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PubMed2001

Inhaled corticosteroids, combined with long-acting beta(2)-agonists, improve the perception of bronchoconstriction in asthma.

The relationship between asthma medication and the perception of asthma symptoms is of interest for daily practice. Poor perception of asthma symptoms might influence patients' health care behavior and subsequently might lead to undertreatment and deterioration of their disease. This study investigated the influence of the chronic use of short-acting and long-acting beta(2)-agonists, compared with the additional use of inhaled corticosteroids on the perception of histamine-induced bronchoconstriction. Patients with asthma (33 male and 31 female, mean age 35 +/- 11 yr, FEV(1) 87 +/- 14% of the reference value, PC(20) geometric mean 1.08 mg/ml (95% CI: 0.76-1.52) were selected and randomly allocated to the use of either a short-acting beta(2)-agonists (salbutamol, n = 22) or a long-acting beta(2)-agonists (formoterol, n = 22) or placebo (n = 20), which has been used for 12 wk. This medication treatment was repeated exactly 1 yr later, with patients receiving the same medication plus an inhaled corticosteroid. Perception of histamine-induced bronchoconstriction was measured at the start of each treatment period and every 4 wk thereafter. Subjects quantified their sensation of respiratory discomfort during the challenge tests on a modified Borg scale. The perceptive "sensitivity" for changes in FEV(1) was analyzed by the linear regression slope (alpha) "Borg versus percentage fall in FEV(1)." The "absolute perceptual magnitude" was determined by the perception score at the 20% fall in FEV(1) (PS(20)). The additional use of inhaled corticosteroids during the second year resulted in an improved perception of histamine-induced bronchoconstriction (slope alpha) compared with the first year for only the long-acting beta(2)-agonists group (p value 0.036). This improvement was not observed for the "absolute perceptual magnitude" (PS(20)). The additional use of inhaled corticosteroids during chronic use of long-acting beta(2)-agonists improves the perceptive "sensitivity" for changes in FEV(1) during histamine-induced bronchoconstriction, which was not observed for short-acting bronchodilators. This result might indicate that the positive effects on perception of airway obstruction might be another reason (besides the beneficial effects on the clinical condition) for prescribing a combination of long-acting beta(2)-agonists and inhaled steroids.

Administration, Inhalation↗

PubMed1992

Limitation of maximal bronchoconstriction in living dogs.

Fourteen dogs were studied to determine whether (1) interdependence between airways and parenchyma can limit maximal bronchoconstriction under static conditions in vivo, and (2) stretching of airway smooth muscle during tidal breathing can attenuate muscle shortening and account for the limited bronchoconstriction previously observed in response to increasing doses of methacholine (MCh). In six dogs the left lung was ventilated while 50% MCh was nebulized into the airways of the right lower lobe (RLL) held at constant transpulmonary pressures (PL). Airway closure, as assessed by an alveolar capsule technique during small oscillations in lobar volume, occurred at PL less than or equal to 7.5 cm H2O. To assess the effects of tidal breathing, pulmonary resistance (RL) was measured in four dogs after MCh nebulization into the RLL during tidal breathing while the left lung was separately ventilated. In another four dogs the whole lung was challenged with MCh. At each MCh concentration, RL values in the RLL were much higher than in the whole lungs (30-fold at the highest MCh concentration), showing that maximal bronchoconstriction in response to MCh is much greater in the RLL than in the whole lung. We conclude that neither interdependence nor tidal breathing can fully explain limited maximal bronchoconstriction in living dogs.

Airway Resistance↗

PubMed1993

Inhibition of platelet-activating factor-induced bronchoconstriction by the leukotriene D4 receptor antagonist ICI 204,219.

We determined whether platelet-activating factor (PAF) caused bronchoconstriction through the release of leukotrienes (LT) by studying the effect of a potent LTD4 receptor antagonist, ICI 204,219, on PAF-induced bronchoconstriction in normal subjects. Eight males (age 20 to 36 yr) were given either 40 mg ICI 204,219 orally or matching placebo on 2 study days separated by 2 wk in a double-blind crossover study. Specific airway conductance (SGaw) was measured after inhalation of nebulized PAF (45 micrograms). ICI 204,219 caused a significant inhibition of PAF-induced bronchoconstriction as assessed by comparison of the maximum fail in SGaw or of the area under the curve of the time course of SGaw. ICI 204,219 did not inhibit PAF-induced neutropenia. PAF-induced bronchoconstriction is mediated largely by the release of sulfidopeptide leukotrienes in normal men.

Adult↗

PubMed1993

Bronchoconstriction-induced hyperinflation assessed by thoracic area measurement in guinea pigs.

The changes in end-expiratory lung volume (EELV) accompanying histamine-induced bronchoconstriction were compared for two routes of drug administration in anesthetized, paralyzed, and mechanically ventilated guinea pigs. Changes in EELV were estimated from measurements of thoracic cross-sectional area, assessed from the voltage induced by an external uniform magnetic field in a pickup coil encircling the rib cage. Increasing doses of histamine were administered as bolus injections in Group 1 (n = 7) and as nebulizations in Group 2 (n = 7). After each bronchial challenge, the maximum change in EELV and the associated intrinsic positive end-expiratory pressure (PEEPi) were measured at the same time. In both groups, bronchoconstriction was accompanied by an increase in EELV, which was related to the degree of bronchoconstriction and reached about 70 to 100% of the basal functional residual capacity. The increases in EELV were linearly related to the PEEPi values (p < 0.001) and did not depend on the route of histamine administration. These results indicate that dynamic hyperinflation is not the only mechanism involved in lung volume response to bronchoconstriction and suggest that gas trapping may have occurred in alveolar spaces.

Administration, Inhalation↗

PubMed1995

Prevention of bronchoconstriction by an orally active local anesthetic.

Stimulation of airway irritant receptors produces reflex bronchoconstriction that can be prevented by pretreatment with anticholinergic drugs or local anesthetics delivered by aerosol or intravenously. We compared therapeutic doses of an orally administered local anesthetic, mexiletine hydrochloride, and intravenously administered lidocaine at blocking histamine-induced bronchoconstriction in five basenji-greyhound dogs, using high-resolution computed tomography (HRCT) to directly measure changes in airway size. In the dogs given placebo, a histamine infusion decreased airway area to 61 +/- 2% (mean +/- SEM) of control (p < 0.01). Mexiletine pretreatment completely prevented histamine-induced airway constriction, with an airway area that was 94 +/- 4% of the control value during the histamine infusion (p = 0.07 compared with baseline). Mexiletine serum levels were therapeutic (1.7 +/- 0.3 mg/L). Similarly, pretreatment with lidocaine significantly blunted the airway constriction provoked by intravenous histamine. In lidocaine-pretreated dogs, histamine decreased airway area to 79 +/- 4% of baseline (p < 0.01). As in the case of mexiletine, lidocaine serum levels were also therapeutic (2.4 +/- 0.3 mg/L). Mexiletine was more effective than lidocaine at preventing histamine-induced bronchoconstriction (p = 0.02). These data suggest that orally administered local anesthetics may be useful in preventing irritant-induced bronchoconstriction in humans.

Animals↗

PubMed2002

Respiratory sensation and ventilatory mechanics during induced bronchoconstriction in spontaneously breathing low cervical quadriplegia.

Intensity of dyspnea during induced bronchoconstriction in asthma is strongly related to the reduction in inspiratory capacity (IC) as a result of dynamic hyperinflation. To determine the role of rib cage and intercostal muscle afferents in symptom perception during bronchoconstriction, we measured the relationship between dyspnea intensity and IC during induced bronchoconstriction in six subjects with complete C4-C7 quadriplegia who did not require assisted ventilation. Spirometry, lung volumes, breathing pattern, esophageal pressure (Pes), and dyspnea intensity (Borg Scale) were measured during high-dose methacholine bronchoprovocation up to 256 mg/ml or a maximum change (Delta) in FEV(1) of 50%. Contemporaneous control data from subjects with asthma (n = 12) who had completed the same protocol were used for comparison. At maximum response in quadriplegia, FEV(1) decreased by 1.42 +/- 0.18 L (62 +/- 4%predicted) (mean +/- SEM), and IC decreased by 0.89 +/- 0.12 L (30 +/- 4%predicted). Dyspnea at maximum response was rated "moderate" to "severe": Borg 3.6 +/- 0.3. The predominant qualitative respiratory sensations were inspiratory difficulty and unsatisfied inspiration. The best correlate of dyspnea (Borg) was DeltaIC(%predicted) (p < 0.0005), whereas changes in FEV(1), Pes-derived measurements and breathing pattern did not contribute further to the strength of this relationship. Dyspnea intensity, quality, and changes in spirometry and lung volumes at maximum response were similar to those reported previously in asthma. The relationship between dyspnea intensity and DeltaIC(%predicted) was linear and consistent across groups. We conclude that the quality and intensity of dyspnea during methacholine-induced bronchoconstriction and dynamic hyperinflation was not altered by extensive chest wall deafferentation.

Adult↗

PubMed2004

Dual tachykinin NK1/NK2 antagonist DNK333 inhibits neurokinin A-induced bronchoconstriction in asthma patients.

Inhalation of neurokinin A (NKA) causes bronchoconstriction in patients with asthma. In vitro both tachykinin NK1 and NK2 receptors can mediate airway contraction. In this study the authors examined the effects of a single dose of the dual tachykinin NK1/NK2 receptor antagonist, DNK333, on NKA-induced bronchoconstriction in asthma. A total of 19 male adults with mild asthma completed a randomised, double-blind, placebo-controlled crossover trial. Increasing concentrations of NKA (3.3x10(-9) to 1.0x10(-6) mol x mLP(-1)) were inhaled at 1 and 10 h intervals after a single oral dosing with either DNK333 (100 mg) or a placebo. It was observed that DNK333 did not affect baseline lung function but did protect against NKA-induced bronchoconstriction in those patients. The mean log10 provocative concentration causing a 20% fall in forced expiratory volume in one second for NKA was -5.6 log10 mol x mL(-1) at 1 h after DNK333 treatment and -6.8 log10 mol x mL(-1) after placebo. This was equivalent to a difference of 4.08 doubling doses, which decreased to a difference of 0.90 doubling doses 10 h after treatment. The results shown in this report indicate that DNK333 blocks neurokinin A-induced bronchoconstriction in patients with asthma.

Administration, Inhalation↗

PubMed1995

Facial cooling, but not nasal breathing of cold air, induces bronchoconstriction: a study in asthmatic and healthy subjects.

Reflex-mediated bronchoconstriction in cold climates may be more important than it has previously been thought. This issue has seldom been studied using physiological methods. We wanted to investigate, using physiological methods, what triggers the bronchoconstriction occurring at cold ambient temperature during resting nasal ventilation: cooling of the skin of the face or cooling of the nasal cavity. Three experiments were carried out in 15 stable asthmatics and 10 healthy volunteers: 1) a whole-body exposure to subfreezing temperature in an environmental chamber, during which the subjects breathed cold air through the nose; 2) a similar exposure to subfreezing temperature except that the subjects now breathed warm air through the mouth from outside the chamber; and 3) nasal breathing of subfreezing air from a heat exchanger whilst the subjects sat at room temperature. Spirometric values and facial skin temperature were measured both during and after the exposures. Maximal decrements (means +/- standard errors) of forced expiratory volume in one second (FEV1) in experiments 1, 2 and 3 were: 5.8 +/- 0.8, 5.1 +/- 0.7 and 2.1 +/- 0.5%, respectively (p < 0.001). Only the two experiments in the environmental chamber induced significant bronchoconstriction. All responses were of similar magnitude in the asthmatic and the healthy subjects. The cooling of the skin of the face seems to be the trigger for the bronchoconstriction during resting nasal ventilation at cold ambient temperature both in asthmatic and nonasthmatic subjects.

Adult↗

PubMed1996

Role of thromboxane-A2 and cholinergic mechanisms in bronchoconstriction induced by cigarette smoke in guinea-pigs.

Acute exposure to cigarette smoke provokes bronchoconstriction and increases the concentration of thromboxane (Tx) A2 in bronchoalveolar lavage (BAL) fluid. The purpose of this study was to investigate the role of TxA2 and cholinergic mechanisms in the airway response induced by exposure to cigarette smoke in guinea-pigs. Anaesthetized animals were exposed to 200 puffs of smoke for 10 min. The amount of Evans blue dye extravasated into the bronchial tissue was then measured BAL was performed to determine cell counts and the concentration of TxB2, a stable metabolite of TxA2. The effects of pretreatment with a Tx synthase inhibitor, OKY-046 (10 mg.kg-1), and/or atropine (1 mg.kg-1) were evaluated. Exposure to cigarette smoke caused significant bronchoconstriction (284 +/- 33% of baseline pulmonary resistance (RL)) and plasma extravasation (30.0 +/- 3.8 vs 16.8 +/- 2.6 ng.mg-1 of sham control; main bronchi). OKY-046 or atropine significantly inhibited the bronchoconstriction to a similar extent, without affecting the plasma extravasation. Combined use of these compounds had no additive effect. The cigarette smoke caused significant increase in TxB2 (48 +/- 10 vs 14 +/- 1 pg.mL-1 of sham control) in BAL fluid, which was abolished by OKY-046 but not by atropine. The cellularity in BAL fluid was not different among groups. These results suggest that the bronchoconstriction induced by cigarette smoke is partially mediated by thromboxane A2, which is dependent on a cholinergic pathway.

Animals↗

PubMed1991

Effect of tranilast on endothelin-induced bronchoconstriction in guinea pigs.

Tranilast, an anti-asthmatic drug with anti-allergic properties, inhibited endothelin (ET)-induced asthmatic like respiratory obstruction in guinea pigs when administered orally at 200 mg/kg 1 h prior to the intravenous injection of ET. ET also caused a bronchoconstriction detected as an increase in inflation pressure in Konzett-Rössler apparatus. Tranilast (200 mg/kg, p.o. 1 h before ET) inhibited ET-induced increased inflation pressure. ET-induced bronchoconstriction detected as an increase in inflation pressure was clearly inhibited by the administration of indomethacin (used as a reference drug) at doses of 1 and 5 mg/kg 30 min prior to onset of the reaction. In addition to the above in vivo experiments, tranilast at concentrations between 10(-5) and 10(-4) g/ml inhibited ET-induced contraction of isolated guinea pig tracheal muscle, whereas indomethacin did not affect this in vitro response. In order to elucidate the inhibitory mechanism of tranilast on ET-induced bronchoconstriction, the effects in Ca(2+)-free medium and on ET-induced histamine and prostaglandin F2 alpha release from tracheal muscle were investigated. Consequently, tranilast did not affect ET-induced contraction of guinea pig tracheal muscle in Ca(2+)-free Tyrode's solution and ET induced neither histamine nor PGF2 alpha release. These results suggest that tranilast inhibits ET-induced bronchoconstriction by inhibiting the ET-induced calcium influx into tracheal muscle.

Animals↗

PubMed1993

Effects of MKS-492 on antigen-induced bronchoconstriction and allergic reaction in guinea pigs and rats.

Effects of R[+]-8-([1-[3,4-dimethoxyphenyl]-2-hydroxyethyl]amino) -3,7-dihydro-7-[2-methoxyethyl]-1,3-dimethyl-1H-purine-2,6-dione (MKS-492), a reported type III isozyme inhibitor of cyclic nucleotide phosphodiesterase, on antigen- or platelet activating factor (PAF)-induced bronchoconstriction and allergic reactions in guinea pigs and rats were investigated. 1) MKS-492 inhibited antigen-induced bronchoconstriction in guinea pigs. Aminophylline also inhibited the reaction. 2) MKS-492 inhibited PAF-induced bronchoconstriction and inhibited the increase in airway responsiveness to histamine in guinea pigs, although aminophylline failed to affect these reactions. 3) MKS-492 relaxed guinea pig tracheal muscle in vitro more potently than aminophylline. 4) MKS-492 inhibited leukotriene B4 (LTB4)-induced airway eosinophilia in guinea pigs. 5) MKS-492 inhibited passive cutaneous anaphylaxis and mediator-induced skin reactions in rats more potently than aminophylline. Both drugs inhibited antigen- and phospholipase A2-induced histamine release from guinea pig lung tissue. 6) MKS-492 inhibited PAF-induced O2- generation from guinea pig alveolar macrophages. These results indicate that MKS-492 is a more potent inhibitor of allergic bronchoconstriction and PAF- or LTB4-induced inflammatory reactions in guinea pigs and the allergic cutaneous reactions in rats when compared to aminophylline.

Aminophylline↗

PubMed2003

Effects of muscarinic receptor antagonists with or without M2 antagonist activity on cholinergic reflex bronchoconstriction in ovalbumin-sensitized and -challenged mice.

To investigate whether the inhibition of muscarinic M(2) receptors results in the enhancement of reflex bronchoconstriction under airway hyperresponsiveness, we evaluated the effects of muscarinic antagonists with or without M(2) antagonist activity on methacholine (MCh)- and SO(2)-induced airway responses in ovalbumin (OVA)-sensitized and -challenged mice. In this model, similar airway hyperresponsiveness to MCh (12 mg/ml) was observed on Days 31 and 37 (2.2-fold and 2.7-fold, respectively). However, airway hyperresponsiveness to SO(2) (0.05 l/min) on Day 37 was less than that on Day 31 (4.0- and 2.7-fold on Days 31 and 37), indicating reflex bronchoconstriction was enhanced on Day 31 in comparison to Day 37. Ipratropium (0.03 - 0.3 mg/ml, inhalation) and Compound A (0.1 - 3 mg/kg, p.o.) inhibited MCh-induced responses on Days 31 and 37. Although ipratropium (0.03 - 1 mg/ml) dose-dependently inhibited SO(2)-induced responses on Day 31, ipratropium at a dose of 0.1 mg/ml significantly increased SO(2)-induced responses on Day 37 (162.2% of the corresponding control). On the other hand, Compound A (0.03 - 0.3 mg/kg, p.o.) inhibited SO(2)-induced responses without any increases on Days 31 and 37. These results suggest that two different conditions of reflex bronchoconstriction are presented in this model: 1) SO(2)-induced responses are enhanced by dysfunctional M(2) receptors on Day 31; 2) the dysfunctional M(2) receptors are partially restored on Day 37. In addition, the inhibition of the restored M(2) receptors further enhance reflex bronchoconstriction.

Animals↗

PubMed2005

Paradoxical bronchoconstriction with albuterol administered by metered-dose inhaler and nebulizer solution.

OBJECTIVE: To report a case of a patient who experienced bronchoconstriction following both a single dose of albuterol via metered-dose inhaler and a subsequent rechallenge with nebulized albuterol and review previously published case reports of albuterol-induced paradoxical bronchoconstriction. CASE SUMMARY: A 92-year-old white man with a history of chronic obstructive pulmonary disease was prescribed an albuterol inhaler for treatment of cold symptoms. Within 30 minutes of his first inhalation, he became short of breath and had difficulty speaking. During emergency department examination for the initial event, the bronchospasm improved with administration of oxygen 15 L/min via a non-rebreather mask. Two hours later, the patient received albuterol via nebulizer and experienced stridor, shortness of breath, and severe bronchospasm. He was admitted, treated with methylprednisolone, and discharged the following day. DISCUSSION: Paradoxical bronchoconstriction is a rare complication of bronchodilator therapy. Although theories have been proposed about components of albuterol solutions and preservatives as causative agents, the true mechanism of the phenomenon remains unknown. Several previous case reports described bronchospasm with albuterol given via tablet, inhaler, and nebulizer. In 2 of these cases, symptoms recurred upon rechallenge; however, none of these cases demonstrates rechallenge using albuterol as both the index and challenge agent. In our patient, paradoxical bronchoconstriction was considered to be probable according to the Naranjo probability scale. CONCLUSIONS: beta(2)-Agonists are generally well-tolerated medications. However, clinicians should remain vigilant in their monitoring of adverse effects so they will be able to provide immediate care and minimize the chance of an unfavorable outcome.

Administration, Inhalation↗

PubMed1994

Inhibitory effect of a selective thromboxane synthetase inhibitor, OKY-046, on acetaldehyde-induced bronchoconstriction in asthmatic patients.

We recently reported that inhaled acetaldehyde causes bronchoconstriction indirectly via histamine release in patients with asthma. The purpose of this study was to investigate a role of thromboxane A2 in acetaldehyde-induced bronchoconstriction in asthmatic airways. We investigated the bronchial response to inhalation of ascending doses (5, 10, 20, and 40 mg/ml) of acetaldehyde in nine asthmatic subjects who were treated with placebo or OKY-046, a selective thromboxane A2 synthetase inhibitor, of 200 mg twice a day for 3 days, and 200 mg on the fourth day (test day) in a double-blind, randomized, placebo-controlled, crossover fashion. Percentage decreases in FEV1 caused by 20 and 40 mg/ml of acetaldehyde inhalation were significantly (p < 0.05 and p < 0.01, respectively) prevented by the pretreatment with OKY-046. Geometric mean value (geometric standard error of the mean) of acetaldehyde concentration producing a 20 percent fall in FEV1 (PC20-Ac-CHO) was significantly (p < 0.01) greater with the OKY-046 pretreatment (72.2 [1.1] mg/ml) than with the placebo pretreatment (19.8 [1.2] mg/ml). We conclude that thromboxane A2 is one of contributors to acetaldehyde-induced bronchoconstriction in asthmatic subjects. It suggests that thromboxane A2 may play an important role in endogenous histamine-induced bronchoconstriction caused by acetaldehyde in asthmatic airways. We believe that this is a first report on the interaction between endogenous histamine and thromboxane A2 in asthmatic subjects.

Acetaldehyde↗

PubMed1998

Influence of beclomethasone and salmeterol on the perception of methacholine-induced bronchoconstriction.

BACKGROUND: Patient evaluation of asthma severity and medication needs is mostly based on respiratory symptoms and may be influenced by changes in perception of bronchoconstriction-induced sensations. However, the influence of asthma medication on the ability to perceive symptoms is still to be documented. This study evaluated the effects of short-term and regular use of salmeterol on the perception of methacholine-induced bronchoconstriction (MIB) in subjects with mild asthma, using inhaled salbutamol on an "as required" basis (n=15), and in subjects with moderate asthma, using daily inhaled beclomethasone (mean daily dose, 640 microg; n=15) in addition to salbutamol to control their asthma. METHODS: Methacholine challenges (MC) were performed at entry into the study, and then before, 1, and 12 h following inhalation of 50 microg of salmeterol or a placebo, after a 15-day baseline period; and after 4 weeks of twice daily use of those treatments. The measurements were then repeated with the alternate treatment after a 15-day washout period. Finally, a last MC was performed after another 15-day washout period. For each MC, the perception score of bronchoconstriction-associated breathlessness at 20% fall in FEV1 (PS20) was evaluated on a modified Borg scale from 0 to 10. RESULTS: Subjects using regular beclomethasone had a higher baseline PS20 than those using only salbutamol (means: 3.06 0.06 and 2.01+/-0.07, p=0.0001). Short- and long-term use of salmeterol did not change significantly the PS20 compared with placebo (p>0.05) in either group (with or without corticosteroid). Although there were some intraindividual variations, mean PS20 did not vary significantly throughout the study. CONCLUSION: These observations show that the perception of bronchoconstriction-associated breathlessness is not influenced by regular use of salmeterol. Patients using inhaled corticosteroids show a greater perception of MIB.

Administration, Inhalation↗

PubMedDate not supplied

Recovery from bronchoconstriction and bronchodilator tolerance.

Until recently, researchers believed that tolerance or tachyphylaxis to the bronchodilator effects of beta-agonists did not occur. However, recent studies examining the recovery from bronchoconstriction have clearly shown that an impaired response to beta-agonists occurs in patients who have been using regular beta-agonist treatment. This tolerance develops with both long- and short-acting beta-agonists and is not affected by treatment with inhaled steroids. It develops rapidly, reaching a maximum within 1 wk of starting beta-agonists, and has been demonstrated after methacholine, hypertonic saline, mannitol, and exercise-induced bronchoconstriction. The observed reduction in the bronchodilator response is proportional to the severity of bronchoconstriction. Therefore, although individuals with stable asthma show little evidence of tolerance, those with severe bronchospasm have a markedly reduced bronchodilator response to beta-agonists. Almost all asthmatics show evidence of tolerance when tested in the setting of bronchoconstriction, although the extent of this tolerance varies. The reasons for this interindividual variation are not understood. Bronchodilator tolerance is difficult to study in the clinical setting because nearly every patient has used multiple doses of beta-agonist before seeking medical attention. However, there is compelling evidence that the response to rescue beta-agonist treatment is reduced in those who use regular long- or short-acting beta-agonists. The extent to which this phenomenon contributes to asthma morbidity and mortality remains to be determined.

Bronchoconstriction↗

PubMed1997

Comparison between peak expiratory flow and forced expiratory volume in one second (FEV1) during bronchoconstriction induced by different stimuli.

To evaluate the sensitivity of peak expiratory flow (PEF), obtained by portable peak flow meter, in detecting mild changes in airway caliber as assessed by forced expiratory volume in 1 sec (FEV1), we studied 184 subjects who underwent different bronchial challenge tests for suspected bronchial asthma. We measured FEV1 and PEF during bronchoconstriction induced by different stimuli: allergen, methacholine, toluene diisocyanate vapors, exercise, or distilled water inhalation; a total of 186 tests were examined. Before and at different times after challenge, FEV1 was measured, and immediately after, PEF was obtained by Mini-Wright or Assess Peak Flow Meter; each time FEV1 and PEF were taken as the best of three satisfactory tracings. The median FEV1 change from baseline value of all steps in the different challenge tests was 7.5% (range: 0-66%). The correlation coefficients between FEV1 and PEF percent changes in different challenge tests were low (Spearman's p: 0.27-0.69), with high scattering of the data. The concordance between classes of percent changes in FEV1 and PEF was also low (Cohen's weighted kappa: 0.28-0.42). In subjects with a FEV1 fall > 15% after challenge, the median PEF change after bronchoconstriction was lower than the corresponding FEV1 change [17% (0-52) vs. 27% (17-66)]. When different cutoff limits of PEF percent change were considered, the sensitivity of PEF to detect a significant change in FEV1 (15 or 20% change) during bronchoconstriction was low; specificity was in general higher than sensitivity. We conclude that PEF and FEV1 changes are poorly related during mild bronchoconstriction induced by different stimuli. The low sensitivity of PEF to detect mild changes in airway caliber may represent a limit in the use of PEF in the day-to-day monitoring of asthma.

Allergens↗

PubMed2000

Oral montelukast compared with inhaled salmeterol to prevent exercise-induced bronchoconstriction. A randomized, double-blind trial. Exercise Study Group.

BACKGROUND: Montelukast, an oral, once-daily leukotriene receptor antagonist, provides protection against exercise-induced bronchoconstriction. OBJECTIVE: To evaluate the effect of 8 weeks of therapy with salmeterol aerosol or montelukast on exercise-induced bronchoconstriction in adults with asthma. DESIGN: 8-week multicenter, randomized, double-blind study. SETTING: 17 asthma treatment centers in the United States. PATIENTS: 191 adults with asthma who had documented exercise-induced bronchoconstriction. INTERVENTION: Qualified patients were randomly assigned to double-blind treatment with montelukast (10 mg once in the evening) or salmeterol (50 microg [2 puffs] twice daily). MEASUREMENTS: Changes in pre-exercise and postexercise challenge values; percentage inhibition in the maximal percentage decrease in FEV1; the area above the FEV1-time curve; and time to recovery of FEV1 at days 1 to 3, week 4, and week 8 of treatment. RESULTS: By day 3, similar and statistically significant reductions in maximal percentage decrease in FEV1 were seen with both therapies. Sustained improvement occurred in the montelukast group at weeks 4 and 8; at these time points, the bronchoprotective effect of salmeterol decreased significantly. At week 8, the percentage inhibition in the maximal percentage decrease in FEV1 was 57.2% in the montelukast group and 33.0% in the salmeterol group (P = 0.002). By week 8, 67% of patients receiving montelukast and 46% of patients receiving salmeterol had a maximal percentage decrease in FEV1 of less than 20%. CONCLUSIONS: The bronchoprotective effect of montelukast was maintained throughout 8 weeks of study. In contrast, significant loss of bronchoprotection at weeks 4 and 8 was seen with salmeterol. Long-term administration of montelukast provided consistent inhibition of exercise-induced bronchoconstriction at the end of the 8-week dosing interval without tolerance.

Acetates↗