Nocturnal Asthma Symptoms Research Articles

Effects of budesonide and bambuterol on circadian variation of airway responsiveness and nocturnal symptoms of asthma

Effects of the inhaled corticosteroid budesonide and the oral beta-agonist bambuterol on the nocturnal worsening of asthma were studied in patients with allergic asthma with a circadian peak expiratory flow variation greater than or equal to 15% (group 1, n = 8) and less than 15% (group 2, n = 9). Airflow limitation and airway responsiveness to histamine were measured during 24 hours after 4 weeks of treatment with (A) 0.4 mg budesonide at 8 AM and 8 PM, (B) 20 mg bambuterol at 8 PM, and (C) placebo, in a randomized, crossover design. Patients in group 1 had worse nocturnal symptom scores and a greater airway responsiveness than patients in group 2; in addition, patients in group 1 had a larger increase in responsiveness during the night (1.1 versus 0.6 doubling concentrations [DC]). Both budesonide and bambuterol improved responsiveness more at night than during daytime, thus decreasing circadian variation: at 4 AM, increases in PC20 were 2.0 DC after budesonide and 0.8 DC after bambuterol, compared with placebo. Bambuterol reduced circadian variation in FEV1, but in contrast to budesonide, did not improve 24-hour mean levels of FEV1 and PC20. Both drugs beneficially influenced nocturnal symptoms; the effects of budesonide were stronger than those of bambuterol. Our findings demonstrate that budesonide and bambuterol reduce nocturnal airway responsiveness and asthma symptoms and suggest a relationship between the degree of airway responsiveness and the presence of nocturnal symptoms of asthma.

Treatment of Nocturnal Asthma with Pulsed-Release Albuterol

The treatment of nocturnal asthma remains a challenge. We investigated the use of a pulsed-released albuterol in ten patients with nocturnal symptoms of asthma. In a randomized, double-blind, placebo-controlled, crossover designed study, we tested the use of 8 mg of pulsed-release albuterol sulfate (Proventil Repetabs) vs placebo. The pulsed-release albuterol significantly blunted the overnight drop in FEV1, improved peak flow readings in the morning, and decreased subjective awakenings from sleep. We conclude that pulsed-released albuterol is an effective therapeutic option in patients with nocturnal asthma.

Reassessment of the role of theophylline in the current therapy for nocturnal asthma.

Symptoms of asthma commonly increase at night for a variety of reasons. While different options are available for the management of nocturnal asthma, theophylline has maintained a prominent role in treating this problem, and it is widely promoted as a first-line agent. Very recent reports stress the use of anti-inflammatory agents as the drugs of choice for the long-term treatment of asthma. Using the key words "asthma," "theophylline," "bronchodilators," "adrenal cortex hormones," "beclomethasone," "triamcinolone acetonide," and "disodium cromoglycate," the MEDLINE files were searched from 1982 to the present. Articles dating before 1982 were accessed from cross-reference of the more recent articles. Sustained-release theophylline preparations are effective in decreasing the rate of exacerbations of nocturnal asthma symptoms, but theophylline has risks of major toxicity and serum concentrations must be monitored. Inhaled corticosteroids are also useful in controlling nocturnal asthma, and they reduce inflammation, which is the basic problem in asthmatics. Inhaled anticholinergics and oral controlled-release albuterol are also helpful in reducing symptoms of nocturnal asthma. A suggested approach to managing nocturnal asthma includes corticosteroids inhaled through a spacer device at optimum doses, adding inhaled albuterol or oral sustained-release albuterol and then ipratropium with a spacer. If control is not maintained with this regimen, sustained-release theophylline may add benefit to inhaled steroid therapy in reducing nighttime asthma symptoms. Long-acting inhaled beta 2 agonists show promise and could be the adjunctive treatment of choice when they become available in the United States.

A trial of ranitidine in asthmatic children and adolescents with or without pathological gastro-oesophageal reflux

In order to study the importance of gastro-oesophageal reflux (GOR) as a trigger of asthma the effect of inhibition of gastric acid secretion on asthma was assessed in a double-blind, cross-over, placebo-controlled trial over four weeks in 37 children and adolescents (mean age 14 yrs) with bronchial asthma. Ranitidine 300 mg, (150 mg if B.W. was less than 40 kg) was given as a single evening dose during four weeks. In previous investigations 18 of the 37 patients had been shown to have pathological GOR by 24 h pH monitoring in the oesophagus. The remaining 19 patients with normal GOR served as controls for possible effects of ranitidine on asthma, not related to reduction of GOR. A modest (30%) but statistically significant reduction of nocturnal asthma symptoms was produced by ranitidine in the patients with pathological GOR when compared to those with normal GOR. There was a significant correlation between the improvement in asthma symptoms and the degree of acid reflux. Side-effects of ranitidine were negligible. Acid reflux appears to be only a weak stimulus for bronchoconstriction in children and adolescents with bronchial asthma and pathological GOR. Further confirmative trials with more potent inhibitors of gastric acid secretion are, however, warranted.

Use of inhaled corticosteroids in patients with mild asthma.

A double blind, parallel group study was carried out to investigate the effect of inhaled budesonide in a moderate (200 micrograms) and a low (100 micrograms) twice daily dosage compared with the effect of placebo in 103 adults with mild symptomatic asthma. Subjects recorded peak expiratory flow (PEF), asthma symptoms, and beta 2 agonist consumption at home for a period of seven weeks (a one week run in and six weeks' treatment). Morning baseline PEF (around 80% of predicted normal) increased non-significantly to 88% with 200 micrograms budesonide daily and to 90% (p less than 0.05) with 400 micrograms, compared with 81% with placebo. Evening PEF (around 94% of predicted normal) did not change significantly with active or placebo treatment. By comparison with placebo, there was a significant decrease in nocturnal asthma symptoms and beta 2 agonist consumption. The changes during the day were less pronounced and significant only for 400 micrograms budesonide daily. No significant differences between the two active treatments were detected. It is concluded that low doses of inhaled budesonide are effective in patients with mild symptomatic asthma, particularly for night time symptoms and early morning lung function. The early introduction of inhaled corticosteroids for patients with mild asthma and night time symptoms may improve their quality of life during the night and early morning.

Comparison of a Combination of Fenoterol with Ipratropium Bromide (Duovent) and Salbutamol in Young Adults with Nocturnal Asthma

In a randomized, double-blind, double-dummy, crossover study consisting of two 1-month periods with a 2-week 'run-in' we compared the effects of a combination of fenoterol with ipratropium bromide (Duovent, Boehringer Ingelheim) and salbutamol administered by standard metered dose inhalers in conventional dosage in young adults with nocturnal asthma. Seventeen patients were studied, all were aged between 19 and 35 years and showed 'morning dip' associated with nocturnal symptoms of cough, wheeze and breathlessness. They recorded morning and evening peak flows and symptoms of nocturnal asthma on diary cards. Over the 10 weeks of the study there was no difference between Duovent and salbutamol in any of the parameters measured.

Plasma and saliva theophylline levels and pulmonary function in asthmatic patients after a sustained-release theophylline preparation (‘Nuelin’ SA)

SummarySustained-release theophylline ('Nuelin SA) given twice daily in a weight-related dose to 16 asthmatic patients maintained theophylline serum levels within the therapeutic range. On Day 14, these levels were associated with a statistically significant increase in PEFR (p<0.01) from the mean pre-treatment values of 271 litres/min. The mean trough PEFR value was 20% greater and the mean PEFR at noon 41% greater than the pre-treatment value. There was a reduction in nocturnal and early morning asthma symptoms. Measurement of drug concentration in saliva is attractive since it is non-invasive. In this study, the correlation of theophylline levels in saliva and serum was good (r = 0.95). It would seem that once steady-state theophylline serum and saliva levels have been measured, monitoring of theophylline treatment using saliva measurements may be possible within the limitations reported.