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PubMed1996

Lack of a role for bradykinin in allergen-induced airway microvascular leakage and bronchoconstriction in the guinea pig.

We have investigated the role of bradykinin in allergen-induced airway microvascular leakage and bronchoconstriction in sensitized guinea pigs. We used a selective bradykinin B2 receptor antagonist, HOE140, which has been shown to prevent the airway effects induced by bradykinin. Lung resistance (RL) was measured for 6 min after challenge with allergen. Extravasation of Evans blue dye into airway tissues was used as an index of the airway microvascular leakage. Aerosolized ovalbumin (5 mg/ml, 30 breaths) induced a significant increase in RL and leakage of dye in the trachea, main bronchi and intrapulmonary airways in the ovalbumin-sensitized guinea pigs. HOE140 given by inhalation (200 microM, 60 breaths) had no effect on the airway microvascular leakage and bronchoconstriction induced by the allergen. I.v. HOE140 (200 nmol/kg) did not significantly inhibit these airway responses. We conclude that bradykinin-mediated mechanism may not play a significant role in airway microvascular leakage or bronchoconstriction induced by allergen.

Administration, Inhalation↗

PubMed2000

Preventive effect of 2 and 10 mg of sodium cromoglycate on exercise-induced bronchoconstriction.

UNLABELLED: This double-blind, randomised and cross-over study was designed to compare the preventive effect against exercise-induced bronchoconstriction (EIB), defined as the percentage decrease in FEV1 > or = 15% after 6 min of exercise, of 2 mg and 10 mg of sodium cromoglycate (SCG), administered through a metered dose inhaler via spacer, in asthmatic children. Each of the 30 subject (age 11.6 +/- 3.2 years) was tested on five occasions. For inclusion, EIB in test1 was required. In tests 2 to 5, all subjects inhaled 2 mg or 10 mg of SCG 20 min and 120 min before exercise in a randomised order. In order to assess excretion of eosinophil protein X (EPX) accompanying EIB, urine samples were collected before and after exercise. The mean percentage fall in FEV1 (+/- SD) in test 1 was 26.8 +/- 9.8%. Inhalation of 2 mg and 10 mg of SCG 20 min before exercise provided a significant preventive effect in 83% and 77% and inhalation 120 min before exercise provided a preventive effect in 63% and 70%, respectively (n = 30). Variance analysis did not reveal a statistically different absolute fall in FEV1 after exercise when both doses (120 min before exercise) were compared (P = 0.356). In an unselected subgroup of 12 children, urinary EPX increased after the challenge without SCG premedication (test 1) (mean change: +48.7 micrograms/mmol creatinine, P = 0.034), whereas no significant increase was found in case of SCG premedication (mean change in microgram/mmol creatinine): 2 mg/20 min: +12.1; 2 mg/120 min: +8.5; 10 mg/20 min: -10.4 and 10 mg/120 min: -23.5; P > 0.1). CONCLUSION: Administration of 10 mg of sodium cromoglycate is no more effective in preventing exercise-induced bronchoconstriction than 2 mg regardless of whether the medication is given 20 or 120 min before exercise. The preventive effect of sodium cromoglycate on exercise-induced bronchoconstriction in asthmatic children is associated with the inhibition of urinary eosinophil protein X excretion.

Administration, Inhalation↗

PubMed2001

Effect of inhaled heparin on water-induced bronchoconstriction in allergic asthmatics.

OBJECTIVE: The aim of this study was to investigate the effect of inhaled heparin on bronchoconstriction induced by ultrasonically nebulised distilled water (UNDW) in allergic asthmatics. METHODS: Eight atopic asthmatics, hyperresponsive to UNDW, were selected for this randomised, placebo-controlled, crossover double-blind study. On two consecutive days, these subjects underwent a UNDW challenge 45 min after inhaling aerosolised heparin (1000 U/kg) or placebo. RESULTS: Neither heparin nor placebo had a significant effect on base-line forced expiratory volume in 1 s (FEV1), but heparin significantly attenuated UNDW-induced bronchoconstriction, as shown by its efficacy in preventing the decreases in FEV1 produced by all doses of water (in comparison with placebo: P < 0.05 after 2 ml water; P < 0.01 after 4, 8 and 16 ml water). CONCLUSION: Inhaled heparin is able to exert a protective effect against the bronchoconstrictive response to UNDW in allergic asthmatics, and this action is likely due to inhibition of mast cell degranulation.

Administration, Inhalation↗

PubMed1992

Effect of Hoe 140, a new bradykinin receptor antagonist, on bradykinin- and platelet-activating factor-induced bronchoconstriction and airway microvascular leakage in guinea pig.

We have investigated the effect of a new bradykinin receptor antagonist, Hoe 140 (D-Arg- Hyp3,Thi5,D-Tic7,Oic8]-bradykinin), on bradykinin- and platelet-activating factor (PAF)-induced bronchoconstriction and airway microvascular leakage in anesthetized guinea pigs. Extravasation of Evans blue dye and lung resistance were measured simultaneously. Both i.v. (15 nmol/kg) and inhaled bradykinin (1 mM, 45 breaths) caused a significant increase in lung resistance and leakage of dye at all airway levels. Hoe 140 (100 nmol/kg i.v.) almost completely inhibited these airway responses induced by bradykinin except for dye extravasation in trachea induced by inhaled bradykinin. Inhaled PAF (3 mM, 30 breaths) significantly increased lung resistance and leakage of due at all airway levels, but Hoe 140 had no effect on these responses. Bradykinin-induced bronchoconstriction and airway microvascular leakage are predominantly mediated by activation of B2 receptor, since Hoe 140 is a B2 receptor antagonist. Bradykinin receptor-mediated mechanisms do not play an important role on inhaled PAF-induced bronchoconstriction and microvascular leakage.

Administration, Inhalation↗

PubMed1993

Role of vagus nerves in resiniferatoxin-induced bronchoconstriction of guinea pigs.

To study the role of vagal afferent C-fibers in resiniferatoxin (RTX)-induced bronchoconstriction in vivo, 30 guinea pigs weighing 347 +/- 28 g were evenly and randomly divided into five groups: Group 1, control; 2, chronic vagotomy; 3, local capsaicin (acute); 4, local capsaicin (chronic); and 5, systemic capsaicin. Each animal was anesthetized with pentobarbital sodium, cannulated with a tracheal cannula and venous catheter, paralyzed with gallamine triethiodide, and artificially ventilated. All animals were pretreated with atropine and phenoxybenzamine. Immediately after RTX was intravenously injected, each animal in the control group exhibited profound decreases in maximal expiratory flow, dynamic respiratory compliance, and total lung capacity, as well as an increase in functional residual capacity, indicating severe airway constriction. Animals in Groups 2-4 exhibited partial abolishment, while those in Group 5 showed complete abolishment of the RTX-induced bronchoconstriction. In 12 additional animals (6 animals each in control and chronic vagotomy groups), chronic vagotomy caused also suppressive effects on capsaicin-induced airway constriction. At one min, our data demonstrate that 36-51% of noncholinergic bronchoconstriction is due to the vagal component while the remaining constriction is due to the nonvagal component. Thus, the nonvagal component plays a significant role in this type of tachykinin-mediated airway constriction.

Afferent Pathways↗

PubMed1995

On the use of the alveolar capsule technique to study bronchoconstriction.

Using the alveolar capsule technique, we studied the time courses of respiratory mechanical parameters at various sites on the lung surface during bronchoconstriction. Six mongrel dogs were anesthetized, tracheostomized, paralyzed and artificially ventilated (12-25 ml/kg, 19-22 breaths/min). Sternotomy was performed and alveolar capsules were glued to various parts of the lungs. Tracheal pressure and flow and alveolar pressure were measured continuously for 25 min after i.v. bolus injections of histamine (0, 0.05, 0.5, 5.0, 50.0 mg). The challenges were spaced 1 h apart. Estimates of lung tissue resistance and elastance were obtained with our recursive least-squares estimator (Lauzon and Bates, J. Appl. Physiol., 1159-1165, 1991). We found that the time courses of the parameters of most capsules were initially uniform but quickly diverged as bronchoconstriction developed. Also, we found that the differences in time course of mechanics between alveolar regions either developed randomly with step-like features presumably reflecting intermittent opening and closing of the airways leading to the various alveolar capsules, or in a progressive dose-dependent manner, possibly reflecting a gradual but structurally pre-set pattern of bronchoconstriction, or with a combination of these two patterns. We explain our results in terms of inhomogeneous mechanical properties of the lungs and examine some artifacts introduced by the alveolar pressure measurement technique.

Animals↗

PubMed1991

Determination of plasma leukotrienes in antigen-induced bronchoconstrictive guinea pigs.

Convenient extraction and radioimmunoassay methods for measurement of leukotrienes C4 and D4 (LTC4 and LTD4) in biological fluids are described. LTC4 or LTD4 in plasma was extracted with acetonitrile, and the extract was washed with dichloromethane then adjusted to pH 3.5 or 6.0, respectively. Each leukotriene was partially purified by using a C18-bonded silica cartridge and quantitated by radioimmunoassay. Amounts of LTC4 and LTD4 in the range of 0.025-1.6 ng could be assayed in plasma. This procedure was employed to examine the increase in plasma LTC4 (0.249 +/- 0.036 ng/ml) and LTD4 (1.399 +/- 0.235 ng/ml) of guinea pigs during intravenous challenge-induced anaphylactic bronchoconstriction, and the suppression of the increase of bronchoconstriction and leukotrienes by the administration of 5-lipoxygenase inhibitors such as E6080 (6-hydroxy-2-(4-sulfamoylbenzyl-amino)- 4,5,7-trimethylbenzothiazole hydrochloride), AA861 (2,3,5-trimethyl-6-(12-hydroxy-5,10-dodecadiynyl)-1,4-benzoquinone ) and phenidone. On the other hand, LTC4 and LTD4 were not detected in plasma after an inhaled challenge, though significant bronchoconstriction was provoked. It was concluded that the present study validates a new technique for quantitating plasma leukotrienes on the basis of pH and a suitable method for evaluating the pharmacological efficacy of 5-lipoxygenase inhibitors.

Administration, Inhalation↗

PubMed1991

The effect of inhalation of the leukotriene receptor antagonist, SK&F 104353, on leukotriene C4- and leukotriene E4-induced bronchoconstriction in subjects with asthma.

The effect of prior inhalation of the sulfidopeptide leukotriene receptor antagonist, SK&F 104353 (963 +/- 43.7 micrograms; mean +/- SEM), on (LTC4)- and leukotriene E4 (LTE4)-induced bronchoconstriction has been studied in six subjects with asthma (six male subjects, aged 24 to 36 years). Inhalation challenges with either synthetic LTC4 or LTE4 were performed after prior inhalation of aerosolized SK&F 104353 or placebo in a double-blind, randomized fashion. Airway responsiveness to each agonist was determined by the cumulative dose of agonist required to induce a 35% fall in specific airway conductance (PD35) as determined by linear interpolation of the log dose-response curve. There was no change in baseline specific airway conductance after inhalation of either placebo or SK&F 104353. LTC4- and LTE4-induced bronchoconstrictions were significantly inhibited by aerosolized inhalation of SK&F 104353 30 minutes before challenge. The geometric mean (GM) PD35 of LTC4 on the open-therapy and placebo-therapy days was 0.043 nmol (range, 0.01 to 0.1 nmol) and 0.036 nmol (range, 0.01 to 0.1 nmol), respectively. On the treatment day with SK&F 104353, it was not possible to obtain a GM PD35 LTC4 up to a maximum concentration of 0.52 nmol LTC4 (p less than 0.01). The GM PD35 of LTE4 on the open-therapy and placebo-therapy days was 0.30 nmol (range, 0.13 to 0.76 nmol) and 0.39 nmol (range, 0.14 to 0.9 nmol), respectively. On the treatment day with SK&F 104353, it was not possible to obtain a GM PD35 LTE4 up to a maximum concentration of 5 nmol LTE4 (p less than 0.005). Thus, LTC4- and LTE4-induced bronchoconstrictions are both inhibited by SK&F 104353.

Administration, Inhalation↗

PubMed1993

The contribution of neurogenic reflexes to hypertonic saline-induced bronchoconstriction in asthma.

BACKGROUND: Hypertonic saline induces bronchoconstriction in most patients with asthma; however, the mechanisms involved are not clearly understood. We have investigated the role of neurogenic mechanisms in hypertonic saline-induced bronchoconstriction. METHODS: The effect of pretreatment with the anticholinergic drugs atropine and ipratropium bromide and the local anesthetic drug lidocaine on hypertonic saline responsiveness was studied in 11 subjects with asthma. Ultrasonically nebulized hypertonic saline challenge was given in a dose-response manner to determine the provocative dose of hypertonic saline-laden air required to produce a fall in forced expiratory volume in 1 second (FEV1) of 20% or greater (PD20HS). A control PD20HS with no pretreatment was measured before randomization, and on the next three visits PD20HS was determined after pretreatment with each of the following: intramuscularly administered atropine, inhaled ipratropium bromide, and inhaled lidocaine. RESULTS: The baseline mean FEV1 values increased by 3.5% and 4% 30 minutes after administration of atropine and ipratropium bromide, respectively, and decreased by 5.8% at 10 minutes after inhalation of lidocaine. These changes in the baseline FEV1 were not significant and did not have any effect on the PD20HS response. Premedication with atropine, ipratropium bromide, and lidocaine resulted in increases of 2.5, 2.0, and 2.6 times in mean PD20HS, respectively. CONCLUSIONS: The protection afforded by the drugs was variable in the individual subjects and not related to age, sex, baseline FEV1, provocative concentration of histamine causing a 20% fall in FEV1 or use of the inhaled corticosteroids. The protection afforded by anticholinergic and local anesthetic drugs suggests the contribution of neurogenic reflexes in the pathogenesis of hypertonic saline-induced bronchoconstriction in asthma.

Adult↗

PubMed1993

Adenosine-induced bronchoconstriction and its inhibition by nedocromil sodium.

The inhalation of adenosine or adenosine-5'-monophosphate (AMP) causes a reproducible and transient bronchoconstriction in both atopic and nonatopic asthmatic subjects that is not followed by a late-phase response. The response may be prevented by prophylactic treatment with histamine H1-receptor antagonist, local anesthetics, and atropine, which suggests that both mast cell mediator release and neuronal reflexes are involved. Adenosine- and AMP-induced bronchoconstriction are both blocked by cromolyn sodium and nedocromil sodium, with the PD20FEV1 for the latter approximately four times lower than that of cromolyn sodium in atopic asthmatic patients and approximately 2.3 times lower than that of cromolyn sodium in nonatopic asthmatic patients. We suggest that AMP-induced bronchoconstriction, in combination with other indirect-acting provicants, may be used to determine the effectiveness and mechanism of action of antiasthmatic drugs.

Adenosine↗

PubMedDate not supplied

Effect of the selective 5-HT2 antagonist ketanserin on adenosine-induced bronchoconstriction in asthmatic subjects.

In eight asthmatic subjects a randomized, double-blind, placebo controlled study was performed to investigate the effect of inhaled ketanserin, a 5-HT2 receptor blocking agent, in a dose of 10 mg given 30 min before test, on adenosine-induced bronchospasm. The protective effect of ketanserin was significant in all patients, even though it altered basal bronchomotor tone in only two subjects. On the contrary, ketanserin did not inhibit histamine-induced bronchoconstriction in four of these eight asthmatics, even though it modified sensitivity and reactivity in one of them. The results suggest that ketanserin influence on adenosine bronchial reactivity and sensitivity was not due to the bronchodilator effect of ketanserin itself or to its antihistaminic activity. We have no certain explanation for the inhibition of adenosine-induced bronchoconstriction elicited by ketanserin. It is possible that 5-HT may play, at least in part, a role as mediator of adenosine-induced bronchoconstriction.

Adenosine↗

PubMed1993

Role of leukotrienes and platelet activating factor in allergic bronchoconstriction and their interactions in guinea pig airway in vivo.

Membrane-derived lipid mediators have been considered to play a major role in pathogenesis of bronchial asthma. Recently specific antagonists and synthetase inhibitors of some chemical mediators have been developed and many studies on their anti-asthmatic effects are ongoing. But the importance of and the interactions of each mediator are still unclear. We examined the role of leukotrienes (LTs) and platelet activating factor (PAF) in immediate asthmatic response (IAR) and interactions between these lipid mediators in guinea pig airways in vivo using a specific LTs antagonist AS-35 and a specific PAF antagonist Y-24180. We confirmed the activity of each antagonist, as AS-35 and Y-24180 inhibited bronchoconstriction induced by respective agonist inhalation. AS-35 inhibition IAR but Y-24180 did not, indicating that LTs play a major role in IAR but PAF does not. AS-35 did not influence PAF-induced bronchoconstriction and Y-24180 did not inhibit LTs-induced bronchoconstriction, showing that there is no interaction between LTs and PAF.

Animals↗

PubMed1994

A method for measuring the effects of anticholinergics on histamine-induced bronchoconstriction in normal subjects. Oxitropium bromide provides dose-dependent protection.

To study whether it would be possible to assess anticholinergic drugs in normal subjects with histamine-(HIST) induced bronchoconstriction, three doses of oxitropium bromide (100, 200 and 400 micrograms) was inhaled in random order by twelve normal volunteers in a single-blind, placebo-controlled study. Dose response slope [DRS = maximal percentual fall in pulmonary function/maximal noncumulative histamine dose (mumol)] was used as an index of bronchial reactivity, and was calculated for FEV1 (DRSFEV1) and area under the flow-volume curve (DRSAEFV). The bronchial reactivity and its reproducibility was first tested with a standard provocation method. An abbreviated, single-dose, method was used in the measurement of the effects of oxitropium. The reproducibility of HIST-provocations were good with intraclass correlations of 0.97 and 0.99 for logDRSFEV1 and logDRSAEFV, respectively. However, DRSAEFV seemed to be better in this respect as DRSFEV1. Also, the single-dose method gave results that were comparable to the standard one. The largest dose of oxitropium diminished the median DRS from 2.6 to 0.01 and from 5.2 to -0.2 for FEV1 and AEFV, respectively. All oxitropium doses differed significantly from placebo (P < 0.01) and from each other (P < 0.05) with DRSAEFV-values, but when DRSFEV1 was used, a significant difference was detected only between placebo and active treatment (P < 0.01). In conclusion, since the vagal mechanisms seem to be the predominant system mediating HIST-induced bronchoconstriction in normal subjects, it is possible with DRSAEFV to evaluate the efficacy of anticholinergics against HIST-induced bronchoconstriction in these subjects.

Adult↗

PubMed1995

Asthmatic symptoms, airway responsiveness and recognition of bronchoconstriction.

During an epidemiological investigation of asthma in an occupational setting, 1126 subjects completed a modified Medical Research Council respiratory questionnaire, then underwent airway responsiveness measurements as PD20FEV1 to methacholine. Previous experience of bronchoconstriction was assessed in the 481 subjects with measurable airway responsiveness (PD20FEV1 < 6400 g) by asking 'have you ever felt like this before' at the end of their methacholine challenge tests, i.e. when the subjects were bronchoconstricted by FEV1 decrements of at least 20%. The responses to this question bore no relationship to the previously administered questionnaire responses about wheezing, chest tightness, coughing, or breathlessness. However, there was an inverse relationship with PD20FEV1 measurements (P < 0.001), the positive response rate to the question falling from 92% among those with PD20FEV1 < 50 micrograms to 27% among those with PD20FEV1 in the highest measurable range (3200-6400 micrograms). This suggests that airway responsiveness measurements are a more reliable guide to subjects' previous experience of substantial bronchoconstriction (i.e. asthma) than are the responses to respiratory questionnaires.

Adult↗

PubMed2005

Protective effect of ipratropium bromide on bronchoconstriction induced by sulfur dioxide exposure during apricot sufurization processes that causes asthma-like syndrome in agricultural environment.

We previously showed that apricot sulfurization workers are exposed to high concentrations of sulfur dioxide (SO2), resulting in an asthma-like syndrome. The aim of this study was to investigate whether pre-treatment of ipratropium bromide protects bronchoconstriction induced by SO2 exposure during apricot sulfurization processes that causes asthma-like syndrome. Firstly, pulmonary function tests were measured before and immediately after SO2 exposure due to processes of apricot sulfurization in 21 healthy volunteer apricot sulfurization workers who did not use any medication in apricot farms. One week later, same measurements were repeated in the same workers when they were working in same farm but they were administered two puffs of ipratropium bromide (20 microg per dose) before 30 min second SO2 exposure for protection of SO2-induced bronchoconstriction. Occupational SO2 exposure caused significant decrement in forced vital capacity (FVC), forced expiratory volume (FEV1) and forced mid-expiratory flow rate (FEF25-75%) in the worker and these decrements were prevented by ipratropium bromide given 30 min before SO2 exposure. This result suggests that pre-treatment of ipratropium bromide protects SO2-induced bronchoconstriction in healthy worker during apricot sulfurization processes that causes asthma-like syndrome in agricultural environment.

Agricultural Workers' Diseases↗

PubMed2004

Budesonide/formoterol in a single inhaler rapidly relieves methacholine-induced moderate-to-severe bronchoconstriction.

Inhalers containing corticosteroids and long-acting beta2-agonists are becoming increasingly important in asthma management. A rapid effect is important to patients, particularly during exacerbations. We compared the onset of bronchodilation and patient-perceived relief from dyspnoea following single-inhaler budesonide/formoterol or salmeterol/fluticasone in a model of acute bronchoconstriction. A randomised, double-blind, double-dummy, single-dose, crossover study included 27 outpatients with asthma (mean age 35 years; mean FEV1 90% predicted normal). Immediately following methacholine-induced bronchoconstriction (fall in FEV1 > or = 30%), patients inhaled budesonide/formoterol (160/4.5 microg, 1 or 2 inhalations; Symbicort Turbuhaler), salmeterol/fluticasone (50/250 microg; Seretide Diskus) or placebo on 4 study days. Lung function and Borg score were assessed for 30 min. During methacholine-induced provocation (final mean FEV1 62.5% of baseline), mean Borg score increased 10-fold (from 0.3 to 3.0 units). Hereafter, mean FEV1 at 3 min improved significantly more after budesonide/formoterol 1 and 2 inhalations (37 and 38%, respectively) than after salmeterol/fluticasone (23%; P < 0.001) or placebo (10%; P < 0.001). Median recovery times to 85% of baseline FEV1 were shorter for budesonide/formoterol (1 or 2 inhalations: 3.3 and 2.8 min, respectively) than salmeterol/fluticasone (8.9 min; P < 0.001) and placebo (> 30 min). One min after budesonide/formoterol, dyspnoea was significantly reduced (Borg score -0.86 units, both doses) compared with salmeterol/fluticasone (-0.55 units; P < 0.05) and placebo (-0.23 units; P < 0.001). Budesonide/formoterol provides immediate bronchodilation, faster than salmeterol/fluticasone, which patients can feel during acute methacholine-induced bronchoconstriction.

Adolescent↗

PubMed2005

The distribution of ventilation during bronchoconstriction is patchy and bimodal: a PET imaging study.

Recent PET imaging data from bronchoconstricted sheep (Vidal Melo et al., 2005) showed that V /Q distributions were bimodal and topographically patchy, but including a substantial heterogeneity at scales <2.2 ml. In this paper, we reanalyze the experimental data to establish the contribution of ventilation (V (r)) heterogeneity to the bimodality in V /Q . This analysis demonstrates that the distribution of V (r) during bronchoconstriction was bimodal with large patches of severe hypoventilation occupying an average of 41% of the imaged lung. The degree of hypoventilation to these regions was highly correlated with the degree of oxygenation impairment, but was quite variable amongst animals in spite of consistent degrees of mechanical obstruction. Remarkably, those regions were found to be hyperventilated before methacholine and their degree of hyperventilation was correlated with their degree of hypoventilation during bronchoconstriction. These data suggest that improving the uniformity of ventilation at baseline may be a desirable therapeutic target if the risk of severe hypoxemia during asthma attacks is to be minimized and/or the distribution of inhaled pharmaceuticals is to be optimized.

Animals↗

PubMed2006

Determinants of the bronchodilation response to salbutamol on histamine-induced bronchoconstriction.

Assessment of the bronchodilation response to short-acting beta2-adrenoreceptor agonists on pharmacologically induced bronchoconstriction has often been used to investigate airway smooth muscle beta2-adrenoreceptor function. However, little is known about factors affecting this response. In the present study, the bronchodilation response to 0.2 mg of salbutamol on histamine-induced bronchoconstriction was assessed in 101 steroid-naïve asthmatic subjects. The associations of the response with a wide range of challenge procedure-related variables, clinical asthma severity indicators, and blood markers of airway inflammation were investigated. The response was re-assessed after 6 and 12 weeks' therapy with inhaled budesonide. Baseline FEV1, final histamine concentration, and the maximal fall in FEV1 explained 35-59% of the total variation in the response to salbutamol, depending on the index chosen to express the response. Serum concentration of myeloperoxidase, an index of neutrophilic inflammation, was associated with a poor response. The preceding week daily PEF variation, rescue bronchodilator use, severity of asthmatic symptoms, blood eosinophil count, and serum eosinophilic cationic protein and eosinophilic protein X concentrations were not associated with the response. The salbutamol response seemed to diminish during budesonide treatment but when adjusted by the challenge procedure-related variables the treatment effect vanished. In conclusion, the bronchodilation response to salbutamol on histamine-induced bronchoconstriction is largely determined by challenge procedure-related variables. It seems to be unrelated to the clinical severity of asthma and is not affected by treatment with inhaled corticosteroids. Neutrophilic airway inflammation may be associated with a poor response.

Administration, Inhalation↗