Controlled trial of intravenous corticosteroids in severe acute asthma.

BACKGROUND: The value of corticosteroids in severe acute asthma continues to be debated. METHODS: Ninety consecutive patients admitted to the emergency room with severe acute asthma were studied in a randomised, double blind, controlled trial to determine the efficacy of corticosteroids. Eighty two patients completed the study. All received oxygen therapy and intensive bronchodilator treatment. The patients were divided into three groups for steroid treatment, receiving intravenous methylprednisolone 10 mg/kg every four hours for 48 hours (29 patients, group A); intravenous methylprednisolone 2 mg/kg every 4 hours for 48 hours (27 patients, group B); or no intravenous corticosteroids (26 patients, group C). RESULTS: There were no differences on admission among the three groups in forced expiratory volume in one second (FEV1), forced vital capacity (FVC), peak expiratory flow (PEF), or arterial oxygen or carbon dioxide tension; and the rates of recovery in FEV1, FVC, and PEF were similar. CONCLUSIONS: Corticosteroids given with bronchodilators have not shown a beneficial effect in the first 48 hours of recovery of severe acute asthma. Only in those patients who failed to respond by the third hour of treatment, and in those who were previously taking oral corticosteroids, does a favourable, though not statistically significant, effect appear to occur.     

Peak flow variation in childhood asthma: correlation with symptoms, airways obstruction, and hyperresponsiveness during long term treatment with inhaled corticosteroids

BACKGROUND: Guidelines for asthma management focus on treatment with inhaled corticosteroids and on home recording of peak expiratory flow (PEF). The effect of maintenance treatment with inhaled corticosteroids on PEF variation and its relation to other parameters of disease activity were examined in 102 asthmatic children aged 7-14 years. METHODS: During 20 months of treatment with inhaled salbutamol, with or without inhaled budesonide (600 micrograms daily), forced expiratory volume in one second (FEV1), the dose of histamine required to provoke a fall in FEV1 of more than 20% (PD20), the percentage of symptom free days, and PEF variation were assessed bimonthly. PEF variation was computed as the lowest PEF as a percentage of the highest PEF occurring over 14 days, the usual way of expressing PEF variation in asthma self-management plans. For each patient using inhaled corticosteroids within subject correlation coefficients (rho) were computed of PEF variation to the percentage of symptom free days, FEV1, and PD20. RESULTS: PEF variation decreased significantly during the first two months of treatment with inhaled corticosteroids and then remained stable. The same pattern was observed for symptoms and FEV1. In contrast, PD20 histamine continued to improve throughout the whole follow up period. In individual patients predominantly positive associations of PEF variation with symptoms, FEV1, and PD20 were found, but the ranges of these associations were wide. CONCLUSIONS: During treatment with inhaled corticosteroids the changes in PEF variation over time show poor concordance with changes in other parameters of asthma severity. When only PEF is monitored, clinically relevant deteriorations in symptoms, FEV1, or PD20 may be missed. This suggests that home recording of PEF alone may not be sufficient to monitor asthma severity reliably in children.     

Time course of change in oxygen saturation and peak expiratory flow in children admitted to hospital with acute asthma.

The time course for recovery of the arterial oxygen saturation (SaO2) in acute childhood asthma is unknown. Serial measurements of SaO2 were made in 47 children during an acute attack of asthma that required admission to hospital. Adequate serial peak expiratory flow (PEF) measurements were possible in 28 children (mean age 8.3 years; group A), but not in the other 19 children (mean age 3.2 years; group B). Measurements of PEF and SaO2 were recorded twice daily before and 30 minutes after they had received salbutamol by nebuliser. Initial SaO2 values (mean (SD) %) were similar in groups A and B at 92.2 (3.5) and 92.4 (2.9). For the children in group A, PEF plateaued 36 hours after admission and SaO2 plateaued 12 hours later. Mean PEF improved after each dose of nebulised salbutamol during the first 36 hours, whereas mean SaO2 increased only after the first dose. SaO2 increased more rapidly in group B. Length of hospital stay was not related to initial SaO2 or PEF values. These data suggest that in children admitted to hospital for acute asthma arterial oxygen saturation is low at admission, recovers more slowly than airway function, reflects bronchodilatation with salbutamol only when SaO2 is low, and recovers more rapidly in younger children than in older children.     

Comparative efficiency of nebulized adrenaline and salbutamol in severe acute asthma. A randomized,controlled prospective study

OBJECTIVE: To compare nebulized salbutamol and nebulized adrenaline in acute severe asthma (ASA). STUDY DESIGN: Prospective controlled study. PATIENTS AND METHODS: October 1998 at May 99, 44 patients (31 women and 13 men, 35 +/- 11 yrs) with ASA (defined as peak expiratory flow rate (PEF) < 150 l min-1 and normo- or hypercapnia) were randomized to receive either nebulized salbutamol (n = 22), 10 mg/h-1 during 2 h then 5 mg every 4 h or nebulized adrenaline (n = 22), 6 mg/h-1 during 2 h then 3 mg every 4 h. The efficacy was assessed by PEF, forced expiratory volume in one second (FEV1) and Fischl's score during eight hours and by arterial blood gases during the first hour. Side-effects were evaluated by heart rate, systolic blood pressure, serum potassium and blood glucose. Statistical tests: Wilcoxon, Fischer exact, ANOVA and Scheffe's test. RESULTS: Both groups were similar with respect to age, sex, severity, duration of asthma and length of crisis. With the two treatments, PEF increased significantly but no statistical difference were observed between the two groups during the eight hours: 117.7 +/- 41.6 l min-1 to 203.3 +/- 56.9 l min-1 in the salbutamol group; 116.4 +/- 36.8 l min-1 to 217.3 +/- 188.8 l min-1 in the adrenaline group; p = 0.77. FEV1, Fischl's score and arterial blood gases did not differ significantly between treatments at every time interval. There were no significant difference between the two groups in terms of side-effects. The intravenous way was necessary at 3 cases of the salbutamol group and 4 cases of adrenaline group (NS). CONCLUSION: The results suggest that nebulized adrenaline is as effective as nebulized salbutamol in the ASA without significant side-effects. The nebulization could reduce systemic effects of adrenaline.     

Subcutaneous adrenaline versus terbutaline in the treatment of acute severe asthma.

Subcutaneous adrenaline and terbutaline have been compared in a double blind study of 20 patients with acute severe asthma presenting to an accident and emergency department. Ten patients received adrenaline 0.5 mg (0.5 ml) and 10 terbutaline 0.5 mg (0.5 ml) subcutaneously. Further treatment with nebulised salbutamol (5 mg), hydrocortisone (200 mg), and aminophylline (0.9 mg/kg/hour) was started 15 minutes later. All patients reported a reduction in chest tightness within three minutes of receiving both adrenaline and terbutaline and reported no adverse effects. Mean baseline values of peak expiratory flow (PEF) and forced expiratory volume in one second (FEV1) did not differ significantly between the adrenaline group (130 1 min-1 and 0.83 l) and the terbutaline group (111 1 min-1 and 0.63 l). After administration of adrenaline PEF had increased by 21% and FEV1 by 40% five minutes after the injection, and by 35% and 64% at 15 minutes. Terbutaline caused a 23% increase in PEF and a 37% increase in FEV1 at five minutes, and a 40% and 58% increase at 15 minutes. There was no significant difference in PEF, FEV1, heart rate, blood pressure, or pulsus paradoxus between the two groups at any time. Continuous electrocardiographic recording showed no abnormalities in either group. Thus in this study subcutaneous adrenaline (0.5 mg) and terbutaline (0.5 mg) produced effective rapid bronchodilatation without serious side effects.     

Posture and nocturnal asthma.

To investigate whether the supine posture caused sustained bronchoconstriction and could thus contribute to the development of nocturnal asthma, nine patients with nocturnal asthma were studied on two consecutive days, lying supine for four hours on one day and sitting upright for four hours on the other, the order of the two postures being randomised. Peak expiratory flow (PEF), forced expiratory volume in one second (FEV1), and forced vital capacity (FVC) were measured immediately before and after the four hours and over the subsequent hour. There was no significant difference between the erect and supine posture for PEF (248 v 248 l/min), FEV1 (1.31 v 1.22 l), or FVC (2.34 v 2.28 l) at the end of the four hours, nor did any significant change develop subsequently. Thus the supine posture is not associated with prolonged bronchoconstriction. As each patient had previously shown an average overnight fall in PEF of more than 20%, this study strongly suggests that the supine posture is not an important cause of overnight bronchoconstriction.     

Comparison of the effects of intravenous and oral montelukast on airway function: a double blind, placebo controlled, three period, crossover study in asthmatic patients

BACKGROUND: Montelukast, a leukotriene receptor antagonist, improves parameters of asthma control including forced expiratory volume in one second (FEV(1)) when given orally to patients aged six years or older. This study was undertaken to compare the effect on FEV(1) of intravenous and oral montelukast and placebo during the 24 hour period following administration. METHODS: Fifty one asthmatic patients (FEV(1) 40-80% predicted and > or =15% improvement after inhaled beta agonist) were enrolled in a double blind, single dose, three period, crossover study to receive intravenous montelukast (7 mg), oral montelukast (10 mg), or placebo in a randomised fashion. The primary end point was area under the curve (AUC)(0-24 h) of the percentage change from baseline in FEV(1). Additional end points were maximum percentage change in FEV(1) and percentage change at different time points. RESULTS: Compared with placebo, intravenous and oral montelukast significantly increased the AUC(0-24 h) (means of 20.70%, 15.72%, and 7.75% for intravenous, oral and placebo, respectively; no statistical difference between intravenous and oral). The difference in least square means from placebo for intravenous montelukast was 13.27% (95% CI 7.07 to 19.46), p<0.001 and for oral montelukast was 7.44% (95% CI 1.20 to 13.68), p = 0.020. The maximum percentage change in FEV(1) was not significantly different for intravenous and oral montelukast (difference in least square means 6.78% (95% CI -0.59 to 14.15), p = 0.071). The mean percentage change in FEV(1) for intravenous montelukast was greater than for oral montelukast within the first hour (15.02% vs 4.67% at 15 min, p< or =0.001; 18.43% vs 12.90% at one hour, p<0.001 for intravenous and oral montelukast, respectively (placebo 3.05% at 15 minutes, 7.33% at one hour). Intravenous and oral montelukast were similar to placebo in the frequency of adverse events. CONCLUSIONS: The onset of action for intravenous montelukast was faster than for oral montelukast and the improvement in airway function lasted over the 24 hour observation period for both treatments. Although not well understood, there was a trend toward a greater improvement in FEV(1) with intravenous than with oral montelukast. These findings suggest that leukotriene receptor antagonists should be investigated as a treatment for acute severe asthma.     

Formoterol, a new long acting beta 2 agonist for inhalation twice daily, compared with salbutamol in the treatment of asthma.

Sixteen patients with stable chronic asthma participated in a double blind crossover study comparing the new inhaled long acting beta 2 agonist formoterol with salbutamol. Inhaled (n = 15) and oral steroid (n = 1) treatment were maintained at the same daily dose throughout the study. For four weeks the patients received either formoterol 24 micrograms twice daily or salbutamol 400 micrograms twice daily, plus additional puffs (with the same drug) when needed. Asthma symptoms, additional puffs of beta 2 agonist, peak expiratory flow (PEF), and side effects were recorded daily. During treatment with formoterol the patients used fewer additional puffs of beta 2 agonist, had better symptom scores, less disturbed sleep, more days without additional aerosol, and higher PEF both morning and evening than during salbutamol treatment. Thus formoterol 24 micrograms twice daily gave long lasting bronchodilatation and asthma symptoms were well controlled with regular twice daily administration.     

Twelve month comparison of salmeterol and salbutamol as dry powder formulations in asthmatic patients. European Study Group.

BACKGROUND: Salmeterol is a potent selective beta 2 agonist that has been shown to have a duration of action in excess of 12 hours. In this study salmeterol and salbutamol were compared over a three month period with a further extension of nine months. METHODS: Three hundred and eighty eight patients with mild to moderate reversible airways obstruction (forced expiratory volume in one second (FEV1) > 50% predicted) were randomised to receive salmeterol (50 micrograms) twice daily or salbutamol (400 micrograms) four times daily, both by dry powder, in a double blind parallel group study. During the first three months detailed assessment of efficacy was made with recording of morning and evening peak expiratory flow rates (PEF), asthma symptoms, and bronchodilator use when necessary for the relief of symptoms. Patients continued in the study for a further nine months with the salbutamol dose reduced to 400 micrograms twice daily. Lung function was measured at the clinic and safety data were collected during this period. RESULTS: Salmeterol produced a significantly higher mean morning PEF (mean difference compared with salbutamol 21 (95% CI 12-31) l/min), and a significant reduction in mean diurnal variation in PEF (from 30 l/min at baseline to 11 34 l/min at baseline to 32 l/min during salbutamol treatment). Salmeterol also reduced day and night symptoms and use of rescue bronchodilator. FEV1 increased with both salmeterol and salbutamol treatment over the 12 month treatment period. For both treatments the number of patients reporting exacerbations of asthma and the frequency of these exacerbations remained constant during the study. Thirty six patients in the salmeterol and 49 in the salbutamol group withdrew during the 12 months of the study. CONCLUSIONS: In this study salmeterol (50 micrograms twice daily) was more effective than salbutamol (400 micrograms four times daily) in the control of asthma over three months, and more effective than salbutamol (400 micrograms twice daily) over a further nine months. Neither salmeterol nor salbutamol was associated with any worsening of control of asthma.     

Randomised pragmatic comparison of UK and US treatment of acute asthma presenting to hospital

BACKGROUND: Systemic corticosteroids and inhaled beta(2) agonists are accepted first line treatments for acute severe asthma, but there is no consensus on their optimum dosage and frequency of administration. American regimens include higher initial dosages of beta(2) agonists and corticosteroids than UK regimens. METHODS: In a prospective, pragmatic, randomised, parallel group study, 170 patients of mean (SD) age 37 (12) years with acute asthma (peak expiratory flow (PEF) 212 (80) l/min) presenting to hospital received treatment with either high dose prednisolone and continuous nebulised salbutamol as recommended in the US or lower dose prednisolone and bolus nebulised salbutamol as recommended in the UK by the BTS. RESULTS: Outcome measures were: deltaPEF at 1 hour (BTS 89 l/min, US 106 l/min, p=0.2, CI -8 to 41) and at 2 hours (BTS 49 l/min, US 101 l/min, p<0.0001, CI 28 to 77); time to discharge if admitted (BTS 4 days, US 4 days); rates of achieving discharge PEF (>60%) at 2 hours (BTS 64%, US 78%, p=0.04); time to regain control of asthma as measured by PEF >/=80% best with 相似文献   

Addition of salmeterol versus doubling the dose of fluticasone propionate in patients with mild to moderate asthma

BACKGROUND: The objective of this multicentre, randomised, double blind, parallel group study was to compare the efficacy and safety of the addition of salmeterol with that of doubling the dose of fluticasone propionate in asthmatic patients not controlled by a low or intermediate dose of inhaled corticosteroids. METHODS: After a four week run in period of treatment with fluticasone propionate (100 micrograms twice daily if pre-trial dose was 400-600 micrograms inhaled corticosteroids or 250 micrograms twice daily if pre-trial dose was 800-1200 micrograms inhaled corticosteroids), 274 patients were randomised to treatment for 12 weeks with either salmeterol 50 micrograms twice daily plus the run in dose of fluticasone propionate or twice the run in dose of fluticasone propionate (200 or 500 micrograms twice daily). Outcome measures were daily records of peak expiratory flow (PEF), symptom scores, and clinic lung function. RESULTS: The improvements in both the morning and evening PEF were better in the salmeterol than in the fluticasone propionate group, the mean increase in morning PEF being 19 l/min higher (95% CI 11.0 to 26.1) and in evening PEF being 16 l/min (95% CI 18.4 to 24.0) higher in the salmeterol group. The increase in forced expiratory volume in one second (FEV1) was 0.09 1 greater in the salmeterol group than in the fluticasone propionate group after four weeks of treatment (95% CI 0.01 to 0.18), but not after 12 weeks. Both regimens showed an increase in symptom free days and a reduction in the need for rescue salbutamol both during the day and the night, but these improvements were greater in the salmeterol group. There were no significant differences between the groups in adverse effects or in the number of rescue course of oral corticosteroids. CONCLUSIONS: In this group of patients still symptomatic despite 100 or 250 micrograms fluticasone propionate twice daily, the addition of salmetterol caused a greater improvement in lung function and symptom control than doubling the dose of fluticasone propionate.     

Long term clinical comparison of single versus twice daily administration of inhaled budesonide in moderate asthma.

BACKGROUND--Inhaled steroids are widely used in the treatment of mild to moderate asthma. However, long term compliance with inhaled steroids is poor and administration of a single daily dose may improve compliance. METHODS--A double blind, randomised study was performed to determine whether inhaled steroids given once daily at bedtime are as efficacious as a twice daily regimen in the long term maintenance of moderate asthmatic patients. Forty adults of mean age 37 years with moderate asthma (mean (SE) forced expiratory volume in one second (FEV1) 73.6 (1.4)% predicted, mean morning peak expiratory flow (PEF) 328 l/min) were randomised to receive either a twice daily dose (400 micrograms morning and bedtime) of inhaled budesonide (group A) or a once daily dose of 800 micrograms (group B) and were followed for a period of 12 months. Asthma symptom scores (assessed according to a modified Borg scale), inhaled beta 2 agonist consumption, and peak expiratory flow rates were recorded daily. Spirometry and airways responsiveness to methacholine (PC20) were measured at the end of each period of three months of treatment. RESULTS--There was no difference between the two groups at baseline and during the follow up period in the PC20 for methacholine. However, a difference was seen between the two groups in the mean daily number of beta 2 agonist inhalations (1.4 (0.1) puffs/patient/day in group A v 2.3 (0.1) in group B), the PEF variability (episodes of decrease in PEF of > 20%) (0.22 (0.01) episodes/patient/day in group A v 0.40 (0.02) in group B), and for asthma symptom scores (0.30 (0.04) in group A v 0.42 (0.06) in group B) for the 12 month period of the study. CONCLUSIONS--Although both regimens provide good clinical control, twice daily doses of 400 micrograms inhaled budesonide are more effective than a single dose of 800 micrograms at bedtime in the long term control of stable moderate asthma.     

Comparison of short courses of oral prednisolone and fluticasone propionate in the treatment of adults with acute exacerbations of asthma in primary care.

BACKGROUND: Oral corticosteroids used in short courses for acute asthma are regarded as safe, although the frequent use of these drugs may result in patients suffering from systemic side effects. It has become common practice for patients to increase their own inhaled corticosteroid intake when their asthma goes out of control, but it has never been established whether a high dose of inhaled corticosteroid can be as effective as a short course of oral corticosteroid in the treatment of acute exacerbations. METHODS: A multicentre, randomised, double blind, double dummy, parallel group study was undertaken to determine whether the introduction of a high dose of inhaled fluticasone propionate (2 mg daily) is as effective as a short reducing course of oral prednisolone (starting at 40 mg/day and reducing by 5 mg every other day) in the treatment of acute exacerbations of asthma not considered severe enough for admission to hospital but requiring treatment with oral corticosteroid. RESULTS: Four hundred and thirteen adult asthmatic subjects who presented to their general practitioner with an acute exacerbation of asthma were recruited in 47 general practices in the United Kingdom. Treatment failures, defined as a reduction in peak expiratory flow (PEF) to below 60% of the patient's best/predicted value on two consecutive occasions or persistent symptoms with no improvement on three consecutive days, occurred in 23% of patients who received oral prednisolone and 27% who received inhaled fluticasone propionate (difference in percentage of treatment failures 4.3, 95% CI -4.1 to 12.8, p = 0.31). In each group 48% were classified as treatment successes, defined as a 10% or greater increase in percentage best/predicted morning PEF. Both treatments were equally well tolerated. CONCLUSIONS: There is no evidence of a significant difference in efficacy between a reducing dose course of oral prednisolone and high dose inhaled fluticasone propionate in mild exacerbations of asthma which do not require admission to hospital.     

Prazosin in the treatment of chronic asthma.

The role of prazosin, an alpha 1 adrenoceptor blocker, was investigated in patients with chronic stable asthma who continued to have symptoms despite conventional treatment. Forty patients were entered into a double blind, placebo controlled, crossover trial to examine the effect of adding oral prazosin (2 mg twice daily) to previous medication for three weeks. Sixteen patients withdrew from the study. The remaining 24 patients showed no significant change in peak expiratory flow, FEV1, forced vital capacity (FVC), FEV1/FVC ratio, diary card symptom scores, or dose of beta sympathomimetic.     

Effect of inhaled piriprost (U-60, 257) a novel leukotriene inhibitor, on allergen and exercise induced bronchoconstriction in asthma.

The leukotrienes, a group of oxidative metabolites of arachidonic acid, have potent pharmacological actions on human airways. We have investigated the effects of a leukotriene synthesis inhibitor, piriprost (U-60, 257) administered by inhalation on allergen and exercise induced bronchoconstriction in 12 subjects with allergic asthma. Subjects underwent diagnostic challenges with allergen and treadmill exercise to define the strengths of the stimuli required to reduce the FEV1 to about 25% of baseline (PS25). On separate study days subjects inhaled either piriprost 1 mg or vehicle placebo, followed 15 minutes later by the PS25 allergen or exercise. The FEV1 was measured at regular intervals before and after challenge up to 60 minutes. After allergen challenge in six subjects peak expiratory flow (PEF) was measured for the following 20 hours. When compared with placebo, inhalation of piriprost had no significant protective effect on the fall in FEV1 at any time point within 60 minutes of allergen or exercise challenge. In the four subjects with a documented late asthmatic reaction 2-12 hours after allergen challenge piriprost had no protective effect when compared with placebo. In the subjects who recorded PEF over 20 hours after allergen challenge there was no significant difference between piriprost and placebo. Piriprost was appreciably more irritant to the respiratory tract than was placebo. On the assumption that inhaled piriprost was bioavailable in the airways, this study casts doubt on any theory of a pivotal role for leukotrienes in the pathogenesis of acute exercise and allergen induced airway bronchoconstriction in asthma.     

Auranofin in the treatment of steroid dependent asthma: a double blind study.

BACKGROUND: Long term administration of oral corticosteroids in patients with asthma may be associated with serious side effects. Non-steroidal anti-inflammatory drugs, including gold salts, have been shown to reduce the need for systemic corticosteroid treatment in uncontrolled studies. The effect of oral gold (auranofin) on asthma symptoms, lung function, and the need for oral prednisone treatment was investigated. METHODS: A 26 week randomised, double blind, placebo controlled, parallel group trial of auranofin was performed in 32 patients with moderately severe chronic asthma who required an oral corticosteroid dose of at least 5 mg prednisone a day (or equivalent) or 2.5 mg/day prednisone plus more than 800 micrograms/day inhaled corticosteroids. Auranofin was given orally in a dose of 3 mg twice daily. Asthma symptoms, lung function, and adverse effects were assessed at regular intervals. After 12 weeks of treatment prednisone dosage was tapered down by 2.5 mg every two weeks if the patient was clinically stable. Asthma exacerbations were treated with short courses of high doses of oral steroids. RESULTS: Twenty eight of the 32 patients, 13 in the placebo group and 15 in the auranofin group, completed the study. The total corticosteroid reduction achieved after 26 weeks of treatment was significantly greater (4 mg) in the auranofin group than in the placebo group (0.3 mg). The number of exacerbations requiring an increase of steroids was greater in the placebo group (2.1) than in the active group (0.9). A significant increase in FEV1 of 6.4% predicted occurred in the auranofin group during the study and there was a reduction of asthma symptoms such as wheezing and cough. There was no difference between the groups in peak flow measurements or in the number of asthma attacks. The incidence of side effects of auranofin was low, but exacerbations of constitutional eczema were noticeable. CONCLUSION: Auranofin provides an effective adjunct to treatment for steroid dependent asthma, leading to a reduction of oral steroid dose.     

Effect of regular terbutaline on the airway response to inhaled budesonide.

BACKGROUND: The rebound increase in bronchial reactivity and fall in forced expiratory volume in one second (FEV1) following treatment with beta agonists seen in several studies has occurred regardless of concurrent steroid therapy. Little is known about the effect of adding beta agonists to corticosteroids, but in a recent study regular treatment with terbutaline appeared to reduce some of the beneficial effects of budesonide. The effects of budesonide alone and in combination with regular terbutaline treatment on lung function, symptom scores, and bronchial reactivity were therefore examined. METHODS: Sixteen subjects with mild stable asthma inhaled budesonide 800 micrograms twice daily for two periods of 14 days with terbutaline 1000 micrograms three times daily or placebo in a double blind crossover fashion. FEV1 and the dose of histamine or adenosine monophosphate (AMP) causing a 20% fall in FEV1 (PD20) were measured before and 12 hours after the final dose of treatment, and changes from baseline were compared. Seven day mean values for daily morning and evening peak expiratory flow (PEF) values, symptom scores, and rescue medication were compared before and during treatment. RESULTS: Morning and evening PEF rose more with budesonide plus terbutaline than with budesonide alone, with a mean difference of 19 l/min occurring in the evening (95% confidence interval (CI) 2 to 36). There was no difference in symptom scores during treatment. Following treatment the mean increase in FEV1 was 150 ml higher with budesonide alone (95% CI-10 to 300). There was no difference between treatments in change in histamine and AMP PD20. CONCLUSIONS: Evening PEF was greater when budesonide was combined with regular terbutaline. There was no evidence of a difference in bronchial reactivity following the two treatment regimens. The findings of a previous study were not confirmed as the reduction in FEV1 after budesonide and terbutaline was smaller and not statistically significant. Further work is needed to determine whether this disparity in findings in the two studies is due to a type 2 statistical error in this study or a spurious finding in the previous study.     

Comparison of inhaled beclomethasone dipropionate 1000 micrograms twice daily and oral prednisone 10 mg once daily in asthmatic patients.

BACKGROUND--Glucocorticosteroids are widely used as drugs of first choice in the treatment of moderate to severe asthma. The effects of inhaled steroids in high doses have been compared with oral prednisone in asthmatic patients in a double blind crossover study. METHODS--The trial consisted of a two week run in period followed by two four week treatment periods separated by a four week washout. During the treatment period patients took either 1000 micrograms beclomethasone dipropionate twice daily and placebo tablets once daily, or 10 mg prednisone daily in one morning dose and placebo inhaler twice daily. The effects of treatment on the provocative dose of histamine producing a 20% fall in FEV1 (PC20 histamine), peak flow measurements at home, and spirometric measurements in the clinic, as well as on the basal and stimulated plasma cortisol levels were measured. RESULTS--Seventeen patients with asthma completed the study. After four weeks of treatment beclomethasone dipropionate showed a significantly better effect on morning peak expiratory flow rate than prednisone. There was a trend to a greater improvement in the PC20 histamine in patients receiving beclomethasone dipropionate than in those receiving prednisone. There were no significant differences in spirometric values, symptom scores, or basal and stimulated cortisol levels between the treatments. The within treatment analysis showed a significant effect of prednisone on stimulated cortisol levels but not of beclomethasone dipropionate. CONCLUSIONS--Beclomethasone dipropionate 1000 micrograms twice daily has a slightly greater therapeutic effect in this population of asthmatic patients than 10 mg of prednisone once a day with less effect on adrenocortical function.     

Effect of dietary sodium on the severity of bronchial asthma.

BACKGROUND: A high sodium intake has been found to increase bronchial reactivity in men with asthma. The effects of change in sodium intake on peak flow rate have not been determined. METHODS: The effect of changing dietary salt intake for two weeks on the severity of asthma as measured by peak expiratory flow (PEF) was studied in 17 patients with mild asthma in an open randomised crossover trial. PEF measurements were made by the patients in their own homes. Patients were placed on three levels of dietary sodium intake: normal, low, and high. Sodium intake was assessed by 24 hour urine collection. RESULTS: The mean (SD) urine sodium was 147 (45), 84 (32), and 201 (73) mmol/24 hours in the normal, low, and high sodium intake periods respectively. There were no significant differences in PEF or PEF amplitude (highest--lowest PEF), an index of asthma lability, between the three dietary salt periods. CONCLUSION A low and high dietary salt intake for two weeks has no effect on peak expiratory flow in patients with mild asthma.     

Comparison of circadian variations using FEV1 and peak expiratory flow rates among normal and asthmatic subjects.

BACKGROUND--Most studies that describe circadian variations in asthma have used maximum rate of peak expiratory flow (PEF) rather than forced expiratory volume in one second (FEV1) to assess airway calibre. This study was designed to assess circadian variations in PEF and FEV1 measured simultaneously and to compare variations in these measurements in normal and asthmatic subjects in a stable clinical state. METHODS--Twenty nine subjects (nine asthmatic subjects on bronchodilators, 10 on inhaled steroids, and 10 normal controls) were asked to record their PEF and FEV1 with a new portable instrument every two hours during the day and once on waking at night for two weeks. Circadian variations were examined in different ways using arithmetical indices and cosinor analysis. RESULTS--78% of PEF values and 75% of FEV1 values were considered to be reproducible and were included in the analysis. Variations obtained using PEF did not differ from those obtained using FEV1. Significant cosinor variations were found in at least 50% of recording days for most of the subjects and showed the same features as for arithmetical indices. Daily variations in PEF and FEV1 were significantly correlated with airway calibre and PC20 methacholine (r approximately 0.5 to approximately 0.6). CONCLUSIONS--PEF is as satisfactory as FEV1 for describing circadian variations among normal subjects and stable asthmatic subjects.