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1.
This study of 183 ambulatory patients with steroid-dependent asthma was conducted to evaluate the efficacy and safety of nebulized bitolterol mesylate solution (0.2%) compared to isoproterenol hydrochloride solution (0.3%). A double-blind, randomized, parallel-group, repetitive-dose design was followed at nine centers for 3 months. Patients received either 1.0 mg of bitolterol or 1.5 mg of isoproterenol three times a day with a closed, intermittent-flow nebulization system. Pulmonary function was evaluated on four 8-hour office visits at approximately 30-day intervals. Efficacy was based on a 15% increase in FEV1 over baseline. Both medications resulted in bronchodilatation within 5 minutes, whereas nebulized bitolterol was statistically superior (p less than 0.05) to nebulized isoproterenol in terms of duration of action and area under the curve. The mean FEV1 response to bitolterol therapy remained greater than 15% over baseline for 5 to 8 hours on the four test days compared to 2 to 4.75 hours for isoproterenol therapy. Both medications were well tolerated. Adverse reactions were transient, and most were mild to moderate. Tremor was the most frequent side effect occurring in approximately 30% of the patients in both groups. There were no clinically significant laboratory changes or electrocardiographic findings. Nebulized bitolterol mesylate was found to be a safe and effective bronchodilator in steroid-dependent patients with asthma.  相似文献   

2.
Cetirizine, a major human metabolite of hydroxyzine, preserves the histamine H1-antagonist activity of the parent compound but poorly penetrates the blood-brain barrier, thus minimizing sedative and anticholinergic effects. In 10 young (mean age 27.7 years) subjects with mild asthma (FEV1 greater than 70% predicted), we evaluated the bronchodilator and protective efficacy of 5, 10, and 20 mg of cetirizine against bronchospasm induced by histamine inhalation (0.03 to 20 mg/ml) in comparison with placebo and hydroxyzine, 25 mg, using a random, double-blind crossover design. The provocative concentration of histamine causing a 20% decline in FEV1 for all 10 subjects from the postdiluent control value was more than fourfold greater after each active drug than after placebo. Cetirizine, 5 to 20 mg, provided significantly greater protection against histamine-induced bronchospasm than hydroxyzine (p less than 0.001); moreover, a dose-dependent protective effect was noted with cetirizine. Significant bronchodilation was also found: at 60 minutes, FEV1 increased significantly after all active antihistamines compared to placebo and after 20 mg of cetirizine compared to hydroxyzine (p less than 0.05). FEV1 increased significantly at 120 minutes after hydroxyzine and after cetirizine in both the 20 and 10 mg doses compared to placebo (p less than 0.05). We conclude that in subjects with mild asthma, orally administered cetirizine provides significant dose-dependent protection against histamine-induced bronchoconstriction, which in the doses studied is superior to that produced by the parent compound, hydroxyzine. In addition, cetirizine in 5 to 20 mg doses causes acute bronchodilation. These results suggest a possible role of cetirizine in asthma therapy.  相似文献   

3.
Salmeterol (SM) is a novel beta 2-adrenoceptor agonist with a duration of action in excess of 12 hours. Evidence from in vitro studies has also demonstrated that, unlike the short-acting beta 2-agonists, such as salbutamol (SB), it may have some anti-inflammatory properties. With a randomized, double-blind, crossover design, we have compared the inhibitory effects of SM (50 micrograms) and SB (200 micrograms) delivered by metered-dose inhaler on allergen-induced bronchoconstriction, changes in airway reactivity, and urinary leukotriene (LT) E4 excretion in 12 atopic subjects with mild asthma. The immediate bronchoconstriction to allergen was significantly reduced by both beta 2-agonists (p less than 0.005), when reduction was expressed either in terms of maximum fall in FEV1 at 15 minutes after allergen (percent fall in FEV1, mean +/- SEM: 6.2 +/- 4.9, SM; 5.7 +/- 2.5, SB; 40.4 +/- 6.3, placebo) or the area under the FEV1 time curve (AUC) for the first 120 minutes after allergen. Four hours after challenge, results in the SB-treated and placebo-treated groups were not significantly different and demonstrated a small persistent bronchoconstriction compared to bronchodilatation in the SM-treated group (percent fall in FEV1, respectively, 9.3 +/- 3.7, 14.3 +/- 7.1, and -6.3 +/- 2.7; p less than 0.005, SM versus SB; p less than 0.02, SM versus placebo). Expressed in terms of AUC, only SM significantly reduced bronchoconstriction in the period 120 to 240 minutes after allergen (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)  相似文献   

4.
Pupillary responses and airway reactivity in asthma   总被引:1,自引:0,他引:1  
Pupillary responses to phenylephrine and carbachol and airway reactivity were determined in 19 drug-free persons with mild allergic asthma, 21 nonatopic control subjects, and six asymptomatic atopic control subjects. The concentration of phenylephrine required to dilate the pupil 1 mm, obtained by interpolation on the dose-response curve, was taken as a measure of alpha-adrenergic sensitivity. This concentration was significantly lower for subjects with asthma than for atopic or nonatopic control subjects (1.11 +/- 0.68% [mean +/- SD], 1.86 +/- 0.81%, and 1.52 +/- 0.67%, respectively; p less than 0.05 by analysis of variance). The concentration of carbachol required for pupillary constriction of 1 mm, obtained by interpolation on the dose-response curve, was taken as a measure of cholinergic sensitivity. This value was significantly lower for subjects with asthma than for atopic or nonatopic control subjects (0.23 +/- 0.12%, 0.41 +/- 0.14%, and 0.35 +/- 0.19%, respectively; p less than 0.05 by analysis of variance). Pupillary alpha-adrenergic and cholinergic sensitivity were significantly correlated (Spearman's rank correlation coefficient, Rs = 0.42, p less than 0.05). Both alpha-adrenergic and cholinergic sensitivity of the pupils correlated with airway reactivity expressed as concentration of methacholine causing a 20% fall in FEV1 (Rs = 0.35, p less than 0.05, and Rs = 0.45, p less than 0.05, respectively). The autonomic aberrations cannot be attributed to drug use or significantly abnormal pulmonary mechanics. Autonomic abnormalities are associated with allergic asthma and may contribute to the airway reactivity characteristic of the disease.  相似文献   

5.
Eight subjects with asthma inhaled on separate occasions leukotriene E4 (LTE4) (6.1 nmol, geometric mean), methacholine, and diluent, which produced an average 41.0%, 37.0%, and 3.3% decrease in specific airway conductance (SGaw), respectively. When the SGaw had recovered to baseline levels at 60 minutes after challenge, the provocative dose of inhaled histamine that produced a 35% decrease in SGaw (PD35) was determined. The histamine PD35 observed after inhalation of LTE4 was 0.46 mumol, and this was significantly less than the histamine PD35 observed after inhalation of methacholine (0.88 mumol; p less than 10(-4) and diluent (0.97 mumol; p less than 10(-5). Histamine responsiveness was also enhanced by a fiftyfold lower dose of LTE4 (p = 0.005), and the enhancement was less than that elicited by the higher dose of LTE4 in the same individuals (p = 0.02). The changes in histamine PD35 during a 1-week period after LTE4 and methacholine challenges were compared in four subjects with asthma. There was a time-dependent enhancement in histamine responsiveness that reached a maximal of 3.5-fold at 7 hours after LTE4. The enhancement had disappeared by 1 week. Similar changes were not observed after methacholine challenge, which elicited the same degree of bronchoconstriction as LTE4. Inhalation of LTE4 in five normal subjects that produced a mean 37.6% decrease in SGaw did not change histamine responsiveness for up to 7 hours. These findings suggest that LTE4 may play a role in the perpetuation of nonspecific airway hyperresponsiveness in bronchial asthma.  相似文献   

6.
The duration of the protective effect of 50 and 100 micrograms of inhaled salmeterol against methacholine-induced bronchoconstriction was compared with that of 200 micrograms of inhaled salbutamol in 12 patients with asthma with a baseline FEV1 of at least 70% and a provocative concentration of inhaled methacholine causing a 20% fall in FEV1 (PC20) greater than or equal to 8 mg/ml. The study was placebo controlled, double blind, randomized, and crossover. The bronchodilating effect was no longer significant 4 hours after inhalation of salbutamol, whereas the effect was still present 12 hours after administration of 50 and 100 micrograms of salmeterol. All active treatments caused PC20 to increase at 1 hour (p less than 0.05). PC20 (milligrams per milliliter) thus reached 3.7 +/- 0.8 after placebo, 13.8 +/- 3.0 after 50 micrograms of salmeterol, 23.2 +/- 4.7 after 100 micrograms of salmeterol, and 13.9 +/- 3.4 after 200 micrograms of salbutamol. The protective effect of 200 micrograms of salbutamol was no longer significant at 4 hours, whereas both doses of salmeterol protected against methacholine challenge up to 12 hours after inhalation (p less than 0.01). An increased incidence of tremor (2/12) and palpitations (2/12) was recorded after inhalation of 100 micrograms of salmeterol. We conclude that inhalation of 50 or 100 micrograms of salmeterol causes a long-lasting bronchodilatation and protects against methacholine-induced bronchoconstriction for at least 12 hours.  相似文献   

7.
BACKGROUND: Maintaining asthma control is a major objective of therapy. Traditionally, the effectiveness of asthma therapy has been judged primarily by its effect on airway function rather than on multiaspect asthma control. OBJECTIVE: An inhaled corticosteroid and a leukotriene receptor antagonist were compared to determine whether they provided equivalent effects, as judged by days of asthma control. METHODS: In a randomized, multicenter, double-blind, placebo-controlled, parallel-group study, asthmatic patients (n = 782) with FEV(1) percent predicted values of between 50% and 85% and a weekly average beta-agonist use of more than 2 puffs per day were randomized to receive montelukast (10 mg daily), beclomethasone (200 microg twice daily), or placebo treatment for 6 weeks in a double-dummy fashion. We examined the distribution of the primary end point: percentage of days of asthma control. Secondary end points included FEV(1), albuterol use, occurrence of an asthma attack, asthma flare-up, rescue corticosteroid use, sustained asthma control, and adverse experiences. RESULTS: The percentage of days of asthma control was almost identical between the montelukast and beclomethasone groups (98% overlap in the distribution). Montelukast was at least equal to beclomethasone, and both were greater than placebo on the basis of frequency of asthma attacks, asthma flare-ups, and rescue corticosteroid use. Beclomethasone had a greater effect than montelukast and both treatments were better than placebo at improving FEV(1). CONCLUSIONS: Montelukast was as effective as beclomethasone, as judged by indices of clinical control other than FEV(1). When evaluating the outcome of montelukast therapy, FEV(1) might underestimate clinical effectiveness.  相似文献   

8.
We have previously demonstrated that the neuropeptide, neurokinin A (NKA) (substance K), causes bronchoconstriction in subjects with asthma. In a double-blind, crossover study we investigated the effect of nedocromil sodium on NKA-induced bronchoconstriction in subjects with asthma. Twelve patients with mild asthma (mean FEV1 percent predicted +/- SE, 87.3 +/- 3.4) inhaled on 2 separate days either nedocromil sodium, 4 mg, or placebo, as two puffs from a metered-dose aerosol, 30 minutes before challenge with NKA. NKA was inhaled at three concentrations (10(-7), 3.10(-7), and 10(-6) mol/ml). The specific airway conductance (SGaw) and FEV1 were measured before and 5 and 15 minutes after each concentration step. On the placebo-treatment day, NKA caused a concentration-dependent decrease in SGaw and FEV1 (mean log for the provocative concentration of NKA causing a 35% fall in SGaw [10(-7) mol/ml], 0.49; mean log for the provocative concentration of NKA causing a 15% fall in SGaw [10(-7) mol/ml], 0.90). The inhalation of 4 mg of nedocromil sodium reduced the decrease in both SGaw and FEV1. The maximal percentage decrease in SGaw on the nedocromil sodium-treatment day was 27 +/- 5.2 (versus placebo, 53.3 +/- 5.4; p less than 0.05), and the maximal percentage decrease in FEV1 was 5.5 +/- 1.4 (versus placebo, 12.4 +/- 2.3; p less than 0.05). The dose-response curves for NKA after nedocromil sodium treatment were significantly shifted to the right compared to the curve after placebo-treatment. We conclude that nedocromil sodium protects against NKA-induced bronchoconstriction in subjects with asthma.  相似文献   

9.
Procaterol and albuterol, beta agonists, were studied using a placebo-controlled, repeated exercise challenge design in order to assess their duration of effectiveness in both bronchodilation and in modifying exercise-induced asthma (EIA). Fifty-three subjects aged 12 to 50 years who had at least a 20% drop in FEV1 during a screening exercise tolerance test were entered. Subjects took two inhalations of procaterol (10 micrograms/inhalation), albuterol (90 micrograms/inhalation), or placebo. Thirty minutes later they exercised on a treadmill at a workload sufficient to induce greater than or equal to 80% aerobic O2 consumption for six minutes. Pulmonary function was measured before and serially for 30 minutes after exercise. The same exercise challenge was repeated three, six, and nine hours after drug administration. Both procaterol and albuterol bronchodilated and modified EIA at 30 minutes and three hours, mean drops in FEV1 being 8.2 and 9.7% respectively at 30 minutes and 16.8 and 16.3% at three hours. This was compared with placebo falls of 30% and 26%. At six hours the subjects' response was similar after both procaterol and albuterol, and fewer subjects had a 20% fall in FEV1 than with placebo, although protection afforded by both beta agonists was substantially less than at three hours. Both drugs were tolerated well.  相似文献   

10.
We have investigated separate and interactive effects of corticosteroids and bronchodilators on airflow obstruction and airway hyperresponsiveness. Twelve allergic subjects with asthma were treated in a double-blind, crossover, randomized study with budesonide, 1.6 mg daily for 3 weeks, prednisone, 40 mg daily, for 8 days, and placebo. After each period, dose-response curves were measured on 4 study days with doubling doses of salbutamol, ipratropium, a combination of salbutamol and ipratropium, and placebo until a plateau in FEV1 was reached. A histamine challenge was then performed, and the provocation concentration causing a 20% fall in FEV1 (PC20) was calculated. The budesonide and prednisone regimens were equipotent. FEV1 was 81.2% of predicted after budesonide, 81.0% predicted after prednisone, and 67.5% predicted after placebo, bronchodilatation thus being 13.7% predicted (budesonide) and 13.5% predicted (prednisone). PC20 improved with 2.17 doubling concentrations (DCs) after budesonide, and 1.86 DCs after prednisone, compared with that of placebo. Salbutamol caused stronger bronchodilatation than ipratropium (26.2% versus 14.7% predicted) and a better protection against histamine challenge (3.95 versus 1.12 DC). The effects of corticosteroids and bronchodilators on FEV1 and PC20 were, in general, additive. This study emphasizes different modes of action on both airflow obstruction and airway hyperresponsiveness by corticosteroids and bronchodilators, and it demonstrates no enhancement of bronchodilator action by corticosteroids.  相似文献   

11.
Although some studies have clearly demonstrated tachyphylaxis to inhaled histamine in subjects with asthma, other studies have not. We speculated that histamine tachyphylaxis might be related to the degree of bronchial hyperreactivity (BHR) to histamine. We undertook three successive bronchial histamine challenges in two groups of 10 subjects with asthma chosen on the basis of their baseline BHR. In the group with mild asthma, the baseline provocative concentration of histamine causing a 20% fall in FEV1 (PC20) was greater than 2.5 mg/ml, and in the group with severe asthma, the baseline PC20 histamine was less than 1 mg/ml. The second and third histamine challenges in each subject were performed when FEV1 values had recovered to within 5% of the baseline FEV1 before the first challenge. There was no significant shift in reactivity to histamine from the first to the third challenge in either group. The geometric mean PC20 (+/- geometric SE) for the group with mild asthma was 4.27 (3.86 to 4.72) mg/ml for the first challenge and 5.42 (4.47 to 6.57) mg/ml for the third challenge. There was a mean increase of 0.34 doubling dilutions in PC20 for the group with mild asthma from the first to the third challenge, although this did not reach statistical significance. For the group with severe asthma, the geometric mean PC20 was 0.48 (0.39 to 0.59) mg/ml for the first challenge and 0.47 (0.38 to 0.59) mg/ml for the third challenge. There was no trend in this group toward any increase in PC20.(ABSTRACT TRUNCATED AT 250 WORDS)  相似文献   

12.
Background Magnesium is a cation with smooth muscle relaxant and anti-inflammatory effects and may therefore have a role in the therapy of asthma. Several studies have investigated the effects of intravenous magnesium in acute or stable asthma, but little is known about the effects of inhaled magnesium. Objective To measure the effects of a single inhaled nebulized dose of 180 mg magnesium sulphate on airway reactivity to a direct-acting bronchoconstrictor (histamine) and an indirect-acting bronchoconstrictor (adenosine monophosphate [AMP]) in asthmatic subjects. Objective Two separate randomized, double-blind, placebo-controlled crossover studies, each involving 10 asthmatic subjects. In the histamine study, airway reactivity to histamine was measured and lung function allowed to recover spontaneously over 50 min before administering nebulized magnesium sulphate or saline placebo. Airway reactivity to histamine was then measured at 5 and 50 min. In the AMP study, a single measurement of airway reactivity was made 5 min after magnesium or placebo. Results In the histamine study, the provocative dose required to reduce FEV1 by 20% (PD20FEV1) was significantly lower after magnesium than after placebo, by a mean (95% CI) of 1.02 (0.22–1.82) doubling doses at 5 min (P= 0.018), and 1.0 (0.3–1.7) doubling doses at 50 min (P= 0.01). In the AMP study, PD20FEV1 was also significantly lower at 5 min after magnesium than after saline, by 0.64 (0.12–1.16) doubling doses (P= 0.023), though this difference was not statistically significant after adjustment for differences in baseline FEV1 on the two study days. Conclusions Inhaled magnesium did not protect against the effects of these direct and indirect bronchoconstrictor stimuli in subjects with asthma, and may have increased airway reactivity to histamine.  相似文献   

13.
Eight nonsmoking subjects with asthma, nonresponsive to the bronchoconstrictive effect of oral propranolol, were studied. The airway response to increasing concentrations of histamine aerosol was assessed by measuring FEV1. The threshold provocative dose of histamine needed to cause a 20% fall in starting FEV1 (PD20) was measured by log dose-response curve. Histamine challenge was performed in duplicate after premedication with placebo or 40 mg of propranolol on separate days. The mean starting FEV1 did not change significantly after placebo and after propranolol administration. The mean PD20 values after propranolol (0.37 mg/ml and 0.32 mg/ml, respectively, for the first and the second challenge) were significantly lower (p less than 0.01) than mean control PD20 values (1.36 mg/ml and 1.48 mg/ml, respectively, for the first and the second challenge). These results indicate that propranolol increases airway responsiveness to histamine, even in those subjects with asthma in whom propranolol has little bronchoconstrictive effect.  相似文献   

14.
BACKGROUND: During conventional daytime studies of beta(2)-agonists, 1 puff of a metered-dose inhaler often produces a near maximum bronchodilator response. Consequently, the US Food and Drug Administration-approved dose of albuterol is only 1 to 2 puffs every 4 to 6 hours. OBJECTIVE: To determine whether a higher dose of albuterol is required to normalize lung function during nocturnal asthma. METHODS: Fifteen subjects (age, 18-37 years) were treated with albuterol metered-dose inhalers in a randomized crossover manner at the onset of nocturnal symptoms while sleeping in the Clinical Research Center and during the day when they were asymptomatic. The dose was doubled at 15-minute intervals to 16 cumulative puffs. RESULTS: The mean +/- SD predose FEV(1) was lower at night than during the day (44% +/- 12% vs 68% +/- 9% predicted; P=.0001). The maximum FEV(1) achieved was also lower at night (84% +/- 15% vs 90% +/- 12%; P=.02). The nocturnal dose-response curve was shifted to the right. The median (25th, 75th percentiles) dose required to achieve 80% of the subject's personal best FEV(1) was substantially higher at night (5 [1, 19] vs 0.4 [<0.25, 2] puffs; P=.02), and the median time to achieve this endpoint was longer (47 [21, 90] vs 10 [0.2, 42] minutes; P=.005). No significant systemic effects were observed. CONCLUSION: At night, the response was slower and required a higher dose because more severe airway obstruction was present on awakening. These results suggest that studies establishing the clinical dose of a beta(2)-agonist or assessing the equivalence of different formulations should be conducted in subjects with more severe reversible airway obstruction than is present during conventional daytime studies.  相似文献   

15.
The present study assessed the persistence of cigarette-smoke reactivity and the effects of drug pretreatment on bronchial responsiveness to environmental tobacco smoke (ETS). Two groups of subjects were chosen for the study. Group I consisted of 15 atopic smoke-sensitive subjects with asthma, six of whom were defined “reactors” and nine “nonreactors” to ETS challenge. Group II consisted of 15 atopic subjects without asthma and with documented upper respiratory tract symptoms on exposure to ETS. All subjects were challenged for 2 to 6 hours with mechanically generated ETS in a static inhalation chamber. Five / six subjects in group I, who were previously demonstrated as reactors 24 months earlier, remained reactive within 1 to 2 hours of continuous ETS exposure. Pretreatment with albuterol, cromolyn, and a combination of albuterol and cromolyn 30 minutes before ETS exposure significantly diminished airway reactivity to ETS. All nine previous nonreactors in group I remained nonreactive despite rechallenge with ETS for up to 6 hours. Group II subjects challenged under identical conditions did not reveal a significant decline in FEV, on challenge with ETS. These studies demonstrate the persistence of ETS reactivity during a 2-year period. Although cromolyn sodium and/or albuterol can protect against reactivity, mechanisms of ETS-induced airway reactivity remain unknown.  相似文献   

16.
Allergen-induced increase in airway hyperresponsiveness can be used as a model of airway inflammation for assessing antiasthma pharmacologic agents. Steroids and cromolyn, but not beta-agonists, inhibit this increase; theophylline, recently suggested as having anti-inflammatory effects, has not been evaluated in this model. Six atopic subjects with asthma and with late asthmatic responses (N = 5) and postallergen reduction in a provocative concentration of methacholine causing a 20% fall in FEV1 (PC20) (N = 6) were studied. Sustained-release theophylline (Theo-Dur; Astra Pharmaceuticals Canada, Ltd., Mississauga, Canada), 300 mg, and placebo were administered single-blind twice daily for eight doses up to 1 hour before allergen inhalation; cromolyn sodium, 10 mg, was administered in a single dose 10 minutes before allergen inhalation on another day as a "positive control." Mean theophylline levels were in the low therapeutic range, 57 +/- 17 and 58 +/- 13 mumol/L 1 and 8 hours after the last tablet. The FEV1 was 7% and 9% greater after the seventh and eighth doses of theophylline versus placebo (p less than 0.05). Theophylline also produced a significant (p less than 0.05) twofold increase in methacholine PC20. There was a 40% (p = 0.06) reduction in early asthmatic fall in FEV1 and a 25% (not significant) reduction in late FEV1 fall when theophylline was compared to placebo. Theophylline did not influence the geometric mean allergen-induced fall in methacholine PC20 delta log PC20; this was true individually in five of the six subjects. By contrast, cromolyn sodium inhibited all aspects of the allergen response completely.(ABSTRACT TRUNCATED AT 250 WORDS)  相似文献   

17.
Anticholinergic agents have been widely used in the management of asthma. The use of scopolamine has been limited by significant side effects. Transdermal delivery of scopolamine (TS) has, however, been used successfully for the prevention of motion sickness. The purpose of this study was to determine if TS would decrease methacholine-induced bronchospasm in a group of subjects with mild asthma. Bronchoprovocational challenges with inhaled methacholine were performed on three separate occasions in 10 male subjects who each had a past history of asthma. After a baseline challenge, each subject received, in a double-blinded fashion, either a placebo patch or TS patch. The challenge was then repeated after at least 36 hours, and the alternate patch was then dispensed. The provocative dose producing a fall in FEV1 by 20% from baseline was then calculated by linear regression analysis. No significant change in baseline pulmonary function was noted with placebo patch or TS. With the use of TS, there was a small but significant increase in the provocative dose producing a fall in FEV1 by 20% from baseline for the group (p less than 0.05). In conclusion, we were able to demonstrate that a TS patch worn for a short period of time, can significantly decrease airway reactivity to methacholine in some patients with hyperactive airways.  相似文献   

18.
Degree and duration of bronchial hyperreactivity (BHR) after environmental tobacco smoke (ETS) inhalation was assessed in 31 smoke-sensitive subjects with asthma who exhibited lower airway symptoms on ETS exposure (group I) and 39 smoke-sensitive subjects without asthma who manifested only upper airway symptoms on cigarette-smoke exposure (group II). Subjects were challenged with ETS for 4 hours in a static-test chamber. The atmosphere was continuously monitored for airborne particulate levels (800 cpm), total suspended particulates (1266 +/- 283 micrograms/m3), and airborne nicotine levels (226 +/- 49 micrograms/m2). Methacholine challenges were performed before and serially after cigarette-smoke exposure, and the provocative dose causing a 20% fall in FEV1 was determined. Five of the 31 smoke-sensitive subjects with asthma and none of the smoke-sensitive subjects without asthma reacted to cigarette-smoke challenge (greater than or equal to 20% fall from baseline FEV1). Thirty-two percent (10/31) of the subjects with asthma demonstrated increased BHR at 6 hours, 29% (9/31) at 24 hours, and 13% (4/31) up to day 14 after ETS challenge. Of the subjects without asthma, 18% (7/39) demonstrated increased BHR at 6 hours, 10% (4/39) at 24 hours, and 8% (3/39) at 3 weeks. These studies demonstrated an increase in BHR after cigarette-smoke challenge in a number of study subjects (although they were clinically asymptomatic) and suggest that prolonged subclinical airway inflammation can occur in the absence of demonstrable change in airway caliber on exposure to ETS.  相似文献   

19.
Beta-adrenergic responses in drug-free subjects with asthma   总被引:2,自引:0,他引:2  
Young atopic subjects with asthma who had taken no medication for 30 days and had normal pulmonary function were compared to atopic and nonatopic control subjects in several measures of beta-adrenergic response. Subjects with asthma required a larger dose of infused isoproterenol (14.3 +/- 3.9 ng/kg/min) to increase pulse pressure by a target greater than 22 mm Hg than nonatopic control subjects (8.7 +/- 3.3 ng/kg/min). Asymptomatic atopic control subjects had intermediate sensitivity (12.0 +/- 6.0 ng/kg/min) (F = 3.67; p less than 0.05). At the dose of infused isoproterenol producing the target pulse pressure response, the increase in low-frequency (1 to 8 cycles per minute) heart rate variability was less in subjects with asthma (107 +/- 34% increase in normal subjects versus 9 +/- 21% increase in subjects with asthma; p less than 0.05). In addition, subjects with the least beta-adrenergic responsiveness had the most reactive airways. Airway reactivity (assessed by the provocative concentration of methacholine causing a 20% fall in FEV1) correlated with both the dose of isoproterenol required for the target pulse pressure response (Rs = -0.46; p less than 0.05) and the isoproterenol-induced increase in low-frequency heart-rate variability (Rs = 0.47; p less than 0.05). In contrast, in lymphocytes and granulocytes from these same subjects, the cAMP response to isoproterenol and beta-adrenergic receptor number were identical in normal subjects and subjects with asthma and unrelated to airway reactivity or to cardiovascular beta-adrenergic responses. Thus, different results for beta-adrenergic responsiveness in subjects with asthma are obtained in different tests in the same subjects.  相似文献   

20.
To assess whether mast cell and eosinophil (EOS) degranulation occurs in the airway of subjects with moderately symptomatic asthma, we have measured levels of preformed mast cell-derived mediators (histamine and tryptase) and EOS-derived mediators (major basic protein and EOS-derived neurotoxin) in bronchoalveolar lavage fluid (BALF) obtained from patients with symptomatic (N = 14) and asymptomatic asthma (N = 9) and patients without asthma (N = 6). Both the FEV1 (1.52 +/- 0.33 L:55% +/- 15% of predicted FEV1) and the forced expiratory flow at 50% (FEF50) (1.11 +/- 0.62 L/sec:26% +/- 14% of predicted FEF50) in the patients with symptomatic asthma were significantly lower than the corresponding values for FEV1 (3.16 +/- 0.45 L:86% +/- 10% of predicted FEV1) and the FEF50 (4.04 +/- 1.54 L/sec:71% +/- 25% of predicted FEF50) in the patients with asymptomatic asthma. Levels of histamine (4.8 +/- 5.0 ng/ml versus 0.2 +/- 0.2 ng/ml) (p = 0.05), EOS-derived neurotoxin (420.6 +/- 959.4 ng/ml versus 12.6 +/- 7.7 ng/ml) (p = 0.05), major basic protein (31.4 +/- 46.6 ng/ml versus less than 9 ng/ml) (p = 0.05), and percent EOSs (10.6% +/- 7.0% versus 1.1% +/- 0.9% of BAL cells) (p = 0.0006) were all significantly elevated in BALF from symptomatic compared to asymptomatic patients with asthma. The elevated levels of tryptase (13.2 +/- 14.8 ng/ml versus 3.9 +/- 3.9 ng/ml) in BALF from symptomatic compared to asymptomatic patients with asthma approximated, but did not reach, statistical significance. Spontaneous histamine release from BAL mast cells of symptomatic patients with asthma was 46% +/- 5% compared to 5% +/- 2% in asymptomatic patients with asthma. In response to antihuman IgE, histamine release from BAL mast cells recovered from asymptomatic patients with asthma increased to 25% +/- 10%, whereas in BAL mast cells of symptomatic patients with asthma, no anti-IgE potentiation of histamine release occurred. This study suggests that mast cell and EOS degranulation is ongoing in the airway of patients with moderately symptomatic asthma.  相似文献   

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