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Single nucleotide polymorphisms (SNPs) at chromosome 17q21 confer an increased risk of early-onset asthma. The objective was to study whether 17q21 SNPs modify associations between early respiratory infections and asthma. Association analysis was conducted in 499 children (268 with asthma, median age 11 yrs) from the Epidemiological Study on the Genetics and Environment of Asthma (EGEA). The 12-yr follow-up data were used to assess persistent or remittent asthma in young adulthood. Respiratory infection before 2 yrs of age was assessed retrospectively. For the 12 17q21 SNPs studied, the odds ratios (OR) for association between infection and early-onset asthma (age at onset

Background: Although uncontrolled asthma remains frequent, determinants of asthma control are poorly studied., Objectives: The aim was to estimate the distribution and the phenotypic characteristics of asthma control in 2 groups of subjects defined by the use of inhaled corticosteroids (ICS) in the past 12 months, in the Epidemiological study on the Genetics and Environment of Asthma, bronchial hyperresponsiveness and atopy (EGEA)., Methods: Five hundred one adult current patients with asthma who participated in the follow-up of the EGEA study were included. Asthma control was assessed from survey questions reflecting asthma control, as defined in the 2006 Global Initiative for Asthma guidelines. The factors analyzed were age, sex, educational level, body mass index, active and passive smoking, sensitization to aeroallergens, total IgE, rhinitis, chronic cough/phlegm, and age at asthma onset. Analyses were stratified according to ICS use., Results: Uncontrolled asthma was more frequent in ICS users (27.6%, 35.0%, and 37.4% with controlled, partly-controlled, and uncontrolled asthma respectively) compared with non-ICS users (60.0%, 23.9%, and 16.1%, respectively). In ICS users, chronic cough or phlegm and female sex were independently and significantly related to uncontrolled asthma. In non-ICS users, high total IgE and sensitization to molds were associated with uncontrolled asthma. Smoking and rhinitis were not associated with asthma control., Conclusion: Optimal asthma control remained unachieved in the majority of patients with asthma in this study. Factors associated with uncontrolled asthma were different in ICS users (chronic cough/phlegm, female sex) and non-ICS users (high total IgE and sensitization to molds).

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.

Background/objectives: There is evidence that exposure to air pollution affects asthma, but the effect of air pollution on asthma severity has not been addressed. The aim was to assess the relation between asthma severity during the past 12 months and home outdoor concentrations of air pollution., Methods: Asthma severity over the past 12 months was assessed in two complementary ways among 328 adult asthmatics from the French Epidemiological study on the Genetics and Environment of Asthma (EGEA) examined between 1991 and 1995. The four-class severity score integrated clinical events and type of treatment. The five-level asthma score is based only on the occurrence of symptoms. Nitrogen dioxide (NO(2)), sulphur dioxide (SO(2)) and ozone (O(3)) concentrations were assigned to each residence using two different methods. The first was based on the closest monitor data from 1991 to 1995. The second consisted of spatial models that used geostatistical interpolations and then assigned air pollutants to the geo-coded residences (1998)., Results: Higher asthma severity score was significantly related to the 8-hour average of ozone during April-September (O(3)-8 h) and the number of days (O(3)-days) with 8-hour ozone averages above 110 microg.m(-3) (for a 36-day increase, equivalent to the interquartile range, in O(3)-days, odds ratio 2.22 (95% confidence interval 1.61 to 3.07) for one class difference in score). Adjustment for age, sex, smoking habits, occupational exposure, and educational level did not alter results. Asthma severity was unrelated to NO(2). Both exposure assessment methods and severity scores resulted in very similar findings. SO(2) correlated with severity but reached statistical significance only for the model-based assignment of exposure., Conclusions: The observed associations between asthma severity and air pollution, in particular O(3), support the hypothesis that air pollution at levels far below current standards increases asthma severity.

Rationale: It has been shown that country living protects against asthma, which may be explained by microbial exposures., Objectives: To study whether single nucleotide polymorphisms (SNPs) in CD14 and Toll-like receptor (TLR) 2, TLR4 and TLR9 genes are associated with asthma in adults, and whether these SNPs modify associations between country living and asthma., Methods: Twenty-five SNPs in CD14, TLR2, TLR4, and TLR9 genes were genotyped in adult subjects from the French Epidemiological study on the Genetics and Environment of Asthma, Bronchial Hyperresponsiveness, and Atopy (EGEA). We conducted a case-control analysis on unrelated subjects (239 with asthma and 596 without asthma), and a family-based association test (FBAT) in 192 families ascertained through probands with asthma., Measurements and Main Results: The TLR2/+596 C allele was associated with an increased risk for asthma in both case-control and family-based analyses (under a dominant model, odds ratio [OR] 1.91 and 95% confidence interval [CI] 1.34-2.72, P = 0.0003; Z statistics from FBAT = 2.48, P = 0.01). In skin prick test (SPT) positive subjects, the CD14/-260 C allele was negatively associated with asthma (additive model, OR 0.66; CI 0.48-0.91). Significant gene-environment interactions between variation in CD14 and TLR genes and country living during childhood were found for ten SNPs. In SPT positive subjects carrying CD14/-260 CC, country living protected against asthma (OR, 0.32; 95% CI, 0.12-0.85), whereas country living was not associated with asthma in subjects who were atopic and carrying CD14/-260 T (OR, 1.11; 95% CI, 0.65-1.90) (gene-environment interaction, P < 0.05)., Conclusions: TLR2 and CD14 SNPs were associated with asthma and atopic asthma respectively. In addition, CD14, TLR2, TLR4, and TLR9 SNPs modified associations between country living and asthma.

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.

Polymorphisms in ADAM33, the first gene identified in asthma by positional cloning, have been recently associated with psoriasis. No replication study of this association has been published so far. Data available in the French EGEA study (Epidemiological study on Genetics and Environment of Asthma, bronchial hyperresponsivensess and Atopy) give the opportunity to attempt to replicate the association between ADAM33 and psoriasis in 2002 individuals. Psoriasis (n = 150) has been assessed by questionnaire administered by an interviewer and a sub-sample of subjects with early-onset psoriasis (n = 74) has been identified based on the age of the subjects at time of interview (<40 years). Nine SNPs in ADAM33 and 11 SNPs in PSORS1 were genotyped. Association analysis was conducted by using two methods, GEE regression-based method and a likelihood-based method (LAMP program). The rs512625 SNP in ADAM33 was found associated with psoriasis at p = 0.01, the usual threshold required for replication (OR [95% CI] for heterozygotes compared to the reference group of homozygotes for the most frequent allele = 0.61 [0.42;0.89]). The rs628977 SNP, which was not in linkage disequilibrium with rs512625, was significantly associated with early-onset psoriasis (p = 0.01, OR [95% CI] for homozygotes for the minor allele compared to the reference group = 2.52 [1.31;4.86]). Adjustment for age, sex, asthma and a PSORS1 SNP associated with psoriasis in the EGEA data did not change the significance of these associations. This suggests independent effects of ADAM33 and PSORS1 on psoriasis. This is the first study that replicates an association between genetic variants in ADAM33 and psoriasis. Interestingly, the 2 ADAM33 SNPs associated with psoriasis in the present analysis were part of the 3-SNPs haplotypes showing the strongest associations in the initial study. The identification of a pleiotropic effect of ADAM33 on asthma and psoriasis may contribute to the understanding of these common immune-mediated diseases.

Background: Health-related quality-of-life (HRQL) has been poorly studied in large samples of asthmatics from the general population. HRQL and its relationship to asthma-severity were assessed among 900 asthmatics enrolled in the European Community Respiratory Health Survey., Methods: Among asthmatics, 864 completed the short form-36 (SF-36) questionnaire and 477 also completed the Asthma Quality-of-life Questionnaire (AQLQ). A 4-class asthma-severity scale, combining clinical items, forced expiratory volume in 1 s and the level of treatment and the different asthma-severity components (each of the clinical items and hospitalization) were studied in relation to HRQL., Results: Mean SF-36 Physical Component Summary (PCS) and Mental Component Summary (MCS) scores (45.5 and 48.8 respectively) were lower than expected in a general population. The mean total AQLQ score was 5.8. The AQLQ score and to a lesser extent the PCS score were significantly related to the 4-class asthma-severity scale, although the risk of having a lower HRQL score did not vary proportionally across the levels of severity. Asthma-severity had no impact on the MCS score. Asthma attack frequency and hospitalization were associated with both total AQLQ and PCS scores, whereas nocturnal symptoms and lung function were more strongly related to the AQLQ and PCS score respectively., Conclusion: In population-based asthmatics, the specific AQLQ questionnaire, and also to a lesser extent the generic SF-36 questionnaire, were sensitive to asthma-severity. Frequencies of asthma attacks, of nocturnal symptoms and hospitalization for asthma have independent impact on HRQL.

Asthma and bronchial hyper-responsiveness (BHR), an asthma-related phenotype, result from many genetic (G) and environmental (E) factors. Passive exposure to tobacco smoke (ETS) in early life is one of these risk factors. Following a genome scan for asthma and associated phenotypes conducted in 295 French Epidemiological study on the Genetics and Environment of Asthma, our present aim was to investigate interactions between genetic susceptibility to asthma and to BHR with passive ETS using two different methods: the predivided sample test (PST) and the mean interaction test (MIT). PST and MIT consider the identical by descent (identity by descent) distribution at all markers in affected sib-pairs with 2, 1 or 0 sib(s) exposed to ETS. While the PST allows detection of both linkage and G x E interaction, the MIT tests for linkage by taking into account a possible interaction. Among the six regions detected at P

Although many genome screens have been conducted for asthma as a binary trait, there is limited information regarding the genetic factors underlying variation of asthma expression. Phenotypes related to variable disease expression include time to asthma onset and variation in clinical expression as measured by an asthma score built from EGEA data. A recent genome scan conducted for this score led to detection of a new region (18p11) not revealed by analysis of dichotomous asthma. Our goal was to characterize chromosomal regions harboring genes underlying time to asthma onset and to search for pleiotropic QTL influencing both time to asthma onset and the asthma score. We conducted a genome-wide linkage screen for time to asthma onset, modeled by martingale residuals from Cox survival model, in EGEA families with at least two asthmatic sibs. This was followed by a bivariate linkage scan of these residuals and asthma score. Univariate linkage analysis was performed using the Maximum Likelihood Binomial method that we extended to bivariate analysis. This screen revealed two regions potentially linked to time to asthma onset, 1p31 (LOD = 1.70, P = 0.003) and 5q13 (LOD = 1.87, P = 0.002). Bivariate linkage analysis led to a substantial improvement of the linkage signal on 5q13 (P = 0.00007), providing evidence for a pleiotropic QTL influencing both variation of time to asthma onset and of clinical expression. Use of quantitative phenotypes of variable disease expression and suitable statistical methodology can improve the power to detect new regions harboring genes which may play an important role in onset and course of disease.

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.

Background: Delineating asthma subphenotypes is of interest to understand the cause of the disease. Few studies have addressed the interrelationships of quantitative asthma-related traits., Objective: We sought to study the interrelationships of allergy markers and FEV(1) in relation to asthma and sex in children and adults., Methods: Total IgE levels, skin prick test (SPT) positivity, eosinophil counts, and FEV(1) were assessed in 299 asthmatic cases (children and adults) recruited in chest clinics and 309 nonasthmatic population-based control subjects in the French Epidemiological Study on the Genetics and Environment of Asthma, Bronchial Hyperresponsiveness, and Atopy., Results: Allergy parameters were significantly higher in asthmatic cases than in control subjects for children and adults and for both sexes. Sex and age modified the pattern of concordance of high IgE levels, SPT positivity, and eosinophilia among asthmatic cases, with the greatest overlap in male children (64%) and the lowest in male adults (18%). Patterns of change over the lifespan of IgE levels, eosinophil counts, and FEV(1)/height(2) varied, with the acceleration of FEV(1) decrease being particularly evident in asthmatic adults. In adult cases and control subjects, SPT positivity (particularly to indoor allergens) was significantly related to IgE levels but not to eosinophil counts. The association of eosinophil counts with IgE levels was evident only in children. Environmental factors (smoking, pets, and country living) did not alter the patterns observed., Conclusions: Each allergy-related phenotype showed a distinct relation with asthma, with the role for eosinophils being different than that for IgE levels and SPT responses., Clinical Implications: Taking age and sex into account is essential for understanding the interrelationships of the various allergy-related phenotypes to asthma status.

Background: The T-cell immunoglobulin domain and mucin domain (TIM) gene family and the gene for IL-2-inducible T-cell kinase (ITK), located in chromosome 5 q 33 and potentially involved in the T-cell proliferation and differentiation, are good candidate genes for allergic diseases., Objective: We assessed the role of polymorphisms in the TIM family genes and ITK in atopy, eczema, and asthma., Methods: Twenty-one polymorphisms in the TIM-ITK gene cluster were genotyped in 564 children enrolled in the Tucson Children's Respiratory Study. Skin prick tests to common allergens were performed at age 6.1 years (n=508), age 10.8 years (n=539), and age 16.6 years (n=424). Asthma and eczema were assessed by questionnaire at these 3 points. Averaged relative risks were estimated., Results: One 15-bp insertion/deletion in exon 4 of TIM 1 was significantly related to atopy and eczema (relative risk associated with carrying at least 1 rare allele=1.24 [1.07--1.45], P=.005; and 1.43 [1.01--2.01], P=.004, respectively). The 3 tested single nucleotide polymorphisms (SNPs) in TIM 3 were significantly related to atopy and eczema. One of them, at position +4259 calculated from the translation start site, predicts a putative change in the amino acid sequence of the protein, and was the most strongly related to atopy (relative risk=1.28 [1.12--1.47]; P=.0003). SNPs in the 5' genomic region in ITK, which show moderate linkage disequilibrium with those in TIM 3, had an independent effect on atopy. None of the polymorphisms studied was related to asthma., Conclusion: Our findings support a potential role for SNPs in TIM 1, TIM 3, and ITK, independent of each other, in allergic diseases.

Asthma severity in relation to body mass index (BMI) has rarely been studied. The relation between BMI and asthma severity was studied by sex in 366 adults with asthma from the Epidemiological Study on the Genetics and Environment of Asthma, a case-control and family study on asthma. Factors related to asthma severity and BMI such as smoking, FEV(1), bronchial hyperresponsiveness, and dyspnea were taken into account. The influence of early menarche was studied to assess the potential role of hormonal factors. Clinical asthma severity in the last 12 months was assessed by a score (0-7) based on the frequency of asthma attacks, persisting symptoms between attacks, and hospitalization. Asthma severity, which was unrelated to sex, increased with BMI in women (p = 0.0001) but not in men (p = 0.3). In women, the association remained after adjustment for age, FEV(1), smoking habits, and BMI-adjusted dyspnea and taking into account familial dependence (p = 0.0001). The association between BMI and severity was stronger in women with early menarche than in women without early menarche (p interaction = 0.02). Findings support the hypothesis of hormonal factors involved in the severity of asthma.

Rationale: The severity of asthma has been defined by various criteria in epidemiology, but their relationships have been rarely studied., Material and Methods: The interrelationships between various asthma severity criteria (clinical severity in the past 12 months) (score 0-7), functional (FEV1), therapy (inhaled steroids used in the past 12 months) and hospitalization during life were studied. Bivariate (OR) and multivariate (factorial analyses, log-linear models) analyses were applied in asthmatic children (n=135) and adults (n=213) recruited in chest clinics for the EGEA study (Epidemiological Study on the Genetics and Environment of Asthma)., Results: In asthmatics, the proportion of severe asthma was highly dependent on the definition used. Whatever the statistical method used, FEV1 in children was unrelated to treatment, hospitalization and the clinical score. In adults, the clinical score was not associated with hospitalization, treatment and FEV1, these last three criteria being highly related to each other., Conclusion: Results support the hypothesis of the multidimensional character of severity of asthma.

Rationale: Severe asthma is a real public health problem because of its consequences on patients and its economic cost. Nevertheless, few epidemiological studies have focussed on severe asthma. The aim of this state of the art review is to describe the criteria used to estimate asthma severity and to assess the prevalence of severe asthma from population-based epidemiological studies., Observations: Asthma severity has been defined in various ways in epidemiology, with criteria based on symptoms, hospitalisation, ventilatory function, discomfort caused by asthma attacks, and treatment. A high variability in the prevalence of severe asthma is observed, resulting mostly from the lack of standardisation in the phenotypes used, but also from a real geographical heterogeneity. Nevertheless, the prevalence of severe asthma may be reasonably estimated between 1 and 3% of the general population, both in children and adults., Conclusion: Data from the literature show a lack of standardisation of the severe asthma phenotype. Further epidemiological studies are needed to understand the geographical variability in severe asthma prevalence.

The aim of this study was to assess the short-term reproducibility and the validity of reported ETS (environmental tobacco smoke) exposure, with a special emphasis on the potential misclassification related to personal or family history of asthma. Analyses were based on the data on the Epidemiological study on the Genetics and Environment of Asthma, bronchial hyperresponsiveness and atopy (EGEA), a case-control study of asthma that included first degree relatives of asthmatic cases. The study was comprised of 348 families of asthmatics recruited in six chest clinics throughout France and 416 population-based controls. For studying the validity of ETS reports, personal active smoking histories reported by family members were taken as reference. The reproducibility of ETS exposure report was good, and independent of asthma. The validity of the report of maternal and paternal smoking in childhood and spouse smoking during life was high (overall agreement > or = 84%). Mothers of asthmatic children significantly underreported their smoking habits when questioned on their children's passive tobacco exposure. Offspring of parents who had stopped smoking underestimated their ETS exposure in childhood. In conclusion, interviews with mothers on their personal active smoking habits may provide a more accurate estimate of their asthmatic child's passive exposure than asking mothers specifically about their children's passive exposure. There was no indication that asthma status (either of the parent/spouse or of the respondent) by itself influences the report of ETS exposure during childhood or adulthood.

Background: Although allergy is highly associated with childhood asthma, it is not well known if there is a relationship between the intensity of allergic sensitization and asthma severity., Objective: The objectives of the study were to examine the relationships between several markers of allergy and asthma severity in asthmatic children included in the Epidemiological study on the Genetics and Environment of Asthma, bronchial hyper-responsiveness and atopy (EGEA)., Methods: The population comprised 216 asthmatic children below 16 years of age. Total IgE and blood eosinophil counts were measured and skin prick tests to 11 aeroallergens were performed. The intensity of the allergic sensitization was assessed by the number of positive skin prick tests and by skin weal sizes. Asthma severity was measured with four criteria: a clinical severity score, history of hospitalization for asthma, FEV1% predicted and inhaled steroid use in the last 12 months., Results: Most of the children were sensitized to at least one aeroallergen (88.2%). Atopy was not related to the severity of asthma, except for a tendency for a more severe clinical score in non-atopic children. The type and intensity of the allergic sensitization were not associated with any criteria of asthma severity. Total IgE was significantly increased in children treated with inhaled corticosteroids and in children ever hospitalized for asthma (P-values 0.009 and 0.04, respectively). Eosinophil counts were not related to asthma severity., Conclusion: Our results suggest that severe childhood asthma may be related to a high level of total IgE but not to blood eosinophil counts. The lack of positive relationships between both atopy and the intensity of allergic sensitization with asthma severity supports the hypothesis of different risk factors being associated with asthma and with the severity of asthma.

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.

Familial resemblance of asthma is well known but epidemiological research focused on familial resemblance of asthma severity is scanty. We studied whether asthma and asthma severity in first-degree relatives of cases with asthma were related to asthma severity of the index case. The analysis was based upon the examination of 944 subjects (348 cases, 239 relatives with asthma, and 357 subjects without asthma) and upon the information on 3467 first- degree relatives of probands. The risks of asthma in relatives of adult and pediatric cases were significantly higher than in relatives of subjects without asthma (OR 3.4 [95% CI 2.5-4.7] and 4.5 [2.6- 8.1], respectively). Proportions of asthma in relatives were not related to the asthma severity of cases for the three severity criteria studied (clinical score, FEV(1) % predicted, and inhaled corticosteroid use). Using both regression models and intraclass correlation coefficients, there was a significant familial resemblance for the clinical severity score (ICC = 0.23 and 0.23) and for FEV(1) (ICC = 0.19 and 0.25) among families of pediatric and adult probands, respectively. In conclusion, asthma occurrence in relatives may be independent of the severity of the cases with asthma, but results suggest familial resemblance in the severity of asthma when it occurs.

Background: Glucocorticoids may increase bone fragility via mechanisms independent from their bone mass reducing effect., Objective: To study relationships between osteoporotic fractures and bone mineral density in patients on long-term glucocorticoid therapy., Patients and Methods: We studied 121 women with a mean age of 60.4 +/- 14.3 years on long-term glucocorticoid therapy (cumulative dose > or = 1 g of prednisone equivalent, duration > or = 6 months) for rheumatoid arthritis (n = 38), polymyalgia rheumatica or giant cell arteritis (n = 26), connective tissue disease (n = 15), asthma (n = 14), another inflammatory joint disease (n = 14), or another condition (n = 14). The control group was composed of 125 subjects who had the same mean age and met the same exclusion criteria as the case group. Bone mineral density was measured at the lumbar spine and femoral neck using a Hologic QDR 4500 unit. In subjects with back pain, radiographs of the thoracic and lumbar spine were obtained to look for fractures., Results: The odds ratio for a bone mineral density decrease of one standard deviation at the femoral neck was 1.68 (1.20-2.35) in patients with a cumulative glucocorticoid dose of 10 g of prednisone equivalent and 1.67 (1.22-2.29) in those with a glucocorticoid therapy duration of 2 years. Sixty-eight fractures were recorded in 56 patients (46% of the overall patient group). Even after adjustment on age, glucocorticoid therapy duration, and dose, mean bone mineral density values at the lumbar spine and femoral neck were significantly lower in the subgroup of patients with fractures than in the subgroup without fractures. Sensitivity and specificity of bone mineral density at the femoral neck and/or lumbar spine for the diagnosis of vertebral fracture and/or peripheral fracture were 73% and 51%, respectively. In the stepwise logistic regression model, factors explaining the presence of fractures were as follows, in hierarchical order: age; absence of calcium/vitamin D supplementation, femoral neck T-score, and glucocorticoid dose., Conclusion: Our data are compelling evidence that bone mineral density is a major determinant of the fracture risk in patients with glucocorticoid-induced osteoporosis.