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Background: A study was undertaken to investigate the relationship between birth anthropometric measures and the subsequent development of asthma, airway hyperresponsiveness, and atopy in later childhood., Methods: A longitudinal study was performed on 734 subjects (71%) from a cohort of children born in Dunedin, New Zealand in 1972-73. The birth anthropometric measures were available from hospital records and the main outcome measures of reported asthma, skin prick tests, and methacholine hyperresponsiveness were measured at the age of 13 years, while the serum total IgE was measured at 11 years., Results: After adjustment for other factors, infants with a larger head circumference at birth tended to have higher serum total IgE at 11 years of age (p = 0.02) but IgE was not associated significantly with birth length or birth weight. The adjusted odds ratio for raised serum IgE (>150 IU/ml) in infants with a head circumference of 37 cm or more was 3.4 (95% CI 1.4 to 7.9). In contrast, recent asthma symptoms were positively associated with birth length (p = 0. 04) but not with head circumference. The adjusted odds ratio for asthma in the previous two years in infants with a birth length of 56 cm or more was 6.4 (95% CI 2.0 to 19.8). Infants with a birth weight of less than 3.0 kg had an odds ratio for reported asthma of 0.2 (95% CI 0.0-0.6). There were no significant associations of any of the birth parameters with skin prick positivity, reported hay fever, or eczema., Conclusions: These results suggest that increased fetal growth is related to an increased risk of asthma and atopy in childhood. The precision of the findings is limited by the small numbers in the extreme categories of each birth parameter, but the results are consistent with intrauterine programming of the developing respiratory and immune systems.

Strains of Escherichia coli that produce Vero cytotoxin (VTEC) commonly cause diarrhoea, haemorrhagic colitis and haemolytic-uraemic syndrome in many northern hemisphere countries. In these countries, serotype O157:H7/H-predominates and has caused large food-borne outbreaks of infection. In contrast, few cases of infection with this serotype have been reported in New Zealand. Over a 3-month period, 484 stool specimens submitted to medical laboratories in Dunedin were screened for E. coli O157:H7/H-using sorbitol MacConkey agar, Y1 and Vero cell assays. Where possible, Vero cytotoxin production was confirmed by an ELISA test. Specimens from children aged 12 years or less were additionally screened for non-O157 VTEC. In the specimens of the children tested, O157:H7/H-VTEC was not isolated, but VTEC belonging to other serogroups were isolated from the children. Of interest was the detection of other species of Enterobacteriaceae, which produced a cytopathic effect on Vero cells. This study confirms the low incidence of infection with O157:H7/H- VTEC in New Zealand and suggests that non-O157 VTEC is a more important cause of diarrhoeal disease.

Background: Previous studies have not resolved the importance of several potential risk factors for the development of childhood atopy, airway hyperresponsiveness, and wheezing, which would allow the rational selection of interventions to reduce morbidity from asthma. Risk factors for these disorders were examined in a birth cohort of 1037 New Zealand children., Methods: Responses to questions on respiratory symptoms and measurements of lung function and airway responsiveness were obtained every two to three years throughout childhood and adolescence, with over 85% cohort retention at age 18 years. Atopy was determined by skin prick tests at age 13 years. Relations between parental and neonatal factors, the development of atopy, and features of asthma were determined by comparison of proportions and logistic regression., Results: Male sex was a significant independent predictor for atopy, airway hyper-responsiveness, hay fever, and asthma. A positive family history, especially maternal, of asthma strongly predicted childhood atopy, airway hyperresponsiveness, asthma, and hay fever. Maternal smoking in the last trimester was correlated with the onset of childhood asthma by the age of 1 year. Birth in the winter season increased the risk of sensitisation to cats. Among those with a parental history of asthma or hay fever, birth in autumn and winter also increased the risk of sensitisation to house dust mites. The number of siblings, position in the family, socioeconomic status, and birth weight were not consistently predictive of any characteristic of asthma., Conclusions: Male sex, parental atopy, and maternal smoking during pregnancy are risk factors for asthma in young children. Children born in winter exhibit a greater prevalence of sensitisation to cats and house dust mites. These data suggest possible areas for intervention in children at risk because of parental atopy.

Bronchial responsiveness to methacholine was measured in a birth cohort of New Zealand children at ages 9, 11, 13, and 15. Overall bronchial hyperresponsiveness (BHR) decreased with age. While the response at age 9 was significantly related to responsiveness, symptom severity, and low lung function at age 15, these relationships were much closer when bronchial response levels after age 9 were taken into account. Also, among children who were unresponsive to methacholine at age 15, those with previous BHR had more frequent wheeze and lower lung function than those whose previous tests were all unresponsive. Both the overall tendency to BHR and the tendency to retain BHR were closely related to high serum IgE levels (determined at age 11) and to positive allergy skin tests (determined at age 13). These evidences of allergy, closely related to the severity and course of methacholine response, appeared to be important determinants of the frequency of wheeze and the degree of impairment of lung function at the end of follow-up. In view of the variability in BHR, a single estimate of bronchial responsiveness taken at an arbitrary point in time may not be an accurate index of the overall tendency to BHR.

Background: Many factors have been found to relate univariately to bronchial responsiveness (BR), but their independent relationships are often unclear because many are interrelated., Objective: The purpose of this study was to present a multivariate analysis of the closeness of the association of various factors that are related univariately to BR, including allergy skin tests., Methods: The results of methacholine challenge were transformed into a continuous variable (BRindex), which has a nearly Gaussian distribution. With stepwise multiple regression, the closeness of the association of the independent variables with BRindex was evaluated., Results: Of the 11 skin tests applied, four showed independent relationships to BRindex (mite, cat, dog, and Aspergillus species). The sizes of these skin test reactions were correlated with BRindex, and their sum appeared to maximize the overall correlation of allergy skin tests with BRindex (r = 0.516). The lowness of the ratio of forced expiratory volume in 1 second to vital capacity and of percent predicted forced expiratory volume in 1 second added significantly to the skin tests in correlating with BRindex, (multiple r = 0.621). Adding diagnoses and symptoms increased the multiple r to 0.685., Conclusions: The size of the reactions to the four skin tests noted above showed much closer correlations with BR than total serum IgE had shown at age 11, and the relationship was present in asthmatic and nonasthmatic subjects.

Background: Sheepskin bedding might increase house dust mite exposure and so explain some of the increasing prevalence of severity of childhood asthma., Methods: Relationships between use of different types of bedding, and diagnoses of asthma, symptoms of wheezing, skin prick test evidence of house dust mite sensitivity, and airway responsiveness to methacholine, were examined retrospectively in a birth cohort of children followed longitudinally to age 15 years., Results: In the whole cohort, no associations were identified to suggest a causal relationship between use of any type of bedding and development of features of asthma. Although not an a priori hypothesis, we noted that among children with a family history of atopic disease, those who were house dust mite sensitive were more likely to have used an innerspring mattress (29.6% vs 10.2% who had not used an innerspring mattress, p = 0.005)., Conclusion: In this subgroup, increased airway responsiveness and mite sensitivity were significantly associated with use of innerspring mattresses, although whether this is a causal or secondary association is not certain. Use of a sheepskin in the bed in early childhood was not an additional risk factor for the development of asthma.

While airway hyperresponsiveness is usually associated with a diagnosis of asthma or symptoms of wheezing, some individuals with rhinitis show airway hyperresponsiveness as do some with no symptoms whatsoever. We have studied the correlations between symptoms, airway hyperresponsiveness and atopy as determined by skin-prick tests in a cohort of New Zealand children. A total of 662 members of a birth cohort were studied at age 13 years using a respiratory questionnaire, skin-prick tests to 11 common allergens, and an abbreviated validated methacholine challenge test to determine airway responsiveness. Airway hyperresponsiveness (methacholine PC20 FEV1 < or = 8 mg/ml) was strongly correlated with reported asthma and current wheezing (P<0.0001) and also with atopy, especially to house dust mite and cat (P<0.0001). As weal size for both house dust mite and cat increased, so did the proportion of children with airway hyperresponsiveness. All children with diagnosed asthma and airway hyperresponsiveness were atopic. Skin-test reactions to house dust mite and cat were strongly correlated with any degree of measurable airway responsiveness (PC20 FEV1 < or = 25 mg/ml) in children with rhinitis (P<0.00001), and remained significantly correlated even in children without current asthma, without asthma ever and without rhinitis (P<0.001). Atopy is a major determinant of airway hyperresponsiveness in children, not only in those with reported histories of asthma and wheezing, but also in the absence of any history suggesting asthma and rhinitis.

The relationship between atopy and pulmonary function in children, and how these relate directly or indirectly to airway hyperresponsiveness, is uncertain. We have examined these relationships in a sample of 13-year-old children. A questionnaire on respiratory symptoms, skin-prick tests to 11 common allergens, spirometry and an abbreviated methacholine challenge test were completed by 662 members (341 boys) of a birth cohort of New Zealand children followed longitudinally to age 13. There was a significant relationship between the presence and degree of atopy, and baseline pulmonary function. Low FEV1/VC ratios were associated with a greater likelihood of airway responsiveness, not only in subjects with diagnosed asthma, but also in the full cohort and in the sub-group of 426 children who denied asthma or current wheeze. The relationships between baseline FEV1/VC and airway responsiveness were stronger in atopic than in non-atopic children, with the strongest relationships in children sensitive to house dust mite and/or cat dander. In the presence of atopy, progressively lower levels of lung function were strongly associated with a higher prevalence of airway responsiveness (P<0.001). In non-atopic subjects, only those with the most impaired lung function (FEV1/VC < 75%) showed any substantive prevalence of airway responsiveness. The relationship between the degree of atopy and the FEV1/VC ratio, although significant in univariate analysis, became completely non-significant after accounting for airway responsiveness. In 13-year-old children, atopy, especially to house dust mite and cat dander, was correlated with pulmonary function expressed as FEV1/VC ratio. Airway responsiveness likewise correlated with impaired baseline lung function. The apparent relationship of lung function to atopy occurred primarily as a result of the relationship between atopy and airway responsiveness. Atopy and impaired lung function were additive factors predicting airway responsiveness.

Reasons for the gender differences in prevalence rates for asthma remain unclear. We have examined the relationships between allergen skin-test reactions and diagnoses of hay fever and asthma in New Zealand boys and girls examined at the age of 13 years. Information on current and past wheezing, diagnosed asthma, and hay fever was obtained for 662 subjects (341 boys) of a birth cohort followed longitudinally to the age of 13 years, using a physician-administered questionnaire. Atopic status was determined by skin-prick tests to 11 common allergens. The proportion of 13-year-old boys with current asthma was 1.6 times higher and of ever-diagnosed asthma 1.4 times higher than in girls, but the prevalence of recurrent wheeze (> or = three episodes per year) not diagnosed as asthma, or of hay fever, was not significantly different between the sexes. The prevalence of diagnosed asthma increased with increasing numbers of positive skin tests, but hay fever without asthma was little affected above one positive skin-test. Boys had a greater prevalence of any positive skin-test (50.1% vs 37.1%), two or more positive tests (29.3% vs 21.8%), and responses to house dust mite (34.0% vs 23.1%) and cat (14.7% vs 11.2%). Gender differences for asthma became insignificant when adjusted for skin-test responsiveness to house dust mite and/or cat. The proportion of children with diagnosed asthma increased with increasing size of weals to house dust mite and cat dander. Gender differences in allergen sensitivities partly explain the gender differences in diagnosed asthma in children. In both sexes, risk of asthma was primarily associated with sensitization to indoor allergens (house dust mite and cat), and was related to the magnitude of the skin-test response, while the risk of hay fever was primarily associated with grass pollen sensitivity.

The relationship of bronchial responsiveness (BR), assessed by methacholine challenge, to serum IgE, baseline ventilatory function, and symptoms or diagnoses suggesting an atopic disorder were examined in 522 11-year-old New Zealand children. BR was assessed by the presence or absence of a PC20 25 mg/ml or less and by calculating a continuous index of the decline of the FEV1 during the methacholine test. The latter facilitated multivariate analyses and revealed significant relationships to predictor variables even in those considered "nonresponsive" by PC20 criteria. There was a close relationship of BR to the baseline FEV1/vital capacity ratio, seen even in patients with known asthma, but this relationship was seen only in subjects with at least moderate levels of serum IgE. There was a less close relation of BR to percent predicted FEV1, but this persisted even after accounting for the FEV1/vital capacity ratio and was present regardless of the level of serum IgE. Reported asthma was associated with increased BR independent of all other factors, but other diagnoses and symptoms contributed relatively little to the prediction of BR once the serum IgE and lung function were taken into account. The overall results are compatible with the concept that IgE is a critical factor in the development of bronchial responsiveness in childhood.

We examined growth of spirometric lung function in 696 children of European ancestry who were followed from ages 9 to 15 years and stratified according to their degree of responsiveness to methacholine inhalation challenge, atopic status, and respiratory symptoms. Subjects were participants in the longitudinal Multidisciplinary Health and Development Study in Dunedin, New Zealand. Forced expired volume in 1 second (FEV1), and vital capacity (VC) were measured at 9, 11, 13, and 15 years of age, concurrently with assessment of airway responsiveness determined by the concentration of methacholine causing a 20% fall in FEV1 (PC20 FEV1). Atopic status was assessed at age 13 by skin-prick testing to 11 allergens. In children demonstrating airway hyperresponsiveness, FEV1 increased with age at a slower rate, and the FEV1/VC ratio had a faster rate of decline through childhood, compared to non-responsive children. Subjects with positive skin tests to house dust mite and cat dander also had lower mean FEV1/VC ratios than the control group. Any reported wheezing was associated with slower growth of FEV1 and VC in males. We conclude that in New Zealand children with airway responsiveness and/or atopy to house dust mite or cat growth of spirometric lung function is impaired.

In this study we examined the longitudinal effects of smoke exposure on lung function in a cohort of New Zealand children observed from 9 to 15 yr of age. Possible exposures included in utero exposure from mothers smoking during pregnancy, passive smoke from parents, and active smoking by the children. Lung function measures of forced expiratory volume in one second (FEV1) and vital capacity (VC) were measured biennially and ratios (FEV1/VC) were computed. The data were analyzed using longitudinal methodology, and all subjects with at least one pulmonary function test and responses to the questions concerning smoke exposures were included (n = 634). Subjects reporting wheeze or asthma were examined as a separate subgroup. In the whole cohort, no significant detrimental effects were detected for absolute FEV1 or VC in either sex, related to active or passive smoke exposures. Parental smoking was, however, associated with persistent but mild and nonprogressive impairment of the FEV1/VC ratio in males, an effect that was present at the time lung function measurements were first made. This effect was not seen in females. In children with reported wheeze or asthma, parental smoking had progressive, more serious, and clinically significant effects on the FEV1/VC ratio among adolescents of both sexes, causing a mean reduction in FEV1/VC ratios by age 15 of 3.9% in males and 2.3% in females, in contrast to the observed increase in FEV1/VC ratios with age seen in nonexposed wheezing children. We conclude that passive smoking is a major contributing factor to the development and persistence of airflow limitation in wheezing children.

Background: Although asthma diagnosed by a physician is known to be related to serum IgE levels, it is not known whether there is a relation between the level of IgE and airway hyperresponsiveness to a methacholine challenge. The characteristics of asymptomatic persons that predispose them to airway hyperresponsiveness are also unknown., Methods: We studied the relation between the serum total IgE level and airway hyperresponsiveness in the presence or absence of asthma and other atopic diseases in a birth cohort of children. Data from a questionnaire regarding respiratory symptoms, plus measurements of the serum total IgE level and airway responsiveness to inhaled methacholine, were obtained for 562 11-year-olds in New Zealand., Results: The boys had a higher prevalence than the girls of current diagnosed asthma (13 percent vs. 6 percent), current symptoms of wheezing (22 percent vs. 15 percent), and airflow obstruction at base line (6 percent vs. 1 percent) and had a wider distribution of IgE levels, although mean IgE levels (120.8 IU per milliliter in the boys and 98.1 IU per milliliter in the girls) did not differ significantly between the sexes. The prevalence of diagnosed asthma was strongly related to the serum IgE level (P for trend less than 0.0001). No asthma was reported in children with IgE levels less than 32 IU per milliliter, whereas 36 percent of those with IgE levels greater than or equal to 1000 IU per milliliter were reported to have asthma. This relation with the serum IgE level was not explained by a concomitant diagnosis of allergic rhinitis or eczema. Airway hyperresponsiveness to a methacholine challenge also correlated very highly (P less than 0.0001) with the serum IgE level. This relation remained significant even after the exclusion of children with diagnosed asthma (P less than 0.0001) and of all children with a history of wheezing, allergic rhinitis, or eczema (P less than 0.0001)., Conclusions: Even in children who have been asymptomatic throughout their lives and have no history of atopic disease, airway hyperresponsiveness appears to be closely linked to an allergic diathesis, as reflected by the serum total IgE level.

To determine the prevalence and severity of childhood asthma in New Zealand we studied 815 children from a birth cohort by questionnaire, clinical examination and pulmonary physiological measurements at age 9 years. More than 19% of the sample had experienced wheezing in the previous year, and 11% had wheezed in the month before assessment. In all, 220 of 815 children (27.1%) had had wheezing episodes by age 9; in 34 (4.2%) episodes had been of sufficient frequency to warrant regular anti-asthma treatment. Only 32% of all wheezing children were reported by their parents to suffer from asthma, and, in groups matched for frequency of symptoms, treatment given for wheezing was influenced strongly by whether or not the label of 'asthma' had been given. The detailed history provided most information useful in diagnosing asthma; clinical examination, peak flow records, spirometry and bronchial provocation testing provided only limited additional information. A wide spectrum of frequency and severity of recurrent wheezing disorders was evident in New Zealand children. Throughout all degrees of severity, prevalence rates appeared higher than those reported in studies from the United Kingdom.

Children with moderate and severe, mild, and trivial asthma were compared with a group of children who did not have asthma on a range of measures including family social background (socioeconomic status, family adversity, family environment), intelligence, reading, spelling, and behaviour. None of the background measures significantly differentiated among the groups. The group of children with moderate and severe asthma was found to have a significantly lower mean score for verbal intelligence, full scale intelligence, and spelling than those with mild asthma, but did not differ significantly from the remainder of the sample. Children with mild asthma were found to have slightly higher reading scores.

A method for measuring rotavirus antibody in human sera has been established using enzyme-linked immunosorbent assay (ELISA). A Simian strain of rotavirus (SA11) was used as the antigen. Serum eluted from dried blood spots on good quality chromatography paper was found suitable for analysis. Paired serum samples from children with gastroenteritis have shown a brisk antibody response in association with the presence of rotavirus in the faeces. Community studies indicate that although all older children and adults tested have detectable antibodies to rotavirus, there is a significant rise in the number of individuals with high titre antibody in the child bearing age group, after which the levels diminish. This finding suggests that repeated infections occur throughout childhood and early adult life.

The prevalence of bronchial hyperreactivity to inhaled methacholine and of a clinical history of symptoms of asthma was determined in a birth cohort of 9 year old New Zealand children. A history of current or previous recurrent wheezing was obtained in 220 of 815 children. Of 800 who had spirometric tests, 27 (3.4%) had resting airflow obstruction (FEV1/FVC less than 75%). Methacholine challenge was undertaken without problem in 766 children, the abbreviated protocol being based on five breaths and four concentrations. A fall in FEV1 of more than 20% was observed in 176 children (23% of challenges, 22% of the full cohort) after inhalation of methacholine in concentrations of up to 25 mg/ml. The prevalence of bronchial reactivity in children with symptoms was related to the frequency of wheezing episodes in the last year, and the degree of reactivity to the interval since the last episode. Sixty four children (8.0%) with no history of wheeze or recurrent dry cough were, however, also responsive to methacholine 25 mg/ml or less, while 35% of children with current or previous wheezing did not respond to any dose of methacholine. Bronchial challenge by methacholine inhalation was not sufficiently sensitive or specific to be useful as a major criterion for the diagnosis of asthma in epidemiological studies. The occurrence of airway reactivity in children without symptoms of asthma, however, raises the possibility that adult onset asthma and the development of airways obstruction in some subjects with chronic bronchitis could have origins in childhood.

Rotavirus infection is commonly found in young infants admitted to hospital with gastroenteritis. An enzyme-linked immunosorbent assay (ELISA) for virus diagnosis is described and the results of testing stool specimens from 497 children with gastroenteritis, 192 neonates and 247 asymptomatic six month old infants are presented. Rotavirus infection was found in 45 percent of all children with gastroenteritis but only in 4.7 percent of neonates and 2 percent of asymptomatic infants. These results do not support the proposal that children in our community have a high incidence of subclinical infections.

A solid-phase radioimmunoassay method has been developed for the detection of rotavirus in the form of a purified antigen and in stool. The parameters of the radioimmunoassay were examined and optimized to give high sensitivity and same-day results. Compared with electron microscopy, the assay is up to 10 times as sensitive for detection of the virus in stool and up to 128 times as sensitive for detection of a purified virus antigen. In a field study on stool specimens it was at least as efficient as electron microscopy.

Much discussion has taken place over the recently published mortality statistics for infants and young children. These statistics are critically examined and conclusions reached. Suggestions with regard to the improving of Child Health Services are made.

Asthma was reported by 6.2 percent of 2347 inhabitants of a Dunedin residential area. Symptoms occurred within the past two years in 4.2 percent. In this group the majority showed evidence of atopy by skin reactivity and elevation of serum immunoglobulin E. Airways obstruction was detected by spirometry in 62 percent and 56 percent demonstrated increased bronchial reactivity to histamine aerosols. Less than half used bronchodilator aerosols for relief and only 18 per cent were treated with prophylactic disodium cromoglycate.

Serial titres of rotavirus specific IgG and IgM have been measured in children and adults living in a small community over a 2 1/4-year period. In all age groups the mean titres of rotavirus specific IgG and IgM rose and fell in parallel with the changes in frequency of gastroenteritis symptoms in the community but after the time when respiratory symptoms reached their peak. Gastroenteritis symptoms were seen most commonly in the children but were also frequent in adults, especially the women. Titres of rotavirus specific IgG changed with age, increasing through childhood into early adult life, but decreased thereafter only to increase again in those over the age of 50 years. Females had higher levels of IgG in all age groups but especially among the children and 30-49-year-old women. The high levels of IgG did not protect the young adults from symptomatic gastroenteritis. Detectable levels of rotavirus specific IgM occurred in all age groups but more commonly in children aged under 10 years and in young adults. Raised levels of IgM were uncommon in the elderly, who rarely suffered gastroenteritis symptoms. An epidemiological model is proposed in which the older members of the community act as a reservoir of rotavirus, passing the infection to the children, who then infect the young adults.

The associations between skin sensitivity to various common allergens and the development of childhood asthma were ascertained in a longitudinal study of a birth cohort of New Zealand children up to the age of 13 years. Of 714 children skin-tested, 45.8% were sensitive to at least one of 11 allergens, the most common responses being to rye grass pollen (32.5%), house dust mite (30.1%) and cat dander (13.3%). Allergen-specific relative risk analysis, controlled for the effect of sensitivity to other allergens, demonstrated that sensitivity to house dust mite and to cat dander were highly significant independent risk factors associated with the development of asthma (whether defined as recurrent typical respiratory symptoms, increased airway responsiveness, or the concurrent presence of both), whereas grass sensitivity was not a significant independent risk factor for asthma.

A 13 year old girl with a ring 15 chromosome is described. The only major clinical abnormalities were shortness of stature and mental dullness. The usefulness of a chromosomal investigation in patients who have relatively minor mental and/or physical defects is emphasised.