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PubMed1984

Different, dose-dependent effects of verapamil inhalation on histamine-induced bronchoconstriction in anaesthetized dogs.

Different, dose-dependent effects of verapamil inhalation on histamine-induced bronchoconstriction in anaesthetized dogs are reported. Cumulative histamine dose-response curves were obtained on three groups each consisting of six dogs. These groups were: A - after atropine sulphate (1 mg/kg); B - after atropine sulphate and verapamil (approximately 0.5 mg/kg); C - after atropine sulphate and verapamil (approximately 5.0 mg/kg). Total lung resistance (R1) was measured as the indicator of bronchoconstriction. The mean maximal response of R1 in B was significant greater (p less than 0.01) than in A and C, while no significant difference was observed between A and C. A possible mechanism is postulated.

Aerosols↗
PubMed1984

Mechanism of bronchoconstrictive effects of aerosolized buffered saline in asthmatics.

Bronchoconstriction, measured by spirometry and body plethysmography, has been reported with deep breaths of air and of aerosolized buffered saline (ABS) (0.5% sodium chloride and phosphate buffer), in some stable asthmatics. To investigate the mechanisms of this phenomenon, we measured airway resistance (Raw) and functional residual capacity (FRC) in ten asthmatics after deep breaths of ABS, tidal breaths of ABS, tidal breaths of unbuffered normal saline (0.9% sodium chloride) and tidal breaths of 0.5% sodium chloride (ABS without phosphate) on different days. Raw and FRC increased with deep breaths and tidal breaths of ABS in all asthmatics, but not with tidal breaths of normal saline and unbuffered 0.5% sodium chloride. Thus the phosphate buffer rather than the hypoosmolarity of aerosolized buffered saline causes bronchoconstriction in asthmatics.

Adult↗
PubMedDate not supplied

Disodium cromoglycate inhibits bronchoconstriction by kerosine aerosol in rabbits.

To determine whether or not disodium cromoglycate (DSCG) inhibits the bronchoconstriction induced by inhalation of kerosene aerosol in rabbits, we carried out a study in 31 normal rabbits which were divided into four groups. DSCG was administered through the tracheal cannula twenty minutes before exposure to kerosene aerosol. Twenty and forty milligrams of DSCG as total doses inhibited kerosene induced bronchoconstriction in large airways (RL), but 5 mg of drug did not have any effect. DSCG at any tested dose did not inhibit the decreased dynamic lung compliance (CL) which was observed after kerosene aerosol. Our findings suggest that DSCG at high dose inhibit the bronchoconstrictor effect of kerosene in large airways of rabbits.

Aerosols↗
PubMed1984

[Pirbuterol and salbutamol aerosol for exercise-induced bronchoconstriction].

Exercise-induced bronchoconstriction was produced in 12 asthmatic patients after a 6 minutes run on a 10% steep treadmill ergometer. FEV1 decreased by 12-73% (average 27%) of the control value measured before the run. The rather severe exercise-induced bronchoconstriction remained constant for 10-20 minutes after the run. 21 minutes after the run two puffs of a bronchodilator (salbutamol 0.2 mg or pirbuterol 0.4 mg) were inhaled in an open randomized cross-over fashion at intervals of 1 to 3 days. Following both bronchodilators FEV1 returned to the control value within 5 minutes. There was no significant difference between the bronchodilating effect of salbutamol versus pirbuterol. Furthermore, no significant differences were observed in pulse rates after inhalation of the two selective beta-2-stimulators. In our trial both pirbuterol and salbutamol seemed to be well tolerated; side effects were not observed for either drug.

Adult↗
PubMed1983

Deep-inspiration induced bronchoconstriction: a mechanism for beclomethasone aerosol intolerance.

We studied 17 asthmatic patients complaining of coughing attacks, with or without asthma, when inhaling beclomethasone dipropionate aerosol (Becotide). Specific airway resistance (SRaw) was measured immediately after a maximal inspiration (MI) and after Becotide inhalation. The effect of a second inhalation of Becotide was measured 10 min after inhalation of salbutamol. MI and Becotide induced large, but transient, SRaw increases in all patients; in addition, the latter induced coughing reactions. After salbutamol pretreatment, Becotide inhalation did not increase SRaw but coughing usually persisted. In 6 patients only, the increase in SRaw after Becotide was larger than that observed after MI. In those patients, placebo and Aldecine (similar to Becotide except for the metering valve) aerosols induced SRaw increases similar to that observed after Becotide. These data suggest that Becotide-induced bronchoconstriction is mainly related to the deep breath required for the inhalation. Non-specific irritation of the airways was probably responsible for the additional bronchoconstriction noticed in some patients.

Aerosols↗
PubMed1984

Effect of inhaled diphemanil methylsulfate, a parasympatholytic agent, on histamine induced bronchoconstriction in asymptomatic asthmatics.

Parenterally administered diphemanil methylsulfate, a quarternary ammonium compound with both parasympatholytic and direct bronchial smooth muscle relaxing properties, has been found effective in the treatment of bronchial asthma. The present study was undertaken to test the effectiveness of inhaled diphemanil in preventing histamine induced bronchoconstriction in asymptomatic adult asthmatics. Twenty subjects, aged 19-40 years (average 25) were studied, each on three different days, observing an interval of at least 70 hours between testing. On day one, airway sensitivity to inhaled histamine was determined. On days two and three, histamine challenge was repeated 20 minutes after inhalation of either diphemanil (2 mg) or its vehicle in a double-blind crossover design. Airway sensitivity was assessed by determining cumulative log dose units of inhaled histamine required to provoke a 20% decline in FEV1 (log PD20 - FEV1). Diphemanil did not prevent histamine induced bronchoconstriction nor did it significantly affect log PD20 - FEV1 (p = 0.59). We conclude that a 2 mg dose of diphemanil, administered by oral inhalation 20 minutes before histamine challenge, is ineffective in protecting against induced bronchospasm in asymptomatic adult asthmatics.

Administration, Intranasal↗
PubMedDate not supplied

Regional hypoventilation and bronchoconstriction during pulmonary air embolism.

The hypothesis that experimental pulmonary air embolism would lead to bronchoconstriction in the upper lungs and a shift in ventilation toward the lower lung regions was tested in anaesthetized and paralyzed dogs. During constant rate air infusion (0.15 ml X kg-1 X min-1), regional distribution indices were obtained using radioactive xenon boli injected at the mouth at residual volume. The results show that there was a shift of inspired xenon toward the dependent lungs after 30 min of air infusion and that this shift was accompanied by a rise in pulmonary artery pressure, a slight decrease in vital capacity, a significant increase in closing volume and an increase in airway resistance. Inspiring 5% CO2 after the shift did not reverse the distribution of xenon boli. Intravenous injection of isoproterenol after the changes had occurred, on the other hand, invariably returned the distribution toward control values. These findings indicate that hypoventilation and bronchoconstriction occurred in the non-dependent lungs during pulmonary air embolism.

Airway Resistance↗
PubMed1982

Effects of intravenous and aerosol nifedipine on prostaglandin F2 alpha and histamine-induced bronchoconstriction in anesthetized dogs.

The effect of nifedipine, a calcium slow channel blocking drug, was investigated by varying routes of administration in a canine model of pharmacologically induced bronchoconstriction. Control bronchopulmonary responses, i.e., increases in pulmonary resistance (RL) and decreases in dynamic lung compliance were accomplished by aerosols of prostaglandin F2 alpha and histamine in normal pentobarbital-anesthetized beagles. When infused i.v. within the range 200 to 400 micrograms/kg, nifedipine afforded significant protection vs. RL changes due to prostaglandin F2 alpha (84--89% inhibition). Aerosol pretreatment by nifedipine (0.1 and 1.0%) also produced significant inhibition in RL changes caused by prostaglandin F2 alpha. A single i.v. injection (200 micrograms/kg) of nifedipine provided significant protection against RL changes due to a histamine challenge for 240 min. The onset of protection occurred within 15 min and maximum protection occurred during the 60 to 90-min period after the single injection of nifedipine. A single aerosol pretreatment of nifedipine (0.1%) significantly blocked RL changes against successive histamine aerosol challenges at 15-, 30- and 60-min time periods. Infused nifedipine failed to have any relaxant effect on the resting base line of either RL or dynamic lung compliance, whereas aerosolized nifedipine did decrease resting airway tone intrinsically, although not significantly. In addition, cardiovascular side effects by the aerosol route were slight compared to those observed by the i.v. route of nifedipine. Therefore, delivery of a calcium channel antagonist by either the aerosol or i.v. route can inhibit pharmacologically induced bronchoconstriction.

Aerosols↗
PubMed1981

Inhibition of methacholine-induced bronchoconstriction with reproterol, a new beta agonist-xanthine derivative.

This study compared the efficacy of single oral doses of a new beta adrenergic agonist-xanthine derivative, reproterol, with placebo by measuring the degree of induced bronchodilation and inhibition of response to methacholine challenge in patients with bronchial asthma. In comparison with placebo, 30 mg reproterol was an effective bronchodilator. Attenuation of the response, but not complete blockage of the methacholine-induced bronchoconstriction, was observed with 30 mg reproterol. Methacholine-induced bronchoconstriction is of use in assessing effect and mechanism of the action of new pharmacologic agents.

Adult↗
PubMed1982

Effect of chronic non-immunologically mediated bronchoconstriction on bronchial smooth muscle in the guinea pig.

Immature guinea pigs underwent eight weeks of methacholine-induced wheezing on a daily basis. At the end of the study the treated guinea pigs showed less of a weight gain than control animals. Relative dry tracheal weight was greater in the methacholine group than in controls. However, there were no differences noted on histologic examination of the lungs between the treated and control animals. Although experimentally induced amounts of bronchoconstriction may not be extrapolated to the same degree as seen in asthma, these findings suggest that repeated bronchoconstriction alone is not the cause of the smooth muscle hypertrophy and hyperplasia found in asthma.

Animals↗
PubMed1981

Lidocaine aerosols do not prevent allergic bronchoconstriction.

To test the effectiveness of local anesthetic aerosols in asthma, we compared the protection afforded by lidocaine and saline aerosols to bronchoconstriction provoked by inhalation of Ascaris antigen aerosols in five previously sensitized, anesthetized Basenji-Greyhound, crossbred dogs. Pulmonary resistance (RL) was determined by the method of Von Neergaard and Wirz, and blood lidocaine levels were determined by gas chromatography. Lidocaine, 4%, was administered as an aerosol for 10 minutes before challenge with Ascaris antigen and again during the 10-minute challenge with Ascaris antigen. Lidocaine aerosols frequently elicited a slight increase in RL before antigen challenge, whereas saline aerosols did not alter RL. Despite a large dose (approximately 10 mg/kg), which produced blood levels of 0.6 to 3.3 micrograms/ml, lidocaine afforded no protection against antigen challenge: RL increased from a control mean of 4.2 +/- 1.7 (SEM) cm H2O/liters/sec to 26.9 +/- 9.3 after challenge in lidocaine-treated dogs, and from 2.9 +/- 0.6 to 22.8 +/- 5.1 in saline-treated dogs. In contrast, lidocaine aerosols prevented the 7-fold increase in RL elicited by challenge with citric acid aerosols, demonstrating an adequate block of irritant reflexes. The failure of lidocaine aerosols to protect against antigen-induced bronchoconstriction indicates that the concentrations achieved in lung by this route are inadequate to relax smooth muscle directly.

Aerosols↗
PubMed1996

ETB receptor mediating pulmonary hypertension and bronchoconstriction induced by endothelin-1 in the guinea pig.

Endothelin (ET-1) caused dose-related contraction of isolated superfused bronchus and pulmonary artery and bronchoconstriction and pulmonary vascular hypertension of the heart lung preparation (HLP) of guinea pig. The specific ETA receptor antagonist BQ 123 completely blocked the responses of the pulmonary artery, but failed to affect those of bronchus and of HLPs. The specific ETB receptor agonist Sarafotoxin S6c caused contractions of bronchus, but not of pulmonary artery, and bronchoconstriction and pulmonary hypertension in HLPs. It is concluded that non-ETA subtype receptors, perhaps ETB, appear to be the main responsible for the potent pulmonary hypertensive effects of ET-1.

Animals↗
PubMed1999

Effect of different inhaled bronchodilators on recovery from methacholine-induced bronchoconstriction in asthmatic children.

Two hundred fourteen children with mild to moderate asthma were studied to determine bronchodilator effects 5 min after administration of five different metered dose inhaler (MDI) aerosol formulations available in our country, and results were compared to placebo. Methacholine bronchial challenge was performed by the tidal breathing method, using increasing concentrations until a fall in forced expired volume in 1 s (FEV(1)) >/=20% was achieved (PC20). Immediately after FEV(1) had fallen 20% or more, children were randomly allocated into 1 of 6 groups to receive: salbutamol 200 microg (S), fenoterol 200 microg (F), salbutamol 200 microg + beclomethasone 100 microg (S + B), fenoterol 200 microg + ipratropium bromide 80 microg (F + IB), salmeterol 50 microg (SM), and placebo (P). The bronchodilator effect was determined by measuring FEV(1) 5 min after inhalation of medications. Nonparametric tests were used for statistical analysis. The six groups were similar in anthropometric and in respiratory characteristics. All five inhaled aerosols containing beta-agonists caused a significant bronchodilator effect as compared to placebo. However, the effect was significantly greater in the groups treated with F or F + IB (P < 0.05) compared to other formulations. We conclude that the five types of aerosols used in this study are able to reverse methacholine-induced bronchoconstriction 5 min after inhalation of a bronchodilator.

Administration, Inhalation↗
PubMed2004

Dynamic lung morphology of methacholine-induced heterogeneous bronchoconstriction.

Hyperpolarized (HP) 3helium (3He) dynamic MRI was used to investigate airway response in rats following intravenous (i.v.) bolus administration of a contractile agent, methacholine (MCh). The method provides direct visualization of the ventilated regions within the lung. Heterogeneous bronchoconstriction following the i.v. MCh injection was evident using this technique. These 3He dynamic lung images revealed that the inspired fresh air was shunted to the less-constricted regions after the MCh challenge in a similar manner as described by Laplace's relationship for the stability between adjacent alveoli. The airways in the more-constricted regions became nearly closed, resulting in air trapping, while the airways in the less-constricted regions remained effectively open, leading to overinflation. These data suggest a lung model of airway constriction partitioned into ventilated and nonventilated regions. These nonventilated regions are heterogeneously distributed in the lung and this distribution cannot be deduced from spirometric measurement of the whole lung. We demonstrate that a combination of functional 3He images and anatomical 1H images provide an effective method to diagnose regional lung abnormalities in rats.

Animals↗
PubMed2001

Therapeutic equivalence of three metered-dose inhalers containing salbutamol (Albuterol) in protecting against methacholine-induced bronchoconstriction in children with asthma.

Many pharmaceutical companies sell salbutamol in metered-dose inhalers (MDI) for the treatment of asthma. However, the therapeutic equivalence of the more recently released generic products has not been compared with the original patented product in children. Twenty children with mild to moderate asthma, presently asymptomatic and with normal lung function, were randomly allocated to receive 200 microg of inhaled salbutamol (Albuterol) from three MDIs prepared by different manufacturers: the original Glaxo product and two generic products. The three drug formulations and placebo were given 10 min before a methacholine challenge test to determine the degree of protection provided against methacholine-induced bronchoconstriction (MIB) by each salbutamol aerosol. Tests were performed on 4 consecutive days. Doubling concentrations of methacholine were inhaled until the forced expired volume in 1 sec (FEV(1)) decreased by 20% from its baseline value. Compared to placebo, all patients increased significantly the provocation concentration that decreased FEV(1) by 20% (PC(20)) by more than one doubling concentration after inhaling each of the three salbutamol aerosols. The effectiveness was not significantly different between medications (P = 0.8). There was a small but significant difference among MDIs in aerosol particle size and total and fine-particle dose released per actuation. However, no relation was found between aerosol particle size or released dose and the protective effect. This study shows that the three tested brands of salbutamol MDI protected asthmatic children equally from MIB. When prescribing these salbutamol MDIs to prevent symptoms triggered by nonspecific stimuli in asthmatic children, the selection may be based on cost-benefit criteria.

Adolescent↗
PubMed1993

Assessment of forced expiratory volume-time parameters in detecting histamine-induced bronchoconstriction in wheezy infants.

A new technique recently introduced allows the measurement of infant lung function from lung volumes raised by a pump prior to generation of forced expiratory flow-volume (FEFV) curves. Forced expiratory volume-time (FEV1) parameters rather than traditional flow parameters are used. The aim of this study was to assess the usefulness of FEV1 parameters in detecting airway responsiveness to histamine in recurrently wheezy infants. Ten infants (age 7-18 months) sedated with 80 mg/kg chloral hydrate underwent a histamine inhalation challenge. Throughout the challenge FEFV curves were generated from end-tidal inspiration. Raised FEFV curves, from a lung volume preset by 15 cmH2O inflation pressure, were gathered at baseline and after the final concentration of histamine. The mean fall from baseline was 47% in maximal flow at functional residual capacity (VmaxFRC) (P < 0.0005), 15.5% in FEV0.5 (P < 0.0001), 13.5% in FEV0.75 (P < 0.005), and 11.0% in FEV1.0 (P = 0.057), after the final concentration of histamine delivered. Tidal volume and inspiratory volume reached above FRC between pre- and posthistamine did not change. Mean oxygen saturation fell significantly from 97 to 93%. We conclude that FEV1 parameters adequately detect reduced lung function during histamine-induced bronchoconstriction and appear suitable for histamine challenge testing in infants.

Bronchoconstriction↗
PubMed1994

Frequency distribution of breath sounds as an indicator of bronchoconstriction during histamine challenge test in asthmatic children.

In order to study changes in respiratory sounds associated with acute bronchoconstriction and -dilatation, breath sounds of 11 children with asthma (age range, 10-14 years) were recorded at the chest and at the trachea during histamine challenge test and after subsequent bronchodilatation. The changes in frequency spectra of breath sounds were compared with simultaneous changes in forced expiratory volume in 1 second (FEV1). In seven children who responded to histamine with a decrease in FEV1 of more than 15%, there was a significant relationship between percentage change in FEV1 (delta FEV1) and percentage change in median frequency (delta F50) of expiratory breath sounds recorded at the chest (r = 0.865; beta = -0.706, P = 0.0001) and at the trachea (r = 0.888; beta = -1.12, P = 0.0001). The association between breath sound intensity and FEV1 was weaker. Based on ANOVA, the increase of F50 during the challenge test was significantly larger in children who responded to histamine than in those who were non-responsive (P = 0.0016). At the chest, a decrease of 15% in FEV1 corresponded to an increase of 8% in expiratory F50. The provocative dose of histamine inducing a decrease of 15% in FEV1 (PD15FEV1) and the provocative dose causing an increase of 8% in F50 (PD8F50) were significantly related (r = 0.927, P = 0.003). We conclude that spectral analysis of breath sounds can be used to indicate airway obstruction during bronchial challenge tests in children, and may be adapted for tests in pre-school children. The results suggest that the same mechanisms that induce airflow limitation due to inhaled histamine may generate an increase in frequency content of breath sounds in children with asthma.

Adolescent↗
PubMed2005

Prolonged effect of montelukast in asthmatic children with exercise-induced bronchoconstriction.

Accumulating evidence shows that cysteinyl leukotrienes are the most important mediators in exercise-induced bronchoconstriction (EIB). In contrast to several studies in adults, there are few long-term studies of leukotriene receptor antagonists (LTRAs) in children with EIB. The aim of this study was to assess the prolonged clinical and bronchoprotective effects of montelukast in asthmatic children with EIB. We randomly assigned 64 asthmatic children with EIB. Forty subjects received montelukast (5 mg/day), and 24 subjects received placebo once daily for 8 weeks. Exercise challenge was performed before and after 8 weeks of treatment. Of the 40 patients in the montelukast group, 28 patients crossed over after 8 weeks. The response was measured as asthma symptom score, maximum percent fall in forced expiratory volume in 1 sec (FEV(1)) from pre-exercise baseline, and time to recovery of FEV(1) to within 10% of pre-exercise baseline (time to recovery). Following 8 weeks of treatment with montelukast, the montelukast group compared with placebo showed significant improvements in all endpoints, including asthma symptom score, maximum percent fall in FEV(1) after exercise, and time to recovery. In the cross-over group, even 8 weeks after stopping montelukast treatment, all endpoints were significantly and persistently improved. These results indicate that montelukast provides clinical protection from airway hyperresponsiveness in asthmatic children with EIB, and suggest that LTRAs may be useful for the long-term management of asthmatic children with EIB.

Acetates↗