Early life risk factors for adult asthma: a birth cohort study of subjects at risk.

BACKGROUND: Prediction of adult asthma is important, and early prevention strategies should be targeted at those most at risk. Identifying high-risk children at an early age, however, is currently difficult. OBJECTIVE: We sought to determine those factors present in early life that predict an increased risk of adult asthma. METHODS: A prospective cohort study of subjects at risk of asthma and atopy was undertaken in Poole, England. One hundred babies of atopic parents were recruited at birth. During the first 5 years of life, subjects were recalled annually, all respiratory events were reported, and skin prick tests and total serum IgE measurements were performed. At 11 and 22 years, bronchial hyperresponsiveness was also measured. Seventy-three subjects were followed up at 5 years, 67 at 11 years, and 63 at 22 years. RESULTS: Twenty-three (37%) adult subjects reported wheezing within the previous 12 months. Fifteen (25%) of these subjects showed signs of bronchial hyperresponsiveness and were regarded as asthmatic. Wheezing before the age of 2 years occurred in 28% and was not significantly related to adult asthma (odds ratio, 0.3; 95% CI, 0.03-1.7; P = .19). A positive skin prick test response to hen's egg, cow's milk, or both in the first year was independently predictive of adult asthma (odds ratio, 10.7; 95% CI, 2.1-55.1; P = .001; sensitivity, 57%; specificity, 89%). CONCLUSION: Prediction of adult asthma remains difficult. In this study of subjects at risk of atopy, skin sensitivity to hen's egg or cow's milk in the first year was predictive of adult asthma.

A randomised controlled trial to assess the relative benefits of large volume spacers and nebulisers to treat acute asthma in hospital.

OBJECTIVES: To compare the clinical effectiveness, acceptability, and cost benefit of administering beta2 agonists by means of a metered dose inhaler and large volume spacer with conventional nebulisers to children admitted to hospital with acute asthma. METHODS: A randomised controlled trial was conducted over five months. Sixty one children older than 3 years admitted to a large teaching hospital and a district general hospital with acute asthma completed the study. Children received either 5 mg of salbutamol up to one hourly by jet nebuliser, or up to 10 puffs of salbutamol 100 microg by means of a metered dose inhaler and spacer up to one hourly. RESULTS: Median hospital stay was 40 hours in the nebuliser group and 36.5 hours in the spacer group. Asthma disability scores at two weeks after discharge were significantly improved in the spacer group. Drug costs were pound 14.62 less for each patient in the spacer group. CONCLUSIONS: Large volume spacers are an acceptable, cost effective alternative to nebulisers in treating children admitted with acute asthma, provided that the children can use the mouthpiece, and symptoms are not severe. Their use facilitates effective home treatment by parents, with subsequent reduction in morbidity and re-admission rates.

Double blind placebo controlled trial of nebulised budesonide for croup.

AIMS: To determine whether nebulised budesonide improves the symptoms or shortens the duration of stay of children admitted to hospital with a clinical diagnosis of croup. METHODS: A prospective, randomised, double blind placebo controlled trial. Patients received either nebulised budesonide or placebo every 12 hours. The main outcome measures were duration of inpatient stay and croup scores at 30 minutes, one, two, four, 12, and 24 hours. RESULTS: 87 patients (89 admissions) aged 7-116 months entered the trial. Nebulised budesonide was associated with a significant improvement in symptoms at 12 hours (95% confidence interval (CI) 1 to 3) and 24 hours (95% CI 0 to 3). Patients with an initial croup score above 3 demonstrated a significant improvement in symptoms at two hours (95% CI 1 to 3). Nebulised budesonide was also associated with a 33% reduction in the length of stay (95% CI 2% to 63%) when the confounding variables of age, initial croup score, and coryzal symptoms were taken into consideration. CONCLUSIONS: Nebulised budesonide is an effective treatment for children admitted to hospital with a clinical diagnosis of croup.

Exposure to house dust mite allergen of children admitted to hospital with asthma.

Eighty-two children admitted to hospital with exacerbations of asthma were studied to determine how many were exposed to house dust mites at the time of admission and displayed immediate hypersensitivity to house dust mites. The concentration of house dust mite allergen (Der p I) was measured in dust obtained from the child's mattress, bedroom floor and living room floor. Sixty-two (75%) children admitted had been exposed to > 10 microg Der p I/g. Sixty-seven (82%) children were sensitive to house dust mite (RAST > or = 1 +, or weal > or = 3 mm): 49 (60%) children were both exposed and sensitive. In contrast in a control group of 44 children, 31 (70%) (n.s.) were exposed to > 10 microg Der p I/g, 10 (23%) (P<0.001) were sensitive to house dust mite, and 7 (16%) (P<0.001) were both exposed and sensitive. Seventy-three homes were revisited 6 months after the child's initial admission. During the preceding month 14 children had been readmitted, 12 were fully investigated; of these 10 were both sensitive to house dust mite and still exposed to > 10 microg Der p I/g. In contrast, of the remaining 62 children who were not readmitted, only 19 were both sensitive and still exposed to > 10 microg Der p I/g (P<0.001). In conclusion, the majority of children admitted to hospital with exacerbations of asthma were exposed to house dust mite allergen and were house dust mite sensitive. Further the results suggest that continued exposure to higher concentrations of mite allergen may be associated with the risk of readmission.

Natural history of asthma in childhood--a birth cohort study.

A cohort of 67 babies at risk of developing atopic disorders was followed up prospectively for 11 years. Clinical assessment and skin prick allergen sensitivity testing were performed annually over the first five years. At 11 years the cohort was restudied, symptoms were assessed by questionnaire, and bronchial reactivity (BHR) to histamine was measured. On the basis of skin testing, 35 children were atopic and 32 remained non-atopic. The expression of atopy increased with age. The lifetime prevalence of eczema, wheeze, and hay fever were 46%, 63%, and 56% respectively. The yearly period prevalence of hay fever increased with age, that of eczema declined, while that for wheeze showed a bimodal distribution with a peak before the age of 2 years and a gradual increase thereafter. Of the 21 children who wheezed before their second birthday, most never wheezed again and did not show BHR at 11 years. Of the 21 children whose first wheezing was after 2 years of age, 17 were still wheezing at 11 years and 12 showed BHR. Of the children who wheezed before 2 years of age, 10 were or became atopic, compared with 20 of the 23 children who wheezed at 11 years. These findings suggest that childhood asthma is a heterogeneous condition with atopy being strongly associated with the persistence of wheeze.

Longitudinal study of cholesterol values in 68 children from birth to 11 years of age.

Sixty eight children born in 1977 who were taking part in an unrelated study of childhood asthma were selected to have their serum cholesterol concentrations measured at birth, and at 4 months and 1, 2, 3, 4, 5, and 11 years of age. Concentrations of high density lipoprotein were measured at 5 and 11 years. Cholesterol values increased rapidly from birth and plateaued at 1 year. There was a further small rise just before puberty. Tracking of values was seen after the age of 1 year, but did not become established until 4 years of age. The cholesterol concentrations in girls were marginally higher than those in boys. The mean (SD) values of cholesterol (mmol/l) for boys were: at birth, 1.7 (0.4); at 1 year, 3.9 (0.9); at 5 years, 5.2 (1.9); and at 11 years, 5.0 (0.7). For girls the corresponding figures were; at birth, 1.9 (0.6); at 1 year, 4.7 (1.0); at 5 years, 4.6 (0.7); and at 11 years, 5.1 (0.7). The mean (SD) high density lipoprotein concentrations (mmol/l) for boys were: at 5, 1.16 (0.35) and at 11, 1.51 (0.23). For girls they were 1.28 (0.30) and 1.56 (0.27), respectively. The serum cholesterol concentrations in these children were high compared with published figures from north America.

Exposure to house-dust mite allergen (Der p I) and the development of asthma in childhood. A prospective study.

BACKGROUND AND METHODS: Children with asthma commonly have positive skin tests for inhaled allergens, and in the United Kingdom the majority of older children with asthma are sensitized to the house-dust mite. In a cohort of British children at risk for allergic disease because of family history, we investigated prospectively from 1978 to 1989 the relation between exposure to the house-dust mite allergen (Der p I) and the development of sensitization and asthma. RESULTS: Of the 67 children studied in 1989, 35 were atopic (positive skin tests), and 32 were nonatopic. Of the 17 with active asthma, 16 were atopic (P less than 0.005), all of whom were sensitized to the house-dust mite, as judged by positive skin tests and levels of specific IgE antibodies (P less than 0.001). For house-dust samples collected from the homes of 59 of the children in 1979 and from 65 homes in 1989, the geometric means for the highest Der p I exposure were, respectively, 16.1 and 16.8 micrograms per gram of sieved dust. There was a trend toward an increasing degree of sensitization at the age of 11 with greater exposure at the age of 1 (P = 0.062). All but one of the children with asthma at the age of 11 had been exposed at 1 year of age to more than 10 micrograms of Der p I per gram of dust; for this exposure, the relative risk of asthma was 4.8 (P = 0.05). The age at which the first episode of wheezing occurred was inversely related to the level of exposure at the age of 1 for all children (P = 0.015), but especially for the atopic children (r = -0.66, P = 0.001). CONCLUSIONS: In addition to genetic factors, exposure in early childhood to house-dust mite allergens is an important determinant of the subsequent development of asthma.

A subclass IgG4-specific antigen-binding radioimmunoassay (RIA): comparison between IgG and IgG4 antibodies to food and inhaled antigens in adult atopic dermatitis after desensitization treatment and during development of antibody responses in children.

A liquid-phase, antigen-binding radioimmunoassay measuring subclass IgG4 antibody (ab) to allergens has been developed. This assay, which uses monoclonal anti-IgG4 to bind IgG4, allows direct comparison of class (IgG)- and subclass (IgG4)-specific ab levels. These assays used radiolabeled purified allergens, Der p I (Ag P1) from the dust mite Dermatophagoides pteronyssinus, Lol p I (Rye 1), from ryegrass pollen, hen's egg ovalbumin, and beta-lactoglobulin from cow's milk. We have investigated IgG4 abs in several clinical situations. The results confirm that IgG ab responses to both inhalants and food proteins unequivocally include IgG4 ab. On average, the proportion of IgG4 ab to these antigens is far higher than the contribution of IgG4 to total IgG. In patients with adult atopic dermatitis, levels of both class and subclass ab were higher than in control subjects; however, the ratio of IgG4:IgG varied widely in patients and control subjects. During desensitization treatment of patients with perennial rhinitis, levels of IgG4 ab to Der p 1 increased sharply, but there were also increases in the total IgG ab responses so that the percentage contribution of IgG4 was only moderately increased (mean values: before, 29%; after, 36%). In a prospective study of children from atopic families, IgG4 abs to food proteins were detectable as early as 3 months. IgG abs to hen's egg ovalbumin and beta-lactoglobulin from cow's milk increased to a maximum at 3 years and declined by 5 years. However, specific IgG4 as a percentage of specific IgG increased progressively from a mean value of approximately 15% at 6 months to approximately 50% at 5 years of age.(ABSTRACT TRUNCATED AT 250 WORDS)

Parental smoking, breast feeding, and respiratory infection in development of allergic diseases.

Environmental factors were examined as determinants of clinical disease in a five year prospective study of 73 children born to atopic parents. Clinical follow up for evidence of eczema and wheezing was combined with regular skin testing, immunoglobulin assay, and respiratory viral culture where appropriate. Thirty six children developed eczema, which was often associated with a positive result of a skin test to ingestants in the first year and inhalants by the fifth year. Thirty two children developed one or more episodes of wheeze. Fifteen children wheezed once only, and not all of these developed atopy. No pattern of respiratory infection in early life was characteristic of children with recurrent wheeze. There was a significant difference in parental smoking habits between children with and without episodes of wheeze at the fifth birthday. No protective effect of breast feeding could be shown. The development of allergic disease in susceptible children is influenced by many environmental factors. Advice to families about reduction of environmental allergens continues to pose problems, but parents should be advised to avoid smoking in the child's presence.

Cardiorespiratory patterns occurring in infants during and after recovery from respiratory tract infection.

During and after respiratory tract infections in 29 hospitalized infants, 12 cardiorespiratory measurements were performed on 24-hour recordings of ECG and respiratory activity. These measurements were compared with similar data obtained from 110 age-matched control infants without infection. Respiratory and heart rates during the state of regular breathing were increased during infection, as compared with recordings made after recovery. The numbers of short apneic pauses 3.6 to 6.0 seconds and greater than 6.0 to 12.0 seconds in duration, together with the duration of the overall longest apneic pause per recording, were reduced during infection compared with after recovery. The total durations of periodic breathing and of periodic apnea per recording were also reduced during infection compared with after recovery. These effects were consistent in 27 of the 29 cases, but in two, periodic breathing levels during infection exceeded the 90th percentile in age-matched controls and were reduced after recovery. Measurements made after recovery tended to conform more closely to values in the control infants. None of the 29 infants studied subsequently died or suffered chronic respiratory problems. This study suggests that prolonged apneic pauses or increased numbers of short pauses are not usually a consequence of respiratory tract infection in normal infants.

Development of IgE and IgG antibodies to food and inhalant allergens in children at risk of allergic disease.

In a prospective study of 92 children with at least one atopic parent, the development of the specific antibody responses to food and inhalant allergens during the first 5 years of life were assessed. By the radioallergosorbent test egg specific IgE antibody occurred in about 30% of the children with the mean peak concentration at 12 months. By the second year the prevalence of this antibody had increased whereas the mean concentration had decreased. Milk specific IgE antibody could not be shown in any subject, including four whose skin tests yielded positive results. Food specific IgG antibody was noted by antigen binding radioimmunoassays at 3 months in most children. These responses had peaked and began to fall by the fifth year. In contrast few children had detectable IgE or IgG antibody to inhalant allergens before the first 2 years of life. Both the concentration and prevalence of specific antibody, however, increased from the second to the fifth year and was greater in children whose skin tests yielded positive results. Breast feeding was associated with an increase in the prevalence of positive results from skin tests but was not associated with detectable IgE antibody to both food proteins, a lower concentration of IgG antibody to cows' milk, and was not associated with protection against the development of disease. A high level of exposure to dust mite was associated with an increased prevalence of positive results from skin tests to dust mite and appreciably higher antibody concentration. This study indicates differences in the humoral responses to food and inhalant allergens. Environmental factors appear to influence the development of these responses.

Nebulised sodium cromoglycate in recurrently wheezy preschool children.

A double blind crossover study of nebulised sodium cromoglycate in 27 asthmatic preschool children was carried out over a one year period. All subjects had sufficiently severe asthma to have had at least one admission to hospital. The active treatment was sodium cromoglycate 20 mg (in 2 ml) administered by a nebuliser four times daily. Assessment was made by a diary card and clinical examination. Results were analysed in 24 subjects who completed the study. Statistical analysis allowed for order of treatment and seasonal effects. Significant results in favour of treatment with sodium cromoglycate were obtained for night cough, day activity, percentage of symptom free days, and overall severity of asthma. During active treatment there was no reduction in the rate of admissions to hospital or intravenous drugs used. The wheeze score during the week after an upper respiratory tract infection was not reduced during treatment with sodium cromoglycate. Nebulised sodium cromoglycate is a tedious prophylactic treatment for the young asthmatic child but is useful when other treatments have failed.

Confidential paediatric inquiry into neonatal deaths in Wessex, 1981 and 1982.

From 1 January 1981 to 31 December 1982, 66 256 births and 386 neonatal deaths were recorded in the Wessex Regional Health Authority, giving a neonatal mortality of 5.8/1000 live births. An experienced consultant paediatrician undertook a confidential inquiry into each death shortly after it had been reported. One hundred and forty four deaths (37%) were found to be due to lethal or severe malformations, an incidence of 2.2/1000 births. Of the 242 normally formed infants, 111 (46%) died within 24 hours of birth. Seventy seven (32%) weighed over 2500 g at birth. Factors operating before delivery accounted for 104 (43%) of the deaths of normally formed infants. The commonest factors were short gestation and low birth weight, and intrauterine hypoxia and birth injury. Factors after delivery accounted for 81 deaths (33%), the commonest being infections and sudden infant deaths. In the remaining 57 deaths (24%) it seemed that a combination of factors before and after birth had led to the death. Factors before birth thus played a part in two thirds of all deaths. Possible adverse factors in medical care were sought in 154 potentially viable babies and were identified in 38--that is, 10% of all neonatal deaths. Better provision and training of district staff in immediate care at birth would achieve more in lowering neonatal mortality in Wessex than the setting up of a regional unit specializing in advanced neonatal intensive care. Moreover, the greatest scope for improving the outcome of childbirth in Wessex would be offered if there were further advances in obstetric rather than neonatal care.

Growth retardation in asthma: role of calorie deficiency.

Height and weight were recorded and nutrient intake assessed during a 1-year period in 8 short asthmatic children who subsequently received energy supplements for a further year. None received systemic steroids. Total energy intakes in 6 of the children were reduced but no relationship between intakes and linear growth was found. Linear growth performance did not improve despite the fact that energy intake was normalised by supplementation, although some children showed an accelerated weight gain. We suggest that calorie supplementation is not effective for promoting optimal linear growth in short asthmatic children.

Respiratory infections in the first year of life in children at risk of developing atopy.

Ninety-two infants, each of whom had one parent with asthma or hay fever, were followed up from birth to age of 1 year and 72 to the age of three years. During the first year of life respiratory symptoms, eczema, and respiratory viral infections were all reported. Within the first year 24 babies developed eczema; 28 had a wheal of 1 mm in diameter or more on prick skin testing with cutaneous allergens. Forty-three children had one or both of these characteristics and formed an atopic subgroup; by the same criteria, 49 children were non-atopic. The number of respiratory infections in the two groups was not significantly different; similar viruses were isolated from both groups. These viruses were associated with both upper and lower respiratory tract infections. Wheezing was a clinical feature in 12 children during lower respiratory tract infections. Of these babies six were atopic in the first year of life. Of the six non-atopic babies, one had eczema in the second year and five children developed raised total serum IgE values within the 3 years.