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At least 415 records · Page 23Linked to original sources

PubMed1999

Large porous particles for sustained protection from carbachol-induced bronchoconstriction in guinea pigs.

PURPOSE: To determine whether a new formulated albuterol aerosol could sustain inhibition to bronchoconstriction for approximately one day in guinea pigs challenged with carbachol. METHODS: Large and porous particles, comprising a combination of endogenous or FDA-approved excipients and albuterol sulfate, were prepared by spray drying using a NIRO portable spray drier. The anesthetized animals inhaled 5 mg of large porous or small nonporous particles by forced ventilation via cannulae inserted in the lumen of their exposed tracheae. At regular intervals over a period of 36 hours after drug delivery, airway resistance was determined in response to carbachol challenge dose. RESULTS: Whereas inhalation of small nonporous albuterol particles protected from the carbachol-induced bronchoconstriction for up to 5 hours, inhalation of large porous albuterol particles produced a significant inhibition of carbachol-induced bronchoconstriction for at least 16 hours. CONCLUSIONS: The absence of substantial side effects, verified over a period of 24 hours by evaluating cardio-respiratory parameters as well as pulmonary inflammation, supports the utility of large porous albuterol particles for sustained therapies in asthma and other types of lung disease.

Administration, Inhalation↗

PubMed1999

Increased airway responsiveness to acetaldehyde in asthmatic subjects with alcohol-induced bronchoconstriction.

Bronchial responsiveness to acetaldehyde, a main factor in alcohol-induced bronchoconstriction, and methacholine were compared between 10 subjects with alcohol-induced bronchoconstriction and 16 asthmatic subjects without alcohol sensitivity. In the alcohol-sensitive group, the geometric mean (geometric SEM (GSEM)) of the provocative concentration of methacholine (PC20,meth) and acetaldehyde (PC20,acet) causing a 20% fall in forced expiratory volume in one second were 0.947 mg x mL(-1) (GSEM 0.139) and 21.0 mg x mL(-1) (GSEM 0.112), respectively, which were not significantly different from those in the nonalcohol-sensitive group, which were 0.634 mg x mL(-1) (GSEM 0.115) and 31.7 mg x mL(-1) (GSEM 0.077), respectively. The ratio of airway responsiveness to acetaldehyde relative to methacholine (log PC20,acet/PC20,meth) was 1.345+/-0.093 (mean+/-SEM) in the alcohol-sensitive group, which was significantly different from the value of 1.699+/-0.059 in the nonalcohol-sensitive group (p=0.0025). A significant correlation was observed between PC20,meth and PC20,acet in both the alcohol-sensitive group (r=-0.742, p=0.0115) and nonsensitive group (r=0.882, p<0.0001). In conclusion, the airways of asthmatic subjects with alcohol-induced bronchoconstriction have a selective hyperresponsiveness to acetaldehyde.

Acetaldehyde↗

PubMed1997

Capsaicin and neurokinin A-induced bronchoconstriction in the anaesthetised guinea-pig: evidence for a direct action of menthol on isolated bronchial smooth muscle.

1. For many years menthol has been used in the treatment of respiratory disorders although, a bronchodilator effect of menthol has yet to be described. Using the bronchoconstrictors capsaicin (acting via stimulating the release of neuropeptides from sensory afferents) and neurokinin A (NKA) we have raised airways resistance in the guinea-pig (GP) and studied the effect of menthol on both capsaicin and NKA-induced bronchoconstriction in vivo. In vitro the effect of menthol on acetylcholine (ACh) and KCl precontracted GP bronchi was also studied. 2. GP (n = 13) were anaesthetized (urethane 1.5 g kg-1, i.p.) and a bolus injection of capsaicin (7.5 micrograms ml-1, i.v.) or infusion of NKA (1 microgram min-1, i.v.) was given either in the presence of air (0.81 min-1) or air impregnated with menthol vapour (7.5 micrograms l-1) freely breathed from a tracheal cannula via a T-piece. Airways resistance (Raw) and ventilation were measured throughout. Bronchi of mean internal diameter (1029 + 73.6 microns; n = 24) were removed from GP (n = 16) and mounted in the Cambustion myograph. Bronchial rings were maximally precontracted with 80 mM KCl or 2 mM ACh. Relaxation due to a cumulative dose of menthol (1- 3000 microM) was measured. 3. Menthol produced a significant (P < 0.05) 51.3% reversal of the capsaicin-induced increase in Raw, and also inhibited the significant (P < 0.05) reduction in minute ventilation (Ve) associated with the capsaicin-induced increased in Raw. Menthol also caused a significant (P < 0.05) 41% reversal of the NKA-induced increase in Raw. The NKA-induced decrease in Ve was again significantly (P < 0.05) reversed with menthol inhalation. Menthol caused a significant (P < 0.001) dose-dependent relaxation of KCl and ACh precontracted bronchi. 4. We have shown that menthol attenuates both capsaicin and NKA-induced bronchoconstriction in vivo and relaxes KCl and ACh preconstricted bronchi in vitro. Menthol inhibition of NKA and capsaicin-induced bronchoconstriction could be, in part, explained by a direct action of menthol on bronchial smooth muscle.

Airway Resistance↗

PubMed1998

A partial involvement of histamine in ultrasonically nebulized distilled water-induced bronchoconstriction in guinea-pigs.

1. Inhalation of ultrasonically nebulized distilled water (UNDW) can induce bronchoconstriction only in asthmatics, but mechanisms of the response are not well known. We recently reported a guinea-pig model of UNDW-induced bronchoconstriction (UNDW-IB) in which UNDW induces bronchoconstriction when UNDW is inhaled 20 min after a challenge with aerosolized ovalbumin (OA) in passively sensitized, anaesthetized and artificially ventilated guinea-pigs. 2. To elucidate the role of histamine in the UNDW-IB, we examined the effects of antihistamines, diphenhydramine hydrochloride (DH) and chlorpheniramine maleate (CP), and measured histamine content in bronchoalveolar lavage fluid (BALF) in the animal model. 3. DH in doses of 0.1, 1.0 and 10 mg kg(-1) and CP in doses of 0.01, 0.1 and 1.0 mg kg(-1) administered intravenously 15 min after the OA challenge partially reduced the UNDW-IB at 1 and 2 min after the UNDW inhalation in a dose-dependent manner. Histamine content in BALF recovered 10 min after the UNDW inhalation following the OA provocation was significantly increased compared with that after saline inhalation and before the UNDW inhalation following the OA challenge. 4. Intravenous atropine in a dose of 0.5 mg kg(-1) or inhaled disodium cromoglycate in concentrations of 1 and 10 mg ml(-1) did not alter the UNDW-IB. 5. These results suggest that histamine is involved in part in the UNDW-IB in our animal model.

Administration, Inhalation↗

PubMed2003

Perception of bronchoconstriction in obstructive pulmonary diseases (disease-specific dyspnoea).

The perception of dyspnoea differs between subjects with obstructive pulmonary diseases, partly because the underlying mechanisms for bronchoconstriction are different. We investigated the perception of bronchoconstriction in subjects with bronchiectasis, asthma and chronic bronchitis and possible contributing factors. Forty-seven non-smoking subjects with bronchiectasis, 50 subjects with asthma and 31 with chronic bronchitis were challenged with histamine. The Borg score was assessed before and after each challenge. The perception score corresponding to a fall in the forced expiratory volume in 1 s (FEV(1)) by 20% (PS(20)) was calculated. The mean values of DeltaBorg/DeltaFEV(1) (the Borg score change divided by the change in FEV(1) as a percentage of the baseline FEV(1)) and PS(20) of subjects with bronchiectasis and chronic bronchitis were significantly lower than in subjects with asthma after histamine challenge. The ratio of non-perceivers was higher in bronchiectasis (25.5%) and in chronic bronchitis (32.3%) than in asthma (4.0%). When all subjects were considered, DeltaBorg/DeltaFEV(1) values were significantly related to female sex ( r (2)=11.5%, P =0.0001), but not to age, duration of the disease, PD(20) or baseline FEV(1)%. The present study indicates that perception of histamine-induced bronchoconstriction is lower in patients with bronchiectasis and chronic bronchitis than in asthmatic patients, and that sex partially contributes to this difference.

Adult↗

PubMed1998

Role of tachykinins in distilled water-induced bronchoconstriction in guinea-pigs.

BACKGROUND: An inhalation of ultrasonically nebulized distilled water (UNDW) induces bronchoconstriction only in asthmatics, but the mechanism underlying the response is not fully understood. We recently showed that bronchoconstriction occurs immediately after UNDW is inhaled 20min after an aerosolized antigen challenge in passively sensitized guinea-pigs. OBJECTIVE: This study was conducted to examine the role of tachykinins in this response. METHODS: Passively sensitized animals were anaesthetized and artificially ventilated, and changes in pressure at the airway opening (Pao) were measured as an overall index of airway narrowing. A tachykinin NK1 and NK2 dual receptor antagonist, FK224, and a tachykinin NK1 selective antagonist, FK888, were intravenously administered 15 min after the antigen challenge. The effects of capsaicin desensitization and a neutral endopeptidase inhibitor, phosphoramidon, were also examined. RESULTS: FK224 and FK888 significantly (P < 0.05 and P < 0.05, respectively) reduced the time course curve of the increase in Pao caused by UNDW inhalation in a dose-dependent manner. The percentage increase in Pao from the preantigen challenge value at 1 min after the UNDW inhalation was 267.4+/-17.1, 358.0+/-33.7 and 412.4+/-27.6% with 10 mg/kg of FK224, 1.0 mg/kg of FK224 and vehicle, respectively, (P<0.01 between 10 mg/kg of FK224 and vehicle) and the value was 254.4+/-48.5% with 10 mg/kg of FK888, 327.1+/-57.6% with 1.0 mg/kg of FK888 and 418.5+/-39.0% with vehicle, respectively (P < 0.05 between 10 mg/kg of FK888 and vehicle). The capsaicin desensitization, but not phosphoramidon, significantly reduced the UNDW-induced increase in Pao. CONCLUSION: These results suggest that tachykinins, at least substance P, are involved in a part of the UNDW-induced bronchoconstriction in our guinea-pig model.

Animals↗

PubMed1993

Preventing bronchoconstriction in exercise-induced asthma with inhaled heparin.

BACKGROUND: We have previously reported that inhaled heparin prevents allergic bronchoconstriction in sheep and inhibits the anti-IgE-mediated release of histamine from mast cells in vitro. Since the release of such mediators has been implicated in exercise-induced asthma, we investigated whether inhaled heparin could also attenuate the bronchoconstrictor response in this disease. METHODS: On five days we studied 12 subjects with a history of exercise-induced asthma. On day 1 they underwent a standardized exercise challenge on a treadmill to document the presence of exercise-induced asthma. Minute ventilation was estimated with a calibrated respiratory inductive plethysmograph. The workload was increased until the heart rate reached 85 percent of the predicted maximal value, and was sustained for 10 minutes. The magnitude of bronchoconstriction was assessed by measuring specific airway conductance before and after the exercise. On day 2 the partial-thromboplastin time was measured in plasma obtained before and after the subjects inhaled a nebulized solution of heparin (1000 U per kilogram of body weight). On days 3 through 5 the subjects were pretreated with 4 ml of inhaled heparin (1000 U per kilogram), cromolyn sodium (20 mg), or placebo according to a single-blind, randomized, crossover design and underwent exercise challenge 45 minutes later. To exclude the possibility that heparin had any direct effect on airway smooth muscle, bronchial provocation with histamine was induced in five subjects on two further days after pretreatment with either heparin or placebo. RESULTS: Inhaled heparin and cromolyn sodium had no effect on specific airway conductance at base line, but did attenuate the exercise-induced decreases in this variable: the mean (+/- SE) maximal decrease five minutes after exercise was 9 +/- 5 percent after pretreatment with heparin, as compared with 22 +/- 5 percent after pretreatment with cromolyn and 35 +/- 2 percent after pretreatment with placebo. Heparin did not change the partial-thromboplastin time and did not modify the bronchoconstrictor response to histamine. CONCLUSIONS: Inhaled heparin prevents exercise-induced asthma without influencing histamine-induced bronchoconstriction. This non-anticoagulant action of heparin is more likely to be related to a modulation of mediator release than to a direct effect on smooth muscle.

Administration, Inhalation↗

PubMed2005

Roflumilast inhibition of pulmonary leukotriene production and bronchoconstriction in ovalbumin-sensitized and -challenged Guinea pigs.

This study investigated the effects of roflumilast, a PDE4 inhibitor, on slow-reacting substance of anaphylaxis (SRS-A)-mediated bronchoconstriction and pulmonary leukotriene (LT) release in ovalbumin (OVA)-sensitized and -challenged guinea pigs. Animals were treated with roflumilast orally (0.04, 0.12, 0.4, or 4 mg/kg) or placebo 1 hour before OVA challenge. Bronchoconstriction was quantified by measuring airway conductance (Gaw) and dynamic lung compliance (Cdyn). Roflumilast significantly attenuated the decrease in Gaw (50% inhibitory dose [ID50] = 0.33 mg/kg) and Cdyn (ID50 = 0.25 mg/kg) in a dose-dependent manner and significantly inhibited Cys-LT (ID50 = 0.06 mg/kg) and LTB4 (ID50 = 0.05 mg/kg) release versus placebo-treated animals. Roflumilast did not affect LTD4-induced bronchoconstriction. These findings support the role of roflumilast as an anti-inflammatory treatment for asthma.

Allergens↗

PubMed2001

Perception of bronchoconstriction in elderly asthmatics.

The impaired perception of bronchoconstriction in asthmatic patients may increase the risk of severe exacerbation. To characterize the perception of bronchoconstriction in elderly asthma patients, we compared the perception in older patients with that of younger patients. To determine the influence of perception of long-standing diseases, we further evaluated the perception in early-onset elderly asthma patients and in late-onset elderly asthma patients. The study group consisted of 80 stable asthmatic patients. The patients were grouped according to their age (group 1, < 60 years, n = 37, group 2, > or = 60 years, n = 43). Each group was separated into two subgroups according to the duration of symptoms (late-onset asthma 1A and 2A, < 5 years, early-onset asthma 1B and 2B, > or = 5 years). A histamine inhalation test was performed for each patient. Dyspnea was assessed by modified Borg scale. The Borg score in forced expiratory volume in 1 sec (FEV1) reduction by 20% was determined as perception score 20 (PS20). The mean perception scores of the elderly asthmatic patients were significantly lower than those of the younger asthmatic patients (group 1, PS20 = 2.35 +/- 0.17; group 2, PS20 = 1.37 +/- 0.12, p < 0.0001). The differences of mean perception score (PS20) between early- and late-onset subgroups were insignificant (IA, 2.63 +/- 0.30 and IB, 2.07 +/- 0.16, p = 0.101; 2A, 1.36 +/- 0.19 and 2B, 1.59 +/- 0.120, p = 0.91). The mean perception scores of male asthmatic patients were significantly lower than those of female patients (p = 0.03). There was a correlation between PS20 and % FEV1 in the younger group (r = 0.392, p = 0.02), but not in the elderly group (r = 139, p = 0.375). The correlation between PS20 and PD20 in both younger and elderly group was insignificant (p > 0.05). Elderly asthmatics perceive less intense respiratory distress for a decrease of 20% in FEV1 than do younger asthmatics. This underperception of bronchoconstriction may result in a delay in medical care during an acute asthmatic episode. Thus, we strongly recommend that elderly asthmatic patients should be followed up more frequently and closely.

Adult↗

PubMed1999

I.v. lidocaine worsens histamine-induced bronchoconstriction in dogs.

We have assessed the effect of lidocaine (lignocaine) on histamine-induced bronchoconstriction by direct visualization with a superfine fibreoptic bronchoscope. Seven mongrel dogs were anaesthetized with pentobarbital (pentobarbitone) 30 mg kg-1 followed by 2 mg kg-1 h-1 and pancuronium 200 micrograms kg-1 h-1. The trachea was intubated with a tracheal tube containing a second lumen for insertion of a 2.2-mm fibreoptic bronchoscope. This allowed estimation of the bronchial cross-sectional area (BCA) of the third bronchial bifurcation of the right lung. We used NIH image, a public domain image processing and analysis program. Bronchoconstriction was produced with a bolus dose of histamine 10 micrograms kg-1 i.v. followed by continuous infusion of 500 micrograms kg-1 h-1. After 30 min the following i.v. doses of lidocaine were given: lidocaine 0 (saline), 0.01, 0.1, 1.0 and 10 mg kg-1 at 10-min intervals. BCA was assessed 90 s after each dose. Arterial blood sampling was performed for measurement of plasma catecholamines. Lidocaine 1.0 and 10 mg kg-1 significantly reduced histamine-decreased BCA from 69.7 (SEM 4.1)% to 59.8 (7.3)% and 34.3 (6.8)%, respectively. Plasma concentrations of catecholamines decreased significantly after lidocaine 10 mg kg-1 i.v. In addition, there was a significant correlation between percentage decreases in plasma concentrations of epinephrine (adrenaline) and norepinephrine (noradrenaline) and reduction in %BCA (epinephrine-BCA, P < 0.01, r = 0.674; norepinephrine-BCA, P < 0.01, r = 0.510). This study suggests that i.v. lidocaine may exacerbate histamine-induced bronchoconstriction by a sympatholytic effect. This may have therapeutic implications for patients with acute asthma or anaphylactic shock who may become dependent on circulating catecholamines.

Anesthetics, Intravenous↗

PubMed2000

Spasmolytic effects of prostaglandin E1 on serotonin-induced bronchoconstriction and pulmonary hypertension in dogs.

In this study, we simultaneously evaluated the spasmolytic effects of prostaglandin E1 (PGE1) on serotonin-induced bronchoconstriction and pulmonary hypertension. Eleven mongrel dogs (8-12 kg) anaesthetized with pentobarbital were assigned to two groups: saline (n = 4) and PGE1 (n = 7). Bronchoconstriction and pulmonary hypertension were elicited with serotonin 10 micrograms kg-1 + 1 mg kg-1 h-1 and assessed as the percentage change in bronchial cross-sectional area (BCA) measured by bronchoscopy and pulmonary vascular resistance (PVR), respectively. Thirty minutes after starting the serotonin infusion, saline or PGE1 0 (saline), 0.01, 0.1, 1.0 or 10 micrograms kg-1 i.v. was given. %BCA and %PVR (basal = 100%) were assessed before and 30 min after serotonin, and 30 and 60 min after saline (saline group) or 5 min after each dose of PGE1 (PGE1 group). In the saline group, pulmonary hypertension and bronchoconstriction were stable. In the PGE1 group, PGE1 at > or = 0.1 microgram kg-1 significantly decreased %BCA and 10 micrograms kg-1 almost fully reversed the constriction (from mean (SEM) 56.2% (4.9%) to 94.4% (3.7%)). %PVR was significantly decreased at 10 micrograms kg-1 (from 230% (24%) to 176% (11%)) only. We suggest that PGE1 may produce bronchodilation rather than pulmonary vasodilation.

Alprostadil↗

PubMed2006

Physiologic implications of helium as a carrier gas for inhaled nitric oxide in a neonatal model of Bethanecol-induced bronchoconstriction.

OBJECTIVE: To compare heliox to nitrogen-oxygen (nitrox) as a carrier gas for inducible nitric oxide (iNO) in the presence of pharmacologically inhaled bronchoconstriction. We hypothesized that respiratory resistance and gas exchange would improve when iNO is delivered with heliox. DESIGN: Interventional laboratory study. SETTING: An academic medical research facility in the northeastern United States. SUBJECTS: Sedated, ventilated newborn piglets. INTERVENTIONS: Newborn piglets (n = 16; 2.3 +/- 0.1 kg) were placed on a flow-controlled ventilator and given intravenous Bethanecol (2 x 1 mg/kg followed by 1 mg/kg/hr) to induce bronchoconstriction. Piglets were randomized to heliox or nitrox (Fio2 = 0.3) and given 80 ppm iNO. MEASUREMENTS AND MAIN RESULTS: Hemodynamics, blood chemistry, and pulmonary mechanics were recorded at 30-min intervals for 2 hrs. Bethanecol dosing increased inspiratory respiratory resistance (cm H2O/L/min; p < .01) and decreased respiratory compliance (mL/cm H2O/kg; p < .01). Following carrier gas assignment, hemodynamics and respiratory compliance were similar between groups and respiratory resistance decreased (p < .01) in the heliox group. Over 2 hrs with iNO therapy, Paco2 increased (p < .01) whereas blood pH decreased (p < .01) in the heliox group. Respiratory resistance trended downward, oxygenation index improved (p < .01), and blood methemoglobin levels trended higher for nitrox compared with heliox. CONCLUSIONS: The INOvent was effective for controlling heliox delivery of iNO. Despite marked reduction in respiratory resistance with heliox gas ventilation in a neonatal model of pharmacologic bronchoconstriction, nitrox might perform better as a delivery vehicle for iNO.

Animals↗

PubMed2004

Clinical and functional responses to salbutamol inhaled via different devices in asthmatic patients with induced bronchoconstriction.

AIMS: This study aimed at evaluating changes in airway patency, lung volumes and perception of breathing discomfort intensity following salbutamol administration via the Diskus dry-powder inhaler (DPI) or a pressurized metered-dose inhaler with the Volumatic valved holding chamber (pMDI + Volumatic) in asthmatic patients with methacholine-induced bronchoconstriction. METHODS: On six different study days, 18 patients inhaled methacholine until forced expiratory volume in 1 s (FEV(1)) decreased by approximately 35% of baseline. Following placebo, 200 and 400 microg of salbutamol through the pMDI + Volumatic or the Diskus, changes in FEV(1), volume-adjusted mean forced expiratory flow from 25 to 75% of the forced vital capacity (isoFEF(25-75)), lung volumes and breathing discomfort intensity, assessed by visual analogue scale (VAS) score, were repeatedly measured over a 60-min observation period. RESULTS: Induced bronchoconstriction was accompanied by obvious reductions in lung volumes and increases in VAS score. After salbutamol administration, FEV(1) and VAS score changes were similar in all experimental conditions. However, following 400 microg salbutamol via pMDI + Volumatic, isoFEF(25-75) values increased up to 4.48 l s(-1) (95% confidence interval 4.06, 4.90), a significantly (P < 0.01) higher value than those attained in all other experimental conditions. Independently of the salbutamol dose, lung volumes rose to significantly (P < 0.01) higher levels in pMDI + Volumatic than in Diskus trials. The low salbutamol dose via the pMDI + Volumatic and the high dose via the DPI increased isoFEF(25-75) and lung volumes to similar extents. CONCLUSIONS: Salbutamol via the pMDI + Volumatic provides greater isoFEF(25-75) and lung volume increases in asthmatic patients with induced bronchoconstriction; salbutamol-induced changes in VAS scores poorly reflect those in small airway patency. The lack of differences in FEV(1) increases observed after 200 and 400 microg salbutamol may reflect attainment of the flat portion of the dose-response curve using either device.

Administration, Inhalation↗

PubMed1993

Effect of cetirizine, a potent H1 antagonist, on platelet activating factor induced bronchoconstriction in asthma.

Effect of cetirizine, a potent and specific H1 receptor antagonist, was examined on platelet activating factor-induced bronchoconstriction in 10 patients (5 male, mean [s.e.m.] aged 37.4 [3.6] years) with mild asthma in a placebo controlled, double-blind cross-over study. Airway responses were assessed by measuring specific airway conductance (SGaw). Patients were challenged with a single dose (12-96 micrograms) of PAF that had previously produced a 35% fall in SGaw. PAF challenges were performed after single dose (15 mg) and 1 week's treatment (15 mg twice daily) of cetirizine. There was no significant difference in pre- and post-treatment baseline values of SGaw on different study days and the percentage changes after cetirizine were 38.7 (7.01) and 45.6 (5.52) compared to 50.2 (2.89) and 43.9 (7.26) with placebo respectively. Similarly mean (s.e.m.) area under curve (AUC-SGaw/time course response) was 391 (143) and 514 (85) with cetirizine compared to 565 (37) and 461 (94) with placebo respectively. The difference was not statistically significant. There was no difference in facial flushing and feeling of warmth between cetirizine and placebo. We conclude that PAF induced bronchoconstriction in humans is not mediated by histamine release and that H1 receptor antagonists do not modify PAF induced bronchoconstriction.

Adult↗

PubMed1994

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

The endogenous tachykinins exhibit a range of properties which may be 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 bronchoconstriction in man in vivo, six atopic asthmatic patients, with a mean FEV1 value of 3.38 +/- 0.76 l, 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 phosphoramidon 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 l) in comparison with the control solution (3.31 +/- 0.79 l). Inhaled NKA produced a dose-dependent fall in FEV1 values in all the subjects studied with a mean PD15 value of 20.91 x 10(-9) mol. Phosphoramidon administered by inhalation elicited a significant (P < 0.01 vs baseline and control solution) potentiation in the airway responsiveness to inhaled NKA, the NKA PD15 value decreasing to 9.45 x 10(-9) mol. The present study confirms that inhaled NKA induces a dose-related bronchoconstriction in asthmatic patients and demonstrates that inhaled phosphoramidon potentiates NKA-induced bronchoconstriction.

Adolescent↗

PubMed1991

Effect of cetirizine on histamine-induced bronchoconstriction and bronchoalveolar cells.

The effect of the histamine H1 receptor antagonist (cetirizine) on histamine-induced bronchoconstriction and inflammatory cells in bronchoalveolar lavage fluid was studied in 12 healthy volunteers. In previous studies we have observed an increased number of inflammatory cells, albumin and hyaluronan in the bronchoalveolar lavage (BAL) fluid 24 h after an inhalation challenge test with histamine-chloride. In the present study certirizine blocked the histamine-induced bronchoconstriction but did not influence the cell counts in the bronchoalveolar lavage fluid. Our result suggests that the histamine-induced bronchoconstriction but not the recruitment of inflammatory cells in the BAL fluid is mediated by histamine H1 receptors.

Adult↗

PubMed1992

Histamine-induced bronchoconstriction in conscious guinea pigs measured by strain-gauge transduction. A new method.

A new objective method for measuring histaminedihydrochloride-induced bronchoconstriction in conscious guinea pigs has been developed. The aim of the present work was to investigate whether identical results could be obtained when the clinical observation of conscious guinea pigs with symptoms of respiratory distress (bronchoconstriction) was compared to an objective measuring technique of this parameter. An evaluation of the repeatability of the method was made and the respiration frequence (fR) and histaminedihydrochloride challenge concentration were compared to see whether there was a correlation between the two. Consequently, an apparatus was built that allowed simultaneous recording of breathing pattern and clinical observation of the animal being challenged. The breathing pattern was recorded by a strain-gauge transducer, connected to a measuring bridge, and the curves obtained on a jet ink x-y writer were used for calculating changes in duration of expiratory phase (Te) and fR. During the attacks of histaminedihydrochloride-induced bronchoconstriction a significantly prolonged Te could be calculated from the respiration curves. A high degree of agreement was found between this objective measure and clinically observed respiratory distress. The repeatability of the method was comparable to that of corresponding methods used for histaminedihydrochloride challenge in man. No obvious correlation was found between changes in fR and histaminedihydrochloride challenge concentration.

Animals↗

PubMed1996

Inhaled lysine acetylsalicylate (L-ASA) attenuates histamine-induced bronchoconstriction in asthma.

When administered by inhalation, histamine provokes dose-related bronchoconstriction in asthmatic subjects mainly by a direct activation of histamine H1-receptors on airway smooth muscle. However, little is known of the change in airway responsiveness to histamine after cyclooxygenase blockade. The aim of the study was to investigate the effect of the potent cyclooxygenase inhibitor, lysine acetylsalicylate (L-ASA), administered by inhalation on histamine-induced bronchoconstriction in a group of 16 asthmatic subjects. The subjects studied attended the laboratory on four separate occasions to receive nebulized L-ASA (solution of 90 mg/ml) or matched placebo (glycine solution of 30 mg/ml) 15 min before bronchoprovocation tests with histamine and methacholine in a randomized, double-blind order. Changes in airway caliber were followed as forced expiratory volume in 1 s (FEV1), and agonist responsiveness was expressed as the provocative concentration causing a 20% fall in FEV1 from baseline (PC20). Administration of both L-ASA and glycine solution caused a small but significant acute fall in FEV1 from baseline, which returned to normal within 15 min. When compared to placebo, inhaled L-ASA reduced the airway responsiveness to histamine in 13 of the 16 subjects studied, the geometric mean (range) values fro PC20 histamine increasing significantly (P < 0.001) from 1.72 (0.13-5.49) mg/ml to 3.31 (0.36-12.00) mg/ml after placebo and L-ASA, respectively. No significant change in airway responsiveness to methacholine was recorded after L-ASA. Acute administration of L-ASA by inhalation protects the asthmatic airways against histamine-induced bronchoconstriction, thus suggesting that endogenous prostaglandins may play a contributory role in the airways response to histamine in human asthma.

Administration, Inhalation↗