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Background: Sensitization and symptoms of allergic disease are strongly correlated, but little is known about the early clinical precursors of the development of allergen sensitization in childhood. The aim of this study was to identify these predictors, and to examine separately the effect of early sensitization on subsequent wheeze, asthma, rhinitis and eczema., Methods: In the Childhood Asthma Prevention Study, children with a family history of asthma were assessed for allergen sensitization, total serum IgE, wheeze, asthma, eczema and rhinitis at ages 18 months and 5 years. To examine predictors, at 18 months, for subsequent sensitization, children who were non-sensitized at 18 months and had data on sensitization at 5 years were investigated, n=375. To examine the predictors, at age 18 months, of subsequent onset of symptoms, children who did not have wheeze, asthma, eczema or rhinitis at 18 months were followed-up at 5 years, n=177., Results: Among children who were non-sensitized at age 18 months, the presence of eczema [adjusted relative risk (aRR), 1.67, 95% confidence interval (CI) 1.20-2.33], but not wheeze, asthma or rhinitis, was an independent predictor of the onset of sensitization by age 5 years. Among children who were asymptomatic at age 18 months, sensitization to any allergen at 18 months was an independent predictor for the presence of wheeze (aRR 2.41, 95% CI 1.28-4.55), asthma (aRR 4.66, 95% CI 1.88-11.54) and rhinitis (aRR 1.77, 95% CI 1.08-2.90), but not for the development of eczema (aRR 0.78, 95% CI 0.23-2.64) at 5 years., Conclusion: In non-sensitized children, eczema, but not wheeze, asthma or rhinitis is a predictor for subsequent development of sensitization. This suggests that early childhood eczema, rather than wheeze and rhinitis, may promote subsequent allergen sensitization and raises the possibility that early management of eczema may reduce the prevalence of sensitization in children.

We examine the nature of the immune responses to inhaled skin particles and query whether early exposure could play a role in providing protection against the development of allergic disease. Currently, the main hypothesis used to explain environmental modulation of allergic diseases, the 'hygiene hypothesis', is linked exclusively to microbial exposures acting upon the innate immune system. However, many of the exposures sustaining this hypothesis also involve co-exposure to skin flakes from humans or animals. Such skin flakes contain a complex mixture of antigens, glycolipids and small peptides that may induce immune responses. Should these responses prove relevant to the modulation of allergic diseases, it provides new opportunities to better understand the epidemic of allergic disease and to develop new interventions for its prevention.

Background: Measurement of exposure to the dust mite allergen Der p 1 is important in asthma research and is potentially useful in managing asthma. As no single measure can capture all characteristics of an exposure, it is important to recognize differences in the available methods of measuring exposure to Der p 1., Methods: Fourteen bedrooms and living rooms were sampled using four methods for 1 week. Airborne allergen was sampled by static Institute of Occupational Medicine samplers. Settling dust was collected on Petri dishes and an adhesive-membrane system (A-book). Vacuumed reservoir dust samples were collected from floors at the end of 1 week. Der p 1 was measured in all samples by enzyme-linked immunosorbent assay, except A-books, in which it was measured by Halogen immunoassay., Results: All four methods intercorrelated moderately (r range = 0.40-0.64, P = 0.04), except between allergen in reservoir dust (as microg/m2 and microg/g dust) and settling dust by Petri dishes (P = 0.2). Reservoir allergen, expressed as microg/m2, did not correlate with any measure, except reservoir allergen expressed as microg/g (r = 0.39, P = 0.04). No differences in these associations occurred between bedrooms and living rooms., Conclusions: While the four methods examined correlated moderately, all have practical advantages and difficulties. No method can be considered as ideal for measuring individual exposure. For practicality, use of vacuum cleaner and Petri dish methods are recommended.

Background: In temperate climates, exposure to house dust mite (HDM) allergens is the strongest environmental risk factor for childhood asthma. Environmental modifications to limit exposure have the potential to reduce the prevalence of asthma. The aim of this study was to reduce allergen exposure for children at high risk of developing asthma., Methods: A total of 616 pregnant women were randomized to HDM intervention and control groups. The control group had no special recommendations whereas the intervention group was given allergen impermeable mattress covers and an acaricidal washing detergent for bedding. Children were visited regularly until 18 months of age to have dust collected from their bed., Results: Der p 1 concentrations in the control group increased from 5.20 microg/g at 1 month to 22.18 microg/g at 18 months but remained low in the intervention group, ranging from 3.27 microg/g at 1 month to 6.12 microg/g at 18 months., Conclusions: In a high HDM allergen environment, a combined approach using physical barriers and an acaricidal wash, is effective in reducing HDM allergen concentrations in bedding. However, even with these control measures in place, HDM allergen levels remained high by international standards.

Allergic rhinitis is associated with exposure to inhaled allergens. Allergic sensitization to the fungus Alternaria is common, especially in warm climates, but the relevance of sensitization to Alternaria in the generation of rhinitis has not been elucidated. The aim of this study was to determine whether natural exposure to Alternaria induces rhinoconjuctivitis symptoms in Alternaria-sensitized children. Symptoms of rhinoconjuctivitis in 132 atopic (measured by skin prick tests) children (aged 7-12 years) in inland New South Wales Australia were measured using parent-completed questionnaires in summer and winter 1998. Airborne concentrations of Alternaria spores and grass pollen were measured throughout the study period using a Burkard volumetric trap. The relation between airborne concentrations of Alternaria spores and symptoms of rhinoconjunctivitis was examined using Wilcoxon's matched pairs signed ranked test and generalized estimating equations. The proportion of children atopic to Alternaria reporting symptoms of rhinitis was significantly higher in the summer, when airborne concentrations of Alternaria were high, than in the winter, when airborne concentrations were low (66.2% vs. 38.2% for nasal symptoms at night, p = 0.0001, 70.6% vs. 51.52% for nasal symptoms during the day, p = 0.02). The proportion of children using anti-allergic treatment was also higher in summer than in winter (anti-allergic medication for the nose 39.7% vs. 17.7%, p = 0.0003). A strong correlation between airborne concentrations of grass pollen and Alternaria was found (R = 0.94, p < 0.001). However, when all children atopic to ryegrass were excluded from the analyses, significant associations between symptoms and season remained. We conclude that exposure to Alternaria spores may be an important cause of allergic rhinoconjunctivitis.

Background: In parts of coastal Australia, house dust mite allergen concentrations in homes are often very high with at least 80% of homes in Sydney exceeding concentrations of 10 microg of allergen per gram of fine dust. In this study, we report the relation between characteristics of the home environment and house dust mite allergen concentrations at three sites in Sydney homes., Methods: A total of 616 families were recruited as part of the Childhood Asthma Prevention Study (CAPS). Information about the home environment and structural aspects of the home was collected using a questionnaire. Samples of dust were collected from the parents' bed, the bedroom floor and the living room floor and assayed for Der p 1., Results: A total of 68% of participants' beds, 65% of bedroom floors and 56% of living room floors had Der p 1 concentrations above 10 microg/g, with the highest concentrations of allergen in the bed. The most significant predictor of high Der p 1 concentrations in the bed and floors was the age of the home. We also found that beds with mattresses over two years old and with woollen or synthetic blankets or synthetic quilts had higher Der p 1 concentrations. Carpeted floors had higher Der p 1 concentrations than hard floors., Conclusion: The finding that high Der p 1 allergen concentrations in homes with carpets and older mattresses indicates that control strategies directed at these sources are likely to be effective in reducing exposure. Alternatives such as the use of house dust mite impermeable mattress encasings on older mattresses may also be effective in reducing exposure.

Background: House-dust-mite allergen content differs between houses and is thought to be a function of the housing characteristics and furnishing choices that affect indoor microclimate and mite proliferation. The importance of these features may differ with regional climates., Methods: Concentrations of mite allergen were analysed as a function of housing features. Information on housing features was collected by questionnaire in 50 houses in two towns in a dry inland region of Australia. Mite allergen (Der p 1) was measured by ELISA in dust samples collected on five occasions over 2 years from beds and floors., Results: Der p 1 was detected in all houses. Many housing features did not influence mite allergen concentrations. However, the presence of evaporative cooling increased mite allergen by 3.34-fold in beds (P=0.007) and 3.94-fold in floors (P=0.003). Mite allergen was threefold higher in mattresses >5 years old, and synthetic and feather duvets tended to have higher and lower levels of mite allergen, respectively., Conclusions: In houses in dry, inland regions of Australia, evaporative cooling and older mattresses are associated with higher concentrations of mite allergen. Alternative forms of air conditioning to evaporative cooling may be useful for control of mite allergen in dry regions.

Objective: To compare the prevalence and risk factors for wheeze, asthma diagnosis and hayfever in Aboriginal and non-Aboriginal children living in rural towns in Australia., Design and Setting: Cross-sectional study in two towns in rural NSW, Australia, 1997., Participants: Primary school children (aged 7-12 years) classified by their parents as being of Aboriginal (n = 158) or of non-Aboriginal (n = 1,282) origin., Main Outcome Measures: Atopy measured by skinprick tests and respiratory symptoms measured by parent-completed questionnaire., Results: Aboriginal children were less likely to be atopic (36.2% v 45.6%; 95% CI for the difference, -17.6 to -1.3) and to have hayfever (23.3% v 35.2%; 95% CI for the difference, -19.1 to -4.6) than non-Aboriginal children, but were equally likely to have had wheeze (31.0% v 27.3%) and asthma (39.4% v 39.3%). Among Aboriginal children, having had bronchitis before age two was a strong risk factor for wheeze (adjusted odds ratio (aOR), 9.3; 95% CI, 2.8-30.2) and asthma (aOR, 19.3; 95% CI, 4.7-79.3) and having a parent with hayfever was a strong risk factor for hayfever (aOR, 17.9; 95% CI, 3.5-90.8), but these risk factors were weaker among non-Aboriginal children., Conclusions: Asthma and wheeze are equally prevalent in Aboriginal and non-Aboriginal children living in the same towns, but appear to have a different aetiology.

Background: In inland NSW, Australia, allergic sensitization to the fungi Alternaria and Cladosporium and to pollen is common and an important risk factor for asthma., Objective: We report the results of a series of experiments designed to assess the nature of personal exposure to these airborne allergenic particles. We have tested the effect of exposure conditions and level of activity on measurements of the personal exposure., Method: Personal Air Samplers (PAS) and Nasal Air Samplers (NAS) were employed. NAS are fitted just inside the nose and collect inhaled particles by impaction, while the PAS use a pump-operated filter with constant air flow (2 L/min). Thirty-three subjects (adults and children) used both NAS and PAS simultaneously for four one hour periods during which they performed activities or rested, both inside and outside their homes. Samples were analysed by light microscopy. Alternaria spores, Cladosporium spores, grass pollen and nongrass pollen were counted., Results: Both samplers detected substantial variation in exposure between subjects. Between members of the same household, the intrahouse correlation coefficient ranged from < 0 - 0.38. Levels of pollen grains and fungal spores inhaled were higher during periods of activity than during rest, and higher while subjects were outdoors than indoors. During the active outdoor period, the number of Alternaria spores inhaled ranged from 4 to 794 (median 11) spores/hr, Cladosporium from 0 to 396 (median 4) spores/hr, grass pollen from 0 to 81 (median 1) grains/hr and nongrass pollen from 0 to 72 (median 5) grains/hr., Conclusion: This is the first study to quantify individual inhaled levels of allergenic fungal spores and pollen under normal domestic circumstances. Exposure can be substantial and highly variable between individuals. The amount of particles inhaled relates both to location of the individual and activity being performed, independent of age group.

There is a dose-response relation between the level of exposure to house dust mite allergen and the risk of acquiring sensitization to this allergen as well as the risk of developing asthma. This relation is apparent at levels of exposure below 10 microg/g. In communities where nearly all houses have house dust mite allergen levels above this threshold, all susceptible individuals will be affected, and the relation to house dust mite exposure will not be apparent. Although these observational data would suggest that reducing exposure to house dust mite allergen should lessen the risk of developing sensitization and asthma, definitive evidence from randomized controlled trials is not yet available. Of the many clinical trials of house dust mite avoidance as therapy for asthma, only a few have produced sustained, substantial reductions in allergen levels in the bed. These effective interventions all included allergen-impermeable encasement of mattresses along with other strategies. In most trials where allergens levels were successfully reduced, there were clinical benefits for patients with asthma.

Background: To interpret individual measurements of house dust mite (HDM) allergen and to design and analyse HDM studies it is necessary to quantify the variability which is inherent in the measurement of this exposure., Objective: To estimate the repeatability of one method of HDM allergen measurement., Methods: We analysed data from one or more HDM allergen measurements in 215 houses included in four previous studies conducted in Sydney (a high allergen environment) and Busselton, Western Australia (a moderate allergen environment). Samples were collected from the bed by vacuuming above and below the sheets and inside the pillow case and from the bedroom and living room floors by vacuuming a 1 m2 area for 1 min. Extracts from aliquots of fine dust from each sample were assayed for HDM allergen Der p I using a monoclonal antibody enzyme linked immunosorbent assay (ELISA). The values for HDM allergen were positively skewed and the suitability of a log transformation was established by the resulting normal distribution and stable within-site variance., Results: The range of single determination (within which the true value lies with 95% certainty) was 3.1-fold for samples from the bed and 3.5-fold for samples from the floor. The coefficient of repeatability (the ratio beyond which a change between two estimates is established with 95% certainty) was 4.9 for the bed and 5.8 for the floor., Conclusion: We estimate that, to detect a twofold difference or change in allergen levels, 35 houses per group will be required in cross-sectional studies and 30 houses per group in parallel-group, randomized controlled trials. We recommend that beds be sampled by collecting dust from the layer of bedding below the bottom sheet. A single site within the bedroom floor may be taken as representative of this site but this is not true for the living-room floor.

To measure the association between changes in house dust mite (HDM) allergen Der p I exposure and changes in the severity of asthma, we re-analysed data from a clinical trial in which 34 HDM-allergic subjects with asthma (18 women, mean age 35 years) were followed for between 3 and 12 months. The concentration of Der p I in fine dust from the bed, the bedroom floor and the living room floor was measured at 3-monthly intervals along with assessment of subjects' spirometric function and airway hyperresponsiveness (AHR, measured by histamine inhalation test). Daily symptom scores, morning peak expiratory flow rate and peak flow variability were measured throughout the study period. The mean Der p I concentration in the bed at baseline was 25.4 micrograms/g (95% CI: 15.8-40.6). During the course of the study large within-subject fluctuations were observed in allergen concentrations and in the measurements of the severity of asthma. Changes in allergen concentration in the bed were significantly correlated with changes in AHR (P = 0.003) and symptom score (P = 0.04). Changes in allergen concentration in the living room floor were correlated with changes in symptom scores (P = 0.01). Although these correlations were significant the magnitude of the effect was relatively modest. We conclude that a large reduction in HDM allergen concentration, particularly in the bed, results in a modest reduction in AHR and improvement in symptoms in HDM-allergic subjects with asthma.

To test the effectiveness of a house dust mite (HDM) allergen avoidance strategy we conducted a randomized controlled trial in 35 atopic subjects with asthma, aged 13 to 60 living in Sydney - a high HDM allergen environment. After a 3 month run-in period, subjects were randomized to active allergen avoidance treatment (n = 17) or placebo (n = 18) groups and followed for 6 months. The active treatment involved placing impermeable covers over the mattress, pillows and duvet and spraying the remaining bedding, as well as the carpets and furniture, with a tannic acid/acaricidal spray. Subjects kept a daily record of symptoms and peak expiratory flow rates and had 3 monthly assessments of lung function and airway hyperresponsiveness (AHR). Dust samples were collected from the bed, the bedroom floor and the living room floor at 3 monthly intervals and 2 weeks after the treatment. Mean HDM allergen levels at baseline at these sites were, in the active group, 15.5, 9.6 and 10.2 micrograms Der p I/g of fine dust, and, in the placebo group 25.7, 11.8 and 6.3 micrograms/g. Two weeks after the allergen avoidance treatment the HDM allergen level in the beds was reduced to 29% of baseline (95% CI 16-50%, P = 0.038 compared with placebo), but was not significantly different at 3 or 6 months. There was also no significant effect of the allergen avoidance treatment on symptom scores, peak flow variability, lung function or AHR P > 0.1).(ABSTRACT TRUNCATED AT 250 WORDS)

The beds, carpets and furnishings in 15 houses were sprayed with a solution containing tannic acid and an acaricide in an attempt to reduce allergen concentrations. Dust was collected from these sites for 4 weeks following spraying and the mite allergen Der p I concentration was measured and compared with baseline concentrations. In a subgroup of houses, counts of live mites and estimates of aeroallergen were also made. Four untreated houses were monitored over the same period. In dust samples collected 3 days after spraying, the mean concentrations of Der p I in beds, carpets and furniture were 23%, 28% and 26% of the pretreatment levels. All these reductions were significant compared to untreated controls. Samples collected 4 weeks after treatment were not significantly different to baseline for each group. After the initial reduction, the rate of increase in allergen concentration was significantly greater in the spray-only beds than in the beds which had been both sprayed and fitted with occlusive covers. Both aeroallergen and live mites continued to be detected in houses after treatment with the spray. These studies suggest that such sprays are only temporarily effective when applied at the manufacturer's recommended volumes and additional approaches are required to control the bulk of allergens in houses.

Background Atopy in early life is heterogeneous in timing of onset, remission and persistence and in the nature of specific sensitization to allergens. However, this heterogeneity is not well characterized. Objective Our aim was to define longitudinal phenotypes of atopy between ages 1.5 and 8 years, and to assess the relationship of the atopy phenotypes to the risk of asthma, eczema and rhinitis at 8 years of age. Methods We used latent class analysis (LCA) to define atopy phenotypes using data from skin prick tests that were performed at 1.5, 3, 5 and 8 years in participants in the Childhood Asthma Prevention Study (CAPS). Results Four phenotypes were defined: late mixed inhalant sensitization; mixed food and inhalant sensitization; house dust mite (HDM) monosensitized; and no atopy. All three atopic phenotypes were associated with asthma, eczema and rhinitis, but the strongest association, particularly for asthma, was with the mixed food and inhalant sensitization phenotype. Conclusion & clinical relevance We have used a LCA model to define atopy phenotypes empirically. The finding of a strong association between the mixed food and inhalant sensitization class and the presence of asthma and poor asthma control at age 8 years implies that food sensitization in early life may be of greater significance for subsequent risk of asthma than previously thought. [ABSTRACT FROM AUTHOR]

Background: House dust mite (HDM) allergy is closely linked to the expression of asthma and other allergic diseases. Understanding factors influencing variation in allergen may help in controlling allergic disease. The objective of this study was to investigate the effects of seasonal changes in climate, type of bed used in very early childhood and anti-mite interventions on HDM allergen concentration. Methods: Participants were enrolled in a randomized-controlled trial of HDM avoidance. Der p 1 was measured in dust samples from children’s beds on 13 occasions, from birth to age 5 years, between 1997 and 2004. Bed types were categorized as bassinette, cot or bed. The effects of study month, type of bed and intervention group on HDM allergen concentration were estimated by multiple linear regression. The relation between climatic variables and HDM allergen concentration was investigated using a polynomial distributed lag model. Results: House dust mite allergen concentrations were initially low in cots and bassinettes in 1997/1998, peaked in bassinettes and beds between 1999 and 2001 and then slowly declined during the period 2002/2004. Seasonal fluctuations occurred with minima in summer and two- to threefold higher maxima during late autumn. Allergen peaks were correlated with relative humidity peaks 2 months previously. Seasonal changes in allergen were not affected by the HDM avoidance intervention. Conclusions: House dust mite allergen concentrations in Sydney beds fluctuate approximately two- to threefold on an annual cycle, partly determined by relative humidity, with peaks in late autumn and minima in summer. Fluctuations of this magnitude might be sufficient to influence asthma symptoms. [ABSTRACT FROM AUTHOR]

Background Although longer duration of breastfeeding and later introduction of solid foods are both recommended for the prevention of asthma and allergic disease, evidence to support these recommendations is controversial. Objective To examine the relation between infant feeding practices and the risk of asthma and allergic disease at age 5 years. Methods A cohort of children with a family history of asthma in Sydney, Australia, was followed from birth to age 5 years. Data on infant feeding practices and on early manifestations of eczema were collected prospectively. The presence of eczema, asthma and atopy (positive allergen skin prick tests) were determined at age 5 years. Results In 516 children evaluated at age 5 years, there was no significant association between the duration of breastfeeding or timing of introduction of solid foods and protection against asthma or other allergic disease, after adjustment for confounding factors. However, breastfeeding for 6 months or more and introduction of solid foods after 3 months were both associated with an increased risk of atopy at age 5 years ( P=0.02 and 0.01, respectively). There was no significant association between the presence of eczema at 4 weeks and at 3 months and continued breastfeeding beyond those times. Conclusion Longer duration of breastfeeding and later introduction of solid foods did not prevent the onset of asthma, eczema or atopy by age 5 years. [ABSTRACT FROM AUTHOR]

Summary Background Although allergy to latex is a well-characterized phenomenon, some hospitals continue to provide staff with powdered latex gloves as an option to low- or non-powdered gloves. Objective We aimed to measure the extent to which inhalation of latex particles could be reduced by the use of protective masks or by replacing powdered latex gloves with non-powdered latex gloves. Methods Twenty healthcare workers in a hospital setting wore nasal air samplers (NAS) and Institute of Occupational Medicine (IOM) samplers for four 20-min periods. Subjects wore powdered gloves, non-powdered gloves and no gloves during three sampling periods, and in the fourth, subjects applied an aerosol barrier face-mask or a particulate face-mask (N95) while wearing powdered gloves. All samples were stained for particles bearing Hev b 5 allergen by the Halogen assay. Results All subjects inhaled Hev b 5 bearing particles in all sampling periods. IOM samplers collected particles at 70% of the rate of NAS. The number of particles inhaled while wearing powdered gloves was 23.8-fold higher than when not wearing gloves and 9.7-fold higher than when wearing non-powdered latex gloves (P < 0.0001). Wearing an aerosol barrier mask did not significantly reduce the number of particles inhaled ( P = 0.108), while use of particulate masks significantly reduced the number of particles inhaled by 17.4-fold ( P = 0.003). Conclusions Use of non-powdered gloves is the most effective method of reducing occupational aeroallergen exposure to latex arising from gloves. However, secondary protection using particulate masks is a valid alternative, and may be helpful for preventing respiratory sensitization. [ABSTRACT FROM AUTHOR]

Background: Exhaled nitric oxide (eNO), which has been proposed as a measure of airway inflammation, is increased in atopic subjects. This raises the question of whether eNO provides any additional information about airway inflammation in asthmatic subjects, other than as a marker for atopy. A study was undertaken to determine whether eNO levels in a population of atopic children are associated with sensitisation or natural exposure to specific allergens, and to examine the relationship between eNO, airway responsiveness, and current respiratory symptoms.Methods: Exhaled NO and airway responsiveness to histamine were measured in winter and in summer in 235 children aged 8-14 years who had been classified as atopic by skin prick testing. Current respiratory symptoms, defined as wheeze or cough during the month preceding the test, were measured by a parent completed questionnaire. Airway hyperresponsiveness (AHR) was defined as a dose response ratio (DRR) of >8.1 (% fall in forced expiratory volume in 1 second (FEV(1))/micromol + 3).Results: Sensitisation to house dust mite was associated with raised eNO levels in winter while sensitisation to Cladosporium was associated with raised eNO levels in both winter and summer. Grass pollen sensitisation was not associated with raised eNO levels in either season. Exhaled NO correlated significantly with DRR histamine (r=0.43, p<0.001) independently of whether the children had current symptoms or not. In children with current wheeze, those with AHR had eNO levels 1.53 (95% CI 1.41 to 1.66) times higher than those without AHR (p=0.006). Neither DRR (p=1.0) nor eNO levels (p=0.92) differed significantly between children with or without persistent dry cough in the absence of wheeze.Conclusions: In atopic children, raised eNO levels are associated with sensitisation to perennial allergens, but not to seasonal allergens such as grass pollen. In this population, an increase in eNO is associated with AHR and current wheezing, suggesting that eNO is more than just a marker for atopy. [ABSTRACT FROM AUTHOR]