Mortality among subjects with chronic obstructive pulmonary disease or asthma at two respiratory disease clinics in Ontario

BACKGROUND:

Chronic obstructive pulmonary disease (COPD) and asthma are common; however, mortality rates among individuals with these diseases are not well studied in North America.

OBJECTIVE:

To investigate mortality rates and risk factors for premature death among subjects with COPD.

METHODS:

Subjects were identified from the lung function testing databases of two academic respiratory disease clinics in Hamilton and Toronto, Ontario. Mortality was ascertained by linkage to the Ontario mortality registry between 1992 and 2002, inclusive. Standardized mortality ratios were computed. Poisson regression of standardized mortality ratios and proportional hazards regression were performed to examine the multivariate effect of risk factors on the standardized mortality ratios and mortality hazards.

RESULTS:

Compared with the Ontario population, all-cause mortality was approximately doubled among subjects with COPD, but was lower than expected among subjects with asthma. The risk of mortality in patients with COPD was related to cigarette smoking, to the presence of comorbid conditons of ischemic heart disease and diabetes, and to Global initiative for chronic Obstructive Lung Disease severity scores. Individuals living closer to traffic sources showed an elevated risk of death compared with those who lived further away from traffic sources.

CONCLUSIONS:

Mortality rates among subjects diagnosed with COPD were substantially elevated. There were several deaths attributed to asthma among subjects in the present study; however, overall, patients with asthma demonstrated lower mortality rates than the general population. Subjects with COPD need to be managed with attention devoted to both their respiratory disorders and related comorbidities.     

Comparison of serum biomarkers between patients with asthma and with chronic obstructive pulmonary disease

Objective: Asthma and chronic obstructive pulmonary disease (COPD) have distinct pathophysiological mechanisms but sometimes share similar clinical manifestations. Distinguishing between these diseases is important. This study compared the profiles of serum biomarkers between patients with asthma and those with COPD. Methods: Serum levels of the chitinase like protein YKL-40, periostin, interleukin (IL)-18, and chemokine (C--C motif) ligand 18 (CCL18) were measured in asthma patients (n = 20), COPD patients (n = 16), and normal controls (n = 20). Results: Serum levels of YKL-40 were higher in COPD patients [median (range), 55 (17–565) versus 208 (74–922) ng/mL, p < 0.0001], but no differences were observed between asthma and COPD patients after adjusting for age and forced expiratory volume in 1 s (FEV₁). No differences in serum levels of periostin, IL-18, or CCL18 were observed between the patient groups. Total IgE and airway hypersensitivity were negatively correlated (r = ?0.485, p = 0.007). CCL18 levels were related to patients’ age in asthmatic patients (r = ?0.562, p = 0.010). Serum levels of CCL18 and IL-18 were positively correlated in patients with COPD (r = 0.696, p = 0.003). Conclusions: No differences in the serum profiles of periostin, IL-18, or CCL18 were observed between patients with asthma and those with COPD. Serum levels of YKL-40 were not different between asthma and COPD patients after adjusting for age and FEV₁. There were negative correlation between CCL18 and age in patients with asthma and positive correlation between IL-18 and CCL18 in patients with COPD.     

Empowering family physicians to impart proper inhaler teaching to patients with chronic obstructive pulmonary disease and asthma

BACKGROUND:

Patients with chronic obstructive pulmonary disease (COPD) and asthma depend on inhalers for management, but critical errors committed during inhaler use can limit drug effectiveness. Outpatient education in inhaler technique remains inconsistent due to limited resources and inadequate provider knowledge.

OBJECTIVE:

To determine whether a simple, two-session inhaler education program can improve physician attitudes toward inhaler teaching in primary care practice.

METHODS:

An inhaler education program with small-group hands-on device training was instituted for family physicians (FP) in British Columbia and Alberta. Sessions were spaced one to three months apart. All critical errors were corrected in the first session. Questionnaires surveying current inhaler teaching practices and attitudes toward inhaler teaching were distributed to physicians before and after the program.

RESULTS:

Forty-one (60%) of a total 68 participating FPs completed both before and after program questionnaires. Before the program, only 20 (49%) reported providing some form of inhaler teaching in their practices, and only four (10%) felt fully competent to teach patients inhaler technique. After the program, 40 (98%) rated their inhaler teaching as good to excellent. Thirty-four (83%) reported providing inhaler teaching in their practices, either by themselves or by an allied health care professional they had personally trained. All stated they could teach inhaler technique within 5 min. Observation of FPs during the second session by certified respiratory educators found that none made critical errors and all had excellent technique.

CONCLUSION:

A physician inhaler education program can improve attitudes toward inhaler teaching and facilitate implementation in clinical practices.     

Childhood asthma and GOLD‐defined chronic obstructive pulmonary disease

Background: Current understanding of chronic obstructive pulmonary disease (COPD) is that it results from an interaction of genetic and environmental factors. This study aimed to investigate the strength of association of various known risk factors for COPD. Methods: Detailed written questionnaires, full pulmonary function tests and atopy testing were completed in 749 people, aged 25–75 years, recruited from a random population sample. COPD was defined, using Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines, as a post‐bronchodilator forced expiratory volume in 1 s/forced vital capacity (FEV₁/FVC) ratio <0.7. Results: The prevalence of COPD was higher in men (OR 1.7 (95% CI 1.1–2.7)) and increased with increasing age (OR per decade older 2.1 (95% CI 1.7–2.7)). COPD was more frequent in current and ex‐smokers and increased with increasing pack years (OR per 10 pack years 1.3 (95% CI 1.1–1.5)). On a logit scale, a diagnosis of asthma as a child conferred a similar risk as an increase in age of 22 years or 62 pack years of cigarette smoking. Conclusion: Childhood asthma emerged with the strongest association for GOLD‐defined COPD. Possible explanations for this are suggested, including limitations of the current GOLD spirometric definition of COPD, a chance observation because of the high prevalence of both disorders in this population, or alternatively childhood asthma is a risk factor for COPD.     

Role of bronchodilators in chronic obstructive pulmonary disease

The prevalence of chronic obstructive pulmonary disease (COPD) continues to be on the rise. Bronchodilators are first line agents for the symptomatic management of this disease and have proven to be effective in both stable disease status and exacerbations. The stepwise escalation of therapy for COPD according to severity has been outlined in international guidelines. Different classes of bronchodilators exist. The most experience is available for short-acting beta-agonists and anticholinergics. These agents are mainly recommended for the treatment of mild COPD and for symptomatic patients on an as needed basis. Long-acting beta-agonists and anticholinergics have been developed more recently. They are more convenient to use for patients with advanced disease who require maintenance therapy with bronchodilators, and have been shown in this group of patients to provide superior efficacy compared with short-acting agents. Tiotropium, a long-acting anticholinergic, appears to be particularly powerful and may eventually replace ipratropium as the primary agent for COPD treatment. In contrast, the usage of theophylline, which used to be part of the mainstay of treatment for COPD, has declined, mainly secondary to a narrow therapeutic margin and side effects, but it is inexpensive and still has its role. New agents like phosphodiesterase-4-inhibitors are interesting substances that may become important adjuncts in COPD management, but there is limited experience so far. None of the bronchodilators have been shown to change outcome in COPD, but this issue is under active investigation.     

A pulmonary rehabilitation program for patients with asthma and mild chronic obstructive pulmonary diseases (COPD)

The effects of a pulmonary rehabilitation program on 44 patients with chronic obstructive pulmonary disease (COPD) were compared to a control group. The treated group was admitted to the program for a period of three months. The program consisted of several parts, such as physical training, health education, and psychological and social matters. Before participation, the patients were thoroughly examined and provided with optimal medical treatment. Both groups were assessed by means of biometrical tests and questionnaires for a period of 2 years. The rehabilitation group improved significantly in endurance, psychological parameters, and consumption of medical care. Working days increased and their way of life became more active. Smoking habits and body fat percentage decreased. Bronchial hyperreactivity, need for pulmonary drugs, and coughing and sputum production did not improve in the rehabilitation group compared to the control group. Airway obstruction, expressed as forced expiratory volume in one second, and complaints of dyspnea, allergy and hyperreactivity scores on questionnaires improved only in the short term (<1 year), but did not improve significantly in the long term. This study shows that pulmonary rehabilitation can result in improvements in patients with asthma or COPD who have many complaints despite the fact that their pulmonary function is not severely disturbed.     

外周血白介素-17检测在气道慢性炎症性疾病诊断中的临床价值

目的探讨外周血CD4+T细胞亚群Th17代表性细胞因子IL-17在哮喘、慢性阻塞性肺疾病(COPD)以及哮喘COPD重叠综合征(ACOS)等气道慢性炎症性疾病鉴别诊断中的临床价值。方法收集哮喘患者26例、COPD患者33例及ACOS患者14例的血清、临床资料及实验室检查资料,检测哮喘、COPD、ACOS患者外周血IL-17等细胞因子、炎症介质、外周血白细胞分类计数、血清免疫球蛋白亚型以及肺通气功能,并进行组间比较。健康体检者69例作为对照。结果 Th17细胞因子IL-17在哮喘及ACOS组升高较COPD组更为明显(P0.01)。调节性T细胞的主要细胞因子IL-10在哮喘患者中的水平明显低于COPD患者(P0.05)。外周血炎症细胞比例、免疫球蛋白亚型在哮喘、COPD、ACOS鉴别诊断中具有一定参考价值。但肺通气功能指标对于以上三者的鉴别价值有限。哮喘及ACOS组患IL-17与肺通气功能指标呈负相关关系。结论 IL-17作为新型Th17细胞分泌的代表性细胞因子,在鉴别上述疾病中具有重要的参考价值。Th17/Treg细胞失衡可能是难治性哮喘的潜在发病机制。     

气道高反应性在COPD和哮喘的比较

目的 探讨慢性阻塞性肺疾病(chronic obstructive pulmonary diseases,COPD)和支气管哮喘(简称哮喘)患者在组胺支气管激发试验中气道高反应性(airway hyperresponsiveness,AHR)的不同.方法 将我院2008～2010年间诊断为COPD和哮喘的并经随访一年处于稳定期的患者共80例,其中COPD组39例,哮喘组41例,均行支气管组胺激发试验,观察FEF25％～75％/FVC(肺活量为25％～75％时最大呼气流量与用力肺活量的比值)在两组患者的变化.结果 COPD组FEF25％～75％和FEF25％～75 ％/FVC均明显低于哮喘组(P值均＜0.01);以激发试验阳性的两组患者为对象分别进行简单相关分析,在COPD组和哮喘组中FEF25％～75％/FVC与Log10DRS呈负相关(r分别为-0.510和-0.466,P＜0.05),与PD20FEV1呈正相关(r分别为0.518和0.487,P＜0.05),说明相对于肺容积而言,气道容积越小,气道收缩性越强,反应性越高.随后在以气道收缩性指标Log10DRS为因变量,以年龄、体表面积、FEV1％及FEF25％～75 ％/FVC为自变量进行线性回归分析,在COPD组FEV1％对Log10DRS较FEF25％～75％/FVC影响大(P＜0.05),而哮喘组不存在这情况.结论 在COPD中AHR患者并不少见,其发生机制与哮喘是不同的.     

The volumetric response to bronchodilators in stable chronic obstructive pulmonary disease

A significant proportion of patients with COPD show post-bronchodilator improvement in lung volume even though this response is rarely considered when classifying subjects as having reversible or irreversible airway disease. We studied 266 patients with a clinical and physiological diagnosis of COPD who underwent pulmonary function testing and had their spirometric response to 5 mg salbutamol assessed. After the bronchodilator 125 (47%) patients increased their forced vital capacity by more than the known variability of the test while 60 (23%) showed only a volume response without improvement in expiratory flow. These 'volume responders' had greater degrees of airflow obstruction-lower FEV(1) (p < 0.001) and FEV(1)/FVC (p < 0.05)-and a higher residual volume at rest (p = 0.005) with similar degrees of emphysema measured by K(CO). Subjects with evidence of greater dynamic airway collapse, assessed by the ratio of early to mid expiratory flow, were less likely to have a flow response but more likely to have a volume response after salbutamol (p < 0.005). This would be compatible with volume response being commoner in patients who exhibit tidal expiratory flow limitation. We suggest that post-bronchodilator absolute change in FVC provides important additional physiological information when interpreting bronchodilator reversibility testing.     

Pharmacologic interventions in chronic obstructive pulmonary disease: bronchodilators

Chronic obstructive pulmonary disease (COPD) is a treatable disease characterized by progressive airflow limitation. Prevention of disease progression, improvement of symptoms, exercise tolerance, health status, and decrease in exacerbations and in mortality are the main goals of the management of COPD. Bronchodilators play a pivotal role in the treatment of symptomatic patients with COPD. Inhaled short-acting bronchodilators are currently recommended for rescue of symptoms in patients with mild disease, whereas inhaled long-acting bronchodilators are recommended as first-line agents for maintenance therapy in patients with moderate and severe disease and those with daily symptoms. Long-acting bronchodilators improve symptoms, exercise tolerance, and health status, and reduce exacerbations in patients COPD. However, their effects on long-term decline in lung function and mortality are currently under investigation. When symptoms are not sufficiently controlled by the use of one bronchodilator, combining bronchodilators of different classes may be a more effective approach. In fact, recent evidence supports the regular use of a combination of a long-acting beta2-adrenoceptor agonist and a long-acting anticholinergic agent in patients with severe COPD. Combining a long-acting beta2-adrenoceptor agonist with an inhaled corticosteroid has also been shown to be more effective than the use of either agent alone. The use of theophylline has declined in recent years because of its narrow therapeutic index, and should be reserved as a third-line option in patients with very severe disease. Several novel bronchodilators are now in different stages of development for use alone or in combination with other agents.     

Cough in chronic obstructive pulmonary disease

Patients with chronic obstructive pulmonary disease (COPD) most commonly complain of cough, production of phlegm and breathlessness. The cough reflex sensitivity is heightened compared with that in healthy volunteers and is similar to that in subjects with asthma. The degree of airflow obstruction does not predict cough reflex sensitivity or objective cough counts, implying an independent process. Objective cough rates seem to be relatively low in COPD, despite frequent reporting of the symptom by patients. The relative contribution of cough to disability in COPD seems to be small, if assessed by subjective reporting. Effective treatments for cough in COPD have not yet been identified. Improved outcome measures of cough, a better understanding of the mechanisms underlying cough, and the importance of cough to patients is required to progress in this field.     

支气管舒张剂联合雾化吸入在慢性阻塞性肺疾病中的应用

COPD是一种具有气流受限特征的可以预防和治疗的疾病,气流受限不完全可逆,呈进行性发展,并与肺部对香烟烟雾等有害气体或有害颗粒的异常炎症反应有关.     

Advances in chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) is characterised by progressive airflow limitation in the presence of identifiable risk factors. Inflammation is the central pathological feature in the pathogenesis of COPD. In addition to its pulmonary effects, COPD is associated with significant extrapulmonary manifestations, including ischaemic heart disease, osteoporosis, stroke and diabetes. Anxiety and depression are also common. Spirometry remains the gold standard diagnostic tool. Pharmacologic and non‐pharmacologic therapy can improve symptoms, quality of life and exercise capacity and, through their effects on reducing exacerbations, have the potential to modify disease progression. Bronchodilators are the mainstay of pharmacotherapy, with guidelines recommending a stepwise escalating approach. Smoking cessation is paramount in managing COPD, with promotion of physical activity and pulmonary rehabilitation being other key factors in management. Comorbidities should be actively sought and managed in their own right. Given the chronicity and progressive nature of COPD, ongoing monitoring and support with timely discussion of advanced‐care planning and end‐of‐life issues are recommended.     

白细胞介素17在大鼠慢性阻塞性肺疾病和支气管哮喘模型中的变化及意义

目的了解白细胞介素17(IL17)在大鼠慢性阻塞性肺疾病(COPD)和支气管哮喘(简称哮喘)模型中的变化。方法SD雄性大鼠随机分为COPD组(13只)、哮喘组(11只)、吸烟组(11只)和正常对照组(12只);观察各组大鼠气道病理改变,采用酶联免疫吸附测定(ELISA)法检测大鼠支气管肺泡灌洗液(BALF)及肺组织匀浆IL17水平;免疫组化及图像分析法检测肺组织IL17及胞间黏附分子1(ICAM1),CD3、CD4、CD8的表达。结果COPD组和哮喘组肺组织匀浆IL17和BALF中IL17均显著增高,与正常对照组和吸烟组比较差异有显著性(P均<001);COPD组IL17主要在支气管上皮细胞内表达,哮喘组则在气道周围单核淋巴细胞内表达;COPD组和哮喘组IL17表达量均显著高于正常对照组及吸烟组(P<001或<005)。COPD组肺组织匀浆IL17与BALF中中性粒细胞(r=0676,P=0002)以及BALF中IL17与小气道平滑肌增生均呈正相关(r=0641,P=0046);肺组织匀浆IL17与ICAM1呈正相关(r=0550,P=0051);哮喘组肺组织匀浆IL17分别与BALF中嗜酸粒细胞(r=0884,P=0001)和肺组织CD3T细胞呈正相关(r=0812,P=0002)。结论COPD中IL17可能通过增强ICAM1的表达等途径促进中性粒细胞在气道内聚集,参与对COPD气道炎症的调节。IL17在哮喘中的作用可能与其促进嗜酸粒细胞在气道内聚集有关。     

Mechanisms of atherothrombosis in chronic obstructive pulmonary disease

Patients affected by chronic obstructive pulmonary disease (COPD) have an increased risk of atherothrombotic acute events, independent of smoking and other cardiovascular risk factors. As a consequence, myocardial ischemia is a relevant cause of death in these patients. We reviewed studies concerning the potential mechanisms of atherothrombosis in COPD. Bronchial inflammation spreads to the systemic circulation and is known to play a key role in plaque formation and rupture. In fact, C-reactive protein blood levels increase in COPD and provide independent prognostic information. Systemic inflammation is the first cause of the hypercoagulable state commonly observed in COPD. Furthermore, hypoxia is supposed to activate platelets, thus accounting for the increased urinary excretion of platelet-derived thromboxane in COPD. The potential metabolic risk in COPD is still debated, in that recent studies do not support an association between COPD and diabetes mellitus. Finally, oxidative stress contributes to the pathogenesis of COPD and may promote oxidation of low-density-lipoproteins with foam cells formation. Retrospective observations suggest that inhaled corticosteroids may reduce atherothrombotic mortality by attenuating systemic inflammation, but this benefit needs confirmation in ongoing randomized controlled trials. Physicians approaching COPD patients should always be aware of the systemic vascular implications of this disease.     

慢性阻塞性肺疾病与支气管哮喘患者血浆抗菌肽LL-37水平的比较

目的比较慢性阻塞性肺疾病(COPD)与支气管哮喘(哮喘)患者血浆中LL-37水平的异同,以期对COPD的鉴别诊断有所帮助.方法研究对象为2016年5月至2017年4月于北京医院就诊的COPD、哮喘患者和同期健康体检者.根据2014年COPD全球策略的病情严重程度评估标准,将纳入的COPD患者分为(A+B)组和(C+D)组2个亚组.检测各组血浆中LL-37水平,比较各组间LL-37水平的差异,并探讨LL-37水平与肺功能等指标之间的关系.结果共纳入COPD组患者129例,其中(A+B)组69例,(C+D)组60例;哮喘组患者60例;健康体检者60例(对照组).对照组、哮喘组、COPD组的血浆LL-37水平分别为(19.7±4.8)μg/L、(18.7±4.5)μg/L、(17.8±4.2)μg/L,各组间比较差异无统计学意义.(C+D)组血浆LL-37水平[(15.2±2.6)μg/L]明显低于哮喘组[(18.7±4.5)μg/L]、对照组[(19.7±4.8)μg/L]和(A+B)组[(20.1±4.0)μg/L](F=6.422,P<0.001).COPD患者血浆LL-37水平与第1秒用力呼气容积(FEV1)、FEV1%pred之间均呈显著正相关(r=0.488、0.554,P=0.005、0.001),与改良英国医学研究委员会呼吸困难量表呼吸困难指数之间呈显著负相关(r=-0.397,P=0.022).结论急性加重风险较高的COPD患者血浆中的LL-37水平明显低于哮喘患者和健康人.     

Cardiovascular risk in chronic obstructive pulmonary disease

Cardiovascular disease (CVD) contributes significantly to morbidity and mortality in COPD. There is a high prevalence of traditional risk factors in this patient group including smoking, sedentary behaviour and low socio-economic class. However, large studies have shown that airflow limitation is an independent risk factor for CVD. Therefore there may be a 'COPD effect' that contributes to CVD in this condition, adding to the body of evidence that COPD has important systemic consequences, as well as being a lung disease. In this article, we review the evidence for CVD in COPD. Next, we examine systemic factors present in COPD, and link these to the pathogenesis of atherosclerosis, including inflammation, oxidative stress and hypoxia. Finally, we review those studies that have investigated therapeutic interventions in COPD that may modify cardiovascular risk.