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Biomedical subjects

S T Weiss

Publications and source records attributed to S T Weiss.

At least 55 records · Page 3Linked to original sources

Relation of body mass index to asthma and atopy in children: the National Health and Nutrition Examination Study III.

BACKGROUND: An increase in the prevalence of obesity and asthma over recent decades has been reported in affluent societies. Both overweight and obesity have been shown to be inversely related to having been breastfed, which is also a potential protective factor against childhood atopic diseases. The aim of this analysis was to explore the relation of body mass index (BMI) to asthma and atopy in a large representative sample of the United States population. METHODS: Children aged 4-17 years were included in the NHANES III survey. Prevalences of atopic diseases and potential confounding factors such as exposure to environmental tobacco smoke, birth weight, breast feeding, and household size were assessed using structured interviews with parents. Height and weight were measured, and BMI was calculated as kg/m(2) and transformed into Z scores. Children underwent skin prick tests for atopy to a battery of food and inhalant allergens. RESULTS: The prevalence of asthma (8.7% v 9.3% v 10.3% v 14.9%, p=0.0001) and atopy (48.6% v 50.5% v 53.0% v 53.2%, p=0.05) rose significantly with increasing quartiles of BMI. After adjustment for confounders, a significant positive association between BMI and asthma remained (adjusted OR 1.77, 95% confidence interval 1.44 to 2.19 between the highest and lowest quartiles of BMI), whereas no independent relation between BMI and atopy was evident. No effect modification by sex or ethnic group was seen. CONCLUSIONS: The effects of increased BMI on asthma may be mediated by mechanical properties of the respiratory system associated with obesity or by upregulation of inflammatory mechanisms rather than by allergic eosinophilic inflammation of the airway epithelium.

Adolescent↗

Linkage analysis of alpha 1-antitrypsin deficiency: lessons for complex diseases.

OBJECTIVES: Severe alpha 1-antitrypsin (A1AT) deficiency is the one proven genetic risk factor for chronic obstructive pulmonary disease (COPD). Familial aggregation has been demonstrated for COPD among individuals who do not have A1AT deficiency, but linkage analysis of COPD has not been reported. To investigate the optimal phenotype definitions and analytical methods for the linkage analysis of COPD, we examined a set of 28 A1AT- deficient families containing 155 individuals. We have used the protease inhibitor (PI) type as a genetic marker rather than a disease gene, and we have performed linkage analysis between PI type and serum A1AT level and spirometry-related phenotypes. METHODS: Linkage analysis was performed on the quantitative phenotypes forced expiratory volume at 1 s (FEV(1) as % predicted), the ratio of FEV(1) to forced vital capacity (FEV(1)/FVC as % predicted), and serum A1AT level using the variance component approach in SOLAR, the generalized estimating equation approach in RELPAL, and the model-based classical lod score method in LINKAGE. Linkage analysis with qualitative A1AT and spirometry phenotypes was performed using a model-based method (LINKAGE) and a model-free method (GENEHUNTER). Adjustments for smoking effects were investigated under each method. RESULTS: All of the methods demonstrated linkage of PI type to serum A1AT level. Interestingly, however, the other quantitative phenotypes provided only weak evidence for linkage of PI type to lung disease. Better evidence for linkage of lung disease to PI type was found using a moderate or a mild threshold for the definition of airflow obstruction. CONCLUSIONS: For linkage analysis of spirometry phenotypes in A1AT deficiency, qualitative phenotypes provided stronger evidence for linkage than quantitative phenotypes. Possible contributors to the stronger evidence for linkage to qualitative spirometry phenotypes include the ascertainment scheme and the nonnormality of the pulmonary function data in PI Z subjects. This study provides guidelines for studies of the genetics of COPD unrelated to A1AT deficiency.

Female↗

Clinical predictors of health-related quality of life depend on asthma severity.

The National Asthma Education and Prevention Program guidelines define asthma severity before treatment by lung function and symptoms. It has been assumed, but not demonstrated, that improvement in these measures would translate into improvement in health-related quality of life (HRQL). Because HRQL is an important outcome in asthma management, we asked what are the determinants of HRQL? To address this question, we retrospectively analyzed HRQL data, as measured by the Juniper Asthma Quality of Life Questionnaire, in subjects with mild versus moderate-severe asthma from two clinical trials. We examined whether these traditional clinical outcomes have different relationships to HRQL depending on asthma severity. We also assessed whether the relationship between clinical outcomes and HRQL in subjects with moderate-severe asthma would change when subjects improved to mild-moderate disease with controller medication treatment. Lung function was not an independent predictor or determinant of HRQL at any level of asthma severity, whereas intensity of shortness of breath predicted HRQL at all levels of asthma severity. Rescue beta-agonist use independently predicted HRQL in subjects with mild asthma, but not in those with moderate-severe asthma. In subjects with moderate-severe asthma who improved to mild-moderate disease with controller treatment, rescue beta-agonist use predicted HRQL. We conclude that the independent determinants of HRQL vary according to asthma severity and change with asthma treatment.

Adult↗

Asthma, rhinitis, and skin test reactivity to aeroallergens in families of asthmatic subjects in Anqing, China.

In industrialized countries with a Western lifestyle, sensitization to perennial aeroallergens is strongly associated with asthma, whereas sensitization to seasonal aeroallergens is closely related to allergic rhinitis. Little is known, however, about the relation between skin test reactivity to aeroallergens and either asthma or rhinitis in mainland China. We studied 10,009 members of 2,544 families in Anqing (China) that were selected on the basis of physician-diagnosed asthma in at least two siblings. Generalized estimating equations were employed to study the association between skin test reactivity to aeroallergens and either asthma or rhinitis. After adjustment for age, sex, intensity of smoking, skin test reactivity to other aeroallergens, and household correlations, sensitization to dust mite was an independent predictor of both asthma (OR = 1.3, 95% CI = 1.1 to 1.5, p = 0.008) and rhinitis (OR = 1.3, 95% CI = 1.0 to 1.8, p = 0.04). Sensitization to mold was significantly associated with asthma (OR = 1.6, 95% CI = 1.1 to 2.3, p = 0.008), and sensitization to silk was an independent predictor of rhinitis (OR = 1.5, 95% CI = 1.1 to 2.2, p = 0.02). Although 46.9% of the study participants were sensitized to at least one allergen, only 3.5% of study subjects reported nasal symptoms consistent with rhinitis. Among asthmatic subjects, 6.2% reported nasal symptoms. Whereas sensitization to perennial aeroallergens was associated with asthma among families of asthmatic subjects in rural China, sensitization to silk was the strongest predictor of rhinitis in this population. Our findings also suggest that allergic rhinitis is far less common among asthmatic subjects in rural China than in asthmatic subjects in industrialized countries with a Western lifestyle.

Adolescent↗

Association of asthma with beta(2)-adrenergic receptor gene polymorphism and cigarette smoking.

Recent studies have suggested that two polymorphisms of the beta(2)-adrenergic receptor (beta(2)AR) gene at codons 16 (arginine to glycine) and 27 (glutamine to glutamate) affect an individual's airway responsiveness, or response to acute or chronic beta(2)-agonist therapy but are not risk factors for asthma. We hypothesize that there is an interaction effect on asthma between the beta(2)AR gene polymorphisms and cigarette smoking. A case-control study was conducted in 128 asthma cases and 136 control individuals identified from 10,014 studied subjects in rural Anqing, China. Allele-specific polymerase chain reaction (PCR) was used to genotype beta(2)AR gene polymorphisms. Multiple logistic regression was used to adjust for potential confounding factors. We found a marginally significant interaction between cigarette smoking and beta(2)AR-16 genotype after adjusting for important confounding factors (p = 0.06). Specifically, we found that compared with never-smoking Gly-16 homozygotes, those ever-smokers who are Arg-16 homozygotes had a significantly increased risk of asthma (odds ratio [OR] = 7.81; 95% confidence interval [CI]: 2.07 to 29.5). This association showed a clear dose-response relationship with the number of cigarettes smoked. However, there was no significant association of asthma with polymorphisms of the beta(2)AR at position 27 (OR = 1.38; 95% CI: 0.69 to 2.73). Our study suggests a gene-environment interaction between the Arg-16 genotype and ever cigarette smoking with respect to the susceptibility of an individual to asthma.

Adult↗

Airway responsiveness and peak flow variability in the diagnosis of asthma for epidemiological studies.

Airway responsiveness and variability in peak expiratory flow (PEF) are widely used as objective diagnostic measures of asthma, but it is not clear how these variables should be calculated or adjusted to obtain the highest diagnostic validity for physician-diagnosed asthma in the community. Data from a community-based sample of 1,513 adults has been used. Airway responsiveness to methacholine and 7-day PEF data were obtained in 1991, asthma and respiratory symptoms were diagnosed by questionnaires in 1991 and 1999. Airway responsiveness was expressed as the provocative dose causing a 20% fall in forced expiratory volume in one second (PD20), two-point and least-squares regression slopes. PEF variability was expressed as daily amplitude, weekly standard deviation and mean of the two lowest readings. Continuous measures were adjusted for measures of baseline airway calibre by linear regression. Measures of airway responsiveness had greater sensitivity for specificity for self-reported diagnosed asthma than expressions of PEF variability, before and after adjustment for airway calibre. Diagnostic validity was substantially better in adults aged <50 yrs; PD20 provided the best sensitivity for specificity (61% for 95% at 8.3 micromol). In those aged > or =50 yrs, no measure was closely related to diagnosed asthma. In younger age groups, provocative dose causing a 20% fall in forced expiratory volume in one second provides a valuable objective measure of asthma for epidemiological studies, but is unable to distinguish between asthma and chronic obstructive pulmonary disease in older people.

Adult↗

The relation between peripheral blood leukocyte counts and respiratory symptoms, atopy, lung function, and airway responsiveness in adults.

STUDY OBJECTIVES: Eosinophils and neutrophils play major roles, respectively, in the pathogenesis of asthma and COPD, and it is well recognized that levels of these cells in peripheral blood are increased in relation to their pulmonary involvement. However, the relation between peripheral blood cell counts of the other major leukocyte groups and these lung diseases or markers of allergy or airflow obstruction is less clear. We have therefore investigated the association between peripheral blood levels of eosinophils, neutrophils, basophils, monocytes, and lymphocytes and the occurrence of chronic respiratory symptoms, atopy, lung function, and bronchial hyperresponsiveness, and the modifying effect of age, in adults. DESIGN: A cross-sectional general population study. SETTING: Data on > 2,000 British adults, who originally participated in a study of diet and lung health, were analyzed using multiple linear and logistic regression to adjust for potential confounders, including age, sex, and smoking history. RESULTS: We found that, like eosinophils, the peripheral basophil count was increased in relation to asthma and associated symptoms, and to airway hyperreactivity and increased total IgE, but differed from eosinophils in that basophils were unrelated to atopy. Monocytes were predominantly associated with symptoms indicative of obstructive airway disease, in similar relation to neutrophils, but both of these leukocyte counts were also increased in asthma patients in older age groups. Lymphocyte counts were unrelated to any objective or subjective marker of disease. CONCLUSIONS: If peripheral blood cell counts reflect pulmonary involvement of these leukocyte groups, basophils and monocytes may play a distinct role in the pathogenesis of allergic and nonallergic respiratory disease.

Adolescent↗

Association of airway responsiveness with asthma and persistent wheeze in a Chinese population.

STUDY OBJECTIVES: Data from a cross-sectional study were analyzed to examine the association of increased airway responsiveness with physician-diagnosed asthma and persistent wheeze. DESIGN: Two methods for calculating the provocative dose that decreases the airflow rate by 20% (PD(20)) were used as indexes for increased airway responsiveness: (1) a 20% drop in FEV(1) calculated from baseline FEV(1) (PD(20)b), and (2) a 20% drop in FEV(1) from FEV(1) measurements after inhalation of saline solution (PD(20)s). Both PD(20)b and PD(20)s were measured through induction by varying doses of methacholine. SETTING: Anqing, Anhui Province, China. PARTICIPANTS: Study subjects were 8 to 74 years of age and were classified into four groups: children (< 15 years old), young adults (15 to 29 years old), adults (30 to 44 years old), and older adults (> or 5 years old). INTERVENTIONS: The differences in estimated odds ratios of airway hyperresponsiveness with asthma and wheeze, sensitivity and specificity, and coefficients of variation were compared between PD(20)b and PD(20)s. The sample for analysis consisted of 10,284 subjects from 2,663 nuclear families with complete data on wheeze, asthma, and major potential confounding factors. MEASUREMENTS AND RESULTS: The prevalence of asthma in this sample was lowest in subjects with no demonstrable PD(20) and had a reverse dose-response relationship with PD(20) across all age groups. Using the receiver operating characteristic, the sensitivity and specificity of the PD(20)s or PD(20)b were found to be almost identical. A similar trend was found for persistent wheeze, although the estimated odds ratios for persistent wheeze appeared slightly smaller than those for physician-diagnosed asthma. CONCLUSIONS: This study demonstrates a dose-response relationship between increased airway responsiveness and asthma and wheeze in this Chinese population. PD(20)s or PD(20)b yielded virtually indistinguishable results, which indicated that either of the two tests could serve as an index of airway hyperresponsiveness.

Adolescent↗

Risk factors for childhood asthma in Costa Rica.

BACKGROUND: Little is known about factors determining the pathogenesis and severity of asthma in Latin American countries. Costa Rica, one of the most prosperous Latin American nations, has a very high asthma prevalence. OBJECTIVE: To examine the relation between potential risk factors and childhood asthma in Costa Rica. METHODS: Cross-sectional study of 214 schoolchildren aged 10 to 13 years participating in phase II of the International Study of Asthma and Allergies in Childhood. RESULTS: After adjustment for age, gender, area of residence, maternal smoking during pregnancy, and airway responsiveness to hypertonic saline solution, sensitization to house dust mites was associated with asthma (odds ratio [OR], 2.2; 95% confidence interval [CI], 1.1 to 4.4; p = 0.02). In the multivariate analysis, parental education no higher than high school (OR, 3.0; 95% CI, 1.4 to 6.4; p < 0.01) and parental history of asthma (OR, 2.6; 95% CI, 1.3 to 5.2; p < 0.01) were also independent predictors of childhood asthma. CONCLUSIONS: Sensitization to house dust mites, low parental education, and parental history of asthma are associated with asthma in Costa Rica.

Adolescent↗

Relationship between asthma medication and antibiotic use.

STUDY OBJECTIVES: Increasing morbidity due to asthma and antimicrobial resistance among human pathogens are both major public-health concerns. Numerous studies describe the overuse of antibiotics in general populations and underuse of anti-inflammatory medications by asthmatic patients. However, little is known about the relationship between asthma medication and antibiotic use in asthmatics. Specifically, we tested the hypothesis that higher use of bronchodilator and anti-inflammatory medication by asthmatics, as a marker of problematic asthma, is associated with greater antibiotic use. We also test the hypothesis that physicians who are low prescribers of anti-inflammatory medications are high prescribers of antibiotics. DESIGN: We conducted a retrospective cohort study evaluating asthma medication and antibiotic use by children and adults with asthma and the prescribing of these medications by primary-care physicians. SETTING/PATIENTS: Subjects were continuously enrolled asthma patients aged 6 to 55 years receiving care in an urban, group-model, health maintenance organization. INTERVENTIONS: None. MEASUREMENT AND RESULTS: Main outcome measures were (1) antibiotic use by asthmatics stratified by low, moderate, and high bronchodilator use; (2) antibiotic use by asthmatics stratified by no, intermittent, and long-term anti-inflammatory use; and (3) correlation between physician-level anti-inflammatory agent to bronchodilator ratio (AIF:BD) and their rate of antibiotic prescribing. We found that (1) high bronchodilator users received 1.72 antibiotics per person-year (95% confidence interval [CI], 1.62 to 1.83), whereas low bronchodilator users received 1.23 antibiotics per person-year (95% CI, 1.19 to 1.27; p < 0.0001); (2) long-term users of anti-inflammatory agents received 1.85 antibiotics per person-year (95% CI, 1.76 to 1.95), whereas those not receiving an anti-inflammatory agent received 0.95 antibiotics per person-year (95% CI, 0.90 to 1.00; p < 0.0001); and (3) despite variations in physician AIF:BDs and antibiotic prescribing, respectively, these measures were not correlated. CONCLUSIONS: Antibiotic use and asthma medication use are positively associated in a cohort of asthma patients. Greater effort is needed to define the appropriate role of antibiotics in asthma management.

Adolescent↗

Impact of inhaled antiinflammatory therapy on hospitalization and emergency department visits for children with asthma.

OBJECTIVE: Although the efficacy of inhaled antiinflammatory therapy in improving symptoms and lung function in childhood asthma has been shown in clinical trials, the effectiveness of these medications in real-world practice settings in reducing acute health care use has not been well-evaluated. This study examined the effect of inhaled antiinflammatory therapy on hospitalizations and emergency department (ED) visits by children for asthma. DESIGN: Defined population cohort study over 1 year. Setting. Three managed care organizations (MCOs) in Seattle, Boston, and Chicago participating in the Pediatric Asthma Care-Patient Outcome Research and Treatment II trial. Participants. All 11 195 children, between 3 to 15 years old, with a diagnosis of asthma who were enrolled in the 3 MCOs between July 1996 and June 1997. OUTCOME MEASURES: We identified children with 1 or more asthma diagnoses using automated encounter data. Medication dispensings were identified from automated pharmacy data. Multivariate logistic regression analysis was used to calculate effects of inhaled antiinflammatory therapy on the adjusted relative risk (RR) for hospitalization and ED visits for asthma. RESULTS: Over 12 months, 217 (1.9%) of children had an asthma hospitalization, and 757 (6.8%) had an ED visit. After adjustment for age, gender, MCO, and reliever dispensing, compared with children who did not receive controllers, the adjusted RRs for an ED visit were: children with any (>/=1) dispensing of cromolyn, 0.4 (95% confidence interval [CI]: 0.3, 0.5); any inhaled corticosteroid (ICS), 0.5 (95% CI: 0.4, 0.6); any cromolyn or ICS combined (any controller), 0.4 (95% CI: 0.3, 0.5). For hospitalization, the adjusted RR for cromolyn was 0.6 (95% CI: 0.4, 0.9), for ICS 0.4 (95% CI: 0.3, 0.7), and for any controller 0.4 (95% CI: 0.3, 0.6). A significant protective effect for both events was seen among children with 1 to 5 and with >5 antiinflammatory dispensings. When the analysis was stratified by frequency of reliever dispensing, there was a significant protective effect for controllers on ED visits for children with 1 to 5 and with >5 reliever dispensings and on the risk of hospitalization for children with >5 reliever dispensings. CONCLUSIONS: Inhaled antiinflammatory therapy is associated with a significant protective effect on the risk for hospitalization and ED visits in children with asthma. Cromolyn and ICSs were associated with similar effects on risks.asthma drug therapy, inhaled antiinflammatory agents, health maintenance organizations, hospitalization, emergency department.

Administration, Inhalation↗

Sensitization to silk and childhood asthma in rural China.

OBJECTIVE: Sensitization to perennial aeroallergens is associated with asthma in industrialized countries with a Western lifestyle. Because silk products are commonly used in Chinese society, we were interested in examining the relation between sensitization to silk and asthma. DESIGN: Cross-sectional study of 871 children in 503 families living in Anqing, a predominantly rural province of China. RESULTS: After adjustment for age, gender, familial correlations, and sensitization to other aeroallergens, skin test reactivity to silk was an independent predictor of asthma (odds ratio = 2.6; 95% confidence interval = 1.2-5.7). This association became stronger after inclusion of the eosinophil count and history of parasitic diseases of the participants in the multivariate model (odds ratio = 3.6; 95% confidence interval = 1.4-8.9). CONCLUSION: Because sericulture is an important activity in China and other countries throughout the world, sensitization to silk may influence the pathogenesis and severity of asthma in people living in these nations.

Allergens↗

Beta2-adrenergic receptor genetics.

The beta2-adrenergic receptor (beta2AR) is a positional candidate gene for asthma located on 5q31-33. There are 17 known polymorphisms in this gene. A determination of the functional significance of these polymorphisms is complicated by the lack of haplotypic assessment in most functional assays. The beta2AR gene is not an asthma-susceptibility gene but appears to be a minor determinant for lung function. The gene also has clear pharmacogenetic effects. Further work is needed to fully define the effects of haplotype on function, disease phenotype and pharmacogenetic effect.

Animals↗

Histamine airway hyper-responsiveness and mortality from chronic obstructive pulmonary disease: a cohort study.

BACKGROUND: Smoking and airway lability, which is expressed by histamine airway hyper-responsiveness, are known risk factors for development of respiratory symptoms. Smoking is also associated with increased mortality risks. We studied whether airway hyper-responsiveness is associated with increased mortality, and whether this risk was independent of smoking and reduced lung function. METHODS: We followed up 2008 inhabitants of the communities of Vlagtwedde, Vlaardingen, and Meppel (Netherlands), who had histamine challenge test data, from 1964-72 for 30 years. Follow-up was 99% successful (29 patients lost to follow-up) with 1453 participants alive and 526 deaths (246 died from cardiovascular disease, 54 from lung cancer, and 21 from chronic obstructive pulmonary disease [COPD]). FINDINGS: Mortality from COPD increased with more severe hyper-responsiveness; relative risks of 3.83 (95% CI 0.97-15.1), 4.40 (1.16-16.7), 4.78 (1.27-18.0), 6.69 (1.71-26.1), and 15.8 (3.72-67.1) were associated with histamine thresholds of 32 g/L, 16 g/L, 8 g/L, 4 g/L, and 1 g/L, respectively, compared with no hyper-responsiveness. These risks were adjusted for sex, age, smoking, lung function, body-mass index, positive skin tests, eosinophilia, asthma, and city of residence. INTERPRETATION: Increased histamine airway hyper-responsiveness predicts mortality from COPD. Although this trend was more pronounced in smokers, an increasing proportion of COPD deaths with increasing hyper-responsiveness was also present among individuals who had never smoked.

Adolescent↗

Parasites and asthma/allergy: what is the relationship?

Asthma prevalence is increasing in Western industrialized countries. The infectious theory of asthma onset hypothesizes that lower levels of IL-12 result in reduced T(H)1 stimulation and failure of the neonate to deviate from its T(H)2 bias at birth. Helminthic infections may influence T(H)2 immune responses and hence immune development. Although ecologic data would support a protective effect of parasitic infection on asthma development, this may be due to other exposures. To date, there is no conclusive evidence that parasitic infection protects against asthma development.

Animals↗

Children at risk for asthma: home allergen levels, lymphocyte proliferation, and wheeze.

BACKGROUND: Allergic asthma is a common childhood disease. Although T-lymphocyte activation plays a critical role in allergic asthma, the environmental factors promoting lymphocyte activation in children are not well defined. OBJECTIVE: In a cohort of children at risk for asthma (n = 114), we determined whether the levels of cockroach (Bla g 1 or 2), house dust mite (Der f 1), and cat allergen (Fel d 1) in the home during infancy was associated with subsequent allergen-specific lymphocyte proliferation in later life. METHODS: Dust samples from multiple sites in the home were collected at 3 months of age and were measured for allergen levels. Serial questionnaires were applied. At a median age of 2 years, PBMCs were isolated and lymphocyte proliferation to the home allergens and PHA was determined. RESULTS: Increased lymphocyte proliferative responses to Bla g 2 were associated with higher home levels of Bla g 1 or 2 (P for trend with kitchen Bla g levels =.011), in analyses adjusting for cold in the past week. Proliferative responses to Der f 1 were higher in homes with family room levels of Der f 1 > or =10 microg/g dust than in homes with Der f 1 <2 microg/g, but differences were not significant in analyses adjusting for cold (P =. 15). Repeated wheeze in the first 2 years of life was associated with increased allergen-specific and PHA proliferative responses. CONCLUSION: Early-life cockroach allergen exposure at 3 months of age predicts allergen-specific lymphocyte proliferative responses at a median of 2 years of age.

Air Pollution, Indoor↗