Intravenous aminophylline in the treatment of acute bronchospastic exacerbations of chronic obstructive pulmonary disease

Often chronic obstructive pulmonary disease (COPD) patients treated for acute exacerbations receive intravenous (IV) aminophylline in addition to inhaled bronchodilators that may raise serum levels of theophylline into the toxic range. A double-blind, randomized study of 52 men with COPD who came to the emergency department for treatment of exacerbations was initiated to establish the efficacy and safety of this common practice. After history and physical examination, patients were treated with 28% oxygen by Venturi mask and 0.3 cc metaproterenol sulfate in 2.5 cc saline by nebulizer; an IV line was started and patients received either aminophylline or D5W. Measurements included baseline and two-hour serum theophylline levels, pulmonary function tests, and symptom questionnaires. Mean values from the entire group showed decreases in respiratory rate, cardiac rate, and pulsus paradoxus, and increases in forced expiratory volume in one second (FEV1) and vital capacity (VC) over a two-hour treatment period (P less than .01). Despite the increase in serum theophylline in the treatment group, the demographic, clinical, pulmonary function, and outcome data were found to have no statistically significant differences when compared to control patients. The data were then analyzed according to serum theophylline levels. Theophylline level greater than 20 micrograms/mL occurred in 15 patients with no untoward effects; premature ventricular contractions (PVCs) were no more frequent in this group than in those with lower serum theophylline levels. A theophylline level greater than 10 micrograms/mL after two hours of treatment resulted in the following differences, which were not statistically significant: mean FEV1 response less than or equal to 10 micrograms/mL vs greater than 10 micrograms/mL, 20% vs 28%; mean VC change, 17% vs 30%; or mean emergency department returns in one week, 0.1 vs 0.26. In our experience, oxygen and inhaled metaproterenol are effective treatment for exacerbations of COPD.     

The effect of inhaled salmeterol, alone and in combination with fluticasone propionate, on management of COPD patients

Introduction: Airway inflammation is a known pathological feature of chronic obstructive pulmonary disease (COPD). We examined the effect of inhaled salmeterol, alone and in combination with fluticasone propionate, on the management of patients with COPD. Methods: Forty male COPD patients were randomly divided into two groups; group 1 (n = 20) were treated with long‐acting ß2‐agonist, and group 2 (n = 20) with long‐acting ß2‐agonist and inhaled glucocoticoid each day for 3 months. Pulmonary function tests (PFTs), including forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1) and peak expiratory flow (PEF), were measured at the beginning, 1 and 2 months after treatment and at the end of the study. The frequency of using inhaled salbutamol/day and the 6‐min walk distance were also measured at four different visits. The frequency of exacerbation was also recorded during the 90‐day treatment period in the two groups. Results: FEV₁, FVC and PEF were significantly higher after 30 days of treatment with fluticasone propionate (mean change from baseline in group 2: 155 mL, 200 mL and 70 L/s, respectively; P < 0.001). Six‐minute walk distance also increased significantly (mean change from baseline: 160 m; P < 0.001), and there was a 70%–80% reduction in the use of inhaled salbutamol (P < 0.001). All improvements were maintained over the remainder of the study period. Exacerbations over the 90‐day treatment period were significantly fewer than in the same 90‐day period in the previous year (2.8 ± 0.7 vs 0.8 ± 0.9; P < 0.001). In contrast, only PEF increased significantly with treatment in group 1 (salmeterol treatment alone). Conclusions: These results indicated that inhaled corticosteroids may be beneficial in some patients with COPD. Please cite this paper as: Mansori F, Nemat Khorasani A, Boskabady MH and Boskabady M. The effect of inhaled salmeterol, alone and in combination with fluticasone propionate, on management of COPD patients. Clin Respir J 2010; 4: 241–247.     

慢性阻塞性肺疾病患者同型半胱氨酸水平变化及意义探讨

目的 探讨慢性阻塞性肺疾病(COPD)患者不同病期血浆同型半胱氨酸、血浆谷胱甘肽(GSH)水平的变化,以了解同型半胱氨酸在COPD患者发生、发展过程中的作用及其临床意义.方法 2006年1月至2008年6月收集46例COPD急性发作期患者(COPD急性发作期组)、45例COPD缓解期患者(COPD缓解期组)及38例健康受试者(健康对照组).测定各组的多项指标:吸烟指数、体质量指数、血浆同型半胱氨酸、血浆GSH、肺功能和动脉血气.结果 ①COPD急性发作期组血浆同型半胱氨酸高于健康对照组和COPD缓解期组,(31.93±26.19) μmol/L vs (10.79±2.32) μmol/L,(21.98±9.13) μmol/L,三组比较差异有统计学意义(F=13.08,P＜0.01).②COPD缓解期组血浆GSH明显低于健康对照组和COPD急性发作期组,(71.72±76.36) mg/L vs (166.38±63.51) mg/L,(145.18±80.41) mg/L,三组比较差异有统计学意义(F=19.11,P＜0.01).③COPD患者不论急性发作期,还是缓解期,血浆同型半胱氨酸与GSH均呈明显负相关(COPD急性发作期:r=0.579,P＜0.01;COPD缓解期:r=-0.721,P＜0.01);COPD急性发作期血浆GSH与第一秒用力呼气容积/用力肺活量呈正相关(r=0.488,P＜0.05).结论 COPD患者存在高同型半胱氨酸血症,血浆同型半胱氨酸参与COPD的氧化应激.     

Factor V leiden homozygosity, dyspnea, and reduced pulmonary function

BACKGROUND: Factor V Leiden homozygosity predisposes patients to deep venous thrombosis and major pulmonary thromboembolism. Consequently, factor V Leiden homozygosity could, via unrecognized repeated minor pulmonary thromboemboli, cause chronic pulmonary disease. We tested the hypothesis that factor V Leiden homozygosity is associated with pulmonary symptoms and signs. METHODS: We studied a general population sample of 9253 individuals from the Copenhagen City Heart Study who were examined in 1991-1994. Of these, 6475 participants were also examined in 1976-1978 and/or 1981-1983. End points were dyspnea and lung function. RESULTS: Among 20 factor V Leiden homozygotes, a mean +/- SD of 32% +/- 11% had severe dyspnea compared with 6% +/- 0.3% of 8534 noncarriers (chi(2) test; P<.001). The corresponding adjusted odds ratio for severe dyspnea was 5.4 (95% confidence interval, 1.9-15.7). During follow-up, forced expiratory volume in 1 second and forced vital capacity were 5% to 10% lower in homozygotes vs noncarriers (analysis of variance; P = .003 and P = .03). The annual mean +/- SD loss of forced expiratory volume in 1 second and forced vital capacity was 39 +/- 8 mL/y and 35 +/- 8 mL/y in homozygotes vs 21 +/- 10 mL/y and 15 +/- 10 mL/y in noncarriers (t test; P = .03 and P = .04), respectively. Factor V Leiden heterozygosity (n = 699) did not influence pulmonary symptoms and signs. CONCLUSION: We demonstrate a previously unrecognized clinical presentation of factor V Leiden homozygosity with severe dyspnea and decreased pulmonary function.     

Improvements with tiotropium in COPD patients with concomitant asthma

BACKGROUND: Chronic obstructive pulmonary disease (COPD) and asthma have different diagnostic criteria and treatment paradigms. Both are common and can occur in the same patient. We sought to determine the spirometric effects of tiotropium in COPD patients with concomitant asthma. METHODS: A 12-week randomized, double-blind, placebo-controlled, parallel group trial with tiotropium 18 mcg daily was performed. Patients continued usual respiratory medications except for inhaled anticholinergics. Inclusion criteria: Physician diagnosis of COPD and asthma, age >or= 40 years, smoking >10 pack years, post-bronchodilator forced expiratory volume in 1s (FEV(1))<80% predicted, FEV(1)/forced vital capacity (FVC)<70%, >or= 12%, and >or= 200 ml increase in FEV(1) following inhaled bronchodilator, treatment with inhaled steroids >or= 1 year. Spirometry was measured serially for 6h on days 1, 29 and 85. RESULTS: Four hundred and seventy-two patients were randomized. Baseline characteristics were balanced. Mean age=59.6 years, 61.4% were men, and FEV(1)=1.55l (53.0% predicted). Improvements at 12 weeks with tiotropium were observed for the primary endpoint FEV(1) area under the curve (AUC) from 0 to 6h (difference=186+/-24 ml, p<0.001) and for morning pre-dose FEV(1) (difference=98+/-23 ml, p<0.001). Significant differences in favor of tiotropium were observed for pre-dose FVC (difference=128+/-34 ml, p<0.001) and FVC AUC 0-6h (difference=232+/-35 ml, p<0.001). Compared to baseline, the mean weekly number of daily puffs of prn salbutamol was reduced by 0.05+/-0.12 puffs/day in the placebo group and by 0.50+/-0.12 puffs/day in the tiotropium group at week 12 (p<0.05). CONCLUSIONS: Patients with COPD and concomitant asthma achieve spirometric improvements with tiotropium along with symptomatic benefit as seen by reduced need for rescue medication.     

CF: an X-ray database to assess effect of aerosolized tobramycin

This paper assesses the effectiveness of aerosolized tobramycin (TOBI) on cystic fibrosis (CF) lung disease, using a radiologic tool. The published tool, the age-based severity curve (ABS), is derived from Brasfield scoring of chest X-rays (CXR). This study evaluates both the usefulness of the ABS as an assessment tool and the effectiveness of TOBI. Thirty-eight patients were treated with TOBI. Twenty-four treated with dornase alfa were excluded. Fourteen patients, aged 2 months to 22 years (mean, 17 months of TOBI treatment), comprised the study group. Radiographs were obtained over a mean of 7.8 years (SD = 6.5 years; range, 9 months-18 years). Two hundred and eighty-two CXR of TOBI patients were analyzed following the ABS protocol. Rate of decline in radiologic status of the TOBI group and ABS were compared. Also, TOBI was assessed by comparing rate of decline before and after initiation of treatment. The TOBI group's radiologic assessment was compared to its rate of decline in pulmonary function studies and published population data. Rate of decline in ABS was 0.175 Brasfield points/year vs. 0.150 points/year in the TOBI group (P < 0.001). Before treatment, the TOBI group's rate of decline was 0.169 Brasfield points/year; after treatment, it was 0.150 points/year (P = 0.02). Forced vital capacity revealed a statistically significant slowing in rate of decline on TOBI. Although not statistically significant, rate of decline in forced expiratory volume at 1 sec showed a similar trend. The degree of slowing in decline is similar to that previously reported for pulmonary function studies.     

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。     

Theophylline and salbutamol improve pulmonary function in patients with irreversible chronic obstructive pulmonary disease.

To investigate the efficacy of bronchodilators in patients with irreversible chronic obstructive pulmonary disease (COPD), we conducted a double-blind, randomized, four-phase, crossover comparison between placebo, oral theophylline, inhaled salbutamol, and a combination of both drugs in 12 patients with stable COPD (mean age, 63 years) whose increase in forced expiratory volume in 1 s (FEV1) was less than or equal to 15 percent following 200 micrograms of inhaled salbutamol. Patients received two weeks of therapy with each of the test regimens. Both theophylline and salbutamol resulted in statistically significant improvement in FEV1, forced vital capacity (FVC), slow vital capacity (SVC), residual volume (RV), airway resistance (Raw), and maximum expiratory flow rate at 50 percent of vital capacity (V50). In most instances, there were no significant differences between theophylline and salbutamol. Combination therapy produced significantly greater improvement in FEV1, FVC, V50, Raw, and RV than either agent alone. The two drugs interacted in an additive fashion. Neither of the drugs, used singly, significantly reduced the severity or incidence of symptoms. The reduction in dyspnea and wheeze during combination therapy approached statistical significance (p = 0.06) and patient preference was significantly in favor of the combination regimen. None of the active treatments produced significantly more side effects than placebo. We conclude that theophylline and inhaled salbutamol produce significant, and approximately equal, improvement in pulmonary function in patients traditionally classified as suffering from "irreversible" COPD. The combination of theophylline and inhaled salbutamol generally results in additional improvement over that obtained with either drug used alone and this improvement is reflected by reduced symptomatology and treatment preference.     

Induced tolerance to nebulized colistin after severe reaction to the drug.

Daily nebulized colistin therapy has been used as maintenance therapy for patients with chronic Pseudomonas aeruginosa infection and in treatment protocols aimed at eradicating early P aeruginosa infection. Colistin-induced nephrotoxicity and mild neurotoxic effects have been described but hypersensitivity reactions are rare. However, bronchial constriction has been reported associated with the inhalation of the antibiotic. We report the case of a 63-year-old man who had been diagnosed with bronchiectasis and bronchopleural fistula and who developed severe bronchospasm when using nebulized colistin. A skin prick test (80 mg/mL) with colistin was performed and was negative. An intradermal test was not performed due to its possible irritant effect. As our patient suffered from a tobramycin-resistant P aeruginosa infection, we started a procedure to induce tolerance to 80 mg colistin (8 mg, 16 mg, 24 mg, 32 mg, 40 mg, 80 mg) nebulized in 30-minutes-intervals. No changes in forced expiratory volume in 1 second values were observed and the patient continues on treatment twice daily after the tolerance induction with no new episodes of bronchospasm.We report the first successful procedure to induce tolerance to colistin after escalating doses of inhaled colistin.     

慢性阻塞性肺疾病患者3年健康相关生活质量的变化及危险因素的分析

目的 探讨生活中COPD患者3年健康相关生活质量(health-related quality of life,HRQoL)的变化规律及影响生活质量变化的可能危险因素.方法 基于慢性呼吸病管理中心数据库3年的COPD患者临床资料,采用回顾性研究,利用圣乔治呼吸问卷(Saint George's Respiratory Questionnaire,SGRQ)评估HRQoL,分析SGRQ随时间变化规律;根据SGRQ 3年变化值进行分组,利用Logistic回归探寻影响HRQoL变化的危险因素.结果 60例COPD患者中63.3％～83.3％的患者经吸入激素联合长效支气管舒剂治疗后,SGRQ总分及各部分评分与基线值比较无明显上升(t值分别为:0.147、-0.014、0.335、0.227,P值均＞0.05),FEV1、FEV1％pred、6分钟步行距离较基线值下降(t值分别为:3.943、6.974、3.977,P值均＜0.05),BODE指数较基线值上升(t=-9.916,P＜0.05);其中生活质量相对稳定者36例(60％),多因素Logistic回归提示BODE指数升高是HRQoL下降的独立危险因素(OR =1.686,P=0.017),重度急性加重次数对其下降亦有影响(OR=3.316,P=0.052).结论 生活中大部分COPD患者经吸入激素联合长效支气管舒张剂治疗后生活质量相对稳定,除药物影响外,BODE指数升高是生活质量下降的独立危险因素,重度急性加重次数可能也对健康相关生活质量的变化具有预测价值.     

Inhaled steroids in patients with bronchiectasis.

The effect of inhaled beclomethasone diproprionate (1500 micrograms day-1) on symptoms, pulmonary function and sputum production was examined in a double-blind, placebo-controlled, cross-over study in 20 patients with bronchiectasis. An 18% reduction in daily sputum production (P less than 0.003) was observed on treatment with inhaled steroid compared to placebo. A small, significant, improvement in morning peak expiratory flow rate (P less than 0.03) and forced expiratory volume in 1 s (P less than 0.03) was seen but the absolute changes are unlikely to be of clinical importance. Symptom scores for cough improved significantly (P less than 0.02). Inhaled steroids may have a role in the management of bronchiectasis by reducing cough and sputum production.     

Effect of temperature on lung function and symptoms in chronic obstructive pulmonary disease.

The present study investigated whether falls in environmental temperature increase morbidity from chronic obstructive pulmonary disease (COPD). Daily lung function and symptom data were collected over 12 months from 76 COPD patients living in East London and related to outdoor and bedroom temperature. Questionnaires were administered which asked primarily about the nature of night-time heating. A fall in outdoor or bedroom temperature was associated with increased frequency of exacerbation, and decline in lung function, irrespective of whether periods of exacerbation were excluded. Forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) fell markedly by a median of 45 mL (95% percentile range: -113-229 mL) and 74 mL (-454-991 mL), respectively, between the warmest and coolest week of the study. The questionnaire revealed that 10% had bedrooms <13 degrees C for 25% of the year, possibly because only 21% heated their bedrooms and 48% kept their windows open in November. Temperature-related reduction in lung function, and increase in exacerbations may contribute to the high level of cold-related morbidity from chronic obstructive pulmonary disease.     

The effect of Pseudomonas aeruginosa on pulmonary function in patients with bronchiectasis.

Bronchiectasis patients are susceptible to infection with Pseudomonas aeruginosa. Isolation is associated with increased severity of disease, greater airflow obstruction and poorer quality of life. It is not known whether infection by P. aeruginosa is a marker of disease severity or contributes to disease progression. Consecutive non-cystic fibrosis adult bronchiectasis outpatients (n = 163) with multiple sputum cultures and follow-up pulmonary function tests were designated, according to isolation of P. aeruginosa, as "never infected" (group 1; n = 67), "intermittently isolated" (group 2; n = 82) and "chronically infected" (group 3; n = 14). Based upon change in forced expiratory volume in one second (FEV(1)) % predicted levels at >or=2 yrs after presentation, longitudinal behaviour was characterised as "improvement" (>or=10% rise), "decline" (>or=10% fall) or "stability". Baseline pulmonary-function tests and longitudinal behaviour were examined in relation to pseudomonas status. There was no difference between the groups in age, sex, smoking habit or length of follow-up. Baseline FEV(1) levels were highest in group 1 (mean+/-sd: 77.4+/-24.3) and higher in group 2 (67.3+/-25.7) than in group 3 (55.2+/-18.5). The same significant trends were seen for baseline FEV(1)/forced vital capacity ratios and diffusing capacity of the lung for carbon monoxide levels. Subsequent longitudinal behaviour was linked to baseline FEV(1) levels, which were lowest in patients with improvement and lower in association with decline than with stability. However, longitudinal behaviour did not differ between groups 1, 2 and 3, either before or after adjustment for baseline FEV(1) levels. Infection by Pseudomonas aeruginosa occurs in bronchiectasis patients with more severe impairment of pulmonary function but does not influence rate of decline in pulmonary function either before or after adjustment for baseline disease severity. Thus, Pseudomonas aeruginosa is a marker of bronchiectasis severity but is not linked to an accelerated decline in pulmonary function.     

The bronchodilator test with increasing doses of terbutaline in chronic obstructive pulmonary disease patients

There is no uniform consensus on the dose of bronchodilator to be used in the bronchodilator test (BDT). The objective of the study was to determine the dose of inhaled terbutaline that can safely achieve a greater number of positive BDT in patients with chronic obstructive pulmonary disease (COPD). The study was prospective and single blinded. One-hundred and fifty patients with stable COPD were included. Their mean (+/-SD) age was 67.4 (8.8) years. Their mean forced expiratory volume in the first second (FEV1) was 1.14 (0.48) l (41% of the predicted value). A baseline spirometry was performed and a second 20 min after the inhalation of placebo. Three consecutive doses of 500 microg of inhaled terbutaline were administered and a new spirometry was performed after each one. A multivariate analysis based on the comparison of the repeated means was performed in order to analyse the spirometric changes achieved after the different doses of bronchodilator. The increase of FEV1 and forced vital capacity (FVC) with the two first doses of terbutaline was statistically significant; the increase of the peak expiratory flow (PEF) was significant after the three doses administered. The number of positive BDT were 40, 47 and 60 after each dose of terbutaline (P=0.004). The higher dose of terbutaline was more useful in identifying patients with significant bronchoreversibility and, moreover, was well tolerated. We suggest that this dose (1500 microg) should be routinely used in performing the BDT.     

Racial and gender differences in susceptibility to tobacco smoke among patients with chronic obstructive pulmonary disease

BACKGROUND: Although chronic obstructive pulmonary disease (COPD) has been considered a disease of Caucasian men, recent data show mortality rising faster among women and African-Americans. Some have suggested these groups are more susceptible to tobacco smoke. We examined this issue in our own population of COPD patients. METHODS: Beginning in March 2003 we prospectively developed a COPD research database to facilitate recruitment for clinical trials. Enrollees are recruited from clinics and paid advertising and their demographics, medical/smoking histories, and spirometric data are recorded. We examined the smoking histories and pulmonary function of enrollees over 45, with 20 pack-years of smoking, FEV(1)/FVC (forced expiratory volume forced vital capacity) <0.70, and a race-adjusted post-bronchodilator FEV(1)<80%. The primary outcome was the loss of lung function per pack-year smoked, or Susceptibility Index (SI), calculated using the formula: (% predicted FEV(1)-100)/pack-years. RESULTS: A total of 585 patients enrolled during the study period and 330 met our inclusion criteria. Caucasians were older than African-Americans (63 vs. 58, P=0.0003) and had more pack-years of smoking (57 vs. 43, P=0.0003). There were no differences in lung function or bronchodilator reversibility among the racial or gender subgroups. Caucasians had less loss of lung function per pack-year smoked than African-Americans (SI=-1.02% vs. -1.34%, P=0.007) and men less than women (SI=-0.98% vs. -1.21%, P=0.001). Caucasian males appeared relatively protected from tobacco smoke (SI=-0.93%), while African-American women appeared most susceptible (SI=-1.42%). CONCLUSIONS: There are important differences in racial and gender susceptibility to tobacco smoke among patients with COPD. African-American females appear to be at highest risk and may benefit most from smoking cessation.     

Pulmonary function tests, high-resolution computerized tomography, α1-antitrypsin measurement, and early detection of pulmonary involvement in patients with systemic sclerosis

OBJECTIVE: Pulmonary disease represents a major complication of systemic sclerosis (SSc). However, pulmonary involvement is commonly silent. In this study, we investigated the relationship between serum alpha1-antitrypsin and other means of assessing pulmonary involvement. METHODS: Twenty-two patients affected by SSc were studied (mean age 37.6+/-14.3 years, mean duration of disease 9.9+/-11.9 years). Fourteen had the diffuse form of disease (dSSc) and eight had the limited form (lSSc). All patients underwent pulmonary function tests, high-resolution computed tomography (HRCT) of the lungs, echocardiography, and serum assessment of alpha1-antitrypsin. RESULTS: Mean percentage of predicted values of forced vital capacity was lower in patients with dSSc than with lSSc (72.3+/-17.8 vs 74.5+/-8, P=NS). Mean percentage of predicted values of forced expiratory volume in 1-s forced vital capacity (FEV1/FVC) was lower in patients with lSSc (79.8+/-7.5 for lSSc vs 84.4+/-7.8 for dSSc, P= NS). The overall HRCT score was 5.6+/-5.9 with no significant difference between disease subgroups. Pulmonary hypertension was detected in two cases, both with dSSc. Alpha1-antitrypsin was significantly higher in patients than in controls (P < 0.01), with no significant difference between disease subgroups, and correlated significantly with ground glass opacities in H RCT (P < 0.05) and the detection of diffusion defects (r= -0.61, P<0.01). No significant correlation was observed between skin score or degree of dyspnea with HRCT score, lung volume, or carbon monoxide diffusing capacity. CONCLUSION: Restrictive lung disease was more pronounced in patients with dSSc. Alpha1-antitrypsin levels correlated significantly with ground glass opacities, an early finding of pulmonary involvement in SSc. Extent and severity of skin involvement and degree of dyspnea were not related to pulmonary involvement.     

The functional impact of an individualized, graded, outpatient pulmonary rehabilitation in end-stage chronic obstructive pulmonary disease

OBJECTIVE: To evaluate the functional impact of an individualized outpatient pulmonary rehabilitation program in end-stage chronic obstructive pulmonary disease (COPD). METHODS: Patients with end-stage COPD were admitted into a 6-week comprehensive outpatient pulmonary rehabilitation program that was "packaged" for each patient. We compared spirometric parameters, exercise tolerance, level of breathlessness, and intensity of work before and after rehabilitation. RESULTS: Of 45 eligible patients, only 14 consented to participate in the study. All 14 patients had forced expiratory volume in 1 second <35% of predicted, and 10 patients (72%) had a 6-minute walk test <180 m. The level of breathlessness was between 7 (moderate to severely breathless) and 10 (maximally breathless) on the Visual Analogue Scale in all patients. After the program, there was significant improvement in the FEV 1 P = 0.04), forced vital capacity P = 0.0045), 6-minute walk test P = 0.00047), and shuttle-walk test (9 of 14 patients). All patients had some improvement in level of dyspnea. CONCLUSIONS: Individualized outpatient pulmonary rehabilitation in end-stage COPD can produce a measurable improvement in spirometry and exercise tolerance with a favorable impact on the level of physical activity.     

血浆解聚素-金属蛋白酶 8可辅助诊断老年慢性阻塞性肺疾病患者的病情严重程度

目的：探讨血浆解聚素-金属蛋白酶8(ADAM8)水平在老年慢性阻塞性肺疾病(COPD) 急性加重期（AECOPD）诊断和病情评估中的价值。方法：收集229例老年COPD患者的临床资料，其中稳定期记为COPD组(98例)，急性加重期记为AECOPD组(131例)，参照2019年修订的《慢性阻塞性肺疾病全球创议》指南，根据患者病情的综合评估情况分为A、B、C、D组。同时选取无慢性呼吸系统疾病的老年健康体检者40例为对照组。比较各组的基线资料、动脉血气、肺功能指标以及血浆ADAM8水平，分析血浆ADAM8与各指标的相关性以及对COPD急性加重的诊断价值。结果：血浆ADAM8水平在对照组、COPD组、AECOPD组，以及A、B、C、D组中均依次升高，任意2组间比较，差异有统计学意义(P均<0.05)。血浆ADAM8水平与白细胞计数、中性粒细胞与淋巴细胞比值、红细胞分布宽度、纤维蛋白原、D-二聚体以及PaCO2呈显著正相关 (P=0.000)，与嗜酸性粒细胞计数、PaO2、第1秒用力呼气量/用力肺活量(FEV1/FVC)及第1秒用力呼气容积占预计值百分比(FEV1% pred)呈显著负相关(P=0.000)。血浆ADAM8水平诊断AECOPD的最佳临界值为114.47ng/mL，曲线下面积为0.881，敏感度为77.00%，特异性为88.90%，约登指数为0.659，95%置信区间为0.834~0.929。结论：老年COPD 患者血浆中ADAM8水平明显升高，是评估COPD严重程度以及急性加重期的辅助指标。     

Pulmonary permeability in coeliac disease and inflammatory bowel disease

Respiratory disease and subclinical pulmonary abnormalities are recognised complications of both coeliac disease (CD) and inflammatory bowel disease (IBD) but the pathogenesis of the lung disease remains uncertain. We have studied lung function, including permeability measured by clearance of inhaled technetium-99m diethylene triamine pentaacetic acid in 25 patients with IBD, 18 patients with CD on a gluten-free diet, and in 20 normal controls, all without respiratory symptoms. In IBD there was evidence of obstruction to airflow (mean forced expiratory volume in 1 s/forced vital capacity equals 75.8%, control 81%; p less than 0.05) but no change in pulmonary permeability (half-time clearance equals 70.3 vs. 69.2 min). In CD airflow was not significantly different from control (forced expiratory volume in 1 s/forced vital capacity equals 80%) but there was an increase in pulmonary permeability (half-time clearance equals 48.9 min; p less than 0.01). These findings suggest that the mechanisms of lung disease in CD differs from that in IBD and supports the hypothesis of a common mucosal defect in lung and small intestine in CD allowing increased permeability.