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.

Mortality due to farmer's lung in Finland.

Fatal cases of farmer's lung (FL) are rare. We found, based on death certificates, 13 cases of FL with a fatal outcome in Finland between 1980 and 1990. Compared with incidence data from the years 1980 to 1982, the mortality was estimated as 0.7 percent. On average, death occurred 8 years after the diagnosis of FL. One patient died acutely after a heavy mold exposure. The other patients had chronic disease. Among them the immediate cause of death was pneumonia in seven patients, respiratory insufficiency in four, and pneumothorax in one patient. The majority of these patients with a fatal outcome had suffered from symptoms of FL for more than 1 year before the diagnosis was established and fibrotic changes were already visible in the chest radiograph at the time of the diagnosis.

Effect of cold air on exercise capacity in COPD: increase or decrease?

STUDY OBJECTIVE: To clarify the effect of cold air on exercise capacity in COPD. DESIGN: Cycle ergometer tests under different environmental conditions. SETTING: Pulmonary function laboratory and an environmental chamber at a university hospital. PARTICIPANTS: Eighteen patients with stable COPD; 14 completed the study. INTERVENTIONS: A preliminary cycle ergometer test followed by two incremental, symptom-limited cycle ergometer tests, one at 24 degrees C and the other at -20 degrees C. MEASUREMENTS: On the first study day: arterial blood gas analysis, 12 to 15 s maximal voluntary ventilation, maximal expiratory flow-volume curves before and 1 h after inhalation of 80 microg of ipratropium bromide, and diffusion capacity of the lung. During the exercise challenges: spirometric indices, minute ventilation (VE), oxygen consumption (VO2), carbon dioxide production (VCO2), facial skin temperature, and heart rate. The feeling of dyspnea was assessed with a visual analogue scale. RESULTS: The maximal work load was 87.5+/-7.3 W at -20 degrees C compared with 96.4+/-6.9 W at 24 degrees C (p<0.05). Accordingly, the exercise duration was shorter in the cold. Exercise dyspnea was more severe in the cold at equal work loads. The shortening of exercise duration induced by cold air correlated with the enhancement of exercise dyspnea. Furthermore, cold air cooled the facial skin and induced immediate bronchoconstriction. VE, VO2, VCO2, and heart rate did not differ between the warm and cold challenges. CONCLUSIONS: Cold air decreases exercise capacity in COPD, probably by increasing exercise dyspnea.

Effect of whole-body exposure to cold and wind on lung function in asthmatic patients.

To assess the effect of subfreezing temperature and wind on lung function in asthmatic patients, an exposure to subfreezing temperature at rest, a moderate exercise challenge at subfreezing temperature, and a similar exercise challenge at room temperature were performed in 19 stable asthmatic subjects in an environmental chamber with an artificial wind. The mean maximal falls in FEV1 were 5.3, 11.7, and 4.8 percent, respectively. The two challenges at subfreezing temperature caused statistically significant changes in FEV1, but the exercise challenge at room temperature had no effect. A large variation in the sensitivity to cold was found. The time courses of the responses varied between the challenges, suggesting at least partially different mechanisms. The results indicate that even moderate exercise can cause severe bronchoconstriction in certain stable asthmatic subjects at climatic conditions similar to the Scandinavian winter. The importance of reflex mechanisms causing bronchoconstriction in physiologic conditions is discussed.

Hypersensitivity pneumonitis due to native birds in a bird ringer.

A bird fancier who had only been exposed to native birds, mostly owls, developed a sever hypersensitivity pneumonitis with a very insidious onset.

Familial aggregation of IgG antibody response to antigens associated with farmer's lung.

The levels of circulating IgG antibodies to Aspergillus umbrosus, Aspergillus fumigatus, Thermoactinomyces vulgaris, and Micropolyspora faeni were determined by enzyme immunoassay in 197 subjects selected for a study of farmer's lung (FL). The material consisted of five study groups: 37 patients with clinically confirmed FL, 31 spouses of the patients, 44 immediate relatives of the patients, 35 immediate relatives of the patients' spouses, and 50 unrelated people who were spouses of the 79 people in both relative groups. The mean titres of IgG antibodies to all four microbes were highest in patients with clinically established FL. In the other groups the mean titre of Aspergillus umbrosus, a mould found much more frequently in Finnish farm environments than other moulds under study, was significantly higher (p less than 0.01) in the relatives of FL patients than in other people. This finding remained irrespective of whether the subjects had suffered from FL symptoms or not or whether they worked or lived on the same farm as the patient or on a different one. The difference in the mean titre was not due to the differences between the study groups in age, sex, smoking habits, atopic background, frequency of handling of plant materials, or time interval from the most recent handling of visibly mouldy hay. The results imply that genetic factors may be important in the IgG antibody response to microbial antigens associated with FL.

Comparison between oral procaterol and salbutamol in patients with bronchial asthma.

The efficacy of procaterol, a new beta 2-selective sympathomimetic drug, was compared with that of salbutamol and placebo in a double-dummy crossover study in 20 asthmatic patients. Procaterol (0.1 mg orally) was given twice daily and salbutamol (4 mg orally) 3-times a day. The study was made up of four consecutive 4-day treatment periods including two periods of plain placebo. A significant direct bronchodilating effect of both procaterol and salbutamol could be seen in PEF values, measured 4-times a day, compared with the effect of placebo (p less than 0.01 for both). Procaterol was slightly superior to salbutamol. The afternoon and evening PEF values during the procaterol period did not differ from the values during the placebo period. In symptom scores, there was significantly more tremor during the procaterol period than during the placebo period (p less than 0.01). Both procaterol and salbutamol produced more palpitation than placebo (p less than 0.05). The study shows that oral procaterol is a potent bronchodilator. The doses of procaterol and salbutamol were not equivalent. Procaterol with the dose used in the study was more potent. Despite this, the duration of the bronchodilator effect of procaterol on a twice daily dosage did not seem to be long enough in all patients.

One-year economic evaluation of intensive vs conventional patient education and supervision for self-management of new asthmatic patients.

The purpose was to compare the short-term cost-effectiveness of intensive vs conventional education and supervision for the self-management of mild asthmatic patients. Consecutive newly diagnosed asthmatic patients (n = 162) were randomized into an intervention group (IG) and a control group (CG) with 1 yr of treatment and follow-up. Intensive education was given to 77 patients at visits every third month in the outpatient clinic. Eighty CG patients received conventional education and advice at the baseline visit only. All patients received similar inhaled anti-inflammatory treatment. At baseline and at 12 months standard clinical lung functions and health-related quality of life (HRQOL) were measured, the latter by the disease-specific St George's Respiratory Questionnaire and the generic 15D. Furthermore, the use of extra health care services, medication and sickness days were recorded. The IG experienced a significant improvement in all clinical and HRQOL outcome variables. The same applied to the CG except spirometric values. The groups differed significantly only in terms of FEV1 (P < 0.05) in favour of the IG. There was a significant difference between the groups in extra costs. The mean cost was FIM 2351 per patient (294 Pounds sterling) in the CG and FIM 2757 per patient (345 Pounds) in the IG, of which the intervention cost was FIM 1978 per patient (247 Pounds). In 1 yr follow-up the intensive education programme did not prove to be cost effective but was dominated by the conventional one regardless of what effectiveness measure was used. Also, a purely monetary cost-benefit calculation showed that the intervention resulted in a negative net benefit (loss) of FIM 406 per patient (51 Pounds). A longer follow-up may be needed before definitive conclusions about the cost-effectiveness of this kind of intervention can be drawn.

Long-term (3-year) economic evaluation of intensive patient education for self-management during the first year in new asthmatics.

Patient education and self-management programmes have proved effective in many studies with short follow-up periods. We studied the 3-year cost-effectiveness of an intensive programme of patient education and supervision for self-management. The study consisted of 162 consecutive newly diagnosed asthmatics who were randomized either into an intervention group (IG) receiving intensive patient education and supervision for self-management at an outpatient clinic during the first year, or a control group (CG) receiving conventional education at the baseline visits only. Both groups had 2 additional years of follow-up. Lung functions and health-related quality of life (HRQOL) were measured. Extra direct and indirect costs were recorded. At 3 years the differences in forced expiratory volume in 1 s (FEV1) and in peak expiratory flow (PEF) were significantly better in the IG being in (% predicted) respectively 5.3 (95% CI 0.6-10.0) and 4.4 (95% CI 0.1-8.7), (P < 0.05). The airway responsiveness (PD15) did not differ significantly, but the improvement from baseline to 3 years was significantly greater in the IG, being 0.40 dose steps (95% CI 0.05-0.75) (P < 0.05). HRQOL scores did not differ significantly. The risk for sickness day was less in the IG with a RR of 0.6 (95% CI 0.50-0.69) (P = 0.000) and among patients who used the PEF meter. The compliance was similar in both groups when measured by the PEF-based self-management. There was no statistically significant difference in costs, although there was a consistent tendency for lower costs in the intensive programme. The intensive programme was more effective in terms of FEV1, PEF and improvement in PD15 and equally effective in terms of other lung functions and HRQOL, but there was no clear difference in the costs.

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.

The diagnostic value of cold air hyperventilation in adults with suspected asthma.

The diagnostic value of isocapnic hyperventilation of cold air (IHCA) is not fully established. All 342 adult patients in whom IHCA had been performed because of a clinical suspicion of asthma between 1992 and 1994 were analysed retrospectively in the authors' hospital. In addition, 26 healthy subjects were recruited. According to strict criteria, the patients were divided into asthmatics and symptomatic non-asthmatics. For the calculations of sensitivity, specificity and accuracy, the symptomatic non-asthmatic group served as a control. The post-test probability of asthma after IHCA was determined for all the possible pre-test probabilities by applying Bayes' theorem. A linear regression model was used to investigate the factors associated with the reactivity to IHCA. A single 4-min IHCA and skin prick tests were performed in the healthy subjects. Of the 287 patients in the final analysis, 113 were defined as asthmatics and 174 as symptomatic non-asthmatics. The accuracy was highest using a 9.0% fall in forced expiratory volume in 1 s (FEV1) as a cut-off value; the specificity was then 86.8% and the sensitivity 31.9%. The authors found IHCA to be a useful diagnostic test only if the pre-test probability of asthma is between 0.30 and 0.56. The positive final diagnostic gain of IHCA is 22% at its best, but the negative gain is negligible for all possible pre-test probabilities. Factors associated with reactivity to IHCA were young age and, to a lesser extent, a history of cold-weather-associated respiratory symptoms and pre-challenge bronchial obstruction. If a rigid cut-off value for a positive response is used in all age groups, the specificity of IHCA is good but the sensitivity is unacceptably low in adults. The diagnostic value of IHCA might increase if age is taken into account when defining the cut-off value.

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.

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.

Severe farmer's lung following a workplace challenge.

A severe attack of farmer's lung developed in a dairy farmer after a workplace challenge. The patient showed full recovery after corticosteroid therapy. If a workplace challenge is considered necessary in the diagnosis of farmer's lung, care should be taken to avoid unnecessarily heavy exposure to the offending antigens.

Asthma in patients with farmer's lung during a five-year follow-up.

OBJECTIVES: This study assessed the incidence of asthma in patients with farmer's lung. METHODS: The study population consisted of 1031 patients who had occupational farmer's lung diagnosed from 1983 to 1988. The cases of farmer's lung were registered in the nationwide Register of Occupational Diseases by the Finnish Institute of Occupational Health, and all the patients in the study had received compensation from the insurance company for an occupational disease. The diagnosis of asthma was based on entitlement to a special refund for asthma medication costs from the national sickness insurance program. RESULTS: Seventy-four cases of asthma were found among farmers with farmer's lung up to the end of the 5 years following the year of the diagnosis for farmer's lung. The prevalence of asthma was 1% in the year preceding the diagnosis. In the year of the diagnosis and during the 5 year of follow-up, asthma was diagnosed in an additional 6% of the patients. CONCLUSIONS: The results of this study confirm previous findings of a low prevalence of asthma before the onset of farmer's lung in small groups of patients. However, the results also indicate that the incidence of asthma increases during the first years after an episode of farmers lung. For example, in the present study, asthma was apparent in 7% of the patients 5 years after the diagnosis of farmer's lung.

Powered dust respirator helmets in the prevention of occupational asthma among farmers.

OBJECTIVES: This study investigated the value of powered dust respirator helmets in the treatment of farmers with occupational asthma. METHODS: The study population consisted of 33 asthmatic agricultural workers, 24 with occupational asthma induced by cow dander or grains, 2 with other forms of atopic asthma, and 7 with nonatopic asthma. The efficiency of a powered dust respirator helmet with a P2-class filter in preventing asthmatic symptoms was assessed for 1 year. Morning and evening peak expiratory flow rates and daily symptoms of the subjects were monitored for 3 months without the use of the helmet and for 10 months with the helmet. RESULTS: Objective evidence of protection was obtained for farmers with occupational asthma. The morning peak flow rate increased and the variation in daily peak flow rate and the symptoms of cow-barn rhinitis diminished significantly during the helmet period. In the group of farmers with nonatopic asthma there was no improvement in peak flow rate or symptoms of asthma, although some of these farmers also seemed to benefit from helmet use. CONCLUSIONS: The results of this study suggest that especially dairy farmers with occupational asthma benefit from the use of a powered dust respirator helmet.

In vitro inhalation behaviour and therapeutical response of salbutamol particles administered from two metered dose aerosols.

In this study the particle size, as well as the in vitro deposition and the immediate bronchodilating effect on asthmatic patients, of two salbutamol inhalation aerosol preparations (Ventoline, Glaxo, UK, and salbutamol inhalation aerosol, Orion Pharmaceutica, Finland) were compared. The in vitro deposition study was performed using the modified Sierra Andersen cascade impactor. The bronchodilating effect of inhaled aerosol doses were monitored by measuring peak expiratory flow (PEF) values. In the clinical study, the pulse and blood pressure of the patients, as well as the side effects, were also recorded. Due to the anatomy and physiology of human lungs, the accepted optimum size for inhaled drug particles is under 5 microns, and preferably under 2 microns. Over 95% of the drug particles in both aerosol preparations were under 5 microns. 30% of the salbutamol particles in the Ventoline inhalation aerosol were under 2 microns, whereas in Orion salbutamol aerosol 14% of the drug particles were under 2 microns. Respectively 23% of Ventoline and 19% of the Orion salbutamol preparation penetrated into the therapeutically most significant imitated alveolar stages of the modified cascade impactor. Both salbutamol aerosols showed a clear clinical efficacy in the bronchodilating test. In addition, no significant differences existed in the bronchodilating effect of these inhalation aerosols. In conclusion, although there seemed to be a slight difference in the particle size distribution and in the in vitro inhalation behaviour, this variation did not have any effect on the clinical response.