The superiority of combination beclomethasone and salbutamol over standard dosing of salbutamol in the treatment of chronic asthma.

We studied the clinical effect of a combination aerosol containing salbutamol and beclomethasone dipropionate in comparison to doubling the standard dose of salbutamol from an inhaler. Fifty-seven patients completed the double-blind, crossover study. They were treated with either an aerosol of 100 micrograms beclomethasone dipropionate and 200 micrograms salbutamol or 400 micrograms salbutamol alone. Both regimens were administered four times a day for 4 weeks. The patients showed significant improvement in FEV1, PEFR, and symptom scores after treatment with beclomethasone dipropionate and salbutamol compared with pre-trial values and with treatment with double the dose of salbutamol. The patients demonstrated a clear preference for treatment with the combination of beclomethasone dipropionate and salbutamol. Regular treatment with beclomethasone dipropionate in addition to salbutamol as a combination inhaler provides much better control of asthma than merely increasing the dose of salbutamol in those patients poorly controlled on standard doses of inhaled bronchodilators.

Methacholine bronchial challenge using a dosimeter with controlled tidal breathing.

A new inhalation synchronised dosimeter triggered by low inspiratory flow rates has been assessed. The methacholine challenge test using dosimeter nebulisation with controlled tidal breathing was compared with continuous nebulisation using De Vilbiss No 40 nebulisers with deep inhalations in 11 asthmatic subjects. Within subject PD20 FEV1 values were lower with the dosimeter method than with the continuous nebulisation method (geometric means 158 and 588 micrograms). The repeatability of the dosimeter method with controlled tidal breathing was studied in 11 asthmatic subjects, and the 95% range for a single measurement was +/- 0.72 doubling doses of methacholine. The dosimeter method has greater efficacy because aerosol is delivered during the first part of an inhalation, minimising loss of aerosol outside the respiratory tract. The dosimeter technique combined with controlled tidal breathing appears to be a useful method for carrying out standardised non-specific bronchoprovocation tests.

Aerosol deposition in automatic dosimeter nebulization.

A new dosimeter nebulization method was studied in 10 asthmatics and 8 normal volunteers by delivering fixed doses of 99mTc-traced radioaerosol in 0.2 s periods of tidal breathing. Two separate inspiratory phases were studied with the onset of nebulization, when in the earlier phase 15% and in the later phase 60% of tidal volume was inhaled. Further, bronchodilator administration was analogically assessed in the asthmatics. In healthy subjects, the total lung deposition was 17% greater in the earlier phase (p less than 0.005) than in the later one. In asthmatics, the difference was not significant. The losses of aerosol outside the lower respiratory tract were minimized, in the mouthwashing 0.3% and in the exhaled air 1.4%. The onset of nebulization (early or late) had no significant effect on bronchodilation with salbutamol in asthmatics. We conclude that the present dosimeter method is useful for efficient delivery of radioaerosols and drugs, and for standardization of bronchoprovocation.

Bronchodilator effects of a fenoterol metered dose inhaler and fenoterol powder in asthmatics with poor inhaler technique.

Thirty-seven per cent of 204 consecutive asthmatic patients using metered dose inhalers (MDI) regularly had faulty inhaler technique. Twenty patients with poor technique volunteered for bronchomotor tests. The bronchodilator effects of 0.2 mg of fenoterol in MDI form, 0.2 mg of fenoterol in powder form and a placebo powder were compared. Mean peak expiratory flow (PEF) and forced expiratory volume in 1 s (FEV1) values after 0.2 mg of fenoterol in MDI form were only slightly different from those after placebo. Inhalation of 0.2 mg of fenoterol powder was, however, followed by a highly significant (p less than 0.001) increase in measured expiratory indices. PEF and FEV1 values were significantly higher after fenoterol powder than after fenoterol in MDI form (PEF, p less than 0.01 at 5 min, p less than 0.001 at 15 min, and p less than 0.05 at 60 min, FEV1, p less than 0.01 1 h after drug administration). Poor MDI technique can severely impair the effect of bronchodilator drugs. Use of a bronchodilator in powder form is more reliable in these patients.

Exposure of water consumers to mesophilic actinomycetes.

In autumn 1978 an epidemic of respiratory disease resembling allergic alveolitis occurred in a small Finnish community. The disease was caused by repeated exposures to tap water aerosol. The raw water of the community and the sand filters of the purification system were heavily contaminated with mesophilic actinomycetes. Fourteen different strains of actinomycetes were isolated. Exposed persons with and without symptoms as well as unexposed control persons were tested for antibodies against five of these actinomycetes and against Enterobacter agglomerans. Both the exposed and the control persons had antibodies to actinomycetes but the exposed persons had antibodies against more actinomycete strains than the control persons. Precipitating antibodies against E. agglomerans were also found in control persons as well as in patients. There was a significant difference between the patients and the exposed healthy persons in bacterial agglutination tests with flagellar antigen of one E. agglomerans strain. However, the role of mesophilic actinomycetes and E. agglomerans in the aetiology of the disease could not be firmly established.

Plasma glucagon response during exercise-induced asthma.

Plasma glucagon levels and peak expiratory flow rates (PEF) were determined before and after treadmill exercise test in 5 atopic patients with exercise-induced asthma (EIA) and in 10 non-atopic patients with EIA, and also in 14 controls without exercise-induced bronchoconstriction. In addition, changes in plasma glucagon were determined during an allergen-inhalation challenge test in 5 asthmatics. Plasma glucagon was determined by radioimmunoassay using antiserum and 125I-labelled glucagon. Plasma glucagon level of atopic asthmatics at rest was significantly lower (P less than 0.05) than in non-atopic EIA patients. In the atopic EIA patients the plasma glucagon level increased by 41 per cent 10 minutes after exercise, whereas in the nonatopic EIA patients it decreased by about 19 per cent. In the controls there were only insignificant exercise-induced changes in the plasma glucagon level. The exercise-induced changes of the plasma glucagon in the atopic EIA patients differed significantly from those in the non-atopic EIA patients (P less than 0.05). No change in plasma glucagon was observed in five asthmatics during inhalation challenge tests with a known positive allergen. The results suggest that the rise in glucagon is a defence mechanism against exercise-induced broncho-constriction.

Effects of acute and long-term bronchodilator treatment on regional lung function in asthma assessed with krypton-81m and technetium-99m-labelled macroaggregates.

We have investigated the effect of acute and long-term bronchodilator treatment on the distribution of ventilation and perfusion in 15 asthmatics using a gamma camera, krypton-81m (for ventilation) and technetium-99m macroaggregate (for perfusion). Individual peak expiratory flow (PEF) values before bronchodilation were slightly or moderately below the predicted values. The simultaneous ventilation images (analysed visually) showed areas of delayed ventilation in all patients (mean distribution score on 3-point scale 2.1). After isoprenaline inhalation (240 micrograms) the mean PEF increased by 24%, but the distribution of ventilation remained virtually unchanged in all patients (mean score 2.0). Simultaneously defects in perfusion could be seen in all patients (mean score 1.5). After intensive treatment, when the mean PEF increased by a further 29%, the distribution scores of ventilation and perfusion fell to 0.8 and 0.9, respectively. The results indicate that, without intensive and long-term treatment, appreciable inequality of ventilation and perfusion are usual consequences of asthma; and suggest that although larger airways are dilated by isoprenaline inhalations residual bronchial obstruction may still remain in some smaller airways, maintaining uneven distribution. Perfusion disturbances seem to be secondary to changes in regional ventilation.

An epidemic of bath water fever--endotoxin alveolitis?

In August, 1978, in Linnavuori industrial community an epidemic broke reaching nearly one half of the population. The acute disease was manifested by severe respiratory symptoms, fever, cough, and dyspnea. The symptoms were connected with the use of hot water. The symptoms of the disease resembled those of allergic alveolitis or humidifier fever. The tap water of the region was found to be heavily polluted. Besides an ample microbial growth a high endotoxin concentration was found. Specific antibodies to the microbes or radiographic lung changes referring to allergic alveolitis were not found. Leukocytosis and reduced diffusion capacities indicating an inflammatory reaction at the alveolar level were in the acute phase. It may be a toxic lung inflammation caused by endotoxins, at least partly at the bronchiolar-to-alveolar level. According to the follow-up, to date the disease has not caused lung damages.

Comparison of ketotifen, disodium cromoglycate and placebo in the treatment of adult patients with mild extrinsic asthma.

Sixty-four patients with mild of moderate extrinsic asthma were treated with placebo for 1 month and thereafter with ketotifen (1 mg twice daily, orally), disodium cromoglycate (inhalation of 20 mg, four times daily), or placebo for 2 subsequent months. The trial was performed at four different centres and the treatments were compared using double-blind technique. We found no difference between the effect of ketotifen, disodium cromoglycate and placebo on the patients' daily measurements of evening peak expiratory flow, daily score values or respiratory symptoms of the number of salbutamol puffs required to control symptoms. There was no difference between the treatment groups with regard to the patients' estimates of changes in airway sensitivity to different non-specific stimuli: fumes, tobacco smoke, cold air, and exercise. The only significant effect of DSCG was a minor (4%) increase in the mean morning value for peak expiratory flow. The findings suggest that the addition of ketotifen or disodium cromoglycate to the regimen is unlikely to give further benefit in asthmatic patients, whose symptoms are reasonably well controlled by small doses of bronchodilating drugs.

Bathing fever epidemic of unknown aetiology in Finland.

Since August, 1978, an epidemic characterised by respiratory symptoms and fever spread rapidly in a restricted area near Tampere, Finland. Four months later over half of the adult population reported intermittent or constant symptoms. The most frequent symptoms were cough, dyspnoea, chills, fever, headaches, muscle pain and aching of joints. The symptoms appeared to be associated with exposure to water vapour derived from tap water. Consequently this disease, which resembled extrinsic allergic alveolitis, was given the name 'bathing fever' for lack of any prevailing diagnosis. In clinical provocation tests lung diffusion capacity usually decreased, the leucocyte count increased, and a slight rise in body temperature was observed. Despite many efforts the specific causative agent in the tap water has not been identified. Neither massive chlorination of the water nor changing the sand filter of the water-works had any significant effect on the quality of the water. Therefore the source of water supply was changed in April, 1979. The symptoms have subsequently disappeared. Present knowledge about bathing fever suggests that, though rare, it may be typical of the Scandinavian type of climate.

Determination of functional residual capacity with 133-xenon radiospirometry. Comparison with body plethysmography and helium spirometry. Effect of body position.

This study was undertaken to estimate the accuracy of 133-xenon radiospirometry for determination of FRC in healthy subjects. Forty healthy volunteers, both smokers and non-smokers, were examined. The FRC of each subject was concurrently determined with radiospirometric, He-dilution in closed circuit, and body plethysmographic methods. The radiospirometric and He-dilution measurements were done in supine and in sitting positions, the body plethysmography on sitting subjects, only. The mean FRC measured by radiospirometry (FRCRS) was 0.72 1 larger than that measured by helium spirometry (FRCHe) in sitting position (P < 0.01). In supine position the FRCRS was 0.65 1 larger than the FRCHe (P < 0.01). The body plethysmography gave FRC (TGV) 0.35 1 larger than the FRCHe sitting (P < 0.01). The FRCHe and the FRCRS in the sitting position were 0.48 and 0.55 1 larger than in the supine position (P < 0.01), respectively. Trapped air correlated significantly (P < 0.01) with the difference FRCRS-FRCHe, when sitting. The results indicate that the FRC determined radiospirometrically is significantly larger than the FRC determined with He-spirometry. The difference is systematic, suggesting that it is caused by 133-xenon dissolved in blood and accumulated in tissues of the thoracic cage and by dissimilar representation of trapped air in FRCRS and FRCHe. With eventual correction of the systematic error, the FRC obtained as a by-product of radiospirometry may be used, e.g. for clinical purposes.