The risk of asthma in relation to occupational exposures: a case-control study from a Swedish city.

The purpose of this study was to estimate the risk of adult asthma in relation to certain occupational exposures. The study was designed as a case-control study in Göteborg, including 321 subjects with asthma, born between 1926 and 1970. Controls (n=1,459) were randomly selected from the same area from registers of the 1986 population. Questionnaire information was collected in 1996, and included occupational exposures and smoking habits. Odds ratios were calculated for exposure before asthma onset, stratified by sex and age-class. The highest risks for asthma were associated with exposure to grain dust (odds ratio (OR) 4.2, 95% confidence interval (CI) 1.6-10.7) and flour dust (OR 2.8, 95% CI 1.1-7.2). Among males, significantly increased risks were observed after exposure to flour dust, welding fumes, man-made mineral fibres, and solvents. Among females, increased risks for asthma were associated with exposures to paper dust and textile dust. In logistic regression models controlling for age, smoking, sex and interacting exposures, increased risks were seen for welding fumes (OR 2.0, 95% CI 15-3.4), man-made mineral fibres (OR 2.6, 95% CI 1.4-7.3) and solvents (OR 2.2, 95% CI 1.2-3.2). The fraction of asthma attributed to occupational exposures after adjusting for sex, smoking and age was 11% (95% CI 7-14%). In conclusion, exposure to welding fumes, man-made mineral fibres, solvents and textile dust is associated with increased risk for asthma.

Specific IgE antibodies in the diagnosis of atopic disease. Clinical evaluation of a new in vitro test system, UniCAP, in six European allergy clinics.

A new immunoassay system utilizing new automatic instrumentation, new software for evaluation of data, and reagents updated for increased speed and accuracy was evaluated. Six clinical studies included 894 consecutive patients. Major symptoms were rhinoconjunctivitis, asthma, atopic dermatitis, and urticaria. The prevalence of inhalant allergy was 54-69%. Phadiatop, detecting atopic sensitization to common inhalant allergens, agreed with clinical diagnosis in 764/836 cases (91.4%). The clinical sensitivity and specificity were 93% and 89%, respectively. The clinical sensitivity and specificity of UniCAP specific IgE derived from 5170 comparisons with clinical diagnosis were 89% and 91%, respectively. Specific IgE measurements in UniCAP and in the Pharmacia CAP System agreed in 266/274 cases (97%). A comparison of the sensitivity and specificity of Pharmacia CAP System RAST in 1987 and with UniCAP specific IgE in 1995 showed equivalent performance without change of efficacy or degradation of IgE antibodies after 8 years. The systems were equivalent also in terms of measured values (r=0.96, slope=1.12), confirming the standardization of allergens and of assay calibration. UniCAP is an efficient laboratory system for routine diagnostic testing of allergy and a valuable tool for basic studies on allergens and antibodies.

Predictors of self-assessed work ability among subjects with recent-onset asthma.

The objective of the study was to find predictors for work disability among adults with recent-onset asthma. The study was performed in a group of 332 subjects with recent-onset asthma. The predictors were ascertained by structured interviews, pulmonary function measurements, methacholine challenge tests and skin prick tests. Asthma severity was classified into mild, moderate or severe, based on the minimum medication required to maintain asthma control. Work ability was based on self-assessment by inquiring about the subjects' present work ability, expressed in percent. The self-reported work ability decreased significantly with increasing number of days off work, indicating that self-reported work ability reflects the actual work ability. The majority (56%) of the subjects reported 100% working ability. Among women, but not among men, working ability was negatively correlated (rs = -0.33) with age. Among subjects with PC20 < 16 mg ml-1 work ability increased with increasing PC20. There was no relation between FEV1, FVC and working ability. Asthma severity and current respiratory symptoms at the work place showed a significant negative relation with work ability. In a logistic regression model, when controlling for age, gender, smoking and weekly working hours, decreased work ability was associated with asthma severity, respiratory symptoms at the workplace and PC20 < or = 4 mg ml-1. In conclusion, the work ability was assessed as normal in most asthmatic subjects. Significant predictors for decreased work ability were asthma severity, workplace-associated respiratory symptoms and bronchial hyperresponsiveness. The results indicate that work ability among asthmatics could be improved by reducing the workplace-associated symptoms, either by reducing the exposure to triggers or by improving the asthma therapy.

Prevalence of bronchial hyper-responsiveness in the southern, central and northern parts of Sweden.

Studies have suggested that there is a higher prevalence of asthma in northern Sweden than in southern Sweden. Bronchial hyper-responsiveness (BHR) has been shown to be associated with asthma. The aim of this study was to explore the prevalence of bronchical hyper-responsiveness in different parts of Sweden. As part of the European Community Respiratory Health Survey (ECRHS), interviews, skin prick tests, lung function tests and methacholine provocation tests of the airways were performed in 1448 randomly selected subjects in southern, central and northern Sweden. The Mefar dosimeter was used according to the ECRHS protocol. The responsiveness was calculated both as the PD20 and as the dose response slope (DRS). BHR was defined as a PD20 of < or = 1.6 mg. Atopy was defined as at least one skin prick test of > or = 3 mm. The prevalence of BHR was 12.7%, 10.6% in men and 15.0% in women. No difference in prevalence was found between the three different regions of Sweden. The prevalence of BHR was higher in women than in men and higher in smokers than in non-smokers. Using multiple logistic regression, with BHR as the dependent variable, atopy, being female, having a low FEV1 (% predicted) and smoking (both own and passive) increased the odds of having BHR, while age and the region of Sweden did not influence BHR. Defining BHR as a PD20 of < or = 1.0 mg or a PD20 of < or = 2.0 mg did not change this. Multiple regression using log DRS as the dependent variable produced the same result. Both BHR and increasing DRS were associated with self-reported wheezing, attacks of shortness of breath during the daytime at rest or after strenuous activity, being awakened by a feeling of tightness in the chest or an attack of shortness of breath. In subjects without self-reported asthma, BHR was associated with self-reported wheezing and attacks of shortness of breath after strenuous activity. In conclusion, we found that the prevalence of BHR in the three investigated areas was 12.7%. We found a trend towards a higher prevalence of BHR in the most northerly of the study areas, but the difference between the areas was not statistically significant. BHR and DRS were associated with atopy, smoking, female sex and FEV1 (% predicted). The reporting of symptoms from the airways was associated with the degree of bronchical responsiveness.

Skin prick tests and specific IgE in adults from three different areas of Sweden.

The aims of this part of the European Respiratory Health Survey were to estimate the prevalence of atopic sensitization to inhalant allergens among adults in three different areas of Sweden and to investigate the association between sensitization and certain risk factors. Randomly selected subjects aged 20-46 years from Göteborg, Uppsala, and Västerbotten were investigated with the skin prick test (SPT), analyses for specific IgE antibodies in serum (specific IgE) and total serum immunoglobulin E (total IgE), and a questionnaire. SPT was performed in 1572 subjects and analyses of specific IgE in 1470. One or more positive SPT were found in 35.6% and one or more positive specific IgE in 31.7%-approximately the same values in all three areas. Birch, grass, cat, and dog were the most frequent sensitizing agents and occurred at similar prevalences, i.e., around 15%, in all areas. The SPT to mite was positive in 14.1% in Göteborg, 7.4% in Uppsala, and 7.9% in Västerbotten. A positive SPT to pellitory of the wall (Parietaria), not described previously in Sweden, was found in 3.4% in Göteborg. Living in Göteborg was independently associated with a higher risk of a positive SPT to mite and Parietaria. Heredity, male sex, and low age were independently associated with atopy. Birth in the Scandinavian countries was independently associated with sensitization to cat, whereas birth in other countries was associated with sensitization to mite. The overall prevalence of atopy was similar in the three Swedish areas, but the sensitizing allergens varied. There is an indication that sensitization is increasing in the population, as low age was associated with sensitization. Sensitization to cat, but not to mite, appears to be particularly important in persons born in the Scandinavian countries.

Do patients with severe asthma run an increased risk from ischaemic heart disease?

BACKGROUND: Knowledge of the mortality outcome of asthma is limited to hospital case series follow-up. METHODS: To provide estimates of the mortality and cause of death in patients with asthma comparison of observed and expected number of deaths in patients with asthma for the observation period 1962-1986 was made. The study group was 262 patients aged 19-81 years with severe asthma. The group was a total sample of patients with a daily treatment of oral steroids more than one year, 1962-1963, from the city of Göteborg. RESULTS: Mortality from all causes was significantly raised among the asthmatics (179 deaths versus 83.5 expected, relative risk (RR) - 2.1, 95% confidence interval (CI) : 1.8-2.5). There was an excess mortality from ischaemic heart disease 58 versus 29.9 deaths (RR = 1.9, 95% CI : 1.4-2.4), especially among women (RR = 2.4, 95% CI : 1.7-2.2). However, there was also an increased mortality from asthma (39 versus 0.4 deaths) and chronic obstructive pulmonary disease (11 versus 0.5 deaths). CONCLUSIONS: These findings suggest that subjects with severe asthma, especially women, have an increased mortality from ischaemic heart disease. The results may reflect confounding, mainly smoking and physical inactivity. Other explanations may be side effects of the antiasthmatic drugs or an effect of longstanding airway obstruction.

Symptoms related to asthma and chronic bronchitis in three areas of Sweden.

Does the prevalence of respiratory symptoms differ between regions? As a part of the European Community Respiratory Health Survey, we present data from an international questionnaire on asthma symptoms occurring during a 12 month period, smoking and symptoms of chronic bronchitis. The questionnaire was mailed to 10,800 persons aged 20-44 yrs living in three regions of Sweden (Västerbotten, Uppsala and Göteborg) with different environmental characteristics. The total response rate was 86%. Wheezing was reported by 20.5%, and the combination of wheezing without a cold and wheezing with breathlessness by 7.4%. The use of asthma medication was reported by 5.3%. Long-term cough and/or morning cough together with problems with phlegm was reported by 12.8%; the prevalence being highest in the most polluted area (Göteborg). When using multivariate analysis, no significant difference in asthma-related symptoms was found between the centres. Women reported cough more frequently, but otherwise gender did not influence symptom prevalence. Our results indicate that bronchitis symptoms occur more frequently in Göteborg, the most polluted of the Swedish centres, but that the prevalence rates of asthma-related symptoms do not differ between these three regions.

Short-term and long-term variation in bronchial response to histamine in asthmatic patients.

Standardized histamine provocations were repeated during remission on 10 atopic bronchial asthmatics, at 14 days (short-term) and after more than 12 months (long-term). During the survey, anti-asthmatic medication was not regularly used. For constructing dose-response curves, four doses of histamine (concentration range 0.015-8 mg/ml) were given at each provocation. Two-fold increasing concentrations of histamine solutions were nebulized and inhaled by tidal volume breathing for 2 min at 5 min intervals. When repeated within 14 days, the coefficient of variation, calculated from maximum fall in FEV1, was 23%. The individual range for similar fall in FEV1 was estimated to 0-1 dose-step. When repeated after more than one year, the corresponding coefficient of variation was 26%, the individual range for similar fall in FEV1 being 0-2 dose-steps. It is concluded that the individual variation in bronchial response to standardized histamine challenge in patients with atopic asthma during remission is small during a period of one to two years.

Standardized allergen provocation test. Variation in bronchial response.

Standardized bronchial allergen provocation with the same individual allergen dose was performed 3-9 times in 20 symptomless adult asthmatic patients at intervals of 1 week or more during 1/2-22 months in order to study variations in bronchial response. The immediate type reaction was recorded by monitoring FEV1, FVC, PEFR and MEF50% for 30-40 min after provocation. FEV1 was highly significantly correlated to the other variables. The coefficient of variation corresponding to maximum decrease in FEV1 was 23%. All provocations were followed by a bronchial reaction within clinically acceptable limits. There was no indication of hypo- or hypersensitization. It is concluded that although many different factors influence the bronchial response, careful standardization of the provocation procedure leads to a moderate variation in bronchial response, making the allergen provocation test suitable for pathophysiological studies and clinical evaluation of anti-asthmatic drugs.

The effects of adrenal corticosteroids on regional adipocyte size in man.

In order to determine the effects of adrenal corticosteroids on regional adipose tissue cellularity groups of age-matched women subjected to long-term treatment with adrenal corticosteroids due to bronchial asthma or rheumatoids due to bronchial asthma or rheumatoid arthritis were compared with control of women. A small group of women suffering from Cushing's syndrome was also examined. Body composition, adipose cellularity in four major subcutaneous regions and metabolic variables were determined. The Cushing's syndrome patients weighed more than the other groups and seemed to have more fat cells while the patients with rheumatoid arthritis showed decreases in body cell mass, body fat and average fat cell size. These differences necessitated a body fat matching between patients and controls before analysis of regional depot fat differences. Body fat, average fat cell size and total fat cell number were similar in patients and controls. The Cushing's syndrome group was too small to allow this matching. All three groups exposed to increased levels of adrenal corticosteroids showed smaller fat cells in the gluteal region in comparison with controls, but no differences in fat cell size in the femoral, epigastrial or hypogastrial regions. This change also corresponded to a diminution of the thickness of subcutaneous plus skin layer in the gluteal region, measured with an ultrasonic technique. All the groups of patients had elevated fasting plasma insulin. The possibility was considered that the observed regional redistribution of fat is characteristic for adrenal corticosteroids.

Long term treatment of steroid dependent asthmatic patients with beclomethasone dipropionate.

In the efforts to avoid the side-effects of the peroral cortisone drugs in the treatment of asthma, trials have been made since the early fifties with the administration of steroids in aerosol form applied direct on the bronchial mucosa. Hydrocortisone as well as prednisolone and dexamethasone have been used with a documented effect on the obstruction. However, the drugs were found to be resorbed and thus resulted in suppression of adrenal function and appearance of Cushing syndrome and other well-known steroid side-effects (12). More recently, beclomethasone dipropionate -- a steroid with potent topical activity -- has been used as a pressurised aerosol. In 1972 Morrow Brown et al. (1) as well as Lal et al. (10) reported a good therapeutic effect with this drug and at the same time found evidence for the opinion that its systemic effect, if any, was insignificant. Less ositive results were reported by Choo-Kang et al. (4) and also by Herxheimer (8), who considered beclomethasone spray not to possess any advantages as compared with the earlier steroids. The purpose of the present study was to assess the clinical value of beclomethasone in the treatment of adult patients previously on long-term oral steroids.