Geodiversity data for Europe.

Geodiversity is an essential part of nature's diversity. However, geodiversity is insufficiently understood in terms of its spatial distribution and its relationship to biodiversity over large spatial extents. Here, we present European geodiversity data at resolutions of 1 km and 10 km. We assess terrestrial geodiversity quantitatively as a richness variable (georichness) using a commonly employed grid-based approach. The data incorporate aspects of geological, pedological, geomorphological and hydrological diversity, which are also available as separate richness variables. To evaluate the data, we correlated European georichness with empirically tested national georichness data from Finland, revealing a positive correlation at both 1 km (rp = 0.37, p < 0.001) and 10 km (rp = 0.59, p < 0.001) resolutions. We also demonstrate potential uses of the European data by correlating georichness with vascular plant species richness in two contrasting example areas: Finland and Switzerland. The positive correlations between georichness and species richness in Finland (rp = 0.34, p < 0.001) and Switzerland (rp = 0.26, p < 0.001) further support the use of our data in geodiversity-biodiversity research. Moreover, there is great potential beyond geodiversity-biodiversity questions, as the data can be exploited across different regions, ecosystems and scales. These geodiversity data provide an insight on abiotic diversity in Europe and establish a quantitative large-scale geodiversity assessment method applicable worldwide. This article is part of the Theo Murphy meeting issue 'Geodiversity for science and society'.

Effect of weight loss on inflammation in patients with mild obstructive sleep apnea.

BACKGROUND AND AIMS: Inflammation may be one mediating mechanism for cardiovascular diseases in obstructive sleep apnea (OSA). However, little is known about subclinical inflammation or the effect of lifestyle intervention on inflammation in early stages of OSA. The aim of this substudy of an existing randomized controlled trial, with post hoc analyses, was to determine the impact of lifestyle changes aimed at weight reduction on inflammatory biomarkers in overweight patients with mild OSA. METHODS AND RESULTS: Patients were randomized to supervised intensive lifestyle intervention group (N=28) or to control group (N=31), which received routine lifestyle advices. Circulating concentrations of pro- and anti-inflammatory mediators were measured before and after the 1-year intervention. The concentrations of two pro-inflammatory mediators, high-sensitivity C-reactive protein (hsCRP) and interleukin (IL)-6, decreased significantly in both groups. Although the changes in inflammatory biomarkers favored the supervised lifestyle intervention, the only significant reduction observed between the groups was for the anti-inflammatory IL-1 receptor antagonist (IL-1RA). The change in hsCRP was associated with apnea-hypopnea index, and improving night-time oxygen saturation was related to tumor necrosis factor alpha. IL-1RA and IL-6 were associated with insulin metabolism. CONCLUSION: Weight loss resulted in reductions in concentrations of some pro- and anti-inflammatory mediators in overweight patients with mild OSA, overall favoring the supervised lifestyle intervention. These findings suggest that more intensive treatment of obesity in OSA patients might be well-justified.

Hypertonic saline cough provocation test with salbutamol pre-treatment: evidence for sensorineural dysfunction in asthma.

BACKGROUND: Cough is one of the most common symptoms of asthma. However, studies using capsaicin, citric acid, or tartaric acid to document cough threshold have repeatedly failed to show statistically significant differences between asthmatic and healthy subjects. The studies using hypertonic aerosols as the cough stimulant have suggested an enhanced sensitivity in asthmatic subjects but the induced bronchoconstriction has made the interpretation of the results difficult. OBJECTIVE: To determine the cough sensitivity to hypertonicity in healthy subjects, patients with chronic cough, and patients with asthma in a setting where the induction of bronchoconstriction is prevented. METHODS: Nineteen healthy subjects, 21 non-asthmatic patients with chronic cough, and 26 asthmatic patients with chronic cough underwent an incremental hypertonic saline challenge including a pre-treatment with 0.4 mg of salbutamol. Spirometry was performed before the challenge, after salbutamol, and after the challenge. The patients with cough also underwent skin testing, histamine challenge, exhaled nitric oxide measurement, ambulatory peak flow monitoring, kept cough diary, and filled in the Leicester Cough Questionnaire. Eighteen patients repeated the saline challenge. RESULTS: The challenge did not induce bronchoconstriction in any group. The osmolality to provoke 15 cumulative coughs was significantly smaller in the asthmatic patients than in the healthy subjects (P<0.001) and in the cough patients without asthma (P=0.04). According to multivariate analysis among all the 47 patients with cough, female sex (P<0.001) and large spontaneous peak flow variation in the ambulatory recording (P=0.001) were associated with high sensitivity to saline. The saline challenge response was well repeatable (intraclass correlation coefficient 0.90). CONCLUSION: The findings of the present study are not affected by induced bronchoconstriction. Asthma or, more specifically, spontaneous, reversible airway obstruction is associated with an enhanced sensitivity to the cough-provoking effect of hypertonic saline. This suggests a pathological function of the sensorineural apparatus in this disorder.

Aspergillus fumigatus challenge increases cytokine levels in nasal lavage fluid.

Several studies have shown an association between exposure in moisture-damaged buildings and adverse health effects. There are several indicator microbes of moisture damage, but Aspergillus fumigatus is one of the best-documented molds provoking health problems in different occupational conditions. We assessed whether inhalation of a commercial A. fumigatus solution would affect cytokine levels (tumor necrosis factor [TNF]-alpha, interleukin [IL]-1beta, IL-4, IL-6, interferon [IFN]-gamma) in nasal lavage fluid (NAL) compared with that evoked by placebo challenge. Twenty-seven subjects were studied: 13 had occupational exposure in a moisture-damaged building, 4 were atopic, and 10 were considered as controls. In all the subjects, the IL-1beta levels were increased significantly both at 6 (p = 0.013) and 24 h (p = .005) after the A. fumigatus challenge compared to placebo. In subjects with previous occupational exposure in a moisture-damaged building, IL-4 concentrations were increased significantly both at 6 (p =.046) and 24 h (p =.008) after the A. fumigatus challenge compared with placebo. Furthermore, in the control group, TNF-alpha levels were significantly increased at 6 h after the A. fumigatus challenge compared to placebo (p = .028). Thus, these data show a link between markers of inflammation in NAL and experimental A. fumigatus challenge.

The effects of Aspergillus fumigatus challenge on exhaled and nasal NO levels.

Several studies have previously shown that exposure to indoor air microbes from moisture-damaged buildings can cause adverse health effects. Aspergillus fumigatus is one of the best-documented moulds causing health problems to those exposed. In this study, inhalation of a commercial A. fumigatus solution was assessed, to establish if it would have effects on fractional exhaled (FeNO) and nasal (FnNO) nitric oxide levels and on lung function. The results were compared with placebo challenge. A total of 28 subjects were divided into three study groups: group 1 had been exposed to occupational mould; group 2 consisted of atopic subjects; and group 3 was a control group. Some 3 h after A. fumigatus challenge, there was a considerable increase in FeNO, and a significant difference was observed between the A. fumigatus and placebo inhalations. The difference was seen in all study groups. No such differences were found in the levels of FnNO or nitrite in nasal lavage fluid. Subjects reported significantly more frequent respiratory tract symptoms after the A. fumigatus inhalation compared with placebo challenge. In conclusion, it was shown here that inhalation challenge of Aspergillus fumigatus elevated fractional exhaled nitric oxide levels. An increase in fractional exhaled nitric oxide may serve as an indicator of respiratory inflammation of acute mould exposure.

The remediation of mold damaged school--a three-year follow-up study on teachers' health.

The health effects in teachers of a mold-damaged school before and during an extensive remediation process were assessed. Health data were collected with self-administered questionnaires from teachers (n=31) working in a moisture and mold damaged school and from the reference group of teachers (n=13) working in a non-damaged school. The questionnaire study was repeated three times. Spirometry was measured in 33 individuals in the spring 1997 and repeated in the spring 1999 and 2000. In the damaged school, a cluster of eight asthma cases was identified, the prevalence of asthma being 26%. Before the remediation, the number of sinusitis episodes was higher (p=0.040) and the mean duration of sick leaves longer (p=0.015) among the study group than in the reference group. A higher prevalence of hoarseness and perceived poor quality of indoor air were reported. During the follow-up, no new asthma cases appeared. After the remediation, bronchitis, conjunctivitis, symptoms of allergic rhinitis and the sum of respiratory infection episodes decreased significantly. Some of the asthmatics had low values in the spirometry but no changes in the lung function were observed at the group level. The remediation of the mold damage had beneficial effects on teachers' health.

Nitric oxide alone is an insufficient biomarker of exposure to microbes in a moisture-damaged building.

Several epidemiological studies have revealed a large variety of adverse health effects related to exposure to microbes in moisture damaged buildings. Recently some evidence has been reported for a biochemical linkage between microbial exposure and the respiratory symptoms suffered by the occupants. The objective of the current study was to evaluate the value of nitric oxide (NO) measurements in determining the inflammatory status of airways in inhabitants of problem buildings. NO was measured by a chemiluminescence analyzer from the exhaled air. In addition, NO was determined as its metabolite nitrite from nasal lavage (NL) and induced sputum (IS) samples and also via the expression of inducible nitric oxide synthase (iNOS) in the cells. Occupants of moisture-damaged and reference schools were studied. The sampling was performed at the end of the spring term, at the end of the summer vacation, during the winter term, and after a 1-wk winter holiday. No statistically significant differences in NO levels were detected between the studied groups or between exposure and vacation periods. iNOS was not detected from IS or NL samples of the exposed occupants. These results suggest that NO measurements alone are not sufficient to quantify airway inflammation when evaluating subjects exposed to microbes present in moisture-damaged buildings.

Threshold levels of purified natural Bos d 2 for inducing bronchial airway response in asthmatic patients.

BACKGROUND: Provocation tests are invaluable in establishing threshold levels and a causal relationship between atopic asthma and a certain allergen source, especially in relation to work-associated exposure. Purified major allergens open possibilities for a more accurate assessment of sensitization. OBJECTIVE: To determine the threshold dose of purified major bovine dander allergen Bos d 2 in bronchial provocation in comparison with the standard allergen and a set of other parameters of allergy. METHOD: Nine consecutive patients referred to hospital for confirming the bovine origin of their occupational asthma were subjected to bronchial provocation tests with purified natural Bos d 2 and a standard bovine dander allergen. Additional tests included bronchial histamine challenge, measurements of total IgE, specific IgE antibody determinations and skin prick tests (SPT) with both allergens. RESULTS: In the provocation tests with Bos d 2, a 15% decrease in the forced expiratory volume in 1 s (FEV1) and/or peak expiratory flow (PEF) values in eight out of nine patients confirmed the predominant role of Bos d 2 in the sensitization. The threshold dose of Bos d 2 varied from 0.1 microg to > 100 microg (median +/- median absolute deviation = 4.5 +/- 3.9 microg). A positive SPT was induced by a median dose of 13.9 +/- 9.8 microg of Bos d 2. Bronchial response to histamine and IgE antibodies against Bos d 2 showed the highest correlations to the provocations results. CONCLUSIONS: The efficacy of Bos d 2 in bronchial provocation in patients with occupational cattle-associated asthma was confirmed and the range of the threshold level was determined. There were individual variations, but the response in provocation remains the reference method for identification of the cause of occupational atopic asthma. SPT and the measurement of specific IgE antibodies, preferably with purified or recombinant major allergens, increase the accuracy of the diagnosis.

Comparison of inflammatory elements in nasal lavage and induced sputum following occupational exposure to moldy-building microbes.

Inflammatory processes in the nasal air passages may reflect corresponding processes in the lower airways due to the similarities in histology of nasal mucosa and bronchi. The objective of the current study was to determine whether the levels of inflammatory markers in nasal lavage fluid could be used as predictors of lower respiratory tract inflammation after exposure to microbes in indoor air of moisture-damaged buildings. Differential cell count, immunochemically measured concentrations of proinflammatory cytokines (Interleukins [IL] IL-1, IL-4, IL-6, and tumor necrosis factor alpha [TNFalpha]) and nitric oxide (NO), assessed as nitrite, were analyzed from nasal lavage (NL) and induced sputum (IS) samples of the occupants (n = 60) working in moisture-damaged and reference school buildings. The measurements of inflammation markers in NL and IS sample pairs, collected on the same day, were compared. Although the levels of NO (p =.026) and IL-4 (p =.014) in NL predicted their levels in IS in a statistically significant manner, their predictive values (6.9% and 7.8%, respectively) were low. There was no significant correlation between the concentrations of the studied proinflammatory cytokines or differential cell counts in NL and IS samples. Our results indicate that measurement of inflammatory mediators in NL is not per se a reliable method to evaluate the inflammatory status of the lower airways after exposure to indoor air pollutants of moisture damaged building. It is possible that NL is a more sensitive indicator of direct exposure to different irritants in inhaled air than is IS. This may be a reflection of the role of nasal mucosa as the primary physicochemical barrier to inhaled air.

Safety, tolerability and acceptability of two dry powder inhalers in the administration of budesonide in steroid-treated asthmatic patients.

The purpose of this randomized, double-blind parallel group study was to compare the safety, tolerability and acceptability of Easyhaler and Turbuhaler dry powder inhalers for the delivery of budesonide 800 microg day(-1) in adult asthmatic patients who had already been treated with inhaled corticosteroids for at least 6 months prior to the study Additionally the efficacy of the products was evaluated. The main objective was to evaluate the systemic safety of budesonide inhaled from Easyhaler (Giona Easyhaler, Orion Pharma, Finland) as determined by serum and urine cortisol measurements. The secondary objective was to compare the tolerability acceptability and efficacy of the two devices in the administration of budesonide. After a 2-week run-in period (baseline), patients were randomized on a 2:1 basis to receive budesonide from Easyhaler (n = 103) or from Turbuhaler (Pulmicort Turbuhaler, AstraZeneca, Sweden) (n = 58) 200 g dose(-1), two inhalations twice daily for 12 weeks. There was no statistically significant change in morning serum cortisol values from baseline to the end of treatment in either group. Urine free cortisol and urine cortisol/ creatinine ratio increased from baseline in both groups. There were no significant differences between the groups in terms of morning serum cortisol, urine cortisol, adverse events or efficacy variables, but Easyhaler was generally considered more acceptable to the patients. In conclusion, at 800 microg day(-1), Giona Easyhaler is as safe and efficacious as Pulmicort Turbuhaler in adult asthmatic patients previously treated with corticosteroids, but more acceptable to patients.

Inflammatory mediators in nasal lavage, induced sputum and serum of employees with rheumatic and respiratory disorders.

Exposure to microbes present in mould-damaged buildings has been linked to increased frequency of various inflammatory diseases. The current study examined differences in inflammatory mediators in nasal lavage (NAL), induced sputum (IS) and serum of occupants with rheumatic or respiratory disorders and their controls, all working in the same moisture-damaged building. Exhaled nitric oxide (NO) measurements, lung function tests, skin-prick tests and health data collection by questionnaire were performed. Concentrations of NO, interleukin (IL)-1, IL-4, IL-6 and tumour necrosis factor-alpha in NAL, IS and serum (excluding NO and IL-1) of the subjects were measured during an occupational exposure period and the vacation period without such exposure. The concentrations of IL-4 in NAL fluid were significantly higher among all occupants during the working period (geometric mean 8.5 microg x mL(-1), range 0-206.5 microg x mL(-1)), as compared to that during vacation (0.4 microng x mL(-1) range 0-3.7 pg x mL(-1)) (p = 0.008). Absence from the work environment also significantly diminished reporting of symptoms. IL-4 levels in the serum of case subjects were significantly higher than in controls. Moreover, employees with respiratory symptoms had markedly higher exhaled NO values than their controls (p = 0.028). In summary, these data suggest that mediators in nasal lavage samples reflect the occupational exposure to moulds, whereas possible indicators of existing disorders are detectable in serum.

Smoking cessation, decline in pulmonary function and total mortality: a 30 year follow up study among the Finnish cohorts of the Seven Countries Study.

BACKGROUND: Permanent smoking cessation reduces loss of pulmonary function. Less is known in the long term about individuals who give up smoking temporarily or quitters with lower initial pulmonary function. Little is known also about the relationship between decline in pulmonary function and mortality. We examined these aspects and the association between smoking, decline in pulmonary function, and mortality. METHODS: Two middle aged male Finnish cohorts of the Seven Countries Study and their re-examinations on five occasions during a 30 year period of follow up were analysed. RESULTS: During the first 15 years (n=1007) adjusted decline in forced expiratory volume in 0.75 seconds (FEV(0.75)) was 46.4 ml/year in never smokers, 49.3 ml/year in past smokers, 55.5 ml/year in permanent quitters, 55.5 ml/year in intermittent quitters, and 66.0 ml/year in continuous smokers (p<0.001 for trend). Quitters across the entire range of baseline FEV(0.75) had a slower decline in FEV(0.75) than continuous smokers. Among both continuing smokers and never smokers, non-survivors had a significantly (p<0.001) more rapid decline in FEV(0.75) than survivors. The adjusted relative hazard for total mortality was 1.73 (95% confidence interval (CI) 1.41 to 2.11) and 1.24 (95% CI 1.02 to 1.52) in the lowest and middle tertiles of decline in FEV(0.75). Never smokers, past smokers, and quitters had significantly lower total mortality than continuous smokers, partly because of their slower decline in FEV(0.75). CONCLUSION: These results highlight the positive effect of smoking cessation, even intermittent cessation, on decline in pulmonary function. Accelerated decline in pulmonary function was found to be a risk factor for total mortality. The beneficial effect of smoking cessation on mortality may partly be mediated through a reduced decline in pulmonary function.

Microbial etiology of community-acquired pneumonia in the adult population of 4 municipalities in eastern Finland.

To determine the etiology of community-acquired pneumonia in the adult population of a defined area, specific antibody responses in paired serum samples, levels of circulating pneumococcal immune complexes in serum samples, and pneumococcal antigen in urine were measured. Samples (304 paired serum samples and 300 acute urine samples) were obtained from 345 patients > or =15 years old with community-acquired, radiologically confirmed pneumonia, which comprised all cases in the population of 4 municipalities in eastern Finland during 1 year. Specific infecting organisms were identified in 183 patients (including 49 with mixed infection), as follows: Streptococcus pneumoniae, 125 patients; Haemophilus influenzae, 12; Moraxella catarrhalis, 8; chlamydiae, 37 (of which, Chlamydia pneumoniae, 30); Mycoplasma pneumoniae, 30; and virus species, 27. The proportion of patients with pneumococcal infections increased and of those with Mycoplasma infections decreased with age, but for each age group, the etiologic profile was similar among inpatients and among outpatients. S. pneumoniae was the most important etiologic agent. The annual incidence of pneumococcal pneumonia per 1000 inhabitants aged > or =60 years was 8.0.

Long-term economic evaluation of intensive patient education during the first treatment year in newly diagnosed adult asthma.

The cost-effectiveness of intensive patient education of guided asthma self-management given during the first treatment year was evaluated after 5 years of follow-up. Consecutive, newly-diagnosed asthmatics (n = 162, age 18-76 years) were randomized for intensive (80 patients) vs. conventional patient education. Effectiveness was evaluated in terms of lung functions, airway hyperresponsiveness (PD15), and quality of life as measured by the generic 15D and disease-specific St. George's Respiratory Questionnaire (SGRQ). Total treatment costs were also estimated. All patients had anti-inflammatory treatment from the beginning. Sixty-four intervention group (IG) patients and 70 control group (CG) patients were evaluated after 5 years. Forced expiratory volume in 1 sec (FEV1) improved only in the IG, and only during the first treatment year. However, PD15 improved throughout the follow-up. The unscheduled healthcare costs were significantly higher in the CG than in the IG (P = 0.04) and the relative risk for sickness days due to asthma was lower in the IG than in the CG, odds ratio 0.33 (95% CI 0.28; 0.40). However, because there was no significant difference between the groups in any outcome variable or in total costs at 5 years, the incremental cost-effectiveness ratio could not be calculated. The first year intervention had only a short-term beneficial treatment effect, which the CG could catch up during the two last follow-up years, except in FEV1. The peak expiratory flow (PEF)-based self-management had no advantage over the symptom-based self-management. However, the intervention had a consistent tendency of being less costly in the long-run. It is possible to conclude tentatively that regular effective medical treatment and control visits during the first treatment year is at least as important for the long-term treatment result as intensive patient education.

Changes in pro-inflammatory cytokines in association with exposure to moisture-damaged building microbes.

Several epidemiological studies have described an association between adverse health effects and exposure to mould and microbes present in the indoor air of moisture-damaged buildings. However, the biochemical linkage between microbial exposure and the large variety of reported respiratory symptoms is poorly understood. In the present study, the authors compared the respiratory symptoms, the production of inflammatory mediators interleukin (IL)-1, IL-4, IL-6, tumour necrosis factor-alpha (TNF-alpha) and cell count in nasal lavage fluid and induced sputum samples of subjects working in moisture-damaged and control school buildings. The sampling was performed and the questionnaires were completed at the end of the spring term, at the end of the summer vacation (2.5 months), during the winter term and after a 1-week winter holiday. The authors found a significant elevation of IL-1, TNF-alpha and IL-6 in nasal lavage fluid and IL-6 in induced sputum during the spring term in the subjects from the moisture-damaged school building compared to the subjects from the control building. The exposed workers reported sore throat, phlegm, eye irritation, rhinitis, nasal obstruction and cough in parallel with these findings. The present data suggests an association between microbial exposure, and symptoms as well as changes in pro-inflammatory mediators detected from both the upper and lower airways.

Reproducibility of measurements of exhaled NO, and cell count and cytokine concentrations in induced sputum.

Sputum induction is a noninvasive, well-tolerated method for studying airway inflammation. When induction with hypertonic saline is repeated at short time-intervals (<24 h), the cell profile of sputum has not been reproducible. To determine the proper interval between sampling cell profiles and cytokine contents of sputum samples that had been induced 48 h apart, were compared. In addition, the inducible nitric oxide synthase (iNOS) expression of sputum cells was compared to the levels of exhaled nitric oxide (NO). Sputum induction and measurement of exhaled NO was performed in 31 healthy nonatopic volunteers. Cell differentials were counted. Concentrations of interleukin (IL)-4, IL-6, tumour necrosis factor (TNF)alpha, eosinophil cationic protein (ECP) were measured in sputum supernatant, and iNOS was determined. Reproducibility of cell counts was high (r=0.836 total cells, r=0.762 neutrophils, r=0.966 eosinophils, r=0.742 macrophages). IL-4 (r=0.398), IL-6 (r=0.566), TNFalpha (r=0.658) and ECP (r=0.501) were also less reproducible in healthy volunteers. Consistent with the low levels of NO in the exhaled air (18.5+/-2.6 ppb and 19.3+/-2.8 parts per billion (ppb) on the two study days, r=0.976, p=0.0000), expression of iNOS was not detected. In conclusion, in healthy subjects, induced sputum cell counts are reproducible. Even though the success rate in nonatopic populations is relatively low, sputum induction appears to be a valid method for detecting inflammatory changes within the airways, when being performed 48 h apart.

Pulmonary function, smoking cessation and 30 year mortality in middle aged Finnish men.

BACKGROUND: Although it is well known that impaired pulmonary function is a strong predictor of mortality and that smoking decreases pulmonary function, little is known about the long term effect of smoking cessation on mortality at different levels of pulmonary function. We have studied the impact of smoking cessation on mortality over the entire range of baseline pulmonary function. METHODS: The study subjects consisted of men aged 40-59 at entry who were the Finnish participants in the Seven Countries Study during 1959-89. RESULTS: In all the participants (n = 1582) impaired forced expiratory volume in 0.75 seconds (FEV(0.75)) was significantly associated with increased all cause mortality. When those who gave up smoking during the follow up period were compared with continuous smokers (n = 860) all cause mortality was found to be decreased among those who quit. The relative adjusted hazard (HR) was 0.71 (95% confidence interval 0.50 to 1.00). The median survival time in those who stopped smoking compared with those who continued to smoke from 1969 onwards was 7.65, 7.59, and 6.30 years longer in the lowest, middle and highest tertiles of adjusted FEV(0.75) distribution, respectively. In those who gave up smoking, mortality from cardiovascular causes was significantly lower (HR 0.60 (95% CI 0.37 to 0.98)). CONCLUSIONS: These findings suggest that smokers across the entire range of pulmonary function may increase their expectation of lifespan by giving up smoking.

Comparison of high and low dose of the inhaled steroid, budesonide, as an initial treatment in newly detected asthma.

The importance of early initiation of inhaled steroids even in mild asthma has been documented in several studies. It is not, however, clear whether the treatment should be started with a high or a low dose of the inhaled steroid. We have compared the effects of high and low dose inhaled steroid, budesonide, in patients with newly detected asthma. We studied 101 adult patients with newly detected bronchial asthma who were without inhaled steroid or any regular pharmacological treatment for their asthma. The patients were randomly allocated to two treatment groups: one to receive 800 microg inhaled budesonide per day and the other to receive 200 microg inhaled budesonide per day. The drugs were given with a Turbuhaler dry powder inhaler. During the 3-month treatment period, no significant differences between the treatment groups were noted in morning or evening PEF values, in spirometric parameters, in asthmatic symptoms or in the use of rescue beta2-agonists. The decrease in bronchial hyperresponsiveness was, however, more marked in the high dose budesonide group, reaching a borderline significance (P=0.10 high vs. low dose budesonide). In addition, in serum markers of asthmatic inflammation significant differences were shown between the treatment groups. The decrease in the number of blood eosinophils during the treatment was more marked in the high dose budesonide group (P=0.02; high vs. low dose budesonide). In serum ECP no change was observed in the low dose budesonide group, but a marked decrease in the high-dose budesonide group (P=0.008; high vs. low dose budesonide). The change was even more marked with regard to serum EPX (P=0.005; high vs. low dose budesonide). Our results support the view that the treatment of newly detected asthma should be started with a high dose of inhaled steroid. The low dose may not be enough to suppress asthmatic inflammation despite good clinical primary response.

Equivalence of two steroid-containing inhalers: easyhaler multidose powder inhaler compared with conventional aerosol with large-volume spacer.

BACKGROUND AND OBJECTIVES: An equivalence study was conducted in which the efficacy and safety of a daily dose of 800 microgram of beclomethasone diproprionate administered via a multidose powder inhaler, Easyhaler, and via a metered-dose inhaler (MDI) with a large-volume spacer were compared in adult, newly diagnosed, steroid-naive asthmatic patients. Acceptability of the medications was also compared. METHODS: One hundred and forty-four patients were recruited into the double-blind, double-dummy, randomised, parallel-group multicentre study. The study treatment period was 8 weeks. It was preceded by a 2-week run-in period. Morning and evening peak expiratory flow (PEF), numbers of inhalations of a sympathomimetic and asthma symptoms were recorded daily. Spirometry and histamine challenge were performed, and health-related quality of life and morning serum cortisol levels measured during control visits. RESULTS: Criteria indicating treatment equivalence were met. The mean of the primary outcome variable, morning PEF, increased significantly, from 426 to 461 litres/min in the Easyhaler group and from 436 to 467 litres/min in the MDI+spacer group. Similar improvements between groups were also seen in relation to all secondary variables. Changes in serum cortisol levels were minor. In 6 out of 10 questions about device acceptability, the majority of patients rated Easyhaler as better than the MDI+spacer combination. CONCLUSION: It was concluded that the devices tested were equivalent in terms of efficacy and safety.

IgG antibodies, chronic bronchitis, and pulmonary function values in farmer's lung patients and matched controls.

We measured IgG antibody levels against eight different microbes in farmer's lung (FL) patients an average of 14 years after the first diagnosed episode of FL and in matched controls. The study population consisted of 87 FL patients and 81 control farmers, matched by age, sex, and smoking habits. Clinical studies included the measurement of IgG antibody levels against Absidia corymbifera, Aspergillus umbrosus, A. fumigatus, Humicola grisea, Saccharopolyspora rectivirgula, Penicillium brevicompactum, Rhodotorula glutinis, and Thermoactinomyces vulgaris, in addition to spirometry, pulmonary diffusing capacity (DL(CO)), and the evaluation of chronic bronchitis. Median IgG antibody levels were two or more times higher in FL patients than control farmers against Ab. corymbifera, S. rectivirgula, and T. vulgaris (P<0.001). Against A. fumigatus, H. grisea, and R. glutinis, FL patients also had significantly higher antibody levels. FL patients often had positive antibody titers against several microbes, whereas control farmers usually had a positive titer against one or two microbes. A positive association between IgG antibody levels and chronic bronchitis and DL(CO) was observed in FL patients, but not in control farmers. It is suggested that the high antibody levels noted in FL patients were due not only to high exposure but also to individual sensitivity to environmental microbes.