Association studies in asthma genetics.
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Asthma↗
Biomedical subjects
S T Weiss
Publications and source records attributed to S T Weiss.
Body mass index and asthma in adults in families of subjects with asthma in Anqing, China.
We conducted a cross-sectional study of 7,109 adults from families of subjects with asthma in the province of Anhui, China. Asthma was defined either as a combination of physician-diagnosed asthma, airway responsiveness to methacholine at < or = 25 mg/ml and two or more respiratory symptoms or asthma attacks ("asthma"); or as a combination of airway responsiveness to methacholine at < or = 8 mg/ml and two or more respiratory symptoms or asthma attacks ("symptomatic airway hyperresponsiveness [AHR]"). After adjusting for intensity of cigarette smoking and other variables, both extremes of the body mass index (BMI) distribution were associated with symptomatic AHR in men and women (p < 0.01). In the multivariate analysis, both under- and overweight were associated with asthma in women, and underweight was associated with asthma in men. Among men, those with BMIs of 16 and 30 kg/m(2) had 2.5 and 2.3 times higher odds of symptomatic AHR, respectively, than those whose BMI was 21 kg/m(2) (95% CI for OR(16 vs. 21 kg/m)(2) = 1.4 to 3.8; 95% CI for OR(30) (vs.) (21) (kg/m)(2) = 1.2 to 5.0). Among women, those with BMIs of 16 and 30 kg/m(2) had 2.0 and 2.3 times higher odds of symptomatic AHR than those whose BMI was 21 kg/m(2) (95% CI for OR(16) (vs.) (21) (kg/m)(2) = 1.3 to 3.1; 95% CI(30) (vs.) (21) (kg/m)(2) = 1.2 to 4.5). Among adults in families of subjects with asthma living in rural China, both underweight and overweight are associated with an increased risk of asthma.
Adult↗
A genomewide search for quantitative-trait loci underlying asthma.
A genomewide screen for quantitative-trait loci (QTLs) that underlie asthma was performed on 533 Chinese families with asthma, by the unified Haseman-Elston method. Nine asthma-related phenotypes were studied, including forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), airway responsiveness as indicated by methacholine (MTCH)-challenge test, serum total immunoglobulin E (TIgE), serum-specific immunoglobulin E, eosinophil count in peripheral blood, and skin-prick tests with three different allergens (cockroach, Dermatophagoides pteronyssinus, and D. farinae). Our study showed significant linkage between airway responsiveness to MTCH and D2S1780 on chromosome 2 (P<.00002) and provided suggestive evidence (P<.002) for six additional possible QTLs: D10S1435 and D22S685, for FEV1; D16S412, for FVC; D19S433, for airway responsiveness to MTCH; D1S518, for TIgE; and D4S1647, for skin reactivity to cockroach. No significant or suggestive evidence of linkage for the other four traits was found.
Adult↗
Exposure-response relationship between paternal smoking and children's pulmonary function.
We conducted a cross-sectional study to investigate paternal smoking and children's pulmonary function in rural communities of Anqing, China. Our analysis included 1,718 children 8 to 15 yr of age whose mothers were never-smokers. Multiple linear regression models were used to estimate the effect of paternal smoking on children's pulmonary function, with adjustment for children's age, sex, weight, height, square of height, asthma, and father's education. When compared with children of never-smoking fathers, children of smoking fathers had small, but detectable deficits in FEV(1) (-36 ml, SE = 20) and FVC (-37 ml, SE = 22). When children of smoking fathers were subdivided into two subgroups, father smoked < 30 cigarettes/day and >/= 30 cigarettes/day, we found that children whose fathers smoked >/= 30 cigarettes/day had the largest deficits in both FEV(1) (-79 ml, SE = 30) and FVC (-71 ml, SE = 34). This monotonic exposure-response relationship remained in all strata when we further stratified our analysis by children's sex and asthma status. Our data also suggested that the relationship was greatest among nonasthmatic girls, although neither sex nor asthma interaction terms were statistically significant. We conclude that there is a monotonic exposure-response relationship between paternal smoking and decline of pulmonary function in children in this rural Chinese population.
Adolescent↗
Childhood infections and asthma: at the crossroads of the hygiene and Barker hypotheses.
The hygiene hypothesis states that childhood asthma develops as a result of decreased exposure to infectious agents during infancy and early childhood. This results in the persistence of the neonatal T helper lymphocyte 2 immunophenotype, thereby predisposing the child to atopic disease. While multiple studies support the hygiene hypothesis in asthma ontogeny, the evidence remains inconclusive; multiple other environmental exposures in early childhood also alter predisposition to asthma. Moreover, the current paradigm for asthma development extends far beyond simple childhood environmental exposures to include fetal development, genetic predisposition, and interactions of the developmental state and genetics with the environment.
Asthma↗
Bone lead and blood lead levels in relation to baseline blood pressure and the prospective development of hypertension: the Normative Aging Study.
Between 1991 and 1997, the authors studied 833 participants of the Normative Aging Study in a substudy of bone lead levels (measured by K-shell x-ray fluorescence), blood lead levels, and hypertension. Among these subjects, 337 were classified as normotensive, and 182 and 314 were classified as having borderline and definite hypertension, respectively, at baseline. These bone and blood lead levels were typical of those of community-exposed men. Among the 519 subjects with no history of definite hypertension at baseline, cross-sectional analyses revealed positive associations between systolic blood pressure and bone lead levels. Of the 474 subjects who were free from definite hypertension at baseline and had follow-up data, 74 new cases of definite hypertension were reported. Baseline bone lead levels were positively associated with incidence of hypertension. In proportional hazards models that controlled for age, age squared, body mass index, and family history of hypertension, an increase in patella (trabecular) lead from the midpoint of the lowest quintile to that of the highest quintile was associated with a rate ratio of definite hypertension of 1.71 (95% confidence interval: 1.08, 2.70). No association was found with blood lead level. These results support the hypothesis that cumulative exposure to lead, even at low levels sustained by the general population, may increase the risk of hypertension.
Adult↗
Use of inhaled anti-inflammatory medication in children with asthma in managed care settings.
BACKGROUND: Many factors affect use of inhaled therapy in asthma. Relatively little is known about current patterns of use of anti-inflammatory medication in children with asthma and whether variations occur with age and use of bronchodilator medication. OBJECTIVE: To study the factors associated with dispensing of anti-inflammatory (controller) asthma medication to children in 3 managed care organizations (MCOs). METHODS: Using automated databases, a 1-year cross-sectional study of children with asthma aged 3 to 15 years cared for in 3 MCOs was used to evaluate the association of age and other factors with controller medication use. RESULTS: A total of 13 352 children were studied. Significantly fewer children aged 3 to 5 years were dispensed any (> or =1) controller medication than older children (P<.001). Among children dispensed 6 or more beta-agonists, only 39% also received 5 or more controller dispensings, with adolescents significantly less likely than younger children to receive 5 or more controllers (33%; P<.001). Significant differences were seen among MCOs in proportions of patients dispensed controller medication. In a multiple logistic regression model, controlling for frequency of beta-agonist dispensing and MCO, significantly lower dispensing of any controller medication was seen for those aged 3 to 5 years (odds ratio [OR], 0.8; 95% confidence interval [CI], 0.7-0.9) and for girls (OR, 0.9; 95% CI, 0.8-0.96). In contrast, for repeated (> or =5) controller dispensing there were significantly fewer dispensings to adolescents (OR, 0.7; 95% CI, 0.6-0.9) and girls (OR, 0.8; 95% CI, 0.7-0.9). CONCLUSIONS: There may be differences in the use of preventive asthma medication in children that are affected by age, sex, and health care organization. Few children with frequent symptoms are using controllers regularly, as is recommended by national guidelines.
Administration, Inhalation↗
Genome-wide linkage analysis in a general population sample using sigma 2A random effects (SSARs) fitted by Gibbs sampling.
We used variance components analysis to investigate the underlying determinants of the quantitative phenotypes (Q1-Q5) and their interrelationships in replicate 42 of the Genetic Analysis Workshop 12 simulated general population. Variance components models were fitted using Gibbs sampling in WinBUGS v1.3. Sigma-squared-A-random-effects (SSARs) were estimated for each phenotype, and were used as derived phenotypes in subsequent linkage analyses. Whole-genome, multipoint linkage analyses were based upon a new Haseman-Elston identity-by descent sib-pair method that takes a weighted combination of the trait-sum and trait-difference. The five quantitative traits simulated were closely correlated with each other and with affection status. The whole-genome screen of quantitative traits associated with the simulated complex disease suggested that one or more major loci regulating Q1 localizes to chromosome 2p and that one or more major loci regulating Q5 may localize to chromosome 1p.
Algorithms↗
Epidemiology and heterogeneity of asthma.
LEARNING OBJECTIVES: The primary objective of this review is to discuss the prevalence, risk factors, and natural history of asthma and its relationship to chronic airflow obstruction. DATA SOURCES: A review of PubMed (National Library of Medicine) articles on these topics for the years 1995 through 2000 was performed. In addition, references identified some other review articles, and discussions with experts in the field were included. The review represents a synthesis of these sources and the expert opinion of the author. STUDY SELECTION: The expert opinion of the author was used to select the relevant data for the review. RESULTS: Asthma is a disease that begins in early childhood with more than 90% of cases diagnosed by the age of 6 years. Recall bias for early life events, coupled with growth and lung function, leads to a high prevalence of the intermediate phenotypes of allergy and airways responsiveness in early adult life. Interaction of these intermediate phenotypes with environmental exposures results in recurrent disease which often appears to be incidental to the practitioner, but is actually a recapitulation of early childhood events. CONCLUSIONS: With the development of half a million new cases each year, asthma could be characterized as an epidemic. Increased airways responsiveness and an asthma diagnosis in later adult life are associated with an accelerated decline in lung function and the development of chronic obstructive lung disease.
Adult↗
Receiver operating characteristics curve analysis of cutaneous skin test reactions to predict hay fever and asthma symptoms in the Normative Aging Study.
BACKGROUND: We used receiver operating characteristic (ROC) curves to determine optimal cutoff values and to evaluate the ability of ragweed, mixed grasses, mixed trees, and house-dust antigens to predict symptoms of hay fever and asthma. METHODS: Between 1984 and 1993, 1386 members of the Normative Aging Study cohort had at least one examination that included evaluation of cutaneous hypersensitivity to common aeroallergens by skin prick testing. Standard questionnaires based on the American Thoracic Society DLD-78 questionnaire obtained information on respiratory symptoms, illness, and smoking habits. RESULTS: Ragweed was the best univariate predictor for both hay fever and asthma symptoms: the area under the ROC curve for hay fever was 0.71 (95%) CI 0.67-0.74); for asthma, it was 0.65 (95% CI 0.55-0.75). For hay fever, dichotomizing the average reaction to four antigens at 2 mm gave a sensitivity of 56% and a specificity of 83%; at 3 mm, the sensitivity was 38% and specificity 92%. For asthma, dichotomizing the skin test reaction at 2 mm gave a sensitivity ranging from 30% for reaction to mixed grasses to 56% for the ragweed antigen reaction. CONCLUSIONS: Although in this older population skin test reactivities did not predict current asthma symptoms with high sensitivity, our results support the use of cutoff values of 2 or 3 mm as commonly used in studies of hay fever symptoms.
Adult↗
The pharmacogenetics of asthma: a candidate gene approach.
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Adrenergic beta-Agonists↗
Case-control association studies in pharmacogenetics.
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Case-Control Studies↗
Expiratory and inspiratory forced vital capacity and one-second forced volume in asymptomatic never-smokers in Norway.
The objectives of this study were to examine within and between individual variation detected during forced expiratory (FE) and forced inspiratory (FI) manoeuvers in a general population and to investigate the dependence of these variables on age, body size, and gender. A random sample of asymptomatic never smokers who had never been exposed occupationally to quartz or asbestos and who were living on the south-western coast of Norway were examined by spirometry; 81% of the individuals invited to attend did so. Of the 488 subjects between 18 and 73 years of age, 98% contributed three acceptable recordings for forced expiratory vital capacity (FVC) and one-second forced expiratory volume (FEV1), 94% contributed three acceptable recordings for forced inspiratory vital capacity (FIVC) and 85% contributed three acceptable recordings for one-second forced inspiratory volume (FIV(1)). The within-subject variation increased with body height and was considerably larger for FIV(1) than for FVC, FEV(1) or FIVC. A four-parameter model of pulmonary function measurement divided by height squared, including a gender term and a linear and quadratic term of age, fit the median of the observed values well. The residuals had a close-to-normal distribution, and the fifth-percentile values were estimated as the lower limit of normal. The peak value of dynamic lung volumes was observed into the middle of the fourth decade of life, and the decline thereafter did not differ greatly between the genders or among the different indices. The forced inspiratory volumes are the first reported in any reference population.
Adolescent↗
Exposure to cockroach allergen in the home is associated with incident doctor-diagnosed asthma and recurrent wheezing.
BACKGROUND: Indoor inhaled allergens have been repeatedly demonstrated to worsen asthma in sensitized individuals, but their role in incident asthma is more controversial. OBJECTIVE: We investigated the relationship between exposure to allergens (dust mite, cat, and cockroach) measured in the home and incident doctor-diagnosed asthma and recurrent wheezing in children born to parents with asthma, allergies, or both. METHODS: From an ongoing longitudinal family and birth cohort study, we identified 222 siblings (median age, 2.87 years) of the index children. Allergen levels in the home were measured from dust samples obtained at the beginning of the study. Incident doctor-diagnosed asthma and recurrent wheezing were determined from questionnaires administered at 14 months and 22 months after the initial questionnaire. RESULTS: Thirteen (5.9%) children were reported to have incident asthma, twenty (9.0%) children had recurrent asthmatic wheezing, and 18 (8.1%) had recurrent wheezing without asthma. Compared with children living in homes with Bla g 1 or 2 levels of less than 0.05 U/g, children exposed to Bla g 1 or 2 levels of 0.05 to less than 2 U/g had a relative risk for incident asthma of 8.27 (95% confidence interval, 1.04-66.04), whereas children exposed to Bla g 1 or 2 levels of 2 U/g or greater had a relative risk for incident asthma of 35.87 (95% confidence interval, 4.49-286.62). Cockroach allergen exposure was likewise a significant predictor for recurrent asthmatic wheezing. Neither dust mite nor cat allergen levels were significantly associated with either outcome. These findings remained after control for several covariates. CONCLUSION: Exposure to cockroach allergen early in life may contribute to the development of asthma in susceptible children.
Air Pollution, Indoor↗
FEV(1) is associated with risk of asthma attacks in a pediatric population.
BACKGROUND: FEV(1) is endorsed by the National Asthma Education and Prevention Program as a means for grading asthma severity. However, few data exist on the relationship between FEV(1) and asthma outcomes during long-term follow-up. OBJECTIVE: We explored the relationship between the percent predicted FEV(1) (FEV(1)%) and subsequent asthma attacks in a longitudinal study of pediatric lung health. METHODS: A retrospective cohort of 13,842 children (100,292 observations) seen annually over a 15-year interval was analyzed for measurement of pulmonary function, and a respiratory questionnaire was completed. Up to grade 9, a standard questionnaire was completed by a parent or guardian; thereafter it was completed by the patient. For each observation, the report of an attack during the past year was paired with FEV(1) recorded at the field survey 1 year earlier. RESULTS: A progressive decrease in the proportion of individuals reporting an attack was associated with increasing decile of FEV(1)%. Two categorization schemes for FEV(1)% were examined: a scheme based on the National Asthma Education and Prevention Program recommendations (<60%, 60%-80%, and >80%), and an alternative scheme (<80%, 80%-100%, and >100%). In multivariate models, FEV(1)% was an independent predictor of attacks: among the parental report group, the odds ratios were 2.1 (95% CI, 1.3-3.4) and 1.4 (95% CI, 1.2-1.6) for FEV(1)% < 60% and FEV(1)% of 60% to 80% compared with FEV(1)% > 80%, respectively; and among the self-report group, odds ratios were 5.3 (95% CI, 2.2-12.9) and 1.4 (95% CI, 1.2-1.7) for FEV(1)% < 60% and FEV(1)% of 60% to 80% compared with FEV(1)% > 80%, respectively. With the alternative classification scheme, the relationship was similar, but the difference in risk between categories of FEV(1)% decreased. CONCLUSION: The strong association between FEV(1)% and risk of asthma attack over the subsequent year supports an emphasis on objective measures of lung function in assessment of risk for adverse asthma outcomes.
Adolescent↗
Association of specific allergen sensitization with socioeconomic factors and allergic disease in a population of Boston women.
BACKGROUND: Socioeconomic differences in allergic disease prevalence have been reported; asthma has been associated with poverty in the United States and hay fever and eczema with relative affluence elsewhere. It is not yet established to what degree such differences in disease prevalence reflect patterns of sensitization and specific allergen sensitivities. OBJECTIVE: We analyzed specific and total IgE measurements in a sample of 458 women, enriched for allergic disease, from the metropolitan Boston area to establish the relation of allergen sensitization to markers of socioeconomic status (SES) and to the prevalence and socioeconomic pattern of allergic disease in this community. METHODS: Total and specific IgE antibodies were measured with the UNICAP System; self-reported allergic disease, household income, education, and race-ethnicity were ascertained with a questionnaire; and a further marker of poverty (percentage living below the poverty level) in the women's area of residence was established on the basis of zip codes. Analysis was performed with SAS statistical software. RESULTS: Markers of low SES were univariately associated with increases in total IgE, number of allergen sensitizations, and levels of specific IgE. Socioeconomic differences in sensitization to cockroach (35% vs 6% in the highest and lowest poverty areas), animal (44% vs 26%), and ragweed (49% vs 23%) allergens were most marked. Sensitization primarily to indoor inhalant allergens (not ragweed or ryegrass) were associated with an increased risk of asthma, even after adjustment for SES. CONCLUSION: We have demonstrated a socioeconomic gradient in sensitization that concords with increased rates of asthma in less affluent communities in this population.
Adolescent↗
The prevalence of environmental exposure to perceived asthma triggers in children with mild-to-moderate asthma: data from the Childhood Asthma Management Program (CAMP).
BACKGROUND: The Childhood Asthma Management Program, a 5-year randomized clinical trial of treatments for childhood asthma, has enrolled and characterized a cohort of 1041 children with mild-to-moderate asthma. OBJECTIVE: We sought to describe self-reported sensitivities and environmental exposures and investigate the relationships between self-report of these exposures as asthma triggers and their prevalence in the home. METHODS: Self-reports of sensitivities and home exposures were obtained by interview with the child or parent. Sensitivities were further assessed by using allergy skin testing (prick or puncture) against a core battery of allergens. Home exposures were further assessed by using analysis of a home dust sample. RESULTS: Environmental exposures were surprisingly common despite self-reported sensitivities to environmental factors. Of patients reporting that cigarette smoking frequently causes asthma symptoms, 26% reported having at least one parent who smokes cigarettes. Thirty-nine percent of patients reporting that exposure to animals frequently causes asthma symptoms live with a furry pet in their home. We found a smaller proportion of homes with a high level of cat allergen (P <.001) among the children who reported that animals frequently or always trigger asthma symptoms compared with those who reported that animals never or occasionally trigger asthma symptoms, suggesting modification of the home environment. No such results were seen for dog exposure. However, clinical symptoms did not reduce exposure to parental cigarette smoking (P =.15), house dust (P =.31), or damp and musty areas (P =.51). CONCLUSION: These data suggest that children with mild-to-moderate asthma are frequently symptomatic and exposed to a wide variety of environmental exposures that are perceived to trigger symptoms by means of self-report. Although environmental modification of asthmatic homes may occur, many children remain exposed to agents that are known to trigger their asthma.
Asthma↗
Cost-effectiveness of inhaled corticosteroids in adults with mild-to-moderate asthma: results from the asthma policy model.
BACKGROUND: Inhaled corticosteroids remain underused among United States-based clinicians in treating mild-to-moderate adult asthma. OBJECTIVE: The purpose of this investigation was to estimate the clinical impact, health-related quality of life, cost, and cost-effectiveness of inhaled corticosteroid therapy in a population of patients aged 18 years and over with FEV(1) = 60% to 100% of predicted normal. METHODS: We performed a cost-effectiveness analysis of quick relievers (eg, short-acting beta-agonists) on an as-needed basis plus inhaled corticosteroid therapy versus quick relievers alone. A mathematical simulation model was developed to forecast symptoms, acute exacerbations, quality-adjusted life-years (QALYs), health care costs, and cost-effectiveness, measured in both dollars per QALY gained and dollars per symptom-free day gained. All evaluation outcomes were discounted at an annual rate of 3% and measured over a 10-year planning horizon. Data on the natural history of disease, drug efficacy, patient preferences, and economic costs were obtained from a variety of observational cohorts, randomized trials, and patient surveys. RESULTS: Over a 10-year period, use of inhaled corticosteroids increases total health costs from roughly $5,200 to $8,400 and improves QALYs from 6.8 to 7.0, implying an incremental cost of $13,500 per QALY gained. Costs per symptom-free day gained are $7.50. Both per-person acute exacerbations and hospitalizations are reduced by 33%. The cost-effectiveness findings are sensitive to the assumed efficacy and side-effects of inhaled corticosteroid therapy. CONCLUSIONS: Inhaled corticosteroids appear to deliver good comparative value in adults with mild-to-moderate asthma. Although more research is needed to understand their impact on preferences regarding side effects and compliance, these findings might be useful for priority-setting in limited resource situations.
Administration, Inhalation↗