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PubMed1984

Exercise and isocapnic hyperventilation-induced bronchoconstriction in asthma: relevance of circulating basophils to measurements of plasma histamine.

The relationship of airway cooling during exercise to changes in airway caliber, plasma histamine levels, and circulating basophils was investigated in eight allergic asthmatic and eight normal subjects. In asthma matched RHE during exercise and ICH produced almost identical bronchoconstriction with maximum falls in SGaw of 61.0 +/- 4.5% and 57.9 +/- 5.2%, respectively. A similar RHE in normal subjects was associated with a 7.9 +/- 3.3% fall in SGaw. The resting plasma-histamine levels were higher in the asthmatic (0.52 +/- 0.06 ng/ml) than in the normal (0.31 +/- 0.07 ng/ml, p less than 0.05) subjects. No significant change in plasma histamine occurred after exercise in either group nor in the asthmatic subjects with ICH. In contrast, exercise but not ICH stimulated an increase in leukocytes, basophils, and total blood histamine in parallel with the airway response that reached a maximum at 2 to 5 min in both normal and asthmatic subjects. There was a positive correlation between basal plasma and total blood-histamine levels (r = 0.67, p less than 0.01) in normal and asthmatic subjects suggesting that basophils contribute significantly to plasma histamine. The spontaneous basophil release of histamine was greater in asthmatic (13.4 +/- 2%) than in normal subjects (6.46 +/- 7%, p less than 0.005), which is consistent with the higher resting plasma-histamine levels in the asthmatic subjects. These findings suggest that plasma-histamine changes with exercise in asthma but not ICH may be related to the associated basophilia and sample handling rather than intrapulmonary mast cell degranulation.

Adult↗
PubMed1987

Effect of terfenadine on methacholine-induced bronchoconstriction in asthma.

The dose-response effect of nonsedating H1 histamine-receptor antagonist, terfenadine, administered orally in single doses, was studied on methacholine-induced bronchoconstriction in nine patients with extrinsic bronchial asthma in a double-blind, placebo-controlled, crossover trial. The doses of terfenadine used were 60 mg, 120 mg, and 180 mg, producing small but significant bronchodilator effect with all three doses at 2 hours. This response was still present at 4 hours. However, the provocative dose causing a 20% fall in FEV1 for methacholine was unaffected by all three doses of terfenadine. The bronchodilator response induced by antihistamines, including terfenadine, suggests an increased resting tone mediated by the constant presence of free histamine in the vicinity of H1 receptors in the airways and that methacholine acts directly on the airway muscarinic receptors and is not involved in local histamine release.

Adolescent↗
PubMed1989

Duration of the effect of a single dose of azelastine on histamine-induced bronchoconstriction.

We studied the duration of the protective effect of azelastine against histamine-induced bronchoconstriction in six subjects with asymptomatic asthma. The study was performed in two periods of five consecutive days each. After a histamine inhalation test, we randomly administered either placebo or a single oral dose of 8.8 mg azelastine in a double-blind crossover fashion. Histamine challenges were repeated 5 hours after ingestion and at 1 PM on the following four days. The geometric means of the dose of histamine (in cumulative breath units [cbu]) necessary to increase specific airway resistance by 100% as compared with baseline (PD100SRaw) were 8.7 and 8.5 cbu before placebo and azelastine, respectively. Placebo did not significantly influence PD100SRaw within 99 hours after treatment. Five and 27 hours after azelastine, PD100SRaw increased to 178.2 and 46.7 cbu, respectively (p less than 0.05). Two patients showed a highly significant protection against the airway effect of histamine even 99 hours after ingestion (p less than 0.01). These data demonstrate a variable duration of the antihistaminic property of azelastine. The prolonged therapeutic effect in some patients may be beneficial in the timing of medication intervals.

Administration, Oral↗
PubMed1979

Effect of prostacyclin on antigen induced immediate bronchoconstriction in asthmatic patients.

The effect of premedication with inhaled prostacyclin (PGI2) on the allergen induced immediate bronchoconstriction was investigated in 10 asthmatic patients, under single blind conditions, by means of a body plethysmograph. Statistical analysis (Dunnett's test) did not show any significant difference between PGI2 and placebo. The possible meaning of these results is discussed.

Adolescent↗
PubMed1995

Plasma atrial natriuretic peptide during spontaneous bronchoconstriction in asthmatics.

The aim of this work was to establish the role of endogeneous ANP during a spontaneous asthma attack. Forced expiratory lung volume in 1 s (FEV1), cardiovascular parameters, and plasma ANP, cAMP, and cGMP were measured for 60 min before and 10 min after treatment with a bronchodilator in 10 asthmatics. The results show that in the presence of moderate bronchoconstriction, FEV1 was 54 +/- 3% (+/-SE); ANP levels initially were slightly elevated at 47 +/- 10 pg/ml and decreased to 26 +/- 3 pg/ml (p < 0.05) over 60 min, with no change in FEV1. Following salbutamol inhalation, FEV1 increased to 77 +/- 4% with no change in ANP. We conclude that endogenous ANP does not act as a bronchodilator in asthmatics with moderate bronchospasm.

Acute Disease↗
PubMed1990

Adenosine-induced bronchoconstriction in human asthmatics: effects of pretreatment with indomethacin or atropine sulfate.

The present investigation was designed to evaluate the effects of pre-treatment with the cholinergic muscarinic receptor antagonist, atropine sulfate, or with the cyclooxygenase inhibitor, indomethacin, on adenosine-induced bronchoconstriction in human asthmatics. Eight male subjects with a FEV1 of greater than 70% of the predicted normal value underwent bronchial provocation challenges with adenosine and with the cholinergic agonist, methacholine, in a double-blind, randomized, cross-over fashion. The log10 of the agonist dose provoking a 20% decrease in FEV1 (log PD20FEV1) was used to assess airways responsiveness. Challenges were performed in the untreated state and 30 min after inhalation of atropine sulfate (0.05 mg/kg). Pre-challenge FEV1 values after atropine inhalation were higher than in the untreated state (p less than 0.01). Without atropine, the log PD20FEV1 values for adenosine were higher than those for methacholine (p less than 0.01). Atropine prevented a decrease in the FEV1 of 20% or more in seven of the eight subjects following inhalation of methacholine up to a concentration of 25 mg/ml, but did not significantly change the log PD20FEV1 for adenosine. The effects of a 75 mg oral dose of indomethacin or placebo, administered in a double-blind, randomized, cross-over fashion two hours before adenosine or methacholine challenge, were assessed in 12 asthmatics. In four subjects (two after placebo and two after indomethacin pretreatment), aerosols of the highest adenosine concentration (10 mg/ml) failed to decrease the FEV1 by 20% or more. In the remaining eight subjects, log PD20FEV1 values for adenosine or methacholine after indomethacin were not significantly different from those after placebo.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗
PubMed1993

Salmeterol provides prolonged protection against exercise-induced bronchoconstriction in a majority of subjects with mild, stable asthma.

In patients with asthma, exercise-induced symptoms are well recognized and frequently limiting. Currently available beta 2-receptor agonists have a short duration of action and breakthrough symptoms may occur. We studied the efficacy of the recently developed long acting inhaled beta 2-agonist salmeterol with respect to protection against exercise-induced bronchoconstriction. Twelve patients with mild to moderate, stable asthma were recruited (age range 21-33 years). They each underwent treadmill exercise tests, with target heart rate of approximately 90% of predicted maximum, 1, 6 and 12 h after a single dose of salmeterol 50 micrograms, salbutamol 200 micrograms and placebo. Patients breathed through a two-way valve, inspiring dry air from a compressed air cylinder via a Douglas bag to maintain constant humidity. The primary efficacy variable analysed was the maximum percentage fall in FEV1 and FVC from pre-exercise readings within the first 30 min post-exercise. At 1 h post-dose there was significant protection in terms of fall in mean +/- SEM FEV1 in response to exercise challenge after either salmeterol (0.83 +/- 6.2%) or salbutamol (3.8 +/- 5.5%) as compared with placebo (27.1 +/- 7.3%). At 6 h post-dose, fall in FEV1 on salmeterol was 11.3 +/- 3.8% as compared with salbutamol, 28.0 +/- 5.7% and placebo, 32.0 +/- 7.0%. At 12 h post-dosing there was still significant protection in terms of fall in FEV1 in the salmeterol treated group, 12.8 +/- 4.9%, as compared with salbutamol, 28.7 +/- 4.9% and placebo, 25.4 +/- 7.3%.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Agonists↗
PubMed1994

Reduced protection against exercise induced bronchoconstriction after chronic dosing with salmeterol.

The purpose of the present study was to assess the degree of protection of inhaled salmeterol against exercise-induced bronchoconstriction (EIB) after chronic compared with single dosing in patients with asthma. Twelve patients with exercise-induced asthma took part in a randomized double-blind crossover study to compare the duration of action of inhaled salmeterol 50 micrograms twice daily for 4 weeks with that of placebo. A standardized exercise test was performed at 6 h and 12 h after dosing on the first and last day of each treatment period. Salmeterol produced significant protection against EIB at 6 and 12 h after the first dose in comparison with placebo, whereas there was no significant attenuation of EIB after 4 weeks of chronic treatment with salmeterol. The percentage fall in FEV1 after exercise challenge at 6 h was (first dose): placebo 34.8 +/- 4.9% vs. salmeterol 11.9 +/- 2.8% (P < 0.05); (4 weeks): placebo 32.9 +/- 5.3% vs. salmeterol 24.0 +/- 4.4% (NS). These results suggest that tachyphylaxis may develop to the functional antagonism of salmeterol against EIB.

Administration, Inhalation↗
PubMed2005

Inhaled hyaluronic acid against exercise-induced bronchoconstriction in asthma.

Hyaluronic acid (HA) is a polysaccharide that is present in human tissues and body fluids. HA has various functions, including a barrier effect, water homeostasis, stabilizing the extracellular matrix, increased mucociliary clearance and elastin injury prevention. It may therefore exert prophylactic activity in the treatment of asthma. We tested the hypothesis that HA inhalation will prevent exercise-induced bronchoconstriction (EIB) in a randomised double-blinded placebo-controlled crossover study. Sixteen asthmatic patients with EIB were included in the study (mean (SD)) (age 24.5 (7.3) yr, FEV1 88.6 (11.3) %predicted, PC20 methacholine (g-mean (SD in DD)) 0.4 (1.5) mg/ml). On two separate visits an exercise challenge was performed 15 min post-inhalation of either HA (3 ml 0.1% in PBS) or placebo (3 ml PBS). The maximum fall in FEV1 and the AUC 30 min post-exercise were used as outcomes. After inhalation of both HA and placebo, baseline FEV1 decreased significantly (HA 4.1 (3.1)%, placebo 2.9 (4.1)%, P<0.017). The maximum fall in FEV1 following exercise challenge was not significantly different between HA versus placebo (median HA 22.50%, placebo 27.20%, P=0.379), as was the AUC (median HA 379.3 min*%fall, placebo 498.9 min*%fall, P=0.501). We conclude that at the current dose, inhaled HA does not significantly protect against EIB. This suggests that HA is not effective as a prophylaxis for EIB in patients with asthma.

Adjuvants, Immunologic↗
PubMed2006

Humidity influences exercise capacity in subjects with exercise-induced bronchoconstriction (EIB).

RATIONALE: Exercise-induced bronchoconstriction (EIB) increases in cold and dry air and decreases in humid air in subjects with asthma. Few reports have reported on the effect of humid environment upon exercise capacity in subjects with EIB. OBJECTIVE: The primary aim of the present study was to examine the effect of changing the humidity of the environmental air upon exercise capacity measured by peak oxygen uptake (V O2 peak), peak ventilation (V Epeak) and peak running speed (V peak) and secondarily to assess the influence of environmental humidity upon EIB in subjects suffering from EIB. METHODS: Twenty subjects (10-45 years old, male/female:13/7) with diagnosed EIB performed exercise testing under standardised, regular environmental conditions, 20.2 degrees C (+/- 1.1) and 40% (+/- 3.3) relative humidity [mean (+/- SD)], and under standardised humid environmental conditions; 19.9 degrees C (+/- 1.0) and 95% (+/- 1.7) relative humidity in random order on separate days. Lung function was measured before and 1, 3, 6, 10 and 15 min after exercise. Heart rate (HR), oxygen uptake (V O2), respiratory gas exchange ratio (RER), breathing frequency (BF) and minute ventilation (V E) were measured during exercise. RESULTS: V O2 peak and V peak increased significantly from 40% to 95% relative humidity of the environmental air, 4.5% and 5.9%, respectively (P = 0.001). HRpeak increased significantly in the humid environment, while BF(peak) decreased significantly. RERpeak and V Epeak did not change significantly. Post-exercise reduction in FEV1 (DeltaFEV1) and FEF50 (forced expiratory flow at 50% of FVC) (DeltaFEF50) significantly decreased after exercise in a humid environment as compared to regular conditions, DeltaFEV1: 12% (7,17) vs. 24% (19,29) [mean (95% confidence intervals)], respectively, DeltaFEF50: 20% (12,29) vs. 38% (30,46), respectively (P < 0.001). CONCLUSION: Exercise capacity (V O2 peak and V peak) markedly improved during exercise in humid air in subjects with EIB, whereas EIB was reduced to the half.

Adolescent↗
PubMed1999

Montelukast versus salmeterol in patients with asthma and exercise-induced bronchoconstriction. Montelukast/Salmeterol Exercise Study Group.

BACKGROUND: Montelukast, a leukotriene receptor antagonist, and salmeterol, a long-acting beta(2)-receptor agonist, each have demonstrated benefits in the treatment of exercise-induced bronchoconstriction (EIB) in short-term studies. Direct comparisons between these agents in long-term studies are limited. OBJECTIVE: We sought to compare montelukast and salmeterol in the long-term treatment of EIB. METHODS: One hundred ninety-seven patients with mild asthma and a postexercise fall in FEV(1) of at least 18% were randomized (double-blind) to receive montelukast 10 mg once daily or salmeterol 50 microg twice daily for 8 weeks. Exercise challenge was repeated at day 3, week 4, and week 8 after randomization near the end of the dosing interval for both drugs. The primary efficacy endpoint was the maximal percent fall in postexercise FEV(1) at week 8. RESULTS: Montelukast was effective in treating EIB without inducing tolerance and provided superior (P </=.001) protection than salmeterol at weeks 4 and 8, with comparable protection at day 3. The frequency of respiratory clinical adverse events (P =.046) and discontinuations because of clinical adverse events (P =.052) were less with montelukast. CONCLUSION: The effect of montelukast was greater than that of salmeterol in the chronic treatment of EIB over a period of 8 weeks in patients with mild asthma as demonstrated by effect size, maintenance of effect, and fewer respiratory clinical adverse events during the study period. Montelukast may be a better alternative to salmeterol as a controller agent for the chronic treatment of EIB.

Acetates↗
PubMed1983

Vasoactive intestinal peptide causes bronchodilatation and protects against histamine-induced bronchoconstriction in asthmatic subjects.

Vasoactive intestinal peptide (VIP) caused significant bronchodilatation in seven asthmatic volunteers when given intravenously at the rate of 6 pmol/kg/min for 15 min during a double-blind study. Tachycardia and cutaneous flushing were observed during the infusion. VIP also ameliorated histamine-induced bronchoconstriction in all subjects. VIP may be an important natural bronchodilator in man and this has implications for the pharmacotherapy of asthma.

Adult↗
PubMed1988

Prevention of exercise-induced bronchoconstriction by inhaled frusemide.

To determine whether inhaled frusemide, a diuretic able to interfere with ion and water movement across airway epithelium, can modify exercise-induced bronchoconstriction, a three-part randomised, double-blind, placebo-controlled study was done in asthmatic patients who had a fall in FEV1 of at least 20% after running up and down a corridor. In the first part the effect of approximately 28 mg frusemide given as an aerosol was compared with that of a placebo. In the second part two doses of inhaled frusemide (approximately 14 mg and 28 mg) were examined. In the third part the effect of 20 mg oral frusemide was tested. Inhaled frusemide had a good and dose-related protective effect, whereas oral frusemide was ineffective. The mean (95% CI) maximum percentage falls in the FEV1 were: 11.5 (14.3-8.7) with frusemide and 33.8 (39.1-28.5) with placebo in the first part of the study; 13.6 (21.6-6.0) with 28 mg frusemide, 19.7 (28.2-11.3) with 14 mg frusemide, and 34.6 (39.4-30.0) with placebo in the second part of the study; and 15.2 (19.9-10.5) with inhaled frusemide, 38.2 (47.1-29.3) with oral frusemide, and 35.3 (45.9-24.7) with placebo in the last part of the study. The findings lend support to the hyperosmolarity hypothesis of exercise-induced asthma and may have therapeutic implications.

Administration, Inhalation↗
PubMed1998

Cold air inhalation and exercise-induced bronchoconstriction in relationship to metacholine bronchial responsiveness: different patterns in asthmatic children and children with other chronic lung diseases.

Cold air inhalation and exercise-induced bronchoconstriction (EIB) have both been used as measures of bronchial responsiveness. Both stimuli are often combined in the Nordic climate. The main objective of the present study was to investigate the climatic influence of cold temperatures upon exercise-induced asthma. The secondary aims were: (a) to assess metacholine bronchial hyper-responsiveness and EIB in children with bronchial asthma (n = 32; mean age 10.8 years) compared to children with other chronic lung diseases (CLD) (n = 26, mean age 10.1 years); and (b) to assess the influence of cold air inhalation upon EIB in the two groups of children. Methods used were: (a) the metacholine concentration causing a reduction in FEV1 of 20% (PC20-M), (b) maximum FEV1 fall (delta FEV1) after submaximal treadmill run (EIB test); and (c) delta FEV1 after submaximal treadmill run while inhaling cold (-20 degrees C) dry air (CA-EIB test). Geometric mean PC20-M did not differ significantly between the asthma children (1.28 mg ml-1) and the CLD children (2.90 mg ml-1). In the asthma children, mean delta FEV1 after EIB test was 12.8% vs 21.8% after adding cold air (P < 0.0001), compared to 5.2 and 7.4%, respectively (P = 0.03), in the CLD group. Maximum sensitivity and specificity for the EIB test were 69.8% at a fall in FEV1 of 6.8%; for the CA-EIB test, 72% at a fall in FEV1 of 10.2%; and for metacholine provocation, 56% at a PC20-M of 1.5 mg ml-1. In conclusion, children with bronchial asthma are substantially more sensitive to cold air than children with CLD, and EIB is markedly increased by cold air inhalation in asthmatic children, maintaining the specificity of the EIB test and increasing the sensitivity. The low sensitivity of the EIB test is probably influenced by the use of inhaled steroids. Metacholine inhalation test has less specificity and sensitivity in discriminating asthma from other chronic lung diseases.

Asthma, Exercise-Induced↗
PubMed2006

Effect of formoterol fumarate treatment on exercise-induced bronchoconstriction in children.

BACKGROUND: Exercise-induced bronchoconstriction (EIB) is common, particularly in children. OBJECTIVES: To compare the protective effect of single doses of formoterol fumarate via Aerolizer with placebo and albuterol in children with EIB. METHODS: In this randomized, double-blind, double-dummy, crossover trial, 23 children (aged 4-11 years) received formoterol, 12 or 24 microg; albuterol, 180 microg; or placebo at 4 separate visits. Protection against EIB was evaluated as the maximum percentage decrease in forced expiratory volume in 1 second (FEV1) from the preexercise value after exercise challenge tests (6-minute treadmill) conducted 15 minutes and 4, 8, and 12 hours after administration of the dose. RESULTS: The maximum percentage decrease in FEV1 after the 4-hour exercise test (primary efficacy variable) was significantly less for formoterol, 12 and 24 microg, vs placebo (P < .001 for both) or albuterol (P = .016 and .010, respectively); albuterol was not significantly different from placebo. Formoterol, 12 and 24 microg, differed from placebo at 8 hours (P = .002 and .001, respectively), with a smaller difference between albuterol and placebo (P = .045). Rescue medication use and a high dropout rate may have biased treatment differences at later time points. Protection against EIB (<20% maximum decrease in FEV1) across all time points was observed for 17 (77%) of 22 and 17 (74%) of 23 children with formoterol, 12 and 24 microg, respectively, compared with 8 (35%) of 23 with albuterol and 6 (27%) of 22 with placebo. CONCLUSIONS: Single doses of formoterol, 12 or 24 microg, are effective in protecting against EIB in children, affording a statistically significantly greater protective effect than placebo or albuterol.

Administration, Inhalation↗
PubMed2006

Onset and duration of protection against exercise-induced bronchoconstriction by a single oral dose of montelukast.

BACKGROUND: Leukotriene modifiers have been shown to protect against exercise-induced bronchoconstriction (EIB) with repeated, chronic dosing. OBJECTIVE: To study the onset and duration of protection against EIB after a single dose of montelukast, a leukotriene receptor antagonist. METHODS: In this randomized, crossover, double-blind study, 51 adult asthma patients with EIB (> or = 20% postexercise decrease in forced expiratory volume in 1 second [FEV1]) received a single oral dose of montelukast (10 mg), or placebo followed by exercise challenge 2, 12, and 24 hours after dosing. The primary end point was maximum percentage decrease in FEV1 from preexercise baseline during 60 minutes after the 2-hour challenge. RESULTS: At 2, 12, and 24 hours after dosing, the maximum decrease in FEV1 was 10.8% +/- 7.9%, 8.4% +/- 7.5%, and 8.3% +/- 7.3% for montelukast and 22.3% +/- 13.1%, 16.1% +/- 10.2%, and 16.9% +/- 11.7% for placebo, respectively (P < or = .001 at each time point). Postexercise recovery was quicker with montelukast than with placebo (P < or = .001); mean (95% confidence interval) differences were -26.8 minutes (-35.1 to -18.4 minutes), -16.0 minutes (-22.9 to -9.2 minutes), and -17.4 minutes (-24.9 to -9.9 minutes) at the 3 time points, respectively. At all time points, area under the curve for percentage decrease in FEV1 during 60 minutes after exercise was smaller after montelukast (P < or = .001); montelukast protected more patients against EIB (P < or = .001). Fewer patients required postexercise beta-agonist rescue at 2 hours after dosing with montelukast (P = .03). CONCLUSION: Montelukast provided significant protection against EIB as soon as 2 hours after a single oral dose, with persistent benefit up to 24 hours.

Acetates↗
PubMed2002

Protection against exercise-induced bronchoconstriction by montelukast in aspirin-sensitive and aspirin-tolerant patients with asthma.

BACKGROUND: Montelukast, a cysteinyl-leukotriene receptor antagonist, was reported to have a protective effect against exercise-induced bronchoconstriction (EIB). Aspirin-induced asthma (AIA) is characterized by overproduction of cysteinyl-leukotrienes. OBJECTIVE: The aim of the study was to compare the response to exercise and the effect of montelukast on EIB in AIA as compared to aspirin-tolerant asthma (ATA). METHODS: A placebo-controlled, double blind, cross-over randomized study was performed in 19 AIA and 21 ATA patients with stable asthma. A single dose of montelukast (10 mg) or placebo (PL), was given orally one hour prior to exercise challenge. FEV1 was measured before and 5, 10, 15 min after exercise and then at 15-minute intervals for 4 h. Urinary LTE4 excretion and blood eosinophil count were measured at baseline, 2 h and 4 h following exercise challenge. RESULTS: Positive bronchial response to exercise was observed in 47.5% of all patients studied. Exercise led to almost identical maximal fall in FEV1 in AIA and ATA patients (23.5% +/- 6.8% vs. 21.8% +/- 12.0%, respectively; P = 0.7). Montelukast, as compared to PL, significantly attenuated EIB in 63.2% of 19 patients with positive exercise test preceded by PL. The mean of maximum fall in FEV1 from the pre-exercise value was 10.2% +/- 13.8 after montelukast as compared to 22.5% +/- 10.2 after placebo (P < 0.001). No significant differences between protective effect of montelukast was observed in AIA as compared to ATA patients (P = 0.63, anova). Urinary LTE4 excretion showed no change following exercise, irrespective of the result of the test in all subjects. CONCLUSION: Patients with AIA and ATA react similarly to exercise challenge and obtain similar protection against EIB by montelukast.

Acetates↗