Thioredoxin-1 Protects against Neutrophilic Inflammation and Emphysema Progression in a Mouse Model of Chronic Obstructive Pulmonary Disease Exacerbation

Background

Exacerbations of chronic obstructive pulmonary disease (COPD) are characterized by acute enhancement of airway neutrophilic inflammation under oxidative stress and can be involved in emphysema progression. However, pharmacotherapy against the neutrophilic inflammation and emphysema progression associated with exacerbation has not been established. Thioredoxin-1 has anti-oxidative and anti-inflammatory properties and it can ameliorate neutrophilic inflammation through anti-chemotactic effects and prevent cigarette smoke (CS)-induced emphysema. We aimed to determine whether thioredoxin-1 can suppress neutrophilic inflammation and emphysema progression in a mouse model of COPD exacerbation and if so, to reveal the underlying mechanisms.

Results

Mice were exposed to CS and then challenged with polyinosine-polycytidylic acid [poly(I:C)], an agonist for virus-induced innate immunity. Airway neutrophilic inflammation, oxidative stress and lung apoptosis were enhanced in smoke-sensitive C57Bl/6, but not in smoke-resistant NZW mice. Exposure to CS and poly(I:C) challenge accelerated emphysema progression in C57Bl/6 mice. Thioredoxin-1 suppressed neutrophilic inflammation and emphysema progression. Poly(I:C) caused early neutrophilic inflammation through keratinocyte-derived chemokine and granulocyte-macrophage colony-stimulating factor (GM-CSF) release in the lung exposed to CS. Late neutrophilic inflammation was caused by persistent GM-CSF release, which thioredoxin-1 ameliorated. Thioredoxin-1 enhanced pulmonary mRNA expression of MAP kinase phosphatase 1 (MKP-1), and the suppressive effects of thioredoxin-1 on prolonged GM-CSF release and late neutrophilic inflammation disappeared by inhibiting MKP-1.

Conclusion

Using a mouse model of COPD exacerbation, we demonstrated that thioredoxin-1 ameliorated neutrophilic inflammation by suppressing GM-CSF release, which prevented emphysema progression. Our findings deepen understanding of the mechanisms underlying the regulation of neutrophilic inflammation by thioredoxin-1 and indicate that thioredoxin-1 could have potential as a drug to counteract COPD exacerbation.     

Airway Epithelial Expression of TLR5 Is Downregulated in Healthy Smokers and Smokers with Chronic Obstructive Pulmonary Disease

The TLRs are important components of the respiratory epithelium host innate defense, enabling the airway surface to recognize and respond to a variety of insults in inhaled air. On the basis of the knowledge that smokers are more susceptible to pulmonary infection and that the airway epithelium of smokers with chronic obstructive pulmonary disease (COPD) is characterized by bacterial colonization and acute exacerbation of airway infections, we assessed whether smoking alters expression of TLRs in human small airway epithelium, the primary site of smoking-induced disease. Microarrays were used to survey the TLR family gene expression in small airway (10th to 12th order) epithelium from healthy nonsmokers (n = 60), healthy smokers (n = 73), and smokers with COPD (n = 36). Using the criteria of detection call of present (P call) ≥50%, 6 of 10 TLRs (TLRs 1-5 and 8) were expressed. Compared with nonsmokers, the most striking change was for TLR5, which was downregulated in healthy smokers (1.4-fold, p < 10(-10)) and smokers with COPD (1.6-fold, p < 10(-11)). TaqMan RT-PCR confirmed these observations. Bronchial biopsy immunofluorescence studies showed that TLR5 was expressed mainly on the apical side of the epithelium and was decreased in healthy smokers and smokers with COPD. In vitro, the level of TLR5 downstream genes, IL-6 and IL-8, was highly induced by flagellin in TLR5 high-expressing cells compared with TLR5 low-expressing cells. In the context that TLR5 functions to recognize pathogens and activate innate immune responses, the smoking-induced downregulation of TLR5 may contribute to smoking-related susceptibility to airway infection, at least for flagellated bacteria.     

A Combined Pulmonary Function and Emphysema Score Prognostic Index for Staging in Chronic Obstructive Pulmonary Disease

Introduction

Chronic Obstructive Pulmonary Disease (COPD) is characterized by high morbidity and mortality. Lung computed tomography parameters, individually or as part of a composite index, may provide more prognostic information than pulmonary function tests alone.

Aim

To investigate the prognostic value of emphysema score and pulmonary artery measurements compared with lung function parameters in COPD and construct a prognostic index using a contingent staging approach.

Material-Methods

Predictors of mortality were assessed in COPD outpatients whose lung computed tomography, spirometry, lung volumes and gas transfer data were collected prospectively in a clinical database. Univariate and multivariate Cox proportional hazard analysis models with bootstrap techniques were used.

Results

169 patients were included (59.8% male, 61.1 years old; Forced Expiratory Volume in 1 second % predicted: 40.5±19.2). 20.1% died; mean survival was 115.4 months. Age (HR = 1.098, 95% Cl = 1.04–1.252) and emphysema score (HR = 1.034, 95% CI = 1.007–1.07) were the only independent predictors of mortality. Pulmonary artery dimensions were not associated with survival. An emphysema score of 55% was chosen as the optimal threshold and 30% and 65% as suboptimals. Where emphysema score was between 30% and 65% (intermediate risk) the optimal lung volume threshold, a functional residual capacity of 210% predicted, was applied. This contingent staging approach separated patients with an intermediate risk based on emphysema score alone into high risk (Functional Residual Capacity ≥210% predicted) or low risk (Functional Residual Capacity <210% predicted). This approach was more discriminatory for survival (HR = 3.123; 95% CI = 1.094–10.412) than either individual component alone.

Conclusion

Although to an extent limited by the small sample size, this preliminary study indicates that the composite Emphysema score-Functional Residual Capacity index might provide a better separation of high and low risk patients with COPD, than other individual predictors alone.     

慢性阻塞性肺疾病与非慢性阻塞性肺疾病吸烟者肺组织蛋白质组学比较分析

吸烟是导致慢性阻塞性肺疾病（COPD）发生发展的主要原因之一.但吸烟者是否发生COPD存在个体差异,其机制尚未完全阐明.蛋白质组学研究能够高效率发现疾病相关蛋白并为深入研究疾病的发病机制提供线索.本研究运用二维凝胶电泳（2-DE）和基质辅助激光解吸电离飞行时间质谱(MALDI-TOF-MS)蛋白质组学研究方法结合生物信息学数据,对吸烟COPD患者和非COPD吸烟者肺组织表达的差异蛋白进行筛选和鉴定,共鉴定出24种差异蛋白,涉及基本代谢酶类、氧化应激相关酶类、凝血/纤溶相关蛋白、蛋白降解相关酶以及细胞生长分化相关蛋白等.本研究结果为进一步探索COPD的发病机制提供了新的线索.     

Correlation of a Decline in Aerobic Capacity with Development of Emphysema in Patients with Chronic Obstructive Pulmonary Disease: A Prospective Observational Study

In patients with COPD, CT assessment of emphysema and airway disease is known to be associated with lung function and 6-minute walk distance. However, it remains to be determined whether low attenuation area (LAA) on CT is associated with aerobic capacity assessed using cardiopulmonary exercise testing (CPET). In this prospective observational study, we repeatedly conducted high-resolution CT and CPET using a treadmill in 81 COPD patients over a median interval of 3.5 years. Two investigators independently scored LAA on images obtained at the aortic arch level, tracheal bifurcation level, and supradiaphragmatic level. Grades for the images of each lung were added to yield the total LAA score. Total LAA score was negatively correlated with peak aerobic capacity (V˙O2) (p<0.001, r = -0.485). LAA scores of the upper (aortic arch level) and the lower (supradiaphragmatic level) lungs were both significantly associated with peak V˙O2. There was a significant correlation between total LAA score and peak CO₂ output (V˙CO2) (p<0.001, r = -0.433). Total LAA score was correlated with oxygen saturation at peak exercise (p<0.001, r = -0.634) and the estimated dead space fraction (p<0.001, r = 0.416). The mean annual change in total LAA score was significantly correlated with those in peak V˙O2 (p<0.001, r = -0.546) and peak V˙CO2 (p<0.001, r = -0.488). The extent of emphysema measured by CT was associated with the results of CPET. The time-dependent changes in CPET data were also correlated with that in total LAA score. CT assessment could be a non-invasive tool to predict aerobic capacity in patients with COPD.     

Cognitive Impairment in Chronic Obstructive Pulmonary Disease

Background/Purpose

Chronic obstructive pulmonary disease (COPD), especially in severe forms, is commonly associated with multiple cognitive problems. Montreal Cognitive Assessment test (MoCA) is used to detect cognitive impairment evaluating several areas: visuospatial, memory, attention and fluency. Our study aim was to evaluate the impact of stable COPD and exacerbation (AECOPD) phases on cognitive status using MoCA questionnaire.

Methods

We enrolled 39 patients (pts), smokers with COPD group D (30 stable and 9 in AECOPD) and 13 healthy subjects (control group), having similar level of education and no significant differences regarding the anthropometric measurements. We analyzed the differences in MoCA score between these three groups and also the correlation between this score and inflammatory markers.

Results

Patients with AECOPD had a significant (p<0.001) decreased MoCA score (14.6±3.4) compared to stable COPD (20.2±2.4) and controls (24.2±5.8). The differences between groups were more accentuated for the language abstraction and attention (p<0.001) and delayed recall and orientation (p<0.001) sub-topics. No significant variance of score was observed between groups regarding visuospatial and naming score (p = 0.095). The MoCA score was significantly correlated with forced expiratory volume (r = 0.28) and reverse correlated with C-reactive protein (CRP) (r = −0.57), fibrinogen (r = −0.58), erythrocyte sedimentation rate (ESR) (r = −0.55) and with the partial pressure of CO₂ (r = −0.47).

Conclusions

According to this study, COPD significantly decreases the cognitive status in advanced and acute stages of the disease.     

The Relation of Serum Myeloperoxidase to Disease Progression and Mortality in Patients with Chronic Obstructive Pulmonary Disease (COPD)

Myeloperoxidase is a strong oxidant stored in primary granules of neutrophils with potent antibacterial and proatherogenic properties. Myeloperoxidase has been implicated in the pathogenesis of chronic obstructive pulmonary disease (COPD). However, the relationship of myeloperoxidase to health outcomes in COPD is not well known. We measured serum myeloperoxidase levels from 4,677 subjects with mild to moderate airflow limitation in the Lung Health Study. Using a Cox proportional hazards model, we determined the relationship of serum myeloperoxidase concentration to the risk of all-cause and disease specific causes of mortality. We found that serum myeloperoxidase concentrations were significantly related to accelerated decline in forced expiratory volume in 1 second (FEV1) over 11 years of follow-up (p<0.0001), and this association persisted after adjustments for age, sex, race, baseline FEV1, and smoking status (p = 0.048). Serum myeloperoxidase concentrations were also associated with increased risk of cardiovascular mortality (p = 0.036). Individuals in the highest quintile of myeloperoxidase had a hazard ratio of cardiovascular mortality of 1.90 (95% confidence interval 1.00–3.58; p = 0.049) compared with those in the lowest quintile, which was particularly notable in patients who continued to smoke (adjusted p-value of 0.0396). However, serum myeloperoxidase concentration was not related to total mortality, respiratory mortality, or deaths from malignancies. In conclusion, increased serum myeloperoxidase levels are associated with rapid lung function decline and poor cardiovascular outcomes in COPD patients, which support the emerging role of myeloperoxidase in the pathogenesis of COPD progression and cardiovascular disease.     

慢性阻塞性肺疾病合并肺曲菌病一例及文献复习

目的:提高对慢性阻塞性肺疾病合并侵袭性肺曲菌病(COPD合并IPA)临床特点、诊断及治疗的认识.方法:回顾性分析2011年4月收治的一例COPD合并IPA患者的临床资料及诊治经过,并复习相关文献.结果:男患,“咳嗽、咳痰30余年,气短3年,加重1月余”入院,肺部CT示双肺多发结节影、空洞影,经抗炎、抗念珠菌治疗无效,CT下肺结节病灶活检病理示肺曲菌.抗曲菌治疗后症状好转、肺部影像明显吸收.结论:COPD合并IPA正逐渐引起重视,临床特征无明显特异性,肺部影像以结节影、空洞影多见,早期常规治疗无效时应积极抗曲菌治疗,可明显改善症状,降低死亡率,病理活检是确诊的依据.     

Epicardial Adipose Tissue in Patients with Chronic Obstructive Pulmonary Disease

Rationale

Epicardial Adipose Tissue (EAT) volume as determined by chest computed tomography (CT) is an independent marker of cardiovascular events in the general population. COPD patients have an increased risk of cardiovascular disease, however nothing is known about the EAT volume in this population.

Objectives

To assess EAT volume in COPD and explore its association with clinical and physiological variables of disease severity.

Methods

We measured EAT using low-dose CT in 171 stable COPD patients and 70 controls matched by age, smoking history and BMI. We determined blood pressure, cholesterol, glucose and HbA1c levels, microalbuminuria, lung function, BODE index, co-morbidity index and coronary artery calcium score (CAC). EAT volume were compared between groups. Uni and multivariate analyses explored the relationship between EAT volume and the COPD related variables.

Results

COPD patients had a higher EAT volume [143.7 (P_25–75, 108.3–196.6) vs 129.1 (P_25–75, 91.3–170.8) cm³, p = 0.02)] and the EAT volume was significantly associated with CAC (r = 0.38, p<0.001) and CRP (r = 0.32, p<0.001) but not with microalbuminuria (r = 0.12, p = 0.13). In COPD patients, EAT volume was associated with: age, pack-years, BMI, gender, FEV₁%, 6 MWD, MMRC and HTN. Multivariate analysis showed that only pack-years (B = 0.6, 95% CI: 0.5–1.3), BMI (B = 7.8, 95% CI: 5.7–9.9) and 6 MWD (B = −0.2, 95% CI: −0.3–−0.1), predicted EAT volume.

Conclusions

EAT volume is increased in COPD patients and is independently associated with smoking history, BMI and exercise capacity, all modifiable risk factors of future cardiovascular events. EAT volume could be a non-invasive marker of COPD patients at high risk for future cardiovascular events.     

Systemic and Pulmonary Vascular Remodelling in Chronic Obstructive Pulmonary Disease

BackgroundChronic Obstructive Pulmonary Disease (COPD) is associated with subclinical systemic atherosclerosis and pulmonary vascular remodelling characterized by intimal hyperplasia and luminal narrowing. We aimed to determine differences in the intimal thickening of systemic and pulmonary arteries in COPD subjects and smokers. Secondary aims include comparisons with a non-smokers group; determining the clinical variables associated with systemic and pulmonary intimal thickening, and the correlations between systemic and pulmonary remodelling changes.MethodsAll consecutive subjects undergoing lung resection were included and divided into 3 groups: 1) COPD, 2) smokers, and 3) non-smokers. Sections of the 5th intercostal artery and muscular pulmonary arteries were measured by histo-morphometry. Four parameters of intimal thickening were evaluated: 1) percentage of intimal area (%IA), 2) percentage of luminal narrowing, 3) intimal thickness index, and 4) intima-to-media ratio.ResultsIn the adjusted analysis, the systemic arteries of COPD subjects showed greater intimal thickening (%IA) than those of smokers (15.6±1.5% vs. 14.2±1.6%, p = 0.038). In the pulmonary arteries, significant differences were observed for %IA between the 2 groups (37.3±2.2% vs. 29.3±2.3%, p = 0.016). Among clinical factors, metabolic syndrome, gender and COPD status were associated with the systemic intimal thickening, while only COPD status was associated with pulmonary intimal thickening. A correlation between the %IA of the systemic and pulmonary arteries was observed (Spearman’s rho = 0.46, p = 0.008).ConclusionsGreater intimal thickening in systemic and pulmonary arteries is observed in COPD patients than in smokers. There is a correlation between systemic and pulmonary vascular remodelling in the overall population.     

Multidrug-Resistant Tuberculosis in Patients with Chronic Obstructive Pulmonary Disease in China

Background

Relatively little is known about the specific relationship and impact from chronic obstructive pulmonary disease (COPD) on multidrug-resistant tuberculsosis (MDR-TB).

Methods

We conducted a retrospective study included patients aged ≥40 years with a confirmed pulmonary TB at three tertiary hospitals (Shandong, China) between January 2011 and October 2014. Univariable and multivariable analyses were performed to identify the relationship of MDR-TB and COPD.

Results

A total of 2164 patients aged ≥ 40 years with available results of drug susceptibility test (DST) and medical records were screened for this study: 268 patients with discharge diagnosis of COPD and 1896 patients without COPD. Overall, 14.2% of patients with COPD and 8.5% patients without COPD were MDR-TB. The rate of MDR-TB were significantly higher in patients with COPD (P<0.05). Migrant (odds ratios (OR) 1.32, 95% confidence interval (CI) 1.02–1.72), previous anti-TB treatment (OR 4.58, 95% CI 1.69–12.42), cavity (OR 2.33, 95% CI 1.14–4.75), and GOLD stage (OR 1.86, 95% CI 1.01–2.93) were the independent predictors for MDR-TB among patients with COPD.

Conclusions

MDR-TB occurs more frequently in patients with underlying COPD, especially those with being migrant, previous anti-TB therapy, cavity and severe airway obstruction.     

聚焦慢性阻塞性肺病治疗药物

慢性阻塞性肺病(COPD) 是肺部进行性疾病,需长期治疗。预计到2020 年,每年COPD 将会导致全球600 多万人死亡。尽管对新型药物开发投资不断增加,但该领域的治疗仍以缓解症状的支气管扩张吸入剂为主,而不是治愈性疗法,故应对COPD 的创新药的研发仍困难重重。与乳腺癌等疾病领域相比,呼吸系统药物的研发成功率不到50%,但每种获批药物的研发成本却翻倍。因此,制药公司致力于药品生命周期的管理,在当前治疗的基础上进一步改进。其策略包括不同种类药物联用、开发新配方和各种剂量剂型,改善疗效,方便给药。其中以长效β 受体激动剂 (LABA)/ 长效毒蕈碱拮抗剂(LAMA) 的定量复方药的需求增长最多。领导市场的GSK 公司的LABA 沙美特罗和吸入型皮质类固醇 (ICS) 氟替卡松的复方药Advair,就是应用以上方法的典型。虽已出现潜在新型靶标,但这些药物还处于早期开发阶段。吸入型LABA/ICS 定量复方药短期内仍是 COPD 治疗领域的主力军。     

Cluster Analysis in Patients with GOLD 1 Chronic Obstructive Pulmonary Disease

Background

We hypothesized that heterogeneity exists within the Global Initiative for Chronic Obstructive Lung Disease (GOLD) 1 spirometric category and that different subgroups could be identified within this GOLD category.

Methods

Pre-randomization study participants from two clinical trials were symptomatic/asymptomatic GOLD 1 chronic obstructive pulmonary disease (COPD) patients and healthy controls. A hierarchical cluster analysis used pre-randomization demographics, symptom scores, lung function, peak exercise response and daily physical activity levels to derive population subgroups.

Results

Considerable heterogeneity existed for clinical variables among patients with GOLD 1 COPD. All parameters, except forced expiratory volume in 1 second (FEV₁)/forced vital capacity (FVC), had considerable overlap between GOLD 1 COPD and controls. Three-clusters were identified: cluster I (18 [15%] COPD patients; 105 [85%] controls); cluster II (45 [80%] COPD patients; 11 [20%] controls); and cluster III (22 [92%] COPD patients; 2 [8%] controls). Apart from reduced diffusion capacity and lower baseline dyspnea index versus controls, cluster I COPD patients had otherwise preserved lung volumes, exercise capacity and physical activity levels. Cluster II COPD patients had a higher smoking history and greater hyperinflation versus cluster I COPD patients. Cluster III COPD patients had reduced physical activity versus controls and clusters I and II COPD patients, and lower FEV₁/FVC versus clusters I and II COPD patients.

Conclusions

The results emphasize heterogeneity within GOLD 1 COPD, supporting an individualized therapeutic approach to patients.

Trial registration

www.clinicaltrials.gov. NCT01360788 and NCT01072396.     

Predicting Daily Physical Activity in Patients with Chronic Obstructive Pulmonary Disease

Background

Objectively measuring daily physical activity (PA) using an accelerometer is a relatively expensive and time-consuming undertaking. In routine clinical practice it would be useful to estimate PA in patients with chronic obstructive pulmonary disease (COPD) with more simple methods.

Objectives

To evaluate whether PA can be estimated by simple tests commonly used in clinical practice in patients with COPD.

Methods

The average number of steps per day was measured for 7 days with a SenseWear Pro™ accelerometer and used as gold standard for PA. A physical activity level (PAL) of <1.4 was considered very inactive. Univariate and multivariate analyses were used to examine the relationship between the 6-minute walking distance (6MWD), the number of stands in the Sit-to-Stand Test (STST), hand-grip strength and the total energy expenditure as assessed by the Zutphen Physical Activity Questionnaire (TEE_ZPAQ). ROC curve analysis was used to identify patients with an extremely inactive lifestyle (PAL<1.4).

Results

In 70 patients with COPD (21 females) with a mean [SD] FEV₁ of 43.0 [22.0] %predicted, PA was found to be significantly and independently associated with the 6MWD (r = 0.69, 95% CI 0.54 to 0.80, p<0.001), STST (r = 0.51, 95% CI 0.31 to 0.66, p = 0.001) and TEEZPAQ (r = 0.50, 95% CI 0.30 to 0.66, p<0.001) but not with hand-grip strength. However, ROC curve analysis demonstrated that these tests cannot be used to reliably identify patients with an extremely inactive lifestyle.

Conclusions

In patients with COPD simple tests such as the 6-Minute Walk Test, the Sit-to-Stand Test and the Zutphen Physical Activity Questionnaire cannot be used to reliably predict physical inactivity.     

Oxygen Therapy Use in Older Adults with Chronic Obstructive Pulmonary Disease

Rationale

Oxygen therapy improves survival and function in severely hypoxemic chronic obstructive pulmonary disease (COPD) patients based on two landmark studies conducted over 40 years ago. We hypothesize that oxygen users in the current era may be very different. We examined trends and subject characteristics associated with oxygen therapy use from 2001–2010 in the United States.

Methods

We examined Medicare beneficiaries with COPD who received oxygen from 2001 to 2010. COPD subjects were identified by: 1) ≥2 outpatient visits >30 days apart within one year with an encounter diagnosis of COPD; or 2) an acute care hospitalization with COPD as the primary or secondary discharge diagnosis. Oxygen therapy and sustained oxygen therapy were defined as ≥1 and ≥11 claims for oxygen, respectively, in the durable medical equipment file in a calendar year. Primary outcome measures were factors associated with oxygen therapy and sustained oxygen therapy over the study period.

Results

Oxygen therapy increased from 33.7% in 2001 to 40.5% in 2010 (p-value of trend <0.001). Sustained oxygen therapy use increased from 19.5% in 2001, peaked in 2008 to 26.9% and declined to 18.5% in 2010. The majority of subjects receiving oxygen therapy and sustained oxygen therapy were female. Besides gender, factors associated with any oxygen use or sustained oxygen therapy were non-Hispanic white race, low socioeconomic status and ≥2 comorbidities.

Conclusions

Any oxygen use among fee-for service Medicare beneficiaries with COPD is high. Current users of oxygen are older females with multiple comorbidities. Decline in sustained oxygen therapy use after 2008 may be related to reimbursement policy change.     

细辛脑联合多索茶碱治疗慢性阻塞性肺病疗效观察

目的:观察细辛脑联合多索茶碱治疗慢性阻塞性肺疾病急性加重期（AECOPD）的临床疗效。方法:将164例AECOPD患者随机分为观察组（82例）和对照组（82例）,对照组予低流量吸氧、抗炎、抗感染、纠正水电解质紊乱等综合治疗,观察组在此基础上加用注射用细辛脑、多索茶碱静脉治疗。观察两组治疗前后症状、体征改善情况及血气分析变化。结果:观察组与对照组临床总有效率分别为93.9%、81.7%（P<0.05）,观察组在发热、咳嗽咳痰、喘息症状消失时间,以及肺部罗音减少50%以上时间均显著短于对照组（P<0.01）,在FEV1、FEV1/FVC、PEF、PaO₂、PaCO₂等指标也显著优于对照组（P<0.01）。结论:在常规治疗基础上加用细辛脑、多索茶碱可以有效提高AECOPD患者的临床疗效。     

细辛脑联合多索茶碱治疗慢性阻塞性肺病疗效观察

目的：观察细辛脑联合多索茶碱治疗慢性阻塞性肺疾病急性加重期（AECOPD）的临床疗效。方法：将164例AECOPD患者随机分为观察组（82例）和对照组（82例）,对照组予低流量吸氧、抗炎、抗感染、纠正水电解质紊乱等综合治疗,观察组在此基础上加用注射用细辛脑、多索茶碱静脉治疗。观察两组治疗前后症状、体征改善情况及血气分析变化。结果：观察组与对照组临床总有效率分别为93．9％、81．7％（P〈0．05）,观察组在发热、咳嗽咳痰、喘息症状消失时间,以及肺部罗音减少50％以上时间均显著短于对照组（P〈0．01）,在FEV1、FEV1／FVC、PEF、PaO2、PaCO2等指标也显著优于对照组（P〈0．01）。结论：在常规治疗基础上加用细辛脑、多索茶碱可以有效提高AECOPD患者的临床疗效。     

FeNO在慢性阻塞性肺疾病急性发作期患者中的临床应用

目的：探讨呼出气一氧化氮浓度(FeNO)在慢性阻塞性肺疾病急性期(AECOPD)患者中的变化情况及与一秒用力呼气容积 (FEV1)的关系。方法：选取上海第九人民医院2013 年8 月~2014 年2 月呼吸内科病区治疗的AECOPD 患者30 例,目前仍在吸 烟或患有哮喘、自身免疫性疾病及肿瘤的患者排除在外。对照组选取18 例健康的体检老年人。入组患者在治疗前先测定FeNO、 FEV1 值及完成CAT 评分,并进行病情分组。治疗后再次测定FeNO、FEV1 %值。结果：治疗前实验组FeNO、FEV1 %水平与对照 组相比有统计学差异(P<0.01)。治疗后实验组FeNO与对照组相比,无统计学差异(P>0.05)。而治疗前后两组间FEV1%变化有统计 学差异(P<0.01)。实验组不同亚组治疗前后FeNO、FEV1 %变化有统计学差异(P<0.05),且治疗前FeNO与FEV1 %呈负相关(r=-0. 098,P=0.042),治疗后FeNO与FEV1 %无明显相关(r=-0.248,P=0.784)。结论：FeNO可反映COPD急性期患者气道慢性炎症控制 情况,且对提示预后有一定意义。     

Time to First Morning Cigarette and Risk of Chronic Obstructive Pulmonary Disease: Smokers in the PLCO Cancer Screening Trial

BackgroundTime to first cigarette (TTFC) after waking is an indicator of nicotine dependence. The association between TTFC and chronic obstructive pulmonary disease (COPD), the third leading cause of death in the United States, has not yet been reported.MethodsWe investigated the cross-sectional association between TTFC and prevalent COPD among 6,108 current smokers in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. COPD was defined as a self-reported diagnosis of emphysema, chronic bronchitis, or both. Current smokers in PLCO reported TTFC, the amount of time they typically waited before smoking their first cigarette of the day after waking, in four categories: ≤5, 6-30, 31-60, or >60 minutes. We used logistic regression models to investigate the association between TTFC and prevalent COPD with adjustments for age, gender, race, education, and smoking (cigarettes/day, years smoked during lifetime, pack-years, age at smoking initiation), and prior lung cancer diagnosis.ResultsCOPD was reported by 19% of these 6,108 smokers. Individuals with the shortest TTFC had the greatest risk of COPD; compared to those with the longest TTFC (>60 minutes) the adjusted odds ratios (OR) and 95% confidence intervals (CI) for COPD were 1.48 (95% CI, 1.15-1.91), 1.64 (95% CI, 1.29-2.08), 2.18 (95% CI, 1.65-2.87) for those with TTFC 31-60 minutes, 6-30 minutes, and ≤5 minutes, respectively (P-trend <0.0001). The association between TTFC and emphysema was similar to that for bronchitis, albeit the ORs were slightly stronger for chronic bronchitis; comparing TTFC ≤5 minutes to >60 minutes, the adjusted OR (95% CI) was 2.29 (1.69-3.12) for emphysema and 2.99 (1.95-4.59) for chronic bronchitis.ConclusionsCurrent smokers with shorter TTFC have increased risk of COPD compared to those with longer TTFC, even after comprehensive adjustment for established smoking covariates. Future epidemiologic studies, including prospective designs, should incorporate TTFC to better assess disease risk and evaluate the potential utility of TTFC as a COPD screening tool for smokers in the clinical setting.