Allergic disease at the age of 7 years after pertussis vaccination in infancy: results from the follow-up of a randomized controlled trial of 3 vaccines.

OBJECTIVE: To prospectively assess sensitization rates and the development of allergic diseases in a follow-up of a randomized controlled pertussis vaccine trial. SETTING: Two-month-old infants were the subject of this double-blind study in 1992 in a collaboration between the Pediatric Clinic and the Primary Care Centers in Linköping. PATIENTS AND INTERVENTION: Allergic diseases were evaluated in 667 children, who were randomized to 1 of 4 vaccine groups: a 2-component, a 5-component, or a whole cell pertussis vaccine (all of which were administered with the diphtheria and tetanus toxoids vaccine) and the diphtheria and tetanus toxoids vaccine alone. Allergy development was assessed by questionnaires (n = 667) and skin prick tests (n = 538) at the age of 7 years. MAIN OUTCOME MEASURES: Allergic diseases and skin prick test results at the age of 7 years. RESULTS: The cumulative incidence of allergic diseases was 34.9%, and was similar in the 4 groups (33.3%-37.3%, P =.89), even after adjusting for family history, sex, pets, dampness, environmental smoking at home, and other living conditions. Positive skin prick test results were more prevalent, however, after vaccination with the 2-component acellular vaccine (19.4%) than in the other 3 groups (11.1%-13.5%, adjusted for confounding factors, P =.01). Furthermore, allergic rhinoconjunctivitis was more common in children who were initially immunized with the 2-component pertussis vaccine and received a booster dose with an acellular vaccine compared with those who received no booster vaccination (relative risk, 3.6; 95% confidence interval, 1.1-12.0). CONCLUSION: Pertussis vaccination in infancy with any of these vaccines was not associated with allergic manifestations at the age of 7 years, apart from a higher prevalence of positive skin prick test results after an experimental 2-component vaccine, which is no longer in use.

A randomized controlled trial of the effect of pertussis vaccines on atopic disease.

BACKGROUND: Pertussis vaccination in infancy has been suggested to increase the risk for development of asthma and allergy. OBJECTIVE: To assess sensitization rates and development of atopic diseases in a prospective randomized controlled trial of pertussis vaccine. PATIENTS AND METHODS: A total of 669 children were randomized to 1 of 4 vaccine groups (2-component acellular pertussis, 5-component acellular pertussis, whole-cell pertussis vaccines, and placebo [diphtheria and tetanus toxoids]). Diphtheria and tetanus toxoids were also given to the children in the pertussis vaccine groups. The children were evaluated by means of questionnaires at age 2 months, 7 months, and 2 1/2 years; skin prick tests at age 7 months and 2 1/2 years; and blinded clinical investigation at age 2 1/2 years. The families were contacted at regular intervals to assess possible adverse effects after the vaccinations and symptoms of whooping cough. RESULTS: The cumulative incidence of atopic diseases was 30% and incidence rates were similar in the 4 groups after adjusting for family history. Exposure to environmental tobacco smoke and home dampness did not confound these results. The frequency of adverse effects did not differ appreciably between atopic and nonatopic children, with the exception that a nodule at the vaccination site was more frequent after whole-cell pertussis vaccination in the nonatopic children. Among 47 children with proven pertussis, atopic disease appeared in 19 (40%). Of these 47 children, 9 (19%) developed asthma, as compared with 58 (9%) noninfected children (P=.03). CONCLUSIONS: We found no support for a drastic increase in allergic manifestations after pertussis vaccination. There was a positive association between whooping cough and asthma by 2 1/2 years of age. There seems to be little reason to withhold pertussis vaccination from infants, irrespective of family history of allergy.

Family therapy in the treatment of severe childhood asthma.

Eighteen children with severe, chronic bronchial asthma were randomly divided into two groups. The families in one group received family therapy while the others served as a control group in a controlled family therapy study. Later the control families were also offered therapy in a before-after therapy design. All children were followed for 3 1/2 yr. Asthma symptoms, functional impairment and the use of drug (from diaries) were rated in ten different ways during eight months before and eight months after the family therapy. Improvement in the clinically most important variable, i.e. general pediatric assessment, was greater in the children in the family therapy group compared to the control group (p less than 0.05) Twelve children who received family therapy showed significant improvement after treatment concerning general pediatric assessment (p less than 0.01), clinical grading (p less than 0.05), peak expiratory flow (p less than 0.05), days with functional impairment/yr (p less than 0.05), no. of doses of inhaled Beta-2-agonists/month (p less than 0.01) and nights when Beta-2-agonists were inhaled (p less than 0.05). The children who only received conventional medical treatment showed no significant change in asthma symptoms. We draw the conclusion that family therapy may represent a valuable therapeutic tool in the management of severe asthma.

Development of asthma in children.

Asthma is a multifactorial disease on genetic basis. Its development is influenced by maternal and environmental factors, i.e. allergens and adjuvants. Early identification of candidates at high risk for development of asthma will enable giving recommendations on preventive measures focussing on exposure to tobacco smoke and other pollutants, indoor and outdoor allergens and possibly viral infections during infancy.

Predictive value of high IgE levels in children.

A group of 207 healthy non-atopic children 0-14 years of age without any known family history of atopic disease was selected for a study of the relation between serum IgE levels and the occurrence of atopic manifestations during an observation period of 18 months; 206 fullfilled the study. Serum IgE was measured by a direct radioimmunological sandwich technique (PRIST). At the follow-up 28 of 32 with an initial IgE level greater than one standard deviation above the mean for the age continued to show a high level (87.5%). The total concordance was 81.1%. Atopic or probable atopic diseases had developed in 75.0% of children 0-1 year of age with an initial IgE above +1 S.D., but in only 6.4% of those from the same age group with a lower initial IgE. Even among children 2-14 years old, it was noticement of atopic disease. Otitis media was more frequent among children with an initially elevated IgE level than among the rest of the children. Determination of serum IgE with the PRIST-technique has been shown to provide a valuable means for predicting future atopic manifestations and may be used as a screening procedure especially in children of atopic parents.

Atopic disease in seven-year-old children. Incidence in relation to family history.

The incidence of atopic disease and its relation to the family history was studied by questionnaire in 1325 children, 7 years of age. A higher incidence of bronchial asthma (2.7%) was found than in a previous Swedish study. The total incidence of atopic disease in the children was 15.1% with a higher level when there was a double parental history of such disease (42.6%) as compared with a single such history (19.8%). When both parents had an identical type of atopic disease, i.e. respiratory or skin, the incidence of atopic disease was higher (72.2%) than when non-identical types occurred in the parents (20.8%). The findings support theories of a polygenic transmission of atopic disease as well as a genetic influence on symptom specificity in such disease and may be of value in genetic counselling.

Atopic allergy and serum IgE concentrations in randomly selected children followed up from 8 to 12 years of age.

A total of 159 children selected at random were followed up from the age of 8 to 12 years regarding the development and cumulated incidence of atopic disease as well as serum IgE concentrations. The cumulated incidence, including healed cases, rose to 25.8%. The highest prevalence was found for allergic rhinitis (12.2%). Serum IgE concentrations decreased significantly in both healthy and atopic subjects, and indicated a peak in total IgE concentration in early school age. The allergy predictive value of elevated IgE concentrations was confirmed. Low concentrations of allergen-specific IgE were found in 14.1% of children healthy before and during the observation period, indicating that transient production of IgE antibodies is a normal phenomenon. Finally, the stability of IgE was excellent during the first 2 years at -20 degrees C but later on concentrations tended to decrease, especially in the lower range.

Hyposensitization in childhood hay fever. A comparison of refined and whole timothy extracts.

Thirty-six children with well-defined criteria for hay fever (mean age 8 and range 4-15 years) were allocated at random for hyposensitization (HS) with a refined (R) or whole (W) timothy pollen extract during 3-4 years. HS was performed as rush HS with the patients hospitalized for about 1 week and thereafter with monthly injections. Scores for symptoms and antihistamine use were recorded during the season before HS and all seasons during HS. Skin and conjunctival tests were made at the start of HS and postseasonally. Blood samples for IgE and IgG measurements were drawn before and during rush HS and pre- and postseasonally each year. The R-group patients tolerated a higher allergen dose at the end of the rush HS than the W-group ones. They also demonstrated a higher, significant increase in total and specific IgE levels within 7 days and specific IgG levels within 60 days after the start of HS. In both groups postseasonal increases in total and specific IgE levels were seen. The IgG levels increased successively during the treatment. The most remarkable difference between the groups was in scores for symptoms and antihistamine use, which in group R decreased significantly while they increased significantly in group W. Based on these data we recommended that HS, if indicated, should be performed with purified allergen extracts.

Soy versus cow's milk in infants with a biparental history of atopic disease: development of atopic disease and immunoglobulins from birth to 4 years of age.

Forty-eight children with a biparental history of atopic disease were followed from birth to 4 years of age. One group was fed soy and the other cow's milk from weaning to 9 months of age. Two-thirds of the children developed symptoms of atopic disease with no significant difference between the groups. No difference was found in the serum immunoglobulins (IgE antibodies, IgA, IgG and IgM) during the observation period. The soy fed children showed transiently lower levels of IgG antibodies to cow's milk but higher levels of IgG antibodies to soy protein. Six children showed cow's milk intolerance and a further five had symptoms possibly related to the use of cow's milk. Withholding cow's milk during the first 9 months did not reduce the incidence of symptoms of cow's milk intolerance from birth to 4 years of age. Thus, no benefit was found from replacing cows' milk with soy. A prolonged breast feeding seems most rational for infants at risk of developing atopic disease, even if the present study did not show evidence of a prophylactic effect of breast milk against the development of atopic disease.

Development of atopic disease in babies whose mothers were receiving exclusion diet during pregnancy--a randomized study.

In a prospective, randomized study, we have monitored the effect of maternal abstention from cow's milk and egg on the development of atopy in babies. Two hundred twelve women were followed from midpregnancy. We report the occurrences of allergies in their babies up to 18 months of age, as assessed by skin prick testing, determination of serum IgE, questionnaires, and blinded physical examination by a pediatric allergist. Whatever the method that was used, there was no statistically significant difference between babies whose mothers received the "diet" or the "nondiet." Other factors known to influence the risk of atopy like heredity, sex, month of birth, breast-feeding, and exposure to tobacco smoke, animal dandruff, and solid food did not differ between the groups. The mothers receiving the exclusion diet, by their own choice, had diminished their intake of milk and egg during lactation also, and therefore, their babies were significantly less exposed to cow's milk before 6 months. Still, atopy was equally abundant among their children. Thus, maternal elimination diet during late pregnancy did not protect the baby against allergy.

Children with asthma: how do they get along at school?

All 13653 children, aged 7-15 years, enrolled in the comprehensive schools of Linköping were investigated with respect to asthma. A questionnaire was sent to 329 pupils, identified with asthma by school nurses. Out of these, 210 (1.5%) stated symptoms during the previous year and they were further studied. Their disease was graded with respect to the stated number of restricted days during the previous year. Grade 1: no restriction (21.4%), grade 2: 1-9 days (36.7%), grade 3: 10-99 days (39.1%) and grade 4: 100 days or more (2.9%). Prescribed drugs were used daily by 43.3%. The median time of absence from school due to asthma was 3 days/year. During physical education 78% had been restricted, during arts and crafts 12% and during other lessons 11%. School districts were ranked with respect to absence, restriction, perceived understanding of asthma and dustiness. Rank correlation coefficients were significant for absence/restriction and understanding.

Terfenadine reduces skin and conjunctival reactivity in grass pollen allergic children.

Terfenadine suspension, 30 mg b.i.d., was compared with placebo in a randomized, double-blind cross-over study in twenty-five children, 6-12 years of age, with grass pollen induced allergic rhinoconjunctivitis. The patients were treated during two 7-day periods separated by a 4-day wash-out period. Efficacy was assessed during a period without provoking pollen in the air. At the end of each treatment period, skin-prick tests were carried out in quadruplicate with three concentrations of grass pollen extracts (identical batches of Pharmalgen) and histamine HCl, 1 and 10 mg/ml, as were conjunctival provocations with the same grass pollen. The mean size of weals caused by allergen and histamine was significantly smaller after terfenadine than after placebo; in fact, terfenadine increased the tolerance to the allergen by a factor of ten. Similarly, the tolerance to conjunctival provocation was significantly increased during terfenadine treatment as compared with placebo. There was no significant difference between the treatments in scores for alertness and salivation. Seasonal symptoms were mild when the children were allowed to use terfenadine in an open follow-up study. Thus, terfenadine reduced specific as well as non-specific reactivity in grass pollen allergic children and caused few side effects.

Topical sodium cromoglycate in atopic dermatitis. A disappointing but informative trial.

Forty children with atopic eczema requiring topical steroids entered a double-blind group comparative study over 12 weeks and were randomized to either 4% sodium cromoglycate (SCG) in an oil-in-water cream or matching placebo cream. The eczema was evaluated on area charts for 20 parts of the body at five clinic visits. In addition, the families kept diaries on symptoms and treatment. After 3 weeks there were small but statistically significant decreases in severity scores recorded at the clinical visits in the SCG group compared with small increases in the placebo group. However, there were no statistically significant differences in the diary card data during the first 3 weeks of treatment or in any other period, nor were significant differences found in any efficacy data collected during the other 9 weeks of the trial. There were no marked differences in treatment opinions, unusual symptoms, skin infections, use of topical steroids or drugs, or acceptability data between the groups. Staphylococcus aureus was found once or twice in cultures from eczema lesions in 31 of 40 children with no marked group difference. The trial showed that there is great need for improved information, family support and topical as well as general treatment in childhood atopic eczema, but topical SCG did not relieve the patients' eczema.

Natural history of bronchial asthma in childhood. A prospective study from birth up to 12-14 years of age.

In a cohort of 1654 consecutively born children followed from birth, the cumulated incidence of asthma up to 11 years was 5.3% and the prevalence 3% between 10 and 11 years of age. The asthma début was prior to 1.5 years in 1/3 and before 3 years in 1/2 of the children. Among 59 children examined at 11.5-14.5 years of age, 16 (27%) had no prevalent asthma. On the other hand, inadequate medication was found in 13, undiagnosed chest deformity in four, and wheezing in seven children. All 54 tested children including those with no prevalent asthma had a PC20 histamine less than 8 mg/ml. Tread mill test gave a significant reaction in 15 children. Animal danders and pollens were the most common allergens giving reactions at skin prick test. Compared to one earlier Swedish study an increase in mite sensitivity was found. Cord-blood IgE concentration and a positive immediate family history of atopic disease had no predictive value for the severity of asthma at this follow-up. A new total asthma score including number of days with functional impact of asthma during the last year and present medication was used for group comparisons. Children with a high score at 11.5-14.5 years had more exercise-induced asthma, more concomitant allergic diseases, earlier asthma start, more chest deformity, hyperreactivity both on tread mill and histamine challenge tests, elevated IgE, positive Phadiatop and more reactions at skin prick test, especially to animals and mites. Bronchial asthma was found more often in children born during August through October, possibly due to unsuitable indoor climate and more virus infections during their first 6 months of life. The severity of the asthma was, however, not influenced by the month of birth. No significant differences were found between boys and girls regarding the age at début, asthma severity at follow-up, or bronchial histamine threshold levels.

Allergy prevention by maternal elimination diet during late pregnancy--a 5-year follow-up of a randomized study.

The 209 mothers to be, enrolled in a randomized, prospective, allergy-prevention study from allergy-prone families, totally abstained from cow's milk and egg from gestational week 28 to delivery. This article presents the development of allergic disease at 5 years of age in their children, compared with the development of allergic disease in the children of the control mothers who took normal food throughout pregnancy. The prevalence of allergic disease could be evaluated in 198 children (95%). Allergic disease was monitored with questionnaires, skin prick testing, serum-IgE determinations, and physical examination. Eczema, allergic rhinoconjunctivitis, and asthma was equally common in the groups. Persistent food intolerance to egg was significantly more common in children of the mothers receiving the diet. This long-term follow-up confirms our previous findings that maternal elimination diet during late pregnancy does not prevent the development of allergic disease in the genetically predisposed child.

Predictors of atopic disease: cord blood IgE and month of birth.

The cumulated incidence of atopic disease before 7 years of age was highly influenced by the cord blood IgE concentration and moderately influenced by the month of birth: obvious atopic disease was more than twice as common in children with high cord blood IgE and born in May than in children with a similar IgE and born in November (P less than 0.05). There was no similarly increased risk for atopic disease among those born in May with low cord blood IgE. Environmental factors thus seem important merely for a high risk population. The findings lend support to family planning when there is especially high genetic risk for atopic disease.