A comparison of 'abruptly stopping' with 'tailing off' oral corticosteroids in acute asthma.

Systemic corticosteroids are almost universally used in the treatment of severe acute asthma but the optimum length of treatment with corticosteroids following recovery from an acute attack of asthma is not established. Thirty-five patients admitted with acute asthma and treated with oral prednisolone 40 mg daily in addition to bronchodilator therapy until full recovery, with stable peak expiratory flow recordings (PEF) within 15% of their previous best PEF or predicted PEF were studied. They were all discharged home on regular inhaled corticosteroids and regular or as required use of bronchodilators and randomized to receive either prednisolone 40 mg daily or placebo for the first 14 days. Median PEF values increased from 31% predicted on admission to hospital to 71% predicted on discharge from hospital in the active treatment group (19 patients) and from 32-73% in the placebo group (16 patients). There was no difference between the two groups in the median values of the forced expiratory volume in one second, forced vital capacity, total lung capacity or diurnal variation in PEF either at the time of discharge from hospital or at 14 and 28 days after discharge from hospital. This study suggests that there is no need to reduce prednisolone gradually following recovery from an exacerbation of asthma, provided systemic corticosteroid treatment is continued until a satisfactory and stable PEF is achieved.

Effect of inhaled budesonide on bronchial reactivity to histamine, exercise, and eucapnic dry air hyperventilation in patients with asthma.

BACKGROUND: It has been suggested that inhaled corticosteroids may provide greater protection against constrictor stimuli that act indirectly such as exercise than those that act directly such as histamine. METHODS: The effects of six weeks treatment with inhaled budesonide (800 micrograms twice daily) on bronchial reactivity to histamine, exercise, and eucapnic voluntary hyperventilation of dry air were compared in a double blind, placebo controlled, non-crossover study in 40 subjects with asthma. Change in bronchial reactivity to histamine and eucapnic hyperventilation over the six weeks was measured as change in the provocative dose of histamine or dry air causing a 20% fall in FEV1 (PD20 histamine and PV20 eucapnic hyperventilation (EVH) of dry air); this was not possible for exercise because of the development of refractoriness. To enable the change in response to all three stimuli to be compared, the response (percent fall in FEV1) to a fixed dose was measured for all three challenge tests. RESULTS: After budesonide there was an increase in PD20 histamine from 0.48 to 2.81 mumol and in PV20 EVH from 364 to 639 litres, and a significant correlation between the changes in PD20 histamine and PV20 EVH (r = 0.63). The median percentage fall in FEV1 in response to eucapnic hyperventilation, exercise, and histamine was similar before budesonide (25.5%, 26.6%, and 24.5%); the reduction in the percentage fall in FEV1 with budesonide was also similar for the three challenges (18.9%, 17.5%, and 16.6%), and all differed significantly from the changes following placebo. There was a significant correlation between change in percentage fall in FEV1 after budesonide with the three stimuli (histamine v exercise: r = 0.48; histamine v eucapnic hyperventilation: r = 0.46; exercise v eucapnic hyperventilation: r = 0.63). CONCLUSION: The similar magnitude of change in bronchial reactivity to all three stimuli after budesonide and the within subject correlation obtained between these changes suggest that corticosteroids act by a common mechanism to protect against eucapnic hyperventilation, exercise, and histamine.

Time course of change in bronchial reactivity with an inhaled corticosteroid in asthma.

The time course of change in FEV1, bronchial reactivity, and daily measures of asthma control (peak expiratory flow, symptoms, and beta 2-agonist inhaler use) was determined during 6 wk of treatment with inhaled budesonide, 800 micrograms twice a day, and for 2 wk following cessation of treatment in 40 asthmatic subjects in a double-blind, placebo-controlled, parallel group study. Histamine reactivity, expressed as the provocative dose of histamine causing a 20% fall in FEV1 (PD20), was measured at intervals during the 8 wk of the study, with more frequent measurements after the first and last dose of drug to provide a detailed profile of change at the start and end of treatment. The first dose of budesonide caused a small increase in median values of FEV1 (0.2 L) and PD20 (1.0 doubling dose of histamine), which was maximum at 6 h. There was a further increase in FEV1 and PD20 over the 6 wk in the budesonide group relative to placebo, the maximum increases (0.53 L, 3.4 doubling doses of histamine) being recorded 6 h after the last dose on Day 42. Following cessation of treatment, FEV1 and PD20 declined and PD20 returned to placebo values at 1 wk. Median PEF increased by 40 and 30 L/min in the morning and evening, respectively, with budesonide treatment. Symptom scores and beta 2-agonist inhaler use were lower in the budesonide group than the placebo group during treatment but tended to be similar (symptom scores) or higher (beta 2-agonist) in the 2 wk following cessation of treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

A comparison of inhaled beclomethasone dipropionate and nedocromil sodium as additional therapy in asthma.

We have compared the effects of inhaled beclomethasone dipropionate (BDP) 400 micrograms day-1 with inhaled nedocromil sodium (NDS) 16 mg day-1 as additional therapy in adults with asthma not fully controlled by regular beta-2-agonist inhalers with, or without, oral theophyllines. Seventeen subjects were entered into a 2-week baseline phase, and subsequently in a double-blind crossover fashion into two 8-week phases of daily BDP or NDS. Subjects recorded daily peak expiratory flow rates, morning and evening (PEF am and pm), symptom scores and beta-2-agonist inhaler use. Thirteen subjects completed the study and the last 2 weeks of each phase were analysed. Compared to baseline, both BDP and NDS caused a significant improvement in PEF am (P less than 0.05), PEF pm (P less than 0.05) and the 'amplitude % mean' (P less than 0.001). Both drugs gave a highly significant improvement in all symptom scores. There was no significant difference between BDP and NDS for PEF am, PEF pm, amplitude % mean, cough and daytime asthma score. However, beta-2-agonist inhaler use and scores for nocturnal asthma and morning tightness were all significantly better in the BDP phase, and may have contributed to its better overall subjective performance. Thus, both NDS and BDP resulted in a significant improvement in asthma control in the subjects studied, and both drugs caused a similar improvement in PEF.

High-dose inhaled albuterol in severe chronic airflow limitation.

Higher doses of inhaled albuterol have been shown to cause slightly more bronchodilatation than standard doses from a metered-dose inhaler in patients with severe chronic airflow limitation. Higher doses, however, carry an increased risk of side effects, and the optimum dose balancing benefit and adverse effects have yet to be established. We have therefore looked at objective and subjective evidence of beneficial and adverse effects after 4 doses of albuterol in 30 patients with chronic bronchitis, severe airflow limitation, and less than 200 ml increase in FEV1 after 200 micrograms inhaled albuterol. Subjects were given placebo, 400 micrograms, 1 mg, 2 mg, and 4 mg albuterol by dry powder inhaler in random order on separate days in a double-blind study, and FEV1, relaxed VC, PEFR, 12-min walk distance, finger tremor, oxygen saturation, heart rate, and arrhythmias were measured at intervals over 6 h. With increasing doses of albuterol, there was a significant dose-related increase in FEV1, VC, and PEFR, the maximal mean changes being 196 ml, 480 ml, and 50 L/min, respectively. The duration of effect was longer with the higher doses. There was a dose-related increase in heart rate, tremor amplitude, and supraventricular ectopic beats and a dose-related fall in oxygen saturation. There was no drug-related effect on the frequency of ventricular ectopic beats either at rest or during the walk tests. The largest increases in walk distance occurred after the 1 and 2 mg doses and the least after the 4 mg dose.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparison of histamine and methacholine for use in bronchial challenge tests in community studies.

Measurement of bronchial reactivity is widely used in epidemiological surveys. Histamine has been compared with methacholine inhalation challenge in two samples of adults from a small town to determine which is the better agent for use in community studies. Increasing doses of histamine and methacholine were given, up to a maximum of 4 and 12 mumol respectively, according to the method of Yan et al, the provocative dose of agonist causing a 20% fall in FEV1 (PD20) being measured. More subjects had a measurable PD20 with methacholine than with histamine, both in a random sample of 108 subjects (25 v 11 subjects, p less than 0.01) and in an additional 95 subjects selected because of wheeze in the last 12 months (67 v 48 subjects, p less than 0.01). Side effects were mild with both agents but histamine caused voice change in more subjects (21% v 11%). Repeatability was assessed in a further group of subjects with wheeze in the last year. The 95% range for a single estimation of PD20 in subjects with a measured PD20 on at least one occasion was +/- 2.5 doubling doses for histamine (n = 25) and +/- 2.1 doubling doses for methacholine (n = 33). Thus methacholine has advantages over histamine for community studies of bronchial reactivity as it is possible to use doses that produce more PD20 measurements with fewer side effects.

Rebound increase in bronchial responsiveness after treatment with inhaled terbutaline.

To investigate whether cessation of regular beta-agonist treatment results in an increase in bronchial responsiveness, two double-blind, randomised crossover studies were done. Subjects with mild asthma were investigated to determine the course of change in bronchial responsiveness, measured as the provocative dose (PD20) of histamine that caused a 20% fall in forced expiratory volume in 1 s after short-term and longer term treatment with an inhaled beta-agonist. In the first study in 8 subjects, 500 and 2000 micrograms terbutaline thrice in 1 day protected against histamine-induced bronchoconstriction, and the increase in PD20 compared with placebo remained high throughout the day and overnight. In the second study 8 subjects received placebo or terbutaline 750 micrograms thrice daily for 14 days. The protection afforded by terbutaline against histamine-induced bronchoconstriction on day 14 was less than that on day 1 by 40% in the morning and 82% in the afternoon. On day 15 PD20 was lower after stopping terbutaline than placebo, with a maximum difference of 1.5 (95% CI 0.6-2.5) doubling-doses of histamine 23 h after the end of treatment. Thus treatment with terbutaline for 1 day did not result in any rebound increase in bronchial responsiveness. Treatment for 2 weeks impaired the ability of terbutaline to protect against histamine-induced bronchoconstriction, and was followed by a rebound increase in bronchial responsiveness after cessation of treatment.

Does aminophylline improve nocturnal hypoxia in patients with chronic airflow obstruction?

The progression of pulmonary hypertension secondary to chronic airflow obstruction is thought to be related to the degree of nocturnal oxygen desaturation. We have studied 11 patients with severe smoking-related hypoxic chronic airflow obstruction (mean FEV1 0.67 L, mean arterial PO2 6.83 kPa) who showed less than 15% reversibility to 200 micrograms inhaled salbutamol delivered by a pressurised aerosol. There was no difference in nocturnal oxygen saturation when a control normal saline was compared to intravenous aminophylline given according to the BNF recommended dosages, despite theophylline levels of 9.20 and 9.03 micrograms ml-1 at the beginning and end of the infusion. There was no improvement overall in FEV1 and FVC by aminophylline, but in individual patients an improvement of FEV1 could be associated with an improvement in mean oxygen saturation. We conclude 1) that there is no benefit in the short-term administration of theophylline in chronic airflow obstruction, 2) that indiscriminate use of theophylline preparation in irreversible airways disease is not justified, but 3) that theophyllines may benefit individual patients.

Maternal antibody and respiratory syncytial virus infection in infancy.

One hundred newborn infants were studied prospectively for 1 year for evidence of infection with respiratory syncytial virus (RSV). The indirect membrane fluorescence technique was used to determine specific antibody in sera. Infection was shown in 29 cases. In 31 infants exposed to an RSV epidemic season, there was no evidence of infection. Maternal antenatal sera were also tested, and wide range of IgG antibody to RSV was found. Mean titre of maternal IgG antibody to RSV was significantly higher (P less than 0.001) in those mothers whose babies remained uninfected than in those whose babies had proved RSV infection before 6 months of age. Babies born to mothers with high levels of IgG antibody to respiratory syncytial virus were protected against infection with this virus during the first months of life when the risk of severe disease was greatest.