Norepinephrine Remains Increased in the Six-Minute Walking Test after Heart Transplantation

OBJECTIVE:

We sought to evaluate the neurohormonal activity in heart transplant recipients and compare it with that in heart failure patients and healthy subjects during rest and just after a 6-minute walking test.

INTRODUCTION:

Despite the improvements in quality of life and survival provided by heart transplantation, the neurohormonal profile is poorly described.

METHODS:

Twenty heart transplantation (18 men, 49±11 years and 8.5±3.3 years after transplantation), 11 heart failure (8 men, 43±10 years), and 7 healthy subjects (5 men 39±8 years) were included in this study. Blood samples were collected immediately before and during the last minute of the exercise.

RESULTS:

During rest, patients’ norepinephrine plasma level (659±225 pg/mL) was higher in heart transplant recipients (463±167 pg/mL) and heathy subjects (512±132), p<0.05. Heart transplant recipient’s norepinephrine plasma level was not different than that of healthy subjects. Just after the 6-minute walking test, the heart transplant recipient’s norepinephrine plasma level (1248±692 pg/mL) was not different from that of heart failure patients (1174±653 pg/mL). Both these groups had a higher level than healthy subjects had (545±95 pg/mL), p<0.05.

CONCLUSION:

Neurohormonal activity remains increased after the 6-minute walking test after heart transplantation.     

Evaluation of Quality of Life with the Chronic Obstructive Pulmonary Disease Assessment Test in Chronic Obstructive Pulmonary Disease and the Effect of Dyspnea on Disease-Specific Quality of Life in These Patients

Purpose

The chronic obstructive pulmonary disease (COPD) assessment test (CAT) was recently introduced for use in assessing disease-specific quality of life and follow-up of patients with COPD. The purpose of this study was to evaluate the effect of the dyspnea on disease-specific quality of life detected by CAT score in patients with COPD.

Materials and Methods

In this study, 90 stable patients with COPD as defined by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria were included. The level of dyspnea was assessed with the Medical Research Council (MRC) dyspnea scale, and disease-specific quality of life was assessed with CAT score.

Results

The mean±SD age was 68.5±10.9 (range 41-97) years. A significant relationship was established between CAT score, MRC dyspnea scale score and GOLD stage in patients with COPD. There was also a positive correlation between dyspnea scale scores and GOLD stage in the patients (p<0.001), as well as positive correlation between CAT score and dyspnea scale score (p<0.001). CAT score showed a significant correlation with hospitalization and exacerbations (p<0.05).

Conclusion

Dyspnea is an important symptom that may impact quality of life in patients with COPD. CAT was shown to be a simple, fast and intelligible measurement of disease-specific quality of life, and was correlated with levels of dyspnea in patients with COPD.     

Severity Staging of Chronic Obstructive Pulmonary Disease: Differences in Pre- and Post-Bronchodilator Spirometry

Purpose

The Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines for chronic obstructive pulmonary disease (COPD) uses the post-bronchodilator spirometry for diagnosis and severity staging. We evaluated differences in the severity classification of COPD, based on pre- and post-bronchodilator spirometry.

Materials and Methods

From 2000 to 2004, 207 COPD patients who underwent spirometry before and after inhalation of 400 µg of fenoterol were analyzed. A responder to the bronchodilator test (BDT) was defined by the American Thoracic Society (ATS) as an increase in forced expiratory volume in one second (FEV₁) or forced vital capacity ≥ 12% and ≥ 200 mL, and by the European Respiratory Society (ERS) as an increase in FEV₁ ≥ 10% of the predicted value. COPD severity was classified according to the 2008 GOLD guidelines.

Results

For the entire study population, the FEV₁ increased by 11.8 ± 12.5% of baseline after BDT and 41.1% and 27.1% of subjects were classified as responders using the ATS and ERS criteria, respectively. Based on pre-BDT spirometry, 55, 85, 58, and 9 patients were classified as Stage I-IV COPD, respectively. Sixty-seven (32.4%) patients changed severity staging after BDT, including 20.0%, 28.2%, 44.8%, and 66.7% of pre-BDT patients Stages I through IV, respectively. More ATS or ERS BDT-responders had a change in severity staging than non-responders (52.9% vs. 18.9% and 62.5% vs. 21.2%, both p < 0.001).

Conclusion

Our data suggest that the severity staging of COPD using pre-BDT spirometry might lead to significant differences as compared to staging, based on post-BDT spirometry, as recommended by the current GOLD guidelines.     

Modified Yupingfeng Formula for the Treatment of Stable Chronic Obstructive Pulmonary Disease: A Systematic Review of Randomized Controlled Trials

Background

Chronic obstructive pulmonary disease (COPD), is a very common disease of respiratory system. An increasing number of clinical trials on Yupingfeng formula in the management of stable COPD have been performed. However, the evidence base for it remains unknown. This review aims at assessing the efficacy, and safety of modified Yupingfeng formula in the treatment of stable COPD through a systematic review of all available randomized controlled trials.

Materials and Methods

Literature retrieval was conducted using four English databases (CENTRAL, PubMed, EMBASE, and ISI Web of Science), and four Chinese databases (CBM, CNKI, VIP, and WANFANG), from respective inception to January 2013, and supplemented with a manual search. Review authors independently extracted the trial data, and assessed the quality of each trial. Methodological quality was assessed by Cochrane risk of bias and Jadad''s scale. The following outcomes were evaluated: (1) lung function; (2) 6-minute walk distance (6MWD); (3) effective rate; (4) serum levels of IgA, IgG and IgE; and (5) adverse events. Data were analyzed using STATA 12.0 software.

Results

A total of nine studies involving 660, stable COPD patients were identified. Patients from all studies included in this review were randomized to receive Yupingfeng formula combined with Western medications in comparison with Western medications. In general, the methodological quality of the included trials was poor. The results of this systematic review indicates that, compared with Western medications alone, the use of Yupingfeng formula, if combined with Western medications could significantly improve FEV₁ (WMD = 0.30L; 95%CI: 0.19, 0.42), FEV₁/FVC ratio (SMD = 0.69; 95%CI: 0.48, 0.91), 6MWD (WMD = 31.73m; 95% CI: 19.29, 44.17), and effective rate (RR = 1.24; 95% CI: 1.10, 1.41), and increase the serum levels of IgA (WMD = 0.25; 95%CI: 0.16, 0.34) and IgG (WMD = 1.10; 95%CI: 0.53, 1.68), but no difference was found in the serum IgE levels (WMD = 0.47; 95%CI: −0.32, 1.27) between the two groups. No serious adverse events were reported.

Conclusions

Within the limitations of this systematic review, we may conclude that compared with Western medications alone, Yupingfeng formula, when combined with Western medications can provide more benefits for patients with stable COPD, without any serious adverse reactions being identified. However, these benefits need to be further confirmed through high-quality prospective placebo-controlled trials that should be strictly conducted in accordance with methodological principles and procedures.     

Reliability and validity of dyspnea measures in patients with obstructive lung disease

Dyspnea, the clinical term for shortness of breath, is the primary symptom and an important outcome measure in evaluations of patients with lung disease. It is a subjective symptom that has proved difficult to quantify. Many dyspnea measures are available, yet it is difficult, based on the existing literature, to determine the most reliable and valid. In this study, we evaluated 6 measures of dyspnea for reliability and validity: (a) Baseline Dyspnea Index (BDI) and Transition Dyspnea Index, (b) UCSD Shortness of Breath Questionnaire (SOBQ), (c) American Thoracic Society Dyspnea Scale, (d) Oxygen Cost Diagram, (e) Visual Analog Scale, and (f) Borg Scale. Subjects were 143 patients (74 women and 69 men) with obstructive lung disease, ages 40 to 86, FEV., 0.36 to 3.53 L, FVC 1.07 to 5.74 L. Dyspnea measures were assessed for test-retest reliability, internal consistency, interrater reliability, and construct validity (i.e.. correlations among dyspnea measures and correlations of dyspnea measures with exercise tolerance, health-related quality of life, lung function, anxiety, and depression). Results suggest that the SOBQ and BDI demonstrated the highest levels of reliability and validity among the dyspnea measures examined. This research was supported by University of California Tobacco Related Disease Research Program Grant 2RT026S, National Heart. Lung, and Blood Institute Grant HL 34732 to Robert M. Kaplan, and National Institutes of Health NHLBI Preventive Pulmonary Academic Award No. HL02215 to Andrew L. Ries.     

Phenotyping airways disease: an A to E approach

The airway diseases asthma and chronic obstructive pulmonary disease (COPD) are heterogeneous conditions with overlapping pathophysiological and clinical features. It has previously been proposed that this heterogeneity may be characterized in terms of five relatively independent domains labelled from A to E, namely airway hyperresponsiveness (AHR), bronchitis, cough reflex hypersensitivity, damage to the airways and surrounding lung parenchyma, and extrapulmonary factors. Airway hyperresponsiveness occurs in both asthma and COPD, accounting for variable day to day symptoms, although the mechanisms most likely differ between the two conditions. Bronchitis, or airway inflammation, may be predominantly eosinophilic or neutrophilic, with different treatments required for each. Cough reflex hypersensitivity is thought to underlie the chronic dry cough out of proportion to other symptoms that can occur in association with airways disease. Structural changes associated with airway disease (damage) include bronchial wall thickening, airway smooth muscle hypertrophy, bronchiectasis and emphysema. Finally, a variety of extrapulmonary factors may impact upon airway disease, including rhinosinusitis, gastroesophageal reflux disease, obesity and dysfunctional breathing. This article discusses the A to E concept in detail and describes how this framework may be used to assess and treat patients with airway diseases in the clinic.     

Oral non-typable Haemophilus influenzae enhances physiological mechanism of airways protection

Oral immunotherapy with inactivated non‐typeable Haemophilus influenzae (NTHi) prevents exacerbations of chronic obstructive pulmonary disease, but the mechanism is unclear. The aim of this study was to determine the mechanism of protection. This was a placebo versus active prospective study over 3 months in 64 smokers. The active treatment was three courses of oral NTHi given at monthly intervals, followed by measurement of bacteriological and immunological parameters. The results can be summarized: (i) NTHi‐specific T cells increased in the placebo treatment group over time (P < 0·05); (ii) the T cell response in the oral NTHi group started earlier than that in the placebo group (P < 0·05); and (iii) serum NTHi‐specific immunoglobulin (Ig)G had significantly greater variation in the placebo group (P < 0·0001). The increase in antibody in placebos over time correlated with exposure to live H. influenzae (P < 0·05) determined from culture of gargles; (iv) reduction in saliva lysozyme over time (P < 0·05) was detected only in the oral NTHi treatment group. These data are consistent with T cell priming of gut lymphoid tissue by aspiration of bronchus content into the gut, with oral immunotherapy augmenting this process leading to enhanced bronchus protection. The evidence for protection was a stable IgG antibody level through the study in the oral NTHi treatment group, contrasting with an increase in antibody correlating with exposure of the airways to H. influenzae in the placebo group. Saliva lysozyme was a useful biomarker of mucosal inflammation, falling after oral NTHi consistent with a reduction in the level of intralumenal inflammation.     

Predicting Factors of Severe COVID-19 in Patients With Asthma: A Korean National Cohort Study

As there are limited data on the disease course of and factors predicting severe coronavirus disease 19 (COVID-19) in patients with asthma, this study aims to perform a detailed analysis of the clinical course of asthmatic patients with COVID-19 and evaluate factors related to severe infection. Of the 5,628 patients confirmed with COVID-19, 128 (2.3%) had asthma. Among the 128 asthmatic patients, 32 (25%) had severe COVID-19 and 96 (75%) had non-severe COVID-19. Among asthmatic patients, those with severe COVID-19 were significantly older and had more dyspnea and fever, more comorbidities, and lower lymphocyte and platelet counts than those with non-severe COVID-19. In multivariable logistic regression analysis, chronic obstructive pulmonary disease (adjusted odds ratio [aOR], 6.49; 95% confidence interval [CI], 1.18–41.81), low lymphocyte proportion (aOR, 0.91; 95% CI, 0.86–0.97), and low platelet count (aOR, 0.99; 95% CI, 0.98–0.99) were independently associated with severe COVID-19.     

Understanding quality improvement at scale in general practice: a qualitative evaluation of a COPD improvement programme

Background

A growing body of knowledge exists to guide efforts to improve the organisation and delivery of health care, most of which is based on work carried out in hospitals. It is uncertain how transferable this knowledge is to primary care.

Aim

To understand the enablers and constraints to implementing a large-scale quality improvement programme in general practice, designed to improve care for people with chronic obstructive pulmonary disease.

Design and setting

A qualitative study of 189 general practices in a socioeconomically and ethnically-mixed, urban area in east London, UK.

Method

Twelve semi-structured interviews were conducted with people leading the programme and 17 in-depth interviews with those participating in it. Participants were local health system leaders, clinicians, and managers. A theoretical framework derived from evidence-based guidance for improvement programmes was used to interpret the findings. A complex improvement intervention took place with social and technical elements including training and mentorship, guidance, analytical tools, and data feedback.

Results

Practice staff wanted to participate in and learn from well-designed collaborative improvement projects. Nevertheless, there were limitations in the capacities and capabilities of the workforce to undertake systematic improvement, significant problems with access to and the quality of data, and tensions between the narrative-based generalist orientation of many primary care clinicians and the quantitative single-disease orientation that has characterised much of the quality improvement movement to date.

Conclusion

Improvement guidance derived largely from hospital-based studies is, for the most part, applicable to improvement efforts in primary care settings, although large-scale change in general practice presents some particular challenges. These need to be better understood and addressed if improvement initiatives are to be effective.     

Invasive pulmonary aspergillosis in chronic obstructive pulmonary disease: an emerging fungal pathogen

Acute invasive pulmonary aspergillosis occurs predominantly in immunocompromised hosts, with increasing numbers of cases of invasive aspergillosis among patients with chronic obstructive pulmonary disease (COPD) being reported. Among 13 cases of invasive aspergillosis diagnosed in COPD patients admitted to the intensive care unit with acute respiratory distress, the only risk factor for invasive fungal infection was corticosteroid treatment. Invasive aspergillosis should be suspected in COPD patients receiving steroid treatment who have extensive pulmonary infiltrates. Survival depends on rapid diagnosis and early appropriate treatment. A decrease or interruption of steroid treatment should be considered as part of the overall therapeutic strategy.     

慢性阻塞性肺疾病动物模型研究概况

慢性阻塞性肺病(chronic obstructive pulmonary disease,COPD)由基因-环境交互作用而致病,目前COPD拟临床研究大多是采用诱发性动物模型。动物选择根据实际需要以鼠、猪和灵长类动物为主。造模方法主要是将可诱发COPD的危险因素,强加于动物以诱导COPD的发生。造模时间的长短则与诱因的性质和暴露量密切相关。模型建成后主要从肺功能、肺部病理改变等方面,并采用血清炎症因子、细胞因子检测等手段对模型进行评价,但在实际操作中尚有待进一步的评估。     

慢性阻塞性肺疾病急性加重期与慢性阻塞性肺疾病并发社区获得性肺炎患者的临床对比

目的 探究慢性阻塞性肺疾病急性加重期与慢性阻塞性肺疾病并发社区获得性肺炎患者的临床对比,旨在为临床的诊断和治疗提供科学依据。方法 选取2017年3月~2018年3月于我院接受治疗的82例COPD患者为研究对象,按照随机数表法分为两组,其中观察组42例为AECOPD患者,对照组40例为COPD合并CAP患者,比较两组患者的临床症状、肺功能以及PCT、CRP水平。结果 观察组患者呼吸困难、咳脓痰、精神差、发热等临床症状的发生率均低于对照组,差异具有统计学意义（P＜0.05）。观察组患者FEV1、FVC、FEV1/FVC分别为（64.15±7.26）ml、（62.85±7.29）ml、（62.03±5.54）%,均高于对照组的（52.51±5.75）ml、（50.85±6.74）ml、（52.34±5.61）%,差异具有统计学意义（P＜0.05）。观察组患者PCT和CRP分别为（0.52±0.07）ng/L和（21.51±1.35）mg/L,均低于对照组的（0.97±0.08）ng/L和（40.05±1.57）mg/L,差异具有统计学意义（P＜0.05）。结论 AECOPD患者与COPD合并CAP患者相比,临床症状发生情况较少,肺功能较好,对患者进行相关检测,能够提高治疗效果。     

慢性阻塞性肺疾病骨骼肌萎缩的治疗现状

慢性阻塞性肺疾病(chronic obstructive pulmonary disease,COPD)不仅是一种局限于呼吸道和肺部的疾病,还是一种可以累及肺外各器官的全身疾病,其肺外效应包括心血管疾病、焦虑和抑郁及骨骼肌萎缩等疾病,其中骨骼肌萎缩严重影响患者的生活质量及预后,造成巨大的社会和经济负担.然而,肌肉组织固有的适应性为骨骼肌萎缩提供了治疗机会.适当的干预措施可逆转或延迟骨骼肌萎缩的发展进程.     

Role of respiratory infection in onset of asthma and chronic obstructive pulmonary disease

There is renewed interest in the possible role of events occurring during early life in determining predisposition to asthma and allergies. Among these events, respiratory illnesses associated with viral infections have been the matter of considerable research interest. There is now evidence suggesting that an immune response to viral infection in early life that is skewed toward an IgE- or an eosinophil-mediated slant is predictive of persistent wheezing symptoms up to the age of 6 years. Genetic and environmental factors (specifically bacterial infection burden) may be important determinants of the maturation of immune responses from a default 'Th-2-like' at birth to mature, non-Th-2-like responses. Homing of Th-2-like responses to the lung may be determined in part by inheritance of bronchial hyperresponsiveness, and in part by the progressive nature of chronic, uncontrolled airway inflammation. The main risk factor for the development of wheezing episodes in children who are not predisposed to allergic asthma is diminished airway function, which can also be detected shortly after birth. These children may stop wheezing later during childhood, but their levels of lung function track with age. It is tempting to speculate that chronic obstructive pulmonary disease may occur more frequently in these children.     

AECOPD患者院内继发肺部真菌感染的临床分析

目的探讨慢性阻塞性肺疾病急性加重期（acute exacerbation chronic obstructive pulmonary disease。AECOPD）肺部真菌感染的临床特点、相关因素及疗效。方法回顾性分析了2008年1月至2009年12月间AECOPD院内继发肺部真菌感染患者46例．并随机抽取相同时期无真菌感染的AECOPD患者46例作对比分析。结果AECOPD院内继发肺部真菌感染患者临床表现无特异性,病原菌以白色念珠菌为主。长期使用广谱高效抗生素和糖皮质激素、低蛋白血症、合并糖尿病以及机械通气是AECOPD院内继发真菌感染的主要危险因素。结论合理正确使用抗生素及糖皮质激素,预防医源性感染,加强营养,尽量缩短住院天数是降低AECOPD院内继发真菌感染发生率的关键因素。     

慢性阻塞性肺疾病患者合并抑郁焦虑情绪的高危因素研究

目的：探讨慢性阻塞性肺疾病(chronic obstructive pulmonary disease,COPD)患者合并抑郁焦虑情绪的高危因素。方法：通过对64例COPD患者进行汉密尔顿抑郁焦虑量表问卷调查并记录相关资料进行分析。结果：相对较高的文化程度是COPD患者产生抑郁焦虑情绪的高危因素。结论：临床医生在给COPD患者诊疗过程中注意患者的精神状态,尤其是有一定文化程度的患者,尽早的进行抑郁焦虑情绪的调查,及时的进行干预治疗。     

气道内高压力促进3种气道重塑相关因子的表达

目的探讨机械通气情况下气道内不同压力水平对气道重塑相关因子表达的影响。方法手术室经全麻行机械通气的42例慢性阻塞性肺疾病(COPD)作为COPD组和33例无基础肺疾病患者作为对照组。机械通气根据吸气峰压(PIP)水平又分为高、中、低压力组(分别为24、22和20 cm H_2O),呼气末正压均为5 cm H_2O。机械通气前及3 h后收集支气管肺泡灌洗液(BALF)。酶联免疫吸附法和Western blot法检测BALF中气道重塑相关因子成纤维生长因子2(FGF-2)、转化生长因子-β1(TGF-β1)和基质金属蛋白酶-9(MMP-9)蛋白表达水平。结果 1)机械通气前COPD组BALF中的FGF-2、TGF-β1和MMP-9蛋白水平明显高于对照组(P0.01)。2)机械通气后对照组在高压力刺激下FGF-2、TGF-β1和MMP-9表达水平升高(P0.05);而COPD组压力刺激下上述3种蛋白表达升高更明显(P0.05),且高压力组中及低压力组(P0.05)。3)相关性分析显示,COPD组BALF中FGF-2、TGF-β1、MMP-9表达水平与气道压力成正相关(P0.01)。结论机械通气时气道内的持续高压力可能通过作用于气道上皮细胞内压力敏感通道进而提高气道重塑因子FGF-2、TGF-β1、MMP-9的表达水平,COPD患者尤为显著。     

Overview of novel therapeutic targets for asthma and chronic obstructive pulmonary disease

Obstructive lung diseases, in particular asthma and chronic obstructive pulmonary disease, are a worldwide health problem that is increasing in incidence. While significant progress has been made in the control of symptoms, further advances must be made in modifying the clinical situation in terms of disease progression. Numerous pathogenetic studies have demonstrated that inflammatory responses play a crucial role in the development of chronic lung obstruction, while current molecular findings have provided a myriad of new and promising therapeutic targets. The aim of this article is to provide an overview of clinically and pharmacologically relevant targets for asthma and chronic obstructive pulmonary diseases, considering currently investigated therapeutic approaches.     

Airway inflammation in asthma and chronic obstructive pulmonary disease with special emphasis on the antigen-presenting dendritic cell: influence of treatment with fluticasone propionate

Asthma is a chronic inflammatory disorder of the airways characterized by variable airflow limitation and airway hyperresponsiveness. The type of inflammatory response in asthma is compatible with a major contribution of professional antigen-presenting cells. The airways in chronic obstructive pulmonary disease (COPD) are also markedly inflamed; however, the predominant types of inflammatory cells and the main anatomical site of the lesion appear to differ from those in asthma. COPD is characterized by reduced maximum expiratory flow and slow forced emptying of the lungs. Steroids are the most prominent medication used in the treatment of asthma and COPD; however, the beneficial effect of steroid treatment in COPD is subject of debate. We investigated the efficacy of fluticasone propionate (FP) treatment in atopic asthmatics and in COPD patients with bronchial hyperreactivity who smoke. The effect of the treatment on bronchial hyperreactivity and indices of the methacholine dose–response curve were analysed, as well as indices of inflammation of the airway mucosa with special emphasis on the antigen presenting dendritic cell. Treatment of allergic asthmatic patients resulted in improvement of lung function (FEV₁), a decrease in bronchial hyperresponsiveness and a decrease of maximal airway narrowing. During the FP-treatment of COPD patients, FEV₁ remained stable, while FEV₁ deteriorated significantly in the placebo group. Therefore, steroid treatment may have a beneficial effect in COPD patients with bronchial hyperresponsiveness (BHR). Since immunohistochemical analysis of bronchial biopsy specimens from asthma and COPD patients show disease-specific aspects of inflammation, the anti-inflammatory effect of FP is obtained through modulation of different cell populations in asthma and COPD.     

云南昆明地区阻塞性睡眠呼吸暂停低通气综合征患者的慢性阻塞性肺疾病流行状况

目的了解云南昆明地区阻塞性睡眠呼吸暂停低通气综合征(OSAHS)患者的慢性阻塞性肺疾病(COPD)的患病情况及重叠综合征(OS)的临床表现。方法回顾性研究4 636例打鼾患者,排除COPD以外慢性呼吸系统疾病,并对患者进行病情评估。测试内容包括AHI(呼吸暂停低通气指数)、BMI(体质量指数)、Epworth嗜睡量表测试和肺功能等。OS确诊的指标是同时满足AHI5次/h并且FEV_1/FVC70%。结果 2006-2012年,云南昆明地区OSAHS患者合并COPD的患病率为10.1%(95%CI 9.1%~11.1%),而且男性OS患病率高于女性,男性为10.2%,女性为9.7%。OS患者平均年龄为(56.9±14.1)岁,平均AHI为(47.46±26.79)次/h,平均FEV_1/FVC为(60.09±23.57)%。多导睡眠监测结果提示,单纯OSASH组和OS组患者夜间存在明显的低氧血症,但是OS组患者更为显著。肺功能检测结果提示,OS患者慢性阻塞性肺疾病病情更严重。结论 OSAHS患者合并COPD在云南昆明地区患病率较高,并且高年龄段患病率达到24%以上。同时OS患者较单纯OSAHS和COPD患者在肺功能和低氧血症病情表现更严重,但是其发病机制尚不能确定。