Influence of the menstrual cycle on airway function in asthmatic and normal subjects

Investigations of premenstrual asthma (PMA) have been based on studies of asthmatics already aware of a deterioration of asthma premenstrually. Little is known, therefore, about relationships between the menstrual cycle and airway function in asthmatics who do not complain of PMA or in normal subjects. We investigated airway function in both of these groups for three or four consecutive menstrual cycles. Daily records of asthma symptoms and peak expiratory flow rates were maintained by 11 asthmatics and 29 normal control subjects. Standard spirometry and serum estradiol and progesterone levels were measured during the follicular, midluteal, and late luteal phases of the menstrual cycle. Airway reactivity to methacholine was tested during the follicular and luteal phases. The normal group showed no significant changes in symptoms, peak flow rates, spirometric parameters, or airway reactivity. Although the asthmatic group also demonstrated no significant changes in spirometry and airway reactivity, asthma symptoms (shortness-of-breath, cough, wheeze, and chest tightness) deteriorated significantly (p less than 0.001) from the follicular to the luteal phase, as did the morning peak flows of the asthmatics (p = 0.045). Airway function and reactivity were not related to hormone levels in either group. This study indicates that asthmatics not previously aware of PMA will record a premenstrual worsening of asthma symptoms and peak expiratory flow rates. These changes are not related to a deterioration in spirometry and airway reactivity or to the absolute levels of circulating progesterone and estradiol.     

Leukotriene Receptor Antagonists: A Good Choice in the Treatment of Premenstrual Asthma?

The aim of this study was to investigate the effects of leukotriene receptor antagonists (LTRAs) on the premenstrual exacerbation of asthma (PMA). Twenty-four female patients with mild asthma were enrolled in the study. Patients were followed for three menstrual cycles and separated into two groups based on whether they exibit premenstrual worsening of asthma symptoms (n = 11) or not (n = 13). During the first month all were treated with only inhaled steroids (IS) (run-in period); during the second month they received IS plus placebo; and during the third month they were given IS plus montelukast. Furthermore, they were advised to use beta ₂ -agonists as needed. Peak expiratory flow rate (PEFR) and symptom scores were recorded during the 3 months. Pulmonary function tests (PFT) and the levels of oestrogen, progesterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) were measured a week before the begining of the menstrual period. At the end of the 3-month period, it was observed that following therapy with montelukast, the patients with PMA showed significant improvement in PEFR variability and symptom scores when compared with the placebo group. Baseline FSH levels were higher, but FSH and other hormone levels and PFTs did not change in these groups. However, in the group without PMA there was no difference between the montelukast or placebo groups in PEFR variability, symptom scores, PFTs, and hormone levels. Based on the data in hand, it could be stated that LTRAs have ensured the control of symptoms and improved PEFR variability in patients with PMA by supressing inflammation. We are of the view that LTRAs would be a right choice in the treatment of patients with PMA.     

Relationship between changes in diurnal variation of expiratory flows, lung volumes and respiratory symptoms after acute asthma

We looked at the comparative recovery of asthma symptoms and changes in airflow obstruction after an acute exacerbation of asthma in 26 asthmatics, aged 18-69 years (mean = 43). In the 4 weeks following the acute episode, they recorded their respiratory symptoms and twice-daily peak expiratory flow rates (PEFR). In 14 subjects, lung volumes were also measured on days 1, 7 and 30. Mean initial FVC and FEV1 [+/- SEM (% predicted)] were 2.30 +/- 0.16 (61%) and 1.18 +/- 0.08 (39%). The rate of improvement of airflow obstruction initially paralleled that of asthma symptoms in subjects with mild or with a recent onset of asthma. On the first study day, diurnal variation of PEFR was minimal, increased rapidly during the first week of treatment and stabilized thereafter. Mean daily delta PEFR was significantly higher in the first than at the fourth week (P = 0.005). Recovery of asthma symptoms was associated with an overall reduction in FRC and RV but there was no significant correlation between FRC or RV and dyspnea score or PEFR. Perception of airflow obstruction was generally lower, improvement of symptoms slower and of smaller amplitude in those with long-standing asthma. In conclusion, during recovery from acute asthma: (1) diurnal variation of PEFR is initially minimal, increases rapidly after beginning steroids and stabilize in the two following weeks; (2) in patients with more than mild or long-standing asthma, and magnitude and range of perception of asthma symptoms is reduced and correlates less with PEFR; and (3) no significant correlation could be found between FRC or RV and dyspnea score or PEFR.     

Gonadotrophin-releasing hormone analogues: a novel treatment for premenstrual asthma.

Premenstrual exacerbation of asthma, as reflected by a reduction in peak expiratory flow rate (PEFR), has been demonstrated in 40-100% of female asthmatics. Epidemiological data demonstrate that admission to hospital with an exacerbation of asthma occurs more frequently perimenstrually. Therapeutic interventions aimed at modifying this precipitating factor, however, remain limited. We report on a 32-yr old female with asthma in whom a marked increase in symptoms and reduction in PEFR occurred premenstrually, necessitating recurrent admissions to hospital. Frequent severe exacerbations resulted in the chronic use of oral maintenance corticosteroids. In order to suppress gonadotrophin secretion and ovarian function, a long-acting gonadotrophin-releasing hormone analogue was administered with a view to inducing a reversible menopause. This resulted in improvement in respiratory symptoms, the absence of PEFR dips premenstrually, a reduction in maintenance prednisolone dosage and no further hospital admissions during a follow-up period of 14 months. The authors propose that gonadotrophin-releasing hormone-analogue therapy is a rational and innovative adjuvant treatment worthy of further study in cases of severe premenstrual asthma.     

围月经期哮喘诊治进展

一些支气管哮喘(简称哮喘)妇女在月经前或月经期哮喘症状可以加重,称之为月经前期哮喘或月经期哮喘,统称为围月经期哮喘.围月经期哮喘相当常见,大约占哮喘妇女的30%～40%.雌二醇、孕酮、阿司匹林、白三烯可能与其发病有关.根据月经前或月经期哮喘症状加重和呼气峰流速降低可以做出诊断.雌二醇、孕酮、白三烯调节剂可以用于围月经期哮喘的治疗.     

Long-acting bronchodilators in premenstrual exacerbation of asthma

Premenstrual exacerbation (PME) of asthma occurs during the 5-10 days leading up to the menses and can be demonstrated in about 40% of asthmatic females. Peak expiratory flow rate (PEFR) and beta2-agonist consumption were recorded during three menstrual cycles in 67 females with mild-severe asthma. All were treated with inhaled glucocorticosteroids (IGC) and beta2-agonists, as required. Following, the patients with a premenstrual reduction in PEFR > 20%, received either salmeterol, 50 microg x 2 day(-1) or placebo, in the 10 days leading up to the menses, in a randomized, double-blind, cross-over design. Thirteen patients (19.4%) showed PME (mean +/- SEM decrease in PEFR 27 +/- 2.2%) in association with a significant increase in the mean daily beta2-agonist consumption. Following administration of salmeterol, there was a complete ablation of the PME in seven patients, a partial ablation in two patients and no effect in the remaining four patients. Only one patient showed a partial ablation of the PME following placebo. There was also a significant decrease in the beta2-agonists consumption in the responders. About 20% of the women with asthma, under chronic IGC treatment, had PME of asthma. In 54% of them, it could be prevented by the use of long-acting bronchodilators (LABD) during the 10 days leading up to the menses, and partially prevented in another 15%.     

Questions relating to premenstrual asthma

The study of asthma in fertile women needs to consider its potentially recurrent exacerbation in a specific phase of the menstrual cycle. Premenstrual asthma (PMA) refers to the deterioration of asthma in some women of fertile age during the premenstrual phase. Prevalence varies considerably according to studies (11%-47.44%) mainly because there is no standardized definition of the illness. There is a possible link between PMA and premenstrual syndrome, which is a set of physical and psychic manifestations that occur in some fertile women during the same premenstrual phase. This relation has been widely studied but there are still several unknowns. PMA etiopathogeny is not known. It involves possible causes such as hormonal variations in the premenstrual phase, the coexistence of atopy, variations during the cycle in substances related to inflammation, like LTC4 leukotrienes, catecholamines, E2 and F2α prostaglandins and certain cytokines. Also considered are psychological factors related to this phase of the menstrual cycle, a high susceptibility to infection or increased bronchial hyperreactivity prior to menstruation. Yet no factor fully explains its etiology, consequently no specific treatment exists. Researchers have investigated hormones, anti-leukotrienes, prostaglandin synthesis inhibitors, diuretics, phytoestrogens and alternative therapies, but none has been shown to be effective.     

Relationship between asthma and gastro-oesophageal reflux: Significance of endoscopic grade of reflux oesophagitis in adult asthmatics

BACKGROUND: The association between asthma and gastro-oesophageal reflux disease (GERD) is well known. The aim of this study was to elucidate the causal relationship between reflux oesophagitis (RE) and asthma. METHODS: Seventy-two adult asthmatics were examined regarding their GERD symptoms, and each underwent an endoscopic examination. According to the Los Angeles classification, we divided the patients into three groups: group 1 (n= 52), no mucosal break; group 2 (n= 15), RE corresponding to grades A or B; group 3 (n = 5), RE corresponding to grades C or D. The asthmatics in groups 2 and 3 received anti-reflux treatment for their GERD for 8 weeks. Their morning and evening peak expiratory flow rates (PEFR), daily variability of the PEFR and daily use of an inhalation bronchodilator were compared before and after this treatment. RESULTS: The percentage of severe asthma and postprandial exacerbation of asthma in group 3 were significantly higher than those in the other two groups. In contrast, the number of eosinophiles and the serum level of immunoglobulin E in group 3 were significantly lower than those in the other two groups. After the antireflux treatment, significant improvements of both PEFR and daily use of the inhalation bronchodilator were observed only in group 3. CONCLUSIONS: The endoscopic severity of RE is associated with the characteristics of adult asthmatics and the treatment of severe RE improved the asthmatics' condition.     

Prednisone-dependent asthma: inflammatory indices in induced sputum.

The kinetics of changes in inflammatory indices in induced sputum from eight prednisone dependent asthmatics whose minimum clinical maintenance and exacerbation doses were known were investigated. The study began on the last day of a course of 30 mg prednisone daily for one week. Thereafter, the daily prednisone was reduced in a structured way to below the maintenance dose. This treatment was continued until a clinical exacerbation occurred. Prednisone 30 mg daily was then given again for one week. The mean duration of prednisone reduction was 7.4 weeks and the median dose was 7.5 mg x day(-1). Increases in sputum eosinophils preceded increases in blood eosinophils by 4 weeks and worsening of symptoms and forced expiratory volume in one second by 6 weeks. The clinical exacerbation was also accompanied by sputum neutrophilia and increases in sputum eosinophil cationic protein (ECP), fibrinogen and interleukin (IL)-5. Treatment with prednisone suppressed median sputum eosinophilia (from 16.3 to 0%, p<0.001), decreased sputum ECP (from 7,480 to 700 microg x L(-1), p = 0.01), but did not improve neutrophil numbers, fibrinogen or IL-5. The results show that the reduction of prednisone treatment in prednisone-dependent asthmatics evokes a severe airway eosinophilic inflammatory response. Clinical and blood indices deteriorate later than those in sputum suggesting that sputum examination may be useful to identify the minimum regular dose of prednisone required in these patients.     

Premenstrual asthma

Gender differences have been recognized in asthma. Specifically in women, an exacerbation in symptoms occurring a few days prior to the onset of menstruation constitutes a phenotype that is not yet fully understood. This phenomenon, called "premenstrual asthma," has been reported to affect upto 40% women with asthma. This article reviews the literature on prevalence, effect of menstrual cycle on symptoms and lung function and discusses the proposed mechanisms of pathogenesis including the effects of female sex hormones on symptoms and beta2 adrenergic receptor function, and the role of airway inflammation. Finally, the various treatment options are presented.     

Spontaneous anovulation causing disappearance of cyclical symptoms in women with the premenstrual syndrome

In the premenstrual syndrome the negative symptoms appear during the luteal phase of the menstrual cycle. Ovulation and the formation of a corpus luteum seem to be of great importance in precipitating the syndrome. In a large group of women with premenstrual syndrome investigated daily with symptom ratings and weekly plasma estradiol and progesterone assays, 8 were found to have one ovulatory and one spontaneously occurring anovulatory menstrual cycle. In both these cycles, the post- and premenstrual phases were compared by testing for recurrence of symptoms. All patients showed a highly significant cyclical worsening of negative premenstrual symptoms during the ovulatory cycles, whereas in the anovulatory cycles the cyclical symptoms disappeared, resulting in relief of the premenstrual syndrome. These results support earlier hypotheses, suggesting that the premenstrual syndrome appears as a result of provoking factors produced by the corpus luteum. This view is in line with earlier therapeutic findings showing that induced anovulation can relieve the premenstrual syndrome.     

Premenstrual Asthma: Prevalence,Cycle-to-Cycle Variability and Relationship to Oral Contraceptive Use and Menstrual Symptoms

The prevalence of asthma is higher in women than men of reproductive age and almost half of all hospitalisations for asthma in women occur during the perimenstrual phase of the cycle. The mechanisms of premenstrual asthma (PMA) are unknown and a definition of PMA has not been clearly presented in the literature. The objective of this study was to determine the prevalence of PMA using a variety of definitions, to investigate the cycle-to-cycle variation in PMA, the effects of oral contraceptive use and the relationship between PMA and premenstrual symptoms. Premenopausal women with asthma (n = 28) were prospectively followed for at least 12 weeks over 2–4 consecutive menstrual cycles. Asthma symptoms, β₂-agonist and inhaled corticosteroid use and morning and evening peak expiratory flow were recorded daily. The following types of PMA definitions were investigated: self-reported PMA, increased symptoms, increased medication use, decreased peak flow or a combination of changes in symptoms, medication and peak flow. Changes of more than 20%, for at least 2 consecutive days of the luteal phase (last 14 days of the cycle prior to menstruation) compared to the early follicular phase average (first 7 days after menstruation) were considered PMA. Using a composite definition where subjects experienced increased symptoms and medication use with or without a change in peak flow, 16 subjects were classified as having PMA (57%), while 12 did not have PMA. Only 4 subjects (25%) had PMA in every cycle examined. Fifty-five percent of subjects who used oral contraceptives had PMA, while 59% of subjects who did not use oral contraceptives had PMA. Women who were defined PMA using the composite definition were more likely than those without PMA to experience a 20% decrease in peak flow during the luteal phase. There was no relationship between asthma symptoms and premenstrual symptoms on day 1 of the menstrual cycle in women with PMA. PMA resulting in increased symptoms and medication use occurred in 57% of subjects studied for 2–4 menstrual cycles. The use of oral contraceptives is not protective and further work is required to elucidate the mechanisms of PMA.     

Effect of exposure to domestic cooking fuels on bronchial asthma

The effect of indoor air pollution due to domestic cooking with biomass fuel and liquefied petroleum gas (LPG) on the course of bronchial asthma was examined in one hundred non-smoking female asthmatics. The parameters for evaluation were symptoms, emergency visits, and drug requirements. The patients also measured peak expiratory flow rate (PEFR) at home five times daily over a period of one week and the levels of carboxyhaemoglobin (COHb) were estimated randomly during clinic visits. The COHb levels (%) were 4.1 +/- 0.9 and 3.5 +/- 0.6 in the two groups with 22-30% of the subjects reporting increased symptoms during cooking. The number of emergency admissions and the daily requirement of steroids were comparable in both the groups. The PEFR values were lower than the predicted values in both the groups at all times. Further, the readings after exposure to cooking fuels were lower than those before cooking in both the groups (p < 0.01) and these values were similar to those observed during early morning records at 6 AM, which were the lowest. It was concluded that exposure to biomass fuel and LPG affect pulmonary function (PEFR) in asthmatics and both types of fuels affect the airway function and symptoms of bronchial asthma in a similar manner.     

The menstrual cycle affects rectal sensitivity in patients with irritable bowel syndrome but not healthy volunteers

BACKGROUND: We have previously shown that the menstrual cycle has no effect on rectal sensitivity of normal healthy women, despite them having looser stools at the time of menses. Patients with irritable bowel syndrome (IBS) often report significant exacerbation of their IBS symptoms with menses, raising the possibility that IBS patients may respond differently to the menstrual cycle. AIM AND METHODS: Rectal responses to balloon distension during days 1-4 (menses), 8-10 (follicular phase), 18-20 (luteal phase), and 24-28 (premenstrual phase) of the menstrual cycle were assessed in 29 female IBS patients (aged 21-44 years), diagnosed by the Rome I criteria. During the course of the study patients completed symptom diaries to assess abdominal pain and bloating (visual analogue scale), and frequency and consistency of bowel habits. In addition, levels of anxiety and depression were assessed using the hospital anxiety and depression questionnaire. RESULTS: Menses was associated with a worsening of abdominal pain and bloating compared with most other phases of the menstrual cycle (p<0.05). Bowel habits also became more frequent (p<0.05) and patients tended to have a lower general well being. Rectal sensitivity increased at menses compared with all other phases of the cycle (p<0.05). There was no associated change in rectal compliance, wall tension, or motility index. Neither was there any difference in resting anal pressure or the distension volumes required to relax the internal anal sphincter during the menstrual cycle. CONCLUSION: These data (1) confirm that IBS symptomatology is exacerbated at menses and (2) show for the first time that in contrast with healthy women, rectal sensitivity changes with the menstrual cycle. These cyclical changes in sensitivity suggest that women with IBS respond differently to fluctuations in their sex hormonal environment or its consequences compared with healthy females.     

Effects Of Theophylline Withdrawal in Well-Controlled Asthmatics Treated with Inhaled Corticosteroid

We examined effects of theophylline withdrawal in 17 adult asthmatics whose symptoms were well controlled under a treatment of a combination of theophylline and inhaled beclomethasone dipropionate (iBDP). We measured daily symptoms, daily peak flow values, spirometry, peripheral blood eosinophil count (EOS), and serum eosinophil cationic protein (sECP) at intervals of 1-3 weeks for 3 months after theophylline withdrawal. Twelve patients experienced exacerbation of asthma (exacerbation group), whereas the remaining 5 patients exhibited no symptoms (stationary group). In the exacerbation group, forced expiratory volume in 1 sec (FEV₁) and percent vital capacity (%VC) gradually decreased until exacerbation of asthma, and the extent of these decreases within the first week after the withdrawal was greater compared with that at later than the third week. decreased in both the exacerbation and stationary groups. In particular, the extent of the velocity of expiratory flow at 25% of the vital capacity/height () decrease in the exacerbation group was much greater than that of FEV₁ or %VC in this group. Neither EOS nor sECP changed significantly during the clinical course in any patient. The rapid decrease in FEV₁ and %VC after the withdrawal suggests that under treatment with iBDP, theophylline causes direct bronchodilating effects on smooth muscle, rather than anti-inflammatory effects. These results also suggest the importance of theophylline on peripheral as well as central airways.     

Comparison of Mometasone Furoate Dry Powder Inhaler and Fluticasone Propionate Dry Powder Inhaler in Patients with Moderate to Severe Persistent Asthma Requiring High-Dose Inhaled Corticosteroid Therapy: Findings from a Noninferiority Trial

Background. Inhaled corticosteroids (ICSs) are one of the suggested first-line therapies for patients with persistent asthma of moderate severity. Methods: The efficacy and safety of mometasone furoate (MF) 400 μg twice daily (BID) and fluticasone propionate (FP) 500 μ g BID administered for 12 weeks via dry powder inhaler (DPI) were compared in a noninferiority trial, in adults with moderate-to-severe persistent asthma. The primary variable was the change from baseline in am peak expiratory flow rate (PEFR). pm PEFR, forced expiratory volume in 1 second (FEV₁), asthma symptoms, rescue medication use, response to therapy, exacerbation rates, and adverse events were also assessed. Results. The lower bound of 95% CIs for treatment differences in the primary variable ranged from 2.6% to 5.6% throughout the 12-week study and were within the prespecified noninferiority range. No significant between-group differences were observed in lung function, rescue medication use, response to therapy, exacerbation rates, or adverse events. At most of the weeks assessed, there were no between-group differences in asthma symptoms. Most adverse events were mild-to-moderate. Conclusion. MF-DPI 400 μ g BID was therapeutically equivalent to FP-DPI 500 μ g BID in patients with moderate-to-severe persistent asthma.     

Effects of a Short Course of Pranlukast Combined with Systemic Corticosteroid on Acute Asthma Exacerbation Induced by Upper Respiratory Tract Infection

Background. Upper respiratory tract infections (URIs) represent the most frequent cause of acute asthma exacerbation. Systemic corticosteroid (CS) is presently recommended for URI-induced asthma exacerbation, although it might inhibit cellular immunity against respiratory virus infection. Objectives. To determine the effects of adding a short course (2 weeks) of a leukotriene receptor antagonist (LTRA) to systemic CS on URI-induced acute asthma exacerbation. Methods. Twenty-three adult asthmatics (mean age, 42.8 ± 9.8 y; Male:Female, 10:13) with URI-induced acute asthma exacerbation confirmed by a questionnaire and physical findings were randomly assigned to receive either oral prednisolone (PSL) alone or oral PSL plus the LTRA pranlukast (PRL) for 2 weeks (PSL + PRL). The cumulative doses of PSL and the amount of time required to clear asthma-related symptoms were determined. Levels of respiratory syncytial virus (RSV) RNA and influenza viral (IV) antigen in nasopharyngeal swabs were also determined. Results. Adding PRL significantly reduced the cumulative dose of PSL and tended to reduce the time required to clear asthma-related symptoms. Either RSV or IV was detected in about one-third of the patients. Conclusion. The combination of an LTRA and CS might be more useful than CS alone for treating URI-induced acute exacerbation of asthma and reducing the cumulative CS dose.     

Time course and recovery of exacerbations in patients with chronic obstructive pulmonary disease

Although exacerbations of chronic obstructive pulmonary disease (COPD) are associated with symptomatic and physiological deterioration, little is known of the time course and duration of these changes. We have studied symptoms and lung function changes associated with COPD exacerbations to determine factors affecting recovery from exacerbation. A cohort of 101 patients with moderate to severe COPD (mean FEV(1) 41.9% predicted) were studied over a period of 2.5 yr and regularly followed when stable and during 504 exacerbations. Patients recorded daily morning peak expiratory flow rate (PEFR) and changes in respiratory symptoms on diary cards. A subgroup of 34 patients also recorded daily spirometry. Exacerbations were defined by major symptoms (increased dyspnea, increased sputum purulence, increased sputum volume) and minor symptoms. Before onset of exacerbation there was deterioration in the symptoms of dyspnea, sore throat, cough, and symptoms of a common cold (all p < 0.05), but not lung function. Larger falls in PEFR were associated with symptoms of increased dyspnea (p = 0.014), colds (p = 0.047), or increased wheeze (p = 0.009) at exacerbation. Median recovery times were 6 (interquartile range [IQR] 1 to 14) d for PEFR and 7 (IQR 4 to 14) d for daily total symptom score. Recovery of PEFR to baseline values was complete in only 75.2% of exacerbations at 35 d, whereas in 7.1% of exacerbations at 91 d PEFR recovery had not occurred. In the 404 exacerbations where recovery of PEFR to baseline values was complete at 91 d, increased dyspnea and colds at onset of exacerbation were associated with prolonged recovery times (p < 0.001 in both cases). Symptom changes during exacerbation do not closely reflect those of lung function, but their increase may predict exacerbation, with dyspnea or colds characterizing the more severe. Recovery is incomplete in a significant proportion of COPD exacerbations.     

Formoterol, a new long-acting bronchodilator for inhalation

The aim of this study was to evaluate if treatment with inhaled formoterol is appreciated by asthmatics and whether it causes tachyphylaxis. Twenty stable asthmatics were included in a randomized, double-blind, crossover study. They were treated for two weeks either with formoterol or salbutamol, with one week washout inbetween. They were given 12 micrograms formoterol or 200 micrograms salbutamol twice daily and instructed to use additional spray doses on demand. On a diary card they recorded the number of doses, asthma symptoms and peak expiratory flow rate (PEFR) before every dose. Forced expiratory volume in one second (FEV1) dose-response curves for salbutamol (total dose 1.3 mg) were performed before and after each treatment period to evaluate development of tachyphylaxis. There was a significant difference in favour of formoterol concerning symptoms, PEFR recordings, spray consumption, and preference. Fifteen patients preferred formoterol and two salbutamol. The dose-response curves before formoterol and before, as well as after salbutamol were almost identical. After formoterol the curve had changed; both basal and maximum values were higher than before. Thus, no evidence of tachyphylaxis was found, compared to the ordinary beta-stimulant treatment.     

Once daily theophylline in childhood asthma

A new sustained-release theophylline preparation has been designed with the purpose of providing 24-hour protection against bronchospasm in asthmatics when given as a single dose. Fifteen children with moderate asthma completed a double-blind, placebo-controlled crossover trial of this product given once a day before bed. There was a significant fall in night symptoms (P less than 0.05), a rise in the mean early morning peak expiratory flow rate (PEFR) (P less than 0.01) and a fall in the number of mornings on which PEFR was less than 2 SD under the mean for height (P less than 0.01). An improvement in mean day symptom scores and evening PEFR was not significant. Thus we have shown that this product given once a day before bed is suitable for this way.