(9R)-9-chloro-11-17-dihydroxy-17-(2-hydroxy-1-oxoethyl)-10-13-16-trimethyl-6-7-8-11-12-14-15-16-octahydrocyclopenta[a]phenanthren-3-one and Bronchial-Hyperreactivity

Topics: Administration, Inhalation; Adrenergic beta-Agonists; Albuterol; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Beclomethasone; Bronchi; Bronchial Diseases; Bronchial Hyperreactivity; Bronchitis; Constriction, Pathologic; Drug Therapy, Combination; Eosinophilia; Glucocorticoids; Humans; Salmeterol Xinafoate; Theophylline

Topics: Administration, Inhalation; Adult; Anti-Inflammatory Agents; Asthma; Beclomethasone; Bronchial Hyperreactivity; Bronchodilator Agents; Budesonide; Follow-Up Studies; Forced Expiratory Volume; Forecasting; Glucocorticoids; Humans; Lung Diseases, Obstructive; Peak Expiratory Flow Rate; Pregnenediones; Randomized Controlled Trials as Topic; Smoking; Vital Capacity

Recently, bronchial asthma has been widely recognized as a chronic inflammatory disorder of the airways. In the course of inflammation, many kinds of inflammatory cells such as lymphocytes, especially Th2 lymphocytes, mast cells, eosinophills, bronchial epithelial cells interact each other by so-called cytokine network. Bronchial hyperreactivity, which is a characteristic phenomenon in bronchial asthma, is induced as a result of bronchial inflammation. According to the inflammation theory of pathogenesis of bronchial asthma, anti-inflammatory treatment using inhaled corticosteroid is recommended as the first choice of asthma therapy. Bronchial biopsy proved decrease of the number of infiltrating inflammatory cells such as T lymphocytes, eosinophils and mast cells in the bronchial submucosal tissue after inhaled steroid treatment. Improvement of bronchial reactivity after inhaled steroid therapy was also reported. Recently, a certain group of so-called steroid resistant asthma has been known and the mechanism of it is now under investigation.

Topics: Administration, Inhalation; Anti-Inflammatory Agents; Asthma; Beclomethasone; Bronchi; Bronchial Diseases; Bronchial Hyperreactivity; Cytokines; Eosinophils; Humans; Inflammation; Inflammation Mediators; Mast Cells; T-Lymphocytes

Effects and actions of DSCG and corticosteroids in the airways could not essentially evaluated at the same situation, before the inhaled BDP had been used. Each of the drugs have been shown to reduce both immediate and late phase responses in experimentally induced asthma, exercise induced bronchospasm, and bronchial hypersensitivity to histamine especially after the prolonged pretreatment of BDP. DSCG probably targets nonspecifically the surfaces of relevant cells including mast cells and eosinophils, but BDP are known to act specifically and/or nonspecifically on the gene transcription in the various types of cells including eosinophils, lymphocytes, and resident cells. Many informations on the systemic side effects of BDP will be still required.

Topics: Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Asthma; Beclomethasone; Bronchial Hyperreactivity; Cromolyn Sodium; Eosinophils; Humans; Inflammation Mediators; Mast Cells; Transcription, Genetic

Beclomethasone dipropionate has now been used for more than 10 years during which our knowledge of how to use inhaled corticosteroids has gradually improved: high dose initial treatment followed by progressive reduction down to the minimum effective dosage; administration in 2 daily doses when the asthma is stable and 4 daily doses in case of instability; mild and transient undesirable effects, often minimized by a correct use of the inhaler; effectiveness assessed from bronchial hyper-reactivity and respiratory function tests, reduction or avoidance of oral corticosteroid therapy, or results of association with other treatments, and in particular bronchodilators. When exactly should inhaled corticosteroid therapy should be started and how long should it be pursued are controversial points, but an early and prolonged treatment must probably be recommended.

Topics: Administration, Inhalation; Adrenergic beta-Agonists; Adult; Asthma; Beclomethasone; Bronchial Hyperreactivity; Candidiasis, Oral; Drug Therapy, Combination; Humans; Pituitary-Adrenal System

The clinical relevance of increased ventilation heterogeneity, a marker of small-airways disease, in asthmatic patients is unclear. Ventilation heterogeneity is an independent determinant of airway hyperresponsiveness (AHR), improves with bronchodilators and inhaled corticosteroids (ICSs), and worsens during exacerbations, but its relationship to asthma control is unknown.. We sought to determine the association between ventilation heterogeneity and current asthma control before and after ICS treatment.. Adult subjects with asthma had lung function and asthma control (5-item Asthma Control Questionnaire [ACQ-5 score] ≥1.5 = poorly controlled, ACQ-5 score ≤0.75 = well controlled) measured at baseline. A subgroup with AHR had repeat measurements after 3 months of high-dose ICS treatment. The indices of ventilation heterogeneity in the regions of the lung where gas transport occurs predominantly through convection (ventilation heterogeneity in convection-dependent airways [Scond]) and through diffusion (ventilation heterogeneity in diffusion-dependent airways [Sacin]) were derived by using the multiple-breath nitrogen washout technique.. At baseline (n = 105), subjects with poorly controlled asthma had worse FEV(1), fraction of exhaled nitric oxide measured at 200 mL/s (Feno), Scond, and Sacin values. In the treatment group (n = 50) spirometric, Feno, residual volume (RV)/total lung capacity (TLC), AHR, and Scond values significantly improved. Asthma control also improved (mean ACQ-5 score, 1.3-0.7; P < .0001). The change in ACQ-5 score correlated with changes in Feno (r(s) = 0.31, P = .03), Sacin (r(s) = 0.32, P = .02), and Scond (r(s) = 0.41, P = .003) values. The independent predictors of a change in asthma control were changes in Scond and Sacin values (model r(2) = 0.20, P = .005).. Current asthma control is associated with markers of small-airways disease. Improvements in ventilation heterogeneity with anti-inflammatory therapy are associated with improvements in symptoms. Sensitive measures of small-airway function might be useful in monitoring the response to therapy in asthmatic subjects.

Topics: Adult; Anti-Asthmatic Agents; Asthma; Beclomethasone; Bronchial Hyperreactivity; Bronchial Provocation Tests; Female; Humans; Male; Nitric Oxide; Plethysmography; Skin Tests; Spirometry

Bronchial hyper-reactivity (BHR) provides a tool for asthma diagnosis, assessment of severity and response to treatment. The effect of beclomethasone dipropionate in ultrafine particles (BDP-HFA) on BHR as measured by the adenosine challenge test in young children has not yet been determined. Our aim was to determine the effect of BDP-HFA (100 μg twice daily) on BHR as evaluated by a reduction of 20% from baseline FEV1 (PC20-FEV1) values in young asthmatic children.. Twenty-one young children (13 males), mean age 4.95 ± 1.05 years, with partially controlled or controlled asthma completed a double-blind randomized, placebo-controlled, cross-over study. Each child received 4 weeks of treatment with either 100 μg BDP-HFA twice daily or placebo, and after a 2-week washout period the other way around. Primary outcomes were PC20-FEV1 concentration, and the stage number at which FEV1 values dropped by 20%.. Following 4 weeks of treatment, median PC20-FEV1 was 81.28 mg/mL while on BDP-HFA, compared with 9.64 mg/mL on placebo (p < 0.001). The median increase in stages required to achieve PC20 on BDP-HFA compared with placebo was three (95% CI 2.28-4.86).. Four weeks of treatment with BDP-HFA resulted in significantly decreased BHR in young children.

Topics: Adenosine Monophosphate; Anti-Asthmatic Agents; Beclomethasone; Bronchial Hyperreactivity; Child, Preschool; Cross-Over Studies; Double-Blind Method; Female; Humans; Male; Particle Size

Bronchial hyperresponsiveness to 5-adenosine mono-phosphate (AMP) is a marker of airway inflammation. Inhaled corticosteroids and antileukotrienes are used as anti-inflammatory drugs for the treatment of asthma. To find out if these two drugs exert their protection in an additive fashion, we compared the effects of acute treatment with inhaled beclomethasone (BDP) and montelukast (ML), alone or in combination, on methacholine and AMP induced bronchoconstriction. 15 asthmatic patients undertook methacholine and AMP challenges at baseline and after receiving ML or BDP, alone or in combination, in a randomized, double-blind, double-dummy placebo-controlled, crossover design. BDP pretreatment significantly increased the AMP PC(20) value (68.34+/-15.9mg/mL) as compared to placebo (22.87+/-5.7mg/mL). Combined treatment, BDP plus ML, afforded a further significant increase of AMP PC(20) (154.57+/-55.0mg/mL) as compared to each single treatment. The significant protection exerted by combined treatment as compared to each single active treatment was also demonstrated by the change of AMP PC(20) doubling dose as compared to placebo and each single active treatment. Our findings suggest that these two agents exert their acute additive protection against AMP induced bronchoconstriction acting on distinct inflammatory pathways and their combined use might provide greater protection against inflammatory response elicited by AMP than either drug alone.

Topics: Acetates; Administration, Inhalation; Adolescent; Adult; Anti-Inflammatory Agents; Asthma; Beclomethasone; Bronchial Hyperreactivity; Bronchial Provocation Tests; Bronchoconstriction; Cross-Over Studies; Cyclopropanes; Double-Blind Method; Drug Synergism; Drug Therapy, Combination; Female; Forced Expiratory Volume; Humans; Male; Quinolines; Sulfides; Treatment Outcome; Young Adult

Rhinitis and asthma are currently recognized as manifestations of a single syndrome, the chronic allergic respiratory syndrome. Nearly all individuals with asthma have rhinitis, and severe rhinitis has been associated with worse outcomes in asthma patients. Intranasal treatment has been reported to be beneficial for the lower airways.. This was a randomized, double-blind, placebo-controlled study. The objective was to evaluate the effects that treatment with intranasal beclomethasone dipropionate (BDP; 400 microg/d) has on nasal and bronchial symptoms, as well as on lung function test results and bronchial responsiveness to histamine in patients with allergic rhinitis and asthma. We evaluated 33 patients, divided into two groups: treatment (n = 17); and placebo (n = 16). Over the course of the 125-day study period, each patient reported daily rhinitis and asthma symptoms, as well as the need for additional medication. All patients were submitted to spirometry and histamine challenge at baseline and at each subsequent evaluation (on days 50 and 75).. In comparison with the patients in the placebo group, those in the BDP treatment group presented significantly fewer nasal symptoms on day 50 and fewer asthma symptoms on day 75 (p < 0.01 for both); required rescue medications less often; and presented a significantly lower degree of bronchial responsiveness to histamine on day 75 (p < 0.01).. In this study, intranasal BDP was effective in treating rhinitis as well as asthma. The benefits for the lower airways were observed only after prolonged treatment and might be better evaluated through nonspecific bronchial challenge.

Topics: Administration, Intranasal; Adolescent; Adult; Asthma; Beclomethasone; Bronchial Hyperreactivity; Double-Blind Method; Female; Glucocorticoids; Histamine; Humans; Male; Respiratory Function Tests; Rhinitis; Young Adult

Bronchial thermoplasty is a bronchoscopic procedure to reduce the mass of airway smooth muscle and attenuate bronchoconstriction. We examined the effect of bronchial thermoplasty on the control of moderate or severe persistent asthma.. We randomly assigned 112 subjects who had been treated with inhaled corticosteroids and long-acting beta2-adrenergic agonists (LABA) and in whom asthma control was impaired when the LABA were withdrawn to either bronchial thermoplasty or a control group. The primary outcome was the frequency of mild exacerbations, calculated during three scheduled 2-week periods of abstinence from LABA at 3, 6, and 12 months. Airflow, airway responsiveness, asthma symptoms, the number of symptom-free days, use of rescue medication, and scores on the Asthma Quality of Life Questionnaire (AQLQ) and the Asthma Control Questionnaire (ACQ) were also assessed.. The mean rate of mild exacerbations, as compared with baseline, was reduced in the bronchial-thermoplasty group but was unchanged in the control group (change in frequency per subject per week, -0.16+/-0.37 vs. 0.04+/-0.29; P=0.005). At 12 months, there were significantly greater improvements in the bronchial-thermoplasty group than in the control group in the morning peak expiratory flow (39.3+/-48.7 vs. 8.5+/-44.2 liters per minute), scores on the AQLQ (1.3+/-1.0 vs. 0.6+/-1.1) and ACQ (reduction, 1.2+/-1.0 vs. 0.5+/-1.0), the percentage of symptom-free days (40.6+/-39.7 vs. 17.0+/-37.9), and symptom scores (reduction, 1.9+/-2.1 vs. 0.7+/-2.5) while fewer puffs of rescue medication were required. Values for airway responsiveness and forced expiratory volume in 1 second did not differ significantly between the two groups. Adverse events immediately after treatment were more common in the bronchial-thermoplasty group than in the control group but were similar during the period from 6 weeks to 12 months after treatment.. Bronchial thermoplasty in subjects with moderate or severe asthma results in an improvement in asthma control. (ClinicalTrials.gov number, NCT00214526 [ClinicalTrials.gov].).

Topics: Adrenergic beta-Agonists; Adult; Asthma; Beclomethasone; Bronchi; Bronchial Hyperreactivity; Bronchoscopy; Catheter Ablation; Female; Follow-Up Studies; Forced Expiratory Volume; Glucocorticoids; Humans; Hyperthermia, Induced; Male; Middle Aged; Muscle, Smooth; Peak Expiratory Flow Rate; Quality of Life

The aim of our study was to analyze the effect of recreational swimming on lung function and bronchial hyperresponsiveness (BHR) in patients with mild persistent asthma. This study included 65 patients with mild persistent asthma, who were divided into two groups: experimental group A (n = 45) and control group B (n = 20). Patients from both groups were treated with low doses of inhaled corticosteroids (ICS) and short-acting beta2 agonists salbutamol as needed. Our program for patients in group A was combined asthma education with swimming (twice a week on a 1-h basis for the following 6 months). At the end of the study, in Group A, we found a statistically significant increase of lung function parameters FEV1 (forced expiratory volume in 1 sec) (3.55 vs. 3.65) (p < 0.01), FVC (forced vital capacity) (4.27 vs. 4.37) (p < 0.05), PEF (peak expiratory flow) (7.08 vs. 7.46) (p < 0.01), and statistically significant decrease of BHR (PD20 0.58 vs. 2.01) (p < 0.001). In Group B, there was a statistically significant improvement of FEV1 3.29 vs. 3.33 (p < 0.05) and although FVC, FEV1/FVC, and PEF were improved, it was not significant. When Groups A and B were compared at the end of the study, there was a statistically significant difference of FVC (4.01 vs. 4.37), FEV1 (3.33 vs. 3.55), PEF (6.79 vs.7.46), and variability (p < 0.001), and statistically significantly decreased BHR in Group A (2.01 vs. 1.75) (p < 0.001). Engagement of patients with mild persistent asthma in recreational swimming in nonchlorinated pools, combined with regular medical treatment and education, leads to better improvement of their parameters of lung function and also to more significant decrease of their airway hyperresponsiveness compared to patients treated with traditional medicine.

Topics: Adrenergic beta-Agonists; Adult; Albuterol; Asthma; Beclomethasone; Bronchial Hyperreactivity; Female; Histamine; Humans; Hypersensitivity, Immediate; Male; Patient Education as Topic; Respiratory Function Tests; Swimming

Inhaled corticosteroids (ICS) are the most effective anti-inflammatory agents available for the treatment of asthma but they produce only modest effects on airway inflammation and non-specific bronchial hyperresponsiveness (BHR). However, little is known about the possibility that treatment with ICS might cause additional protection on BHR to inhaled tachykinins such as neurokinin A (NKA).. Therefore, we compared the effects of beclomethasone dipropionate (BDP) on the degree of BHR to inhaled histamine and NKA in a double-blind, controlled, cross-over study of asthmatic patients.. Patients attended the laboratory before and after each 6 weeks treatment period to undertake concentration-response studies with histamine and NKA. Bronchial responsiveness to both funs was expressed as the provocative concentration producing a 20% decrease in FEV(1) from baseline (PC(20)).. BDP therapy attenuated the constrictor response to both agonists to a similar degree, their geometric mean (range) PC(20) values increasing from 0.47 (0.21-1.41) mg/ml to 2.43 (0.51-4.50) mg/ml (P<0.01, post-salb vs. post-BDP treatment) and from 101.7 (27.3-356.1) microg/ml to 666.7 (151.5-1,000) microg/ml (P<0.01, post-salb vs. post-BDP treatment) for histamine and NKA, respectively.. Airway responsiveness to histamine and NKA is reduced by BDP to the same extent. As a result of these findings, provocation with NKA is unlikely to provide additional useful information in the assessment of airway inflammation in asthma.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adrenergic beta-Agonists; Adult; Albuterol; Analysis of Variance; Asthma; Beclomethasone; Bronchial Hyperreactivity; Bronchial Provocation Tests; Cross-Over Studies; Dose-Response Relationship, Drug; Double-Blind Method; Female; Histamine; Humans; Male; Neurokinin A; Statistics, Nonparametric

Rhinitis and asthma are considered to be synchronic or sequential forms of the same allergic syndrome. Treating the inflammation associated with allergic rhinitis influences the control of asthma. However, few studies have investigated the effect of treating perennial rhinitis on persistent asthma and vice versa. We determined the effects of inhaled or topical nasal beclomethasone dipropionate (BDP) administered separately or in combination on the control of asthma and bronchial hyperresponsiveness (BHR) in patients with the rhinitis/asthma association.. A double-blind, parallel, three-group study.. Outpatient clinic of Pulmonary Division/Heart Institute (InCor) and the Division of General Internal Medicine, University of Sao Paulo Medical School, Sao Paulo, Brazil.. Seventy-four patients with mild-to-moderate asthma and allergic rhinitis (median age, 25 years).. Patients received nasal or inhaled BDP separately or in combination for 16 weeks after a 2-week placebo run-in period.. Nasal and pulmonary symptoms, as well as pulmonary function and BHR, were compared among the three groups after 4 weeks and 16 weeks of treatment. Patients in all three groups demonstrated a progressive and significant decrease in nasal and pulmonary symptoms, which started after 4 weeks (p < 0.05) and continued through the end of treatment (p < 0.001). Clinical improvement was similar and parallel in the three groups. Asthma-related morbidity, evaluated by quantifying absence from work, emergency department visits, and nighttime awakenings, also decreased in the three groups (p < 0.05).. Failure to consider treatment of rhinitis as essential to asthma management might impair clinical control of asthma. Furthermore, these data suggest that asthma and rhinitis in some patients can be controlled by the exclusive use of nasal medication.

Topics: Adolescent; Adult; Asthma; Beclomethasone; Bronchial Hyperreactivity; Double-Blind Method; Female; Glucocorticoids; Humans; Male; Multivariate Analysis; Rhinitis, Allergic, Perennial

The tulobuterol transdermal therapeutic system (TTS) is the world's first commercially available transdermal preparation of tulobuterol, a beta-2 stimulant, that can maintain effective blood tulobuterol levels for 24 hours when applied once daily. In the present study, a total of 36 adult patients with mildly persistent (Step 2) or moderately persistent (Step 3) bronchial asthma 19 who were using inhalational steroids and 17 who were not used tulobuterol TTS for one year and underwent measurement of peak expiratory flow (PEF) once daily. Peripheral eosinophil count, serum eosinophil cationic protein (ECP) level and airway responsiveness (Dmin) were evaluated at 6 months and 1 year after the start of the study. PEF exhibited significant improvements at 6 months and 1 year in patients treated with or without inhalational steroids, while serum ECP was improved significantly only in the patients on inhalational steroids. Patients not using inhalational steroids exhibited no significant exacerbation of Dmin at either 6 months or 1 year: One-year treatment with tulobuterol TTS did not appear to cause tachyphylaxis. The significant improvements in Dmin at 6 months and 1 year in the patients using inhalational steroids suggested that inhalational steroids offer beneficial effects in controlling airway inflammation. Tulobuterol TTS is considered quite beneficial in improving quality of life (QOL) in patients with bronchial asthma because its incidence of adverse effects including palpitations and shivering is significantly lower than those of oral preparations, because of its remarkable improvement of pulmonary function and symptoms of airway obstruction without increasing airway responsiveness even after repeated use, and because it is simple to use and offers excellent clinical efficacy.

Topics: Administration, Cutaneous; Administration, Inhalation; Adrenergic beta-Agonists; Aged; Androstadienes; Asthma; Beclomethasone; Bronchial Hyperreactivity; Delayed-Action Preparations; Drug Therapy, Combination; Female; Fluticasone; Humans; Inflammation; Male; Middle Aged; Peak Expiratory Flow Rate; Quality of Life; Severity of Illness Index; Terbutaline; Time Factors; Treatment Outcome

To examine the relationship between changes in quality of life and measures of lung function and bronchial hyper-responsiveness (BHR) during treatment with high-dose inhaled corticosteroids in patients with uncontrolled asthma.. Thirty patients with uncontrolled asthma currently receiving inhaled corticosteroids (median dose 550 microg/day) were treated with beclomethasone dipropionate (BDP) dry powder 2000 microg/day for 4 weeks. Patients completed the Asthma Quality of Life Questionnaire (AQLQ), underwent bronchial challenge with methacholine and spirometry, and made entries in asthma diary cards at baseline and after treatment with beclomethasone dipropionate.. The mean change in overall AQLQ score improved significantly (p < 0.05) during the 4-week period by 0.57 (95% CI 0.29-0.84, p < 0.05), representing a minimal important difference, with similar improvements in individual domains. Change in overall AQLQ score correlated significantly with FEV(1) (p < 0.001), forced mid-expiratory flow between 25-75% of vital capacity (FEF(25-75)) [p < 0.05] and morning PEF (p < 0.05), but not with methacholine PD(20) i.e. the provocative dose of methacholine causing a 20% fall in FEV(1).. Quality-of-life scores related to changes in lung function but not BHR during short-term high-dose inhaled corticosteroid therapy for uncontrolled asthma.

Topics: Administration, Inhalation; Adult; Aged; Asthma; Beclomethasone; Bronchial Hyperreactivity; Dose-Response Relationship, Drug; Glucocorticoids; Humans; Lung; Middle Aged; Quality of Life; Respiratory Function Tests

To evaluate the effect of adding zafirlukast or low-dose theophylline to a beclomethasone dipropionate (BDP) extra-fine hydrofluoroalkane aerosol on bronchial hyperresponsiveness as the primary outcome variable.. Twenty-four patients with mild-to-moderate asthma were studied using a randomized crossover design with the following three treatment blocks: (1) beclomethasone, 100 microg/d, alone for the first 2 weeks followed by 400 microg/d alone for the next 2 weeks; (2) beclomethasone, 100 microg/d, followed by 400 microg/d, with the addition of zafirlukast, 20 mg bid; (3) beclomethasone, 100 microg/d, followed by 400 microg/d, with the addition of theophylline, 200 to 300 mg bid. Measurements were made after 2 and 4 weeks of each treatment and at pretreatment baseline.. The mean trough plasma theophylline concentration was 6.7 mg/L, coinciding with the anti-inflammatory target range (ie, 5 to 10 mg/L). The provocative dose of methacholine causing a 20% fall in FEV(1) (as doubling dose difference from baseline) was significantly (p < 0.05) greater with beclomethasone, 100 microg, plus zafirlukast (1.1 doubling dose) but not with beclomethasone, 100 microg, plus theophylline (0.7 doubling dose) compared to beclomethasone, 100 microg alone (0.4 doubling dose), but not compared to beclomethasone, 400 microg alone (1.1 doubling dose). There were also significant (p < 0.05) differences between beclomethasone, 100 microg, plus zafirlukast (but not BDP, 100 microg, plus theophylline) vs beclomethasone, 100 microg, alone in terms of nitric oxide level, midexpiratory phase of forced expiratory flow, and peak expiratory flow. There were no further significant improvements observed with the addition of zafirlukast or theophylline to beclomethasone, 400 microg.. A leukotriene receptor antagonist, but not low-dose theophylline, conferred significant additive anti-inflammatory effects to therapy with a low-dose inhaled corticosteroid but not to that with a medium dose of an inhaled corticosteroid. Thus, optimizing the dose of inhaled corticosteroid as monotherapy would seem to be the logical first step, which is in keeping with current guidelines.

Topics: Administration, Inhalation; Administration, Oral; Adult; Anti-Asthmatic Agents; Asthma; Beclomethasone; Bronchial Hyperreactivity; Child; Cross-Over Studies; Drug Administration Schedule; Female; Humans; Indoles; Leukotriene Antagonists; Male; Middle Aged; Phenylcarbamates; Respiratory Function Tests; Sulfonamides; Theophylline; Tosyl Compounds

Exhaled nitric oxide (eNO) is an easily measured marker of airway inflammation. This study was undertaken to evaluate the usefulness of serial eNO in investigating the dose-response relationship for inhaled beclomethasone (BDP), and to compare eNO with other markers of airway inflammation. Following withdrawal of inhaled corticosteroid (ICS) therapy, 65 patients entered a double-blind, parallel-group, placebo-controlled trial of 50, 100, 200 or 500 microg x BDP x day(-1) for eight weeks. eNO and spirometry were performed weekly and a hypertonic saline challenge with sputum induction was performed at the beginning and end of treatment. The relationship between the dose of ICS and changes in eNO and forced expiratory volume in one second (FEV1) was linear at 1 week and at the end of treatment. A linear dose-response relationship was also seen for sputum eosinophils. Changes in eNO correlated significantly with changes in sputum eosinophils. Changes in the provocative dose of saline causing a 15% fall in FEV1 saline did not differ across the treatment groups nor did they correlate with changes in other measurements. Exhaled nitric oxide may be used to assess the dose-response relationship for the anti-inflammatory effects of inhaled beclomethasone. The relationship found in this study was linear over the dose range 0-500 microg x day(-1) soon after commencing therapy and continued over time.

Topics: Administration, Inhalation; Adult; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Beclomethasone; Breath Tests; Bronchial Hyperreactivity; Dose-Response Relationship, Drug; Double-Blind Method; Eosinophils; Female; Humans; Inflammation; Male; Middle Aged; Nitric Oxide; Peak Expiratory Flow Rate; Saline Solution, Hypertonic; Sputum

The aim of this study was to compare the efficacy of BDP 200 microg bid via metered dose inhaler, using HFA-134a (Chiesi Farmaceutici S.p.A., Parma, Italy) versus CFC (Becotide, Allen & Hanburys, U.K.) as a propellant. 172 adult patients (86 in each group) with stable mild persistent asthma who completed a 7-day run-in period were randomized to receive a 6-week treatment in a double-blind, double dummy, parallel-group design; 164 patients completed the study. Morning and evening PEFR, use of rescue salbutamol, number of day-time and night-time asthma attacks, number of night-time awakenings and clinical symptoms were recorded daily on a diary card. Pulmonary function tests (FEV(1), FVC, PEFR, and MEF(50)) were measured at the clinic before and after the 1-week run-in period, and after 3 and 6 weeks of treatment. A challenge test with inhaled methacholine was completed at baseline and at the end of the treatment period to assess potential bronchial hyper-reactivity in a subgroup of subjects (n = 65; 34 HFA, 31 CFC). In accordance with asthma of mild severity (FEV(1) predicted over 90% in both groups), a small improvement in lung function compared to baseline was seen for both treatments, significantly for FEV(1) in BDP HFA and MEF(50) in both groups. The two formulations of BDP had similar efficacy for the primary outcome variable morning PEFR (ITT population mean difference 5.8 L/min; C.I. -4.9 to +16.5) as well as for the secondary outcomes of evening PEFR and clinic FEV(1). There were small improvements in methacholine PD(20) and PC20 in both groups, with no significant difference between treatments. A total of 22 and 19 drug-related adverse events were reported in the BDP HFA and CFC groups, respectively; most events were of seasonal nature or were local effects due to the use of inhaled corticosteroids. It can be concluded that the newly developed formulation of BDP given via HFA-134a seems to provide similar asthma control, compared with the same low daily dose of the active drug delivered via CFC. Further studies are needed using higher doses in moderate to severe asthma to confirm these preliminary findings.

Topics: Administration, Inhalation; Adult; Aerosol Propellants; Aerosols; Analysis of Variance; Anti-Asthmatic Agents; Asthma; Beclomethasone; Bronchial Hyperreactivity; Chlorofluorocarbons; Double-Blind Method; Female; Humans; Hydrocarbons, Fluorinated; Male; Middle Aged; Nebulizers and Vaporizers; Respiratory Function Tests

Treatment with inhaled corticosteroids reduces bronchial hyperresponsiveness and relieves airways obstruction in patients with asthma. Up to now, it is unknown whether initial improvements are maintained over a long period of time. Therefore, we assessed whether initial improvements in FEV(1), provocative concentration of histamine causing a 20% fall in FEV(1) (PC(20)), and peak expiratory flow (PEF) persist with a constant dose of inhaled corticosteroids. Furthermore, we investigated whether FEV(1), PC(20), PEF indexes, and symptom scores improve after increasing the dose of inhaled corticosteroids in patients who did not respond sufficiently to treatment with beclomethasone dipropionate (BDP), 800 microg/d.. Sixty-eight patients with bronchial hyperresponsiveness and airways obstruction completed a previous study on 3 years of treatment with terbutaline, 500 microg qid, and BDP, 200 microg qid. Fifty-eight of these patients participated in the current extension of another 2.5 years of follow-up. Every 6 months, FEV(1) and PC(20) were measured. Five patients dropped out of the study, one for pulmonary reasons. Forty-four patients continued treatment with BDP, 800 microg/d (BDP-800 group), and 9 patients received a higher dose of BDP (500 microg tid; BDP-1,500 group) after the first 3 years because of a rapid decline in FEV(1) (> 50 mL/yr) despite BDP treatment during the previous study period.. After the initial improvement, the mean slope of individual regression lines for FEV(1), PC(20), and morning PEF were - 28 mL/yr, - 0.01 doubling concentrations per year, and 0.6 L/min/yr, respectively, in the BDP-800 group. In the BDP-1,500 group, there were no statistically significant improvements in FEV(1), PC(20), PEF indexes, and symptom scores after increasing the dose of BDP.. We conclude that initial improvements in FEV(1), PC(20), and PEF are well preserved over 5 years in patients with obstructive airways diseases who are treated with terbutaline and BDP. In the patients who responded sufficiently to 800 microg/d of BDP, there was no accelerated decline in FEV(1) compared with the general population. Increasing the dose of BDP in a small group of patients with an accelerated fall in FEV(1) (initially treated with a moderate dose of BDP) resulted in no significant improvement in FEV(1), PC(20), PEF indexes, and symptom scores.

Topics: Administration, Inhalation; Adult; Anti-Asthmatic Agents; Asthma; Beclomethasone; Bronchial Hyperreactivity; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Long-Term Care; Lung Volume Measurements; Male; Middle Aged; Terbutaline; Treatment Outcome

To observe the systemic side effects of low dose inhaled Beclomethasone dipropionate (BDP) in children with mild asthma.. 30 children with mild asthma were randomly divided into 3 groups to receive treatment with inhaled placebo (group A), BDP 200 micrograms/d (group B) and BDP 400 micrograms/d (group C) respectively. Bronchial hyperresponsiveness (BHR), height growth, bone mineral density (BMD), calcium and phosphate metabolism and hypothalamic-pituitary-adrenal axis (HPAA) function were measured.. Inhaled BDP of 200 micrograms/d and 400 micrograms/d reduced BHR in mild asthmatic children and there was no significant difference between two groups [log(PD20-FEV1)]:(2.04 +/- 0.47) micrograms to (2.70 +/- 0.13) micrograms in group A and (1.94 +/- 0.46) micrograms to (3.15 +/- 0.18) micrograms in group B (P < 0.01). Serum osteocalcin, calcium, phosphate, alkaline phosphatase, basic cortisol and BMD didn't change significantly after BDP treatment in three groups (all P > 0.05) [In group A, B and C, concentrations serum osteocalcin were (29 +/- 12) micrograms/L, (22 +/- 6) micrograms/L, (31 +/- 11) micrograms/L, serum calcium: (2.49 +/- 0.11) mmol/L, (2.39 +/- 0.28) mmol/L, (2.20 +/- 0.35) mmol/L, serum phosphate: (1.8 +/- 0.6) mmol/L, (1.7 +/- 0.7) mmol/L, (1.5 +/- 0.4) mmol/L, radius BMD: (0.44 +/- 0.02) g/cm2, (0.42 +/- 0.05) g/cm2, (0.40 +/- 0.10) g/cm2, ulna BMD:(0.35 +/- 0.04) g/cm2, (0.36 +/- 0.08) g/cm2, (0.32 +/- 0.07) g/cm2, serum alkaline phosphatase: (410 +/- 113) U/L, (337 +/- 99) U/L, (351 +/- 122) U/L, serum basic cortisol: (350 +/- 86) nmol/L, (407 +/- 199) nmol/L, (365 +/- 71) nmol/L, lumbar spine (L4-5) BMD: (0.64 +/- 0.06) g/cm2, (0.59 +/- 0.08) g/cm2, (0.62 +/- 0.09) g/cm2 respectively]. Height growth had a trend of reducing after BDP treatment though not reaching statistical difference. Height standard deviation score (SDS): 1.1 +/- 0.7 to 1.2 +/- 0.9 in group A, 1.3 +/- 0.7 to 1.3 +/- 0.9 in group B and 1.1 +/- 0.7 to 1.0 +/- 0.7 in group C. Serum cortisol after ACTH stimulation reduced significantly in group C [(621 +/- 199) nmol/L to (482 +/- 97) nmol/L, P < 0.01].. The results of this study suggest that 200 micrograms/d BDP can reduce BHR significantly and has no detected systemic side effects in mild asthmatic children, and 400 micrograms/d BDP can reduce serum cortisol after ACTH stimulation. The long-term dose of BDP should be controlled to be less than 400 micrograms/d in children with mild asthma.

Topics: Administration, Inhalation; Adolescent; Adrenal Cortex Hormones; Anti-Asthmatic Agents; Asthma; Beclomethasone; Bronchial Hyperreactivity; Child; Dose-Response Relationship, Drug; Female; Glucocorticoids; Humans; Male; Single-Blind Method

Treatment with inhaled corticosteroids improves symptoms and reduces bronchial hyperresponsiveness (BHR) associated with asthma. Delivery of drugs into the lung is dependent on the inhaler device. Furthermore, environmental concerns regarding the use of chlorofluorocarbon propellants in pressurised inhalers and patient acceptability of inhaler devices both influence the extent of use of different delivery systems.. To compare the efficacy of beclomethasone dipropionate (BDP) administered via a novel multidose dry-powder inhaler (DPI) and a conventional pressurised metered-dose inhaler (pMDI) with spacer in patients with BHR.. A randomised, double-blind, crossover study was carried out in a group of 27 patients (aged 19-55 years) with a clinical diagnosis of reversible airway disease, who demonstrated BHR to methacholine (PD(20) < or =6.4 mg). Each patient received BDP (< or =2 mg/day) via the DPI or pMDI, for periods of 4 weeks. The randomised treatment periods were preceded by 3-week washout periods when no corticosteroid was used. Five clinic visits marked the start and end of each study phase. The primary efficacy endpoint was BHR as defined by the pharmacodynamic parameter, PD(20), which was determined at the start and end of each treatment period. Clinical endpoints including lung function, symptoms and adverse events were also evaluated.. Both treatments caused a significant decrease in BHR (p<0.05 vs. pre-treatment values). Mean +/- SD changes in log PD(20) were: DPI 0.59+/-1.29; pMDI 0.59+/-0.94 mg. There was no statistically significant difference between treatments and no evidence of a carry-over effect between treatments on BHR. Clinical efficacy and safety parameters also demonstrated no statistically significant treatment differences, and patients found the DPI easier to use.. Efficacy of BDP in reducing BHR is comparable via the DPI and pMDI plus spacer.

Topics: Administration, Inhalation; Adult; Analysis of Variance; Asthma; Beclomethasone; Bronchial Hyperreactivity; Cross-Over Studies; Dose-Response Relationship, Drug; Double-Blind Method; Equipment Design; Female; Follow-Up Studies; Humans; Male; Methacholine Chloride; Nebulizers and Vaporizers; Respiratory Function Tests; Statistics, Nonparametric

In the United Kingdom, about 40% of patients with asthma are homozygous for the glycine-16 beta(2)-adrenoceptor polymorphism, which predisposes them to agonist-induced down-regulation and desensitization of the beta(2)-adrenoceptor. We assessed the effects of adding treatment with either a long-acting beta(2)-agonist (inhaled formoterol, 12 microg twice daily) or a leukotriene receptor antagonist (oral zafirlukast, 20 mg twice daily) to inhaled corticosteroid therapy in patients with this genotype.. We enrolled 24 patients with mild to moderate asthma who were being treated with inhaled corticosteroids. Patients were randomly assigned to receive one of three treatments (placebo, zafirlukast, or formoterol in addition to inhaled corticosteroids) for 1 week each in a crossover fashion, separated by a 1-week placebo run-in and washout period. Measurements of bronchoprotection (measured as the provocative dose of methacholine that produced a 20% decline in forced expiratory volume in 1 second [FEV(1)]), exhaled nitric oxide (a surrogate marker of airway inflammation), and symptoms were made before each treatment and 12 hours after the last dose of each treatment.. Both formoterol and zafirlukast were equally effective in maintaining asthma control compared with placebo: the geometric mean-fold difference in the methacholine provocative dose was 1.5-fold (95% confidence interval [CI]: 1.1- to 2.2-fold) for zafirlukast and 1.9-fold (95% CI: 1.2- to 2.9-fold) for formoterol. As compared with placebo, zafirlukast caused a significant suppression in exhaled nitric oxide (1.7-fold difference in geometric mean values, 95% CI: 1.1- to 2.6-fold) but formoterol did not (1.2-fold difference, 95% CI: 0.8- to 1.9-fold). Diary cards showed significant (P <0.05) improvements in the peak flow with formoterol (morning and evening) and zafirlukast (evening) as compared with placebo.. Formoterol and zafirlukast maintained asthma control in patients who might be genetically predisposed to fare worse with long-acting beta(2)-agonists. The reduction in exhaled nitric oxide with zafirlukast suggests that it may have anti-inflammatory effects in addition to those seen with inhaled corticosteroids.

Topics: Administration, Inhalation; Adrenergic beta-Agonists; Adult; Aged; Anti-Asthmatic Agents; Asthma; Beclomethasone; Bronchial Hyperreactivity; Bronchodilator Agents; Confidence Intervals; Cross-Over Studies; Ethanolamines; Female; Forced Expiratory Volume; Formoterol Fumarate; Genotype; Glucocorticoids; Glycine; Homozygote; Humans; Indoles; Leukotriene Antagonists; Male; Middle Aged; Nitric Oxide; Phenylcarbamates; Placebos; Polymorphism, Genetic; Receptors, Adrenergic, beta-2; Sulfonamides; Tosyl Compounds

It has been reported that intranasal corticosteroids can influence bronchial hyperresponsiveness (BHR) in asthmatic subjects with seasonal rhinitis. The purpose of the present study was to evaluate the effect of intranasal fluticasone propionate and beclomethasone dipropionate on BHR and bronchial calibre (forced expiratory volume in one second, FEV(1)) in children and young adults with seasonal rhinitis and mild asthma during two consecutive grass pollen seasons.. In the first pollen season 25 patients aged 8-28 years were included in a double blind, placebo controlled study. The active treatment group used fluticasone aqueous spray 200 microgram once daily. In the second pollen season 72 patients aged 8-28 years participated in a double blind, placebo controlled study of a similar design to that of the previous year except that an additional treatment group of patients using beclomethasone 200 microg twice daily was included. FEV(1) was measured before and after three and six weeks of treatment; BHR to methacholine (PD(20)) was measured before and after six weeks of treatment.. In the first season the mean (SD) logPD(20) of the patients decreased significantly both in the fluticasone group (from 2.43 (0.8) microgram to 1.86 (0.85) microgram) and in the placebo group (from 2.41 (0.42) microgram to 1.87 (0.78) microgram) without any intergroup difference in the change in logPD(20). In the second pollen season the mean logPD(20) in the fluticasone, beclomethasone, and placebo groups did not change significantly.. Intranasal steroids did not influence BHR during two grass pollen seasons in children and young adults with seasonal rhinitis and mild asthma.

Topics: Administration, Intranasal; Adolescent; Adult; Allergens; Androstadienes; Anti-Allergic Agents; Anti-Asthmatic Agents; Asthma; Beclomethasone; Bronchial Hyperreactivity; Child; Double-Blind Method; Female; Fluticasone; Forced Expiratory Volume; Humans; Male; Patient Compliance; Pollen; Rhinitis, Allergic, Seasonal; Treatment Outcome

To assess the role of bronchial hyperreactivity (BHR) in patients with mitral stenosis and to evaluate the effect of inhaled corticosteroids in treating these patients.. Histamine bronchial provocation testing was performed in 23 patients with mitral stenosis. Patients with BHR were randomized into beclomethasone treatment and placebo group. Patients without BHR were also treated with beclomethasone as controls.. 15 patients showed BHR. His PD20-FEV1 were significantly higher after 6 weeks treatment (P < 0.05), and symptom scores significantly lower(P < 0.05) in beclomethasone treatment group while remained unchanged in placebo group(P > 0.05).. BHR is commonly found in patients with symptomatic mitral stenosis. Beclomethasone can significantly decrease bronchial reactivity to histamine and improve symptoms in patients with mitral stenosis.

Topics: Administration, Inhalation; Adult; Anti-Asthmatic Agents; Beclomethasone; Bronchial Hyperreactivity; Female; Humans; Male; Mitral Valve Stenosis; Treatment Outcome

Home exposure to high levels of house dust mite allergen has been shown to aggravate airways reactivity and asthma.. The purpose of this study was to determine whether specific house dust mite control measures could reduce exposure levels and asthma severity.. This double-blinded, randomized trial compared asthma progression over 1 year in children whose homes received standard environmental control intervention with those whose homes received aggressive intervention for dust mite elimination. The primary end point was doubling in PD20 methacholine.. Symptom scores and quality-of-life scores were similar for the standard and aggressive intervention groups. PD20 methacholine doubling occurred in 9 members of the aggressive intervention group vs 4 control patients (P <.05). Dust mite levels decreased in the aggressive intervention homes compared with the standard intervention homes (P <.05).. Aggressive dust mite intervention decreased dust mite levels and improved bronchial hyperresponsiveness.

Topics: Adolescent; Air Pollution, Indoor; Allergens; Animals; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Antigens; Asthma; Beclomethasone; Bronchial Hyperreactivity; Child; Cromolyn Sodium; Dust; Environmental Pollutants; Glycoproteins; Humans; Methacholine Chloride; Mites; Respiratory Function Tests; Socioeconomic Factors; Triamcinolone

While inhaled steroids (IS) are increasingly recognized as having a more rapid onset of action than was once thought, little is known about the early changes in objective measures of respiratory function that follow the inhalation of repeated doses. These early effects were examined in a randomized, double-blind, placebo-controlled, crossover study of 20 children aged 10-16 years with stable mild asthma. Beclomethasone dipropionate (BDP) 2,000 mcg, fluticasone propionate (FP) 400 mcg, and placebo were given twice daily for three doses. Airway hyperreactivity (AHR) to methacholine (PC20), pulmonary function tests (PFT: FVC, FEV1, FEF25-75%), and the rate of recovery from methacholine-induced bronchospasm following administration of salbutamol were determined at 8 h (after 1 dose) and at 32 h (after three doses). At 8 h, minor improvements in AHR were demonstrated, averaging 0.32 doubling doses in PC20. At 32 h, significant improvements in AHR and PFTs were present, averaging 0.92 doubling doses in PC20, 3.96% of predicted values in FEV1, and 7.74% of predicted values in FEF25-75%. No significant changes occurred in FVC. There were no significant differences between the effects of BDP and FP. Inhaled steroids were associated with a slower response to salbutamol following methacholine challenge testing at 32 h. We conclude that IS, given in repeated high doses, result in significant improvements within 32 h in both AHR and PFTs, along with changes in response to beta2 agonists. These effects are likely to be the result of the topical activity of IS.

Topics: Administration, Inhalation; Adolescent; Androstadienes; Anti-Asthmatic Agents; Asthma; Beclomethasone; Bronchial Hyperreactivity; Bronchial Provocation Tests; Child; Cross-Over Studies; Double-Blind Method; Female; Fluticasone; Glucocorticoids; Humans; Male; Respiratory Function Tests; Respiratory Mechanics; Treatment Outcome

In school children with atopic asthma the beneficial effects of disodium cromoglycate (DSCG) and beclomethasone dipropionate (BDP) are well-established. In preschool children, wheezing is quite common, and in the majority of cases the symptoms are episodic and reported to be associated with viral infections rather than atopy. We compared the efficacy of regular treatment with DSCG and BDP for prevention of wheezing in preschool children. We were interested to establish whether regular treatment with inhaled anti-inflammatory drugs could lead to a decrease in bronchial responsiveness. In 15 patients (median age, 56 months; range, 43-66 months) bronchial responsiveness was assessed by measuring specific airway resistance (sRaw) during a histamine provocation test. The concentration of histamine eliciting a 100% increase in sRaw (PC100his) was determined. In a double-blind crossover study, patients inhaled either DSCG 10 mg three times a day or BDP 100 microg three times a day for 2 months. After a wash-out period, treatment was changed to BDP or DSCG, respectively. Daily peak flow measurements were carried out, and exacerbations were noted. PC100his was measured at the start and end of each treatment period. No significant decrease in bronchial responsiveness was seen (PC100his DSCG: before 1.3, after 1.66 mg/ml, Pvalue not significant; BDP: before 1.1 after 1.22 mg/ml, Pvalue not significant). Significantly higher morning peak flows were observed on BDP therapy (160 on BDP vs. 150 L/min on DSCG, P < 0.03). BDP treatment resulted in significantly fewer wheezing exacerbations (7 vs. 16, P < 0.005) compared with DSCG therapy. We conclude that in preschool children with episodic virally induced wheezing, BDP therapy was superior to DSCG aerosol treatments for the prevention of exacerbations of wheezing, although no significant effect on bronchial responsiveness was noted during either treatment protocol.

Topics: Administration, Inhalation; Airway Resistance; Anti-Asthmatic Agents; Beclomethasone; Bronchial Hyperreactivity; Bronchial Provocation Tests; Chi-Square Distribution; Child, Preschool; Cromolyn Sodium; Cross-Over Studies; Double-Blind Method; Female; Forced Expiratory Volume; Humans; Male; Peak Expiratory Flow Rate; Respiratory Sounds; Respiratory Tract Infections; Statistics, Nonparametric; Virus Diseases

The measurement of exhaled nitric oxide (ENO) is recognized as a marker of airway inflammation. ENO was measured in 10 nonsteroid-treated asthmatics at recruitment, during 3 weeks of inhaled beclomethasone (1000 microg/day) and for 3 weeks after withdrawal. Baseline ENO was increased in asthma compared with nonasthmatics (85.0+/-54.5 vs. 24.5+/-14.8 ppb, p < 0.0001). After inhaled steroid, there was no significant change in forced expiratory volume in 1 sec (FEV1) and forced vital capacity (FVC), but methacholine PC20 rose significantly (p = 0.0345). ENO (mean+/-SD; % baseline) fell after 1 week on steroid to 60.6+/-31.1 and rose to 95.3+/-46.1 at 1 week after withdrawal. ENO did not correlate with PC20 or FEV1. The changes in ENO and PC20 were inversely correlated (r2 = 0.325). ENO may be an index of airway inflammation and therapeutic response in bronchial asthma.

Topics: Administration, Inhalation; Adult; Asthma; Beclomethasone; Breath Tests; Bronchial Hyperreactivity; Bronchial Provocation Tests; Cross-Over Studies; Female; Forced Expiratory Volume; Humans; Inflammation; Male; Methacholine Chloride; Nitric Oxide; Vital Capacity

To test the hypothesis that inhaled salbutamol or beclomethasone will reduce the frequency of cough in children with recurrent cough. A secondary aim was to determine if the presence of airway hyperresponsiveness (AHR) can predict the response.. Randomised, double blind, placebo controlled trial.. During a coughing phase, 43 children (age 6-17 years) with recurrent cough were randomised to receive inhaled salbutamol or placebo (phase I) for 5-7 days and then beclomethasone or placebo (phase II) for 4-5 weeks, and in a subgroup of children for 8-9 weeks. The children used an ambulatory cough meter, kept cough diaries, and performed the capsaicin cough sensitivity, hypertonic saline bronchoprovocation, and skin prick tests.. Salbutamol or beclomethasone had no effect on cough frequency or score, irrespective of the presence of AHR.. Most children with recurrent cough without other evidence of airway obstruction, do not have asthma and neither inhaled salbutamol nor beclomethasone is beneficial.

Topics: Administration, Inhalation; Adolescent; Adrenergic beta-Agonists; Albuterol; Beclomethasone; Bronchial Hyperreactivity; Child; Cough; Double-Blind Method; Drug Therapy, Combination; Female; Glucocorticoids; Humans; Lung; Male; Placebos; Recurrence; Spirometry; Treatment Failure

Airway inflammation is a major factor in the pathogenesis of asthma. Inducing sputum by hypertonic saline is a noninvasive method of assessment of the airway inflammation in asthmatic patients. To investigate sputum induction as a method for assessing airway inflammation and to evaluate the effect of inhaled beclomethasone dipropionate (BDP) in asthmatic patients, we examined the bronchial hyperresponsibility (BHR), pulmonary function and differential cell counts in induced sputum of the patients before and after BDP therapy. In asthmatic patients, the percentage of eosinophils in induced sputum was significantly higher than that in non-asthmatic subjects. Ten patients with atopic asthma (four men and six women; mean [+/- SD] age, 30.5 +/- 12.4 years) participated. Their mean percentage of eosinophils (% eosinophils) in induced sputum fell from 22.9 +/- 7.2% to 13.9 +/- 8.3% (p < 0.05) by 3 months of BDP treatment. The percentage of eosinophils in induced sputum before BDP treatment was significantly correlated with the ratio of the forced expiratory volume in one second to the forced vital capacity (FEV1%) at baseline (r = -0.75, p < 0.05), but not with log Dmin at baseline (p = 0.18). The change in FEV1% between at baseline and post-treatment correlated significantly with the change in the sputum eosinophil percentage (r = -0.79, p < 0.01). In addition, there was a significant correlation between the change of log Dmin and the change of the sputum eosinophil percentage (r = -0.64, p < 0.05). In conclusion, analysis of induced sputum is a safe, noninvasive, repeatable and useful method to assess the clinical condition of bronchial inflammation in patients with bronchial asthma.

Topics: Administration, Inhalation; Adult; Anti-Asthmatic Agents; Asthma; Beclomethasone; Bronchial Hyperreactivity; Bronchial Provocation Tests; Eosinophils; Female; Humans; Lymphocyte Count; Male; Middle Aged; Regression Analysis; Sensitivity and Specificity; Sputum; Treatment Outcome

To better understand the effects of corticosteroid inhalation on asthma and asymptomatic bronchial hyperresponsiveness (BHR).. A double blind, randomized study was conducted to compare the effects of beclomethasone dry powder (BDP, 600 micrograms/day) inhalation with placebo on BHR and asthmatic symptoms in 59 students (12-18 yrs) for one year.. After one year of treatment, lgPD20-FEV1 increased significantly in asthmatics in the BDP group (0.385 +/- 0.424 vs 1.187 +/- 0.603 mumol histamine). Thirty percent of asthmatics in BDP group and 86% in the control group developed symptoms in this year (P = 0.076). There was no significant difference in lgPD20-FEV1 between the BDP and the control group in asymptomatic BHR students. However, none in the BDP group of asymptomatic BHR students developed asthmatic symptoms compared with 3 cases (15%) in control group. The accumulative symptom score showed significant difference between the BDP group and the control group in asymptomatic BHR students (1.50 +/- 2.54 vs 5.58 +/- 6.22, P < 0.01).. The results suggested that BDP could significantly relieve the severity of BHR and symptoms in asthmatics, and could have some prophylactic effects on the development of asthma in those with asymptomatic BHR.

Topics: Administration, Inhalation; Adolescent; Anti-Asthmatic Agents; Asthma; Beclomethasone; Bronchial Hyperreactivity; Child; Double-Blind Method; Female; Forced Expiratory Volume; Humans; Male

Isocapnic hyperventilation with cold air (IHCA) is a reliable technique for assessing indirect bronchial hyperresponsiveness in patients with asthma. Impedance measurement of the respiratory system by the forced pseudorandom noise oscillation technique is a sensitive technique to assess changes in bronchial tone after IHCA. The aim of this study was to evaluate the effect of 6 weeks of treatment with beclomethasone dipropionate, 1,000 microg x day-1, on IHCA in asthmatic patients, measured with both forced oscillation technique and flow-volume recordings. Forty patients with mild asthma were included in this double-blind, placebo-controlled parallel-group study. Stratification on the basis of sex was performed to overcome differences in airway diameter. At entry and every 2 weeks during the treatment period, IHCA was performed and patient diaries were evaluated. Characteristic changes in forced oscillation parameters after IHCA were observed in all patients. After 6 weeks of treatment, BDP-treated patients showed statistically significant differences in impedance measurements after IHCA, manifested by significant attenuation of resistance at 8 Hz (p<0.01), slope of the frequency-resistance curve (p<0.01), reactance at 8 Hz (p=0.01), and resonant frequency (f0) (p<0.02). Flow-volume recordings showed only a statistically significant change in the decrease of inspiratory vital capacity (IVC) (p=0.01). Furthermore, a significant correlation was observed between serum immunoglobulin E (IgE) levels and the effect of BDP on IHCA, measured with forced oscillation technique. In this study, beclomethasone dipropionate, 1,000 microg x day(-1) for 6 weeks, decreased indirect bronchial hyperresponsiveness as assessed by cold air bronchoprovocation in asthmatic patients. The forced oscillation technique proved a more sensitive method of detecting changes in bronchial tone than flow-volume recordings.

Topics: Adult; Airway Resistance; Anti-Asthmatic Agents; Asthma; Beclomethasone; Bronchial Hyperreactivity; Bronchial Provocation Tests; Cold Temperature; Double-Blind Method; Female; Forced Expiratory Volume; Humans; Male; Peak Expiratory Flow Rate

An inhaled glucocorticoid is currently the medication of choice for long-term control of persistent asthma in children. The role of long-acting beta2-adrenergic-receptor agonists, such as salmeterol, needs to be defined.. We conducted a randomized, double-blind, placebo-controlled, parallel-group, one-year study of 241 children (mean [+/-SD] age, 9.3+/-2.4 years) with clinically stable asthma and less than one month of prior glucocorticoid use. We compared inhaled beclomethasone dipropionate (200 microg twice daily) with salmeterol xinafoate (50 microg twice daily) and placebo (lactose). The primary outcome measure, airway responsiveness (as assessed with a methacholine challenge) was evaluated before treatment; after 3, 6, 9, and 12 months of treatment (12 and 36 hours after study medications had been withheld); and 2 weeks after the end of treatment. Spirometry, symptoms, use of rescue medication (200 microg of albuterol inhaled as needed), and adverse effects were also assessed.. During months 1 through 12 overall, beclomethasone was associated with significantly less airway hyperresponsiveness than salmeterol (P= 0.003) or placebo (P<0.001). This effect was lost two weeks after treatment had been stopped. As compared with placebo, beclomethasone was associated with less variability between morning and evening in the peak expiratory flow (P=0.002), as was salmeterol (P=0.02). Beclomethasone was also associated with a reduced need for albuterol as rescue therapy (P<0.001) and fewer withdrawals because of asthma exacerbations (P=0.03), but salmeterol was not (P=0.09 and 0.55, respectively). During months 1 through 12, linear growth was 3.96 cm in the children receiving beclomethasone, as compared with 5.40 cm in the salmeterol group (P=0.004) and 5.04 cm in the placebo group (P=0.018). Height was not measured after treatment ended.. Beclomethasone was effective in reducing airway hyperresponsiveness and in controlling symptoms of asthma, but it was associated with decreased linear growth. Salmeterol was not as effective as beclomethasone in reducing airway hyperresponsiveness or in controlling symptoms; however, it was an effective bronchodilator and was not associated with rebound airway hyperresponsiveness, masking of symptoms, or adverse effects.

Topics: Administration, Inhalation; Adolescent; Adrenergic beta-Agonists; Albuterol; Asthma; Beclomethasone; Bronchial Hyperreactivity; Bronchodilator Agents; Child; Double-Blind Method; Female; Glucocorticoids; Growth; Humans; Male; Placebos; Pulmonary Ventilation; Salmeterol Xinafoate

The efficacy of nedocromil sodium (NED) (8mg twice daily) in controlling the clinical symptoms of asthma (score symptoms), the pulmonary parameters (FEV1, FVC) and bronchial hyperreactivity to histamine was assessed. The study was performed in double-blind, cross-over and placebo-controlled way in 16 patients suffering from nonatopic, stable, moderate asthma treated with beclomethasone dipropionate (from 400 micrograms to 800 micrograms). NED and placebo were administered in a randomized way with 8-week wash-out period. Bronchial reactivity to histamine, was measured as the amount of histamine causing a 20% fall in FEV1 (PC20H in mg/ml). Treatment with NED did not change asthma symptom scores, FVC and FEV1. Decreased usage of beta 2-agonist was observed. NED did not influence bronchial hyperreactivity to histamine (xg PC20H was respectively 0.09 and 0.11 mg/ml after placebo and 0.06 and 0.08 after NED). The authors conclude that studies with NED in nonatopic asthmatics should be continued, but the dosage of the drug ought to be bigger and the time of treatment ought to be longer.

Topics: Adult; Aged; Asthma; Beclomethasone; Bronchial Hyperreactivity; Double-Blind Method; Drug Administration Schedule; Drug Interactions; Female; Histamine; Humans; Male; Middle Aged; Nedocromil; Respiratory Function Tests; Treatment Outcome

Occupational asthma (OA) is a useful model for the study of asthma in humans. The possibility that inhaled corticosteroids, in addition to withdrawal from the workplace, could improve clinical and functional recovery from OA can be hypothesized. We assessed clinical, functional, and behavioral characteristics of 32 subjects (22 male, 10 female), in all but one of whom OA was confirmed by specific inhalation challenges induced by either high- (n=13) or low-molecular-weight (n=19) agents within 3 mo after cessation of exposure. In this randomized, crossover, double-blind study, subjects (paired for baseline PC20 and duration of symptoms after exposure) received either placebo or 1,000 micrograms of inhaled beclomethasone daily for 1 yr, followed by the alternate medication for 6 mo. Various clinical, functional, and behavioral parameters were examined at each 3-mo visit. Significant improvement in clinical (nocturnal symptoms, cough), functional (morning and evening peak expiratory flow rates), and behavioral (quality of life) parameters were detected in the active-treatment period, although the magnitude of the improvement was relatively small. Side effects (oropharyngeal, reduced cortisol) were similar in the placebo and treatment groups. Distinguishing subjects who started with the active preparation from those who were given placebo first showed that most clinical and behavioral parameters improved in the former instance, whereas there was no significant difference in the latter. We conclude that inhaled corticosteroids induce a small but significant overall improvement of the asthmatic condition in subjects with occupational asthma caused by high- and low-molecular-weight agents after withdrawal from exposure. The beneficial effect is, however, more pronounced if inhaled steroids are given early after diagnosis.

Topics: Administration, Inhalation; Adult; Allergens; Anti-Asthmatic Agents; Asthma; Beclomethasone; Bronchial Hyperreactivity; Bronchial Provocation Tests; Candida albicans; Cough; Cross-Over Studies; Double-Blind Method; Female; Forced Expiratory Volume; Glucocorticoids; Humans; Hydrocortisone; Male; Middle Aged; Molecular Weight; Occupational Diseases; Occupational Exposure; Oropharynx; Peak Expiratory Flow Rate; Quality of Life; Vital Capacity

A study was done to compare the efficacy and safety of the coprescription of salmeterol 50 microgram twice daily or 100 microgram twice daily with beclomethasone dipropionate (BDP) 500 micrograms twice daily (SALM 50 and SALM 100) with BDP 1,000 microgram twice daily (BDP 1,000) in patients with asthma not controlled by BDP 500 microgram twice daily (or the equivalent). Following a run-in period, 738 patients at 72 centers were randomized to treatment for 24 wk in a double-blind, parallel-group study during which they maintained a daily record of peak expiratory flow rates (PEFRs) and symptom scores. At about 40 of the centers, bronchial hyperresponsiveness (BHR) to histamine was measured during and at 3 and 14 d after stopping treatment. Both groups taking salmeterol showed an improvement of more than 45 L/min in their morning PEFR and 30 L/min in their evening PEFR, compared with respective improvements of 16 L/min and 6 L/min in the group taking BDP 1,000. Both the SALM 50 and SALM 100 groups had a significantly increased percentage of symptom-free and rescue-free days and nights compared with the BDP 1,000 group, and there was no difference between the two salmeterol groups. None of the treatments altered BHR. Exacerbation rates did not differ among the three groups. We conclude that in this selected group of symptomatic patients taking BDP 500 micrograms twice daily, the addition of salmeterol provides better improvement in lung function and symptom control, without altering BHR or increasing exacerbation rates, than does doubling the dose of BDP.

Topics: Administration, Inhalation; Adolescent; Adrenergic beta-Agonists; Adult; Aged; Albuterol; Anti-Asthmatic Agents; Asthma; Beclomethasone; Bronchial Hyperreactivity; Bronchial Provocation Tests; Bronchodilator Agents; Double-Blind Method; Drug Combinations; Female; Forced Expiratory Volume; Histamine; Humans; Lung; Male; Middle Aged; Peak Expiratory Flow Rate; Salmeterol Xinafoate

60 patients aged 16 to 46 years with seasonal allergic rhinitis were selected for study. Daily symptom scores of seasonal allergic rhinitis and nonspecific bronchial hyperresponsiveness to histamine (PC20H in mg/ml) before, during the pollen season and after 3 weeks of treatment with loratadine, beclomethasone dipropionate were evaluated. The control group received oxymetazoline. Nonspecific bronchial hyperresponsiveness for 11 patients (18.3%) before the seasons was observed. At the beginning of the season frequency of nonspecific bronchial hyperresponsiveness increased to 26.3% and to 36.8% after 3-week treatment course. Bronchial hyperresponsiveness was not related to any of the way of treatment. The patients treated with beclomethasone dipropionate and oxymetazoline showed significant relief of nasal symptoms. The patients without bronchial hyperresponsiveness showed lower value of symptom scores.

Topics: Adolescent; Adult; Anti-Allergic Agents; Beclomethasone; Bronchial Hyperreactivity; Female; Humans; Loratadine; Male; Middle Aged; Nasal Decongestants; Oxymetazoline; Rhinitis, Allergic, Seasonal

Both smoking and asthma are associated with inflammatory changes in the lung, which may be suppressed with the help of exogenous anti-inflammatory drugs or by the endogenous defense system. Lipocortin-1 (LC-1; annexin-1) is an anti-inflammatory protein present in respiratory tract secretions. We report an inverse correlation between extracellular LC-1 concentration and the bronchoconstrictor prostaglandin (PG) D2 [n = 15, Spearman rank correlation coefficient (rS) = -0.597, P < 0.05] in bronchoalveolar lavage fluid (BALF) from allergic asthmatic patients, together with positive correlations between extracellular LC-1 per milliliter BALF and the prostacyclin (PGI2) metabolite 6-keto-PGF1 alpha (n = 15, rS = 0.480, P < 0.05) and between LC-1 per milliliter BALF and concentration of histamine causing a 20% decrease in forced expired volume in 1 s (n = 15, rS = 0.720, P < 0.01) in these subjects. We found no significant difference between the LC-1 concentration in BALF from nonsmoking asthmatic patients who were receiving inhaled glucocorticoid therapy (2 x 100 micrograms beclomethasone 4 times/day for 2.5 yr; median 186 ng LC-1/mg albumin; n = 6) and those who were not (median 126 ng LC-1/mg albumin; n = 12), perhaps because inhaled drugs deposit predominantly in central airways, which are poorly represented in bronchoalveolar lavage. Both asthmatic and healthy volunteers who smoked had higher levels of LC-1 in their BALF than did their nonsmoking counterparts (e.g., asthmatic smokers, median 317 ng LC-1/mg albumin, n = 10; asthmatic nonsmokers, median 162 ng LC-1/mg albumin, n = 18; P < 0.05), perhaps because smokers' lungs contain more alveolar macrophages, cells that release LC-1. We observed a positive correlation between BALF LC-1 and bronchoalveolar lavage cell number (n = 16, rS = 0.821, P < 0.001). Increased extracellular LC-1 may be part of a protective response of the lung to inflammatory insult. Regulation of prostanoid levels might be one mechanism by which LC-1 suppresses inflammation.

Topics: 6-Ketoprostaglandin F1 alpha; Administration, Inhalation; Adult; Annexin A1; Anti-Inflammatory Agents; Asthma; Beclomethasone; Bronchial Hyperreactivity; Bronchoalveolar Lavage Fluid; Eicosanoids; Female; Glucocorticoids; Histamine; Humans; Male; Middle Aged; Pulmonary Alveoli; Respiratory Function Tests; Smoking

Cetirizine is a non-sedating H1 antihistamine which is effective in the treatment of allergic rhinitis and urticaria. It inhibits eosinophil and basophil chemotaxis in late cutaneous allergic reactions in skin windows. Its effect on early (EAR) and late asthmatic reactions (LAR) is less certain.. We examined the effect on EAR and LAR of 3 days treatment with oral cetirizine (15 mg twice daily) compared with a single dose of inhaled beclomethasone 10 min prior to allergen challenge in a placebo-controlled (oral and inhaled) double-blind cross-over design with three treatment arms separated by 14 days.. Cetirizine did not significantly inhibit either the EAR or LAR documented by maximum percentage fall in FEV1 (0-3 and 6-9 h) or as area under the curve (AUC between 0 and 3 and 6-9 h). Beclomethasone inhibited the LAR compared with placebo (P = 0.02) when expressed as AUC (6-9 h). This did not quite reach statistical significance (P = 0.06) when expressed as maximal percentage late fall in FEV1 between 6 and 9 h. A greater than twofold increase in airways responsiveness to methacholine was observed 3 h after challenge which was significantly reduced by beclomethasone compared with placebo (P < 0.02) and cetirizine (P < 0.05). The data suggest that oral cetirizine does not significantly inhibit either the EAR or LAR. Beclomethasone inhibited both the early increase in airways responsiveness and the subsequent LAR. Our study also confirms the view that early increases in airway responsiveness precede the late response and suggests that these associated events are not dissociable by the pharmacological treatments employed in this study.

Topics: Administration, Inhalation; Administration, Oral; Adult; Allergens; Antigens, Dermatophagoides; Asthma; Beclomethasone; Bronchial Hyperreactivity; Cetirizine; Cross-Over Studies; Double-Blind Method; Female; Forced Expiratory Volume; Glycoproteins; Humans; Hypersensitivity, Immediate; Male; Middle Aged; Poaceae; Time Factors

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.. 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.. 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.. 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.

Topics: Adult; Androstadienes; Anti-Asthmatic Agents; Asthma; Beclomethasone; Bronchial Hyperreactivity; Bronchial Provocation Tests; Double-Blind Method; Female; Fluticasone; Forced Expiratory Volume; Humans; Hydrocortisone; Male; Peak Expiratory Flow Rate

To study the effects of an inhaled steroid on airway hyperresponsiveness (AHR) in chronic stable asthma, AHR was measured every month for 1 year in seven patients after their asthma had stabilized, i.e., when they had no wheezing or dyspnea, and their peak expiratory flow rates (PEFR) were at least 80 percent of the highest value. During the study period, no patient wheezed or had dyspnea, and daily variation in PEFR was less than 20 percent. In six patients, FEV1 was stable, and PEFR was always at least 80 percent of the highest value. AHR became less severe, by a factor of at least 2, in five of these six patients, but one patient's condition did not improve. The one patient whose PEFR fell below 80 percent of the highest value had more than a 4-fold increase in the severity of AHR. In conclusion, the severity of AHR can be reduced, even in patients with chronic stable asthma, if daily PEFR can be maintained in an optimal range by long-term use of inhaled corticosteroids.

Topics: Administration, Inhalation; Aged; Asthma; Beclomethasone; Bronchial Hyperreactivity; Chronic Disease; Female; Humans; Male; Middle Aged; Peak Expiratory Flow Rate

Salbutamol alone (400 micrograms per day) or salbutamol together with beclocort (1 mg per day) was used in 20 patients with mild asthma. 12 patients received during a month salbutamol combined with nedocromil (Tilade 8 mg per day). Prior starting treatment and after concluding a histamine provocation challenge was performed allowing to assess the bronchodilating properties of salbutamol. We conclude that: salbutamol alone produced a statistically nonsignificant increase of bronchial hyperactivity; a combination of salbutamol with beclocort or nedocromil did not increase the bronchial hyperactivity; during the three month trial with salbutamol alone or in a combination with a antiinflammatory agent the bronchodilatatory effect of salbutamol remained the same.

Topics: Adult; Albuterol; Asthma; Beclomethasone; Bronchial Hyperreactivity; Drug Therapy, Combination; Female; Humans; Male; Nedocromil; Treatment Outcome

The effect of treatment with topical inhaled corticosteroids was assessed in 15 children of low birth weight (mean (SD) birth weight 1435 (268) g, gestational age 30.5 (2.9) weeks, age at study 8.2 (0.4) years) who were symptomatic and showed a positive airway response to histamine aerosol. The study was of a double blind, placebo controlled, crossover design with four week long treatment periods with inhaled beclomethasone dipropionate (400 micrograms daily) or placebo. Daily symptom scores were recorded and physiological measurements were performed at the beginning and end of each treatment period. There was no significant difference in respiratory symptom score, baseline airway function, or the airway response to histamine between treatment periods. The findings argue against an inflammatory basis for airway hyper-responsiveness in these children and raise questions as to its pathophysiological basis.

Topics: Administration, Inhalation; Beclomethasone; Bronchial Hyperreactivity; Bronchial Provocation Tests; Child; Double-Blind Method; Female; Humans; Infant, Low Birth Weight; Infant, Newborn; Male

Although most patients with obstructive airways disease show some amelioration with long-term inhaled corticosteroid therapy, the extent of improvement may vary considerably between patients. Patients with mild to moderately severe obstructive airways disease (asthma and COPD) were selected if provocative concentration producing a 20% fall in forced expiratory volume in one second (PC20) < or = 8 mg.ml-1, and forced expiratory volume in one second (FEV1) < 95% confidence intervals (CI) of predicted normal. The independent influences of baseline PC20FEV1, inspiratory vital capacity (IVC), bronchodilator response, smoking habits, and allergy both on the "immediate" (within 3 months) response in FEV1 and the change in long-term (from 3 months onwards) slope of FEV1 with inhaled corticosteroids were analysed. Patients had a larger "immediate" improvement in their FEV1 with inhaled corticosteroids with each doubling doses lower PC20, with each ten-fold higher immunoglobulin E (IgE), and if they did not smoke. Total IgE proved a better independent predictor of "immediate" response than specific IgE for house dust mite, skin tests, or blood eosinophils. A more favourable long-term slope of FEV1 was predicted by a larger baseline bronchodilator response, but not by smoking. In conclusion, PC20, total IgE, and smoking habits are independent predictors of immediate treatment response to inhaled corticosteroids. Bronchodilator response is the single independent predictor of changes in long-term slope of FEV1 with corticosteroid treatment.

Topics: Administration, Inhalation; Adult; Asthma; Beclomethasone; Bronchi; Bronchial Hyperreactivity; Double-Blind Method; Drug Therapy, Combination; Female; Forced Expiratory Volume; Humans; Ipratropium; Lung Diseases, Obstructive; Male; Middle Aged; Prognosis; Smoking; Terbutaline

We investigated the effect of 5 months of treatment with inhaled beclomethasone dipropionate (BDP) on the airway responsiveness to methacholine (PD20 FEV1) and to toluene diisocyanate (TDI) in 15 sensitized asthmatic subjects who had been removed from occupational exposure to TDI. After the diagnosis was established by a positive inhalation challenge with TDI, each subject was removed from occupational exposure to isocyanates and treated with either BDP (1 mg twice per day, n = 7) or placebo (n = 8) for 5 months. The study was double blind for parallel groups. P20 FEV1 methacholine was measured before and three times during treatment and then at 6 months, that is, 4 wk after cessation of treatment. Airway sensitivity to TDI was assessed with specific inhalation challenge before treatment and at 6 months. Beclomethasone reduced the airway hyperresponsiveness to methacholine but did not affect the response to TDI. In fact, in the subjects on BDP, P20 FEV1 increased from 0.145 to 0.485 mg (p < 0.05) after 2 months of treatment. A further increase was observed at 4 and 5 months (0.548 and 0.629 mg, respectively, p < 0.01), and the improvement in nonspecific airway responsiveness was maintained after a 1-month washout period (0.637 mg, p < 0.01). In contrast, in the subjects on placebo, P20 FEV1 did not change significantly. At the end of the study, the severity of asthmatic reactions induced by bronchial challenge with TDI was significantly reduced in both groups, but no differences were observed between placebo and BDP.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adolescent; Adult; Asthma; Beclomethasone; Bronchial Hyperreactivity; Bronchial Provocation Tests; Double-Blind Method; Female; Forced Expiratory Volume; Humans; Hydrocortisone; Hypoglycemia; Insulin; Male; Methacholine Chloride; Middle Aged; Occupational Diseases; Placebos; Toluene 2,4-Diisocyanate

Bronchial mucosa inflammation is a hallmark of asthma. Epithelial damage due to inflammatory process may contribute to induce a pattern of rapid and shallow breathing (RSB). Probably due to its effects on inflammatory process, beclomethasone dipropionate (BDP) decreases bronchial hypersensitivity (BH), as assessed in terms of histamine concentration causing a 20 percent FEV1 decrease from saline solution (PC20FEV1); however, no data are available on the effect of BDP on RSB. We studied 32 asymptomatic asthmatic subjects with a severe to moderate levels of BH (PC20FEV1 0.01 to 1.7 mg/ml). After they were randomly assigned to one month of either BDP (2 mg daily, 17 patients) or placebo (15 patients), they inhaled progressively doubling concentrations of histamine phosphate by tidal breathing method. With histamine in seven BDP-treated and in five placebo-treated patients, decrease in FEV1 > or = 20 percent from saline solution was paralleled by a significant decrease in tidal volume (VT), inspiratory time (Ti), and expiratory time (Te), and increase in respiratory frequency (RF). In the remaining patients, histamine failed to change the breathing pattern. In the seven RSB patients, BDP resulted in a smaller VT decrease (p < 0.02) and a smaller RF increase (p < 0.02) with histamine. The five RSB placebo-treated patients were then given one month BDP (2 mg daily): inhaled BDP, but not placebo, resulted both in a significant increase in PC20FEV1 and modulation in histamine-induced changes in breathing pattern. We conclude that high doses of BDP seem to be able to modulate histamine-induced RSB, an effect that might be linked to reversal of airway inflammation.

Topics: Adolescent; Adult; Asthma; Beclomethasone; Bronchial Hyperreactivity; Bronchial Provocation Tests; Female; Forced Expiratory Volume; Histamine; Humans; Male; Middle Aged; Placebos; Respiration; Single-Blind Method; Tidal Volume; Time Factors; Vital Capacity

The effect of treatment of allergic rhinitis with intranasal corticosteroids on lower airway responsiveness was assessed in a randomized, double-blind, placebo-controlled, crossover study. Twenty-one young patients with perennial allergic rhinitis and asthma, with documented lower airway hyperresponsiveness (PC20 methacholine < 8 mg/ml), were treated with intranasal aqueous beclomethasone dipropionate and placebo, each given for 4 weeks. Patients recorded rhinitis and asthma symptom scores and monitored peak expiratory flow rates every morning and evening. Patients recorded global assessment of rhinitis and global asthma symptom scores at the beginning and end of each treatment. PC20 methacholine was performed at baseline and at the end of each treatment period. Intranasal beclomethasone dipropionate significantly reduced global rhinitis symptom scores (p = 0.05) after 4 weeks of treatment. Global asthma scores did not change significantly (p = 0.2). Geometric mean PC20 methacholine improved significantly after 4 weeks of intranasal beclomethasone, but not after placebo (p = 0.04). Daily morning and evening rhinitis symptom scores were lower in patients treated with intranasal corticosteroids over the first 4 weeks of treatment, but carryover effect of steroids precluded comparative analysis of the second 4-week block (morning p = 0.06, evening p = 0.03). Morning asthma scores tended to decrease (p = 0.07). Evening asthma scores were significantly decreased at weeks 2 and 3 (p = 0.001, p = 0.02, respectively). No change in peak expiratory flow rate was seen. This study confirms that treatment of inflammation in the upper airways indirectly improves asthma symptoms and decreases bronchial hyperreactivity. Ignoring inflammation in the upper airway may lead to suboptimal results in asthma treatment.

Topics: Administration, Intranasal; Adolescent; Analysis of Variance; Asthma; Beclomethasone; Bronchial Hyperreactivity; Bronchial Provocation Tests; Child; Circadian Rhythm; Double-Blind Method; Humans; Methacholine Chloride; Rhinitis, Allergic, Seasonal; Time Factors

165 patients (106 males, 59 females) entered an open group comparative study of a 12-week test treatment on bronchial hyperresponsiveness (BHR) determined by methacholine challenge. Patients were randomly allocated to receive nedocromil sodium (4 mg q.i.d.), sodium cromoglycate (10 micrograms q.i.d.) and beclomethasone dipropionate (500 micrograms t.i.d.). At the end of the study, an 2.25-fold increase of the PD20FEV1 was noted in all the treated patients. No significant difference was noted among the treatments.

Topics: Adult; Asthma; Beclomethasone; Bronchial Hyperreactivity; Bronchial Provocation Tests; Bronchodilator Agents; Cromolyn Sodium; Female; Humans; Long-Term Care; Male; Middle Aged; Nedocromil; Quinolones

In a randomized, cross-over study we compared the effects of inhaled nedocromil sodium, 4 mg q.i.d., with inhaled beclomethasone dipropionate, 200 micrograms q.i.d. in 23 atopic asthmatic patients. After a 3 week single-blind placebo period, regarded as the baseline, and after 4 and 8 weeks of active treatment, drug effects were assessed with regard to bronchial hyperresponsiveness to histamine and distilled water, lung function and beta 2-agonist use. After 4 and 8 weeks of treatment, nedocromil sodium reduced the histamine responsiveness (p < 0.005 and p < 0.0005), but not the distilled water responsiveness, and did not improve lung function and peakflow measurements compared to baseline. After 4 and 8 weeks of treatment, beclomethasone caused a significant increase in lung function (p < 0.005) and decrease in bronchial hyperresponsiveness to histamine (p < 0.0005) and distilled water (p < 0.0005) as compared to baseline. beta 2-agonist use was significantly diminished after an 8 week treatment with beclomethasone, whereas nedocromil sodium had no effect. Treatment with beclomethasone was superior to treatment with nedocromil sodium with regard to bronchial hyperresponsiveness to histamine and distilled water (p < 0.0005 and p < 0.005), lung function (p = 0.003), peakflow measurements (p < 0.05) and beta 2-agonist use (p < 0.005).

Topics: Administration, Inhalation; Adolescent; Adult; Anti-Inflammatory Agents, Non-Steroidal; Asthma; Beclomethasone; Bronchial Hyperreactivity; Bronchial Provocation Tests; Double-Blind Method; Female; Forced Expiratory Volume; Histamine; Humans; Male; Middle Aged; Nedocromil; Quinolones; Single-Blind Method; Water

The aim of the study was to evaluate the effects of inhaled steroids (IS) on the improvement of clinical asthma symptoms and on the decrease in bronchial hyperreactivity (BHR). Twenty-four children with severe asthma were given 1,000 micrograms beclomethasone dipropionate (BDP) daily and compared with ten asthmatic control children. The study included the evaluation of daily clinical score, of exercise induced asthma, of bronchial obstruction (forced expiratory volume in 1 sec, FEV1), and of BHR at months 0, 1, 2-3, and 4-5 (M0, M1, M2-3, and M4-5). BHR was assessed by standardized inhaled carbachol provocation measuring plethysmographic specific airway resistance (SRaw). The carbachol dose causing a 40% decrease in specific conductance (SGaw) was determined (PD40 SGaw). Clinical scores decreased at M1 (P less than 0.01) and throughout the study. FEV1 increased at M1 (P less than 0.05), M2-3 (P less than 0.01), and M4-5 (P less than 0.05) compared to M0. PD40 SGaw only increased significantly at M1 and M2-3. No individual correlation was found between clinical scores and PD40 SGaw at any testing, or between the decrease of clinical scores and the decrease of BHR. We conclude that bronchoconstrictive challenge tests do not adequately assess the clinical efficacy of IS. In clinical practice non-specific BHR should be preferentially measured for diagnosing atypical forms of asthma.

Topics: Administration, Inhalation; Adolescent; Airway Resistance; Asthma; Beclomethasone; Bronchial Hyperreactivity; Child; Child, Preschool; Exercise Test; Forced Expiratory Volume; Humans; Time Factors

The efficacy of budesonide (800 micrograms b.d.) and beclomethasone dipropionate (750 micrograms b.d.) in controlling the symptoms of asthma, pulmonary function, bronchial responsiveness to histamine, and adrenal function, was assessed in a double-blind, double-dummy cross-over study of 36 adult chronic asthmatic patients. The patients, the majority of whom were assessed to be affected to a severe degree, were insufficiently controlled in their current regimen of inhaled steroids and/or inhaled and oral bronchodilators. A 2 weeks baseline period preceded 6 weeks of treatment with each of the study drugs. Both treatment groups showed improvements from baseline in clinical assessment of lung function carried out after the first 6 weeks of treatment. No significant differences were seen throughout the entire 12 weeks study, when comparing the effects of the treatments on FEV1, FVC, PEF or the histamine PC20. Asthma severity, symptom score and inhaled bronchodilator use showed the same results after both treatments. It is concluded that inhalations of budesonide and beclomethasone dipropionate in high doses are equally potent in the treatment of severe asthma. There is no significant influence on the adrenal function and no significant side effects during a period equal to that of the present study.

Topics: Administration, Inhalation; Adolescent; Adrenal Glands; Adult; Asthma; Beclomethasone; Bronchial Hyperreactivity; Bronchodilator Agents; Budesonide; Double-Blind Method; Female; Humans; Male; Middle Aged; Models, Statistical; Pregnenediones; Respiratory Mechanics

Airways obstruction and airways hyperresponsiveness are two dominant features in patients with chronic nonspecific lung disease (asthma and chronic obstructive pulmonary disease (COPD)). We set up a study to determine whether long-term (3 yrs) therapeutic intervention directed at airways obstruction and hyperresponsiveness is superior to one directed at airways obstruction alone. Patients were selected on functional criteria (age, baseline forced expiratory volume in one second (FEV1), and airways hyperresponsiveness) and, furthermore, extensively characterized by history, smoking habits, allergy, reversibility of airways obstruction and quality of life. The methodology and practical problems of setting up this large multicentre study are outlined, together with an analysis of baseline data. Standardization of methods and techniques and recruitment of patients required much effort, recruitment taking about twice as long as expected. A 3 month feasibility study allowed us to eliminate minor problems in the protocol. Over a 16 month period, 274 adult patients (18-60 yrs) from the out-patient clinics of six university centres entered the study; 99 met the diagnostic criteria for asthma, 51 for COPD, 88 for asthmatic bronchitis, and 36 could not be classified. Their mean (SD) FEV1% pred was 65.1 (15.2)%. Their geometric mean provoking concentration of histamine producing a 20% fall in FEV1 (PC20 histamine) was 0.28 mg.ml-1. In a multiple regression analysis, more severe airways hyperresponsiveness was associated with lower prechallenge FEV1% pred (p less than 0.0001), higher pack-years of smoking (p = 0.0099), blood eosinophil count (p = 0.0004), skin test reactivity (p = 0.0047) and with female sex (p = 0.0302). We conclude that setting up long-term multicentre trials in chronic nonspecific lung disease (CNSLD) is feasible and that these may offer valuable information on treatment and outcome of the disease.

Topics: Adult; Asthma; Beclomethasone; Bronchial Hyperreactivity; Double-Blind Method; Follow-Up Studies; Forced Expiratory Volume; Humans; Ipratropium; Lung Diseases, Obstructive; Middle Aged; Multicenter Studies as Topic; Pilot Projects; Regression Analysis; Terbutaline; Time Factors; Total Lung Capacity

Disorders of the upper respiratory tract, particularly allergic rhinitis, are commonly associated with bronchial hyperresponsiveness. The latter may be due to postnasal drip or to mediator or chemotactic factors into the lower airways that either directly alter airway reactivity or cause airway inflammation. The aim of this study was to compare the effect of an identical dose of nasal or bronchial corticosteroid administration on bronchial hyperresponsiveness in patients with allergic rhinitis. Eleven patients were studied. All of them were judged atopic on the basis of positive skin tests to common allergens. During control, spirometry, flow-volume curves, and specific airway conductance (SGaw) were measured. Bronchial challenges were then performed with increasing concentrations of carbachol, and dose-response curves were constructed. The concentration of carbachol that decreased SGaw by 35% from baseline (PD35) was determined by interpolating from the dose-response curve. Control measurements were repeated at 1-wk intervals to ensure that PD35 was stable in all the patients. Then the patients received for 2 wk, in a double-blind randomized crossover fashion, a topical administration of either an aerosol of 400 micrograms of beclamethasone dipropionate (B) into the nose (100 micrograms four times per day) or into the bronchi. During each trial period, identical sprays of placebo were used, the latter being administered into the nose when B was administered into the bronchi and vice versa. Measurements were then performed after 2 wk of intranasal administration and after 2 wk of intrabronchial administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Administration, Inhalation; Administration, Intranasal; Adult; Aerosols; Airway Resistance; Beclomethasone; Bronchial Hyperreactivity; Bronchial Provocation Tests; Carbachol; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Hydrocortisone; Male; Prospective Studies; Respiratory Mechanics; Rhinitis, Allergic, Perennial

Corticosteroids increase the expression of β. Human medium and small airways were stimulated by histamine and treated with different concentrations of BDP and FF, administered alone and in combination at concentration-ratio reproducing ex vivo that of the currently available fixed-dose combination (FDC; BDP/FF 100:6 combination-ratio). Experiments were performed in non-sensitized (NS) and passively sensitized (PS) airways. The pharmacological interaction was assessed by using Bliss Independence and Unified Theory equations.. BDP/FF synergistically increased the overall bronchorelaxation in NS and PS airways (+ 15.15% ± 4.02%; P < 0.05 vs. additive effect). At low-to-medium concentrations the synergistic interaction was greater in PS than in NS bronchioles (+ 16.68% ± 3.02% and + 7.27% ± 3.05%, respectively). In PS small airways a very strong synergistic interaction (Combination Index: 0.08; + 20.04% ± 2.18% vs. additive effect) was detected for the total concentrations of BDP/FF combination corresponding to 10.6 ng/ml.. BDP/FF combination synergistically relaxed human bronchi; the extent of such an interaction was very strong at low-to-medium concentrations in PS small airways.. Not applicable.

Topics: Anti-Asthmatic Agents; Beclomethasone; Bronchi; Bronchial Hyperreactivity; Bronchodilator Agents; Drug Synergism; Female; Formoterol Fumarate; Glucocorticoids; Humans; Male; Middle Aged; Organ Culture Techniques

To evaluate the clinical efficiency of tactics to widen the scope of monotherapy with inhaled glucocorticosteroids (IGCS) in asthmatic patients with bronchial cold hyperreactivity (BCHR) during winter to achieve control of the disease in real clinical practice.. An open-label longitudinal study was conducted in a cold period in 106 asthmatics divided into 2 groups: 1) those with BCHR and 2) those with unchanged bronchial reactivity to a cold stimulus. The study involved monitoring the symptoms by the asthma control test, peak expiratory flow rate (PEFR), and spirometry results before and after cold bronchoprovocation testing; assessment of the pattern of bronchial inflammation from the ratios of induced sputum (IS) cell populations; and estimation of the number of asthma exacerbations and emergency care recourses. Group 1 used a stepwise increase of the scope of basic therapy with beclomethasone dipropionate 1000 microg/day until asthma control was achieved, which was followed by the therapy with the stable dose. Group 2 received monotherapy with beclomethasone dipropionate as the stable dosage of < or = 500 microg/day.. After the first 12 weeks of a follow-up, Group 1 showed the most marked positive changes in the intensity of clinical symptoms, forced expiratory volume in one second, and PEFR that remained within the following 12 weeks during the continued therapy with the stable dose of the drug. A preponderance of the eosinophilic and neutrophilic pattern of inflammation was seen in the patients of this group. By the end of the study, there was a decline in the number of IS inflammatory cells. A discriminant model was developed as a tool to predict asthma control achievement in patients with BCHR.. A stepwise increase in the scope of IGCS monotherapy in asthmatic patients with BCHR during winter can yield the results of disease control and the incidence of exacerbations, which are similar to those seen in asthmatics with no signs of BCHR (53 and 49%, respectively).

Topics: Adult; Anti-Asthmatic Agents; Asthma; Beclomethasone; Bronchial Hyperreactivity; Cold Temperature; Discriminant Analysis; Disease Management; Disease Progression; Emergency Medical Services; Female; Humans; Longitudinal Studies; Male; Middle Aged; Respiratory Function Tests; Russia; Seasons

Glucocorticoids are the most effective anti-inflammatory treatment for asthma, and inhaled corticosteroids are the most effective long-term control therapy for persistent asthma. In the present study, to determine the mechanism of the inhibitory effect of glucocorticoids on airway hyperresponsiveness, the effects of glucocorticoids on the expression and activation of PKC-potentiated protein phosphatase 1 inhibitory protein of 17 kDa (CPI-17) were examined in bronchial smooth muscles of antigen-induced airway hyperresponsive rats. Repeated antigen inhalation to animals sensitized with DNP-Ascaris antigen caused a marked bronchial smooth muscle hyperresponsiveness to acetylcholine, accompanied by upregulation and acetylcholine-induced activation of CPI-17 to result in an increase in myosin light chain (MLC) phosphorylation. Treatment with glucocorticoids (prednisolone or beclomethasone, 10 mg/kg, i.p., respectively) significantly inhibited the airway hyperresponsiveness, and markedly reduced both the protein and mRNA levels of CPI-17 in bronchial smooth muscle. The acetylcholine-induced activation of CPI-17, i.e., phosphorylation of CPI-17, was also significantly inhibited by glucocorticoids. Glucocorticoids also prevented the augmented acetylcholine-induced MLC phosphorylation observed in the airway hyperresponsive rats. Therefore, glucocorticoids might inhibit the airway hyperresponsiveness through the inhibition of overexpression and activation of CPI-17.

Topics: Acetylcholine; Animals; Ascaris; Beclomethasone; Bronchi; Bronchial Hyperreactivity; Down-Regulation; Glucocorticoids; Male; Muscle Proteins; Myosin Light Chains; Phosphoproteins; Phosphorylation; Prednisolone; Rats; Rats, Wistar; RNA, Messenger

Allergy does not modify the symptoms and steroid consumption (oral and local) of nasal polyposis (NP) patients after functional endoscopic sinus surgery (FESS).. To assess the role of allergy in the evolution after FESS of patients presenting with the diagnosis of NP.. This was a prospective study of 63 consecutive patients with NP (57% males, mean age 45.8 years), who were analyzed to detect whether the results of a surgical treatment of NP were influenced by the presence of positive allergic tests (Phadiatop). Three nasal criteria were scored: nasal obstruction, posterior rhinorrhea, and the loss of smell. The frequency of asthma was evaluated. Medical treatment of NP after FESS consisted of washing of the nasal cavities, steroid spray, and oral steroid administration. The amount of consumption of steroids (prednisolone and beclomethasone) was studied.. Decrease of all nasal symptoms was not statistically different in the two groups of patients with and without allergy. Cumulative consumption of prednisolone and beclomethasone after surgery was similar in the two groups.

Topics: Adult; Asthma; Beclomethasone; Bronchial Hyperreactivity; Bronchial Provocation Tests; Combined Modality Therapy; Cross-Sectional Studies; Endoscopy; Ethmoid Sinusitis; Female; Follow-Up Studies; Humans; Male; Middle Aged; Nasal Obstruction; Nasal Polyps; Olfaction Disorders; Postoperative Complications; Prednisolone; Recurrence; Respiratory Hypersensitivity

To determine the mechanism(s) of the inhibitory effect of glucocorticoids on airway hyperresponsiveness in allergic bronchial asthma, the effects of systemic treatment with glucocorticoids on bronchial smooth muscle hyperresponsiveness and RhoA upregulation were investigated in rats with allergic bronchial asthma. Rats were sensitized and repeatedly challenged with 2,4-dinitrophenylated Ascaris suum antigen. Animals were also treated with prednisolone or beclomethasone (each 10 mg/kg, i.p.) once a day during the antigen inhalation period. Repeated antigen inhalation caused a marked bronchial smooth muscle hyperresponsiveness to acetylcholine with an upregulation of RhoA. Augmented acetylcholine-induced activation of RhoA and phosphorylation of myosin light chain were observed in bronchial smooth muscles of the antigen-exposed animals. Systemic treatment with either glucocorticoid used inhibited the bronchial smooth muscle hypercontraction until the level of the sensitized control rats that received saline inhalation instead of antigen challenge. Interestingly, both glucocorticoids also inhibited the upregulation of RhoA and augmented acetylcholine-induced activation of RhoA and phosphorylation of myosin light chain. In conclusion, glucocorticoids ameliorated the augmented bronchial smooth muscle contraction by inhibiting upregulation of RhoA. These effects of glucocorticoids may account for, in part, their beneficial effects in the treatment of asthma.

Topics: Acetylcholine; Animals; Anti-Asthmatic Agents; Antigens, Helminth; Ascaris suum; Asthma; Beclomethasone; Bronchi; Bronchial Hyperreactivity; Bronchoconstrictor Agents; Dose-Response Relationship, Drug; Enzyme Activation; Glucocorticoids; Humans; Muscle, Smooth; Myosin Light Chains; Phosphorylation; Prednisolone; Rats; Rats, Wistar; rhoA GTP-Binding Protein; Up-Regulation

These studies were designed to assess the pharmacodynamic interaction between formoterol and beclomethasone dipropionate (BDP) in controlling the bronchoconstriction and inflammatory response induced by various challenges in guinea-pigs and rats. In anaesthetised guinea-pigs, superfusion of the formoterol/BDP combination into the tracheal lumen had significantly more effect than the single components in antagonising the bronchoconstricting and inflammatory responses to acetylcholine or ovalbumin in a standard model of airway hyper-responsiveness. After ovalbumin challenge, the combination completely protected animals from death at doses lower than those effective when given separately. The combination, at doses ineffective individually, even counteracted the development of lung oedema induced by sephadex in the rat. Finally, in tracheal strips from ovalbumin-sensitised guinea-pigs pre-treatment with BDP (30 mg kg(-1) i.m.) completely reversed the rightward shift of the formoterol dose-response curve due to beta(2)-receptor desensitisation. In conclusion, these results indicate that formoterol and BDP together induce a favourable pharmacodynamic interaction which can be considered more than additive, at least in these experimental settings.

Topics: Acetylcholine; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Albuterol; Animals; Anti-Inflammatory Agents; Beclomethasone; Bronchial Hyperreactivity; Bronchoconstriction; Bronchodilator Agents; Dextrans; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Combinations; Drug Synergism; Ethanolamines; Formoterol Fumarate; Guinea Pigs; Inflammation; Male; Ovalbumin; Pulmonary Edema; Rats; Receptors, Adrenergic, beta-2; Trachea

Bronchial hyperresponsiveness (BHR) is not a risk factor for surgery in patients with nasal polyposis (NP).. Management of NP should be primarily medical, and surgery should not be envisaged before a trial of dual steroid therapy. In patients with severe NP resistant to a strict medical treatment, endoscopic sinus surgery is performed, but no prognostic factor for efficacy of surgery is obvious. Some authors suggest that asthma could be a major risk for ineffectiveness of surgery. The aim of this study was to evaluate whether the presence of BHR can be considered a risk factor for ineffectiveness of surgery.. Surgery (with associated medical treatment) was evaluated over a mean follow-up period of 74 months. A total of 63 subjects without and 131 subjects with BHR were operated according to a standardized protocol.. The present study shows that combined surgery and corticosteroid therapy is effective in the treatment of severe NP, producing significant and long-term improvements in symptoms and in the size of nasal polyps. BHR did not influence the outcome. Moreover, the mean amount of prednisolone and beclomethasone necessary after surgery was similar in the two groups.

Topics: Administration, Intranasal; Beclomethasone; Bronchial Hyperreactivity; Combined Modality Therapy; Endoscopy; Female; Follow-Up Studies; Forced Expiratory Volume; Glucocorticoids; Humans; Male; Middle Aged; Nasal Polyps; Otorhinolaryngologic Surgical Procedures; Prevalence; Time Factors; Treatment Outcome

Management of nasal polyposis should be primarily medical. Resorting to intranasal ethmoidectomy should not be envisaged before a trial of dual steroid therapy. Nevertheless, no risk factor for steroid insensitivity in patients with nasal polyposis is actually defined. The aim of this study is to evaluate whether the presence of asthma and/or non-specific bronchial hyperresponsiveness (BHR) can be considered a risk factor for steroid insensitivity.. This study focused on the evaluation of a dual modality, topical and systemic, over a follow-up period of 3 years. A total of 55 subjects with and 45 subjects without BHR were treated according to a standardized therapeutic protocol combining short-term oral administration of prednisolone and a daily intranasal spray of beclomethasone.. Over the follow-up period of 3 years, this dual modality proved to be successful in 93.4% of subjects without BHR and without aspirin idiosyncrasy, in 82.2% of subjects with BHR and without aspirin idiosyncrasy and in 60% of subjects with BHR and aspirin idiosyncrasy. The percentage of patients who underwent surgery after the failure of medical treatment was significantly larger in patients with than without BHR (p < 0.05) and in patients with than without aspirin idiosyncrasy (p < 0.02).. The presence of BHR and/or aspirin idiosyncrasy can be considered a major risk factor for steroid insensitivity in patients with nasal polyposis.

Topics: Administration, Oral; Aerosols; Anti-Asthmatic Agents; Anti-Inflammatory Agents, Non-Steroidal; Antineoplastic Agents, Hormonal; Aspirin; Asthma; Beclomethasone; Bronchial Hyperreactivity; Bronchial Provocation Tests; Drug Hypersensitivity; Drug Resistance; Ethmoid Sinus; Female; Follow-Up Studies; Glucocorticoids; Humans; Male; Middle Aged; Nasal Polyps; Prednisolone; Risk Factors; Tablets; Therapeutic Irrigation; Tomography, X-Ray Computed; Treatment Outcome

Airway wall thickening has been assumed to cause airway hyperresponsiveness, but a protective effect against airway narrowing has also been suggested. We investigated the relationship between airway wall thickness as assessed by helical computed tomography and two components of airway responsiveness, airway sensitivity and reactivity, in patients with stable asthma with (n = 23) and without (n = 22) inhaled steroid treatment. A cross-section of the apical bronchus of the right upper lobe was obtained. Airway wall area corrected by body surface area was measured as an index of wall thickness. Airway sensitivity and reactivity were measured by continuous inhalation of methacholine, on the basis of the methacholine respiratory resistance dose-response curve. The eosinophil count in sputum was determined in 16 patients [steroid (+) group] and 14 patients [steroid (-) group]. In both groups of patients, airway sensitivity was not related to airway reactivity. Airway sensitivity was related to eosinophil count [r = 0.57 in the steroid (+) group and r = 0.49 in the steroid (-) group], but not to airway wall thickness. In contrast, airway reactivity negatively correlated with airway wall thickness [r = -0.56 in the steroid (+) group and r = -0.55 in the steroid (-) group] but not with eosinophil count. Our results suggest that airway wall thickening attenuates airway reactivity in patients with asthma. These findings may have important implications in pathophysiology and in the treatment of airway remodeling.

Topics: Adrenergic beta-Agonists; Aged; Airway Resistance; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Beclomethasone; Bronchial Hyperreactivity; Bronchial Provocation Tests; Bronchoconstrictor Agents; Eosinophils; Female; Forced Expiratory Volume; Humans; Hyperplasia; Hypertrophy; Inflammation; Leukocyte Count; Male; Methacholine Chloride; Middle Aged; Severity of Illness Index; Sputum; Tomography, X-Ray Computed

Exhaled nitric oxide (eNO) has been used as a surrogate of airway inflammation in mild asthma. However, whether eNO levels reflect disease activity in symptomatic asthmatics receiving moderate doses of inhaled corticosteroid (ICS) is more uncertain.. To examine the relationship between eNO levels, sputum and blood eosinophils (SpE and PbE), PD(20) methacholine as a marker of airway hyperresponsiveness (AHR) and clinical status in 28 ICS-treated asthmatic subjects with persistent asthma compared to that in 25 symptomatic asthmatics managed with beta2-agonists alone.. As expected, eNO levels were normalized in ICS-treated subjects and significantly elevated in the beta2-agonist only group (P < 0.001). SpE, PbE and PD20M did not differ between asthmatic groups but FEV1 was significantly worse in ICS-treated subjects (P < 0.01). Exhaled NO levels correlated with PbE within both asthmatic groups (P < 0.005), but with SpE only in ICS-untreated subjects (r(s) = 0.6, P < 0.05). In contrast, PD20M was negatively correlated with eNO and PbE in ICS-treated subjects only (r(s) = - 0.4, r(s) = - 0.4, respectively, P < 0.05). SpE and PbE were strongly correlated in both asthmatic groups (r(s) = 0.8, r(s) = 0.7, respectively, P < 0.005). Exhaled NO levels, SpE and PbE were all positively associated with increased nocturnal awakenings ( P < 0.05) in ICS-treated subjects, but not in ICS-untreated subjects.. In ICS-treated asthma, eNO reflects clinical activity, PbE and AHR but not eosinophilic airway inflammation. Exhaled NO levels are quantitatively and relationally different in asthmatic subjects treated with ICS and continue to have potential for use as a surrogate of asthma pathophysiology in this group.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adrenergic beta-Agonists; Adult; Aged; Anti-Asthmatic Agents; Asthma; Beclomethasone; Biomarkers; Bronchial Hyperreactivity; Cross-Sectional Studies; Drug Monitoring; Eosinophils; Female; Humans; Linear Models; Male; Methacholine Chloride; Middle Aged; Multivariate Analysis; Nitric Oxide; Severity of Illness Index; Sputum; Statistics, Nonparametric

In order to investigate the possible involvement of airway mast cells in bronchial hyperresponsiveness (BHR), we examined whether a patient with systemic mastocytosis would demonstrate BHR against ultrasonically nebulized distilled water (UNDW) and histamine inhalation challenge. A 56-year-old man with systemic mastocytosis underwent both UNDW and histamine inhalation challenge. We also evaluated the effect of beclomethasone dipropionate inhalation (BDI) treatment on the histamine inhalation challenge. The results showed that UNDW inhalation caused no changes in forced expiratory volume in 1 s (FEV1) for this patient. The provocative dose causing a 20% fall (PC20) in FEV1 in the histamine inhalation challenge was 625 microg/mL. After BDI treatment for 8 weeks, the histamine PC20 was still 625 microg/mL. These data suggest that UNDW-induced bronchoconstriction may be independent of airway mast cells and that the mechanism of histamine-induced bronchoconstriction in systemic mastocytosis may be independent of airway inflammation, which is often present in asthmatics.

Topics: Beclomethasone; Bronchi; Bronchial Hyperreactivity; Bronchial Provocation Tests; Humans; Immunohistochemistry; Male; Mast Cells; Mastocytosis, Systemic; Middle Aged

We analyzed the changes in indices of airway hyperresponsiveness, including hypersensitivity and hyperreactivity, during one year of treatment with inhaled corticosteroids. We then investigated on which of them the inhaled corticosteroids had a primary effect. Fifty outpatients with asthma were recruited and treated with inhaled beclomethasone dipropionate. They underwent bronchoprovocation tests on the initial visit and at 3, 6, and 12 months. The dose of methacholine required to produce a 20% fall in the forced expiratory volume in 1 second (PD20-FEV1) was measured to evaluate airway hypersensitivity. A relatively novel index, the percent change in the forced vital capacity (deltaFVC%) at the PD20-FEV1, was assessed as a marker of airway hyperreactivity. PD20-FEV1 and deltaFVC% were assumed to indicate the horizontal shift of the dose-response curve and the vertical change in the maximal response plateau, respectively. Log(PD20-FEV1) and deltaFVC% continued to improve throughout the year (p < 0.001 and p = 0.002, respectively). Log(PD20-FEV1) improved significantly at the 3-month evaluation (p < 0.001), and deltaFVC% improved at the 6-month evaluation (p = 0.012). Log(PD20-FEV1) had no or weak relationships with deltaFVC% at all evaluation points. In conclusion, inhaled corticosteroids continued not only to reverse the leftward shift of the curve, but also to restore the plateau. Furthermore, their effect was reflected primarily by the former rather than the latter: They should be followed separately to examine how much airway inflammation is reduced.

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Anti-Asthmatic Agents; Asthma; Beclomethasone; Bronchial Hyperreactivity; Female; Forced Expiratory Volume; Glucocorticoids; Humans; Male; Middle Aged; Peak Expiratory Flow Rate; Treatment Outcome; Vital Capacity

The outcome of asthma and/or nonspecific bronchial hyperresponsiveness (BHR) associated with nasal polyposis (NP) is uncertain. Over a 4-yr period, we investigated the long-term changes of pulmonary function and BHR in 46 patients with NP. Each subject was assessed for nasal symptoms and tested for allergy skin prick tests, serum total IgE, spirometry, and carbachol challenge at baseline before initiating any treatment (T0). Nasal symptoms evaluation, spirometric measurements, and carbachol challenge were repeated at T1 and at T2 (respectively, 12.7 +/- 0.9 and 47.9 +/- 2. 2 mo after T0). In addition, bronchodilator response was measured at T2. At T0, 25 patients exhibited BHR and 16 of 25 were asthmatic. All patients were treated first with topical steroids for 6 wk (beclomethasone 600 microg/d). Eighteen patients were successfully treated with topical steroids (topical steroids responders). Intranasal ethmoidectomy was performed in 28 patients who did not improve with topical steroids alone (topical steroids nonresponders). Nasal score improved at T1 and remained improved at T2 as compared with T0 in both groups (p < 0.005). Topical steroids nonresponders demonstrated a significant decrease of FEV(1), FEV(1)/FVC ratio, and FEF(25-75) at T1 (p < 0.05) and at T2 (p < 0.0005), whereas no significant change was observed in FEV(1) and FEV(1)/FVC ratio in responders. DeltaFEV(1) (%) between T2 and T0 was not related to the presence of asthma, BHR, or atopy. Bronchodilator response at T2 was similar in the two groups. BHR did not significantly change over the 4-yr follow-up period in the two groups. No change in pulmonary symptoms and/or asthma severity occurred. Our results show that nonreversible airflow obstruction appears over a 4-yr follow-up period in topical steroids nonresponders patients with NP requiring nasal surgery. The long-term contribution of these changes to the development of respiratory symptoms in patients with NP remains to be documented.

Topics: Administration, Intranasal; Adult; Anti-Inflammatory Agents; Asthma; Beclomethasone; Bronchial Hyperreactivity; Bronchial Provocation Tests; Combined Modality Therapy; Ethmoid Sinus; Female; Follow-Up Studies; Humans; Immunoglobulin E; Intradermal Tests; Lung Volume Measurements; Male; Middle Aged; Nasal Polyps; Prospective Studies; Respiratory Hypersensitivity; Spirometry

Airway hyperresponsiveness (AHR), in which airway inflammation has been reported to be a key factor, is an important component of asthma. However the precise role of inflammation in AHR is still unclear. In this report, airway inflammatory changes were assessed using hypertonic saline-induced sputum examination and exhaled nitric oxide analysis, and the relation between AHR to methacholine, airway calibre forced expiratory volume in one second (FEV1) and airway inflammatory indices examined. Furthermore, the changes in these variables were also examined by means of 8 weeks' open uncontrolled inhaled steroid administration (800 microg x beclomethasone x day(-1)). Asthmatic subjects had higher eosinophil counts and bradykinin concentration in induced sputum and higher exhaled NO levels, and showed AHR to methacholine. Baseline AHR significantly correlated with FEV1 but not with indices of inflammation in sputum or exhaled air. Steroid inhalation therapy was associated with a reduction in eosinophil and bradykinin concentration in sputum and NO levels in exhaled air and an improvement in FEV1 and AHR. The changes in FEV1 and AHR were significantly related to changes in markers in sputum and exhaled air (p<0.01 for each). These results suggest that baseline airway hyperresponsiveness can be predicted from the airway calibre but not from inflammatory parameters in sputum or exhaled air. In contrast, the reversible component of airway hyperresponsiveness appeared to be associated with the reduction in airway inflammation.

Topics: Administration, Inhalation; Adult; Anti-Asthmatic Agents; Asthma; Beclomethasone; Bronchial Hyperreactivity; Bronchial Provocation Tests; Female; Fenoterol; Forced Expiratory Volume; Humans; Male; Methacholine Chloride; Nitric Oxide; Sputum

The relationship between airway inflammation and asthma severity in corticosteroid-treated asthma is unclear.. Our purpose was to characterize the inflammatory cell profile of the airway lumen and epithelium in corticosteroid-treated asthma and to relate these findings to clinical and physiologic markers of asthma severity.. Adults (n = 20) with asthma received standardized high-dose inhaled corticosteroid therapy with beclomethasone 2000 microgram per day for 8 weeks. Airway responsiveness to methacholine and hypertonic (4.5%) saline solution was then assessed, followed by sputum induction and, 1 week later, bronchoscopy with bronchoalveolar lavage and bronchial brush biopsy to assess inflammatory cells.. Clinical asthma severity was associated with airway hyperresponsiveness. Metachromatic cells were the main granulocyte present in bronchial brush biopsy specimens and correlated with airway responsiveness to saline solution (r = -0.75), methacholine (r = -0.74), peak flow variability (r = 0.59), and clinical asthma severity (r = 0.57). Eosinophils were the main granulocyte present in sputum and correlated with airway responsiveness to saline solution (r = -0.63) but not with other clinical markers of asthma severity. Bronchoalveolar lavage cell counts were not related to clinical asthma severity.. In asthmatic patients treated with cortico-steroids, the dominant inflammatory effector cell in the epithelium is the metachromatic cell, and in sputum it is the eosinophil. These cells correlate with the degree of airway hyperresponsiveness. Clinical asthma severity correlates with airway responsiveness and epithelial metachromatic cells. Induced sputum eosinophils and airway responsiveness to hypertonic saline solution may be useful markers of airway inflammation for clinical practice.

Topics: Adult; Asthma; Beclomethasone; Bronchi; Bronchial Hyperreactivity; Bronchitis; Bronchoalveolar Lavage Fluid; Dose-Response Relationship, Drug; Eosinophils; Female; Glucocorticoids; Humans; Male; Mast Cells; Peak Expiratory Flow Rate; Severity of Illness Index

If the nitric oxide (NO) diffusing capacity of the airways (DNO) is the quantity of NO diffusing per unit time into exhaled gas (q) divided by the difference between the concentration of NO in the airway wall (Cw) and lumen, then DNO and C(w) can be estimated from the relationship between exhaled NO concentration and expiratory flow. In 10 normal subjects and 25 asthmatic patients before and after treatment with inhaled beclomethasone, DNO averaged 6.8 +/- 1.2, 25.5 +/- 3.8, and 22.3 +/- 2.7 nl/s/ppb x 10(-3), respectively; C(w) averaged 149 +/- 31.9, 255.3 +/- 46.4, and 108.3 +/- 14.3 ppb, respectively; and DNOC(w) (the maximal from diffusion) averaged 1,020 +/- 157.5, 6,512 +/- 866, and 2,416 +/- 208.5 nl/s x 10(-3), respectively. DNO and DNOC(w) in the asthmatic subjects before and after steroids were greater than in normal subjects (p < 0.0001), but C(w) was not different. Within asthmatic subjects, steroids caused C(w) and DNOC(w) to fall (p < 0.0001), but DNO was unchanged. DNOC(w) after steroids, presumably reflecting maximal diffusion of constitutive NO, was positively correlated with methacholine PC(20) and FEV(1)/FVC before or after steroids. The increased DNO measured in asthmatic patients may reflect upregulation of nonadrenergic, noncholinergic, NO-producing nerves in airways in compensation for decreased sensitivity of airway smooth muscle to the relaxant effects of endogenous NO.

Topics: Administration, Inhalation; Adult; Anti-Asthmatic Agents; Asthma; Beclomethasone; Bronchial Hyperreactivity; Case-Control Studies; Female; Humans; Male; Nitric Oxide; Nitric Oxide Synthase; Nitric Oxide Synthase Type II; Pulmonary Diffusing Capacity

To evaluate bekotid and bekodisk effects on bronchial reactivity and sensitivity.. Bronchial reactivity and sensitivity were studied in a comparative study of two corticosteroids for inhalation--bekotid and bekodisk--in 37 patients with bronchial asthma. Unlike bekotid, bekodisk does not contain freon which irritates mucosa of the upper respiratory tracts and bronchi. The examination included clinical and allergological tests, provocative inhalation tests, peak flowmetry, assessment of bronchial resistance and external respiration function.. Bekodisk treatment reduced the number of asphyxia episodes, sensitivity to carbacholine, the need in inhalation sympathomimetics, improved external respiration function.. Determination of reactivity and sensitivity of the bronchi is essential for comparison of drugs against bronchial asthma. Bekodisk significantly lowers reactivity to nonspecific mediatory substances, is simple and available in application, is more tolerable than bekotid.

Topics: Administration, Inhalation; Airway Resistance; Anti-Asthmatic Agents; Asthma; Beclomethasone; Bronchial Hyperreactivity; Bronchial Provocation Tests; Bronchoscopy; Carbachol; Cholinergic Agonists; Evaluation Studies as Topic; Female; Glucocorticoids; Humans; Hydroxycorticosteroids; Male; Treatment Outcome

It has been demonstrated previously that exhaled nitric oxide (eNO) is increased in steroid-naive asthmatics and that inhaled steroids reduce eNO in these patients. Cigarette smoking has also been reported to reduce the eNO in healthy volunteers. Recently a correlation has been demonstrated between eNO and airway hyperresponsiveness in steroid-naive, mild asthmatics. We hypothesized that cigarette smoking would reduce the eNO level in steroid-naive asthmatics and might, therefore, affect the correlation between eNO and airway hyperresponsiveness.. Comparison of eNO in healthy smoking and nonsmoking volunteers with the level of eNO in steroid-naive and steroid-treated asthmatics. Correlate the eNO level with the provocative concentration of histamine causing a 20% fall in FEV1 (PC20hist) in the asthmatic smoking and nonsmoking patients.. University outpatient asthma clinic.. eNO levels and PC20hist were measured in three different asthmatic patient groups (group A = 29 steroid-naive, nonsmoking asthmatics; group B = 19 steroid-treated, nonsmoking asthmatics; and group C = 13 smoking, steroid-naive asthmatics) and in two healthy volunteer groups (group D = 18 nonsmoking; and group E = 16 smoking).. eNO in group A was significantly increased compared with the values in groups B and D (21.8+/-12.7, 12.8+/-4.9, and 10.6+/-2.2 parts per billion [ppb], respectively). Cigarette smoking decreased eNO in healthy volunteers (7.4+/-1.8 ppb, group E) as well as in steroid-naive asthmatics (12.7+/-5.1 ppb, group C). There was a significant correlation between eNO and PC20hist in group A (r = -0.45, p < 0.05); this correlation was, however, lost in both groups B and C.. Cigarette smoking and inhaled steroids reduce the eNO in patients with mild asthma to a comparable extent. Because the correlation between eNO and airway hyperresponsiveness was lost in steroid-treated and smoking, steroid-naive asthmatics, we question the value of eNO as a marker of airway inflammation, at least in mild asthmatics who are already being treated with inhaled steroids or who are currently smoking.

Topics: Administration, Inhalation; Adult; Anti-Inflammatory Agents; Asthma; Beclomethasone; Bronchial Hyperreactivity; Case-Control Studies; Female; Glucocorticoids; Humans; Male; Nitric Oxide; Smoking

Endogenously released nitric oxide (NO) has been detected in the exhaled air of humans. Exhaled NO (NOexh) levels have been significantly increased in patients with inflammatory airways disorders such as asthma, and NOexh has been suggested to be a usable marker of airway inflammation. In the present study, NOexh levels were measured both in steroid-treated and untreated subjects with mild asthma, and were correlated with the degree of airway hyperresponsiveness (AHR), measured as the dose of histamine that produced a 20% decrease in FEV1 (PC20histamine). NOexh levels, which were significantly increased in steroid-naive patients (Group A1: NOexh = 21 +/- 11 ppb; n = 56) in comparison with levels in control subjects (Group B: NOexh = 10 +/- 2 ppb; n = 20; p < 0.001), correlated significantly with the PC20histamine (r = -0.65; p < 0.0001). The NOexh level was significantly lower in patients with chronic cough of other causes than bronchial asthma (Group A2: NOexh = 11 +/- 3 ppb; n = 18) when compared with the level in subjects with mild asthma (Group A1: p < 0.001). Therefore, the noninvasive measurement of NOexh allowed us to discriminate, among patients with respiratory complaints, between those with and without AHR. In asthmatic subjects treated with inhaled steroids, the NOexh levels were significantly lower (Group A3: NOexh = 13 +/- 5 ppb; n = 25) than in untreated subjects (Group A1; p < 0.01), and there was no relationship with the PC20histamine (r = -0.18, p = NS). These findings confirm that NOexh reflects AHR in patients with mild asthma who have not already been treated with inhaled steroids. Patients treated with inhaled steroids had an NOexh level comparable to levels in control subjects, although AHR could still be demonstrated.

Topics: Adrenergic beta-Agonists; Adult; Airway Obstruction; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Beclomethasone; Biomarkers; Bronchial Hyperreactivity; Bronchial Provocation Tests; Chronic Disease; Cough; Dyspnea; Female; Forced Expiratory Volume; Glucocorticoids; Histamine; Humans; Male; Nitric Oxide; Respiration; Respiratory Sounds

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.. Open study at two different points in time.. Outpatient pulmonary clinic.. Eighteen asthmatic subjects.. 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).. 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.

Topics: Adolescent; Adult; Anti-Inflammatory Agents; Asthma; Beclomethasone; Bronchial Hyperreactivity; Bronchial Provocation Tests; Child; Female; Forced Expiratory Volume; Glucocorticoids; Humans; Male; Middle Aged; Treatment Outcome

Nasal polyposis (NP) is commonly associated with nonspecific bronchial hyperresponsiveness (BHR) and/or asthma. The aim of this prospective study was to investigate the changes of pulmonary function and BHR in patients with nasal polyposis. Forty-four consecutive patients with NP were included in the study and were followed for 12 mo. Nonspecific BHR was assessed by a carbachol challenge test to determine the provocating dose (PD20) necessary to decrease FEV1 by 20% from baseline values; 17 of 22 patients who demonstrated BHR also exhibited asthma. Spirometric measurements and carbachol challenge were performed before initiating any treatment and 12 mo later. All patients were treated first with beclomethasone (600 microg/d). Intranasal ethmoidectomy was performed in 23 patients who did not improve when treated with topical steroids alone (nonresponders); in contrast, 21 patients were successfully treated with beclomethasone alone (responders). PD20 significantly decreased in the group of nonresponders (p = 0.018), whereas it remained unchanged in responders (p = 0.95). FEV1 (% pred) and FEF25-75 (% pred) significantly decreased in nonresponders (p < 0.001), whether BHR existed or not, whereas no significant change was observed in responders. Our results demonstrate that nonresponders who required nasal surgery exhibited an enhancement of BHR and a slight but significant decrease of FEV1 and FEF25-75 values. However, no change in pulmonary symptoms and/or asthma severity occurred. Clinical and functional follow-up of these patients should assess the long-term evolution of these parameters and their clinical relevance.

Topics: Adolescent; Adult; Aged; Beclomethasone; Bronchial Hyperreactivity; Bronchial Provocation Tests; Carbachol; Female; Forced Expiratory Volume; Glucocorticoids; Humans; Male; Maximal Midexpiratory Flow Rate; Middle Aged; Nasal Polyps; Prospective Studies; Pulmonary Ventilation; Vital Capacity

Efficacy of inhalation corticosteroids becotide and becodisk was compared in 24 patients with bronchial asthma. Becodisk has the advantage of not containing freon which irritates upper airways and bronchial mucosa. Clinical, allergological, bronchial resistance, provocative carbacholine tests, external respiration tests, peakflowmetry demonstrated that becodisk reduced the number of asthma attacks, lowered the need in inhalation sympathomimetics, improved external respiration function, decreased bronchial sensitivity to carbacholine. Determination of specific and nonspecific bronchial reactivity is thought essential in comparing efficacy of asthma chemotherapy. Becodisk significantly reduces bronchial reactivity to nonspecific mediator substances, is simple in use and well tolerated. It is recommended for basic therapy in various bronchial asthma forms managed with local corticosteroids.

Topics: Administration, Inhalation; Adolescent; Adult; Asthma; Beclomethasone; Bronchial Hyperreactivity; Bronchoconstriction; Female; Glucocorticoids; Humans; Hydroxycorticosteroids; Lung; Male; Middle Aged; Respiration

The present study was designed to investigate the effects of immunotherapy (IT) with an extract of Dermatophagoides pteronyssinus (Alergo-Merck Depot) during a 27-month period in patients with allergic asthma to house-dust mites. We included 11 patients (mean age 18 years) treated with a combination of IT and inhaled beclomethasone dipropionate (BDP) in comparison to another 11 (mean age 22 years) treated with BDP alone. We evaluated symptom scores, salbutamol use, peak expiratory flow rates (PEFR), spirometry, and bronchial hyperresponsiveness (BHR) during 18 months of therapy with BDP and in the 9 months after BDP interruption. The two kinds of treatment were efficient and comparable in relation to symptom score, salbutamol use, morning PEFR, FVC, and FEV1, but patients treated with IT and BDP had a faster improvement of BHR and PEFR variability. The interruption of BDP after 18 months of therapy was linked to an impairment of all end points, which were more pronounced in patients previously treated only with BDP. These findings suggest that in selected asthmatic patients allergic to house-dust mites, the association of IT and BDP is more effective than therapy with this inhaled steroid alone due to a faster and more striking improvement during the first months of treatment and to a lower rate of relapse after the interruption of therapy with BDP.

Topics: Administration, Inhalation; Adolescent; Adult; Albuterol; Allergens; Animals; Antigens, Dermatophagoides; Asthma; Beclomethasone; Bronchial Hyperreactivity; Child; Female; Glycoproteins; Humans; Immunotherapy, Active; Male; Mites; Peak Expiratory Flow Rate; Spirometry

Effects of reducing or stopping inhaled beclomethasone dipropionate (BDP) on airway hyperresponsiveness (AHR) were evaluated in stable chronic asthma. In 16 patients, after the best control (no symptoms, peak expiratory flow rate [PEF] > 80% best) was achieved for at least 3 months, the dose of BDP was reduced to 2/3 to 1/2. No differences were observed in the mean FEV1, PEF and AHR between before and 3 months after the reduction of BDP. In 7 patients, after the almost normal level of AHR was achieved, the dose of BDP was gradually reduced and then discontinued. Three out of the 7 patients had maintained the adequate level of AHR over 14 months, but in the other 4 patients AHR deteriorated below normal level and re-administration of BDP was needed due to worsening of symptoms and PEF. In conclusion, a gradual reduction of the dose of BDP is possible, if the best control is achieved for at least 3 months. The possibility of discontinuation of BDP may exist in some patients after achieving adequate AHR.

Topics: Administration, Inhalation; Adult; Anti-Inflammatory Agents; Asthma; Beclomethasone; Bronchial Hyperreactivity; Chronic Disease; Female; Humans; Male; Middle Aged; Peak Expiratory Flow Rate

We studied retrospectively the effect of long-term treatment with an inhaled corticosteroid on bronchial hyperresponsiveness (BHR) and clinical asthma in moderate-severe asthmatic subjects. Fifty-eight patients who had used beclomethasone dipropionate (BDP) over one year, were enrolled in this study. BHR was measured before and after treatment with BDP by the methods recommended by Japanese Society of Allergology. Moreover we examined the clinical factors and the frequency of acute exacerbations. The results as follows: 1) The mean age was 48.8 years and the mean asthma history was 9.2 years. The mean dose and mean time of BDP administration was 801 micrograms/day and 28.1 months, respectively. 2) Patients during BDP treatment over one year showed about 6-fold mean improvements in BHR, but there were many patients who showed no improvements in BHR. 3) We retrospectively divided all the patients into two groups. Namely, the improved group (n = 25) showed more than 4 fold improvement in BHR and unchanged group (n = 33), less than 4-fold. But there were no significant differences in clinical characteristics and %FEV1 during treatment with BDP. 4) The unchanged group had more near fatal episodes in the past than the improved group. 5) There was significant decrease in acute exacerbation during treatment with BDP, but the unchanged group had more acute exacerbations than the improved group during treatment with BDP. These results indicates that there are many patients who had no improvement on BHR with long term BDP treatment and they have more acute exacerbations due to various stimuli. In conclusion, asthma is recognized chronic inflammatory disease and inhaled corticosteroid therapy has been recommended as the first line therapy. We must further study the clinical problems and underlying mechanisms concerning about treatment with an inhaled corticosteroid.

Topics: Anti-Asthmatic Agents; Asthma; Beclomethasone; Bronchial Hyperreactivity; Female; Glucocorticoids; Humans; Long-Term Care; Male; Middle Aged; Retrospective Studies

To evaluate the effects of anti-inflammatory drugs on bronchial hyperresponse in patients with mild asthma, We examined inhaled beta 2-agonists, beclomethasone dipropionate (BDP) and suplatast tosilate. The results were as follows: 1. Inhaled beta 2-agonists, which have no direct anti-inflammatory effect, significantly improved bronchial hyperresponsiveness with inhalation of less than 6 puffs/day except tenoterol, but not with more than 6 puffs/day for two years. Patients with asthma therefore should use no more than 6 puffs/day of inhaled beta 2-agonists. Combined use of BDP and inhaled beta 2-agonists further improved bronchial hyperresponsiveness. This can be achieved by concurrent use of BDP, which has a potent anti-inflammatory effect. 2. Low dose BDP (200 micrograms/day), which is recommend in the Japanese guidelines for asthma treatment increased peak expiratory flow and improved bronchial hyperresponsivenss significantly during 8 weeks of treatment, but by 4 weeks after the end of BDP treatment, peak expiratory flow and bronchial hyperresponsiveness had worsened. Because we don't know the detail past history of patients with mild asthma, the patients must be treated with a relatively high dose of BDP (800 micrograms/day), which did improved bronchial hyperresponsiveness and significantly reduced the numbers of eosinophils and EG2 positive cells in the bronchial mucosa of patients with mild asthma. 3. Suplatast tosilate, which exerts its anti-inflammatory effect by suppressing IL-4 and IL-5 was given to patients with mild asthma for 6 weeks. Suplatast tosilate significantly increased peak expiratory flow and significantly improved bronchial hyperresponsiveness. It also signiticantly reduced the number of eosinophils and EG2 positive cells in the bronchial mucosa of eight patients with mild asthma. Therefore this drug may be useful for the treatment of patients with mild asthma.

Topics: Administration, Inhalation; Administration, Oral; Adult; Aged; Anti-Allergic Agents; Anti-Inflammatory Agents; Arylsulfonates; Asthma; Beclomethasone; Bronchial Hyperreactivity; Female; Humans; Male; Middle Aged; Sulfonium Compounds

Histamine challenge testing is used to measure airway responsiveness in asthma. Histamine tachyphylaxis has been demonstrated after repeated challenges in mild asthmatics not using inhaled corticosteroid. Other studies, using subjects with variable severity of asthma, have not demonstrated histamine tachyphylaxis. Forty patients with stable asthma were studied and stratified according to severity of airway hyperresponsiveness and use of inhaled corticosteroid, to examine the effects of these factors on histamine tachyphylaxis. Airway responsiveness was measured as the histamine provocative concentration causing a 20 percent fall in FEV1 (PC20). Twenty subjects had mildly increased airway hyperresponsiveness (PC20 > 1 mg/ml), of whom 10 were using inhaled corticosteroid. Twenty subjects had moderate to severely increased airway hyperresponsiveness (PC20 < 1 mg/ml), of whom 10 were using inhaled corticosteroid. On each of two study days, 1 week apart, two histamine challenges were performed 1 h apart. Histamine tachyphylaxis was found for the entire group on both study days. The geometric mean PC20 increased from 1.0 mg/ml (percent SEM 1.2) to 1.3 mg/ml (percent SEM 1.2) 1 h later on day 1 (p < 0.0005), and 1.1 mg/ml (percent SEM 1.2) to 1.3 mg/ml (percent SEM 1.2) 1 h later on day 2 p < 0.05). Subgroup analysis demonstrated that tachyphylaxis only occurred consistently in subjects with mildly increased airway hyperresponsiveness not receiving inhaled corticosteroid. In this group, the PC20 increased from 2.2 mg/ml (percent SEM 1.2) to 3.2 mg/ml (percent SEM 1.2) on day 1 (p < 0.001), and from 2.5 mg/ml (percent SEM 1.3) to 3.4 mg/ml (percent SEM 1.2) on day 2 (p < 0.05). This study confirms that histamine tachyphylaxis occurs in asthmatics, but is consistently present only in mild, noncorticosteroid-dependent asthmatics.

Topics: Administration, Inhalation; Administration, Topical; Adult; Anti-Inflammatory Agents; Asthma; Beclomethasone; Bronchial Hyperreactivity; Bronchial Provocation Tests; Budesonide; Female; Forced Expiratory Volume; Glucocorticoids; Histamine; Humans; Male; Pregnenediones; Tachyphylaxis

The effect of changes of airway inflammation on airway nonspecific reactivity were studied in 29 patients with chronic asthma. Detailed examinations of bronchial lavage (BAL) fluid and airway responses to histamine, propranolol and exercise were performed before and after treatment. The patients treated with steroids had significant improvements in parameters of BAL fluid cells and mediators with consistent changes of decreasing airway reactivities to propranolol and exercise after treatment. Whereas no significant changes occurred in the patients treated with B2-agonist either in inflammatory parameters or airway responses. On the other hand, airway response to histamine changed little in all asthmatic patients. Our study implied that inhibiting the airway inflammation in asthmatics may lead to marked decrease of airway response to non-mediator stimuli but fail to attenuate bronchial hyperresponse to mediator stimuli like histamine.

Topics: Adult; Albuterol; Asthma; Beclomethasone; Bronchial Hyperreactivity; Bronchial Provocation Tests; Bronchoalveolar Lavage Fluid; Exercise Test; Forced Expiratory Volume; Histamine; Humans; Inflammation; Middle Aged; Propranolol

In a group of 14 patients with non-atopic asthma the effect on nedocromil sodium (8 mg/day) on bronchial reactivity, lung function parameters and doses of glucocorticosteroid in inhalation was studied. There was the significant reduction in beclomethasone doses, a rise in FEV1, FEF25-75 and decrease of PC20 histamine during 6 weeks of nedocromil therapy.

Topics: Administration, Inhalation; Adult; Asthma; Beclomethasone; Bronchial Hyperreactivity; Female; Humans; Male; Middle Aged; Nedocromil; Respiratory Function Tests

The effect of antiallergic agents (DSCG) (disodium cromoglycate, ketotifen, and ibudilast) and beclomethasone dipropionate inhaler (BDI) on bronchial hyperresponsiveness to histamine inhalation was retrospectively assessed in 72 asthmatic patients with more than a year's duration of the disease. Decrease in bronchial hyperresponsiveness to histamine was observed in 10 out of the 33 (30%) antiallergic-agents-treated patients (group A, mean duration = 7.8 months), in 12 of 19 (63.2%) BDI-treated patients (group B, 6.2 months), but only 2 of the 20 (10%) control patients (group C, 7.8 months). Improvement of histamine PC20 was from 310 to 597 micrograms/ml (P < 0.01) in group A, from 308 to 1622 micrograms/ml (P < 0.0005) in group B, and from 575 to 525 micrograms/ml (NS) in group C. A significant decrease in the peripheral eosinophil count was observed only in group B. The improvement in bronchial hyperresponsiveness was parallel with that of asthmatic symptoms; the percentage of patients becoming symptom-free rose from 12 to 42%, 5 to 89%, and 5 to 20% in groups A, B, and C, respectively. Out of 11 unimproved patients in group A, 7 showed a significant improvement in their histamine PC20 by BDI treatment (mean PC20: 311-->1828 micrograms/ml). These results suggest that BDI might be more effective than antiallergic agents in the treatment of patients with long-standing bronchial asthma.

Topics: Adolescent; Adult; Aged; Asthma; Beclomethasone; Bronchial Hyperreactivity; Bronchial Provocation Tests; Cromolyn Sodium; Female; Forced Expiratory Volume; Histamine; Humans; Immunoglobulin E; Ketotifen; Male; Middle Aged; Pyridines; Retrospective Studies; Vasodilator Agents; Vital Capacity

Topics: Administration, Inhalation; Arachidonic Acid; Asthma; Beclomethasone; Bronchi; Bronchial Hyperreactivity; Humans; Prednisolone; SRS-A

Inhaled corticosteroids provide a relatively trouble free means of treating the airway inflammation of asthma and can allow for the reduction of both oral steroid use and the symptoms in asthmatics using bronchodilators. Conventional doses may not be sufficient to provide control in many patients, and dosing should be tailored to the individual. These higher doses may cause systemic side effects, but these are less than those incurred by using oral prednisone.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Anti-Inflammatory Agents; Asthma; Beclomethasone; Bronchial Hyperreactivity; Fluocinolone Acetonide; Humans; Triamcinolone Acetonide