Farming in childhood, diet in adulthood and asthma history.

The decrease in the number of children living on traditional farms in France during early childhood and changes in diet could both play a role in the increase in asthma prevalence over the last decades. This study aimed to assess 1) the association of farming lifestyle in childhood and asthma, and 2) whether diet in adulthood modifies the association between farming lifestyle in childhood and adult-onset asthma. In the French Etude Epidemiologique des Femmes de la Mutuelle Générale de l'Education Nationale (E3N) study (54,018 females; age 43-68 yrs), three indicators of farming lifestyle were defined: one using individual data (having farmer parents) and two using ecological data (born in a rural area and exposure to cattle). All farming lifestyle indicators were related to childhood- (<16 yrs) and adult-onset asthma (OR (95% CI) values for farmer parents were 0.54 (0.42-0.70) and 0.72 (0.62-0.84), respectively), and to diet in adulthood, in particular to high fruit and low wine intakes. The association between farmer parents and adult-onset asthma was not modified by diet in adulthood. Results extend previous observations in younger cohorts on the protective role of contact with livestock and farming lifestyle on asthma, in particular during childhood.

Heterogeneity of asthma according to blood inflammatory patterns.

RATIONALE: There is increasing interest regarding asthma heterogeneity in relation to inflammatory patterns. OBJECTIVES: To assess phenotypic characteristics, in particular clinical presentation of the disease, in 381 well-characterised adults with asthma from the French Epidemiological study on the Genetics and Environment of Asthma (EGEA) according to their blood inflammatory pattern. METHODS: Four blood inflammatory patterns were defined according to eosinophil (EOS) and neutrophil (NEU) count cut-off points. Samples with > or =250 EOS/mm(3) were classified as EOS(hi) and those with > or =5000 NEU/mm(3) as NEU(hi). Clinical characteristics include typical asthma and chronic obstructive pulmonary disease (COPD)-like symptoms, as well as composite quantitative scores addressing the activity of the disease. RESULTS: A substantial number of those with asthma (56.2%) had the EOS(lo) pattern (<250 EOS/mm(3)). Patients with asthma who had the EOS(hi) pattern had higher immunoglobulin E (IgE), a lower forced expiratory volume in 1 s (FEV(1)) and presented a more active asthma than those with the EOS(lo) pattern. Among those with the EOS(lo) pattern, neutrophil inflammation (NEU(hi)) was related to a less frequent positive skin prick test response (OR 0.44, 95% CI 0.20 to 0.96). Among those with the EOS(hi) pattern, neutrophil inflammation did not explain current asthma or asthma activity, and was significantly related to nocturnal symptoms (OR 5.21, 95% CI 1.44 to 18.8) independently of age, sex, smoking and inhaled corticosteroid treatment. In non-smokers with asthma, COPD-like symptoms, in particular chronic phlegm, were more frequent in those with neutrophil inflammation, independent of eosinophil inflammation (OR 2.35, 95% CI 1.08 to 5.10). CONCLUSIONS: Besides eosinophilia, neutrophil inflammation assessed in the blood is related to specific characteristics of asthma. Considering simultaneously neutrophilic and eosinophilic inflammation may contribute to help to disentangle this complex disease.

Cat sensitization according to cat window of exposure in adult asthmatics.

BACKGROUND: In adults, there is limited information on tolerance to cat, which may be reflected by high IgG4 without IgE sensitization. Early exposure to cat may play a critical role. OBJECTIVE: The aim was to assess among adults the association of Fel d 1 IgG4, Fel d 1 IgE, skin prick test (SPT) response to cat and pet-related symptoms in relation to exposure to cat considering the period of exposure. METHODS: SPT response to cat, specific IgE and IgG4 to Fel d 1 were assessed in 167 asthmatics recruited in chest clinics (40 years of age in average) from the French Epidemiological study on the Genetics and Environment of Asthma (EGEA). Childhood and/or current exposure to cat were studied retrospectively. RESULTS: IgG4 was higher in relation to current cat exposure (0.53 vs. 0.09 ng/mL; P<0.001) and higher in women than in men. The period of cat exposure was significantly related to Fel d 1 IgE, the IgE/IgG4 pattern and cat weal size. The lowest values of Fel d 1 IgE, cat weal size, pet-related nasal or respiratory symptoms were observed in those with both childhood and current exposure as well as the highest proportion of the IgE-/IgG4+ pattern observed in 1.4%, 4.0%, 38.1% and 12.5% of those with -/-, +/-, +/+, -/+ childhood/current exposure, respectively. CONCLUSIONS: Adult asthmatics exposed to cats since childhood present an immunologic pattern with high IgG4 and low IgE. Continuous exposure may maintain a state of immunological tolerance to cat.

Total serum IgE levels are associated with ambient ozone concentration in asthmatic adults.

BACKGROUND: Effects of air pollution exposure on IgE-mediated response in asthmatics are poorly investigated. The aim was to examine the relationship between air pollution concentrations and total IgE levels in adult asthmatics. METHODS: The present study relates to the 369 asthmatic adults from the French Epidemiological study on Genetics and Environment of Asthma (EGEA), with availability of data on both total serum IgE measurements and air pollution concentrations. Geo-statistical models were performed on 4 x 4 km grids to assess individual outdoor air pollution exposure. Annual outdoor concentrations of ozone (O(3)), nitrogen dioxide (NO(2)), sulphur dioxide (SO(2)), and particulate matter smaller than 10 microm size (PM(10)), and concentrations of summer ozone were assigned to subject's home address. RESULTS: The geometric mean of total IgE was 161 IU/ml and the average of O(3) exposure was 44.9 +/- 9.5 microg/m(3). Ozone concentrations were positively related to total IgE levels and an increase of 10 microg/m(3) of O(3) resulted in an increase of 20.4% (95% CI = 3.0-40.7) in total IgE levels. Adjustment for age, gender, smoking habits and previous life in the countryside did not change the results, and an increase of 19.1% (2.4-38.6) in total IgE was observed with O(3). Negative associations observed between NO(2) and total IgE levels disappeared after including O(3) in the models. Neither SO(2) nor PM(10) were correlated with total IgE levels. CONCLUSIONS: Results suggest that O(3) or related ambient pollutants may up-regulate total IgE levels among asthmatic adults.

[Environmental factors for asthma severity and allergy: results from the EGEA study]. / Facteurs environnementaux de l'asthme sévère et de l'allergie: résultats de l'étude EGEA.

INTRODUCTION: EGEA (Epidemiological study on the genetics and environment of asthma, bronchial hyperresponsiveness and atopy), a case control and family study including 2048 individuals, was initiated to look for environmental and genetic risk factors for asthma. A synthesis of the results obtained since 2002 on phenotypic and environmental aspects of asthma severity and allergy are presented in this article. METHODS AND RESULTS: The results support a role for hormonal factors in asthma severity and in various allergic markers of asthma. A greater body mass index was related to a more severe asthma in women with early menarche. Associations between markers of allergy (eosinophils, IgE and atopy) and hormonal dependent events in women (premenstrual asthma, menopause and oral contraceptive use) have been found. In asthmatics, exposure to agents known to be associated with occupational asthma, active and passive smoking were associated with an increased clinical asthma severity score. The study underlines the protective role of country living and exposure to pets in early life on allergy markers in adulthood, supporting the hygiene hypothesis. CONCLUSIONS: New hypothesis will be tested in the near future from the second stage of this survey.

Total circulating IgE and FEV1 in adult men. An epidemiologic longitudinal study.

Epidemiologic data relating total circulating immunoglobulin E (IgE), an objective marker of allergy, to cross-sectional and longitudinal FEV1 as well as to methacholine bronchial hyperresponsiveness were obtained from 310 French adult men surveyed five years apart. Skin prick test responses to common aeroallergens, IgE level, and bronchial hyperresponsiveness were assessed at the end of the follow-up. IgE level was not associated with PD20 to methacholine. Cross-sectionally, age and height-adjusted FEV1 score was inversely related to total IgE level (regression coefficient of FEV1 score on Log[IgE] beta = -.20; p = 0.02). Stratified analysis showed that IgE level was associated with FEV1 score only in nonsmokers (beta = -0.52; p less than 0.001), an association that remained after exclusion of asthmatics. Longitudinally, five-year FEV1 decline was related to IgE in nonsmokers (regression coefficient of FEV1 decline on Log[IgE] beta = 19.9; p = 0.03) and exsmokers (beta = 18.9; p = 0.06) but not in current smokers. The relationship persisted, even if with lesser significance, among exsmokers after exclusion of asthmatics (beta = 17.2) and further exclusion of skin prick test-positive men (beta = 18.8). Whether IgE production also reflects factors other than allergy, possibly nonallergic inflammation, needs further investigations.

[Contribution of epidemiology to the study of allergic response in children]. / L'apport de l'épidémiologie dans l'étude de la réponse allergique infantile.

Allergy is the conjunction of hereditary predisposition and risk factors encountered in the environment, phenomenon which can be observed very early in individual life. The aim of this review is to present the contribution of epidemiology in the study of allergic response in childhood, from sensitization to clinical manifestations as eczema, asthma and rhinitis. The first contribution of epidemiology has consisted in estimating the scatter of the allergic response, the presence of circulating antibodies against allergens (IgE and IgG), the evaluation of immediate hypersensitivity (such as the response to skin prick tests) and the prevalence of clinical manifestations. Then, knowledge of allergic response has been improved by the contribution of aetiological epidemiology. Various risk factors have been described according to the different stages during life in which their effects are observable. In prenatal life, potential risk factors are maternal immunity and smoking during pregnancy. Later in perinatal or neonatal life they are perinatal complications, month of birth and maternal smoking. Lastly, in infancy a role can be played by feeding, immunological deficiencies, infections, parental smoking and early exposure to allergens or pollution. Perceiving these risk factors helps to determine strategies to prevent allergy occurrence.

[Epidemiological study on the Genetics and Environment of Asthma, bronchial hyperresponsiveness and atopy (EGEA) - First results of a multi-disciplinary study]. / Etude Epidémiologique sur les facteurs Génétiques et Environnementaux de l'Asthme, l'hyperréactivité bronchique et l'atopie (EGEA). Premiers résultats d'une étude multidisciplinaire.

The French co-operative epidemiological study EGEA realised in 1991/95 combines a case control study and a study of the families of asthmatic cases. A synthesis of the results already obtained is presented. Smoking was related to IgE, even in asthmatics and was clearly related to the clinical severity of asthma, an aspect insufficiently taken into account. The relationships of occupational exposures to asthma have been assessed using a job exposure matrix. Segregation analyses on IgE have shown, after correction for the mode of ascertainment, the existence of a dominant major gene and familial residual correlation. A systematic genome screen realised in families with 2 asthmatic siblings showed linkage of various regions in the genome implicated to asthma or related phenotypes (1p, 11p, 11q, 12q, 13q, 17q, 19q), coherent with genome screens realised in other studies. Regarding candidate genes, no association was evidenced between asthma and the AF508 mutation of the cystic fibrosis gene. The analysis is still in progress by studies on the heterogeneity of asthma with refined genetic studies and by searching to integrate results regarding environmental and genetic factors and studying their interactions.

Genome screen in the French EGEA study: detection of linked regions shared or not shared by allergic rhinitis and asthma.

In the sample of 295 French EGEA families with at least one asthmatic subject, a genome screen was conducted to identify potential linkage regions specific either to allergic rhinitis (AR) or to asthma as well as those shared by the two diseases. Two binary rhinitis phenotypes based on (1) diagnosis (ARbin1) and (2) symptoms (ARbin2) and a categorical ordered trait (ARcat) were considered. Asthma phenotype was based on answers to a standardized questionnaire plus the presence of bronchial hyper-responsiveness. Linkage analyses were conducted using the maximum likelihood binomial (MLB) method. These analyses provided potential evidence for linkage to three regions in the whole sample: 1p31 for the phenotype defined by ARbin2 plus asthma (P=0.00016), 2q32 for ARbin2 (P=0.00016) and 3p24-p14 for ARcat (P=0.001). Two other regions were detected in the subset of 185 families with at most one asthmatic sib: 9p22 and 9q22-q34 for ARbin1 (P=0.001 and 0.0007, respectively). No region showed evidence for linkage to asthma without being also linked to AR. While 1p31 may contain a genetic determinant common to asthma and AR, 2q32, 3p24-p14, 9p22 and 9q22-q34 are more likely to harbor genetic factors specific to AR.

Allergy markers in respiratory epidemiology.

Assessing allergy by measurement of serum immunoglobulin (Ig) E antibodies is fast and safe to perform. Serum antibodies can preferably be assessed in patients with dermatitis and in those who regularly use antihistamines and other pharmacological agents that reduce skin sensitivity. Skin tests represent the easiest tool to obtain quick and reliable information for the diagnosis of respiratory allergic diseases. It is the technique more widely used, specific and reasonably sensitive for most applications as a marker of atopy. Measurement of serum IgE antibodies and skin-prick testing may give complimentary information and can be applied in clinical and epidemiological settings. Peripheral blood eosinophilia is less used, but is important in clinical practice to demonstrate the allergic aetiology of disease, to monitor its clinical course and to address the choice of therapy. In epidemiology, hypereosinophilia seems to reflect an inflammatory reaction in the airways, which may be linked to obstructive airflow limitation.

[Radioimmunoassay of urinary cotinine: variability of measurements, identification of exposed subjects]. / Dosage radioimmunologique de la cotinine urinaire: variabilité des mesures, identification des sujets exposés.

Urinary cotinine was assessed by a radioimmune assay (RIA) in a random subsample of 63 (out of 285) children aged 5 to 6 from 10 kindergartens in Nancy (N-E France). The result was adjusted for urine concentration by expressing cotinine per mg creatinine. The correlation between two successive determinations was excellent (r = 0.989) and the difference between the two mean values was minimal and non-significant (121.4 +/- 25.9 vs 121.0 +/- 25.0). Expressed in percentage of their mean, the difference between two determinations was on average 8.2%. The urinary cotinine determinations allowed a satisfactory separation of children exposed vs unexposed to parental tobacco smoke.

The protective role of country living on skin prick tests, immunoglobulin E and asthma in adults from the Epidemiological study on the Genetics and Environment of Asthma, bronchial hyper-responsiveness and atopy.

BACKGROUND: Farming environment and traditional lifestyle seem to protect from childhood allergy. OBJECTIVE: The aim is to analyse the relationships of living in the country to asthma, positive skin prick tests and IgE among adults considering various windows of exposure over the life-span. METHODS: The study concerns 805 adults drawn from the Epidemiological study on the Genetics and Environment of Asthma, bronchial hyper-responsiveness and atopy (EGEA) (asthmatic cases, non-asthmatic controls, and parents of cases with and without asthma). Ever living in the country concerned 55% of the subjects. Early (beginning < 1 years), childhood (beginning < or = 16 years), prolonged (duration > or = 10 years) and current life in the country were studied. RESULTS: The results based on the case control and family components of the study show that IgE levels were significantly lower in those who ever lived in the country and in particular in those who lived for > or = 10 years. Positive skin prick tests (SPT) were significantly less prevalent in those who ever lived in the country and in particular in those with childhood (< or = 16 years) exposure. These associations remained independent of age, sex, smoking or asthma with IgE levels of 64 vs. 88 IU/mL; P = 0.004 for those ever living in the country vs. others and odds ratio for SPT positivity of 0.72 (95% CI [0.53-0.98]). In the more specific group with traditional mode of heating in childhood (use of wood) associations were stronger. The association with asthma, studied in parents of asthmatic probands showed that fathers, but not mothers, of asthmatics were significantly less often asthmatic themselves in relation to country living. CONCLUSION: Country life protects from asthma and adulthood allergy. The protective effect is not restricted to exposure in early childhood.

Relationships of haptoglobin level to FEV1, wheezing, bronchial hyper-responsiveness and allergy.

The relationships of haptoglobin level to respiratory and allergic parameters have been assessed in an epidemiological study conducted in a working population surveyed twice 5 years apart. At the first survey conducted in 892 working men, haptoglobin level was significantly related to FEV1 (r = -0.18; P less than 0.001) and smoking habits. After adjustment for smoking, a history of wheezing was significantly related to lower haptoglobin level. A second survey conducted in 304 men of the original sample 5 years later confirmed that haptoglobin was related to FEV1 (r = -0.21; P less than 0.001) and that wheezing was significantly related to hypohaptoglobinaemia (lower decile; P = 0.04). Men who exhibited bronchial hyper-responsiveness to methacholine had haptoglobin levels 0.35 g/l higher than those who did not (P = 0.01). Haptoglobin level was unrelated to IgE level and skin prick tests. These results support the hypothesis of the role of inflammation in both lower lung function and bronchial hyper-responsiveness. They suggest that some heterogeneity exists within subjects with a history of wheezing.

Leukocyte count and bronchial hyperresponsiveness.

The relationship of total and differential blood leukocyte counts with bronchial methacholine response was studied in a population-based sample of 324 men. Geometric mean total leukocyte counts were significantly higher in reactors (6567 cells/mm3) than in nonreactors (5732 cells/mm3; p = 0.003). After adjusting for smoking habits, a factor contributing to both an elevation in peripheral leukocyte count and an increased level of airway responsiveness, reactor status remained significantly associated with leukocyte count. This association also persisted after controlling, with a logistic model, for atopy and common cold (marker of infection) and after excluding men with a history of asthma, chronic bronchitis, or low FEV1. Study of the differential leukocyte counts has shown that an increase was present for almost every type of leukocyte, and particularly evident for neutrophils. Whether these findings reflect an association between bronchial hyperresponsiveness and cellular inflammation needs more investigation.

Allergy markers in adults in relation to the timing of pet exposure: the EGEA study.

BACKGROUND: Studies suggest that early childhood exposure to pets may protect from the development of atopy, but limited information is available on adults. The association of allergy markers in adulthood with current and childhood exposure to pets was studied considering retrospectively the window of exposure. METHODS: Immunoglobulin E (IgE), skin prick tests (SPT), eosinophils were related to exposure to pets in 187 adult asthmatic cases and 243 controls from the Epidemiological Study on the Genetics and Environment of Asthma, bronchial hyperresponsiveness and atopy (EGEA) study. Analyses were redone after exclusion of subjects who removed pets or experienced symptoms to animals to take into account selection in that retrospective study. RESULTS: In asthmatic cases, current exposure to pets was unrelated to SPT positivity (+), whereas childhood exposure was significantly related to less SPT+ to any allergen, and to cat in particular, with an association restricted to those exposed before 2 years of age [OR = 0.30 (CI 0.12-0.76)]. Considering the relative timing of exposure in relation to asthma onset showed that the protective effect of exposure to pets occurs for pet exposure starting before asthma onset [OR for SPT+ = 0.19 (CI 0.08-0.48)]. CONCLUSION: Results support the hypothesis that exposure to pets in early life, and in particular before asthma onset, may protect against allergen sensitization in adulthood.

The relation between snoring and smoking, body mass index, age, alcohol consumption and respiratory symptoms.

Potential risk factors for snoring were studied in a population of 457 middle-aged men. Eversnoring was reported by 60% of the men and snoring with an age of onset before or equal to 20 years by 13%. Eversnoring was significantly related to older age, higher body mass index and smoking habits. Alcohol consumption, estimated by questionnaire and gamma-glutamyl transpeptidase was unrelated to a history of snoring. Logistic regression showed that snoring was independently associated with age, body mass index and smoking habits. An exposure-effect relationship clearly appeared between tobacco consumption and snoring. After adjustment for smoking habits, none of the upper or lower respiratory symptoms was significantly related to snoring.

Relationships of total IgE level, skin prick test response, and smoking habits.

Epidemiologic observations on 331 men showed that increased serum IgE concentration was associated with a wheal response to skin prick testing, but also to an erythema response in the absence of any wheal, and to heavy smoking. The association between IgE and the various skin prick test responses remained after taking into account smoking and asthma.

Relationship of upper airways disorders to FEV1 and bronchial hyperresponsiveness in an epidemiological study.

Associations of upper airways disorders (UAD) with forced expiratory volume in one second (FEV1) and bronchial methacholine response were studied, taking smoking habits into account. We used epidemiological data drawn from a population of 324 men, aged 27-58 yrs. Lower FEV1 level was related to hay fever (p = 0.01), usual (p = 0.01) and chronic (p = 0.02) rhinitis and common cold on the day of examination (p = 0.04). Allowance for the major potential confounding factor, tobacco smoking, showed similar results. Bronchial methacholine response was heightened in men reporting hay fever compared to those without (p = 0.01) but also in men reporting chronic rhinitis (p = 0.06), a group which did not exhibit skin prick test positivity more often than other subjects. Exclusion of asthmatics and taking into account smoking and skin prick test positivity yielded mostly similar results. Our data support the hypothesis of an association between lung impairment, as assessed by lower FEV1 and bronchial hyperresponsiveness to methacholine, and different types of UAD, allergic or not.

In utero exposure to parental smoking, cotinine measurements, and cord blood IgE.

The relationship between parental smoking and cord blood IgE has been studied in a survey conducted in 99 unselected newborn infants with a sensitive tests for IgE and cotinine as a biologic marker to validate smoking data. For both cord blood cotinine and maternal urine continine creatinine ratio (CCR), significantly higher levels were observed for smokers compared to nonsmokers. Furthermore, among nonsmokers, passive smokers had significantly higher cotinine levels than true nonsmokers, which demonstrates that cord blood may be used to assess active as well as passive maternal smoking. No association was observed in this study between cord blood IgE and maternal smoking assessed by questionnaire (geometric means of cord blood IgE levels were 0.11 IU/ml for newborn infants of smoking mothers and 0.12 IU/ml for newborn infants of nonsmoking mothers). The same observations were drawn from the analysis of cord blood IgE and cotinine levels, with correlation coefficients of -0.005 for cord blood CCR and 0.003 for maternal CCR. Additional studies are needed to determine whether maternal smoking is causally related to cord blood IgE and by which mechanisms.