Bronchial responsiveness in atopic adults increases with exposure to cat allergen.

RATIONALE: The association of asthma with sensitization and allergen exposure is known to be complex. There have been few studies of bronchial responsiveness in relation to both risk factors in adults. OBJECTIVES: To determine the relation of bronchial responsiveness to allergen exposure and IgE sensitization in a community study taking into account the major determinants of bronchial responsiveness in adulthood. METHODS: Cross-sectional data were drawn from 1,884 participants in 20 centers in the European Community Respiratory Health Survey follow-up, which included measurement of house dust mite and cat allergen in mattress dust samples, and IgE sensitization to four allergens. Bronchial responsiveness to methacholine was expressed as a continuous variable, and analyzed by multiple regression. MEASUREMENTS AND MAIN RESULTS: The trend toward greater bronchial responsiveness with increasing exposure to cat allergen was greater in those sensitized to any of the four allergens than those not sensitized (p = 0.001); there was no significant interaction between cat sensitization and Fel d 1 exposure. No trend was found with house dust mite allergen exposure. The difference in bronchial responsiveness between those exposed to the highest levels compared with the lowest was approximately -2.02 doubling doses of PD20 (95% confidence interval, -3.06 to -0.97), and nearly as great in those exposed to more moderate levels. CONCLUSIONS: Cat allergen exposure at moderate levels may be harmful to all atopic adults. The clinical implication is that it is insufficient to test patients with asthma for cat sensitization; all atopic individuals may benefit from reduced cat exposure.

The relation of adult bronchial responsiveness to serious childhood respiratory illness in the ECRHS.

BACKGROUND: Respiratory symptoms in adulthood have been found to be associated with childhood respiratory infection, but few studies have analyzed adult bronchial responsiveness (BHR) with adequate adjustment for known risk factors. OBJECTIVE: To estimate the relation of BHR with serious childhood respiratory infections in a large population study. METHODS: The European Community Respiratory Health Survey (ECRHS) was a cross-sectional population-based survey in 34 centers. Data on serious respiratory infections before the age of 5 years and possible confounders were obtained from a questionnaire administered in the clinic. Blood samples were taken for measurement of total immunoglobulin E (IgE) and specific IgE to four common allergens, and spirometry and bronchial challenge with methacholine were performed. A continuous measure of BHR was analyzed by multiple regression, in 11,282 participants, in relation to serious respiratory infection and other potential risk factors, adjusted for center and major determinants of adult BHR. RESULTS: Those reporting a serious childhood respiratory infection had greater BHR, by an amount corresponding to approximately 0.23 doubling doses (95% confidence interval 0.02-0.44) of the amount of methacholine causing a 20% fall (PD(20)) in forced expiratory volume in 1s (FEV(1)). All childhood factors explained less than 0.3% of variation in BHR in addition to over 20% by factors measured in adulthood. The relation of BHR to BMI was confined to smokers. CONCLUSIONS: We found an effect of serious childhood respiratory infection on adult BHR, but this was small in comparison to relations of BHR to IgE-sensitization and airway caliber.

Smoking cessation, lung function, and weight gain: a follow-up study.

BACKGROUND: Only one population-based study in one country has reported effects of smoking cessation and weight change on lung function, and none has reported the net effect. We estimated the net benefit of smoking cessation, and the independent effects of smoking and weight change on change in ventilatory lung function in the international European Community Respiratory Health Survey. METHODS: 6654 participants in 27 centres had lung function measured in 1991-93, when aged 20-44 years, and in 1998-2002. Smoking information was obtained from detailed questionnaires. Changes in lung function were analysed by change in smoking and weight, adjusted for age and height, in men and women separately and together with interaction terms. FINDINGS: Compared with those who had never smoked, decline in FEV1 was lower in male sustained quitters (mean difference 5.4 mL per year, 95% CI 1.7 to 9.1) and those who quit between surveys (2.5 mL, -1.9 to 7.0), and greater in smokers (-4.8 mL, -7.9 to -1.6). In women, estimates were 1.3 mL per year (-1.5 to 4.1), 2.8 mL (-0.8 to 6.3) and -5.1 mL (-7.5 to -2.8), respectively. These sex differences were not significant. FEV1 changed by -11.5 mL (-13.3 to -9.6) per kg weight gained in men, and by -3.7 mL per kg (-5.0 to -2.5) in women, which diminished the benefit of quitting by 38% in men, and by 17% in women. INTERPRETATION: Smoking cessation is beneficial for lung function, but maximum benefit needs control of weight gain, especially in men.

Nondifferential disease misclassification may bias incidence risk ratios away from the null.

BACKGROUND AND OBJECTIVE: When estimating incidence risk ratios in follow-up studies, subjects testing positive for the disease at baseline are excluded. Although the effect of disease misclassification on estimated incidence risk ratios has otherwise been extensively explored, the effect of disease misclassification at baseline has not previously been analyzed. STUDY DESIGN AND SETTING: The design was theoretical calculations assuming dichotomous disease and a follow-up study with a baseline and a follow-up examination, analyzed using cumulative incidence. Calculations consider nondifferential misclassification of disease mainly at baseline, but no misclassification of exposure. RESULTS: Nondifferential misclassification of disease at baseline can lead to bias either away or toward null in estimated cumulative incidence risk ratios. This bias is mainly a function of sensitivity at baseline, because imperfect sensitivity leads to failure to exclude all diseased subjects from the follow-up. Imperfect specificity at baseline has less effect. Bias is increased with high true prevalence of disease and low true incidence. Bias is also increased with large differences in true risk ratios at baseline and at follow-up, because observed incidence risk ratios in the presence of misclassification reflect both the true association at baseline and at follow-up. CONCLUSION: Nondifferential disease misclassification at baseline examination of a follow-up study can lead to over- or underestimation of the cumulative incidence risk ratios. The bias can be substantial for disease with low incidence and high prevalence, such as asthma or myocardial infarction. The results underscore the need to select a highly sensitive test for disease at baseline to exclude all diseased subjects from the follow-up.

Patterns of intra-cluster correlation from primary care research to inform study design and analysis.

OBJECTIVE: To provide information concerning the magnitude of the intraclass correlation coefficient (ICC) for cluster-based studies set in primary care. STUDY DESIGN AND SETTING: Reanalysis of data from 31 cluster-based studies in primary care to estimate intraclass correlation coefficients from random effects models using maximum likelihood estimation. RESULTS: ICCs were estimated for 1,039 variables. The median ICC was 0.010 (interquartile range [IQR] 0 to 0.032, range 0 to 0.840). After adjusting for individual- and cluster-level characteristics, the median ICC was 0.005 (IQR 0 to 0.021). A given measure showed widely varying ICC estimates in different datasets. In six datasets, the ICCs for SF-36 physical functioning scale ranged from 0.001 to 0.055 and for SF-36 general health from 0 to 0.072. In four datasets, the ICC for systolic blood pressure ranged from 0 to 0.052 and for diastolic blood pressure from 0 to 0.108. CONCLUSION: The precise magnitude of between-cluster variation for a given measure can rarely be estimated in advance. Studies should be designed with reference to the overall distribution of ICCs and with attention to features that increase efficiency.

Geographical and organisational variation in the structure of primary care services: implications for study design.

AIMS: To evaluate the extent to which structural variation between English general practices is accounted for at higher organisational levels in the National Health Service (NHS). METHODS: We analysed data for 11 structural characteristics of all general practices in England. These included characteristics of general practitioners (GPs), the practice list and the services provided by practices. A four-level random effects model was used for analysis and components of variance were estimated at the levels of practice, primary care group (PCG), health authority and region. RESULTS: The proportion of single-handed practices ranged from 0% to 74% at PCG level and from 14% to 43% in different regions. The proportion of practices providing diabetes services ranged from 0% to 100% at PCG level and from 71% to 96% in different regions. The list size per GP ranged from 1314 to 2704 patients per GP at PCG level and from 1721 to 2225 at regional level. Across the 11 variables analysed, components of variance at general practice level accounted for between 43% and 95% of the total variance. The PCG level accounted for between 1% and 29%, the health authority level for between 2% and 15% and the regional level for between 0% and 13% of the total variance. Adjusting for an index of deprivation and the supply of GPs gave a median 8% decrease in the sum of variance components. CONCLUSION: Geographical and organisational variation in the structure of primary care services should be considered in designing studies in health systems such as the English NHS. Stratified designs may be used to increase study efficiency, but variation between areas may sometimes compromise generalisability.

Designing personable and informative job recruiting web sites: testing the effect of the design on attractiveness and intent to apply.

To date, most of the limited research conducted about the efficacy of corporate job recruiting web sites has been either anecdotal or based on field surveys. In this study, the effects of using a photograph, a friendly text message, and a list of job tasks in job descriptions were measured on undergraduates' ratings of the Personableness and Informativeness of recruiting web sites. In addition, the relationships between ratings of Personableness and Informativeness on perceptions of organizational Attractiveness and Intent to Apply were tested. Use of a photograph increased ratings of both Personableness and Informativeness. Additional results are provided and directions for research suggested.

Air pollution and lung function in the European Community Respiratory Health Survey.

BACKGROUND: The association of long-term air pollution and lung function has not been studied across adult European multi-national populations before. The aim of this study was to determine the association between long-term urban background air pollution and lung function levels, as well as change in lung function among European adults. METHODS: Forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and the ratio thereof (FEV1/FVC) were assessed at baseline and after 9 years of follow-up in adults from 21 European centres (followed-up sample 5610). Fine particles (PM(2.5)) were measured in 2000/2001 using central monitors. RESULTS: Despite sufficient statistical power no significant associations were found between city-specific annual mean PM(2.5) and average lung function levels. The findings also do not support an effect on change in lung function, albeit statistical power was insufficient to significantly detect such an association. CONCLUSIONS: The inability to refuse the null hypothesis may reflect (i) no effect of urban air pollution on lung function or (ii) inherent biases due to the study design. Examples of the latter are lack of individual-level air quality assignment, not quantified within-city contrasts in traffic-related pollution, or the heterogeneity of the studied populations and their urban environments. Future studies on long-term effects of air pollution on lung function could increase statistical power and reduce potential misclassification and confounding by characterizing exposure on the level of individuals, capturing contrasts due to local sources, in particular traffic.

Cat and dust mite allergen levels, specific IgG and IgG4, and respiratory symptoms in adults.

BACKGROUND: Exposure to allergen may induce a modified T(H)2 response characterized by high IgG(4) levels, absence of IgE sensitization, and a decreased risk of allergic respiratory symptoms. OBJECTIVE: To assess the association of IgG(4) level with allergic respiratory symptoms in a community-based sample of adults. METHODS: Information on exposure to cats, respiratory symptoms, and mattress allergen levels was obtained from 2780 adults. Levels of cat and house dust mite (HDM) specific IgE, IgG, and IgG(4) were measured. The association of exposure to allergen with IgG(4) and of IgG(4) with symptoms was assessed. RESULTS: Geometric mean (GM) cat specific IgG and IgG(4) was higher in subjects who had a cat that was allowed in the bedroom than in subjects without a cat (adjusted ratio of GM IgG(4), 1.41; 95% CI, 1.25-1.57). Levels of HDM specific IgG and IgG(4) were similar in subjects with undetectable and high (>20.22 microg/g) mattress Der 1 levels (adjusted ratio of GM IgG(4), 1.02; 95% CI, 0.89-1.17). There was no evidence that high cat or HDM specific IgG(4) levels were associated with less IgE sensitization or with fewer symptoms. CONCLUSION: In this community-based sample of adults, high IgG(4) levels to cat or HDM were not associated with a lower risk of allergic respiratory symptoms. CLINICAL IMPLICATIONS: In adults, high cat allergen exposure does not protect against respiratory symptoms.

Physical activity and bronchial hyperresponsiveness: European Community Respiratory Health Survey II.

BACKGROUND: Identification of the risk factors for bronchial hyperresponsiveness (BHR) would increase the understanding of the causes of asthma. The relationship between physical activity and BHR in men and women aged 28.0-56.5 years randomly selected from 24 centres in 11 countries participating in the European Community Respiratory Health Survey II was investigated. METHODS: 5158 subjects answered questionnaires about physical activity and performed BHR tests. Participants were asked about the frequency and duration of usual weekly exercise resulting in breathlessness or sweating. BHR was defined as a decrease in forced expiratory volume in 1 s of at least 20% of its post-saline value for a maximum methacholine dose of 2 mg. RESULTS: Both frequency and duration of physical activity were inversely related to BHR. The prevalence of BHR in subjects exercising or=4 times a week was 14.5%, 11.6% and 10.9%, respectively (p<0.001). The corresponding odds ratios were 1.00, 0.78 (95% CI 0.62 to 0.99) and 0.69 (95% CI 0.50 to 0.94) after controlling for potential confounding factors. The frequency of BHR in subjects exercising <1 h, 1-3 h and >or=4 h a week was 15.9%, 10.9% and 10.7%, respectively (p<0.001). The corresponding adjusted odds ratios were 1.00, 0.70 (95% CI 0.57 to 0.87) and 0.67 (95% CI 0.50 to 0.90). Physical activity was associated with BHR in all studied subgroups. CONCLUSIONS: These results suggest that BHR is strongly and independently associated with decreased physical activity. Further studies are needed to determine the mechanisms underlying this association.

Incidence of chronic obstructive pulmonary disease in a cohort of young adults according to the presence of chronic cough and phlegm.

RATIONALE: The few prospective studies aimed at assessing the incidence of chronic obstructive pulmonary disease (COPD) in relation to the presence of chronic cough/phlegm have produced contrasting results. OBJECTIVES: To assess the incidence of COPD in a cohort of young adults and to test whether chronic cough/phlegm and dyspnea are independent predictors of COPD. METHODS: An international cohort of 5,002 subjects without asthma (ages 20-44 yr) with normal lung function (FEV(1)/FVC ratio >/= 70%) from 12 countries was followed from 1991-2002 in the frame of the European Community Respiratory Health Survey II. Incident cases of COPD were those who had an FEV(1)/FVC ratio less than 70% at the end of the follow-up, but did not report having had a doctor diagnose asthma during the follow-up. MAIN RESULTS: The incidence rate of COPD was 2.8 cases/1,000/yr (95% confidence interval [CI], 2.3-3.3). Chronic cough/phlegm was an independent and statistically significant predictor of COPD (incidence rate ratio [IRR], 1.85; 95% CI, 1.17-2.93) after adjusting for smoking habits and other potential confounders, whereas dyspnea was not associated with the disease (IRR = 0.98; 95% CI, 0.64-1.50). Subjects who reported chronic cough/phlegm both at baseline and at the follow-up had a nearly threefold-increased risk of developing COPD with respect to asymptomatic subjects (IRR = 2.88; 95% CI, 1.44-5.79). CONCLUSIONS: The incidence of COPD is substantial even in young adults. The presence of chronic cough/phlegm identifies a subgroup of subjects with a high risk of developing COPD, independently of smoking habits.

Obesity and asthma.

There is a large literature on the possible association between obesity and asthma or asthma-like symptoms. However, no previous review has been confined to studies in children and adolescents. Studies vary in definitions of overweight or obesity and in whether outcomes were parent-reported symptoms or doctor-diagnosed asthma; there is no consistency in the findings. Three studies provide evidence for a greater incidence of diagnosed asthma in those obese at baseline compared to those not obese. The evidence for a stronger association in girls than in boys is weak. No study in a Western society has found objective evidence for the association, and results might be due to increased reporting of symptoms in obese children or to diagnostic bias. Intervention studies to prevent or reduce obesity could provide data to support or refute the association.

Cat allergen level: its determinants and relationship to specific IgE to cat across European centers.

BACKGROUND: Cat allergen level in settled house dust and its determinants in Europe are unknown. OBJECTIVE: The aim of this study is to quantify the level of cat allergens in mattress dust, to study its determinants, and to analyze the relationship with cat specific IgE on community level across European centers. METHODS: Trained field workers collected dust from approximately 3000 mattresses during home visits in 22 European Community Respiratory Health Survey II centers. Sieved dust extracts were assayed for cat allergen using a mAb ELISA assay. RESULTS: The overall geometric mean cat allergen was 0.94 microg/g, ranging from 0.12 microg/g in Huelva, Spain, to 3.76 microg/g in Antwerp, Belgium. Current cat owners' homes showed substantially higher levels than past cat owners' and never cat owners' homes (geometric mean and 95% CI, 61.4 microg/g [48.4-77.9] vs 1.37 microg/g [0.97-1.9] vs 0.29 microg/g [0.27-0.31]). Community prevalence of cat ownership was moderately correlated with cat allergen levels in noncat owners (r(s) = 0.50), but not for past or current cat owners. The multilevel model identified community prevalence of cat keeping as the only statistically significant determinant of mattress cat allergen levels for noncat owners. However, averaged cat allergen levels per center were not related to community prevalence of detectable specific IgE to cat. CONCLUSION: Not having a cat in the home is associated with substantially lower Fel d 1 concentration, but does not protect against high Fel d 1 exposure in communities where cat ownership is common. CLINICAL IMPLICATIONS: People (including patients with cat allergy) who do not own cats may be exposed to high levels of cat allergen in their home, particularly if they live in communities with high levels of cat ownership.

Distribution and determinants of house dust mite allergens in Europe: the European Community Respiratory Health Survey II.

BACKGROUND: Several studies in European homes have described allergen levels from the house dust mite species Dermatophagoides pteronyssinus and to a lesser extent Dermatophagoides farinae, but geographic comparisons of exposure levels and risk factors have been hampered by a lack of standardized methods. OBJECTIVE: To study the distribution and determinants of the major house dust mite allergens Der p 1 and Der f 1 in 10 European countries using a common protocol. METHODS: During home visits with 3580 participants of the European Community Respiratory Health Survey II from 22 study centers, mattress dust was sampled and analyzed for Der p 1, Der f 1, and Der 2 allergen. Information on housing characteristics was obtained by both observations and interview. RESULTS: Der 1 and Der 2 allergens were detectable (>/=0.1 mug/g) in 68% and 53% of the samples, respectively. Large differences in allergen levels between study centers were observed, and geographic patterns for Der p 1 and Der f 1 were different. Low winter temperatures reduced Der p 1 rather than Der f 1. Important risk factors for high allergen levels included an older mattress, a lower floor level of the bedroom, limited ventilation of the bedroom, and dampness for Der p 1 but not for Der f 1. CONCLUSION: There are large qualitative and quantitative differences of house dust mite allergen levels in Europe, which can partly be explained by geographic and housing characteristics. CLINICAL IMPLICATIONS: Mite allergen exposure may be reduced by replacing the mattress regularly and increasing ventilation of the bedroom, particularly in winter.

Fetal fibronectin test predicts delivery before 30 weeks of gestation in high risk women, but increases anxiety.

OBJECTIVE: To assess efficacy of cervico-vaginal fetal fibronectin as a predictor of spontaneous preterm birth in a high risk antenatal population, and to evaluate the psychological impact of fetal fibronectin testing. DESIGN: An observational study. SETTING: The antenatal clinic at a tertiary referral hospital. POPULATION: One hundred and forty-six pregnant women with known risk factors for spontaneous preterm birth. METHODS: Women designated as 'at risk' for preterm delivery by clinical history were screened for fetal fibronectin at 24 and again at 27 weeks of gestation. Anxiety levels were assessed by questionnaire and compared with anxiety levels of 206 low risk women also tested for fetal fibronectin. Fetal fibronectin results were disclosed to the woman and her clinician. MAIN OUTCOME MEASURES: Maternal anxiety and efficacy of the 24-week fetal fibronectin test to predict delivery before 30, 34 and 37 weeks of gestation. RESULTS: Maternal anxiety was higher pretesting in those at high risk compared with low risk women undergoing the test. Among the high risk women, anxiety was raised to clinically significant levels in those receiving a positive fetal fibronectin screening test result. In all women, 5%, 9% and 21% delivered <30, <34 or <37 weeks of gestation, respectively. Nine percent (n= 13) tested positive for fetal fibronectin at 24 weeks. Predictive power for fetal fibronectin (24 weeks) was greatest for delivery <30 weeks of gestation, with a likelihood ratio of 15 for a positive test (6/13 positive women delivered before 30 weeks). CONCLUSIONS: Fetal fibronectin was most efficient as a predictor of preterm spontaneous delivery <30 weeks of gestation, but was associated with high levels of anxiety.

An increase in bronchial responsiveness is associated with continuing or restarting smoking.

RATIONALE: Bronchial responsiveness (BHR) has been found to be associated with smoking, atopy, and lower lung function in cross-sectional studies, but there is little information on determinants of change in adults. OBJECTIVES: To analyze change in bronchial responsiveness in an international longitudinal community study. METHODS: The study was performed in 3,993 participants in the European Community Respiratory Health Survey who had bronchial responsiveness measured in 1991-1993, when aged 20 to 44 yr, and in 1998-2002. MEASUREMENTS: Bronchial responsiveness was assessed by methacholine challenge. Serum samples were tested for total IgE, and for specific IgE to four common allergens. Smoking information was obtained from detailed administered questionnaires. Change in bronchial responsiveness was analyzed by change in IgE sensitization, smoking, and lung function, with tests of interaction terms with age and sex. MAIN RESULTS: Continuing and restarting smokers had increasing bronchial responsiveness, approximately equivalent to a mean reduction in PD20 of 0.68 and 0.75 doubling doses, respectively, over 10 yr, in addition to a small increase explained by decline in FEV1. No other risk factor for change in bronchial responsiveness was identified. CONCLUSIONS: Smoking is a risk factor for increasing bronchial responsiveness over and above the effect of decreasing lung function. Neither baseline IgE sensitization nor change in sensitization was shown to be a risk factor for increasing BHR, the latter possibly due to little overall increase or decrease in sensitization.

Change in prevalence of IgE sensitization and mean total IgE with age and cohort.

BACKGROUND: Cross-sectional studies show that the prevalence of IgE sensitization is lower in older age groups than younger age groups. This could reflect either a decrease in sensitization with aging or a higher prevalence of sensitization in more recent birth cohorts. OBJECTIVE: To assess change in IgE sensitization and mean total IgE in young adults as they age. METHODS: Serum specific IgE to common allergens and total IgE were measured on 2 occasions about 9 years apart in 6371 young adults living in 28 centers, mainly in Western Europe, who took part in the European Community Respiratory Health Survey II. Outcomes were analyzed by using generalized estimating equations, and adjustments were made for differences between laboratory measures on the 2 occasions. RESULTS: Overall, there was no net change in the prevalence of sensitization to at least 1 of house dust mite, grass, or cat (net change per 10 years of follow-up, -0.1%; 95% CI, -1.7% to 1.5%), although there was a fall in mean total IgE (ratio of geometric mean total IgE, 0.86; 95% CI, 0.79 to 0.93). There was evidence that sensitization to at least 1 allergen was higher in more recent cohorts, and this was largely explained by a higher prevalence of sensitization to grass. CONCLUSION: The disease burden associated with IgE sensitization in adults, and particularly with IgE sensitization to grass, is likely to continue to increase for some time despite current evidence that the increase in allergy seen in children may have ceased.

Comparing and combining studies of bronchial responsiveness.

BACKGROUND: There is no standardised protocol for the measurement of bronchial responsiveness. Results from different studies are difficult to compare and combine. METHODS: Analyses are divided between those of a continuous outcome, which can be directly standardised as effect size, and those based on a binary outcome. A published method is used to convert an odds ratio to equivalent effect size. RESULTS: The use of effect size allows comparison between studies using a continuous outcome but different protocols, provided the relevant standard deviation is reported. Effect size from a continuous outcome and that derived from an odds ratio from an equivalent analysis gave similar results. CONCLUSIONS: Systematic reviews which include both continuous effect estimates and odds ratios can include both in one meta-analysis, provided relevant standard deviations are published for the former. Authors are encouraged to report these in all fields in which measurement protocols vary.

Obesity and asthma: evidence for and against a causal relation.

The evidence for an association between asthma and obesity in adults, and in children and adolescents, is reviewed. Few studies in adults measured height and weight, whereas the majority in children did. Evidence for the association is strong, but that for a gender interaction is weak. There is sufficient evidence to rule out asthma preceding obesity as an explanation, and that increased perception of symptoms in the obese, or a purely mechanical effect, is responsible. However, direct causality is unlikely, because in children the association is of recent origin, and trends in obesity do not explain the rising prevalence of asthma. Atopy was not associated with obesity in a large adult study. Potential explanations that require further investigation are that gastroesophageal reflux as a result of obesity causes asthma, that physical inactivity may promote both obesity and asthma, and that the diets of obese subjects may potentiate asthma.