Characteristics of COPD phenotypes classified according to the findings of HRCT

The present study was performed to clarify the clinical characteristics of chronic obstructive pulmonary disease (COPD) patients classified into phenotypes according to the dominancy of emphysema and the presence of bronchial wall thickening evaluated by chest high-resolution computed tomography (HRCT). Eighty-five patients with stable COPD (FEV1 < or = 80%) were examined by chest HRCT. Emphysematous changes and bronchial wall thickening were evaluated visually, and COPD patients were classified into three phenotypes: absence of emphysema, with little emphysema with or without bronchial wall thickening (A phenotype), emphysema without bronchial wall thickening (E phenotype), and emphysema with bronchial wall thickening phenotype (M phenotype). Clinical characteristics were compared among the three phenotypes. The A phenotype group showed a higher prevalence of subjects who had never smoked and patients with wheezing, higher values of body mass index (BMI) and DLco, milder lung hyperinflation, and greater reversibility of airflow limitation responsive to inhaled beta2-agonist as compared with the other phenotypes. The degree of emphysema was significantly associated with Brinkman index, lower BMI, decrease in DLco, lower FEV1/FVC. The presence of bronchial wall thickening in A- and M- phenotype was significantly associated with reversibility responsive to treatment with inhaled corticosteroid and sputum eosinophilia. These findings suggest that the morphological phenotypes of COPD show several clinical characteristics and different responsiveness to treatment with bronchodilators and inhaled corticosteroids.     

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     

Interferon therapy induces the improvement of lung function by inhaled corticosteroid therapy in asthmatic patients with chronic hepatitis C virus infection: a preliminary study

STUDY OBJECTIVES: Several reports have suggested that subsets of asthmatic patients with chronic viral infection fail to respond to corticosteroid therapy. Therefore, this study was designed to determine that asthmatic patients with chronic hepatitis C virus (HCV) infection fail to improve lung function by inhaled corticosteroid therapy, and that interferon (IFN) therapy against HCV is effective for such patients. DESIGN: Prospective observational study. SETTING: University hospital. PATIENTS: Forty asthmatic patients with chronic HCV infection. INTERVENTIONS: After a 4-week run-in period, all asthmatic patients received therapy with inhaled beclomethasone dipropionate (BDP), 400 micro g twice daily for 6 weeks. After the first study, all asthmatic patients continued to receive inhaled BDP, and 30 HCV-positive asthmatic patients received IFN-alpha therapy for 6 months. MEASUREMENTS AND RESULTS: Prebronchodilator and postbronchodilator FEV(1) values were examined after a 4-week run-in period, after 6 weeks of BDP therapy, and at 1 year from the end of IFN therapy. After a 4-week run-in period as well as after 6 weeks of BDP therapy, there were no significant differences in either prebronchodilator or postbronchodilator FEV(1) values among the three groups. However, 1 year after the end of IFN therapy, the mean prebronchodilator and postbronchodilator FEV(1) values were significantly higher in the IFN responder group (n = 11) [prebronchodilator FEV(1), 1.93 L (SD, 0.13 L); postbronchodilator FEV(1), 2.28 L (SD, 0.15 L)] than in the IFN nontreatment group (n = 10) [prebronchodilator FEV(1), 1.78 L (SD, 0.10 L); p = 0.01; postbronchodilator FEV(1), 2.07 L (0.13 L); p = 0.005] or the IFN nonresponder groups (n = 19) [prebronchodilator FEV(1), 1.79 L (SD, 0.15 L); p = 0.006; postbronchodilator FEV(1), 2.07 L (SD, 0.18 L); p = 0.002]. Moreover, prebronchodilator and postbronchodilator FEV(1) values were significantly higher only in the IFN responder group at 1 year after the end of IFN therapy than after the 4-week run-in period (prebronchodilator FEV(1), p = 0.028; postbronchodilator FEV(1); p = 0.002) or after 6 weeks of BDP therapy (p = 0.016 and p = 0.004, respectively). CONCLUSIONS: Our findings suggest that chronic HCV infection in asthmatic patients is associated with impaired responses to inhaled BDP therapy and that intervention with IFN reverses such responses only in the IFN responder group.     

Additive effects of prednisolone and beclomethasone dipropionate in patients with stable chronic obstructive pulmonary disease

It remains unclear whether inhaled corticosteroids can produce the maximum benefits of corticosteroids in patients with chronic obstructive pulmonary disease (COPD). To assess the additive effects of 30 mg/day prednisolone to high-dose, inhaled beclomethasone dipropionate (BDP), we conducted a randomised double-blind, placebo-controlled cross-over trial. The study population consisted of 21 men with stable COPD. The mean age of the patients was 69.1 +/- 6.8 years, and FEV(1)was 0.86 +/- 0.28 l. Seventeen out of the 21 patients (81%) were considered susceptible to steroids in a previous trial (FEV(1)increased at least 15% from baseline after receiving 14 days of 30 mg/day prednisolone). All of the patients had been on 1600 microg/day BDP for more than 3 months. Spirometry was performed before the entry, and at the end of 3-week placebo and prednisolone periods. The peak expiratory flow (PEF), symptoms, and Guyatt's Chronic Respiratory Disease Questionnaire (CRQ) as a disease specific health-related quality of life over the last seven days of each period were also evaluated. Although a marginal increase in PEF was found during the prednisolone period, no significant differences in FEV(1), FVC, symptoms or CRQ scores were observed between the two treatment periods. We conclude that the therapeutic effects of steroid therapy may be achieved by the long-term use of high-dose, inhaled corticosteroid in some patients with stable COPD.     

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.     

Short- and long-term efficacy of fluticasone propionate in subjects with early signs and symptoms of chronic obstructive pulmonary disease. Results of the DIMCA study

BACKGROUND: Early treatment with inhaled corticosteroids may prevent progression of irreversible obstruction in COPD, especially in patients with bronchial hyperresponsiveness. We investigated the clinical effects of early introduction of inhaled steroids in subjects showing early signs and symptoms of COPD without a prior clinical diagnosis. METHODS: Study subjects were detected in a general population screening and monitoring program. Those with a moderately accelerated annual FEV1 decline and persistent respiratory symptoms were invited to participate in a 2-year randomized controlled trial comparing fluticasone propionate DPI 250 microg b.i.d. with placebo. Pre- and post-bronchodilator (BD) FEV1, PC20 histamine, functional status (COOP/WONCA charts) and occurrence of exacerbations were periodically assessed. Subjects recorded respiratory symptoms. Post-BD FEV1 decline served as the main outcome. Multivariable repeated measurements analysis techniques were applied. RESULTS: 48 subjects were randomized (24 fluticasone, 24 placebo). After 3 months, the post-BD FEV1 had increased with 125 ml (SE = 68, P = 0.075) and the pre-BD FEV1 with 174 ml (SE 90, P = 0.059) in the fluticasone relative to the placebo group. The subsequent post-BD and pre-BD FEV1 decline were not beneficially modified by fluticasone treatment. There were no statistically significant differences in respiratory symptoms, functional status, or exacerbations favoring fluticasone. Subgroup analysis indicated that the presence of bronchial hyperresponsiveness modified the initial FEV1 response on fluticasone, but not the subsequent annual FEV1 decline. CONCLUSION: Early initiation of inhaled steroid treatment does not seem to affect the progressive deterioration of lung function or other respiratory health outcomes in subjects with early signs and symptoms of COPD. In subjects at risk for, or in an early stage of COPD, long-term inhaled steroid treatment should not be based on a single spirometric evaluation after 3 months.     

Inhaled corticosteroids reduce the severity of bronchial hyperresponsiveness in asthma but oral theophylline does not

In a double-blind crossover study, we compared the relative effects of inhaled beclomethasone dipropionate (BDP) 800 micrograms per day and oral theophylline on the severity of bronchial hyperresponsiveness (BHR) to histamine. Daily doses of theophylline were sufficient to keep serum levels between 55 and 110 mumol/L. The subjects were 26 patients with severe asthma whose symptoms were inadequately controlled by regular treatment with inhaled salbutamol. The severity of BHR improved within 3 wk in the group treated with BDP, whereas no change occurred in the group treated with theophylline. There were no significant changes in FEV1 in either group during the study. When BDP was changed to theophylline there was a deterioration in BHR. Aerosol steroids, rather than theophylline, are the treatment of choice when reduction in the severity of BHR is the aim of treatment in patients with severe asthma.     

Probability and determinants of relapse after discontinuation of inhaled corticosteroids in patients with COPD treated in general practice.

OBJECTIVE: The objective of the study was to assess the probability, and explore determinants of adverse respiratory outcome after discontinuation of inhaled corticosteroid (ICS) treatment in subjects with chronic obstructive pulmonary disease (COPD) diagnosed and treated in general practice. DESIGN: Prospective unblinded ICS withdrawal study. SUBJECTS: 201 ICS treated COPD patients with various degrees of airflow limitation from 45 Dutch general practices. MAIN OUTCOME MEASURES: Probability of and time to exacerbation or unremitting worsening of respiratory symptoms after ICS discontinuation. RESULTS: Mean age was 60.6 (S.D. 9.5) years, post-bronchodilator forced expiratory volume in 1s (FEV1) 65.6 (S.D. 15.7) % predicted. Overall probability of adverse respiratory outcome after ICS discontinuation was 0.37 (95% confidence interval (CI) 0.31, 0.44). Survival analysis showed that age, gender, smoking status and reversibility of airflow limitation were independent predictors of adverse respiratory outcome. For females, the adjusted hazard ratio was 2.14 (95% CI 1.31, 3.50) compared to males. For age, the hazard ratio was 1.05 (95% CI 1.02, 1.08) per year lived. CONCLUSION: Discontinuation of inhaled corticosteroids may harm patients with COPD. The probability of an adverse respiratory outcome may be higher in women, elderly patients, smokers and patients with higher bronchodilator reversibility while on inhaled steroid treatment.     

A comparative study of the effects of ketotifen, disodium cromoglycate, and beclomethasone dipropionate on bronchial mucosa and asthma symptoms in patients with atopic asthma

Asthma is a chronic inflammatory disorder of the airways that is characterized by infiltration of many inflammatory cells into the bronchial mucosa. We compared the effects of ketotifen, disodium cromoglycate (DSCG), and beclomethasone dipropionate (BDP) on inflammatory cells in the bronchial mucosa and on the asthma symptoms of patients with atopic asthma. In this 12-week parallel study, 32 patients were randomly allocated to either the ketotifen group (2 mg day-1, n = 13), DSCG group (8 mg day-1, n = 9) or BDP (400 micrograms day-1, n = 10). Each subject recorded daily asthma symptoms and peak expiratory flow (PEF). Before and after treatment, pulmonary function and bronchial responsiveness to methacholine were evaluated, and fibreoptic bronchoscopy and biopsy were performed before and after treatment. Biopsy specimens were obtained by bronchoscopy. We performed immunohistochemistry using specific monoclonal antibodies for activated eosinophils (EG2), mast cells (AA1), and T cells (CD3, CD4, and CD8). Our clinical findings showed significant improvement in symptom score and bronchial responsiveness (P < 0.01) each) in all groups. Both the DSCG and the BDP groups had significantly better symptom scores than the ketotifen group (P < 0.05, both groups). PEF significantly increased in the DSCG group in comparison to the ketotifen (P < 0.01) and BDP (P < 0.05) groups, FEV1% increased significantly in the DSCG (P < 0.01) and BDP (P < 0.05) groups in comparison to the ketotifen group. Compared with their baseline values, treatment significantly decreased EG2+ activated eosinophils, and CD3+ and CD4+ T cells, in each group (P < 0.01). Both the DSCG (P < 0.05) and the BDP groups (P < 0.01) exhibited significant decreases in AA1+ mast cell count, but this was not observed in the ketotifen group. Comparing before- and after-treatment values, only the DSCG group exhibited a significant decrease in the number of CD8+ T cells (P < 0.01). Ketotifen, DSCG, and BDP all showed anti-inflammatory activity as determined by examination of the bronchial mucosa of asthmatic patients; and both the DSCG and BDP groups had better clinical responses than the ketotifen group.     

Reversibility to a beta2-agonist in COPD: relationship to atopy and neutrophil activation

Chronic obstructive pulmonary disease (COPD) is characterised by limited bronchial reversibility and chronic neutrophilic inflammation. However, in some cases of COPD, eosinophilic inflammation is present. We investigated the relationship between reversibility to beta2-agonist with atopy and neutrophil activation in patients with stable COPD. For this purpose, 38 outpatients with COPD (mean age: 64 years) 12 with asthma (mean age: 51 years) and 13 healthy controls (mean age: 49 years) were tested using increasing doses of inhaled salbutamol (up to 3100 microg). According to their reversibility, COPD patients were divided into two groups: reversible COPD (deltaFEV1 > or = 12% pred, n = 16) and non-reversible COPD (deltaFEV1 < 12% pred, n = 22). Atopy, assessed by skin prick, was found at similar frequencies in both COPD groups. Total serum IgE was higher in COPD patients vs. controls, but did not differ significantly between the COPD groups. The blood eosinophil count was significantly higher in the reversible COPD group than in the non-reversible COPD, and correlated with deltaFEV % pred (Rs = 0.54, P < 0.05), as well as in asthmatics. The non-reversible COPD group had a higher level of spontaneous neutrophil activation (by reduction of nitroblue tetrazolium) versus controls. We conclude that airway reversibility in COPD patients is associated with the degree of blood eosinophilia, but not with the degree of blood neutrophil activation.     

Inhaled beclomethasone improves the course of asthma and COPD.

The effects of inhaled beclomethasone dipropionate (BDP), 800 micrograms daily, on the long-term course of asthma and chronic obstructive pulmonary disease (COPD) were investigated in a prospective, controlled study, over three years. During the first two years, patients were treated with a bronchodilator only (salbutamol or ipratropium bromide). Fifty six patients (28 asthma, 28 COPD), with an unfavourable course of disease during bronchodilator therapy alone (an annual decline in forced expiratory volume in one second (FEV1) of > or = 80 ml.yr-1 in combination with at least one exacerbation.yr-1), were selected for additional treatment with inhaled beclomethasone dipropionate (BDP), 800 micrograms daily, during the third year. The FEV1 and provoking concentration of histamine producing a 20% fall in FEV1 (PC20-histamine) were assessed at six-monthly intervals. In asthma, the annual decline in prebronchodilator FEV1 of -158 ml.yr-1 during bronchodilator therapy alone was followed by a significant increase of 562 ml.yr-1 during months 1-6 of BDP treatment (p < 0.0005). During months 7-12 of BDP, the FEV1 declined slightly with -31 ml.yr-1, which was not statistically different from the annual decline before steroid therapy (p = 0.17). In COPD, the increase of 323 ml.yr-1 during months 1-6 of treatment with BDP was different from the annual decline of -156 ml.yr-1 before BDP (p < 0.05). The PC20-histamine improved by 308 doubling doses during 1-12 months of BDP in asthma (p < 0.05) but not in COPD.(ABSTRACT TRUNCATED AT 250 WORDS)     

Immunohistochemical analysis of bronchial mucosa in severe asthmatics treated with long-term, high-dose inhaled BDP]

To analyze specific mucosal changes in asthmatic patients receiving long-term, high-dose beclomethazone dipropionate (BDP) inhalation therapy, we performed bronchial mucosal biopsies and immunohistochemical analysis of patients who had been treated with or without BDP-inhalation. Our study enrolled 6 chronic severe asthmatics who were treated with 1,800 micrograms/day or more of BDP with regular use for more than 3 years (HD-BDP group), 6 mild asthmatics who were not treated with BDP (non-BDP group), and 6 control subjects. Specimens of bronchial mucosa were stained with anti-EG 2 (eosinophils), anti-UCHLA-1 (T lymphocytes) and anti-tryptase (mast cells). Although limited eosinophil infiltration was observed in the HD-BDP and control groups, a significant increase was noted in the non-BDP group. The infiltration of both T lymphocytes and mast cells exhibited a statistically significant increase in the non-BDP group compared to the HD-BDP and control groups. In chronic severe asthmatics, airway mucosal cell infiltration was reduced by high-dose and long-term inhaled BDP therapy, and BDP also relieved their asthmatic symptoms. However, in mild asthmatics, bronchial mucosal cell infiltration remained high. For such patients, we concluded that initiating BDP therapy from an early stage may bring clinical improvement and help prevent cell infiltration.     

An observational study of inhaled corticosteroid withdrawal in stable chronic obstructive pulmonary disease. ISOLDE Study Group.

Withdrawal of inhaled corticosteroids is known to worsen disease control in bronchial asthma but similar data are lacking in chronic obstructive pulmonary disease (COPD). We hypothesized that clinical exacerbations requiring treatment would occur more often in patients whose inhaled corticosteroids were stopped than in other patients not treated with these agents. We studied 272 patients in mean age 65 (SD 0.8) years, mean FEV1 42.8 (SD 12.6)% predicted, entering the run-in phase of the Inhaled Steroids in Obstructive Lung Disease (ISOLDE) trial. All had been clinically stable for at least 6 weeks and there were no differences in the degree of bronchodilator reversibility, baseline lung function or pack-years of smoking between the 160 patients receiving inhaled corticosteroids and those not so treated. Inhaled corticosteroids were withdrawn in the first week of the study and during the remaining 7 weeks of the study 38% of those previously treated with these drugs had an exacerbation compared to 6% of the chronically untreated group. Patients receiving inhaled corticosteroids reported a longer duration of symptoms but neither this or any other recorded variable predicted the risk of exacerbation. These data suggest that abrupt withdrawal of inhaled corticosteroids should be monitored carefully even in patients with apparently irreversible COPD.     

小剂量皮质类固醇吸入合并小剂量茶碱口服对支气管哮喘 …

目的 研究小剂量茶碱合并小剂量皮质类固醇对哮喘患者的疗产及对下丘脑－垂体－肾上腺轴的影响。方法 ４３例以轻、中度的哮喘患者随机分成两组。茶碱激素组（Ａ）组２１例：给予无水缓释放茶口服,每晚２００ｍｇ,加二丙酸倍氯米松（ＢＤＰ）每天３００μｇ吸入;单纯激素组（Ｂ）组２２例：仅给予ＢＤＰ每天６００μｇ吸入及每晚口服安慰剂,疗程１３周。结果 治疗前、后的症状计分、呼气峰流速值（ＰＥＦ）及其变异率（ＰＥＦ     

A clinical study of serum IgE concentrations in elderly patients with bronchial asthma and chronic obstructive pulmonary disease]

We tested the hypothesis that serum IgE concentrations may be influenced by the severity of respiratory symptoms, impairment of pulmonary functions, and smoking history in elderly patients with bronchial asthma and/or chronic obstructive pulmonary disease (COPD). A total of 325 elderly outpatients aged over 65 years were enrolled in the study: 112 (22 men, 90 women) with bronchial asthma (BA), 135 (118 men, 17 women) with COPD, and 78 (56 men, 22 women) with both COPD and asthma (COPD/BA). The mean ages for the 3 groups were 74.3,76.0 and 76.6 years, respectively; the age differential was not significant. As a group, the male subjects displayed higher serum IgE concentrations than the female subjects. Also, ex-smokers and current smokers showed higher serum IgE concentrations than patients who had never smoked, and patients in the BA group had higher serum IgE concentrations than those in the COPD or COPD/BA groups. Although serum IgE concentrations were increased in BA patients with decreased FEV1.0 levels, the reverse was observed in the COPD patients. Peripheral blood eosinophil counts for men and women were higher in the BA group than in the COPD group. A positive correlation between serum IgE concentration and eosinophil count was observed in the BA group. Although bronchial asthma and COPD in the elderly have been considered to be pathologically similar, the findings of our study suggested they are probably different in terms of serum IgE concentration, pulmonary function, and smoking history.     

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.     

用力吸气流量在COPD和支气管哮喘中的应用

目的 评价用力吸气流量指标在慢性阻塞性肺疾病(COPD)和支气管哮喘中价值。方法 观察COPD80例和支气管哮喘20例在吸入支气管扩张剂后用力吸气流量指标的前后变化。结果 轻度COPD患者和支气管哮喘患者FEV1,FIV1，PEF，PIF，FEF50％，FIF50%指标，在吸入支气管扩张剂前后均有明显的差异。但用力吸气流量指标与用力呼气流量指标在统计学无差别。而中、重度COPD患者FIV1％较FEV1％有显著差异性。结论 在COPD中，在评价支气管的可逆性方面，用力吸气流量具有用力呼气流量同样的效果。甚至在重度COPD患者中．FIV1%比用力呼气流量可能更加敏感。     

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.     

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.     

福多司坦联合小剂量吸入性激素治疗支气管哮喘的临床研究

目的观察福多司坦联合小剂量吸入性糖皮质激素治疗轻中度哮喘的临床效果。方法将40例哮喘患者随机分为两组,实验组给与福多司坦联合小剂量二丙酸倍氯米松气雾剂,对照组给予大剂量二丙酸倍氯米松气雾剂。治疗前后评价PEFRv、FEVl%及不良反应。同时检测治疗前后诱导痰上清中IL-8含量的变化。结果福多司坦联合小剂量吸入性激素治疗轻、中度哮喘可显著降低PEFRv及提高FEVl%(P<0.05),两组间PEFRv改善百分比和FEVl%改善百分比均无明显统计学差异(P>0.05)。两组均可明显降低哮喘患者的诱导痰上清中IL-8的水平。结论小剂量吸入性激素联合福多司坦和大剂量吸入性激素对治疗轻中度哮喘的疗效相当。