Ipratropium bromide (Atrovent) in childhood asthma: a cumulative dose-response study

Thirteen children with perennial bronchial asthma, with a mean age of 11.2 years, were studied concerning the bronchodilatory effect of ipratropium bromide in cumulative doses. All the children had reduced basal forced expiratory flow (FEV1) and bronchial reversibility of at least 20% after inhalation of salbutamol. The study had a double-blind design with a crossover technique. The inhaled dose of ipratropium bromide solution was increased stepwise from 25 micrograms to 500 micrograms and saline was used as the placebo. FEV1 was recorded 20, 40, and 60 minutes after inhalation of the test solution. At the lower ipratropium bromide dose levels no bronchodilatory effect was seen, but 60 minutes after the inhalation of 500 micrograms ipratropium bromide the increase in the FEV1 was significantly greater than that after placebo. Additional inhalation of salbutamol caused no further rise in FEV1. At the 500-micrograms level a fall in the heart rate was noted. No side effects occurred. We concluded that ipratropium bromide has bronchodilatory properties in childhood asthma when given in sufficiently high doses.     

Inhibition of allergen-induced asthma by three forms of sodium cromoglycate

The effect of three forms of sodium cromoglycate (SCG), 20 mg, on allergen-induced early asthmatic responses was examined in ten stable asthmatics. Dose response allergen inhalation tests were performed on five occasions at intervals of from 1 to 2 weeks to determine the provocation concentration producing a 20% reduction (PC20 allergen) in FEV₁. Placebo was given before the first and the last tests to determine the reproducibility of responses to allergen over the study period; reduced responsiveness was observed in eight of the ten subjects. Major changes in levels-of specific serum antibodies of the IgE and IgG classes did not serve to explain the changes in bronchial responses although there was a trend which suggested IgG-related desensitization. The observed changes in bronchial responses and antibody levels illustrate the requirement for tests of reproducibility of responses by the use of placebo controls at the beginning and end of a series of allergen inhalation challenges. SCG as (i) a micronized powder with lactose, (ii) micropellets without lactose, or (iii) an aerosol, were inhaled double-blind, in random order, 5 min before the additional three allergen inhalation tests. PC₂₀ allergen was reduced following SCG in seven subjects; the differences were statistically significant for the group. There was no observed difference in efficacy between the different forms of SCG. In this study, the efficacy of SCG could not be related to age, atopic status, the initial level of allergen-specific IgE antibody, baseline FEV₁, level of bronchial responsiveness to inhaled histamine or an effect of SCG on responsiveness to histamine.     

Allergen-induced increase in non-allergic bronchial reactivity

Non-allergic bronchial hyper-reactivity is a feature of most patients with asthma. We have measured non-allergic bronchial reactivity to inhaled histamine and methacholine in thirteen asthmatic subjects before and after allergen inhalation in the laboratory. The allergen inhalation produced mild early asthmatic responses (19–40% FEV₁ fall) in all thirteen, additional definite late asthmatic responses (17–29% FEV₁ fall) in four, and equivocal late asthmatic responses (5–11% FEV₁ fall) in five. Following allergen inhalation, non-allergic bronchial reactivity increased in seven for up to 7 days. The seven included all four with definite late asthmatic responses and three of the five with equivocal late asthmatic responses. We conclude that allergens make asthma worse, partly through non-allergic mechanisms, and that avoidance of allergens is important in reducing non-allergic bronchial hyper-reactivity.     

Increased bronchial hyperresponsiveness after inhaling salbutamol during 1 year is not caused by subsensitization to salbutamol

Recently, it was suggested that long-term administration of an inhaled beta 2-agonist might increase bronchial hyperresponsiveness (BHR) to histamine, possibly as a consequence of subsensitization to the inhaled beta 2-agonist. To test this hypothesis, we studied two groups of patients with asthma or with chronic obstructive pulmonary disease. An experimental group of 15 patients, inhaling 400 micrograms of salbutamol four times daily during 1 year and subsequently 40 micrograms of ipratropium bromide four times daily for 6 months, and a control group, consisting of 22 patients with the opposite treatment regimen. The BHR, the response in FEV1 to cumulative doses of salbutamol, and the number of beta 2-adrenoceptors and antagonist affinity of these receptors on circulating lymphocytes were assessed at the start of the study and at 6-month intervals for 1 1/2 years. The BHR increased significantly (p = 0.001) during the year salbutamol was inhaled and returned to about the value at the start of the study after inhaling ipratropium bromide for 6 months. No change occurred in the bronchodilating responses to cumulative doses of salbutamol, nor was any change observed in the number and the affinity of beta 2-adrenoceptors on lymphocytes. It was concluded that long-term use of salbutamol caused a small but significant increase in BHR. The increase in BHR was not caused by subsensitization of beta 2-adrenoceptors to salbutamol.     

Non-invasive assessment of bronchial inflammation in asthma: no correlation between eosinophilia of induced sputum and bronchial responsiveness to inhaled hypertonic saline

Bronchial inflammation in mild asthma has been investigated using bronchoscopical techniques. The safety of bronchoscopy in patients with more severe asthma has been questioned. We have used the non-invasive technique of hypertonic saline (HS) inhalation to induce sputum samples for cellular analysis whilst simultaneously yielding a measure of bronchial responsiveness. Ten normal subjects and a heterogenous group of 24 asthmatic patients (range % predicted FEV₁ 43.3-111.5) underwent HS challenge. Sputum samples induced were analysed. Total and differential cell counts between the two groups were compared. The association between bronchial responsiveness to HS and sputum cell counts was examined in the asthma group. Mean maximum fall in FEV₁ for normal subjects was 4.0 (2.1-5.9, 95%CI)% after saline. Geometric mean PD20HS for asthma patients was 7.7 (range 0.68-40.92) ml. Adequate sputum samples were obtained from 9/10 normals and 23/24 asthmatic patients. Sputum from normal subjects contained a median of 3.8 (2.8-8.1, interquartile range)% eosinophils compared with 17.6 (8.9-34.1)% in sputum from asthma patients (P < 0.001). Sputum from asthma patients contained fewer of all other cell types compared with normals, with the difference in macrophages reaching significance. There was no correlation between PD20HS and cell count for any cell type in asthma subjects. Analysis of induced sputum represents a simple, safe, non-invasive and well-tolerated method of assessment of bronchial inflammation, suitable for use in patients with a range of asthma severity. There was no relationship between inflammation, as assessed by sputum cell counts and a measure of ‘Indirect’ bronchial responsiveness.     

Protection by ipratropium bromide and metaproterenol against methacholine and histamine bronchoconstriction

To establish relative protection against methacholine and histamine, 40 μg of ipratropium bromide, an anticholinergic compound, 1.3 mg of metaproterenol or placebo aerosols were administered by metered-dose inhaler prior lo inhalation challenge with methacholine or histamine in nine asthmatic subjects. Double-blind, randomized challenges were performed. Subjects required a mean methacholine dose of l.72 ± 0.73 and 2.46 ± 0.72 (Ln inhalation units), and mean histamine dose of 2.l6 ± 0.65 and 2.68 ± 0.49, to cause a drop of 20% and 35% respectively in the FEV₁ following the placebo. In the methacholine challenges, both ipratropium bromide and metaproterenol had significant protection as compared to placebo (P<0.001). There was no statistical difference in the degree of protection against methacholine between ipratropium bromide and metaproterenol. In histamine challenges, metaproterenol had significant protection as compared to the placebo, while ipratropium bromide did not protect against histamine.     

Protection of nedocromil sodium on bronchoconstriction induced by inhaled neurokinin A (NKA) in asthmatic patients

Neurokinin A (NKA) has been shown to exert a potent contractile action on bronchial smooth muscles both in vitro and in vivo. Although this effect seems to be due either to a direct action of this peptide on specific muscular receptors or to an indirect effect on mast cells and/or nerves, its mechanism of action in bronchial asthma is still unknown. In the present study we have investigated the airway response to inhaled NKA in 10 asthmatic subjects and the activity of the novel pyranoquinoline dicarboxylic acid drug, nedocromil sodium, on this response. Ten asthmatic patients with stable asthma took part in the study consisting of four separate visits. On the first two occasions we derived histamine and NKA PD15 values in absence of any drug treatment. On the following two visits the inhalation challenge with NKA was performed after administration of either nedocromil sodium or matched placebo administered as pressurized aerosols via metered dose inhalers in a randomized double-blind order. Inhaled NKA produced a dose-related fall in FEV1 in all the subjects studied. Inhaled nedocromil sodium had a significant effect on the FEV1 response to NKA inhalation, the geometric mean PD15 value increasing from 16.6 to 32.2 x 10(-9) mol. We conclude that nedocromil sodium attenuates subsequent responsiveness to inhaled NKA in asthmatic subjects.     

Frequent administration by inhalation of salbutamol and ipratropium bromide in the initial management of severe acute asthma in children

A study was performed to compare the efficacy and safety of two therapeutic regimens for the treatment of children presenting to the emergency department with acute asthma. A regimen of inhaled salbutamol alone was compared to inhaled salbutamol combined with ipratropium bromide. Twenty-five children ranging in age from 5 to 15 years were enrolled in the study. Children with FEV1 less than or equal to 55% predicted were eligible to participate in the study. Subjects were randomized in a double-blind fashion into one of two treatment groups. Both groups received an initial dose of salbutamol by nebulizer of 150 micrograms/kg (0.03 cc/kg), followed by six consecutive doses of 50 micrograms/kg (0.01 cc/kg) at 20-minute intervals. In one group of subjects, 250 micrograms (1.0 ml) of ipratropium bromide respirator solution was added to the salbutamol administered at the time of the initial inhalation, and at 40 and 80 minutes, whereas the remaining subjects received a placebo with salbutamol at those times. Formal one-way statistical ANOVA with change in percent predicted FEV1 as a response variable confirmed there was a statistically significant difference at all time points caused by drug regimen during the 150-minute observation period. There was no significant difference in side effects reported in the two groups. Significant additional bronchodilation achieved with salbutamol and ipratropium bromide together indicates that there is likely a substantial cholinergic element to the bronchospasm observed in acute exacerbations of asthma in the pediatric age group.     

A comparison of ketotifen with clemastine, ipratropium bromide and sodium cromoglycate in exercise-induced asthma

Exercise-induced asthma (EIA) was provoked by a standardized treadmill running for 8 min in seven atopic adult asthmatics. The tests were performed using a double-dummy technique after placebo, oral ketotifen, inhaled clemastine. ipratropium bromide and sodium cromoglycate (SCG), in a random single blind-fashion on different days. The mean post-exercise percentage fall in forced expiratory volume in 1 sec (FEV₁) was 47 (s.e. 6.95), 39 (s.e. 8.35), 27 (s.e. 7.17), 23 (s.e. 7.69) and 7.0 (s.e. 4.62)% respectively. There was significantly less mean bronchoconstriction with SCG (P < 0.01), ipratropium bromide and clemastine (P < 0.05) but not with ketotifen. Six out of seven individual patients had significant protection of EIA with sodium cromoglycate, four with ipratropium bromide, three with clemastine but only one with ketotifen. Ipratropium bromide and clemastine were bronchodilators at rest, whereas SCG and ketotifen were not. Despite its claims to work as a mast cell stabilizing drug, ketotifen in a single dose does not have an effect similar to sodium cromoglycate in EIA, nor does it compare with inhaled clemastine or ipratropium bromide.     

Allergen-induced increase in bronchial responsiveness to histamine: relationship to the late asthmatic response and change in airway caliber

Allergen-induced late asthmatic responses are associated with an increase in bronchial responsiveness to histamine. We have examined the relationship between the magnitude of the late asthmatic response and the magnitude and duration of increased histamine responsiveness. Allergen inhalation tests were carried out in 12 asthmatic subjects to induce a mild early asthmatic response (16% to 40% reduction in FEV₁ in the first hour after allergen inhalation); the response was followed over 8 hr to identify the occurrence and magnitude of any late asthmatic response (maximum fall in FEV₁ from baseline between 3 and 8 hr). The provocation concentration of histamine causing a decrease in FEV₁ of 20% (PC₂₀) was measured before and after inhalation of allergen. The magnitude of decrease in PC₂₀ correlated with the magnitude of the late asthmatic response as measured by the percent fall in FEV₁ (r = 0.8, p < 0.002). The duration of decrease in PC₂₀ was from 2 to 74 days and this also correlated with the magnitude of the late response (r = 0.53, p < 0.05). Total lung capacity (TLC), residual volume (RV), FEV₁, maximal expiratory flow-volume curves (on air and He-O₂), and histamine responsiveness were also measured before and at intervals after allergen inhalation. Four of seven subjects still had a reduction in PC₂₀ when the TLC, RV, FEV₁, maximal expiratory flow-volume rates on air (V?₅₀air) and He-O₂ (V?₅₀He-O₂) (measured at an absolute volume corresponding plus 50% of control vital capacity) and ratio of V?₅₀He-O₂ to V?₅₀air were back t preallergen inhalation levels. In two of these subjects volume of isoflow was also back to ±10% of preallergen inhalation levels when the PC₂₀ was still significantly reduced. The results suggest that allergen-induced late asthmatic responses can be associated with an increase in bronchial responsiveness to histamine by mechanisms other than a reduction in baseline airway caliber alone.     

Inhaled sodium fluoride decreases airway responsiveness to acetylcholine analogs in vivo

The study was conducted to characterize the action of NaF, which had relaxing property in carbachol precontracted isolated bovine bronchus, on airway responsiveness challenged by acetylcholine receptor agonists in rats and asthmatic humans.Tracheal flow rate and airway resistance were measured in anaesthetized rats. NaF was delivered either before carbachol challenge or together with carbachol. Patients with mild asthma were challenged with methacholine aerosol, and NaF was delivered when FEV1 fell by more than 20%. The results indicated that: (1) in rats NaF significantly inhibited carbachol-induced bronchial constriction when inhaled prior to carbachol challenge as airway resistances in the NaF and NaF+verapamil groups were significantly lower than those in the control group; (2) NaF significantly reversed carbachol or methacholine-induced bronchial constriction in asthmatic patients. In conclusion, NaF, delivered in form of aerosol, reduced bronchial responsiveness to carbachol in rats and had a bronchodilating effect on rat and human airways precontracted by inhalation of acetylcholine analogs.     

Inhibition of neutral endopeptidase potentiates bronchoconstriction induced by neurokinin A in asthmatic patients

The endogenous tachykinins exhibit a range of properties which may he relevant in the pathophysiology of asthma. Their effects on the airways seem to be modulated by a variety of lung peptidases, including neutral endopeptidase (NEP). In order to evaluate the potential role of endogenous NEP activity in modulating tachykinins-induced bronchconstriction in man in vivo, six atopic asthmatic patients, with a mean FEV₁ value of 3.38 ± 0.76 1, and a histamine PD20 mean value of 0.024 mg. were studied. The influence of inhaled phosphoramidon (a potent NEP inhibitor) was examined against the NKA-induced bronchospasm in a double-blind, placebo-controlled randomized study. Changes in airway calibre were followed as FEV₁ and agonists responsiveness expressed as PD20 and PD15 for histamine and NKA respectively. Patients received nebulized phospharamidon sodium salt (10^?5 M) or a control solution 10 min prior to the bronchoprovocation test with NKA. No significant difference was noticed between any of the study days and after inhaled phosphoramidon on baseline FEV₁ values (3.29 ± 0.90 1) in comparison with the control solution (3.31 ± 0.79 1). Inhaled NKA produced a dose-dependent fall in FEV₁ values in all the subjects studied with a mean PD15 value of 20.91 × 10^?9 mol. Phosphoramidon administered by inhalation elicited a significant (P < 0.0l vs baseline and control solution) potentiation in the airway responsiveness to inhaled NKA, the NKA PD15 value decreasing to 9.45 × 10^?9 mol. The present study confirms that inhaled NKA induces a dose-related bronchconstriction in asthmatic patients and demonstrates that inhaled phosphoramidon potentiates NKA-induced bronchoconstriction.     

Association between bronchodilating response to short-acting β-agonist and non-synonymous single-nucleotide polymorphisms of β2-adrenoceptor gene

BACKGROUND: With beta-agonists being the most widely used agents in the treatment of asthma, in vitro studies reported that beta(2)-adrenergic receptor (ADRB2) polymorphisms are associated with agonist-promoted down-regulation. OBJECTIVE: The present population-based study aimed to evaluate the association between bronchodilating response to inhaled short-acting beta-agonist and two non-synonymous single-nucleotide polymorphisms (SNPs) of ADRB2 (ADRB2-16 and ADRB2-27). METHODS: Two hundred and nine children with reduction in forced expiratory volume in 1 s of more than 20% on methacholine bronchial challenge underwent bronchodilating response testing 5 min after the inhalation of 200 mug of albuterol. Of these 209, 195 gave peripheral blood for genotyping of ADRB2 polymorphisms. RESULTS: The bronchodilating response was significantly higher in subjects with the homozygous Arg16 than in those with the homozygous Gly16. It was further demonstrated that haplotype pairs of the homozygous Arg16Gln27 and of the heterozygous Arg16Gln27/Gly16Glu27 showed the highest bronchodilating responses, and the haplotype pairs of the homozygous Gly16Gln27 the lowest response. As a whole, the bronchodilating response was more positively associated with the combined quantity of Arg16 and Glu27 polymorphisms than with that of Arg16 alone. CONCLUSION: Non-synonymous SNPs of ADRB2 at codons 16 and 27 is significantly associated with bronchodilating response to inhaled short acting beta-agonists.     

Turbuhaler®: a new device for dry powder terbutaline inhalation

The aim of this study was to compare bronchodilator response and adverse effects of terbutaline when administered with the metered dose inhaler (MDI) Bricanyl and with the dry powder inhaler Bricanyl Turbuhaler (BT). Nine adult patients with bronchial asthma participated. The study was of an open crossover design. At 30-min intervals the patients inhaled increasing doses of terbutaline (0.25 mg to 5.0 mg cumulated) from either the conventional MDI or from the BT. After each inhalation FEV1, FVC, heart rate, muscle tremor and adverse effects were recorded. Both treatments, BT and MDI, resulted in a dose-related increase in lung function, without any statistical difference. Taste sensation, muscle tremor and increase in heart rate were observed in both groups. Because of the design of the BT one may assume that inhalation failure can be avoided.     

Reversibility of inspiratory lung function parameters after short-term bronchodilators in COPD

Background

The responsiveness of short-term bronchodilator use on inspiratory lung function parameters (ILPs), including Forced Inspiratory Volume in one second (FIV₁), Inspiratory Capacity (IC), Forced Inspiratory Flow at 50% of the vital capacity (FIF₅₀), Peak Inspiratory Flow (PIF) and on the relationship between these values and dyspnea in COPD subjects has been examined only sparsely in past studies. The aim of this study was to assess the effects of inhaled salbutamol 400 mcg, ipratropium 80 mcg and a placebo on ILP and FEV₁ and their relationship to dyspnea, as measured with a Visual Analogue Scale (VAS).

Methods

A total of 85 subjects with stable COPD participated in a crossover, randomized, double-blind, placebo-controlled study. Spirometry was performed before and after inhalation of salbutamol, ipratropium or a placebo. The primary analysis was performed using 63 participants with absent reversibility.

Results

All ILP and FEV₁ values improved significantly after bronchodilator administration except for FIF₅₀ after ipratropium administration. After administration of both bronchodilators, the mean percent changes from initial values did not significantly differ between the various ILPs and FEV₁. The mean VAS score showed significant improvements after bronchodilator and placebo inhalation but did not significantly correlate with changes in lung function parameters. For each lung function parameter, patients were further classified as responders if the amount of change was greater than the coefficient of repeatability of the test. Response rates did not differ significantly between the various ILPs. Moreover, no significant differences were found between responders and non-responders with respect to dyspnea after bronchodilator inhalation. This finding applied to all ILP and FEV₁ values.

Conclusions

In subjects with COPD, all ILP, FEV₁ values and VAS scores showed significant improvements after bronchodilator use as well as with placebo. However, ILPs were not more sensitive than FEV₁ for detecting responders after bronchodilator use or changes in the VAS score.     

The effect of inhaled verapamil on allergen-induced bronchoconstriction

In eight patients with extrinsic bronchial asthma the effect of inhaled verapamil (3 and 6 mg) was compared with saline on bronchial challenge with extracts of Dermatophagoides pteronyssinus. There was no significant difference in the baseline FEV₁ before and after inhalation of saline or verapamil 2.5 mg/ml. However, verapamil at a higher concentration (5 mg/ml) caused bronchoconstriction in four patients who had to be excluded from the part of the study. Verapamil at both these concentrations failed to have an effect on the allergen-induced bronchoconstriction. These findings suggest that verapamil given by inhalation does not prevent mediator release from the lung mast cells following specific allergen challenge.     

Inflammatory response in bronchoalveolar lavage fluid after inhaling histamine

To examine the influence of the histamine chloride challenge test on the bronchoalveolar lavage cell population, lavage fluid from 15 subjects was collected 24 h after the histamine test, and was compared with the lavage fluid from a reference group of 25 subjects. Inhaled histamine is commonly used to quantitate non-specific bronchial responsiveness. Increase in airway responsiveness after exposure to ozone or allergen is associated with airway inflammation. Bronchoalveolar lavage, has therefore become a valuable tool in the study of bronchoalveolar cells and mediators in subjects with asthma and bronchial hyperresponsiveness. The total cell number and differential cell counts in bronchoalveolar lavage fluid 24 h after inhalation challenge test with histamine-chloride were studied. There was a significant increase in lymphocytes, mast cells and neutrophils after histamine test. The conclusion was that inhaled histamine-chloride can induce an inflammatory cell response in the lung. Thus the histamine-chloride test should not be performed before bronchoalveolar lavage.     

Clinical comparison of inhaled budesonide delivered either via pressurized metered dose inhaler or Turbuhaler®

The aim of this open, randomized cross-over study was to compare the efficacy and safety of inhaled budesonide administered either via a pressurized metered dose inhaler with a 750 ml spacer attached, or via a new dry powder inhaler, Turbuhaler, in 28 patients with stable bronchial asthma. During the 2-week run-in period, the patients received their ordinary inhaled steroid treatment. This was followed by two 4-week periods of active treatment with inhaled budesonide given via Turbuhaler or pressurized MDI. The patients were divided into two groups according to their previous, inhaled steroid doses. Group A received 400 micrograms of budesonide b.i.d, and Group B 800 micrograms of budesonide b.i.d. Diary cards were used by the patients at home to report asthma symptoms, beta 2-agonist consumption, and PEF twice daily, as well as the number of coughs experienced in a 5-min period after steroid inhalation. Budesonide Turbuhaler produced a significantly better effect on morning peak flow than budesonide MDI. The number of coughs in the 5 min after steroid inhalation was significantly lower with the Turbuhaler than with the MDI. In all other parameters recorded (e.g. FEV1, evening PEF, histamine PC20 and other diary measurements) there were no statistically significant differences between the two devices. Turbuhaler was significantly more appreciated than MDI in all questions of preference. The study showed that budesonide via Turbuhaler was at least as effective and safe as budesonide via a pressurized MDI at daily doses of 800 and 1,600 micrograms.(ABSTRACT TRUNCATED AT 250 WORDS)     

Recurrent nocturnal asthma after bronchoprovocation with Western Red Cedar sawdust: association with acute increase in non-allergic bronchial responsiveness

Recurrent nocturnal asthma following a single exposure to Western Red Cedar sawdust was documented by measurements of peak flow rates in two sensitized subjects. The nocturnal asthma followed a dual asthmatic response in the first subject and a late (non-immediate) asthmatic response in the second. Both subjects developed a 10-fold reduction in the dose of histamine required to decrease the FEV₁ by 20%. This cedar-induced increase in non-specific bronchial reactivity was maximal at the time of the recurrent nocturnal asthma, and persisted after nocturnal asthma had ceased and after FEV₁ had returned to normal. We hypothesize that the enhanced non-specific bronchial reactivity which occurs following late asthmatic responses to bronchial challenge is the cause of recurrent nocturnal asthma following single exposure to a sensitizing agent.     

Effect of ethanol on airway caliber and nonspecific bronchial responsiveness in patients with alcohol-induced asthma

No study has investigated the effects of ethanol on bronchial responsiveness in patients with alcohol-induced asthma, although acetaldehyde, which is a metabolite of ethanol and is thought to be a main factor in alcohol-induced asthma, causes both bronchoconstriction and bronchial hyperresponsiveness. The purpose of this study was to investigate the direct action of ethanol on the airway in patients with alcohol-induced asthma. First, we investigated the bronchial response to inhalation of ascending doses (5, 10, and 20%) of ethanol in nine patients with alcohol-induced asthma. Then, the bronchial responsiveness to methacholine was measured in 14 patients who were pretreated with saline or 20% ethanol in a double-blind, randomized, placebo-controlled, crossover fashion. Ascending doses of inhaled ethanol caused no significant changes in FEV₁. The methacholine concentrations producing a 20% fall in FEV₁ (PC₂₀-MCh) after 20% ethanol (0.769 mg/ml, GSEM 1.514) were significantly ( P = 0.0357) higher than those after saline (0.493 mg/ml, GSEM 1.368). This indicates that ethanol has a reducing effect on nonspecific bronchial responsiveness in patients with alcohol-induced asthma; this paper is the first report on the effects of ethanol on bronchial responsiveness.