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PubMed1988

Bronchoconstriction by nebulized metabisulfite solutions (SO2) and its modification by ipratropium bromide.

A nebulized solution of sodium metabisulfite (MBS) induced bronchoconstriction in nine subjects with asthma. An anticholinergic drug, ipratropium bromide (IPRA), in doses (500 to 700 micrograms) which were found to inhibit methacholine-induced bronchoconstriction, protected three of the nine subjects against nebulized MBS. These results suggest that both cholinergic and non-cholinergic reflex mechanisms are involved in MBS-induced bronchoconstriction.

Atropine Derivatives↗

PubMed1988

Methylxanthines inhibit exercise-induced bronchoconstriction at low serum theophylline concentration and in a dose-dependent fashion.

We studied the relationship between attenuation of exercise-induced bronchoconstriction and serum theophylline concentration in a dose-dependent fashion in 11 patients with mild bronchial asthma. In addition, we investigated the protection of equal amounts of theophylline either dissolved in ethylenediamine or in proxyphylline and diprophylline. At 4 separate study days, the patients received one of the following preparations in a double-blind random order: saline solution, 200 mg of theophylline in 19.9 mg of ethylenediamine (TE200), 351 mg of theophylline in 35 mg of ethylenediamine (TE351), and 200 mg of theophylline in 300 mg of propxyphylline and 300 mg of diprophylline (TPD). Fifteen minutes after the end of infusion, a standardized exercise test during cold air breathing was performed. Before and up to 30 minutes after each test, specific airway resistance and FEV, were determined. Postexertional bronchoconstriction after theophylline was expressed by means of a protection index, a value of 0 or 1 meaning no or full protection, respectively. At mean (SD) serum theophylline concentrations of 6.7 (1.3), 10.1 (1.7), and 6.3 (1.4) mg/L, respectively, TE200, TE351, and TPD for specific airway resistance caused a significant bronchodilation (p less than 0.05) and resulted in mean (SD) protection indices of 0.61 (0.15), 0.82 (0.14), and 0.65 (0.20), respectively, being significantly different from 0 (p less than 0.01). The protective effect of TE200 and TPD was equal and significantly less pronounced as compared to TE351 (p less than 0.01). Therefore, theophylline attenuated exercise-induced bronchoconstriction in a dose-dependent fashion with significant protection at serum concentrations of about 6 mg/L. The effect of intravenous theophylline was independent of the diluents.

Adolescent↗

PubMedDate not supplied

Bronchoconstriction due to isocapnic cold air inhalation minimally influences bronchial hyperresponsiveness to methacholine in asthmatic subjects.

The aim of this study was to investigate if bronchial hyperresponsiveness to methacholine could be influenced by a previous bronchoconstriction due to isocapnic inhalation of cold air. Twelve adult asthmatic subjects in a clinical steady state were seen on four different days in a randomized way according to three different sequences. After assessment of spirometry, bronchial responsiveness to inhaled methacholine was determined on each occasion by the provocative concentration causing a fall of 20% in FEV1 (PC20). On two occasions, the methacholine test was preceded by the inhalation of dry cold air which caused significant (greater than 20% change in FEV1) bronchoconstriction. The methacholine test was performed after functional recovery. There was a significant (t = 2.53; p less than 0.05) but minimal (mean changes of 0.65 single two-fold concentration difference) reduction in PC20 after cold air inhalation. It is concluded that cold air-induced bronchoconstriction causes significant but minimal changes in bronchial responsiveness to methacholine in asthmatic subjects.

Asthma↗

PubMedDate not supplied

[The effects of different inhibitors on the bronchoconstriction induced by leukotriene D4 in the isolated and perfused guinea pig lung].

The effects of selective inhibitors of both cyclo-oxygenase and lipoxygenase pathways were studied in the isolated, perfused and ventilated guinea-pig lungs. Leukotriene D4 (0,3 nmol) induced a significant bronchoconstriction. This effect was significantly inhibited by FPL 55712 (a SRS-A antagonist) and by Imidazole or Dazoxiben (specific thromboxane synthetase inhibitors), but aspirin and indomethacin were without significant effect on this bronchoconstriction. Our results suggests that the principal component of leukotriene D4 induced bronchoconstriction in guinea-pig lungs is primary.

Airway Resistance↗

PubMed1985

The effect of dipyridamole on histamine- and adenosine-induced bronchoconstriction in normal and asthmatic subjects.

The effect of intravenous infusion of dipyridamole on histamine- and adenosine-induced bronchoconstriction was studied in 6 normal and 6 allergic asthmatic subjects. Dipyridamole in a single dose of 50 mg over 50 min had no effect upon baseline airway calibre measured as specific airways conductance (sGaw) and the forced expiratory volume in 1 s (FEV1). In the asthmatic subjects adenosine-induced bronchoconstriction was potentiated to a small extent by dipyridamole as indicated by a decrease in the concentration of adenosine required to produce falls from baseline of 40% for sGaw (PCs40) and 20% for FEV (PCf20) from 0.48 mg/ml to 0.32 and 0.37 mg/ml respectively. Dipyridamole had a small protective effect on histamine-induced bronchoconstriction with PCs40 and PCf20 increasing from 0.08 mg/ml to 0.11 and 0.17 mg/ml. In normal subjects dipyridamole failed to reveal a bronchoconstrictor effect of adenosine. These studies demonstrate the complex interaction between dipyridamole and bronchoconstrictor stimuli on the airways.

Adenosine↗

PubMedDate not supplied

[Effect of several antiasthmatic prophylactic drugs on bronchoconstriction induced by kerosene in rabbits].

Various authors have reported the protective effect of disodium cromoglycate (DSCG) against bronchoconstriction induced by cold air, exercise, sulfurdioxide and other agents. We also found in our experimental work the protective effect of DSCG, ketotifen and oxatomide against the contractile effect of various agonists such as histamine prostaglandin F2, acetylcholine and barium chloride on isolated guinea pig intestine and trachea. This suggests an additional effect of these drugs on cholinergic endings and/or directly on smooth muscle fibers in addition to their membrane stabilizing effects on mast cells as it has been suggested by other authors previously. To offer insight into these mechanisms we decided to evaluate the action of ketotifen, oxatomide, ICI 74917 and BRL 10833 using the model of kerosene-induced bronchoconstriction in rabbits. Here the parasympathetic pathways play an important role as it has been demonstrated by us using atropine or vagal section. Ketotifen (5 mg/kg i.v.) and oxatomide (5 mg/kg i.v.) were administered before kerosene aerosol exposure these significantly inhibited kerosene-induced bronchoconstriction, whereas ICI 74917 (10 mg/kg i.v.) and BRL 10833 (10 mg/kg i.v.) lacked this protective effect. These results support our hypothesis that an additional protective effect on smooth muscle and its innervation is involved in the mode of action of the prophylactic antiasthmatic drugs which have been clinically successful.

Airway Resistance↗

PubMed1983

Antagonism of the 5-HT-induced bronchoconstriction in the cat.

In cats in which bronchoconstriction was induced and maintained by infusion of 5-HT, the bronchodilator effects of ketanserin, a related compound, cyproheptadine, clenbuterol and aminophylline were compared. The novel 5-HT2 antagonists ketanserin and R50970 were active in doses of about 10 nmol/kg, cyproheptadine was about 5 times less potent, but had a longer duration of action. Clenbuterol and aminophylline were only partially effective against 5-HT-induced bronchoconstriction. There was no reliable effect of the 5-HT antagonists against carbachol-induced bronchoconstriction.

Animals↗

PubMed1980

A dose-response-like relationship between minute ventilation and exercise-induced bronchoconstriction in young asthmatic patients.

Seven adolescent patients with bronchial asthma performed bicycle exercise tests on several occasions, within 1 week. After the determination of baseline pulmonary function (using spirometry, maximal expiratory flow-volume curves and body plethysmography), all subjects were exercised on the bicycle ergometer for 10 min. On each occasion a different level of minute ventilation (VE, 1/min) was achieved, because of different work performed. Following each exercise test, the degree of exercise-induced bronchoconstriction was assessed. It was found that the degree of bronchoconstriction, as measured by pulmonary function tests, is function of VE measured during exercise. A dose-response-like relationship, i.e., level of VE vs. bronchoconstrictive response, seems to be an important individual characteristic of the airway reactivity of young patients with bronchial asthma.

Adolescent↗

PubMedDate not supplied

Functional assessment of airways bronchoconstriction with nebulized acetyl salicylic acid.

The aim of our study was to verify the functional modifications affecting central and peripheral airways during bronchoconstriction induced by aerosolized aspirin, so as to better understand the pathophysiologic mechanisms of the asthmatic crises in A.S.A. sensitive patients. The preliminary results were presented of a study carried out o 12 asthmatic A.S.A. sensitive patients, 7 of whom were females and 5 males, between the ages of 22 and 57 years. A.S.A. sensitivity was found in their medical history, in some cases, it had been confirmed by oral A.S.A. challenge. Among these patients, 6 were also affected by nasal polyposis. The method used was recently described by Bianco et al. although slightly modified by us: a fresh aqueous solution (18%) of A.S.A. -L is diluted 1:3 in saline; 4 ml of this solution is transferred to a glass nebulizer activated by a small compressor. The patients underwent treatment for 60 sec, during which a dose of approximately 1,8 mg of A.S.A. was inhaled, corresponding to about 40 mg of aspirin taken orally. In comparison with the reactions induced by oral challenge, those obtained with this treatment are easier, faster and confined only to the respiratory system. Before giving A.S.A. to the patients, control tests using saline aerosol were done. The functional assessment was performed under basal conditions, and 1, 15, 30, 60, 90 and 120 minutes following administration of A.S.A. since bronchoconstriction caused by nebulized A.S.A. usually reaches peak values between the 60th and 90th min. after which it gradually decreases over the following two hours. Our results show that, though A.S.A. induced bronchoconstriction prevails at large airways, it also influences the distal tracts of the tracheobronchial tree, since both SRAW, FEV1 and Vmax50C are modified at the same time.

Adult↗

PubMed2000

Dose-responses over time to inhaled fluticasone propionate treatment of exercise- and methacholine-induced bronchoconstriction in children with asthma.

When treating bronchial hyperresponsiveness to so-called direct and indirect stimuli, distinct pathophysiological mechanisms might require differences in dose and duration of inhaled corticosteroid therapy. To test this hypothesis in children with asthma, we investigated the time- and dose-dependent effects of 2 doses of fluticasone propionate (FP, 100 or 250 microg bid.) in improving exercise- (EIB) and methacholine-induced bronchoconstriction during 6 months of treatment, using a placebo-controlled parallel group study design. Thirty-seven children with asthma (aged 6 to 14 years; forced expired volume in 1 sec (FEV(1)) >/=70% predicted; EIB >/=20% fall in FEV(1) from baseline; no inhaled steroids during the past 4 months) participated in a double-blind, placebo-controlled, 3-arm parallel study. Children receiving placebo were re-randomized to active treatment after 6 weeks. Standardized dry air treadmill exercise testing (EIB expressed as %fall in FEV(1) from baseline) and methacholine challenge using a dosimetric technique (expressed as PD(20)) were performed repeatedly during the study. During FP-treatment, the severity of EIB decreased significantly as compared to placebo within 3 weeks, the geometric mean % fall in FEV(1) being reduced from 34.1% to 9.9% for 100 microg FP bid, and from 35.9% to 7.6% for 250 microg FP bid (P < 0.05). These reductions in EIB did not differ between the 2 doses and were sustained throughout the treatment period. PD(20) methacholine improved significantly during the first 6 weeks as compared to placebo (P < 0.04) and steadily increased with time in both treatment limbs (P = 0.04), the difference in improvement between doses (100 microg FP bid, 1.6 dose steps; 250 microg FP bid, 3.3 dose steps) approaching significance after 24 weeks (P = 0.06). We conclude that in childhood asthma, the protection afforded by inhaled fluticasone propionate against methacholine-induced bronchoconstriction is time- and dose-dependent, whereas protection against EIB is not. This suggests different modes of action of inhaled steroids in protecting against these pharmacological and physiological stimuli. This has to be taken into account when monitoring asthma treatment.

Administration, Inhalation↗

PubMedDate not supplied

Use of a head dome system to compare i.v. methacholine-induced bronchoconstriction in conscious vs anesthetized rhesus monkeys.

The use of a newly developed head dome system has allowed measurement of pulmonary function in conscious monkeys. Such information is often desired, so that pharmacological or toxicological effects of administered compounds can be measured in the absence of effects from anesthetic agents. The current study was conducted to gain experience with this method and to allow the determination of the effects of sodium pentobarbital anesthesia (30 mg kg-1 i.v.) on the bronchoconstriction seen during i.v. infusion of methacholine in rhesus monkeys. Bronchoconstriction was measured as changes in respiratory resistance using a Buxco LS20 pulmonary mechanics computer. Four male rhesus monkeys (4.2-5.1 kg) were used. For the anesthetized exposures, the animals were intubated with a 4.0-mm cuffed endotracheal tube attached to a size 'O' Fleisch pneumotachograph. For the conscious exposures, the animals sat in restraining chairs with a custom-built head dome attached to the same pneumotachograph. In both cases, transthoracic pressure was monitored with an intrapleural catheter. Each monkey was infused with methacholine in stepwise doses, while anesthetized and conscious, until a 75% increase in respiratory resistance was seen. The ED50 values of 0.134 and 0.180 mg ml-1 methacholine were not significantly different in anesthetized vs conscious monkeys, respectively.

Airway Resistance↗

PubMed1992

Measurement of bronchial responsiveness in young children: comparison of transcutaneous oxygen tension and functional residual capacity during induced bronchoconstriction and -dilatation.

Demonstration of an increased bronchial responsiveness in preschool children may support the diagnosis of asthma. Most young children cannot perform routine lung function tests. Transcutaneous PO2 (PtcO2) measurement has been applied successfully in young children, and changes in PtcO2 have been shown to correlate well with changes in forced expiratory volume in 1 second (FEV1) during bronchoprovocation testing with methacholine. PtcO2 is, however, an indirect measure of the effect of inhaled spasmogens. As functional residual capacity (FRC) can also be measured by helium dilution spirometry in preschool children, we compared PtcO2 and FRC during methacholine inhalation challenges and after inhaled terbutaline, in order to determine whether FRC is useful as a more direct measure of induced bronchoconstriction and -dilatation than PtcO2. We studied 41 allergic asthmatic children (mean age, 5.2 years) who underwent a methacholine bronchoprovocation test; 38 children received terbutaline 1 h after the final methacholine dose. The provocative concentration of methacholine that caused a 20% decrease of PtcO2 was determined, and changes in FRC and PtcO2 after each methacholine dose step were compared. Similarly, changes in PtcO2 and FRC before, and 15 and 30 min after, terbutaline were compared. All children had a drop in PtcO2 after increasing doses of methacholine; a 20% change was reached in 38 patients. Mean FRC values increased significantly but variably with increasing doses of methacholine, and changes in PtcO2 and FRC did not correlate. After terbutaline, PtcO2 increased slightly but significantly, and FRC again varied unpredictably. In a separate group of 11 children, the effect of terbutaline was assessed directly after the final methacholine dose, when significant bronchoconstriction was still present.(ABSTRACT TRUNCATED AT 250 WORDS)

Asthma↗

PubMed1993

Nedocromil sodium vs. sodium cromoglycate pressurized aerosol in the prevention of bronchoconstriction induced by ultrasonic nebulized distilled water in asthmatic children.

To compare the effectiveness of nedocromil sodium (NS) and sodium cromoglycate (SCG), administered by metered dose inhaler (MDI) with a 700 mL holding chamber (Fisonair Fisons UK) in preventing bronchoconstriction induced by inhalation of ultrasonically nebulized distilled water (UNDW), 12 asthmatic children were studied in a randomized, double-blind, placebo-controlled, intrapatient study. Following a baseline challenge with UNDW, the protective effect of NS, SCG, or placebo was evaluated in each subject. Cumulative doses of delivered nebulized water producing a 20% fall in forced expiratory volume in 1 sec (PD20 UNDW) was measured. Mean (+/- SD) PD20 UNDW was 4.83 (+/- 4.84), 10.16 (+/- 7.05), 1.58 (+/- 0.5), and 15.93 (+/- 0.23) respectively, for baseline, and placebo, SCG, and NS-treated groups. A significant (P < 0.05) protection from UNDW induced bronchoconstriction by NS was observed in comparison with placebo, while no such effect was evident when the children were treated with SCG.

Adolescent↗

PubMed1993

Comparison of efficacy of salbutamol and sodium cromoglycate in the prevention of ticarcillin-induced bronchoconstriction.

Nebulized ticarcillin can cause bronchoconstriction in children with cystic fibrosis (CF). We assessed whether pretreatment with salbutamol or sodium cromoglycate (SCG) would prevent this side-effect using a randomized, double-blind, placebo-controlled design. Fifteen children with CF received pretreatments of saline, SCG, or salbutamol, in random order, one on each day. Baseline lung function was measured before and after pretreatment, and after ticarcillin nebulization. On the control day (saline pretreatment), ticarcillin caused a reduction in forced expiratory volume in one second (FEV1), which was maximal 10 minutes after receiving the aerosol and persisted for 120 minutes. The mean maximal fall in FEV1 was 9%. Pretreatment with salbutamol abolished the fall in FEV1 seen with ticarcillin at all time points. Pretreatment with SCG diminished the maximal fall in FEV1 at 10 minutes (mean, 4%) and resulted in the FEV1 returning to baseline within 120 minutes. These data suggest that pretreatment with salbutamol is more effective in preventing ticarcillin-induced bronchoconstriction in the doses used in routine clinical practice, than it is with SCG.

Adolescent↗

PubMed2006

Montelukast administered in the morning or evening to prevent exercise-induced bronchoconstriction in children.

Montelukast is recommended to be taken in the evening. The effectiveness of this drug to prevent exercise-induced bronchoconstriction (EIB) in children was already evaluated. However, there is no information to determine if this effectiveness could vary depending on dosage time. Children (n = 24) with a documented history of EIB performed an exercise challenge test before starting montelukast treatment. Twelve children were randomly allocated to receive the drug in the morning for 2 weeks, and another 12 to receive it in the evening. After this treatment period and after a week of washout, the children were crossed over. An exercise test was repeated after the first and second periods of treatment. Values obtained after morning or evening dosage were compared with pretreatment values for the whole group of children. There was a significant effect of montelukast for protecting against EIB, measured both as percent of maximum fall in forced expired volume in 1 sec (FEV1) (18.9 +/- 9.7, morning, 18.7 +/- 11.3, evening, vs. 27.5 +/- 9.8, pretreatment; P < 0.05) or as area under the curve (156.4 +/- 102.0, morning, 145.4 +/- 130.6, evening, vs. 294.3 +/- 156.5, pretreatment; P < 0.005). There were no statistical differences between taking the drug in the morning or evening. In conclusion, montelukast, taken for 2 weeks, is equally effective in exercise-induced bronchoconstriction when dosing either in the morning or in the evening.

Acetates↗

PubMed1994

Codeine-induced bronchoconstriction and putative bronchial opiate receptors in asthmatic subjects.

To determine whether a mu opiate agonist can constrict the human airways, the dose of codeine (C) or histamine (H) producing a 40% decrease (PD40) in specific airway conductance (SGAW) was measured in 17 asthmatic and 14 normal subjects. Then, the subjects were skin tested with C and H, and the effect of naloxone (N) and chlorpheniramine (CP) on PD40-C was assessed. In five asthmatic subjects responding to less than 5 mg (16.6 mumol) inhaled C, SGAW was also recorded after oral administration (30 mg) and pharyngeal spraying (5 mg) of C. PD40-C could be determined in 11 of the 17 asthmatics but in none of the normal subjects. This constrictor effect lasted less than 15 min, was unrelated to resting airway caliber, and required a relatively high bronchial sensitivity to H (PD40-H usually less than 0.2 mumol) and high doses of C (11.93 +/- 12.0 mumol). However, in C responders, PD40-C and PD40-H were unrelated. C-induced bronchoconstriction was blunted by N in a dose-dependent fashion and to a mild and inconsistent degree, by CP. Pharyngeal spraying or oral challenge with C failed to change SGAW. Skin sensitivity to H and C was similar in C-responders and non-responders. In conclusion, large doses of inhaled C constrict the airways of asthmatic subjects highly sensitive to H. This effect seems mediated through (mu?) opiate receptors located bronchially rather than centrally, pharyngeally or in the skin. In C-induced bronchoconstriction H liberation plays a contributory but minor role. Skin and bronchial sensitivity to C are unrelated.

Adolescent↗

PubMed2002

Adenosine-mediated bronchoconstriction and lung inflammation in an allergic mouse model.

In this study, we studied the role of adenosine on airway responsiveness and airway inflammation using an allergic mouse model. Mice were sensitized by two i.p. injections of ragweed and three consecutive ragweed aerosol challenges. It was found that inhalation of adenosine causes a dose-related bronchoconstriction in this model. Ragweed sensitized and challenged mice showed increased sensitivity to airway challenge to adenosine compared to control animals. Theophylline, a non-selective adenosine receptor antagonist, blocked adenosine-induced bronchoconstriction, but was unable to inhibit bronchoconstrictor response to methacholine. Mice systemically sensitized and airway challenged with allergen showed a marked airway inflammation manifesting increases in eosinophils, lymphocytes and neutrophils, and decrease in macrophages. Twenty-four hours after airway challenge with allergen, aerosolization of adenosine further potentiated the allergen-induced airway inflammation. Cells in bronchoalveolar lavage fluid after adenosine aerosolization increased by 3.07-fold as compared to control mice, and by 1.8-fold compared to ragweed sensitized and challenged mice. The increases in eosinophils, lymphocytes, and neutrophils caused by allergen were potentiated after adenosine challenge. Unexpectedly, macrophages significantly decreased after adenosine challenge. Theophylline attenuated adenosine-enhanced airway inflammation, but could not reverse allergen-induced airway inflammation. These findings suggested that specific adenosine receptors contribute to airway responsiveness and airway inflammation associated with this model of allergic asthma.

Adenosine↗

PubMed1994

Oxygen radicals in exsanguination-induced bronchoconstriction of guinea pigs.

This study investigated the relationship between oxygen radicals and exsanguination-induced bronchoconstriction using antioxidant in guinea pigs. To accomplish this, two phases of studies were carried out. In phase 1, 34 guinea pigs weighing 342 +/- 11 g were divided into five groups: control (n = 7); acute dimethylthiourea (DMTU, n = 7); chronic DMTU (n = 8); superoxide dismutase (SOD, n = 6); and catalase (n = 6). Animals in the control group were not treated. DMTU, SOD, and catalase were employed for the scavenging of hydroxyl radical, superoxide anion, and hydrogen peroxide, respectively. Ten additional guinea pigs weighing 293 +/- 6 g were divided into two groups in phase 2: sham (n = 6) and chronic apocynin (n = 4). Animals in the sham group received injections of the vehicle, whereas apocynin was used to suppress the production of superoxide anion. All animals were anesthetized, sternotomized, and artificially ventilated. Before (baseline) as well as at fixed intervals 5-30 minutes following the exsanguination, the maximal expiratory flow maneuver was performed and the dynamic compliance (Cdyn) was obtained. Decreases in the maximal expiratory flow at 50% baseline vital capacity and Cdyn were used as indicators of bronchoconstriction. Exsanguination in the control and sham groups caused a gradual increase in airway constriction with time that was significantly ameliorated by chronic DMTU and chronic apocynin pretreatments but was not affected by other acute treatments. These results indicate that chronic treatment with antioxidants ameliorates exsanguination-induced, tachykinin-mediated airway constriction.

Analysis of Variance↗