Terbutaline in COPD comparison between Turbuhaler and chlorofluorocarbon (CFC) inhaler

Patients with chronic obstructive pulmonary disease (COPD) often subjectively benefit from inhaled beta 2-agonists in spite of little or no demonstrable effect in forced expiratory volume in 1 second (FEV1.0). A comparison between the effects of terbutaline administered via a dry powder inhaler (Turbuhaler) and via a chlorofluorocarbon (CFC) inhaler in conjunction with a spacer device (Nebuhaler) was performed in patients with regard to FEV1.0, forced expiratory capacity (FVC), residual volume (RV), and specific conductance (s-Gaw). Fifteen hospitalised patients (11 male) with COPD were studied, each of whom had a diurnal variation in peak expiratory flow (PEF) not exceeding 15% and with a demonstrated volume response to inhaled beta 2-agonists in FVC and/or RV of at least 15%. Patients were administered each of the following five treatments on a single occasion in a randomized order (latin square) in intervals of at least 2 days: placebo, terbutaline via Turbuhaler (1.0 and 2.5 mg) and terbutaline via a CFC inhaler (1.0 mg without and 2.5 mg with Nebuhaler). Inhalation of terbutaline in different doses and from different devices induced a decrease in RV, an increase in FVC, and s-Gaw and a less pronounced increase in FEV1.0. No statistically significant differences between the four terbutaline treatments were seen, but all were significantly different from the placebo. These findings indicate that while patients with COPD may benefit from inhaled terbutaline through decreased hyperinflation, the choice of inhalation device seems to be of little importance for its efficacy.     

Effects of formoterol, salmeterol or oxitropium bromide on airway responses to salbutamol in COPD

We examined whether a pretreatment with formoterol, oxitropium bromide, or salmeterol might modify the dose-response curves to inhaled salbutamol in patients with stable and partially reversible chronic obstructive pulmonary disease (COPD). Sixteen outpatients with partially reversible, stable COPD received 24 microg formoterol, 50 microg salmeterol, 200 microg oxitropium bromide, or placebo on four non-consecutive days. Spirometric testing was performed immediately before inhalation of treatment and after 2 h. A dose-response curve to inhaled salbutamol was then constructed using doses of 100, 100, 200 microg and 400 microg--that is, a total cumulative dose of 800 microg. Dose increments were given at 20 min intervals with measurements being made 15 min after each dose. Formoterol, salmeterol, or oxitropium bromide elicited a significant increase in forced expiratory volume in one second (FEV1) compared with placebo (mean differences (L) = placebo 0.05; formoterol 0.34; salmeterol 0.27; oxitropium bromide 0.23). Dose-dependent increases in FEV1 were seen (mean values (L) before salbutamol and after a cumulative dose of 100, 200, 400, and 800 microg = placebo: 1.06, 1.28, 1.35, 1.39, 1.41; formoterol: 1.33, 1.37, 1.41, 1.44, 1.44; salmeterol: 1.30, 1.33, 1.36, 1.39, 1.42; oxitropium bromide: 1.27, 1.34, 1.37, 1.41, 1.40). Statistical analysis revealed no significant differences in FEV1 and forced vital capacity (FVC) responses to salbutamol after therapy with formoterol, salmeterol, or oxitropium bromide compared with placebo. This study clearly shows that a pretreatment with a conventional dose of formoterol, salmeterol, or oxitropium bromide does not preclude the possibility of inducing a further bronchodilation with salbutamol in patients suffering from partially reversible chronic obstructive pulmonary disease.     

Clinical efficacy of low-dose inhaled budesonide once or twice daily in children with mild asthma not previously treated with steroids

The aim of the present study was to examine the efficacy of low-dose inhaled budesonide (BUD) administered via Turbuhaler once or twice daily on symptoms, lung function and bronchial hyperreactivity in children with mild asthma. One hundred and sixty-three children (mean age 9.9 yrs, 56 females/107 males) with mild asthma (forced expiratory volume in one second (FEV1) 103% of predicted, morning peak expiratory flow (PEF) 87% pred, reversibility in FEV1 3%, fall in FEV1 after exercise 10.4% from pre-exercise value) and not previously treated with inhaled steroids, were included in a double-blind, randomized, parallel-group study. After a two-week run-in period, the children received inhaled BUD 100 microg or 200 microg once daily in the morning, 100 microg twice daily or placebo for 12 weeks. Exercise and methacholine challenges were performed before and at the end of treatment. After 12 weeks of therapy, the fall in FEV1 after an exercise test was significantly less in all three BUD groups (43-5.1%) than in the placebo group (8.6%). Bronchial hyperreactivity to methacholine with the provocative dose causing a 20% fall in FEV1 decreased significantly in the BUD 100 microg twice-daily group compared with placebo (ratio at the end of treatment 156%). Changes in baseline lung function (FEV1 and PEF) were less marked than changes in bronchial responsiveness. In conclusion, low doses of inhaled budesonide, given once or twice daily, provided protection against exercise-induced bronchoconstriction in children with mild asthma and near normal lung function.     

Effect of short- and long-acting inhaled beta2-agonists on exhaled nitric oxide in asthmatic patients

Increased concentrations of exhaled nitric oxide (NO) occur in patients with asthma, and exhaled NO may be useful for assessing the effect of drug therapy on airway inflammation. Beta2-agonists have been proposed to have both proinflammatory and anti-inflammatory effects. We therefore assessed exhaled NO after beta2-agonists in asthmatic patients. Two randomized, double-blind, placebo-controlled studies were conducted. Firstly, exhaled NO was measured in 18 asthmatics (9 taking inhaled glucocorticosteroids (GCS)) before and after nebulized salbutamol (5 mg), or identical placebo (0.9% saline). Exhaled NO and forced expiratory volume in one second (FEV1) were measured at 15 min intervals for 1 h (Study 1). Secondly, the effect of 1 week of treatment with the long-acting beta2-agonist, salmeterol (50 microg b.i.d.), added to either budesonide (800 microg b.i.d.) or placebo, was studied in eight mild asthmatic subjects (Study 2). Exhaled NO was measured by a chemiluminescence analyser, adapted for on-line recording. In Study 1, exhaled NO showed no significant change at any time-point in patients not taking inhaled GCS. In asthmatics on inhaled GCS, exhaled NO increased compared to placebo at 15 and 30 min, but this did not reach statistical significance. In Study 2, treatment with salmeterol increased FEV1, but exhaled NO levels were not significantly changed, either after budesonide treatment (143+/-35 to 179+/-67 ppb), or after placebo (201+/-68 to 211+/-65 ppb). Our results confirm that single high dose salbutamol does not increase exhaled nitric oxide in asthmatics not taking inhaled glucocorticosteroids. Salbutamol may increase exhaled nitric oxide in asthmatics taking inhaled glucocorticosteroids. However, regular use of salmeterol resulted in no change in exhaled nitric oxide, either used alone or in combination with inhaled glucocorticosteroids.     

Relaxin activates the L-arginine-nitric oxide pathway in vascular smooth muscle cells in culture

The effects of usual or low doses of inhaled corticosteroids on airway mucosal inflammation have not yet been examined. We therefore, compared the effects of inhaled beclomethasone dipropionate (BDP) 336 microg x day(-1) on asthma control outcomes and markers of airway inflammation. Twenty-four adult subjects with mild and moderate asthma were randomized to receive either BDP or placebo for four weeks; then subjects entered a single blind four week placebo run-in period. We found that the BDP group had significantly greater improvements in forced expiratory volume in one second (FEV1), morning peak flow, and rescue salbutamol use than the placebo-treated group. The improvement in FEV1 largely reversed one week after treatment was stopped. The decrease in the median percentage of eosinophils in induced sputum in the BDP group from 3.8% to 3.4% was not significant, but because eosinophils increased from 8.4% to 12.7% in the placebo group, there was a significant difference between treatment groups (p=0.03). There was no significant difference between groups during treatment in the levels of eosinophil cationic protein (ECP), tryptase mucin-like glycoprotein, or fibrinogen in induced sputum. The change in FEV1 in the BDP group did not correlate significantly with the change in eosinophil percentage or ECP levels. We concluded that four weeks of treatment with inhaled beclomethasone dipropionate 336 microg x day(-1) was associated with significant improvements in peak flow, forced expiratory volume in one second, and rescue salbutamol use in asthmatic subjects but was not associated with large reductions in markers of eosinophilic inflammation, bronchovascular permeability, or mucus hypersecretion.     

Inhaled dry-powder formoterol and salmeterol in asthmatic patients: onset of action, duration of effect and potency

Salmeterol and formoterol are two long-acting beta2-agonists for inhalation, currently being used in clinical practice. The aim of the present study was to investigate the onset of action, duration of effect and potency of these two beta2-agonists in asthmatic patients. Patients (n=28) were included on the basis of salbutamol stepwise reversibility (100, 100 and 200 microg, given cumulatively; total reversibility > or =15%). In a double-blind placebo-controlled crossover study, the bronchodilating properties of formoterol 6, 12 and 24 microg were compared with the effects of salmeterol 50 microg. Formoterol was given via Turbuhaler and salmeterol via Diskhaler, and forced expiratory volume in one second (FEV1) was monitored during 12 h. Formoterol at all doses had a more rapid onset than salmeterol as judged from bronchodilation at 3 min after the dose. Formoterol at all doses had a similar duration of effect to salmeterol 50 microg, as judged from bronchodilation at 12 h after dose administration. When the relative potency of the two drugs was compared, salmeterol 50 microg was estimated to correspond to formoterol 9 microg (95% confidence interval: 3-19 microg). We confirm that formoterol and salmeterol are both long-acting beta2-agonists, but with some differences in effect profile. We confirm the more rapid onset of action of formoterol compared with salmeterol, and furthermore, no difference in duration of effect is evident.     

Effect of addition of inhaled salmeterol to the treatment of moderate-to-severe asthmatics uncontrolled on high-dose inhaled steroids. European Respiratory Study Group

The aim of this study was to assess the efficacy and safety of inhaled salmeterol 100 micrograms b.d. (SM) versus inhaled salbutamol 400 micrograms q.d.s. (SB), both via the Diskhaler, when added to concurrent treatment, in asthmatic patients who were not controlled on high doses of inhaled steroids (> or = 1,500 micrograms beclomethasone dipropionate (BDP) or equivalent daily). This was a multicentre, parallel group, double-blind study in which 190 patients with a forced expiratory volume in one second (FEV1) or peak expiratory flow rate (PEFR) of 30-75% predicted and 15% reversibility to inhaled bronchodilator were randomized to treatment for 6 weeks. In the SM group, morning PEFR increased from 281 to 315 L-min-1 during treatment and in the SB group from 311 to 315 L.min-1 (p < 0.001). The SM group showed significantly better reduction in diurnal variation, from 39 to 22 L.min-1 during treatment, than the SB group (34 to 37 L.min-1) (p < 0.001). There was a significantly greater improvement in FEV1 in the SM group (from 1.63 to 1.85 L) than in the SB group (from 1.79 to 1.84 L). The SM group had significantly more symptom-free nights than the SB group (p < 0.001), and also more "rescue-free" nights (p = 0.04). The adverse event profile was similar in both groups. This study indicates that in asthmatic patients, not controlled on high-dose inhaled steroids, inhaled salmeterol 100 micrograms b.d. significantly improves lung function and reduces asthma symptoms.     

Bronchodilator response to salbutamol after spontaneous recovery from nonspecific bronchial provocation tests in asthma

Assessment of airway responsiveness by bronchoprovocation and bronchodilatation tests is important in the diagnostic work-up protocol of bronchial asthma and it would be convenient to undertake both tests on the same occasion. However, it is not known whether this can be done accurately. Therefore, this study evaluated the effect of a prior bronchial provocation test on the bronchodilator response to salbutamol after spontaneous recovery of the forced expiratory volume in one second (FEV1) in a group of asthmatic subjects. On two separate occasions at the same time of day, concentration-response studies with inhaled histamine or methacholine, or a sham challenge with normal saline were carried out in a blinded, randomized manner. Changes in airway calibre were followed as FEV1 and agonist responsiveness expressed as the provocative concentration causing a 20% fall in FEV1 (PC20). After either spontaneous recovery or a fixed-duration wait of 45 min (when appropriate), the subjects received 2x100 microg of salbutamol from a metered dose inhaler with a spacer. The bronchodilator response to salbutamol was expressed as a percentage of initial FEV1 (deltaFEV1% init). Bronchial challenge with both agonists failed to alter significantly the airway response to salbutamol, with the deltaFEV1% init mean value (range) being 16.9% (9.0-31.9) and 17.5% (11.6-31.2) on the sham and histamine/methacholine challenge day respectively. It was shown that the degree of bronchodilatation achieved after salbutamol 200 microg is not affected by prior bronchoprovocation testing when enough time is allowed for the airways to recover spontaneously to baseline forced expiratory volume in one second. Thus evaluation of airway responsiveness by both bronchial provocation tests and bronchodilator testing can be assessed reliably within a few hours in asthmatic patients.     

Nurses'' education from a professional viewpoint

Doxophylline, or 2-(7'-theophyllinemethyl)1,3-dioxolane, is a theophylline derivative which has shown interesting bronchodilating activity, and it appears to determine few adverse effects. The aim of the present investigation was to evaluate clinical therapeutic effects of the drug in the treatment of 2 groups of patients suffering from moderate to severe chronic obstructive pulmonary disease differing in acute response to the inhaled beta 2-agonist salbutamol and to compare changes of lung function tests to serum concentration of doxophylline. We studied 67 patients with chronic obstructive pulmonary disease (median age 63 years, 9 females and 58 males) who were all clinically stable at the time of the study. Patients were separated into 2 groups on the basis of their reaction to inhalation of 200 micrograms of salbutamol: those with an increased FEV1 of more than 20% from baseline value (group 1), and those with no increase (group 2). Doxophylline was administered orally at the dose of 400 mg 3 times daily. Serum levels of doxophylline were determined by high-pressure liquid chromatography. Spirometry and blood gas analysis were performed before and 10 days after treatment. Four patients stopped drug assumption because of side effects (3 for dyspepsia and 1 for anxiety). In group 1 (34 patients), a significant increase in SVC, FVC, FEV1, FEF 25-75% and PEFR was observed. In group 1 (29 patients), only PEFR significantly increased. No modifications in blood gas analysis were observed. The mean serum level of doxophylline was 14 micrograms/ml in group 1 and 9 micrograms/ml in group 2: the difference was statistically significant. The relation between serum levels of doxophylline and FVC showed an increase in the parameter up to the concentration of 12-13 micrograms/ml, after which a plateau phase was observed. On the basis of our data, doxophylline appears to have an interesting bronchodilating effect in patients responsive to the inhaled beta 2-agonist salbutamol. The lower limit of the therapeutic range seems to be 12-13 micrograms/ml. The upper limit of the therapeutic range was not determined because it was not possible to obtain serum samples when side effects occurred.     

Dose equivalence and bronchoprotective effects of salmeterol and salbutamol in asthma

BACKGROUND: Salbutamol is the most widely prescribed short acting beta 2 agonist and salmeterol is the first long acting inhaled beta 2 agonist. The dose equivalence of salmeterol and salbutamol is disputed. Estimates of weight-for-weight dose ratio have ranged from 1:2 to 1:16. A study was undertaken to clarify the true dose ratio. METHODS: The bronchoprotection afforded against repeated methacholine challenge by inhaled salmeterol 25 micrograms and 100 micrograms and salbutamol 100 micrograms and 400 micrograms was compared in a randomised, double blind, placebo controlled, crossover trial. Subjects were 16 stable asthmatics with a baseline forced expiratory volume in one second (FEV1) of > or = 65% predicted, screening concentration provoking a fall in FEV1 of 20% (PC20FEV1) of < or = 8mg/ml, and a shift in PC20FEV1 of more than two doubling concentration steps following inhalation of salbutamol 400 micrograms. On five separate occasions subjects underwent methacholine challenge before and 30 and 120 minutes after drug administration. PD20FEV1 was calculated for each challenge. FEV1 at 90 minutes after drug administration was also recorded. RESULTS: Bronchoprotection afforded by salmeterol was increased at 120 minutes compared with 30 minutes and protection by salbutamol was decreased. Protection by both doses of salmeterol was similar to salbutamol 100 micrograms at 30 minutes but significantly greater at 120 minutes. FEV1 at 90 minutes was significantly greater after salmeterol 100 micrograms than after placebo, but there were no other significant differences between treatments. Maximal observed protection was equivalent for salmeterol 100 micrograms and salbutamol 400 micrograms. CONCLUSIONS: The data are compatible with a weight-for-weight dose ratio for salmeterol:salbutamol of < or = 1:4.     

Effects of flutter and PEP mask physiotherapy on symptoms and lung function in children with cystic fibrosis

Recently, the flutter was introduced as a new device to improve sputum expectoration. Preliminary data suggested a significant improvement in expectoration and lung function during flutter treatment in patients with cystic fibrosis (CF). The aim of the present study was to compare the effects of the flutter and the positive expiratory pressure (PEP) mask on symptoms and lung function in children with CF. In a crossover randomized study 22 patients with CF (mean age 12 yrs, range 7-17 yrs) performed physiotherapy using either the flutter or the PEP mask twice a day during two treatment periods of 2 weeks, separated by a one week wash-out period, in a random sequence. Lung function parameters (peak expiratory flow, forced vital capacity (FVC), forced expiratory volume in one second, maximal midexpiratory flow, maximal expiratory flow at 25% of FVC, thoracic gas volume, total lung capacity, residual volume/total lung capacity, airway resistance and specific airway conductance) and changes in transcutaneous oxygen haemoglobin saturation were assessed before and after the first supervised session and at the end of each treatment period. Throughout the study peak flow was measured and symptoms were scored daily. No significant changes in any lung function parameter occurred after a single session or after 2 weeks of physiotherapy with either method. There was no difference in acceptability and subjective efficacy. In conclusion, any superiority of the flutter over the positive expiratory pressure mask technique for expectoration could not be confirmed during 2 weeks of daily treatment in children with cystic fibrosis. Both methods are well accepted by children and do not change lung function. Long-term comparison of both methods, including expectoration measurements, seems to be required for further evaluation of the potential success of physiotherapy in cystic fibrosis.     

Lung function in Indian twin children: comparison of genetic versus environmental influence

The relative contributions of genetic and environmental components in the variability of lung function measurements were studied in 54 twin pairs. Thirty pairs of monozygote (MZ) twins and 24 pairs of dizygotic (DZ) twins were examined. All measurements were made with 9-litre closed-circuit-type expirographs using standard spirometric techniques, except for peak expiratory flow rate (PFER) which was recorded with a Wright peak flow meter. Within-pair variances for inspiratory capacity (IC), vital capacity (VC), forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), forced mid-expiratory flow (FEV25-75%), forced end-expiratory flow (FEF75-85%), maximum expiratory flow (FEF200-1200ml), forced maximum voluntary ventilation MVVF) and PEFR were significantly smaller (p < 0.01) in MZ twins than in DZ twins. Tidal volume (VT), inspiratory reserve volume (IRV), expiratory reserve volume (ERV), forced expiratory volume in 1 second as a percentage of forced vital capacity (FEV1%), and forced expiratory time (FET) were not significantly different. Within-pair correlations were all higher in MZ than DZ twins. All measurements except for VT and PEFR showed high levels of heritability (23-99%). All measurements were positively and significantly correlated with physical characteristics such as weight, standing height, surface area, arm-span, chest circumference and age, except FEV1% and FET. Residual values adjusted for physical characteristics showed similar results to unadjusted values in most cases. These data indicate that major lung function measurements are possibly influenced more by genetic than environmental factors. Genetically influenced measurements show higher levels of heritability estimates and suggest that genetic determination of lung function is possibly independent of the influence of physical characteristics.     

Caring for AIDS patients at home--requirements for development of the concept

Exercise tolerance in chronic obstructive pulmonary disease (COPD) patients treated with oral aminophylline may be different from those treated with high-dose inhaled ipratropium bromide. The purpose of this study was to compare the effects of therapeutic doses of oral aminophylline with high-dose ipratropium bromide on spirometry and exercise tolerance. The study was conducted on three consecutive days in a double-blind, randomized, crossover fashion. Baseline studies obtained on each study day included vital signs, simple spirometry and a symptom-limited maximal cardiopulmonary stress test, after which patients received one of the following treatments on each day: Treatment 1, inhaled ipratropium (total dose of 144 micrograms) with placebo tablets; Treatment 2, inhaled placebo with oral aminophylline (400 mg); Treatment 3, inhaled placebo and placebo tablets. Simple spirometry was repeated at 60 and 120 min after baseline. Vital signs and cardiopulmonary stress testing was repeated at 120 min. Eighteen patients were enrolled in the study, and 17 of these completed the study. There was a significant (P < 0.05) increase in both forced expiratory volume in 1 s (FEV1), from 0.75 (0.21) to 0.92 (0.3), and forced vital capacity (FVC), from 1.8 (0.79) to 2.11 (0.84), with high-dose ipratropium despite prior beta-agonist therapy. Lack of improvement in exercise capacity was noted with ipratropium despite improvement in spirometry. These results suggest that elderly patients with severe COPD may have exercise limitation that is not directly dependent on severity of airflow obstruction. Ipratropium bromide and aminophylline demonstrated no acute effects on exercise capacity.     

Successful myoblast transplantation in primates depends on appropriate cell delivery and induction of regeneration in the host muscle

In a double-blind, cross-over study, we examined the effect of inhaled budesonide (800 microgram twice daily via Turbohaler) on lung function and various markers of airway inflammation including airway responsiveness to methacholine (PC20), exhaled nitric oxide (NO), eosinophils in induced sputum, bronchoalveolar lavage (BAL), and airway biopsies from 14 patients with mild asthma needing beta2- agonist therapy only. After inhaled steroids, there was a significant increase in FEV1 and PC20, and reduction in exhaled NO. Eosinophils in induced sputum and airway biopsy sections were also significantly decreased, although BAL eosinophil counts remained unchanged. At baseline, significant correlations were observed between exhaled NO and PC20 methacholine (r = 0.64, p < 0.05), exhaled NO and peak expiratory flow rate (PEFR) variability (r = 0. 65, p < 0.05), sputum eosinophils and FEV1 (r = -0.63, p = 0.05), and sputum eosinophils and log PC20 methacholine (r = -0.67, p < 0. 05). After treatment with inhaled steroids, there was a significant correlation between eosinophils in biopsy sections, and BAL, with log PC20 methacholine. It is likely that these parameters represent different aspects of the inflammatory process, which are all inhibited by inhaled steroids.     

Comparative influence of a single allergen exposure on the different components of airway response to methacholine

We compared the effects of an allergen challenge on airway responsiveness to methacholine, the slope of the dose-response curve (DRC) and post-methacholine fall in forced vital capacity (FVC) or forced expiratory volume in 1 s (FEV1)/FVC, and determined whether any changes in these parameters were related to the presence and magnitude of the late asthmatic response (LAR) in mild stable asthma. Twenty-three allergic asthmatic subjects had an allergen challenge, preceded and followed 24 (n = 12) and/or 48 (n = 22) h later by a methacholine challenge. Sixteen subjects had a dual asthmatic response to the allergen. On the post-allergen methacholine challenge, as compared with the pre-allergen test, differences in mean fall in FVC or FEV1/FVC at 20% fall in FEV1 and the slope of the DRC did not achieve statistical significance, even in the group with LAR, which showed a significant increase in airway responsiveness at 24 h. There was, however, a correlation between allergen-induced changes in PC20 and (1) the change in post-methacholine FVC fall in the LAR group at 48 h, and (2) the change in the slope of the DRC in the early-asthmatic-response group at 24 h. In conclusion, allergen-challenge-induced changes in airway response to methacholine are heterogeneous among asthmatic subjects and although it may increase airway responsiveness (PC20), particularly in late responders, it minimally affects the other aspects of airway response to methacholine, suggesting that a more powerful or sustained allergic stimulus is required to modify the latter.     

High-dose inhaled steroids in asthmatics: moderate efficacy gain and suppression of the hypothalamic-pituitary-adrenal (HPA) axis. Research Council of the Norwegian Thoracic Society

We wanted to evaluate the improvement in efficacy when increasing the daily dose of inhaled steroids and to compare the efficacy, safety, and tolerance of 1.6 mg beclomethasone dipropionate (BDP) with that of 2.0 mg fluticasone propionate (FP). The study was a randomized, double-blind, 3 month, multicentre study. One hundred and thirty four asthmatics currently using inhaled steroids (0.4-1.6 mg BDP or budesonide (BUD)) were stratified according to pretrial daily steroid use. Within each stratum they were randomized to either 1.6 mg BDP or 2.0 mg FP. A significant increase in the primary efficacy variables, i.e. mean morning and evening peak expiratory flow (PEF) (approximately 20 l.min-1) during the treatment period, was found for both treatments. No significant differences between the drugs were revealed for these primary or any other secondary efficacy variables (use of beta 2-agonists, symptom scores, and PEF, forced vital capacity (FVC), forced expiratory volume in one second (FEV1) recorded at the clinical visits). However, significant differences between treatments occurred regarding decrease of serum cortisol and adrenocorticotropic hormone. We conclude that, although both treatments gave statistically significant increases in efficacy parameters when compared with baseline, the increases were so small that they can be regarded as being clinically unimportant. Daily doses of BDP, 1.6 mg, and FP, 2.0 mg, had comparable effects on lung function. A suppression of the hypothalamic pituitary adrenal (HPA) axis was only found with a daily dose of 2 mg FP.     

Incidence of exercise-induced asthma in children

The incidence of exercise-induced asthma (EIA) was studied in 134 asthmatic and 102 nonasthmatic atopic children and compared to that in 56 nonatopic children. Pulmonary function tests measuring forced vital capacity (FVC) and 1-sec forced expiratory volume (FEV1) were performed on each child prior to and serially for 20 min following free running exercise. The incidences of EIA among the asthmatic and atopic nonasthmatic children were 63% and 41%, respectively. This phenomenon is widespread among allergic children and cannot be accurately predicted from the history. A simple and easily performed outpatient procedure is described for the diagnosis of EIA.     

Measuring hospital performance: are we asking the right questions?

The aim of this randomized cross-over trial was to evaluate the dose effect and systemic absorption of epinephrine nebulized at 2 and 5 mg in comparison with salbutamol (5 mg). Thirteen asthmatic patients (29 +/- 15 years, 4 men and 9 women) were randomly assigned to receive one nebulization of each of the three treatment regimens at 24 h interval. The evaluation concerned forced expiratory volume in 1 second (FEV1), heart rate, respiratory rate and arterial pressure. All measurements were done at baseline, every 15 minutes during the first hour, and hourly thereafter until return to baseline FEV1. Serum potassium was measured at baseline (T0) and sixty minutes after (T60). Plasma levels of epinephrine were measured at T0, T20, T60. Fifteen minutes after the beginning of nebulization FEV1 improved significantly over baseline in the three groups. These changes were similar in the three groups until T45, while FEV1 improvement was significantly greater in A5 and S groups than A2 group (+640 +/- 470 ml, +721 +/- 349 ml, +406 +/- 306 ml in A5, S and A2 groups respectively, p < 0.01). Bronchodilation lasted significantly longer with salbutamol than with epinephrine (p < 0.05). No side effects were recorded in spite of substantial and dose-dependent systemic absorption of epinephrine. CONCLUSION: Increasing epinephrine doses produces greater bronchodilation without additional side effects. However this bronchodilation lasts shorter than with salbutamol.     

An inhaled steroid improves markers of airway inflammation in patients with mild asthma

Airway inflammation can be demonstrated in mildly asthmatic patients who are not treated with inhaled steroids. Current guidelines recommend that inhaled steroids should be introduced in mild asthmatics who use an inhaled beta2-agonist more than once daily. It was postulated that inhaled steroids can have anti-inflammatory effects in patients with even milder disease. The effect of 4 weeks of treatment with budesonide (800 microg twice daily by Turbohaler) was studied in 10 steroid-naive mildly asthmatic patients (forced expiratory volume in one second (FEV1) = 96+/-1.4% predicted) who required an inhaled beta2-agonist less than one puff daily, in a double-blind, placebo-controlled, crossover fashion. Spirometry, exhaled nitric oxide (NO), bronchial responsiveness (provocative concentration causing a 20% fall in FEV1 (PC20)), and sputum induction were performed before and after each treatment period. Following budesonide treatment, there were significant improvements in FEV1, and PC20, in association with a significant reduction in the percentage of eosinophils in induced sputum. Exhaled NO levels tended towards reduction, but the change was nonsignificant. There were also nonsignificant reductions in sputum eosinophil cationic protein and tumour necrosis factor-alpha levels. In conclusion inhaled budesonide can lead to improvements in noninvasive markers of airway inflammation, in association with a small improvement in lung function, even in mildly asthmatic patients who require an inhaled beta2-agonist less than once daily. This suggests a potential benefit of inhaled corticosteroids, even in relatively asymptomatic asthma.     

Exercise induced bronchial lability in normal men and women--a comparison

Normal male (n = 29) and female (n = 39) medical students with a mean age of 19.2 years who were nonsmokers, with no personal history of allergy were studied. The bronchial lability was assessed from peak expiratory flows and forced expiratory spirograms taken before, during and upto 45 minutes after a standard exercise using the Harvard steps. Women had a significantly lower (P < .001) resting FVC, FEV1, FEF 25-75% and PEF as compared to men. Although the exercise lability index was not significantly different in men and women, the latter showed a greater percent increase (P < .02) and a lesser percent decrease (P < .02) of PEF during and after the exercise respectively. They also showed a significantly (P < .005) faster recovery to normal. These results suggest that airway dynamics may be better in women than in men. This could account for the lower incidence and morbidity from respiratory allergic disease seen in women as compared to men.