Mite, cat, and cockroach exposure, allergen sensitisation, and asthma in children: a case-control study of three schools.

BACKGROUND: The amount of allergen necessary to sensitise genetically "at risk" children is unclear. The relation between allergen exposure and asthma is also uncertain. METHODS: To ensure a wide range of allergen exposures the data from case-control studies of asthma in children aged 12-14 years attending three schools in Los Alamos, New Mexico and Central Virginia were combined. Skin prick tests to indoor and outdoor allergens and bronchial hyperreactivity to histamine were assessed in children with and without symptoms of asthma. The concentration of mite, cat, and cockroach allergens in dust from the children's homes was used as a marker of exposure. RESULTS: Three hundred and thirty two children (157 with asthmatic symptoms and 175 controls) were investigated. One hundred and eighty three were classified as atopic on the basis of allergen skin prick tests and 68 as asthmatic (symptoms plus bronchial responsiveness). The prevalence and degree of sensitisation to mite and cockroach, but not cat, was strongly associated in atopic children with increasing domestic concentrations of these allergens. Asthma was strongly associated with sensitisation to indoor allergens (p<10(-6)) and weakly to outdoor allergens (p = 0.026). There was an association between current asthma and the concentration of mite allergen amongst atopic children (p = 0.008) but not amongst those who were specifically mite sensitised (p = 0.16). CONCLUSIONS: The domestic reservoir concentration of mite and cockroach, but not cat, allergen was closely related to the prevalence of sensitisation in atopic children. However, the prevalence of current asthma had a limited relationship to these allergen measurements, suggesting that other factors play a major part in determining which allergic individuals develop asthma.     

Primary prevention of asthma and atopy during childhood by allergen avoidance in infancy: a randomised controlled study

BACKGROUND: Recent increases in the prevalence of asthma and atopy emphasise the need for devising effective methods for primary prevention in children at high risk of atopy. METHOD: A birth cohort of genetically at risk infants was recruited in 1990 to a randomised controlled study. Allergen avoidance measures were instituted from birth in the prophylactic group (n=58). Infants were either breast fed with mother on a low allergen diet or given an extensively hydrolysed formula. Exposure to house dust mite was reduced by the use of an acaricide and mattress covers. The control group (n=62) followed standard advice as normally given by the health visitors. At age 8, all 120 children completed a questionnaire and 110 (92%) had all assessments (skin prick test, spirometry, and bronchial challenges). RESULTS: In the prophylactic group eight children (13.8%) had current wheeze compared with 17 (27.4%) in the control group (p=0.08). Respective figures were eight (13.8%) and 20 (32.3%) for nocturnal cough (p=0.02) and 11 of 55 (20.0%) and 29 of 62 (46.8%) for atopy (p=0.003). After adjusting for confounding variables, the prophylactic group was found to be at a significantly reduced risk for current wheeze (odds ratio (OR) 0.26 (95% confidence interval (CI) 0.07 to 0.96)), nocturnal cough (OR 0.22 (95% CI 0.06 to 0.83)), asthma as defined by wheeze and bronchial hyperresponsiveness (OR 0.11 (95% CI 0.01 to 1.02)), and atopy (OR 0.21 (95% CI 0.07 to 0.62)). CONCLUSION: Strict allergen avoidance in infancy in high risk children reduces the development of allergic sensitisation to house dust mite. Our results suggest that this may prevent some cases of childhood asthma.     

Lung function at one month of age as a risk factor for infant respiratory symptoms in a high risk population

BACKGROUND: Abnormal premorbid lung function is a risk factor for subsequent wheezing in children with one or no atopic parent. This study was undertaken to establish whether early lung function in high risk infants (both parents atopic) was a risk factor for respiratory symptoms in infancy and to examine the influence of maternal asthma, smoking, and allergen exposure during pregnancy on any association. METHODS: Infants were recruited from the NAC Manchester Asthma and Allergy Study cohort at birth. Partial forced expiratory flow volume technique under sedation was carried out to determine maximal flow at FRC (V'maxFRC). Children were followed prospectively and parents completed a standard respiratory questionnaire at one year of age. RESULTS: Sixty nine term infants (34 boys; 88% mothers non-smokers; no household pets) underwent respiratory function testing. Size adjusted V'maxFRC was significantly lower in infants who had recurrent wheeze during the first year of life (mean 1.3 ml/s/cm, 95% CI 0.99 to 1.60) than in those who did not (mean 2.03 ml/s/cm, 95% CI 1.71 to 2.36; p=0.01). V'maxFRC was also significantly lower in infants who had recurrent cough symptoms. In multivariate regression analysis, when adjusted for age at test, sex, maternal asthma, smoking and maternal mattress Der 1 levels, a lower size adjusted V'maxFRC score remained strongly associated with wheezing (OR 0.37, 95% CI 0.18 to 0.77, p=0.007). Maternal smoking also remained an independent risk factor (OR 29.85, 95% CI 2.46 to 362.5, p=0.008). CONCLUSION: Significantly diminished lung function was present in high risk infants who subsequently wheezed and coughed. This was independent of maternal exposure to mite allergen, asthma, and smoking during pregnancy.     

Relationship between exposure to domestic allergens and bronchial hyperresponsiveness in non-sensitised, atopic asthmatic subjects

BACKGROUND: The effect of exposure to allergens not causing sensitisation in atopic asthmatic subjects has not previously been studied. A study was undertaken to assess the degree of asthma severity (measured by spirometry, airway reactivity and exhaled nitric oxide) in atopic asthmatic patients not sensitised to the domestic allergen to which they were exposed. METHODS: Dust samples were collected from the living room carpet and mattress in the homes of 248 subjects and dust mite, cat and dog allergen concentrations were measured. Spirometry, non-specific bronchial reactivity (BR), and exhaled nitric oxide (eNO) were ascertained. Patients' sensitisation status was assessed by skin prick testing. RESULTS: Adult atopic asthmatics not sensitised to mite but exposed to high levels of mite allergen had significantly more severe BR than subjects not exposed to high levels of mite (PD(20), geometric mean (GM) 0.21 mg (95% CI 0.09 to 0.47) v 0.86 mg (95% CI 0.44 to 1.67), mean ratio difference 4.1 (95% CI 1.5 to 11.4), p=0.008). Subjects not sensitised but exposed to high levels of dog allergen also had significantly more severe BR than subjects not exposed (PD20 GM 0.16 v 0.52 mg, mean ratio difference 3.3 (95% CI 1.2 to 9.2), p=0.01). The differences in BR between these groups were still significant after adjusting for confounding factors. This effect of greater airway reactivity was not seen in subjects exposed but not sensitised to cat allergens. CONCLUSION: Atopic asthmatic subjects who are exposed to high levels of dust mite or dog allergens but not sensitised to these allergens have evidence of increased airway reactivity.     

Early allergen exposure, skin prick responses, and atopic wheeze at age 5 in English children: a cohort study

BACKGROUND: For many years it has been assumed that the risk of childhood respiratory allergies is related to allergen exposures in early life. There are, however, few prospective data in support. We aimed to examine this relationship in a representative cohort of children born in Ashford, Kent (UK). METHODS: 625 children (94% of those eligible) were followed from birth to the age of 5.5 years at which time 552 underwent skin prick testing to extracts of house dust mite and cat fur allergens. Maternal reports of wheeze in the last year were collected by interview. These outcomes were related to individual domestic concentrations of Der p 1 and Fel d I allergens estimated from dust collection at the age of 8 weeks. RESULTS: 10% of children were sensitised to house dust mite or cat at age 5.5 years; 7% had atopic wheeze. No significant relationships between allergen exposure and either sensitisation or wheeze were found but, on examination, the exposure-response relationships for both allergens and for each outcome rose steeply at low levels of exposure and were attenuated at high levels of exposure. These patterns were modified by paternal atopy and by birth order. CONCLUSIONS: There are no linear relationships between early allergen exposure and the induction of childhood respiratory allergy; rather, the risks of IgE sensitisation and asthma rise at very low levels of exposure and are attenuated thereafter. These patterns are influenced by parental atopy and birth order. These findings suggest important gene-environment interactions in the development of atopy and asthma and imply that reductions in domestic allergen exposure alone are unlikely to have a major impact in decreasing the incidence of these diseases in childhood.     

Study of modifiable risk factors for asthma exacerbations: virus infection and allergen exposure increase the risk of asthma hospital admissions in children

BACKGROUND: Asthma exacerbation is the most common cause of hospital admission in children. A study was undertaken to investigate the importance of allergen exposure in sensitised individuals in combination with viral infections and other potentially modifiable risk factors precipitating asthma hospital admission in children. METHODS: Eighty four children aged 3-17 years admitted to hospital over a 1 year period with an acute asthma exacerbation (AA) were matched for age and sex with two control groups: stable asthmatics (SA) and children admitted to hospital with non-respiratory conditions (IC). Risk factors were assessed by questionnaires and determination of allergen sensitisation, home allergen exposure, pollen exposure, and respiratory virus infection. RESULTS: Several non-modifiable factors (atopy, duration of asthma) were associated with increased risk. Among the modifiable factors, pet ownership, housing characteristics, and parental smoking did not differ between the groups. Regular inhaled corticosteroid treatment was significantly less common in the AA group than in the SA group (OR 0.2, 95% CI 0.1 to 0.6; p = 0.002). A significantly higher proportion of the AA group were virus infected (44%) and sensitised and highly exposed to sensitising allergen (76%) compared with the SA (18% and 48%) and IC groups (17% and 28%; both p<0.001). In a multiple conditional logistic regression (AA v SA), allergen sensitisation and exposure or virus detection alone were no longer independently associated with hospital admission. However, the combination of virus detection and sensitisation with high allergen exposure substantially increased the risk of admission to hospital (OR 19.4, 95% CI 3.7 to 101.5, p<0.001). CONCLUSIONS: Natural virus infection and real life allergen exposure in allergic asthmatic children increase the risk of hospital admission. Strategies for preventing exacerbations will need to address these factors.     

Damp housing and asthma: a case-control study

BACKGROUND: Several epidemiological studies have reported a higher prevalence of respiratory symptoms in subjects living in damp housing, but links with specific respiratory diseases such as asthma have not been satisfactorily established. METHODS: One hundred and two subjects with physician diagnosed asthma and 196 age and sex matched controls were interviewed; 222 (75%) then agreed to have their dwelling surveyed for dampness. The prevalence of both self-reported and observed dampness in the homes of the asthmatic subjects and controls were compared. Both asthma and the severity of the dampness were quantified so that the possibility of a dose-response relationship could be investigated. RESULTS: Asthmatic subjects reported dampness in their current (odds ratio (OR) 1.92, 95% confidence interval (CI) 1.18 to 3.12) and previous (OR 2.11, 95% CI 1.29 to 3.47) dwellings more frequently than control subjects. The surveyor confirmed dampness in 58 of 90 (64%) dwellings of asthmatic subjects compared with 54 of 132 (41%) dwellings of control subjects (OR 2.62, 95% CI 1.50 to 4.55). This association persisted after controlling for socioeconomic and other confounding variables (adjusted OR 3.03, 95% CI 1.65 to 5.57). The severity of asthma was found to correlate statistically with measures of total dampness (r = 0.30, p = 0.006) and mould growth (r = 0.23, p = 0.035) in the dwelling. Patients living in homes with confirmed areas of dampness had greater evidence of airflow obstruction than those living in dry homes (mean difference in forced expiratory volume in one second (FEV1) 10.6%, 95% CI 1.0 to 20.3). CONCLUSIONS: Asthma is associated with living in damp housing and there appears to be a dose-response relationship. Action to improve damp housing conditions may therefore favourably influence asthma morbidity.


     

Consumption of fresh fruit rich in vitamin C and wheezing symptoms in children. SIDRIA Collaborative Group, Italy (Italian Studies on Respiratory Disorders in Children and the Environment)

BACKGROUND: A beneficial effect of fresh fruit consumption on lung function has been observed in several studies. The epidemiological evidence of the effect on respiratory symptoms and asthma is limited. The consumption of fruit rich in vitamin C was examined in relation to wheezing and other respiratory symptoms in cross sectional and follow up studies of Italian children. METHODS: Standardised respiratory questionnaires were filled in by parents of 18 737 children aged 6-7 years living in eight areas of Northern and Central Italy. The winter intake of citrus fruit and kiwi fruit by the children was categorised as less than once per week, 1-2 per week, 3-4 per week, and 5-7 per week. A subset of 4104 children from two areas was reinvestigated after one year using a second parental questionnaire to record the occurrence of wheezing symptoms over the intervening period. RESULTS: In the cross sectional analysis, after controlling for several confounders (sex, study area, paternal education, household density, maternal smoking, paternal smoking, dampness or mould in the child's bedroom, parental asthma), intake of citrus fruit or kiwi fruit was a highly significant protective factor for wheeze in the last 12 months (odds ratio (OR) = 0.66, 95% confidence intervals (CI) 0.55 to 0.78, for those eating fruit 5-7 times per week compared with less than once per week), shortness of breath with wheeze (OR = 0.68, 95% CI 0.56 to 0.84), severe wheeze (OR = 0.59, 95% CI 0.40 to 0.85), nocturnal cough (OR = 0.73, 95% CI 0.65 to 0.83), chronic cough (OR = 0.75, 95% CI 0.65 to 0.88), and non-coryzal rhinitis (OR = 0.72, 95% CI 0.63 to 0.83). In the follow up study fruit intake recorded at baseline was a strong and independent predictor of all symptoms investigated except non-coryzal rhinitis. In most cases the protective effect was evident even among children whose intake of fruit was only 1-2 times per week and no clear dose-response relationship was found. The effect was stronger (although not significantly so (p = 0.13)) in subjects with a history of asthma; those eating fresh fruit at least once a week experienced a lower one year occurrence of wheeze (29. 3%) than those eating fruit less than once per week (47.1%) (OR = 0. 46, 95% CI 0.27 to 0.81). CONCLUSIONS: Although the effect of other dietary components cannot be excluded, it is concluded that the consumption of fruit rich in vitamin C, even at a low level of intake, may reduce wheezing symptoms in childhood, especially among already susceptible individuals.     

Is exercise testing useful in a community based asthma survey?

BACKGROUND--In hospital clinics exercise challenge is used as a simple, non-invasive, non-pharmacological test for asthma in childhood. Little is known of its value in a community setting. An exercise test was therefore evaluated as an adjunct to a respiratory questionnaire in the course of an asthma survey. METHODS--From a cohort of 4003 primary school children, 607 of 799 with respiratory symptoms answered a detailed respiratory questionnaire. From the same cohort 135 of 229 randomly selected asymptomatic children were also interviewed. A stratified selection of one in four of the children interviewed was then invited to take part in a six minute cold air enhanced exercise challenge test; 128 symptomatic and 26 asymptomatic children attended. RESULTS--Bronchial hyperreactivity, a fall of FEV1 > or = 10% at five, 10, or 15 minutes following the exercise challenge, was identified in 15 of 128 symptomatic children and in one of 26 asymptomatic children. Bronchial hyperreactivity was found in only one of three children with frequent shortness of breath and one of five with frequent wheeze. It was found in 13 of 58 children whose parents were aware of the diagnosis of asthma; in 10 of 26 children who were on regular prophylactic treatment; in only 11 of 70 children with a history of exercise induced symptoms; and seldom in children with mild symptoms. Gestational age and ventilator support in the neonatal period were significant predictors of bronchial hyperreactivity. CONCLUSIONS--Exercise testing enhanced by cold air adds very little to a well designed respiratory questionnaire in community studies of asthma in childhood.     

Cough receptor sensitivity to capsaicin does not change after allergen bronchoprovocation in allergic asthma

BACKGROUND: The relationship between cough receptor sensitivity and eosinophilic inflammation of the airway in patients with asthma remains unclear. METHODS: Eighteen patients with asthma sensitised to house dust mite (HDM) were enrolled in a randomised parallel group study. Patients with asthma whose main symptom was cough were not enrolled in the study. Half the patients were randomly assigned to inhale saline and the other half to inhale HDM allergen. Cough receptor sensitivity to capsaicin, airway responsiveness to histamine, and sputum eosinophils analysed with hypertonic saline inhalation were investigated before and 24 hours after saline or HDM allergen bronchoprovocation. RESULTS: Patients inhaling saline showed no significant changes in sputum eosinophils (from 7.87% (95% confidence interval (CI) 5.08 to 12.19) to 8.60% (95% CI 3.03 to 14.18); p=0.97), airway responsiveness to histamine (from 726.68 micro g/ml (95% CI 251.90 to 2096.36) to 773.01 micro g/ml (95% CI 251.36 to 2377.23); p=0.96), or capsaicin sensitivity (from 7.23 micro M (95% CI 2.45 to 21.31) to 7.24 micro M (95% CI 2.46 to 21.31); p=0.96). Early asthmatic response was induced in all patients, and late asthmatic response was observed in six of nine patients inhaling HDM allergen. Although there were significant increases in sputum eosinophils (from 9.83% (95% CI 6.78 to 14.27) to 21.00% (95% CI 13.85 to 28.15); p<0.01) and airway responsiveness to histamine (from 784.16 micro g/ml (95% CI 318.24 to 1932.24) to 377.81 micro g/ml (95% CI 118.43 to 1205.24); p<0.05) 24 hours after HDM allergen inhalation compared with baseline levels, capsaicin sensitivity did not change significantly (from 5.75 micro M (95% CI 1.91 to 17.30) to 6.20 micro M (95% CI 2.21 to 17.38); p=0.77). CONCLUSIONS: These findings suggest that cough receptor sensitivity to capsaicin is not associated with eosinophilic inflammation of the airway in patients with allergic asthma whose main symptoms are wheezing and dyspnoea but not cough.     

Effect of bradykinin on allergen induced increase in exhaled nitric oxide in asthma

Background: Exposure of patients with atopic asthma to allergens produces a long term increase in exhaled nitric oxide (FE_NO), probably reflecting inducible NO synthase (NOS) expression. In contrast, bradykinin (BK) rapidly reduces FE_NO. It is unknown whether BK suppresses increased FE_NO production after allergen exposure in asthma, and whether it modulates FE_NO via NOS inhibition. Methods: Levels of FE_NO in response to aerosolised BK were studied before (day 3) and 48 hours after (day 10) randomised diluent (diluent/placebo/BK (Dil/P/BK)), allergen (allergen/placebo/BK (All/P/BK), and allergen/L-NMMA/BK (All/L/BK)) challenges (day 8) in 10 atopic, steroid naïve, mild asthmatic patients with dual responses to inhaled house dust mite extract. To determine whether BK modulates FE_NO via NOS inhibition, subjects performed pre- and post-allergen BK challenges after pretreatment with the NOS inhibitor L-NMMA in the All/L/BK period. Results: Allergen induced a fall in FE_NO during the early asthmatic reaction (EAR) expressed as AUC_0–1 (ANOVA, p=0.04), which was followed by a rise in FE_NO during the late asthmatic reaction (LAR) expressed as AUC_1–48 (ANOVA, p=0.008). In the Dil/P/BK period, FE_NO levels after BK on pre- and post-diluent days were lower than FE_NO levels after placebo (difference 23.5 ppb (95% CI 6.2 to 40.9) and 22.5 ppb (95% CI 7.3 to 37.7), respectively; p<0.05). Despite the long lasting increase in FE_NO following allergen challenge in the LAR, BK suppressed FE_NO levels at 48 hours after allergen challenge in the All/P/BK period, lowering the increased FE_NO (difference from placebo 54.3 ppb (95% CI 23.8 to 84.8); p=0.003) to the baseline level on the pre-allergen day (p=0.51). FE_NO levels were lower after L-NMMA than after placebo on pre-allergen (difference 10.85 ppb (95% CI 1.3 to 20.4); p=0.03) and post-allergen (difference 36.2 ppb (95% CI 5.5 to 66.9); p=0.03) days in the All/L/BK and All/P/BK periods, respectively. L-NMMA did not significantly potentiate the pre- and post-allergen reduction in BK induced FE_NO. Conclusions: Bradykinin suppresses the allergen induced increase in exhaled NO in asthma; this is not potentiated by L-NMMA. Bradykinin and L-NMMA may follow a common pathway in reducing increased NO production before and after experimental allergen exposure. Reinforcement of this endogenous protective mechanism should be considered as a therapeutic target in asthma.     

C reactive protein levels are increased in non-allergic but not allergic asthma: a multicentre epidemiological study

BACKGROUND: High sensitivity C reactive protein (HsCRP) is an inflammatory marker known to be related to smoking, obesity, and cardiovascular disease. A study was undertaken to determine whether HsCRP is related to respiratory symptoms, asthma, atopy, and bronchial hyperresponsiveness in population samples from three countries. METHODS: HsCRP was measured in 1289 subjects from three centres in ECRHS II: Reykjavik, Uppsala and Tartu. The HsCRP values ranged from <0.01 mg/l to 70.0 mg/l and were divided into four equal groups (< or = 0.45, 0.46-0.96, 0.97-2.21, and >2.21 mg/l). RESULTS: HsCRP increased with increasing body mass index (r = 0.41; p<0.0001) and was higher in smokers than in never smokers (p = 0.02). A significant relationship was found between increased HsCRP levels and respiratory symptoms such as wheeze, attacks of breathlessness after effort, and nocturnal cough (p<0.0001). The crude odds ratio (95% CI) for the probability of non-allergic asthma was 3.57 (1.83 to 6.96) for subjects in the 4th quartile compared with the 1st quartile of HsCRP. This association remained significant after adjusting for study centre, age, sex, body weight, and smoking history (OR 2.19 (95% CI 1.04 to 4.63)). No significant relationship was observed between HsCRP and allergic asthma or bronchial responsiveness. CONCLUSIONS: Raised levels of HsCRP are significantly associated with respiratory symptoms and non-allergic asthma but not with allergic asthma.     

Fatty acid levels and risk of asthma in young adults

BACKGROUND: There is current interest in the possible protective effect of long chain (n-3) fatty acids from fish in chronic lung diseases such as asthma. The aim of this community based cross sectional study was to determine whether plasma long chain (n-3) fatty acids, as a measure of dietary intake, differed between 1601 young adults with and without asthma. METHODS: Subjects of mean (SD) age 34.6 (7.1) years completed a detailed respiratory questionnaire, food frequency questionnaire, skin prick testing, and lung function tests including methacholine challenge test for bronchial hyperreactivity (BHR) and had venous blood taken for analysis of plasma fatty acids. Plasma fatty acid levels (%) were analysed using multiple logistic regression with alternative definitions of asthma and atopy as the outcomes. RESULTS: Atopy was not associated with any plasma fatty acid. The n-3 polyunsaturated fatty acids and n-6:n-3 ratio were not consistently associated with asthma or atopy. The n-6 polyunsaturated fatty acid dihomo gamma-linolenic acid (DHGLA) was positively associated with current asthma (OR=1.30, 95% CI 1.06 to 1.60), asthma (OR=1.34, 95% CI 1.13 to 1.60), and doctor diagnosed asthma (OR=1.25, 95% CI 1.06 to 1.48). CONCLUSION: Plasma n-3 fatty acids are not associated with a reduced risk of asthma or atopy among young adults. The association of DHGLA with asthma warrants further research to determine a cause-effect relationship.     

Traffic related air pollution as a determinant of asthma among Taiwanese school children

BACKGROUND: There is evidence that long term exposure to ambient air pollution increases the risk of childhood asthma, but the role of different sources and components needs further elaboration. To assess the effect of air pollutants on the risk of asthma among school children, a nationwide cross sectional study of 32 672 Taiwanese school children was conducted in 2001. METHODS: Routine air pollution monitoring data for sulphur dioxide (SO2), nitrogen oxides (NOx), ozone (O3), carbon monoxide (CO), and particles with an aerodynamic diameter of 10 microm or less (PM10) were used. Information on individual characteristics and indoor environments was from a parent administered questionnaire (response rate 93%). The exposure parameters were calculated using the mean of the 2000 monthly averages. The effect estimates were presented as odds ratios (ORs) per 10 ppb changes for SO2, NOx, and O3, 100 ppb changes for CO, and 10 microg/m3 changes for PM10. RESULTS: In a two stage hierarchical model adjusting for confounding, the risk of childhood asthma was positively associated with O3 (adjusted OR 1.138, 95% confidence interval (CI) 1.001 to 1.293), CO (adjusted OR 1.045, 95% CI 1.017 to 1.074), and NOx (adjusted OR 1.005, 95% CI 0.954 to 1.117). Against our prior hypothesis, the risk of childhood asthma was weakly or not related to SO2 (adjusted OR 0.874, 95% CI 0.729 to 1.054) and PM10 (adjusted OR 0.934, 95% CI 0.909 to 0.960). CONCLUSIONS: The results are consistent with the hypothesis that long term exposure to traffic related outdoor air pollutants such as NOx, CO, and O3 increases the risk of asthma in children.     

Atopy phenotype in subjects with variants of the beta subunit of the high affinity IgE receptor

BACKGROUND: Fc epsilon RI plays a central role in atopy, thus genetic variants of Fc epsilon RI-beta may alter receptor function to enhance atopic responses and may manifest as a more severe atopic phenotype and more symptomatic atopic disease. The immunological and clinical features of atopy in children with and without the Leu 181 variant of Fc epsilon RI-beta were compared. METHODS: Sixty British nuclear families, including 10 families with the Fc epsilon RI-beta variant Leu 181, recruited via a young proband with atopic asthma were analysed for atopic parameters including total IgE, specific IgE, and clinical atopic disorder. RESULTS: Compared with other children (combined atopic and non-atopic subjects), maternally inherited Leu 181 was associated with increased levels of total IgE (odds ratio (OR) 4.82, 95% confidence interval (CI) 1.02 to 27.66, p < 0.01) and a positive IgE response to grass pollen allergen (OR 7.45, 95% CI 1.56 to 35.52, p < 0.005) but not wheeze (OR 1.97, 95% CI 0.56 to 7.69), asthma (OR 2.25, 95% CI 0.65 to 7.85), or required medications (OR 0.95, 95% CI 0.29 to 3.14). There were trends for each atopic parameter to be more marked in atopic children with maternally inherited Leu 181 than in atopic children without Leu 181. Children with maternal Leu 181 had significantly raised eosinophils but there was no difference in basophil levels compared with other atopic children. CONCLUSIONS: The Leu 181 variant of Fc epsilon RI-beta, or another identified variant in linkage disequilibrium, may promote the development of atopy.




     

Childhood smoking is an independent risk factor for obstructive airways disease in women

OBJECTIVE: To assess whether starting to smoke in childhood increases the risk of obstructive airways disease (OAD) in adult life. METHODS: A retrospective cohort analysis was undertaken of 12 504 current and ex-smokers in the EPIC-Norfolk cohort. The main exposure was starting to smoke during childhood (age <16 years). Three definitions of OAD were used: doctor diagnosed asthma, doctor diagnosed bronchitis/emphysema, and "any OAD" (doctor diagnosed asthma or bronchitis/emphysema, or taking medication used in the treatment of OAD). RESULTS: Childhood smokers had significantly more pack years of exposure and poorer lung function than subjects who started to smoke in adulthood (>/=16 years). Compared with starting in adulthood, starting to smoke in childhood was associated with a greater risk of bronchitis/emphysema in female smokers (OR 1.79, 95% CI 1.25 to 2.56) and ex-smokers of both sexes (OR 1.29, 95% CI 1.07 to 1.55 in men and OR 1.40, 95% CI 1.05 to 1.85 in women), and of "any OAD" in female smokers (OR 1.72, 95% CI 1.24 to 2.38) and male and female ex-smokers (OR 1.20, 95% CI 1.03 to 1.40 in men and 1.34, 95% CI 1.07 to 1.57 in women). After adjustment for pack years, childhood smoking was associated with poorer lung function (FEV(1) 92.3% predicted in adult smokers and 89.5% in childhood smokers, p = 0.03) and a greater risk of bronchitis/emphysema (adjusted OR 1.55, 95% CI 1.08 to 2.24) and for "any OAD" (OR 1.54, 95% CI 1.10 to 2.13) in female smokers but not in male and female ex-smokers. CONCLUSION: Starting to smoke in childhood is associated with an increased risk of airways disease because of the extra pack years smoked. In women, childhood smoking is itself an independent risk factor for the development of airways disease.     

Early exposure to children in family and day care as related to adult asthma and hay fever: results from the European Community Respiratory Health Survey

BACKGROUND: The literature indicates that early exposure to children in the family and to day care permanently influences the development of allergic disease. A study was undertaken to examine the associations of family size and day care with adult asthma and hay fever and to determine whether these associations are mediated through specific IgE production and whether they vary with allergic predisposition. METHODS: 18,530 subjects aged 20-44 years from 36 areas predominantly in the market economies participated in the European Community Respiratory Health Survey and provided information through interviewer-led questionnaires. 13,932 subjects gave blood samples for measurement of specific IgE. RESULTS: Hay fever was less common in subjects with many siblings (OR=0.92; 95% CI 0.90 to 0.95 per sib). There was a U-shaped relationship between asthma and number of siblings (quadratic effect of siblings, pwheeze=0.014, pFEV(1)=0.016). In subjects without siblings but exposed to children in day care, hay fever was less common (OR=0.76; 95% CI 0.60 to 0.98) and asthma symptoms were more common (ORwheeze=1.48; 95% CI 1.12 to 1.95). Adjustment for specific IgEs did not alter these associations. The inverse association of hay fever with siblings was found in sensitised subjects (OR=0.89; 95% CI 0.84 to 0.94) and in those with parental allergy (OR=0.91; 95% CI 0.85 to 0.97), but not in subjects without such a predisposition (OR=1.02; 95% CI 0.97 to 1.09). CONCLUSION: Subjects exposed to many children at home or in day care experienced less hay fever and more asthma in adulthood. Microbial challenge through children may contribute to a non-allergic immunological development giving less hay fever but more airways infections predisposing to asthma. These effects were not mediated through production of specific IgE. The protective effect of siblings on hay fever was particularly strong in those with an allergic predisposition.     

The home environment and asthma symptoms in childhood: two population based case-control studies 13 years apart

BACKGROUND: Prevalence surveys of asthma and/or wheezing among all children aged between 7 1/2 and 8 1/2 attending state and private schools in the London Borough of Croydon were conducted in February 1978 and February 1991. Two population based case-control studies drawn from the survey responders were used to investigate the association between childhood wheeze and characteristics of the home environment and to assess whether changes in these characteristics between 1978 and 1991 may have contributed to an increase in the population prevalence of wheeze among school children. METHODS: Information on exposure to potential indoor environmental risk factors was obtained from parents by home interview and compared between cases-that is, children with frequent (> or = 5) or in-frequent (1-4) attacks of asthma or wheezing in the past 12 months- and controls, with adjustment for study. Changes in exposure over time were assessed by comparing control groups. RESULTS: Between 1978 and 1991 the population prevalence odds of wheeze increased by 20% (OR 1.20; 95% CI 1.04 to 1.39). Change in parental smoking, gas cooking, pet ownership, and central heating did not appear to explain the rise. Use of non-feather pillows was positively associated with childhood wheeze even after adjusting for other risk factors and after re-coding from non-feather to feather cases thought to have changed pillow in response to symptoms (OR 1.54; 95% CI 1.13 to 2.10). The proportion of control children reportedly using non-feather pillows was 44% in 1978 and 67% in 1991. CONCLUSIONS: Increased use of non-feather pillows was the only domestic indoor exposure studied which appeared to explain a modest rise in prevalence of wheeze from 1978 to 1991. Our analysis attempts to address behavioural change in response to the child's symptoms but an artifact arising from lifelong avoidance of feather bedding in atopic families cannot be entirely discounted.


     

Prevalence and incidence of respiratory symptoms in relation to indoor dampness: the RHINE study

BACKGROUND: An association between indoor dampness and respiratory symptoms has been reported, but dampness as a risk factor for the onset or remission of respiratory symptoms and asthma is not well documented. METHOD: This follow up study included 16 190 subjects from Iceland, Norway, Sweden, Denmark, and Estonia who had participated in the European Community Respiratory Health Survey (ECRHS I). Eight years later the same subjects answered a postal questionnaire that included questions on respiratory symptoms and indicators of indoor dampness. RESULTS: Subjects living in damp housing (18%) had a significantly (p<0.001) higher prevalence of wheeze (19.1% v 26.0%), nocturnal breathlessness (4.4% v 8.4%), nocturnal cough (27.2% v 36.5%), productive cough (16.6% v 22.3%) and asthma (6.0% v 7.7%). These associations remained significant after adjusting for possible confounders. Indoor dampness was a risk factor for onset of respiratory symptoms but not for asthma onset in the longitudinal analysis (OR 1.13, 95% CI 0.92 to 1.40). Remission of nocturnal symptoms was less common in damp homes (OR 0.84, 95% CI 0.73 to 0.97). CONCLUSIONS: Subjects living in damp housing had a higher prevalence of respiratory symptoms and asthma. Onset of respiratory symptoms was more common and remission of nocturnal respiratory symptoms was less common in subjects living in damp housing.     

Home dampness, current allergic diseases, and respiratory infections among young adults

BACKGROUND: The relation between home dampness and respiratory symptoms among adults is well confirmed, but data on specific allergic diseases and respiratory infections is more limited. Individual factors that may enhance susceptibility to the effects of home dampness are mainly unknown. METHODS: The association between home dampness and current physician diagnosed asthma, allergic rhinitis, allergic conjunctivitis, atopic dermatitis, common colds, and bacterial respiratory infections was studied in a questionnaire survey of 10 667 Finnish first year university students aged 18-25 years. The dampness categories analysed were visible mould and visible mould or damp stains or water damage during the last year. In multivariate analyses adjustment was made for parental education, active and passive smoking, type and place of residence, pets, and wall to wall carpets. The interaction effect of atopic heredity and dampness was investigated. RESULTS: Visible mould or damp stains or water damage was reported by 15.0% of the respondents. In multivariate models there was a positive association between home dampness and current asthma, allergic rhinitis, and atopic dermatitis, as well as common colds > or =4 times per year and other respiratory infections, but not between home dampness and allergic conjunctivitis. The strongest association was found between exposure to visible mould and asthma (OR 2.21, 95% CI 1.48 to 3.28) and common colds (OR 1.49, 95% CI 1.18 to 1.87). The risk of current asthma in damp homes was highest among subjects with atopic heredity. CONCLUSIONS: The risk of current asthma, allergic rhinitis, and atopic dermatitis was higher in damp homes. Of the respiratory infections, the risk of common colds was most clearly increased.