Electromyographic monitoring of respiratory muscle activity in dyspneic infants and toddlers

The aim of this study was to investigate whether the changes that occurred in the clinical asthma score (CAS) correlated with the changes in the respiratory electromyographic (EMG) activity over the days during admission to hospital in dyspneic infants and toddlers. Sixteen infants and toddlers (9 males) were studied during admission and 7 days after discharge. The CAS was used to assess the severity of dyspnea and consists of five items: respiration rate, wheezing, retractions, observed dyspnea, and inspiration-to-expiration ratio. Each item was scaled 0, 1, or 2, with a maximum score of 10. Electrical activity from the diaphragm (di) and intercostal muscles (int) was derived from surface electrodes. The logarithm of the EMG-Activity-Ratio (log EMGAR; ratio of mean peak-to-bottom EMG activity during admission to the hospital, to that at baseline, 7 days after discharge) was used as EMG parameter. For assessing the association between the repeated observations of the CAS and the EMG measurements we used the quantity r2 obtained with analysis of covariance. On the day of admission the patients had a mean CAS of 5.9 +/- 1.2. On the day of discharge the mean CAS decreased significantly to 2.1 +/- 1.6, indicating that the CAS returned to normal values. In line with this observation, a significant decrease in the log EMGARdi and log EMGARint was observed during the stay in the hospital. Over all subjects the correlation coefficient (r) of log EMGARdi versus CAS was 0.71, log EMGARint versus CAS was 0.67, and the mean log EMGAR versus CAS was 0.75 (p < 0.01, for all values). The correlation coefficients of subjects of < or = 1 year seemed to be lower than those of subjects of > 1 year of age (p < 0.01) and female subjects showed higher correlation coefficients than males. This study showed a moderate, but significant, relationship between the changes that occurred in the CAS and the changes in respiratory EMG activity during admission to hospital in dyspneic infants and toddlers. Moreover, the correlation coefficients of the combined leads of the intercostals and diaphragm (mean log EMGAR) were higher than those of the separate leads. The EMG measurements would extend diagnostic possibilities and would provide an objective measure to evaluate the clinical course of the disease and the efficacy of therapy in infants and toddlers with recurrent wheezing disorders.     

Effect of salbutamol on respiratory muscle function and ventilation in awake canines

The effect of the beta-agonist bronchodilator salbutamol on respiratory muscles and ventilation is uncertain. The presence of beta2 receptors on skeletal muscles and increased diaphragm contractility in vitro with salbutamol predict a significant effect that has not been confirmed, in vivo in non-fatigued diaphragm or in clinical studies using standard bronchodilator dosages. Therefore, we infused salbutamol at a higher dosage (23.3 microg/min) used clinically for treatment of respiratory emergencies, while measuring directly the length, shortening and EMG activation of costal and crural diaphragm, parasternal intercostal and transversus abdominis muscles, in 10 awake canines. At this salbutamol dosage, ventilation and tidal volume increased significantly during both resting and CO2-stimulated breathing. Salbutamol elicited significant increases in respiratory muscle shortening with much smaller increases in EMG activity, so the proportionally greater muscle shortening per unit EMG showed increased muscle contractility. The effects of salbutamol were not extinguished by inspiratory flow resistance or fluid challenge but were reversed specifically by the beta-blocker, propranolol. This study demonstrates that, in sufficient intravenous dosage, the beta-agonist salbutamol elicits increased ventilation and a beta2 receptor-mediated increase in contractility of respiratory muscles.     

Effect of beclomethasone increment on airflow limitation in asthmatic children treated with high dose beclomethasone]

In order to evaluate the effect of higher dose BDP therapy (1200-1660 micrograms/day), we studied 12 asthmatic children (mean age 9.7 years-old) with airflow limitation on respiratory function test who were asymptomatic with high-dose BDP therapy (800 micrograms/day). After 4 weeks of higher dose BDP therapy, FVC, FEV1 and V50 were significantly improved, but those improvement were insufficient compared with those after salbutamol inhalation. The personal best values after salbutamol inhalation were not different in every parameter of respiratory function test between BDP 800 micrograms/day and 1200 micrograms/day. We conclude that less than 800 micrograms of daily BDP is generally adequate for prevention in most asthmatic children, because higher dose BDP therapy is no more effective on respiratory function in those treated with 800 micrograms of daily BDP, and that the best value of respiratory function after salbutamol inhalation is not always a goal of high dose BDP therapy.     

Inhaled verapamil in histamine-induced bronchoconstriction

Fifteen asthmatic subjects participated in a double-blind trial comparing the protective effects of inhaled verapamil, salbutamol, and saline against inhaled histamine. Inhaling verapamil between four repeated histamine inhalation tests produced no significant protection against histamine-induced bronchoconstriction, while there was significant protection with salbutamol (p < 0.001). Inhaling verapamil before a single inhalation test produced limited but significant protection (p < 0.05) compared with a saline control in eight asthmatic subjects. This small protective effect in the two-treatment study of eight asthmatics suggests that either the protective effect of verapamil is variable among subjects or a preceding histamine inhalation test blocks the verapamil effect.     

Histamine-induced asthma in children: effects on the ventilation-perfusion relationship

Asthma was provoked by histamine inhalation in five children in order to study the hypoxaemia that might ensue and the underlying ventilation-perfusion (VA/Q) mismatching. The distribution of the VA/Q ratios was measured by a multiple inert gas technique before the provocation, during the asthmatic attack and after salbutamol inhalation. All children displayed a unimodal distribution of ventilation and perfusion under baseline conditions. During asthma they all developed a bimodal distribution, one mode lying within normal VA/Q regions but with increased perfusion to regions with VA/Q ratios of 0.1-1, which correlated with the observed hypoxaemia; the other mode was centered on a VA/Q ratio of approximately 10 and the magnitude of this mode correlated with FEV1 in percent of the predicted value. Salbutamol improved the VA/Q distribution and restored the blood gases to normal. We hypothesize that histamine-induced asthma causes a state of hyperinflation which compromises regional ventilation and blood flow, resulting in a VA/Q mismatching with one normal and one high VA/Q mode, and hypoxaemia.     

Utility of relating pulmonary airflow measures to total lung capacity

Among healthy never-smokers, forced expiratory volume in one second (FEV1) and maximal voluntary ventilation (40 breaths per minute, MVV40) divided by total lung capacity (TLC) showed less interindividual variability than FEV1 and MVV40, whereas the interindividual variability of other flow variables increased after division by TLC. FEV1, MVV40 and peak expiratory flow (PEF) divided by TLC had higher Student's t-values than FEV1, MVV40 or PEF in comparisons between 224 smokers and 232 never-smokers or between 137 asthmatic patients and 456 reference subjects. Thus these airflow variables corrected for lung size appear to be generally useful indicators of airflow limitation. In these comparisons, the variables were adjusted for body size. All t-test comparisons were based on an equal number of tests. Forced expiratory flow at 70% of TLC (MEF70%TLC) and the area of the expiratory part of the flow-volume curve had the highest t-values when comparing airflow before and after bronchodilatation in 70 asthmatic subjects, except in subjects with more advanced bronchoconstriction in whom MVV40 ranked highest. For the computation of MEF70%TLC, measured TLC could be substituted with predicted TLC with little loss of discriminatory capacity. Reference equations for forced expiratory flow at different TLC fractions and for FEV1/TLC are given.     

Separate and combined effects of corticosteroids and bronchodilators on airflow obstruction and airway hyperresponsiveness in asthma.

We have investigated separate and interactive effects of corticosteroids and bronchodilators on airflow obstruction and airway hyperresponsiveness. Twelve allergic subjects with asthma were treated in a double-blind, crossover, randomized study with budesonide, 1.6 mg daily for 3 weeks, prednisone, 40 mg daily, for 8 days, and placebo. After each period, dose-response curves were measured on 4 study days with doubling doses of salbutamol, ipratropium, a combination of salbutamol and ipratropium, and placebo until a plateau in FEV1 was reached. A histamine challenge was then performed, and the provocation concentration causing a 20% fall in FEV1 (PC20) was calculated. The budesonide and prednisone regimens were equipotent. FEV1 was 81.2% of predicted after budesonide, 81.0% predicted after prednisone, and 67.5% predicted after placebo, bronchodilatation thus being 13.7% predicted (budesonide) and 13.5% predicted (prednisone). PC20 improved with 2.17 doubling concentrations (DCs) after budesonide, and 1.86 DCs after prednisone, compared with that of placebo. Salbutamol caused stronger bronchodilatation than ipratropium (26.2% versus 14.7% predicted) and a better protection against histamine challenge (3.95 versus 1.12 DC). The effects of corticosteroids and bronchodilators on FEV1 and PC20 were, in general, additive. This study emphasizes different modes of action on both airflow obstruction and airway hyperresponsiveness by corticosteroids and bronchodilators, and it demonstrates no enhancement of bronchodilator action by corticosteroids.     

Further studies on the mechanism of human histamine-induced asthma : The effect of an aerosolized H1 receptor antagonist (diphenhydramine)

This study was designed to better define the mechanism of histamine-induced bronchoconstriction in humans by pharmacologic manipulation of the postulated bronchial histamine receptor sites. Histamine challenges were performed on a heterogeneous group of adult asthmatic subjects. The cumulative units of histamine required for induction of a sustained 20% or greater decrease in FEV1 from baseline were determined. The effect of pretreatment with an aerosolized H1 receptor antagonist, diphenhydramine hydrochloride, was then studied. Analysis of the data showed that the administration of an H1 receptor antagonist prior to histamine challenge significantly blocked the bronchial response to histamine (p less than 0.005). This effect was considered to be due to specific competitive antagonism at the H1 receptor site and suggests the presence of H1 receptors in human bronchial mucosa.     

A comparison of the actions of H1 and H2 antihistamines on histamine-induced bronchoconstriction and cutaneous wheal response in asthmatic patients

The effect of an H1 antihistamine, an H2 antihistamine, and the combination of the two drugs on both histamine-induced bronchoconstriction and dermal whealing was examined in five patients with mild asthma. Chlorpheniramine 8 mg, cimetidine 300 mg, the combination of both, and placebo were administered orally to each patient for a single dose and for seven consecutive doses given every 6 hr after a double-blind, randomized protocol. The airway response to inhaled histamine and the wheal size induced by the intradermal injection of histamine were determined in every patient 2 hr after the final drug dose. The results indicate that a single dose of chlorpheniramine produces a significant increase in the threshold of histamine-induced bronchoconstriction as measured by the provocative histamine dose producing 20% decrease in 1-sec forced expiratory volume (PD20-FEV1), and this effect was significantly enhanced after seven doses. Cimetidine caused a significant decrease in the threshold of histamine-induced bronchoconstriction, but this was not augmented by seven doses. Only chlorpheniramine, when given for seven doses, improved the baseline FEV1 and forced expiratory flow during middle half of forced vital capacity (FEF25%-75%). Chlorpheniramine in both single and multiple doses and the combination of chlorpheniramine and cimetidine given for seven doses produced a significant inhibition of histamine-induced dermal wheals, whereas cimetidine alone had no effect. These results confirm our previous observation that both H1 and H2 receptors are present in the airways of asthmatic patients and that they mediate opposite effects. We also demonstrated a cumulative effect with the repeated administration of chlorpheniramine but not with cimetidine. Finally, the results suggest that the role of H1 and H2 receptors differs in the bronchi from that seen in the dermal vessels of asthmatic patients and are in contrast to those of normals. The H2 receptor effect on histamine-induced skin wheals appears deficient, further supporting earlier suggestions of the presence of an H2 receptor defect in asthmatic patients.     

Longitudinal changes in airflow limitation and airway hyperresponsiveness in patients with stable asthma.

BACKGROUND: There are few long-term studies of the effects of treatment on the natural course of asthma. OBJECTIVE: To investigate the longitudinal changes in airflow limitation and airway hyperresponsiveness (AHR) in asthma. METHODS: We recruited 81 outpatients (never smokers) with stable asthma from the Kyoto University Hospital. They were evaluated for pulmonary function and AHR, expressed by forced expiratory volume in 1 second (FEV1) and the provocation dose that caused a 20% fall in FEV1 (PD20-FEV1), respectively, at entry and every 6 months over 3 years. We used random effects models to estimate the slopes of these changes, and then evaluated the relationship between these changes and their predictive factors. RESULTS: Using random effects models, the percentage of the predicted FEV1 (%FEV1) declined significantly but slightly at a mean rate of 0.5%/year (P = 0.002; 95% confidence interval, 0.3 to 0.8). The mean decline rate of FEV1 was 34 mL/year. However, Log(PD20-FEV1) showed significant improvement at a mean rate of 0.088 cumulative units/year (P < 0.001; 95% confidence interval, 0.053 to 0.122). Multiple regression analysis showed that the baseline values of %FEV1 and Log(PD20-FEV1) were the most significant predictive factors for their subsequent changes, respectively. CONCLUSIONS: In stable asthmatic patients treated according to international guidelines, airflow limitation progressed at a nearly normal rate over 3 years. However, AHR continued to improve despite its ceiling effects. Multiple regression analysis revealed a significant negative relationship between the initial values and the subsequent changes in airflow limitation and AHR, respectively.     

Bronchial hyperreactivity to histamine and methacholine in asthmatic children after inhalation of SCH 1000 and chlorpheniramine maleate.

Nine asthmatic patients with a mean age of 14 yr received bronchial challenges with histamine and methacholine. The challenges were repeated after inhalation of 80 microgram of SCH 1000 (ipratropium bromide) and 5 mg of chlorpheniramine maleate. The provocation doses which produced a 20% fall in forced expiratory volume in 1 sec (FEV1) and the slopes of the dose-response curves were analyzed. SCH 1000 prevented methacholine-induced bronchoconstriction and chlorpheniramine prevented methacholine-induced bronchoconstriction. There was no significant change in the dose-response curve of histamine after SCH 1000 or in the dose-response curve of methacholine after chlorpheniramine. The findings indicate that the mechanisms and receptor sites involved in bronchial provocation by histamine and methacholine are distinctly different. The histamine response is unlikely to be vagally mediated because histamine-induced bronchoconstriction was not prevented by SCH 1000. Both SCH 1000 and chlorpheniramine caused significant bronchodilatation, suggesting the presence of both histamine- and vagal-dependent bronchomotor tone.     

Mechanism of ethanol-induced bronchoconstriction in Japanese asthmatic patients]

Acute ingestion of alcoholic beverages causes no changes in the expiratory airflow rates of most Occidental asthmatic patients. However, asthmatic symptoms are worsened after drinking small amounts of alcohol in Japanese asthmatic patients. Our laboratory results showed that the ingestion of pure ethanol caused a fall in FEV1.0 in about half of the Japanese asthmatic patients tested. The mechanism of ethanol-induced bronchoconstriction remains unclear. In order to investigate this mechanism, we performed oral-provocation tests with 10% ethanol in vivo, and leukocyte histamine release assay induced by ethanol and acetaldehyde in vitro. 55% of asthmatics showed a significant fall in FEV1.0 after ingestion of 10% ethanol (responder). There was no difference in the rise of blood ethanol concentration between the responder group and non-responder group. Acetaldehyde and histamine concentration in the responder group were significantly higher than in the non-responder group. Leukocyte histamine release assay showed that acetaldehyde (2 microM-100 microM) caused dose-dependent histamine release, whereas, ethanol (2 mM-100 mM) had no effect on histamine release. Our data indicate that histamine release from mast cells (or basophils) caused by acetaldehyde may play an important role in ethanol-induced bronchoconstriction. This is the first report on the mechanism of ethanol-induced bronchoconstriction in Japanese asthmatic patients.     

Expiratory activity of the inspiratory muscles during cough.

To investigate the neural mechanism of the expiratory activity of the inspiratory muscles during a cough, EMG of the respiratory muscles were recorded in anesthetized and tracheostomized dogs. A laparoscope was used to minimize injury to the abdominal muscles for implantation of the electrodes into the costal diaphragm. During the expulsive phase of a cough, the diaphragm was active in 7 of 12 dogs and the external intercostal muscle was active in 3 of 6 dogs. During a cough, the expiratory activity of the diaphragm, after the termination of its inspiratory activity, started at 52.9 +/- 24.6 ms, and that of external intercostal muscle started at 51.1 +/- 20.5 ms. The expiratory activity of the internal intercostal muscle and of the transversus abdominis started at 34.3 +/- 13.0 and 27.8 +/- 15.2 ms, respectively. The onset of expiratory activity of the inspiratory muscles is significantly later than that of expiratory muscles. Continuous activity in the expiratory muscles evoked by airway occlusion, i.e., Hering-Breuer reflex, was suppressed during the inspiratory phase of a cough, but not suppressed during the expulsive phase even when the expiratory activity of the diaphragm was observed. We concluded that the expiratory activity of inspiratory muscles is controlled independently of both expiratory activity of the expiratory muscles and inspiratory activity of the inspiratory muscles.     

Role of the diaphragm in trunk rotation in humans

The objectives of the present study were to test the hypothesis that the costal diaphragm contracts during ipsilateral rotation of the trunk and that such trunk rotation increases the motor output of the muscle during inspiration. Monopolar electrodes were inserted in the right costal hemidiaphragm in six subjects, and electromyographic (EMG) recordings were made during isometric rotation efforts of the trunk to the right ("ipsilateral rotation") and to the left ("contralateral rotation"). EMG activity was simultaneously recorded from the parasternal intercostal muscles on the right side. The parasternal intercostals were consistently active during ipsilateral rotation but silent during contralateral rotation. In contrast, the diaphragm was silent in the majority of rotations in either direction, and whenever diaphragm activity was recorded, it involved very few motor units. In addition, whereas parasternal inspiratory activity substantially increased during ipsilateral rotation and decreased during contralateral rotation, inspiratory activity in the diaphragm was essentially unaltered and the discharge frequency of single motor units in the muscle remained at 13-14 Hz in the different postures. It is concluded that 1) the diaphragm makes no significant contribution to trunk rotation and 2) even though the diaphragm and parasternal intercostals contract in a coordinated manner during resting breathing, the inspiratory output of the two muscles is affected differently by voluntary drive during trunk rotation.     

Analysis of growth factors and inflammatory cytokines in exhaled breath condensate from asthmatic children

BACKGROUND: Vascular endothelial growth factor (VEGF), AA isoform of platelet-derived growth factor (PDGF-AA), and epidermal growth factor (EGF) are involved in the pathogenesis of airway inflammation in asthma. These molecules are closely associated with cytokines such as tumor necrosis factor-alpha (TNF-alpha) and interleukin (IL)-4. This study investigates the relation between childhood asthma and levels of these mediators in exhaled breath condensate (EBC). METHODS: EBC was collected from asthmatic children and controls using a disposable collection kit, and the concentrations of VEGF, PDGF-AA, EGF, TNF-alpha and IL-4 in EBC were measured using sandwich enzyme immunoassays. Exhaled nitric oxide concentration was measured by a chemiluminescence analyzer. RESULTS: Thirty-five asthmatic patients aged between 7 and 18 years and 11 controls were recruited. Sixteen patients had intermittent asthma (IA) whereas 19 of them suffered from persistent asthma (PA). A significant correlation was found between IL-4 and TNF-alpha in EBC (rho = 0.374, p = 0.010). PDGF-AA levels in EBC were higher in subjects with diminished FEV1 (p = 0.023) whereas IL-4 concentrations were increased in asthmatics (p = 0.007) as well as subjects with increased plasma total IgE (p = 0.033). Patients with PA receiving high-dose inhaled corticosteroid (ICS) had higher EBC IL-4 concentration than those on low-dose ICS (p = 0.007). Linear regression revealed that PDGF-AA levels in EBC were negatively associated with FEV1 percentage (beta = -0.459, p = 0.006) among the asthmatic patients. CONCLUSIONS: IL-4 in EBC is increased in childhood asthma, and growth factors are detectable in a significant proportion of these children. Increased PDGF-AA is found in asthmatics with more severe airflow limitation.     

Late asthmatic reactions and changes in histamine responsiveness provoked by occupational agents

The temporal and quantitative relationship between increases in airway responsiveness and late asthmatic reactions provoked by inhalation challenge with occupational agents was studied in nine individuals who underwent a total of thirteen active inhalation challenge tests with one of the following agents: toluene diisocyanate (TDI), maleic anhydride (MA), trimellitic anhydride (TMA), carmine, or colophony (pine wood resin). Airway responsiveness to inhaled histamine (histamine PC20) was measured before and at approximately 3 and 24 h after control and active challenge exposure, when, on all but four occasions, FEV1 was within 10% of pre-challenge values. Significant increases (p less than 0.02) in histamine responsiveness were present at 3 h following challenge exposures which subsequently provoked a definite late asthmatic reaction (FEV1 decrease greater than 15% 3-11 h post challenge). These increases in histamine responsiveness were significantly greater than those at 3 h following the challenges which provoked an isolated early (FEV1 decrease less than 6% 3-11 h post-challenge) or equivocal late asthmatic reaction (FEV1 decrease 6-15% 3-11 h post-challenge) (p less than 0.03). Although histamine responsiveness remained high at 24 h after challenges provoking late asthmatic reactions (p less than 0.05), this was less than the increase at 3 h and not significantly different from the PC20 at 24 h after challenges provoking either single early or equivocal late asthmatic reactions.(ABSTRACT TRUNCATED AT 250 WORDS)     

Inhibitory effects of azelastine hydrochloride in alcohol-induced asthma.

BACKGROUND: Alcohol-induced bronchoconstriction is due to high blood concentrations of acetaldehyde, a metabolic product of ethanol, which lead to the release of histamine from basophils and mast cells. OBJECTIVE: We examined the inhibitory effects of azelastine hydrochloride, which inhibits histamine release and blocks H1 receptors, in alcohol-induced asthma. METHODS: Subjects were 13 Japanese asthmatic patients. We measured the change in FEV1 after ingestion of 30 g of pure ethanol. Blood ethanol, acetaldehyde, histamine, leukotriene C4 (LTC4), and thromboxane B2 (TXB2) concentrations were also measured. Alcohol challenge test was repeated in responders after administration of azelastine for 1 week at 4 mg/day. RESULTS: Of 13 asthmatic patients, five (38.5%) tested positive during an ethanol challenge test, represented by a fall more than 20% in FEV1. The responders had a high blood ethanol, and showed a rise in blood acetaldehyde and histamine concentrations, but not in LTC4 or TXB2. After azelastine treatment, there was no significant fall in FEV1 among responders. Neither the rise in blood ethanol nor blood acetaldehyde levels were blunted by treatment with azelastine, but the rise in blood histamine was blunted by this treatment. CONCLUSION: Our results suggest that antihistamine agents may be effective against alcohol-induced asthma by both blocking H1 receptors and inhibiting histamine release.     

Tolerance to the bronchoprotective effect of beta2-agonists: comparison of the enantiomers of salbutamol with racemic salbutamol and placebo.

BACKGROUND: Regular use of racemic salbutamol results in the partial loss of its bronchoprotective effect. The 2 enantiomers of salbutamol, the bronchodilator R-salbutamol and nonbronchodilator S-salbutamol, are now available. OBJECTIVE: We sought to compare the effect of regular use of S-salbutamol, R-salbutamol, racemic salbutamol, and placebo on the bronchoprotective effect of a single dose of racemic salbutamol against methacholine-induced bronchoconstriction. METHODS: Eleven of 13 well-controlled beta2 -agonist-free asthmatic subjects completed a double-blind, randomized study comparing racemic salbutamol 2.5 mg, S-salbutamol 1. 25 mg, R-salbutamol 1.25 mg, and diluent placebo nebulized and inhaled 3 times daily for 6 days (>/=6-day washout period). Ten to 12 hours after the last dose, the subjects performed measurement of FEV1, methacholine PC20, and a repeat methacholine PC20 done 1 hour after the first methacholine test and 10 minutes after 2 puffs (200 microgram) of racemic salbutamol administered from a metered-dose inhaler. The primary endpoint was the methacholine PC20 dose shift (Deltalog PC20/log 2) from before to after administration of 200 microgram of racemic salbutamol. RESULTS: The methacholine dose shift was 3.2 doubling doses (9-fold increase in methacholine PC20 after 200 microgram of racemic salbutamol) during the placebo treatment and was unaltered (3.2) after administration of S-salbutamol. The dose shift was significantly lower after both the R-salbutamol and racemic salbutamol treatments (2.2 and 2.6 doubling doses, respectively); there was no significant difference between R-salbutamol and racemic salbutamol. There was no treatment effect on baseline FEV1, baseline methacholine PC20, or bronchodilation. CONCLUSION: Regular treatment with racemic salbutamol or R-salbutamol, but not S-salbutamol, results in a partial loss of bronchoprotection, without loss of bronchodilation, compared with placebo.     

Perception of dyspnea during exacerbation and histamine-related bronchoconstriction in patients with asthma.

BACKGROUND: Numerous studies have been performed concerning the perception of dyspnea during changes in airway caliber provoked in the laboratory setting, but studies of asthma exacerbation are scarce. OBJECTIVE: To investigate whether the perception of dyspnea during histamine-induced bronchoconstriction might be used to identify patients with asthma who sense dyspnea poorly during exacerbation. METHODS: The perception of dyspnea in 50 patients (45 female, 5 male) with asthma was evaluated at admission with exacerbation and during a stable period. Perceived intensity of dyspnea was estimated using a modified Borg scale. The perception of dyspnea in the stable period 4 to 6 weeks after exacerbation was measured with the histamine challenge test. Perception parameters were defined as the change in Borg score divided by the change in forced expiratory volume in 1 second (FEV1) as a percentage of the baseline FEV1 (deltaBorg/deltaFEV1) and as the Borg score at 20% decrease (PS20Histamine) or increase (PS20Exacerbation) in FEV1. RESULTS: The perception of dyspnea during asthma exacerbation was unrelated to the perception of dyspnea during histamine-induced bronchoconstriction (for deltaBorg/deltaFEV1, beta = .08, P = .50; for PS20, beta = -.11, P = .40). The kappa value for the agreement of poor perceivers at exacerbation and during the stable period was -0.21 (P = .10). However, the intensity of dyspnea caused by histamine-induced bronchoconstriction was lower than that caused by asthma exacerbation (PS20: 1.6 +/- 1.1 vs 2.8 +/- 2.5, respectively, P = .004; deltaBorg/deltaFEV1: 0.08 +/- 0.05 vs 0.21 +/- 0.28, respectively, P = .001). CONCLUSION: The perception of dyspnea during asthma exacerbation is not correlated with the perception of dyspnea during histamine-induced bronchoconstriction. Therefore, the perception of dyspnea during histamine-induced bronchoconstriction cannot be used to identify the asthmatic patients who perceive dyspnea poorly.     

Comparison of the bronchodilator effect of salbutamol between pressure metered dosed inhaler and dry powder inhaler in patients with stable bronchial asthma]

Recently, dry powder inhaler (DPI) was more available than pressure metered dosed inhaler (pMDI) for the inhalation therapy of the respiratory disease. But there are differences in the lung deposition of the drug in these devices. We investigated the bronchodilator effect of salbutamol inhalation with two device, pMDI and Tubuhaler on the stable 8 asthmatic patients. The time course of FEV1 had a no significant difference between two devices. DeltaAUC (=difference between area under the curve for time course of increase in FEV1 via pMDI and via DPI) and Deltamax FEV1 (=difference between maximum increases in FEV1 following inhalation of salbutamol via pMDI and DPI) were defined as the index of difference of bronchodilator effect between the two devices. PMDI was more effective on improving the pulmonary function in subjects with severely decreased FEV1 and FEV1% than DPI. These results may reflect the correlation of inspiratory flow rate and drug deposition. PMDI is still useful on the part of asthmatic patients with decreased pulmonary function.