High doses of inhaled corticosteroids in unstable chronic asthma. A multicenter, double-blind, placebo-controlled study

In a multicenter, randomized, double-blind study, inhaled beclomethasone dipropionate (BDP) 1,500 micrograms/day was compared to placebo in 43 chronic asthmatic patients uncontrolled by inhaled salbutamol and oral theophylline. During the prestudy period, a test of maximal steroid reversibility with oral prednisolone 0.5 mg/kg/day for 14 days was performed. The therapeutic response was measured over an 8-wk period as the ability to maintain the clinical improvement and the optimal pulmonary function induced by prednisolone. During the study, severe asthma exacerbation occurred in one (5%) of the 21 patients who received BDP and in 15 (78%) of the 22 patients who received placebo (p less than 0.001). In patients who received BDP, FEV1 and peak expiratory flow (PEF) remained above the optimal postprednisolone value, with a trend to improvement during the 8-wk study period. In patients who received placebo, FEV1 and PEF decreased and remained below the optimal value. We conclude that, in chronic asthma, inhaled BDP 1,500 micrograms/day maintains the optimal pulmonary function in addition to the clinical benefit induced by a short course of oral corticosteroids.     

Initial improvements in lung function and bronchial hyperresponsiveness are maintained during 5 years of treatment with inhaled beclomethasone dipropionate and terbutaline.

OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.     

Effects of inhaled corticosteroid in elderly patients with chronic obstructive pulmonary disease]

We examined the efficacy of inhaled corticosteroid (beclomethazone dipropionate: BDP) in elderly patients with chronic obstructive pulmonary disease (COPD). Eighty-six patients with COPD were divided into 3 groups: COPD treated without BDP (group 1, n = 26), COPD treated with BDP (group 2, n = 25), and BDP-treated COPD with asthmatic symptoms (group 3, n = 35). Pulmonary function test findings, symptoms, and prognosis for the 3 groups were retrospectively compared. No significant differences in yearly decline of FEV1.0 were observed. Of the patients treated with inhaled corticosteroid (groups 2 and 3), 30% exhibited improved FEV1.0. Of these patients, monthly decline of FEV1.0 correlated negatively with bronchial reversibility in FEV1.0 before and after inhalation of salbutamol (delta FEV1.0) (r = -0.28, p = 0.03). Cough and sputum scores were significantly improved in groups 2 and 3 (p < 0.01). Fewer admissions and episodes of acute exacerbation were noted in groups 2 and 3 than in group 1. From these results, we concluded that inhaled corticosteroid was effective in elderly COPD patients with bronchial reversibility and airway symptoms.     

Effects of withdrawal of inhaled steroids in men with severe irreversible airflow obstruction

Inhaled corticosteroid therapy has proven efficacy for asthmatics, but the benefit for patients with chronic obstructive pulmonary disease (COPD) is less well supported. We hypothesized that withdrawal of inhaled steroids in elderly patients with severe irreversible airway obstruction would not lead to a deterioration in respiratory function. We designed a prospective, double-blind, randomized, placebo-controlled, crossover study to follow spirometry, quality of life questionnaire, six-minute (6-min) walk test, and sputum markers of inflammation during a 6-wk placebo treatment period and a 6-wk treatment period with beclomethasone dipropionate (BDP), 336 microg/d. There were 24 men receiving BDP who entered the study; 15 completed the study. Their mean age was 66.9 +/- 1.9 yr, and mean FEV(1) was 1.61 +/- 0.1 L (47% of predicted). There was a significant decrease in the mean FEV(1 )while using the placebo inhaler (1.70 L versus 1.60 L, baseline versus placebo: 95% CI, 0.002 to 0.195; p < 0.05). There was a decrease in the mean percentage change in FEV(1) for the study subjects during the placebo treatment period as compared with the BDP treatment period (-6.28 versus 5.03%, placebo versus BDP: 95% CI, -23.38 to 0.76; p = 0.06). Six-minute walk test results and sputum analysis for cell count and differential were not significantly different during placebo and BDP treatment periods. Borg scale assessment of dyspnea after exercise was increased while using the placebo inhaler as compared with baseline, and decreased during the BDP treatment period. Chronic Respiratory Disease Questionnaire (CRQ) scores revealed no significant difference between placebo and BDP. This study has demonstrated that in elderly patients with severe irreversible airway obstruction, withdrawal of inhaled corticosteroid therapy leads to a deterioration in ventilatory function and increased exercise-induced dyspnea.     

High-dose beclomethasone: oral steroid-sparing effect in severe asthmatic patients

One hundred and twenty four patients with severe asthma requiring maintenance treatment with oral corticosteroids were included in a multicentre, double-blind, randomized study comparing the effects of inhaled beclomethasone dipropionate (BDP) (250 micrograms.puff-1), beginning with 1,000 micrograms daily, vs placebo (P). Pulmonary function was assessed and dosage of prednisone and BDP (or P) were adjusted every 15 days according to a clinical score. Our results showed, after 3 months: 1) A greater drop-out rate in the P group than in the BDP group (36 vs 6%, respectively, p less than 0.01); 2) A total weaning from prednisone in 76% of patients in the BDP group (mean BDP dosage = 1,270 +/- 340 micrograms.day-1, mean +/- SD), vs 34% in the P group (p less than 0.001). The mean daily dosage of prednisone was reduced from 17 +/- 7.5 mg to 3.1 +/- 7.4 mg in the BDP group vs 15.6 +/- 7.7 mg to 9.1 +/- 9.4 mg in the P group (p less than 0.001) without any relationship between the steroid-sparing effect and the initial dosage of prednisone; 3) Mean change in forced expiratory volume in one second (FEV1) was +7 +/- 21% from the initial value in the BDP group vs -6 +/- 20% in the P group; p less than 0.01. Thus, in patients with severe asthma requiring oral corticosteroids, high-dose BDP has an important oral steroid-sparing effect not related to the initial dosage of oral steroids and allows a better control of airway obstruction than oral corticosteroids alone.     

吸入糖皮质激素治疗非哮喘性慢性阻塞性疾病的研究

目的 研究中等剂量二丙酸氯地米松（ＢＤＰ）短疗程吸入治疗非哮喘慢性阻塞性肺疾病（ＣＯＰＤ）是否有疗效，方法 按照随机，对照，单盲的设计，６１例非哮喘性ＣＯＰＤ患分两组，分别予ＢＤＰ（１０００μｇ．ｄ＾－１）与安慰剂吸入治疗６周，治疗前后测定肺功能一秒钟用力呼气容积（ＦＥＶ１）用力肺活量（ＦＶＣ），最大呼气中段流速（ＭＭＥＦ）值和血浆内纱（ＥＴ－１）的浓度，并记录临床症状记分，生活质量记分，结果     

Acute bronchodilator trials in chronic obstructive pulmonary disease.

Short-term trials of bronchodilator drugs are widely used to assess patients with stable chronic obstructive pulmonary disease (COPD), but there is an uncertainty about the equivalence of the FEV1 response to beta-agonists and anticholinergic drugs, their relative ability to identify patients likely to improve with corticosteroids, the most appropriate way to express the results of these tests, and whether age or allergic status affects the beta-agonist and anticholinergic response differently. We studied 100 consecutive patients with stable COPD (mean FEV1, 0.96 +/- 0.48 L; mean age, 62 +/- 8 yr). Spirometry was measured before and after either 5 mg of nebulized salbutamol or 500 micrograms of nebulized ipratropium bromide and repeated after 2 wk of 30 mg of oral prednisolone daily. Total IgE, specific RAST, and skin prick testing values were recorded. Using modified American Thoracic Society response criteria, 33 patients failed to bronchodilate after the acute trials, 16 responded only to nebulized salbutamol, 17 to nebulized ipratropium, and 34 to both drugs. Twenty-two patients improved after corticosteroids. This was usually detected by a positive acute trial response (salbutamol 90% specific; ipratropium 84% specific). Baseline FEV1 differed between days, and in those who responded on only 1 day, this variation correlating with the response to ipratropium (r = 0.66). Expressing the response criterion as a percentage change in the available bronchodilatation increased the numbers responding with a high baseline FEV1, and vice versa. Neither age nor allergic status was related to the change in FEV1 after either drug in these patients. In COPD patients, testing with high-dose nebulized bronchodilators identifies a substantial number of partially reversible patients whatever age it is employed.(ABSTRACT TRUNCATED AT 250 WORDS)     

The use of high dose inhaled beclomethasone dipropionate as a means of assessing steroid responsiveness in obstructive airways disease

The use of high dose inhaled beclomethasone dipropionate (BDP) as a means of assessing steroid responsiveness in chronic obstructive airways disease (COAD) was assessed in 22 patients in a study involving three consecutive 2-week periods of placebo, inhaled BDP (1500 micrograms daily), and oral prednisolone (30 mg daily). Five of the 22 patients were considered steroid responsive following the course of oral corticosteroids and in each case this responsiveness had been identified by inhaled BDP therapy. It is concluded that high dose inhaled BDP (1500 micrograms daily) may be used to assess corticosteroid responsiveness in COAD.     

Exhaled nitric oxide and hydrogen peroxide in patients with chronic obstructive pulmonary disease: effects of inhaled beclomethasone

There is controversy about the role of inhaled corticosteroids in chronic obstructive pulmonary disease (COPD). Although they appear to have little impact on airways obstruction or its progression, their use may reduce the frequency and/or severity of exacerbations in a subset of patients. We undertook the following study to determine the impact of inhaled corticosteroid on two noninvasive markers of airways inflammation. We assigned 20 stable nonsmoking patients with COPD in random, double-blind crossover fashion to two 2-wk treatment periods with inhaled beclomethasone 500 microg twice daily or matching placebo, followed by a 2-wk washout period. We measured exhaled nitric oxide (ENO), breath condensate H(2)O(2), and flow volume spirometry at weekly intervals. Median baseline ENO was 26.2 (19.3 to 54.8) ppb and fell significantly following 1 and 2 wk of beclomethasone (-10.6 ppb, p = 0.002, and -6.3 ppb, p = 0.013, respectively) but was unchanged by placebo inhalation. Breath condensate H(2)O(2) levels did not change significantly with inhaled beclomethasone or placebo. Although there were no significant changes in FEV(1) with BDP therapy, there was a moderate inverse correlation between changes in ENO and changes in FEV(1) (r -0.50). We conclude that inhaled beclomethasone reduces ENO levels in stable nonsmoking patients with COPD, a finding compatible with an antiinflammatory mechanism of action.     

Prospective,placebo-controlled trial of 5 vs 10 days of oral prednisolone in acute adult asthma

BACKGROUND: The optimal duration of oral steroid treatment in the management of acute adult asthma is unclear. We prospectively studied the effect of 5 vs. 10 days of oral prednisolone in patients with acute asthma requiring hospital admission. METHODS: Each patient received 40 mg of enteric-coated prednisolone daily for 5 days, followed by 5 days of 40 mg prednisolone daily (n=24) or placebo (n=20). All were given their usual inhaled asthma therapy including inhaled corticosteroids. Patients kept PEF and symptom diaries for 21 days. RESULTS: For the 5-day treatment group mean (95% CI) early morning PEF was 6 (-47,+36) l/min lower to day 21 (P=0.78). There was no evidence of differences in other PEF measures (morning post-bronchodilator, evening or worst of day). One patient in each group had an exacerbation requiring further oral steroids during the 21-day observation period. Asthma symptom scores were worse in the 5-day group on days 6-21 but the significance of this finding was uncertain, as a difference had emerged by day 5 (prior to trial entry). CONCLUSIONS: It may be possible to reduce the standard steroid course to 5 days in acute adult asthma, provided all patients receive inhaled steroids and a personal asthma management plan.     

A comparison between inhaled salmeterol and theophylline in the short-term treatment of stable chronic obstructive pulmonary disease

BACKGROUND: International guidelines indicate that the long-acting bronchodilators play a key role in the treatment of patients with chronic obstructive pulmonary disease (COPD). The aim of this study was to assess the short term efficacy and safety of 50 and 100 microg bid inhaled salmeterol, compared with placebo and orally dose titrated slow-release theophylline in patients with stable COPD. METHODS: Thirteen patients (67+/-7 years, three females) with moderate-to-severe COPD (FEV1<70% predicted and >30% predicted) and with poor reversibility (post-bronchodilator FEV1<12% and <200 ml from pre-bronchodilator values) completed this single centre randomised, double-blind, double-dummy, four-phase cross-over clinical trial. Patients were randomised to treatment after a 2-week oral corticosteroid trial and a theophylline titration phase. Each treatment lasted 2 week with a 2-week washout period. Values at the end of treatments were compared. RESULTS: Inhaled salmeterol at both tested doses was better than placebo in improving lung function (FEV1, FVC, and morning PEF) of stable patients with moderate COPD over a period of 2 weeks. Although slight (about 170 ml, 150 ml, and 120 ml/min on average, for FEV1, FVC, and PEF, respectively) the improvement was significant. The effects seem to improve only slightly with the higher dose. Salmeterol appeared to be more effective than theophylline treatment when compared to placebo, as theophylline improved significantly, but less, the FEV1 (about 80 ml, on average) without affecting any of the other lung function variables. Salmeterol 100 microg was significantly better than theophylline in improving morning PEF. Four patients reported five adverse events while receiving placebo and 2 and 3 patients reported 2 and 3 adverse events, respectively, during salmeterol 50 microg and salmeterol 100 microg phases. None was considered drug related. Five patients experienced 13 adverse events with theophylline treatment, four of which were considered drug related. CONCLUSION: Inhaled salmeterol improves lung function in stable patients with moderate-to-severe and poorly reversible COPD. The magnitude of improvement in FEV1 observed in this study is similar to that found in longer and larger studies on similar populations of patients. In those studies, that improvement was associated with a better quality of life and less symptoms. Theophylline determined a smaller improvement in FEV1 with more unpleasant side effects that both doses of inhaled salmeterol, though there was no significant difference. It is concluded that salmeterol is an effective and well tolerated therapy, potentially preferable to theophylline, at least in the short-term management of stable COPD.     

Anti-inflammatory effects of combined budesonide/formoterol in COPD exacerbations

Systemic corticosteroids and additional short-acting beta2-agonists are commonly used in exacerbations of chronic obstructive pulmonary disease (COPD). In this double-blind study, the combination of a high-dose inhaled corticosteroid with a rapid-onset long-acting beta2-agonist was evaluated in the treatment of out-patient COPD exacerbations. The primary aim was to compare 14-day treatment effects of budesonide/formoterol to placebo on sputum eosinophils and, secondarily, on other indices of inflammation, forced expiratory flow in one second (FEV(1)), symptoms, health status, and adverse events. Forty-five patients not using steroids (37 male, 21/24 current/ex smoker, median packyears 38, age 65 years, FEV(1) 61% predicted), experiencing a COPD exacerbation, were treated at home with budesonide/formoterol (320/9 microg 4 times daily), prednisolone (30 mg daily), or placebo for 14 days. Sputum eosinophils were significantly reduced by budesonide/formoterol (-57%) compared to placebo (+24%) (p = 0.01). Budesonide/formoterol reduced total symptom scores significantly (p = 0.01) compared to placebo. The increase in FEV(1) by 2 weeks of treatment with budesonide/formoterol (125 ml) was not significantly different from that of placebo (43 ml) (p = 0.07). Budesonide/ formoterol treatment did not suppress morning serum cortisol compared to placebo (-16%; p = 0.50). In conclusion, budesonide/formoterol reduces sputum eosinophils and improves symptoms in the treatment of out-patient COPD exacerbations.     

Controlled short-term trial of fluticasone propionate in ventilator-dependent patients with COPD

BACKGROUND: There is no agreement about the efficacy of systemic corticosteroids in patients with COPD, but corticosteroids often are employed during exacerbations of the disease. The use of systemic or inhaled corticosteroids in patients in stable condition is even more controversial, even though the more severely affected patients seem to respond better. Unfortunately, in this subset of patients, the use of forced expiratory maneuvers frequently fails to detect significant functional response. Study objectives: We evaluated the short-term effects of an inhaled corticosteroid, fluticasone propionate (FP), on FEV(1) and on the mechanical properties of patients in stable condition with severe COPD and chronic hypercapnic respiratory failure who were receiving long-term ventilatory support. This allowed us to measure respiratory mechanics (RM) passively, thereby avoiding any problems linked with voluntary maneuvers. DESIGN: Randomized, placebo-controlled, crossover study. SETTING: A respiratory ICU. PATIENTS: Twelve hypercapnic COPD patients (mean [+/- SD] PaCO(2), 60+/-11 mm Hg; mean FEV(1), 13+/-5% predicted; and mean FEV(1)/FVC, 31 +/- 7%) were enrolled. INTERVENTIONS: A daily dose of 2,000 microg FP or placebo was administered via metered-dose inhaler during mechanical ventilation for 5 consecutive days. A washout of 72 h was allowed between regimens. MEASUREMENTS: End-expiratory and end-inspiratory airway occlusions were performed to assess static intrinsic positive end-expiratory pressure (PEEPi,st), static compliance of the respiratory system (Cst,rs), maximal respiratory resistance (Rmax, rs), and minimal respiratory resistance (Rmin,rs). The bronchodilator response also was assessed by FEV(1) level. RESULTS: No significant changes were found in RM after administration of the placebo. By day 6, FP had induced the following significant decreases: PEEPi,st, 4.3+/-2.4 to 3.1+/-1.7 cm H(2)O (p<0.01); Rmax,rs, 19.0+/-6.5 to 14.6+/-6 cm H(2)O/L/s (p<0.001); and Rmin,rs, 14.8+/-4.2 to 10.5+/-3.4 cm H(2)O/L/s (p<0.001). The Cst,rs and the effective additional resistance of the respiratory system did not change significantly, the latter suggesting that the major effect of FP was on the airway caliber (Rmin,rs). FEV(1) changes significantly (p<0.01) underestimated the bronchodilator response, as compared with changes in Rmin,rs. CONCLUSIONS: We conclude that in patients in stable condition with severe COPD and chronic hypercapnic respiratory failure, a brief trial of FP may induce a bronchodilator response, mainly related to a reduction in airway resistances, that is not detected by the usual pulmonary function tests.     

舒利迭治疗支气管哮喘临床效果效果研究

目的 探讨舒利迭治疗支气管哮喘的临床效果.方法 支气管哮喘患者108例,随机分为治疗组和对照组(两组分别为54例),其中治疗组吸入糖皮质激素(倍氯米松)、短效β2受体激动剂(硫酸特布他林),以及使用舒利迭(沙美特罗/氟替卡松)治疗,吸入2次/d.对照组吸入倍氯米松和口服特布他林,观察12周,观察患者哮喘临床控制率、第1秒用力呼气容积(FEV1)、最大呼气流速(PEF)及药物不良反应.结果 治疗组有34例(62.9%)达到临床控制,与对照组20例(37.0%)相比,差异有统计学意义(P＜0.05);两组治疗后FEV1、PEF水平均高于治疗前的水平(P＜0.05).结论 应用舒利迭治疗支气管哮喘能有效改善临床症状和降低复发率,优于单纯吸入糖皮质激素.     

Inhaled Fluticasone and Salmeterol Suppress Eosinophilic Airway Inflammation in Chronic Obstructive Pulmonary Disease: Relations with Lung Function and Bronchodilator Reversibility

The aim of this study was to determine whether combined inhaled corticosteroids and long-acting β₂ agonists can suppress eosinophilic inflammation in chronic dostructive plumonary disease (COPD) and to investigate the association between the level of eosinophilia and the degree of bronchodilator reversibility. Sixty-two patients with stable COPD (forced expiratory volume in 1 [FEV₁] of 30%–70% predicted before bronchodilation) were enrolled from our outpatient clinic. Patients received inhaled fluticasone (100 μg)/salmeterol (50 μg) twice daily for two months. Lung function measurements, bronchodilator tests, and sputum induction were performed. The number of inflammatory cells and mediators, including interleukin-8 (IL-8), tumor necrosis factor-α (TNF-α), and eosinophilic cationic protein (ECP), were measured. Treatment with inhaled fluticasone and salmeterol significantly suppressed eosinophilic inflammation in COPD patients with sputum eosinophilia (mean 8.9% ± 2.0% vs. 1.6% ± 0.5%, p = 0.003), but insignificant differences in FEV₁ and FVC between patients with and without eosinophilia suggested that suppression of eosinophilic inflammation had no effect on FEV₁ or FVC. Reduction in the percentage of eosinophils was significantly correlated with decreased levels of ECP (r = 0.48, p < 0.001). Levels of neutrophils, IL-8, and TNF-α were not affected. Sputum eosinophilia was not related to the degree of bronchodilator reversibility. The degree of bronchodilator reversibility did not predict the increase in FEV₁ and FVC after treatment with inhaled corticosteroids/long-acting β₂ agonists. Suppression of eosinophilic inflammation and bronchodilator responsiveness indices were not correlated with clinical outcomes in COPD patients treated with inhaled corticosteroids/long-acting β₂ agonists. Diahn-Warng Perng and Cheng-Che Wu contributed equally to this work.     

Diagnosis and management of stable chronic obstructive pulmonary disease: a clinical practice guideline update from the American College of Physicians, American College of Chest Physicians, American Thoracic Society, and European Respiratory Society

DESCRIPTION: This guideline is an official statement of the American College of Physicians (ACP), American College of Chest Physicians (ACCP), American Thoracic Society (ATS), and European Respiratory Society (ERS). It represents an update of the 2007 ACP clinical practice guideline on diagnosis and management of stable chronic obstructive pulmonary disease (COPD) and is intended for clinicians who manage patients with COPD. This guideline addresses the value of history and physical examination for predicting airflow obstruction; the value of spirometry for screening or diagnosis of COPD; and COPD management strategies, specifically evaluation of various inhaled therapies (anticholinergics, long-acting β-agonists, and corticosteroids), pulmonary rehabilitation programs, and supplemental oxygen therapy. METHODS: This guideline is based on a targeted literature update from March 2007 to December 2009 to evaluate the evidence and update the 2007 ACP clinical practice guideline on diagnosis and management of stable COPD. RECOMMENDATION 1: ACP, ACCP, ATS, and ERS recommend that spirometry should be obtained to diagnose airflow obstruction in patients with respiratory symptoms (Grade: strong recommendation, moderate-quality evidence). Spirometry should not be used to screen for airflow obstruction in individuals without respiratory symptoms (Grade: strong recommendation, moderate-quality evidence). RECOMMENDATION 2: For stable COPD patients with respiratory symptoms and FEV(1) between 60% and 80% predicted, ACP, ACCP, ATS, and ERS suggest that treatment with inhaled bronchodilators may be used (Grade: weak recommendation, low-quality evidence). RECOMMENDATION 3: For stable COPD patients with respiratory symptoms and FEV(1) <60% predicted, ACP, ACCP, ATS, and ERS recommend treatment with inhaled bronchodilators (Grade: strong recommendation, moderate-quality evidence). RECOMMENDATION 4: ACP, ACCP, ATS, and ERS recommend that clinicians prescribe monotherapy using either long-acting inhaled anticholinergics or long-acting inhaled β-agonists for symptomatic patients with COPD and FEV(1) <60% predicted. (Grade: strong recommendation, moderate-quality evidence). Clinicians should base the choice of specific monotherapy on patient preference, cost, and adverse effect profile. RECOMMENDATION 5: ACP, ACCP, ATS, and ERS suggest that clinicians may administer combination inhaled therapies (long-acting inhaled anticholinergics, long-acting inhaled β-agonists, or inhaled corticosteroids) for symptomatic patients with stable COPD and FEV(1)<60% predicted (Grade: weak recommendation, moderate-quality evidence). RECOMMENDATION 6: ACP, ACCP, ATS, and ERS recommend that clinicians should prescribe pulmonary rehabilitation for symptomatic patients with an FEV(1) <50% predicted (Grade: strong recommendation, moderate-quality evidence). Clinicians may consider pulmonary rehabilitation for symptomatic or exercise-limited patients with an FEV(1) >50% predicted. (Grade: weak recommendation, moderate-quality evidence). RECOMMENDATION 7: ACP, ACCP, ATS, and ERS recommend that clinicians should prescribe continuous oxygen therapy in patients with COPD who have severe resting hypoxemia (Pao(2) ≤55 mm Hg or Spo(2) ≤88%) (Grade: strong recommendation, moderate-quality evidence).     

Changes in levels of catalase and glutathione in erythrocytes of patients with stable asthma, treated with beclomethasone dipropionate.

In asthmatic patients, antioxidant defence is decreased. Although inhaled corticosteroids decrease asthmatic inflammation and modulate reactive oxygen species (ROS) generation, little is known of their effect on cellular antioxidant levels. The aim of this study was to evaluate the effect of inhaled beclomethasone dipropionate (BDP; 1,000 microg x day(-1)) on erythrocyte antioxidant levels in stable asthmatic patients. Forty patients with stable, mild asthma were treated in a double-blind, placebo-controlled, parallel-group study with BDP 250 microg, two puffs b.i.d. for 6 weeks. At entry and every 2 weeks during treatment, erythrocyte antioxidant levels, haematological parameters, pulmonary function tests and asthma symptoms were determined. The results show that during treatment with BDP, erythrocyte catalase levels increased (at entry (mean +/-SEM) 41+/-4, after 6 weeks 54+/-4 micromol H2O2 x min(-1) x g haemoglobin (Hb)(-1), p = 0.05 in comparison with placebo). Erythrocyte total glutathione levels significantly decreased after 6 weeks treatment with BDP (from 7.0+/-0.4 to 6.6+/-0.3 micromol x g Hb(-1) (p = 0.04)). In the BDP-treated patients, blood eosinophil counts were higher in patients who responded with an increase in erythrocyte catalase levels during BDP treatment, as compared to those not responding ((mean +/-SEM) 340+/-39 and 153+/-52x10(6) cells x L(-1), respectively, p = 0.05). The present study shows that treatment with inhaled bedomethasone dipropionate results in changes in antioxidant levels in erythrocytes of patients with stable, mild asthma.     

Comparison of budesonide and beclomethasone dipropionate in patients with severe chronic asthma: assessment of relative prednisolone-sparing effects

The relative prednisolone-sparing effects of inhaled budesonide 400 micrograms daily and beclomethasone dipropionate (BDP) 400 micrograms daily were compared in a double-blind crossover study of 26 patients with chronic asthma requiring treatment with BDP and oral prednisolone in a daily dose of 5 mg or greater. During each period of the trial budesonide and BDP were inhaled via conventional pressurized inhalers in a dose of 100 micrograms four times daily. Prednisolone was reduced by 1 mg per month from the patient's normal maintenance dose to zero or to the point at which asthmatic symptoms became unacceptable. The mean reduction in prednisolone dose during BDP treatment was 2.65 mg compared with 1.8 mg at the end of the budesonide period. The difference between the prednisolone-sparing properties of BDP and budesonide assessed in this way in this group of patients was statistically significant in favour of BDP. The mean minimum prednisolone doses at the end of the treatment periods were 3.46 mg for BDP and 4.3 mg for budesonide. Since inhaled steroids were not withdrawn the absolute prednisolone-sparing properties of the two drugs were not assessed, and thus a pharmacological potency ratio cannot be derived from the results. It is concluded that BDP is marginally more potent than budesonide in its prednisolone-sparing properties.     

Stable COPD: predicting benefit from high-dose inhaled corticosteroid treatment.

The role of inhaled corticosteroids in the management of chronic obstructive pulmonary disease (COPD) remains controversial. The purpose of this study was to evaluate whether sputum eosinophilia (defined as eosinophils > or = 3%) predicts clinical benefit from inhaled corticosteroid treatment in patients with smoking-related clinically stable moderate-to-severe COPD. Forty consecutive patients with effort dyspnoea (mean age 67 yrs; 52 pack-yr smoking history; post-bronchodilator forced expiratory volume in one second (FEV1) <60% predicted, consistent with moderate-to-severe smoking-related chronic airflow limitation) were enrolled. Subjects were treated with inhaled placebo followed by inhaled budesonide (Pulmicort Turbuhaler 1,600 microg.day(-1)), each given for 4 weeks. While the treatment was single-blind (subject level), sputum cell counts before and after treatment interventions were double-blind, thus removing bias. Outcome variables included spirometry, quality-of-life assessment and 6-min walk test. Sputum eosinophilia was present in 38% of subjects. In these, budesonide treatment normalised the eosinophil counts and, in comparison to placebo treatment, resulted in clinically significant improvement in the dyspnoea domain of the disease-specific chronic respiratory questionnaire (0.8 versus 0.3) and a small but statistically significant improvement in post-bronchodilator spirometry (FEV1 100 mL versus 0 mL; p<0.05). In conclusion, sputum eosinophilia predicts short-term clinical benefit from high-dose inhaled corticosteroid treatment in patients with stable moderate-to-severe chronic obstructive pulmonary disease.     

Inhaled salmeterol and salbutamol in asthmatic patients. An evaluation of asthma symptoms and the possible development of tachyphylaxis

Salmeterol (SM) is a new beta 2-adrenoceptor agonist for inhaled use that has been shown to produce long-lasting bronchodilation in asthmatic patients. In the present study, evaluating efficacy and possible development of tachyphylaxis after SM, 12 patients with stable asthma were included after the demonstration of reversibility in FEV1 of at least 15% to 200 micrograms salbutamol (SB) or 20% to 500 micrograms SB. At inclusion all patients were receiving treatment with inhaled beta 2-agonists, and 11 of the 12 patients were also receiving inhaled corticosteroids. The patients were treated for two 2-wk periods with either inhaled SM 50 micrograms twice a day or SB 200 micrograms four times a day, following a double-blind, double-dummy, randomized design. The treatment periods were separated by a washout period of 1 wk. Dose-response curves to inhaled SB were obtained the day before and the day after each treatment period. On each of these days, basal FEV1, tremor, heart rate, and blood pressure were recorded and were then followed after the inhalation of 100 + 300 + 900 micrograms SB to obtain a cumulative dose-response curve. During the treatment periods, as well as during the washout week after each treatment, the patients recorded their morning and evening peak expiratory flow (PEF) each day before the inhalation of the study drug. Subjective asthma symptoms were monitored by a visual analog scale after each treatment period. The dose-response curves to SB revealed no signs of a reduced response to SB after any of the treatments, but significant increases in basal FEV1 and FVC were seen after the SM period (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)