Risk factors associated with allergic and non-allergic asthma in adolescents.

INTRODUCTION: Risk factors for asthma have been investigated in a large number of studies in adults and children, with little progress in the primary and secondary prevention of asthma. The aim of this investigation was to investigate risk factors associated with allergic and non-allergic asthma in adolescents. METHODS: In this study, 959 schoolchildren (13-14 years old) answered a questionnaire and performed exhaled nitric oxide (NO) measurements. All children (n = 238) with reported asthma, asthma-related symptoms and/or increased NO levels were invited to a clinical follow-up which included a physician evaluation and skin-prick testing. RESULTS: Asthma was diagnosed in 96 adolescents, whereof half had allergic and half non-allergic asthma. Children with both allergic and non-allergic asthma had a significantly higher body mass index (BMI) (20.8 and 20.7 vs. 19.8 kg/m(2)) (p < 0.05) and a higher prevalence of parental asthma (30% and 32% vs. 16%) (p < 0.05). Early-life infection (otitis and croup) [adjusted odds ratio (OR) (95% confidence interval (CI)): 1.99 (1.02-3.88) and 2.80 (1.44-5.42), respectively], pets during the first year of life [2.17 (1.16-4.04)], window pane condensation [2.45 (1.11-5.40)] and unsatisfactory school cleaning [(2.50 (1.28-4.89)] was associated with non-allergic but not with allergic asthma. CONCLUSION: This study indicates the importance of distinguishing between subtypes of asthma when assessing the effect of different risk factors. While the risk of both allergic and non-allergic asthma increased with increasing BMI, associations between early-life and current environmental exposure were primarily found in relation to non-allergic asthma.

Exhaled nitric oxide levels in school children in relation to IgE sensitisation and window pane condensation.

BACKGROUND: A positive relation between exhaled nitric oxide (NO) levels and allergen exposure has been found in some studies whereas there is less information on how non-allergen environmental factors influences exhaled NO. OBJECTIVE: To study the relationship between exhaled NO levels in schoolchildren in relation to IgE sensitisation and allergenic and non-allergenic environmental factors. METHOD: This study comprised 374 schoolchildren (13-14 years of age) who performed exhaled NO-measurements and skin prick tests. Exposure to allergens, respiratory infections, environmental tobacco smoke and home window pane condensation, the latter an indicator of high humidity and poor ventilation was evaluated through questionnaires. RESULTS: In IgE-sensitised children sensitisation to pets was a more important determinant of exhaled NO than sensitisation to pollen. Higher NO levels were found in cat-sensitised children with a cat or other furred pets at home compared to cat-sensitised children without pets (geometric mean, 24.0 vs. 13.9 ppb, P=0.03). Significantly higher exhaled NO levels were found in non-sensitised children that reported having a cold (5.7 vs. 3.8 ppb, P<0.001) or lived in homes with window pane condensation (7.1 vs. 4.4 ppb, P=0.01) than in non-sensitised children without a cold and window pane condensation, respectively. These associations were not found in children that were sensitised to inhalation allergens. CONCLUSION: Allergen exposure seems to be the most important determinant for exhaled NO levels in IgE-sensitised children whereas in non-sensitised children NO levels were associated with respiratory infections and home window pane condensation.

Cumulative high doses of inhaled formoterol have less systemic effects in asthmatic children 6-11 years-old than cumulative high doses of inhaled terbutaline.

OBJECTIVES: To evaluate high dose tolerability and relative systemic dose potency between inhaled clinically equipotent dose increments of formoterol and terbutaline in children. METHODS: Twenty boys and girls (6-11 years-old) with asthma and normal ECGs were studied. Ten doses of formoterol (Oxis) 4.5 microg (F4.5) or terbutaline (Bricanyl) 500 microg (T500) were inhaled cumulatively via a dry powder inhaler (Turbuhaler) over 1 h (three patients) or 2.5 h (17 patients) and compared to a day of no treatment, in a randomised, double-blind (active treatments only), crossover trial. Blood pressure (BP), ECG, plasma potassium, glucose, lactate, and adverse events were monitored up to 10 h to assess tolerability and relative systemic dose potency. RESULTS: Formoterol and terbutaline had significant beta2-adrenergic effects on most outcomes. Apart from the effect on systolic BP, QRS duration and PR interval, the systemic effects were significantly more pronounced with terbutaline than with formoterol. Thus, mean minimum plasma potassium, was suppressed from 3.56 (95% confidence interval, CI: 3.48-3.65) mmol l(-1) on the day of no treatment to 2.98 (CI: 2.90-3.08) after 10 x F4.5 and 2.70 (CI: 2.61-2.78) mmol l(-1) after 10 x T500, and maximum Q-Tc (heart rate corrected Q-T interval [Bazett's formula]) was prolonged from 429 (CI: 422-435) ms on the day of no treatment, to 455 (CI: 448-462) ms after 10 x F4.5 and 470 (CI: 463-476) ms after 10 x T500. Estimates of relative dose potency indicated that F4.5 microg had the same systemic activity as the clinically less effective dose of 250 microg terbutaline. The duration of systemic effects differed marginally between treatments. Spontaneously reported adverse events (most frequently tremor) were fewer with formoterol (78% of the children) than with terbutaline (95%). A serious adverse event occurred after inhalation of 45 microg formoterol over the 1 h dosing time, that prompted the extension of dosing time to 2.5 h. CONCLUSIONS: Multiple inhalations over 2.5 h of formoterol (4.5 microg) via Turbuhaler) are at least as safe as and associated with less systemic effects than multiple inhalations of the clinically equipotent dose of terbutaline (500 microg) in children with asthma.

Heredity, pet ownership, and confounding control in a population-based birth cohort.

BACKGROUND: The association between pet ownership in childhood and subsequent allergic disease is controversial. Bias related to selection of pet exposure has been suggested as a reason for contradictory study results. OBJECTIVE: The purpose of this investigation was to elucidate how pet exposure depends on family history of allergic disease, smoking, and socioeconomic factors in a prospective birth cohort. METHODS: Parents of 4089 two-month-old children answered a questionnaire that included detailed questions about family history of asthma (maternal, paternal, and sibling), rhinoconjunctivitis, atopic eczema/dermatitis syndrome, pollen and pet allergy, smoking habits, parental occupation, and family pet ownership (cat and dog). Dust samples collected from the mothers' beds were analyzed for Fel d 1 and Can f 1 in a subgroup of the cohort. RESULTS: Cats were less frequently kept in families with parental asthma, rhinoconjunctivitis, or pet or pollen allergy (3.5% to 5.8%) than in families without parental allergic disease (10.8% to 11.8%). Dogs were less common in families with (3.3%) than in families without (5.9%) parental atopic eczema/dermatitis syndrome. Families with smoking mothers and those with low socioeconomic index kept cats and dogs more frequently. Cat allergen levels were lower in homes with than in homes without maternal pet allergy, and this tended to hold true even for homes without a cat. Cat ownership decreased from birth to 2 years of age, especially in families with parental history of allergic diseases. CONCLUSION: There seems to be a selection of pet exposure based on parental history of allergy, maternal smoking, and socioeconomic factors. This has to be taken into consideration in evaluations of risk associations between pet exposure and allergic disease in childhood.

Atopic dermatitis and concomitant disease patterns in children up to two years of age.

There are few prospective studies of atopic dermatitis and co-existing diseases such as respiratory infections in children up to 2 years of age. Using annual questionnaires, we studied the cumulative incidence of atopic dermatitis and concomitant symptoms indicating other atopic diseases and respiratory infections in 0-2-year-old children in a prospective birth cohort of 4089 children. We found associations between atopic dermatitis and asthma (ratio of proportion 1.45, 95% CI 1.16-1.80), allergic rhinoconjunctivitis (RP 2.25, CI 1.77-2.85), adverse reactions to foods (RP 3.20, CI 2.83-3.62), urticaria (RP 2.04, CI 1.80-2.31), acute otitis media (RP 1.13, CI 1.05-1.21), more than one pneumonia during the first and/or second year of life (RP 2.17, CI 1.14-4.15), and use of antibiotics at least twice yearly (RP 1.29, CI 1.07-1.56). The association between atopic dermatitis and respiratory infections persisted after stratification for asthma. There was a higher proportion of atopic disease manifestations, but not respiratory infections, in children with onset of atopic dermatitis during the first year of life than during the second. The study shows that during the first 2 years of life there is a significant association not only between atopic dermatitis and other atopic disease manifestations, but also between atopic dermatitis and respiratory infections manifested in an increased rate of acute otitis media, pneumonia and use of antibiotics.

The BAMSE project: presentation of a prospective longitudinal birth cohort study.

The aims of this prospective and longitudinal project are to establish crucial risk factors for asthma and other allergic diseases in childhood, and to study factors of importance for prognosis at already established allergic disease. Socio-economic factors, such as inequality in health, are also to be addressed. The project started in February 1994. To reach sufficient power, 4,000 children had to be included. In November 1996, this number was reached (4,093). Inclusion in the study was made at 3-4 months of age. At that time, and before induction of allergic disease/ asthma of the child, a questionnaire focused on exposure, genetics and socio-economic factors was answered. Settled dust was sampled for later analysis of furred animal and mite allergens. When the children were aged both 1 and 2 years, their parents were asked to fill in new questionnaires focusing on respiratory and allergic (skin, gastrointestinal) symptoms, but also key variables of exposure. Cases with asthma are identified and, for every case, two matched controls drawn. During the following winter, the homes of cases and controls were investigated and the temperature, indoor humidity, air change rate and NO2 measured. Two hundred cases (5%) were expected to be identified during the first 2 years of the children's lives. Some 479 homes have now been investigated and 97.7% of the original 4,093 children still remain in the cohort. The 2-year symptom follow-up ended in November 1998. The 4-year follow-up started on 1 September 1998 and was planned to be finished in June 2000. Questionnaires (allergic and respiratory symptoms, key variables of exposure at home and day care) are sent out to all 4,093 families. All children are invited for examination, lung function tests (PEF, flow-volume, MVV and oxygen clearance) and physical performance. Blood is taken from all children (20 ml). Allergy screening is performed and specific IgE examined. Blood cells will be frozen to allow for later DNA extraction. In subsets (children with any allergic and/or respiratory manifestation and controls), markers of inflammation in blood and urine will be examined, as well as eosinophils in nasal smear. Interviews are carried out to assess the severity of asthma, type/periodicity of health care given, asthma medication and parental sick leave when appropriate. As a separate project, financed by the EU, outdoor pollution as risk factors for asthma and allergies are to be studied within the BAMSE cohort. A follow-up of 8-9 years is underway.