Is normal bronchial responsiveness in asthmatics a reliable index for withdrawing inhaled corticosteroid treatment?

STUDY OBJECTIVE: Inhaled corticosteroid (ICS) treatment is first-line maintenance therapy in bronchial asthma. However, it is not clear whether and when ICS treatment can be withdrawn. The aim of this open study was to assess whether normalization of bronchial responsiveness could be used as a reliable index to assess the opportunity of ICS treatment withdrawal. DESIGN: Open study at two different points in time. SETTING: Outpatient pulmonary clinic. PATIENTS: Eighteen asthmatic subjects. MEASUREMENTS AND RESULTS: ICS therapy was withdrawn in subjects treated with beclomethasone dipropionate, at the maintenance dose of 889+/-246 microg/d for >3 months. Upon recruitment, all subjects were asymptomatic, had FEV1 >70% of predicted value, and were in treatment with beta2-agonists on an as-needed basis. Eight subjects (group 1) had normal bronchial responsiveness (methacholine provocative dose causing a 20% fall in FEV1 [PD20] >2,000 microg) and 10 subjects (group 2) had bronchial hyperresponsiveness (BHR) (PD20 < or = 2,000 microg). After withdrawal of ICS treatment, subjects were followed up for 3 weeks and were asked to record their asthma symptoms (cough, dyspnea, and wheezing) and their beta2-agonist use. At recruitment and at the end of follow-up, subjects underwent spirometry and a methacholine challenge test. Frequency of asthma exacerbation was similar in subjects with normal bronchial responsiveness (NBR) and in subjects with BHR (50% vs 60%), but subjects with NBR tended to remain asymptomatic for longer than those with BHR (mean+/-SD, 10.7+/-4.4 days vs 5.5+/-3.8 days) (p=0.08). None of the subjects reported any condition that could have triggered exacerbation. Asthma exacerbation was associated with a significant decrease in FEV1 (-105+/-107 mL; p<0.05) and in PD20 (-1,332+/-1,020 microg; p<0.001). CONCLUSIONS: Our study shows that the likelihood of asthma exacerbation is not reduced if ICS treatment is withdrawn when the subjects have NBR, but the exacerbation could be delayed. Further studies in larger populations of asthmatics are needed to confirm these findings.     

Bronchial hyperresponsiveness and toluene diisocyanate. Long-term change in sensitized asthmatic subjects

Long-term change in nonspecific and specific bronchial hyperresponsiveness was studied in 16 subjects with asthma induced by toluene diisocyanate (TDI). A significant positive correlation between months of follow-up and provocative dose inducing a 20 percent fall in FEV1 (PD20FEV1) methacholine was observed in 5 of 16 subjects. In 4 of these 5 subjects, a PD20FEV1 > 1 mg of methacholine was observed 30 to 48 months after the end of TDI exposure. In most subjects, nonspecific bronchial hyperresponsiveness did not change. Nine of 16 subjects became nonresponsive to TDI at follow-up examination, but only 3 of these showed a significant increase in PD20FEV1 methacholine. Seven subjects were still responsive to TDI. Recovery from TDI-induced asthma can occur and only after long-term work cessation. Nonspecific bronchial hyperresponsiveness to methacholine can persist even in the absence of bronchial hyperresponsiveness to TDI, suggesting permanent chronic damage to mechanisms controlling airway tone.     

Evaluation of the inhaled glucocorticosteroid effects on non specific bronchial reactivity with particular reference to the late inflammatory phase in atopic asthma patients. II. The effect of regular administration of budesonide R on specific and non-specific bronchial reactivity

The purpose of the study was to determine whether regular administration of budesonide R decreases inflammation, specific and non-specific bronchial hyperreactivity in allergic asthma patients. The studies were carried out on 16 patients suffering from mild to moderate allergic asthma, sensitive to D. pteronyssinus allergen. After performance of the specific and non-specific bronchial provocation tests, collection of blood samples for an ECP evaluation, the patients were regularly treated with budesonide R, 2 x 320 micrograms for a period of 8 weeks. At the end of the study the BPTs and blood collection were repeated. BPTs with methacholine and D. pteronyssinus were performed according to Ryan's method. After the allergen challenge, early (EAR) and late asthmatic reaction (LAR) were to be observed. After the therapy non-specific BHR to methacholine expressed as PC20FEV1 and specific BHR to allergen (PD20FEV1D. pteronyssinus) and serum ECP concentrations decreased significantly. Although after the treatment with budesonide R, the patients had to inhale much larger amounts of allergen, in order to induce EAR, the number of LAR did not change significantly. After treatment the LAR appeared about 1 hour later and the decrease in FEV1 was less than previously. We conclude that budesonide R decreases the intensity of the inflammation and BHR.     

Bronchial hyperresponsiveness as a predictor of wheezing in a follow-up study of healthy men

We assessed the relationship between bronchial hyperresponsiveness (BHR) and the onset of wheezing 5 years later, by epidemiological analysis of 194 working men without asthma or wheezing at the first examination. In 1985/ 1986 and 1990/1991, subjects answered a British Medical Research Council questionnaire and performed lung function measurements and methacholine challenge tests (total dose 6 mg). BHR was measured in three ways: (1) FEV1 fall > or = 20% (PD20+); (2) the two-point response slope expressed as percentage decline of FEV1/dose, and (3) a four-parameter model: FEV1 at dose (d)/ prechallenge FEV1 = ONE-k(d-delta)+a, where 'k' is the slope of the relative variation of FEV1 with the dose, 'delta' the threshold dose, and 'alpha' a shape factor. In the 13 new wheezers, the mean values of the two-point slope and of k were significantly increased, and the proportion of reactors was almost threefold (the latter was not statistically significant). Among nonsmokers, delta was significantly lower in new wheezers than in the others, whereas the slope and k had similar mean values. Among smokers, new wheezers had increased mean values for the slope and k, and an increased proportion of reactors, whereas delta was not decreased. Thus, BHR was a significant predictor of wheezing, independent of the method of analysis. Moreover, the model distinguished between two components of bronchial response: wheezing was predicted by sensitivity (delta) in nonsmokers, and by reactivity (k) in smokers.     

Bronchodilator response to salbutamol after spontaneous recovery from nonspecific bronchial provocation tests in asthma

Assessment of airway responsiveness by bronchoprovocation and bronchodilatation tests is important in the diagnostic work-up protocol of bronchial asthma and it would be convenient to undertake both tests on the same occasion. However, it is not known whether this can be done accurately. Therefore, this study evaluated the effect of a prior bronchial provocation test on the bronchodilator response to salbutamol after spontaneous recovery of the forced expiratory volume in one second (FEV1) in a group of asthmatic subjects. On two separate occasions at the same time of day, concentration-response studies with inhaled histamine or methacholine, or a sham challenge with normal saline were carried out in a blinded, randomized manner. Changes in airway calibre were followed as FEV1 and agonist responsiveness expressed as the provocative concentration causing a 20% fall in FEV1 (PC20). After either spontaneous recovery or a fixed-duration wait of 45 min (when appropriate), the subjects received 2x100 microg of salbutamol from a metered dose inhaler with a spacer. The bronchodilator response to salbutamol was expressed as a percentage of initial FEV1 (deltaFEV1% init). Bronchial challenge with both agonists failed to alter significantly the airway response to salbutamol, with the deltaFEV1% init mean value (range) being 16.9% (9.0-31.9) and 17.5% (11.6-31.2) on the sham and histamine/methacholine challenge day respectively. It was shown that the degree of bronchodilatation achieved after salbutamol 200 microg is not affected by prior bronchoprovocation testing when enough time is allowed for the airways to recover spontaneously to baseline forced expiratory volume in one second. Thus evaluation of airway responsiveness by both bronchial provocation tests and bronchodilator testing can be assessed reliably within a few hours in asthmatic patients.     

Testing bronchial hyper-responsiveness: provocation or peak expiratory flow variability?

BACKGROUND: Assessing bronchial hyper-responsiveness (BHR) is a main diagnostic criterion of asthma. Provocation testing is not readily available in general practice, but peak expiratory flow (PEF) is. Several guidelines promote the use of PEF variability as a diagnostic tool for BHR. This study tested the agreement between histamine challenge testing and PEF variability, and the consequences for diagnosing asthma. AIM: To investigate the possibility of assessing BHR by PEF variability, using a histamine provocation test as a reference. METHOD: Subjects with signs of symptoms indicating asthma (persistent or recurrent respiratory symptoms or signs of reversible bronchial obstruction) (n = 323) were studied. They had been identified in a population screening for asthma. A histamine provocation test and PEF variability were assessed over a three-week period. Asthma was defined as signs or symptoms together with a reversible airflow obstruction or BHR to the histamine challenge test. BHR was defined as a PC20 histamine of < or = 8 mg/ml or a PEF variability of > or = 15%. Overall correlation between PC20 and PEF variability was calculated using Spearman's rho. Furthermore, a decision tree was constructed to clarify the role of BHR in diagnosing asthma. RESULTS: Thirty-two patients had a reversibility in forced expiratory volume in 1 second (FEV1) of > or = 9% predicted, 131 patients showed a PC20 of < or = 8 and 11 patients had a PEF variability of > or = 15%. Overall correlation was poor at only -0.27 (P < 0.0001). One hundred and fourteen of the 131 patients diagnosed as having asthma when the histamine challenge test was used were not diagnosed by PEF variability. CONCLUSION: PEF variability cannot replace bronchial provocation testing in assessing BHR. This indicates that PEF variability and bronchial provocation do not measure the same aspects of BHR. If BHR testing is required in diagnosing asthma, a bronchial provocation test has to be used in general practice as well.     

Prevalence of bronchial hyper-responsiveness in the southern, central and northern parts of Sweden

Studies have suggested that there is a higher prevalence of asthma in northern Sweden than in southern Sweden. Bronchial hyper-responsiveness (BHR) has been shown to be associated with asthma. The aim of this study was to explore the prevalence of bronchical hyper-responsiveness in different parts of Sweden. As part of the European Community Respiratory Health Survey (ECRHS), interviews, skin prick tests, lung function tests and methacholine provocation tests of the airways were performed in 1448 randomly selected subjects in southern, central and northern Sweden. The Mefar dosimeter was used according to the ECRHS protocol. The responsiveness was calculated both as the PD20 and as the dose response slope (DRS). BHR was defined as a PD20 of < or = 1.6 mg. Atopy was defined as at least one skin prick test of > or = 3 mm. The prevalence of BHR was 12.7%, 10.6% in men and 15.0% in women. No difference in prevalence was found between the three different regions of Sweden. The prevalence of BHR was higher in women than in men and higher in smokers than in non-smokers. Using multiple logistic regression, with BHR as the dependent variable, atopy, being female, having a low FEV1 (% predicted) and smoking (both own and passive) increased the odds of having BHR, while age and the region of Sweden did not influence BHR. Defining BHR as a PD20 of < or = 1.0 mg or a PD20 of < or = 2.0 mg did not change this. Multiple regression using log DRS as the dependent variable produced the same result. Both BHR and increasing DRS were associated with self-reported wheezing, attacks of shortness of breath during the daytime at rest or after strenuous activity, being awakened by a feeling of tightness in the chest or an attack of shortness of breath. In subjects without self-reported asthma, BHR was associated with self-reported wheezing and attacks of shortness of breath after strenuous activity. In conclusion, we found that the prevalence of BHR in the three investigated areas was 12.7%. We found a trend towards a higher prevalence of BHR in the most northerly of the study areas, but the difference between the areas was not statistically significant. BHR and DRS were associated with atopy, smoking, female sex and FEV1 (% predicted). The reporting of symptoms from the airways was associated with the degree of bronchical responsiveness.     

Specific bronchial provocation tests with flour in the diagnosis of occupational bronchial asthma

The gold standard in the diagnosis of occupational asthma is the specific bronchial provocation test (sBPT), but other diagnostic criteria have been proven to have a similar sensitivity, mainly in asthma due to high molecular weight compounds. In order to assess wether some clinical findings can predict the positive response to sBPT, we studied 37 subjects (14 millers and 23 bakers) with suspected occupational asthma who underwent sBPT with wheat flour dust (dust exposure in a small cabin: geometric mean 12.1 mg/m3 for up to 30 min). A positive response to sBPT (FEV1 > 20%) was elicited in 20 subjects (11 early, 4 late, and 5 dual responses). There was no significant difference between subjects with positive or negative sBPT as regards mean age, smoking, length of employment, duration of symptoms, atopy (skin positivity to one or more common allergens) and PD20FEV1 methacholine. The percentage of subjects with work-related symptoms was significantly higher in subjects with positive sBPT with respect to subjects with negative sBPT (81% versus 41.2%, p < 0.01 by chi 2 test); furthermore, FEV1 was significantly lower in subjects with positive sBPT. The percentage of positive skin response to wheat flour extract (mean wheal diameter > or = 3 mm) was mildly but not significantly higher in subjects with positive sBPT (68.4% versus 41.2%). None of the following clinical factors (age < 35 years, asthma symptoms pre-existing occupational exposure, non smokers, atopy and bronchial hyperresponsiveness to methacholine), alone or in combination, were associated with higher prevalence of positive sBPT. We conclude that the response to sBPT in subjects with suspected occupational asthma due to flour dust can not be adequately predicted by other clinical, allergologic and functional data. Therefore, sBPT with flour dust should always be performed in subjects with suspected occupational asthma.     

Comparison of fluticasone propionate and beclomethasone dipropionate on direct and indirect measurements of bronchial hyperresponsiveness in patients with stable asthma

BACKGROUND: Fluticasone propionate is a new inhaled corticosteroid with a 2:1 efficacy ratio compared with beclomethasone dipropionate with regard to lung function and symptom scores, without increased systemic activity. The aim of this study was to investigate whether this was also the case for bronchial hyperresponsiveness, assessed by both a direct (histamine) and an indirect (ultrasonically nebulised distilled water (UNDW)) provocation test. METHODS: Fluticasone propionate, 750 micrograms/day, and beclomethasone dipropionate, 1500 micrograms/day, were compared in a randomised, double blind, crossover study consisting of two six week treatment periods, each preceded by a three week single blind placebo period. Twenty one non-smoking asthmatics (mean forced expiratory volume in one second (FEV1) 74.7% predicted, mean PC20histamine 0.36 mg/ml) completed the study. RESULTS: Fluticasone propionate and beclomethasone dipropionate improved FEV1, peak flow rates, asthma symptoms, and bronchial hyperresponsiveness to the same extent. Both fluticasone propionate and beclomethasone dipropionate caused an increase in PC20histamine (mean 2.29 [95% confidence interval 1.45 to 3.13] and 1.95 [1.07 to 2.84] doubling doses, respectively) and in PD20UNDW (1.12 [0.55 to 1.70] and 1.28 [0.88 to 1.70] doubling doses, respectively). Neither treatment changed morning serum cortisol levels, but fluticasone propionate decreased the number of peripheral blood eosinophils less than beclomethasone dipropionate, indicating smaller systemic effects of fluticasone propionate. CONCLUSIONS: These findings show that fluticasone propionate is as effective as twice the dose of beclomethasone dipropionate on bronchial hyperresponsiveness, assessed by provocation with both histamine and UNDW, without increased systemic activity.     

Potentiating effect of inhaled acetaldehyde on bronchial responsiveness to methacholine in asthmatic subjects

BACKGROUND: It has recently been reported that acetaldehyde induces bronchoconstriction indirectly via histamine release. However, no study has been performed to assess whether acetaldehyde worsens bronchial responsiveness in asthmatic subjects so this hypothesis was tested. METHODS: Methacholine provocation was performed on three occasions: (1) after pretreatment with oral placebo and inhaled saline (P-S day), (2) after placebo and inhaled acetaldehyde (P-A day), and (3) after a potent histamine H1 receptor antagonist terfenadine and acetaldehyde (T-A day) in a double blind, randomised, crossover fashion. Nine asthmatic subjects inhaled 0.8 mg/ml acetaldehyde or saline for four minutes. After each inhalation a methacholine provocation test was performed. RESULTS: Methacholine concentrations producing a 20% fall in FEV1 (PC20-MCh) on the P-A day (0.48 mg/ml, 95% CI 0.21 to 1.08) and T-A day (0.41 mg/ml, 95% CI 0.22 to 0.77) were lower than those on the P-S day (0.85 mg/ml, 95% CI 0.47 to 1.54). There was no change in the PC20-MCh between the P-A and T-A days. A correlation was observed between the logarithmic values of PC20-MCh (log PC20-MCh) on the P-S day and the potentiating effect of acetaldehyde on the methacholine responsiveness [(log PC20-MCh on P-A day)-(log PC20-MCh on P-S day)] (rho = 0.82). CONCLUSIONS: Acetaldehyde induces bronchial hyperresponsiveness in patients with asthma by mechanisms other than histamine release.     

Misoprostol has no favorable effect on bronchial hyperresponsiveness in mild asthmatics

Misoprostol, a synthetic prostaglandin E1 analogue, has been reported to have antibronchoconstricive and antiinflammatory effects in animal studies. We investigated the effect of misoprostol on FEV1 and bronchial hyperresponsiveness (BHR) to histamine in mildly asthmatics. 14 mildly asthmatic patients were given 400 mg/day oral misoprostol. Four patients had to left the study either due to the side effects. The remaining 10 patients (all women and mean age was 33.2 +/- 3.3) underwent the histamine challenge test before and after the treatment with misoprostol. Mean values of FEV1 obtained before and after the treatment were as follows respectively: 2.79 +/- 0.17 L; 2.78 +/- 0.18 L. Mean log PC20 values were as follows respectively: 0.60 +/- 0.23 mg/ml; 0.60 +/- 0.14 mg/ml. There was no difference either in FEV1 and log PC20 values before and after the treatment with misoprostol (p > 0.05). As a result administered misoprostol has no favorable effect on expiratory flow rates and BHR in asthmatic patients.     

Clinical follow-up of an epidemiologic study on asthma and allergies in childhood

The results of a recent epidemiological study in Salzburg (Austria) showed that the prevalence of bronchial hyperresponsiveness (BHR) to hypertonic saline (HS) was 13.7% in schoolchildren aged 12-15 years. In the same study the prevalence of wheezing in the last 12 months was 11.9% and asthma had been diagnosed in 6.3%. To audit the relevance of these results and to offer medical treatment to children with newly diagnosed asthma, we invited all children who had had a positive bronchial provocation test (n = 99) or an abnormal lung function (defined as an FEV1 < 80% of the predicted value; n = 33) for clinical investigation. Seventy-five out of 99 children with BHR and 27/33 with an FEV1 < 80% of the predicted value attended the Respiratory Laboratory and a paediatric pulmonologist assessed the diagnosis on the basis of respiratory symptoms, physical examination and lung function test. In 26/53 children with asthma, the diagnosis was unknown. Although most children had mild asthma and normal lung function, half of these children had reduced physical activity. In 27/53 children with asthma, the diagnosis had already been known but, according to the specialist, had not been adequately treated. In 21/27 children with an FEV1 < 80% of the predicted value, this finding was clinically not relevant. The audit of the epidemiological study supported the assumption that asthma might be underdiagnosed and undertreated in our population.     

Bronchial hyperresponsiveness before and after percutaneous transluminal mitral commissurotomy in patients with mitral stenosis

To study the effects of percutaneous transluminal mitral commissurotomy (PTMC) on bronchial responsiveness to inhaled methacholine in patients with mitral valve stenosis (MS), methacholine inhalation tests and pulmonary function tests were done in 10 patients with MS before and one week after PTMC. The mean log cumulative dose producing a 35% decrease in respiratory conductance (PD35Grs) was significantly higher after PTMC in nine patients in whom PTMC was successful (p < 0.05). There were no significant changes in the results of pulmonary function tests after PTMC. One patient had severe mitral regurgitation after PTMC, and a decrease in PD35Grs. Six of the other nine patients in whom PTMC was successful continued to be hyperresponsive to inhaled methacholine. These data show that bronchial hyperresponsiveness in patients with MS is less severe after PTMC, concomitant with the relief of pulmonary congestion, and they suggest that the remaining bronchial hyperresponsiveness is responsible for peripheral airway narrowing with organic remodeling.     

Vladimir Vladimirovich Sakharov--an outstanding disciple of N. K. Kol''tsov

OBJECTIVES: To measure the levels of exposure to nitrogen trichloride (NCl3) in the atmosphere of indoor swimming pools and to examine how they relate to irritant and chronic respiratory symptoms, indices of pulmonary function, and bronchial hyperresponsiveness to methacholine in lifeguards working in the pools. METHOD: 334 lifeguards (256 men; 78 women) recruited from 46 public swimming pools (n = 228) and 17 leisure centre swimming pools (n = 106) were examined. Concentrations of NCl3 were measured with area samplers. Symptoms were assessed by questionnaire and methacholine bronchial challenge (MBC) test by an abbreviated method. Subjects were labelled MBC+ if forced expiratory volume in one second (FEV1) fell by > or = 20%. The linear dose-response slope was calculated as the percentage fall in FEV1 at the last dose divided by the total dose given. RESULTS: 1262 samples were taken in the 63 pools. Mean NCl3 concentrations were greater in leisure than in public pools. A significant concentration-response relation was found between irritant eye, nasal, and throat symptoms-but not chronic respiratory symptoms-and exposure concentrations. Among women, the prevalence of MBC+ was twice as great as in men. Overall, no relation was found between bronchial hyperresponsiveness and exposure. CONCLUSIONS: The data show that lifeguards exposed to NCl3 in indoor swimming pools are at risk of developing irritant eye, nasal, and throat symptoms. Exposure to NCl3 does not seem to carry the risk of developing permanent bronchial hyperresponsiveness, but this association might have been influenced by self selection. The possibility that subjects exposed to NCl3 are at risk of developing transient bronchial hyperresponsiveness cannot be confidently ruled out.     

Antibody detection after antepartal rhesus prophylaxis: normal values or sensitization

Although poorly reproducible spirometric tests, "test failures," are associated with respiratory morbidity, it is not clear what causes them. Bronchial responsiveness was examined in relation to test failure for forced expiratory volume in 1 s (FEV1.0) (1979 definition of the American Thoracic Society) in 249 bakers, 165 chemical industry workers, and 204 office workers. The first two groups were studied by the same methods and were combined. Test failure was observed in 4%, and for 38% the provocative dose of inhaled methacholine causing a 20% fall in FEV1.0 relative to FEV1.0 after the inhalation of normal saline (PD20) was < or = 120 mumol (7% with a PD20 of < or = 8 mumol). Test failure was not related to the level of PD20. Of the office workers, 3% had test failure, 11% a PD20 of < or = 8 mumol of histamine, and no significant relation was observed. The study does not exclude the possibility that bronchial responsiveness might be related to test failure in patients with airway disease or that a clearer relation might be demonstrable in a larger study, but it does suggest that it is not a major determinant of test failure.     

Discrepancies between diagnosed asthma, asthma-like symptoms and a test for abnormal lung function

For the diagnosis of asthma, it is neither clear to which degree various tests and symptoms identify the same subjects nor how these characteristics are best combined. We assessed the interrelationship between physician-diagnosed asthma, asthma-like symptoms and abnormal airway function in a population based sample of 495 12-15 year old schoolchildren. Participants filled in a questionnaire and underwent baseline spirometry (FEV1%), provocation with treadmill exercise (EXE) and with inhaled methacholine (PD15), and monitoring of peak expiratory flow (PEF) twice daily for two weeks. Most symptomatic subjects with any test positive were identified by PD15 alone (75%) or in combination with PEF monitoring (89%). Although interest agreement was weak (kappa < 0.40 for all pairs), significant associations were found between PD15 and EXE, between PEF and EXE and between FEV1% and PD15. However, PEF variability and methacholine responsiveness seem to identify different varieties of airway pathophysiology, and the combined use of the two tests may be helpful as an epidemiological screening tool for asthma.     

Comparison of bronchial reactivity to ultrasonically nebulized distilled water, exercise and methacholine challenge test in asthmatic children

We studied the responses to ultrasonically nebulized distilled water (UNDW) challenge, exercise challenge and methacholine challenge in asthmatic children. Fifty-four asthmatic and fourteen nonasthmatic control children participated in this study. The UNDW inhalation test was by the methodology described by Anderson. The average output of water was approximately 3.0 mL/min (SD = .1) and inhalation times were 30 seconds, one minute, two minutes and four minutes. Some subjects performed exercise challenge on a bicycle ergometer and methacholine challenge by an Astrograph technique. Twenty-three of 54 asthmatic patients (42.6%) and none of the controls showed a fall in FEV1 greater than 20% with UNDW challenge. The fall in FEV1 with UNDW correlated with that induced by exercise challenge (r = .89) and Log Dmin, which may reflect bronchial sensitivity (r = .70). Our method is not sensitive enough for detecting bronchial hyperresponsiveness in all asthmatic children. Bronchoconstriction induced by UNDW has a similar mechanism of action as exercise and methacholine.     

The detection of cytochrome P450 2E1 and its catalytic activity in rat testis

The aim of this study was to compare the efficacy of 100 micrograms of salbutamol inhaled from a new metered-dose powder inhaler (MDPI, Leiras Taifun, Finland) with that of a same dose of salbutamol inhaled from a conventional pressurized metered-dose inhaler with a large volume spacer (pMDI + S) in protecting against methacholine (Mch) induced bronchoconstriction. This was a 3 day, randomized, cross-over, partly blinded, placebo-controlled multicentre study where the pMDI + S was used as an open control. Twenty-six asthmatic outpatients with a baseline FEV1 > or = 60% of predicted and with bronchial hyperreactivity (PD20 FEV1 < or = 890 micrograms of Mch) were studied. On each study day the patients underwent an Mch provocation 30 min after inhaling placebo from the MDPI or a dose of 100 micrograms of salbutamol from the MDPI and from the pMDI + S. PD20 FEV1 and dose-response slope [DRS; maximal change in FEV1 (%)/dose of Mch (mumol)] were used to evaluate efficacy. The median values of PD20 FEV1 were 250, 622 and 1737 micrograms after placebo MDPI, salbutamol pMDI + S and salbutamol MDPI, respectively. The corresponding DRS values were -11.0%, -4.5% and -2.0% mumol-1. With both parameters, all differences were statistically significant (P < 0.05). In conclusion, 100 micrograms of salbutamol inhaled from Leiras Taifun MDPI offers better protection against Mch-induced bronchoconstriction than 100 micrograms of salbutamol from a pMDI connected to a large volume spacer device.     

The inhibition of yohimbine injected intrathecally on electroacupuncture-induced analgesia and release of beta-endorphin from rat brain

No study has investigated the effects of ethanol on bronchial responsiveness in patients with alcohol-induced asthma, although acetaldehyde, which is a metabolite of ethanol and is thought to be a main factor in alcohol-induced asthma, causes both bronchoconstriction and bronchial hyperresponsiveness. The purpose of this study was to investigate the direct action of ethanol on the airway in patients with alcohol-induced asthma. First, we investigated the bronchial response to inhalation of ascending doses (5, 10, and 20%) of ethanol in nine patients with alcohol-induced asthma. Then, the bronchial responsiveness to methacholine was measured in 14 patients who were pretreated with saline or 20% ethanol in a double-blind, randomized, placebo-controlled, crossover fashion. Ascending doses of inhaled ethanol caused no significant changes in FEV1. The methacholine concentrations producing a 20% fall in FEV1 (PC20-MCh) after 20% ethanol (0.769 mg/ml, GSEM 1.514) were significantly (P = 0.0357) higher than those after saline (0.493 mg/ml, GSEM 1.368). This indicates that ethanol has a reducing effect on nonspecific bronchial responsiveness in patients with alcohol-induced asthma; this paper is the first report on the effects of ethanol on bronchial responsiveness.     

Is bronchial hyperresponsiveness more frequent in women than in men? A population-based study

To test the hypothesis that a greater proportion of women than men react to methacholine challenge and investigate the possible reasons for any differences observed, we recruited 495 subjects 20 to 44 yr of age (50.9% male) in Paris and 304 subjects (51.3% male) in Montpellier (France), as part of the European Community Respiratory Health Survey. The proportion of responders (PD20 < or = 4 mg methacholine) was 33.7% in women and 11.9% in men (odds ratio = 3.8; 95% confidence interval = 2.4-6.0) in Paris and 43.2% in women and 29.5% in men (odds ratio = 1.8; 95% confidence interval = 1.1-2.9) in Montpellier. These differences could not be explained by asthma, respiratory symptoms, atopy, or lung function parameters. In stepwise logistic regressions including sex, asthma, and asthma-like symptoms, nasal allergies, atopy, baseline FEV1, FEV1%pred, FVC, and FEV1%FVC, the odds-ratios for the effect of female sex on PD20 < or = 4 mg methacholine were 5.2 (3.0-9.0) in Paris and 2.2 (1.2-3.8) in Montpellier. Reacting to low doses of methacholine (PD20 < or = 0.5 mg) was associated with asthma and atopy in both men and women. In contrast, reacting to doses between 0.5 and 4 mg was associated with asthma and atopy only in men and with heavy tobacco consumption only in women. We conclude that the excess of hyperresponsiveness in women is not due to their having smaller lung size or airway caliber than men and may be related to a greater susceptibility to smoking.