lower socio‐economic group and autumn birth were significant. Maie sex and low birth‐weight were significant for skin test positivity. Positive family history and low birth‐weight were significant risk factors for any allergy. Low birth‐weight was also a significant risk for skin test reactivity to house dust mite. Genetic and environmental factors have a profound effect on the development of allergic disorders in the first two years of life.

Effect of environmental factors on the development of allergic disorders in infancy.

A total of 1167 infants were followed for 1 year in a population-based prospective study to assess the effect of environmental factors on the development of allergic disorders. Some of these environmental factors are interdependent. Mothers who formula fed their infants smoked more often (p less than 0.001) and tended to belong to lower social classes (p less than 0.01). Logistic regression analysis was performed to adjust for these confounding variables. Maternal smoking adversely affected the prevalence of asthma (p = 0.003) defined as three or more separate episodes of wheezing and total allergy (p = 0.02). Infants in lower socioeconomic groups developed asthma significantly more often (p = 0.03) than infants born in higher socioeconomic groups. There was a nonsignificant trend for infants born in summer to develop asthma more than infants born in winter (p = 0.08). No effect of these factors was observed on eczema, food intolerance, or on the subgroup of infants with definite allergy (clinical disorder with positive skin prick test [SPT]). Exposure to animal dander did not influence the prevalence of clinical disorder, but positive SPT reaction to cat dander was more prevalent in infants who were exposed to cats and/or dogs (p = 0.04). Positive SPT to house dust mite occurred significantly more often in infants who were formula fed (p = 0.05). The environmental factors had a profound effect on the prevalence of asthma but not on other allergic disorders.

Effect of allergen avoidance in infancy on allergic manifestations at age two years

BACKGROUND One hundred twenty children, identified before birth as being at high risk for atopy, were prenatally assigned to prophylactic or control groups. METHODS The infants in the prophylactic group either received breast milk from mothers on an exclusion diet or an extensively hydrolyzed formula. Their bedrooms and living rooms were treated repeatedly with an acaricide, and they used polyvinyl-covered mattresses with vented head areas. The infants in the control group were fed conventionally, and no environmental control was recommended. RESULTS A significant advantage, first demonstrated at 1 year of age, persists for children in the prophylactic group. They have less of any allergy or eczema, but the reduced prevalence of asthma is no longer significant. Only three children in the prophylactic group had positive skin prick test results compared with 16 in the control group, suggesting a significant reduction in sensitization. CONCLUSION A dual approach to allergen avoidance, focusing on foods and aeroallergens, appears to be beneficial in selected high-risk infants. Avoidance of potent allergens in early life increases the threshold for sensitization in these high-risk infants. Whether sensitization has been avoided or merely deferred has yet to be proved.

Cord serum IgE: an insensitive method for prediction of atopy

Cord total serum IgE has been advocated as a screening test to detect infants at high risk of allergy who would be suitable for preventive measures. In a population based prospective study to look at the predictive capacity of cord IgF and family history of atopy 1111 one‐year‐old infants were followed‐up. Cord IgE was measured using the EIA ultra technique (Pharmacia, Uppsala, Sweden). Atopic symptoms developed in 255 (23%) at one year, 183 (16·5%) had probable atopy (clinical disorder but negative skin prick test (SPT)) and 72 (6·5%) had definite atopy (clinical disorder with positive SPT), There was no difference in the mean cord IgE levels in infants with or without atopic manifestations. The cut‐off for IgF was taken at 0·6 ku/1. The specificity of the test was 92% but the sensitivity was only 8·5%. The positive and negative predictive values were 24% and 78% respectively. Family history of atopy is far more sensitive in detecting infants at risk of atopy and little is added by knowledge of cord IgE.

Influence of genetic and environmental factors on the level of IgE at birth

The effect of hereditary and environmental factors on the level of IgE at birlh was assessed in 1319 unselected infants. Cord igE was measured using a new enzyme‐linked immunoassay. EIA Ultra® test. Information on family history of atopy and maternal smoking was obtained using a standard questionnaire. Data on length of gestation and birth weight were obtained from hospital records. Blood for maternal IgE was obtained from 1056 mothers within a week of delivery. Cord IgE levels were higher in infants with a history of atopy in the immediate family (p < 0.01). Male infants had a higher IgE than female (p < 0.01). Maternal IgE correlated positively with cord IgE (r = 0. 3, p < 0.001). There was no effect of length of gestation, birth weight, maternal smoking or month of birth on cord IgE values. It is concluded that the IgE level at birth is determined primarily by genetic factors. No significant effect of environmental factors was demonstrated in this study.

Mizolastine provides effective symptom relief in patients suffering from perennial allergic rhinitis: a double-blind, placebo-controlled study versus loratadine

BACKGROUND Mizolastine is a nonsedating H1 histamine receptor antagonist with additional antiallergic properties currently marketed in Europe for the treatment of seasonal and perennial allergic rhinitis (PAR) and urticaria. OBJECTIVE This multicenter, randomized, double-blind, parallel-group study was conducted to evaluate the efficacy and safety of mizolastine in PAR compared with loratadine and placebo. METHODS After a 1-week placebo run-in period, 428 adult PAR patients received placebo (146 of 428), mizolastine 10 mg (141 of 428), or loratadine 10 mg (141 of 428) once daily for 28 days. Symptoms were evaluated by patients and physicians using a total nasal score, evaluating itching, rhinorrhea, nasal blockade, and sneezing severity. RESULTS Mizolastine treatment resulted in a significantly greater decrease in patient-rated total nasal score than placebo after 2 weeks (D14; -42%, P < 0.001) and at the end of the treatment period (-46%, P = 0.01), and significantly greater than that observed with loratadine at D14 (P = 0.031). No significant difference in change in total nasal score was observed between loratadine and placebo at 2- and 4-week visits. The global safety was satisfactory and the incidence of adverse events was similar in the three treatment groups. CONCLUSIONS Mizolastine provides effective symptom relief in PAR together with a satisfactory safety profile. Improvement with mizolastine was significantly greater than placebo throughout the study despite a large placebo effect. Also mizolastines effects were greater those observed with loratadine after 2 weeks of treatment.

Early intervention for the prevention of atopic dermatitis

Based on a lecture given to the European Society for Pediatric Allergy and Clinical Immunology.