The effect of inhaled 5-hydroxytryptamine (5-HT, serotonin) on airway calibre in man.

Since platelet activation has been incriminated in the pathogenesis of asthma, we have investigated the effect of one of its major granule-derived mediators, 5-hydroxytryptamine (5-HT, serotonin) on airway calibre in normal (12), atopic non-asthmatic (12) and atopic asthmatic subjects (16). On separate days subjects inhaled increasing concentrations of 5-HT and methacholine, and airway response was measured as FEV1, Vmax30 and sGaw. All subjects bronchoconstricted with methacholine, geometric mean provocation concentrations causing a 20% fall in FEV1 (PCf20) for the normal, atopic non-asthmatic and atopic asthmatic subjects being 28.6, 18.3 and 0.71 mM respectively. In contrast, 5-HT up to a maximum concentration of 77 mM had no consistent effect on FEV1, Vmax30 or sGaw in any of the subject groups. Thus, in contrast to a variety of animals, 5-HT is unlikely to serve as a significant bronchoconstrictor mediator in man.     

Inhaled adenosine and guanosine on airway resistance in normal and asthmatic subjects

1 The airway response to the inhaled nucleosides, adenosine (6.7 × 10^-4-6.7 mg/ml) and guanosine (7.3 × 10^-4-1.4 mg/ml) was studied in normal and asthmatic subjects. Airway response, measured in the body plethysmograph, was expressed as percentage change in specific airway conductance (sGaw) from baseline.

2 Inhaled adenosine caused no change in sGaw in normal subjects but produced a dose-dependent reduction in sGaw in both allergic and non-allergic asthmatic subjects (76 and 62% reduction respectively at 6.7 mg/ml).

3 Kinetics of adenosine induced bronchoconstriction were studied in 12 asthmatic subjects who inhaled a single concentration of adenosine. Bronchoconstriction was maximal within 5 min (42% reduction in sGaw) with partial recovery by 30 min.

4 The related nucleoside guanosine caused no change in sGaw in normal or asthmatic subjects.

5 Adenosine, but not guanosine, is a potent bronchoconstrictor in asthma suggesting that it may have a specific pharmacological effect.

     

Effect of an inhaled histamine H3-receptor agonist on airway responses to sodium metabisulphite in asthma.

Histamine H3-receptor agonists inhibit excitatory neuro-transmission in human and guinea-pig airways. Since neural bronchoconstriction may be important in asthma we have studied the effect of a specific H3-receptor agonist R-alpha-methylhistamine (alpha MeHA) on bronchoconstriction induced by the inhaled irritant sodium metabisulphite (MBS) in six mild asthmatic subjects in a randomised double-blind crossover study. Subjects received either alpha MeHA, 10 mg (as a chloride salt) or matched placebo (P) and were then challenged with doubling concentrations of MBS (0.3-80 mg ml-1) nebulised from a dosimeter at 5 min intervals with measurement of specific airway conductance (sGaw) and FEV1 at 2 and 4 min respectively after each inhalation. There was no effect of alpha MeHA on baseline airway calibre and the log concentrations of MBS required to lower sGaw by 50% (log PC50) and FEV1 by 20% (log PC20) were not significantly different after alpha MeHA when compared with placebo, suggesting that selective stimulation of airway H3-receptors does not inhibit MBS-induced bronchoconstriction.     

Effect of intravenous magnesium sulphate on airway calibre and airway reactivity to histamine in asthmatic subjects

In a randomized, double-blind, placebo controlled cross-over study we have investigated the effect of intravenous magnesium on airway calibre and airway reactivity to histamine in 20 subjects with mild to moderate asthma. After baseline measurements of forced expiratory volume in one second (FEV₁), subjects received 100 ml normal saline with or without 2 g of magnesium sulphate by infusion over 20 min. Measurements of FEV₁ were repeated at 5 min intervals throughout the infusion, and the provocative dose of histamine required to drop the FEV₁ by 20% from baseline ( PD ₂₀FEV₁) was determined at 20 min. The area under the curve (AUC) in litre minutes for change from baseline in FEV₁ between 0 and 20 min was significantly higher on the magnesium study day (mean difference in AUC (95% CI) 1.71 (0.02-3.4), P = 0.049). The increase in FEV₁ from baseline with magnesium relative to saline was maximal at 20 min (mean difference (95% CI) 0.13 (0.02-0.23) 1, P = 0.01). Log P D ₂₀FEV₁ to histamine was not significantly different after magnesium and saline (mean difference in log P D ₂₀FEV₁ (95% CI) 0.04 (-0.19 to 0.27), P = 0.7). We conclude that intravenous magnesium is a weak bronchodilator but does not alter airway reactivity at this dose in stable asthmatic subjects.     

沙美特罗/丙酸氟替卡松对哮喘儿童肺功能的改善及临床意义

目的:观察沙美特罗/丙酸氟替卡松对哮喘儿童肺功能改善情况。方法:采用德国Jaeger公司的MasterscreenIOS测定仪,对61例支气管哮喘患儿在沙美特罗/丙酸氟替卡松治疗前后进行通气肺功能(F-V)和脉冲振荡(IOS)检测。观察用力肺活量(FVC)、第一秒用力呼气容积(FEV1)、最大呼气流速(PEF)、呼出25%肺活量时最大呼气流量(FEF25)、呼出50%肺活量时最大呼气流量(FEF50)、呼出75%肺活量时最大呼气流量(FEF75);呼吸阻抗(Zrs)、气道总阻力(R5)、中心气道阻力(R20)、响应频率(Fres)。结果:沙美特罗/丙酸氟替卡松治疗后FVC、FEV1、PEF均明显升高(P<0.001),而Zrs、R5、R20、Fres均明显降低(P<0.05),两者检查结果均有显著统计学意义。结论:吸入沙美特罗/丙酸氟替卡松能改善哮喘儿童的肺通气功能,降低气道阻力,是治疗儿童哮喘的理想药物之一。     

Comparison of the airway response to eye drops of timolol and its isomer L-714,465 in asthmatic subjects.

1. The inadvertent administration of timolol to asthmatic patients continues to cause occasional severe and even fatal attacks of asthma. The (R)-enantiomer of timolol, L-714,465, is four times less potent than timolol in reducing intraocular pressure in man. It is 49 times less potent than timolol on beta 2-adrenoceptors in animals and 13 times less potent on the airways of normal subjects. These findings suggested that L-714,465 might be a safer alternative for the treatment of glaucoma. 2. Ten subjects with mild asthma who bronchoconstricted to timolol eye drops (0.25 or 0.5%) were studied. Airway dose-response curves to timolol (0-2%), L-714,465 (0-4%), and placebo (methyl cellulose) eye drops were performed in a double-blind randomised study in which airway response was measured as change in FEV1 and specific airway conductance (sGaw). 3. L-714,465 and timolol caused dose dependent falls in sGaw and FEV1 with L-714,465 being approximately four times less potent than timolol. The geometric mean dose ratio was 3.89 for FEV1 (95% confidence interval (CI) 1.7-8.7) and 3.93 (95% CI 2-7.8) for sGaw. Since the difference in potency is similar to the reported difference in potency of the two drugs on intraocular pressure we conclude that L-714,465 would not have a greater safety margin than timolol. 4. After completion of the dose-response study eight subjects inhaled ipratropium bromide (72 micrograms) and this caused an increase in FEV1 from 74% to 80% of baseline.(ABSTRACT TRUNCATED AT 250 WORDS)     

Specific antagonism of adenosine-induced bronchoconstriction in asthma by oral theophylline.

The airway response to increasing concentrations of inhaled-adenosine and histamine after oral theophylline or matched placebo was studied in nine asthmatic subjects. Changes in airway calibre were followed as sGaw and FEV1 and concentration-response curves constructed. Inhaled adenosine caused concentration-related bronchoconstriction and was four-five times less potent than inhaled histamine. Theophylline, which achieved a mean plasma level of 15.9 and 16.6 micrograms/ml on the histamine and adenosine study days respectively, caused significant increases in FEV1 (17%) and sGaw (41-53%) whereas placebo had no effect. Theophylline also protected the airways against histamine-and adenosine-induced bronchoconstriction. However theophylline had a greater protective effect against adenosine (concentration-ratio 17.4 for FEV1 and 12.8 for sGaw) than against histamine (concentration ratio 5.6 for FEV1 and 5.4 for sGaw (P less than 0.05]. At therapeutic concentrations theophylline is a specific antagonist of the airway effects of adenosine in addition to being a bronchodilator and a functional antagonist.     

Inhibition of artificially induced cough in man by bronchodilators.

1. The antitussive properties of bronchodilators were evaluated in a total of 47 normal volunteers. 2. Cough was induced by inhalation of ultrasonically nebulized solutions of distilled water and hypotonic saline. 3. Inhaled fenoterol hydrobromide (360 micrograms; 20 volunteers) and inhaled ipratropium bromide (72 micrograms; 14 volunteers) both significantly reduced couch compared with placebo (P less than 0.01). Oral salbutamol sulphate (4 mg; 11 volunteers) and oral pirenzepine hydrochloride (50 mg; 14 volunteers) had lesser effects. 4. Cough inhibition correlated with a small but statistically significant degree of bronchodilatation as measured by specific airway conductance (sGaw) and forced expiratory volume in one second (FEV1) in six normal subjects studied with each treatment in a placebo controlled, double blind study (r = 0.67, P less than 0.001). 5. Small reductions in airway tone are associated with a reduced cough response elicited by inhaled ultrasonically nebulized distilled water.     

Bronchial and cardiac beta-adrenoceptor blockade--a comparison of atenolol, acebutolol and labetalol.

Bronchial and cardiac beta-adrenoceptor blockade have been compared in six normal subjects after three beta-adrenoceptor antagonists. Single and double doses of atenolol (50 and 100 mg), acebutolol (100 and 200 mg) and labetalolol (150 and 300 mg) were studied on separate occasions. 2 Salbutamol airway dose-response curves were obtained by measuring the airway response as the change in specific airway conductance (sGaw) after increasing doses of inhaled salbutamol. Bronchial beta-adrenoceptor blockade was assessed after each drug as the dose of salbutamol needed to cause a 50% increase in sGaw (sGaw D50). 3 Cardiac beta-adrenoceptor blockade was assessed after the same doses of each beta-adrenoceptor antagonist, by measuring the percentage reduction in exercise heart rate from control, after exercise for 5 min at 70% of the subject's maximum work rate. 4 Atenolol 50 and 100 mg caused least bronchial beta-adrenoceptor blockade and the greatest reduction in exercise heart rate. 5 Acebutolol 100 and 200 mg and labetalol 150 and 300 mg produced more bronchial beta-adrenoceptor blockade than atenolol. 6 With this approach new beta-adrenoceptor antagonists can be assessed without putting asthmatic patients at risk.     

Comparative effects of rilmenidine and clonidine on bronchial responses to histamine in asthmatic subjects.

1. The effects of pretreatment with clonidine and rilmenidine, a new alpha 2-adrenoceptor agonist, on the bronchial responses to inhaled histamine were studied on 3 different days in a controlled, double-blind, randomized study in 12 asymptomatic asthmatic subjects. Clonidine and rilmenidine were orally administered as single and equipotent doses of 150 micrograms and 1 mg, respectively. All the subjects were non-smokers with normal lung function tests (forced expiratory volume in one second (FEV1) = 97 +/- 10% predicted FEV1). 2. Histamine (first dose = 543 nmol) was delivered by a breath activated dosimeter (DeVilbiss no. 646 nebulizer) every 5 min; FEV1 was measured in triplicate after each dose and the largest value was analyse. The three dose-response curves were compared by analysis of variance. 3. Both clonidine and rilmenidine decreased arterial blood pressure in all subjects. There was no difference in baseline values and pre-challenge values of FEV1 after placebo, clonidine and rilmenidine on the 3 study days. Compared with placebo, both rilmenidine and clonidine significantly increased the bronchial responses to histamine (P less than 0.05 and P less than 0.01 respectively) an effect which was significantly more marked with clonidine than rilmenidine (P less than 0.05). 4. We suggest that the enhancement of bronchial responsiveness to histamine by clonidine and rilmenidine may result from their effects on both central and peripheral alpha 2-adrenoceptors, and that the lesser aggravation of histamine-induced bronchial obstruction in asthmatic subjects on rilmenidine might be explained by its lesser central and/or greater peripheral effects than clonidine.     

Inhaled histamine increases the rate of absorption of sodium cromoglycate from the lung.

Since many factors may alter lung epithelial permeability (LEP) to water soluble molecules, the effect of histamine on the absorption and clearance of inhaled sodium cromoglycate was examined in seven mildly asthmatic patients with hyperresponsive airways and eight normal subjects. The subjects underwent histamine challenge to determine the provocative concentration of histamine required to reduce the forced expiratory volume in one second (FEV1) by 20% (PC20) from baseline. On two further visits they inhaled either saline placebo or histamine and 5 min later inhaled an aerosol containing sodium cromoglycate. Measurements of FEV1 were made and blood samples taken for analysis of plasma sodium cromoglycate concentration at intervals for 3 h. In the asthmatic group histamine inhalation led to a 24 +/- 4% reduction in FEV1 but had no effect on the normal subjects. When compared with inhaled saline, histamine increased the initial pulmonary absorption of SCG without influencing the total amount of drug absorbed in both asthmatics and normals. These observations suggest that the pharmacokinetics of inhaled sodium cromoglycate may be altered significantly by inflammatory mediators present at the site of drug absorption from the airways.     

Assay-dependent kinetics of heparin: evidence for rapid in vivo activation of heparin.

We have compared bronchodilator dose-response curves to inhaled salbutamol in seven normal and eight asthmatic subjects. In all normal subjects maximal bronchodilatation measured by partial flow volume curves was achieved at a cumulative dose of 110 micrograms. The dose necessary to produce half maximal response (ED50) was 23 +/- 2 micrograms (mean +/- s.e. mean) with a range of 18-28 micrograms. In asthmatic subjects maximal bronchodilatation measured by FEV1 and by maximal flow volume curves was achieved at significantly higher (P less than 0.01) doses of salbutamol with a mean ED50 of 83 +/- 28 micrograms and range of 25-251 micrograms. There was a significant (P less than 0.05) correlation between ED50 and % predicted baseline FEV1. This is more likely to reflect impaired access of drug for airway beta-adrenoceptors than impaired beta-adrenoceptor function in asthma. In five asthmatic subjects dose-response curves to salbutamol and isoprenaline were compared and found to be similar, thus providing no evidence that salbutamol is a partial agonist in vivo, as it appears to be in vitro.     

Safety and pharmacokinetics of inhaled morphine delivered using the AERx system in patients with moderate-to-severe asthma

OBJECTIVE: The safety and pharmacokinetics of inhaled morphine in asthmatic subjects were investigated using the AERx System, a novel aerosol system. METHODS: Twenty subjects with asthma received inhaled placebo and inhaled morphine sulfate, 2.2 mg, 4.4 mg and 8.8 mg, on separate days in a single-blind crossover study. Six of the subjects received an additional open-label dose of 17.6 mg on a separate day. Plasma morphine concentrations and safety evaluations including pulmonary function testing were performed. RESULTS: Mean tmax values were similar following all dose groups at approximately 1-2 minutes. Mean AUC(0-->1) values showed dose proportionality for the first 3 dose groups (6.3, 12.3 and 24.3 ng x h x ml(-1)), the mean AUC(0-->1) for the 17.6 mg dose group was 1.6x that of the 8.8 mg dose group. No statistically significant differences in forced expiratory volume in 1 sec (FEV1) were found for the 2.2 mg, 4.4 mg, or 8.8 mg dose groups; at 17.6 mg, a statistically significant but not clinically meaningful reduction in mean FEV1 (-8.18%) from baseline occurred at 10 minutes compared to placebo, spontaneously returning to baseline by 60 min. Four subjects experienced significant but reversible decreases in FEV1 of > or = 20% compared to baseline and across all dose levels including after placebo, but with no associated increase in dyspnea, wheezing or other adverse events. CONCLUSIONS: Inhaled morphine using the AERx System was absorbed rapidly and demonstrated dose-dependent plasma concentrations. It was well-tolerated and did not cause clinically significant bronchoconstriction in most subjects with moderate-to-severe asthma.     

The effect of tiotropium on the pulmonary diffusing capacity

To our knowledge, there is no data on the effect of tiotropium on pulmonary gas exchange in healthy subjects. The aim of this study was to assess the effects of tiotropium on pulmonary diffusing capacity. Twenty-one healthy volunteers were enrolled for a prospective, randomized, double-blind, placebo-controlled study. Spirometric measurements, including pulmonary-diffusing capacity, were obtained before and after inhalation of drug or placebo. There was a significant decrease in forced vital capacity (FVC) and, consequently, an increase in the forced expiratory volume in one second (FEV1) to FVC ratio after placebo inhalation (p < 0.05), but no changes were found for percent-predicted FVC, FEV1, percent-predicted FEV1, percent-predicted forced expiratory flow (FEF25%-75%), percent-predicted peak expiratory flow (PEF), diffusing capacity of the lung for carbon monoxide (DLCO), single-breath alveolar volume (VA) and DLCO/VA ratio when compared with the baseline. Tiotropium inhalation caused a significant increase in FVC, percent-predicted FEV1, FEV1/FVC and percent-predicted FEF25%-75%, although the decrease in DLCO was insignificant (12.4 +/- 0.9 to 11.4 +/- 0.9). In conclusion, tiotropium does not change the pulmonary-diffusing capacity in healthy volunteers.     

Physiological changes in pulmonary development related to passive smoking and its interaction with active smoking

The growth of pulmonary function between ages 5.5 and 25 years was determined in 1502 observations on 362 subjects from a representative population study of non-Mexican American whites in Tucson. There was an average of 8.8 years of follow-up, with a maximum of 12. The model developed was robust for follow-up of 3-7 observations (3 + years). Respiratory illnesses and smoking had the biggest negative impact on growth of forced expiratory volume in 1 s (FEV1), Vmax 50%/forced vital capacity (FVC) parental smoking and airway obstructive disease (AOD) were important also. Flow measures showed present and more persistent effects of disease and smoking than did FEV1.     

Effects of a thromboxane receptor antagonist on prostaglandin D2 and histamine induced bronchoconstriction in man.

Many prostanoids including are prostaglandin (PG) F2 alpha and PGD2 are potent bronchoconstrictor agents. There is evidence to suggest that airway thromboxane (TP) receptor may act as a common receptor for their bronchoconstrictor actions. We tested the hypothesis that inhaled prostaglandin (PG) D2-induced bronchoconstriction is mediated by interacting with the TP receptor antagonist, ICI 192605, on the bronchoconstrictor response to inhaled PGD2 in a double-blind, placebo-controlled and crossed-over trial in normal subjects. The effect of ICI 192605 on histamine induced bronchoconstriction served as control for non-specific bronchodilatory actions. The study had two phases; the first consisted of two inhaled PGD2 challenge study days, and the second phase was that of inhaled histamine. Each study day was separated by at least a week. On each study day, the challenge tests were carried out 30 min after ingestion of 100 mg ICI 192605 or placebo. Doubling concentrations of agonist were given till more than 35% fall in post-diluent specific airway conductance (sGaw) occurred. The concentration needed to cause a fall in a sGaw of 35% post-diluent value (PC35sGaw) was then determined from linear interpolation of the log dose-response. Eight male subjects (median age 26, range 20-35 years) completed the study. ICI 192605 did not change baseline airway calibre 30 min after ingestion on either PGD2 or histamine study days. ICI 192605 significantly shifted the dose-response curve to inhaled PGD2 to the right by a median of 3.4 fold (Wilcoxon rank sign test, P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Large and small airway responses to procaterol hydrochloride administered through different extension devices in asthmatic patients.

The effects of spacer devices on the magnitude and velocity of large and small airway bronchodilator responses in asthmatic patients who can correctly operate a metered dose inhaler (MDI) remain unclear. According to a double-blinded, randomized, crossover protocol, 14 asthmatic patients were studied on seven separate occasions. On each occasion, patients inhaled doubling methacholine concentrations until forced expiratory volume in 1 second (FEV1) had fallen by 20% of baseline. Changes in forced expiratory flow between 25% and 75% of vital capacity (FEF25-75) were also evaluated. Subsequently, patients were administered 20 or 50 micrograms of procaterol from an MDI either alone or in conjunction with a small- or large-volume spacer device. Changes in FEV1 and FEF25-75 corrected for baseline forced vital capacity (isoFEF25-75) were assessed at 3-minute intervals for 15 minutes and at 30 minutes. Spontaneous recovery was similarly evaluated. The time required to attain significant increases in both FEV1 and isoFEF25-75 was calculated in bronchodilator trials. With 20 micrograms of procaterol, both spacers allowed larger and faster FEV1 increases than the MDI alone (P < 0.01); with 50 micrograms, the velocity and magnitude of FEV1 increases were further enhanced in trials with the MDI alone. The lower procaterol dose via the large-volume spacer determined larger and faster isoFEF25-75 increases than the higher dose via both the small-volume spacer and the MDI alone (P < 0.01). Spacers enhance bronchodilation even in patients using MDIs optimally. Compared with both the small-volume device and the MDI alone, the large-volume spacer allows faster and larger small airway dilation with less than half of the procaterol dose.     

普通肺炎支原体肺炎患儿肺功能检测的临床意义

目的：探讨儿童普通肺炎支原体肺炎（MPP）急性期及恢复期肺通气功能的变化及其检测意义。方法：选取2014年6月至2015年6月在我院住院的5~14岁普通MPP急性期（发病1周内）患儿74例,行常规肺功能检测,随访至恢复期（发病后第3周）,66例再次行常规肺功能检测;另选取同期健康儿童60例作为对照组。结果：普通MPP急性期各项肺功能指标（FVC、FEV1、PEF、FEF25、FEF50、FEF75、MMEF）与FEV1/FCV较恢复期均下降（P均<0.01）;恢复期FVC、FEV1、PEF基本恢复正常,而FEF25、FEF50、FEF75、MMEF较对照组仍有减低（P均<0.01）;急性期与恢复期FEV1/FVC均保持在正常范围。结论：儿童普通MPP急性期存在限制性、阻塞性通气功能障碍及小气道损害,限制性通气功能障碍相对较轻,小气道损害相对较重,而在恢复期限制性及阻塞性肺通气功能障碍明显改善,但仍有小气道损害,故普通MPP小气道损害时间明显较大气道长。肺通气功能检测可以较为客观地反映肺损害的情况,可以判断病情轻重、评估疗效及判断预后。     

Beta-adrenoceptor responses to inhaled salbutamol in normal subjects

Summary The aim of the present study was to quantify and compare the airways and systemic beta-adrenoceptor responses to inhaled salbutamol in normal subjects. Seven non-atopic, normal subjects were given cumulative doubling doses of inhaled salbutamol (100 µg to 4000 µg) or placebo in a single-blind cross-over design. Airways (sGaw, FEF 50%, FEF 25%), tremor, haemodynamic and metabolic responses were measured at each dose increment.There were dose-related changes in sGaw, FEF 50% and FEF 25% up to a plateau at 1.0 mg. Analysis of individual responses showed that most subjects required either 1.0 or 2.0 mg for maximum bronchodilatation, independent of the parameter of airflow. There was no correlation between maximum response and baseline airway calibre. In contrast to airways effects, systemic beta-adrenoceptor responses did not occur until 500 µg, and a ceiling in the dose-response curve was not reached.Therer were significant correlations between air-ways, tremor and haemodynamic responses, and between different metabolic variables. The intraindividual variability was greatest for tremor and sGaw, although this was small in comparison to the size of maximum change with salbutamol. The converse applied to the hypomagnesaemic response.Parts of this paper have been presented in abstract form to the British Pharmacological Society: Liverpool UK (Spring Meeting, April 1988) and Dublin, Eire (Summer Meeting, July 1988)     

Zafirlukast versus budesonide on bronchial reactivity in subjects with mild-persistent asthma

Asthma is one of the most common chronic diseases in children and adults. Recent studies have shown that in asthmatic patients treated with inhaled corticosteroids there is a better disease?s control when adding a second drug, than increasing the corticosteroid?s dose. The aim of this study has been to evaluate the effectiveness and tolerance of zafirlukast, a leukotriene receptor antagonist, versus budesonide in clinically steady patients with mild persistent bronchial asthma. We have enrolled 36 subjects non smokers, with mild persistent bronchial asthma and 12 healthy subjects as control group. At the beginning of this study and at the end of the treatment (8 weeks), all patients underwent complete clinical work-up, pulmonary function testing (FEV1, PEF and FVC) and methacholine challenge test. The patients were divided into 3 groups: group A) 20 mg of zafirlukast twice a day; group B) 400 mg of budesonide twice a day; group C) 20 mg of zafirlukast twice a day and 400 mg of budesonide twice a day. Basal FEV1 and PEF presented no significant statistical differences between control subjects and patients of group A, B and C. After eight weeks there were no significant changes for FEV1 and PEF among the three groups. After therapy a strong significant increase of PD20 was documented in group A (p<0.005), group B (p<0.001) and group C (p<0.005), respect to baseline values. The antileukotriene drugs could be taken as an alternative drug, or in association with low-dose inhaled corticosteroids, in patients with mild persistent asthma, both for their clinical effectiveness and their easy ingestion, which is confirmed in compliance studies on inhaled steroids.