Disease modification in chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) is a preventable and treatable disease in which patients experience a progressive decline in lung function, worsening exercise capacity, and frequent exacerbations. Based on clinical evidence, the progression of COPD could be modified by focus on earlier diagnosis; risk reduction through smoking cessation; symptom reduction with pharmacotherapy, improving health-related quality of life, and pulmonary rehabilitation; and decreasing complications by reducing exacerbations. Smoking cessation has been shown to slow lung function decline and reduce mortality, including deaths due to cardiovascular disease, lung cancer, and other respiratory disease (including COPD).     

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.     

Management of refractory breathlessness with morphine in patients with chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) is a progressive, incurable illness, which leads to significant morbidity over long periods of time and mortality. Treatment aims to reduce symptoms, improve exercise capacity and quality of life, reduce exacerbations, slow disease progression and reduce mortality. However, breathlessness is common in patients with advanced COPD and remains undertreated. As all reversible causes of breathlessness are being optimally managed, consideration should be given to specific non‐pharmacological and pharmacological treatment strategies for breathlessness. Low dose morphine has been shown to reduce safely and effectively breathlessness in patients with severe COPD and refractory dyspnoea. However, despite numerous guidelines recommending opioids in this clinical setting, many barriers limit their uptake by clinicians. Integration of palliative care earlier in the disease course can help to improve symptom control for people with severe COPD and refractory breathlessness. A multidisciplinary approach involving both respiratory and palliative care teams offers a new model of care for these patients.     

Smoking cessation in pulmonary rehabilitation: goal or prerequisite?

It has been more than 35 years since the Surgeon General of the United States released the first report of the Advisory Committee on Smoking and Health. Cigarette smoking has been identified as the most important source of preventable morbidity and premature mortality in North America. During the 1990s, tobacco was the largest single cause of premature death in the developed world. Smoking cessation is followed by immediate health benefits in terms of symptoms and organ function. It dramatically reduces the risk of most smoking-related diseases, including chronic obstructive pulmonary disease and lung cancer. Respiratory rehabilitation has been defined as a multidimensional continuum of services directed to persons with pulmonary disease and their families, usually by an interdisciplinary team of specialists, with the goal of achieving and maintaining the individual's maximum level of independence and functioning in the community. A European Respiratory Society task force on rehabilitation recently commented that respiratory rehabilitation must address medical management including reinforcement of smoking cessation, education of the patient and family, exercise reconditioning, physical and occupational therapy, nutritional support, and long-term oxygen therapy. Many patients have quit smoking by the time they enroll in a pulmonary rehabilitation program. Nevertheless, the inclusion of smokers in respiratory rehabilitation programs remains controversial. Among 14 trials included in a meta-analysis of respiratory rehabilitation of patients with chronic obstructive pulmonary disease (COPD), the smoking status of the patients was reported in 9 of the trials, and only 2 trials stated that smoking was an absolute exclusion criterion for enrollment. Some investigators have used a trial of smoking cessation as an index of the patient's motivation to improve his or her health status. This article describes the effect of smoking on the course of COPD and the opportunity to address smoking in the context of comprehensive rehabilitation. The authors' line of reasoning is that (1) smoking causes COPD and perpetuates the pathophysiologic processes defining the disease, (2) symptomatic COPD does not facilitate smoking cessation, (3) smoking may alter rehabilitation outcomes, and (4) if smoking cessation is not a prerequisite to pulmonary rehabilitation, then a smoking cessation intervention should at least he offered as part of such a program.     

Lung cancer in chronic obstructive pulmonary disease: enhancing surgical options and outcomes

Patients with chronic obstructive pulmonary disease (COPD) are at increased risk for both the development of primary lung cancer, as well as poor outcome after lung cancer diagnosis and treatment. Because of existing impairments in lung function, patients with COPD often do not meet traditional criteria for tolerance of definitive surgical lung cancer therapy. Emerging information regarding the physiology of lung resection in COPD indicates that postoperative decrements in lung function may be less than anticipated by traditional prediction tools. In patients with COPD, more inclusive consideration for surgical resection with curative intent may be appropriate as limited surgical resections or nonsurgical therapeutic options provide inferior survival. Furthermore, optimizing perioperative COPD medical care according to clinical practice guidelines including smoking cessation can potentially minimize morbidity and improve functional status in this often severely impaired patient population.     

Practical approach to establishing pulmonary rehabilitation for people with non‐COPD diagnoses

Pulmonary rehabilitation is a core aspect in the management of patients with chronic respiratory diseases. This paper describes a practical approach to establishing pulmonary rehabilitation for patients with non‐COPD diagnoses using examples from the interstitial lung disease (ILD), pulmonary hypertension (PH), bronchiectasis and lung cancer patient populations. Aspects of pulmonary rehabilitation, including the rationale, patient selection, setting of programmes, patient assessment and training components (both exercise and non‐exercise aspects), are discussed for these patient groups. Whilst there are many similarities in the rationale and application of pulmonary rehabilitation across these non‐COPD populations, there are also many subtle differences, which are discussed in detail in this paper. With consideration of these factors, pulmonary rehabilitation programmes can be adapted to facilitate the inclusion of respiratory patients with non‐COPD diagnoses.     

Smoking-related diseases: the importance of COPD.

SETTING: Smoking plays a major role in a variety of diseases. Despite a strong relationship between smoking and chronic obstructive pulmonary disease (COPD), cardiovascular disease and lung cancer attract greater attention. OBJECTIVE: To assess the burden of illness produced by smoking. DESIGN: Smoking-attributable risk (SAR) and smoking-attributable disease burden (mortality, morbidity, and cost) were estimated for four conditions: COPD, coronary heart disease (CHD), lung cancer, and stroke. RESULTS: Smoking-attributable deaths worldwide were: 1772 580 COPD, 1277 000 CHD, 822 150 lung cancer, and 788 580 stroke. Smoking-attributable disability adjusted life years (DALYs) were: 47 232 000 COPD, 18 106 000 CHD, and 11 052 000 stroke. US smokingattributable costs were: dollar 26.0 billion CHD, dollar 24.9 billion COPD, and dollar 9.0 billion stroke. US smoking-attributable annual hospitalizations were: 520 000 COPD, 460 000 CHD, and 183 000 stroke. CONCLUSIONS: Cardiovascular disease and lung cancer rank high in absolute estimates of disease burden. However, COPD has a more substantial smoking-attributable disease burden. COPD deserves more attention in the health care sector. Smoking cessation programs, pharmacological interruption of the pathophysiology of smoking-related COPD, and effective management of COPD should be key targets of intervention and research.     

Update on the management of COPD

COPD is highly prevalent and will continue to be an increasing cause of morbidity and mortality worldwide. COPD is now viewed under a new paradigm as preventable and treatable. In addition, it has become accepted that COPD is not solely a pulmonary disease but also one with important measurable systemic consequences. Patients with COPD have to be comprehensively evaluated to determine the extent of disease so that therapy can be adequately individualized. We now know that smoking cessation, oxygen for hypoxemic patients, lung reduction surgery for selected patients with emphysema, and noninvasive ventilation during severe exacerbations have an impact on mortality. The completion of well-planned pharmacologic trials have shown the importance of decreasing resting and dynamic hyperinflation on patient-centered outcomes and the possible impact on mortality and rate of decline of lung function. In addition, therapy with pulmonary rehabilitation and lung transplantation improve patient-centered outcomes such as health-related quality of life, dyspnea, and exercise capacity. Rational use of single or multiple therapeutic modalities in combination have an impact on exacerbations and hospitalizations. This monograph presents an integrated approach to patients with COPD and updates their management incorporating the recent advances in the field. The future for patients with COPD is bright as primary and secondary prevention of smoking becomes more effective and air quality improves. In addition, current research will unravel the pathogenesis, clinical, and phenotypic manifestations of COPD, thus providing exciting therapeutic targets. Ultimately, the advent of newer and more effective therapies will lead to a decline in the contribution of this disease to poor world health.     

Modifying the Course of Chronic Obstructive Pulmonary Disease: Looking Beyond the FEV1

Abstract

COPD is defined by airflow limitation that is not fully reversible and is usually progressive. Thus, airflow obstruction (measured as FEV₁) has traditionally been used as the benchmark defining disease modification with therapy. However, COPD exacerbations and extrapulmonary effects are common and burdensome and generally become more prominent as the disease progresses. Therefore, disease progression should be broader than FEV₁ alone. Interventions that reduce the frequency or severity of exacerbations or ameliorate extrapulmonary effects should also be considered disease modifiers. A narrow focus on FEV₁ will fail to capture all the beneficial effects of therapy on disease modification. Although smoking cessation has been unequivocally demonstrated to slow the rate of FEV₁ decline, inhaled corticosteroid–long-acting bronchodilator therapy may also have modest effects according to post hoc analysis. Maintenance pharmacotherapy with inhaled long-acting anti-muscarinic or ®-adrenergic agents or combined ®-adrenergic—inhaled corticosteroid reduces symptoms, improves lung function, reduces the frequency of exacerbations, and improves exercise capacity and HRQL. Pulmonary rehabilitation reduces symptom burden, increases exercise capacity, improves HRQL, and reduces health care utilization, probably through reducing the severity of exacerbations. Smoking cessation, lung volume reduction surgery, inhaled maintenance pharmacotherapy, and pulmonary rehabilitation administered in the post-exacerbation period may reduce mortality in COPD. These improvements over multiple outcome areas and over relatively long durations suggest that disease modification is indeed possible with existing therapies for COPD. Therefore, therapeutic nihilism in COPD is no longer warranted.     

神经生长因子在慢性阻塞性肺疾病大鼠血、肺组织、支气管灌洗液中的表达

目的建立单纯香烟刺激诱导的慢性阻塞性肺疾病(COPD)大鼠模型,并观察神经生长因子(NGF)在香烟刺激COPD大鼠、戒烟1个月COPD大鼠中血、肺组织、支气管灌洗液中的表达变化。方法24只雄性SD大鼠,随机分为正常对照组、COPD组、戒烟1个月COPD组,采用6个月单纯香烟刺激建立COPD大鼠模型。通过观察肺组织病理变化、检测大鼠肺功能、对支气管肺泡灌洗液行分类计数评估COPD动物模型。并测定3组血、肺组织、支气管肺泡灌洗液中NGF蛋白、NGF mRNA表达。结果COPD组、戒烟1个月COPD组大鼠肺组织病理均显示肺气肿形成明显,相比正常对照组,肺顺应性和每分钟通气量均明显下降,气道阻力明显升高(均P<0.05)。COPD组、戒烟1个月COPD组支气管肺泡灌洗液的巨噬细胞总数显著多于正常对照组(P<0.05),但这两组之间差异无统计学意义(P>0.05)。3组血中NGF表达差异无统计学意义(P>0.05),COPD组、戒烟个1月COPD组肺组织、支气管肺泡灌洗液中NGF蛋白、NGF mRNA表达较正常对照组明显升高(均P<0.05),但这两组之间差异无统计学意义(P>0.05)。结论通过6个月单纯香烟刺激成功建立COPD大鼠模型,并且戒烟1个月后,停止造模干预,COPD病变仍持续存在。NGF持续性参与COPD的发生发展,即使戒烟,NGF仍参与肺局部炎症反应。     

Cessation in the use of tobacco – pharmacologic and non‐pharmacologic routines in patients

Introduction: Approximately one‐third of the adult population in industrial countries and 70% in several Asian countries are daily smokers. Tobacco is now regarded as the world's leading cause of death. Approximately two‐thirds of lifelong smokers eventually die because of smoking. Smoking cessation is the most effective action to reduce mortality in patients with chronic obstructive pulmonary disease (COPD) and coronary heart disease. Objective: The aim of this study was to determine the effectiveness of smoking cessation programmes in patients with smoking‐related disorders. Methods: Medline was searched for studies of interventions for smoking cessation in patients. Results: In patients with cardiovascular diseases and COPD, smoking cessation programmes with behavioural support over several months significantly increase quit rates. The intensity of the programmes seems to be proportional to the effect. A long follow‐up period is probably the most important element in the programmes. Even the most intensive programmes are very cost‐effective in terms of cost per life‐year gained. Effective programmes can be delivered by personnel without special education in smoking cessation using simple intervention principles. Conclusions: In patients with smoking‐related disorders, smoking cessation interventions with several months of follow‐up are effective and easily applicable in clinical practice. Wider implementation of such programmes would be a cost‐effective way of saving lives. Please cite this paper as: Quist‐Paulsen P. Cessation in the use of tobacco – pharmacologic and non‐pharmacologic routines in patients. The Clinical Respiratory Journal 2008; 2: 4–10.     

Chronic obstructive pulmonary disease: from unjustified nihilism to evidence-based optimism

Chronic obstructive pulmonary disease (COPD) has been associated with a nihilistic attitude. On the basis of current evidence, this nihilistic attitude is totally unjustified. The disease must be viewed through the lens of a new paradigm: one that accepts COPD as not only a pulmonary disease but also as one with important measurable systemic consequences. COPD is not only preventable but also treatable. Smoking cessation, oxygen for hypoxemic patients, lung reduction surgery for selected patients with emphysema, and noninvasive ventilation during severe exacerbations have all been shown to impact on mortality. In addition, pulmonary rehabilitation, pharmacologic therapy, and lung transplantation improve patient-centered outcomes such as health-related quality of life, dyspnea, exercise capacity, and even exacerbations and hospitalizations. Caregivers should familiarize themselves with the multiple complementary forms of treatment and individualize therapy to the particular situation of each patient. The future for patients with this disease is bright as its pathogenesis and clinical and phenotypic manifestations are unraveled. The advent of newer and more effective therapies will lead to a decline in the contribution of this disease to poor world health.     

Multidisciplinary care of the patient with chronic obstructive pulmonary disease

The National Emphysema Treatment Trial used a multidisciplinary team approach to implement the maximum medical care protocol, including adjustment of medications and outpatient pulmonary rehabilitation for all patients and nutritional and psychological counseling as needed. This article discusses the benefits of such an approach in the care of the patient with chronic obstructive pulmonary disease. Team member roles complement each other and contribute to the goal of providing the highest-quality medical care. The primary focus of the team is to reinforce the medical plan and to provide patient education and support. This article reviews the elements of the initial patient assessment and the functional and nutritional assessment. Patient education focuses on medication use, recognition and management of chronic obstructive pulmonary disease exacerbation symptoms, smoking cessation, advance directives, and travel.     

Pharmacological treatment of chronic obstructive pulmonary disease

None of the drugs currently available for chronic obstructive pulmonary disease (COPD) are able to reduce the progressive decline in lung function which is the hallmark of this disease. Smoking cessation is the only intervention that has proved effective. The current pharmacological treatment of COPD is symptomatic and is mainly based on bronchodilators, such as selective β₂-adrenergic agonists (short- and long-acting), anticholinergics, theophylline, or a combination of these drugs. Glucocorticoids are not generally recommended for patients with stable mild to moderate COPD due to their lack of efficacy, side effects, and high costs. However, glucocorticoids are recommended for severe COPD and frequent exacerbations of COPD. New pharmacological strategies for COPD need to be developed because the current treatment is inadequate.     

慢性肺病住院患者戒烟成功影响因素研究

目的研究住院慢性肺病患者相对于其他住院患者吸烟行为特征的特点及戒烟成功相关影响因素。方法在2014年6月至2015年6期间肺病科连续的慢性肺病住院患者,配对抽取同期于其他科室住院的非慢性肺病患者,填写调查表进行数据分析。结果本调查中吸烟患者均以控制不住烟瘾为继续吸烟主要原因;在慢性肺病患者分组中主要以经济原因为主要戒烟原因,而在非慢性肺病分组中主要以防未病为主;吸烟人群中,大家对戒烟行为的认知是一致的,在戒烟过程中不仅取决于本人的态度是否坚决,还与其对整个过程的信心及外界环境息息相关;在戒烟过程中,戒烟持续时间在很大程度上决定戒烟是否成功。多因素Logistic回归分析发现年龄、月经济收入、饮酒、是否患有其他慢性病、自觉健康状况、尼古丁依赖均影响是否戒烟成功。结论目前慢性肺病患者戒烟能够成功很大程度上是因为随着年龄增大及疾病的进行性加重及经济条件不佳所"被迫"成功的,提示我们在今后的戒烟治疗中,应早期干预,变被动戒烟为主动戒烟。     

Definition, epidemiology and natural history of COPD.

Chronic obstructive pulmonary disease (COPD) is the fifth cause of morbidity and mortality in the developed world and represents a substantial economic and social burden. Patients experience a progressive deterioration up to end-stage COPD, characterised by very severe airflow limitation, severely limited and declining performance status with chronic respiratory failure, advanced age, multiple comorbidities and severe systemic manifestations/complications. COPD is frequently underdiagnosed and under-treated. Today, COPD develops earlier in life and is less gender specific. Tobacco smoking is the major risk factor for COPD, followed by occupation and air pollution. Severe deficiency for alpha(1)-antitrypsin is rare; several phenotypes are being associated with elevated risk for COPD in the presence of risk factor exposure. Any patient presenting with cough, sputum production or dyspnoea should be assessed by standardised spirometry. Continued exposure to noxious agents promotes a more rapid decline in lung function and increases the risk for repeated exacerbations, eventually leading to end-stage disease. Without major efforts in prevention, there will be an increasing proportion of end-stage patients who can live longer through long-term oxygen therapy and assisted ventilation, but with elevated suffering and huge costs. Smoking prevention and smoking cessation are the most important epidemiological measurements to counteract chronic obstructive pulmonary disease epidemics.     

Low awareness of COPD among physicians

Introduction: Early identification of patients with chronic obstructive pulmonary disease (COPD) in the health care system followed by successful smoking cessation may prevent rapid lung function deterioration, development of severe COPD and respiratory failure. Objectives: The aim of this study was to determine the frequency of under‐diagnosed chronic obstructive lung diseases among current smokers. Materials and methods: The under‐diagnosis of COPD among smokers was determined in subjects who participated in a screening procedure aimed at recruiting COPD patients for a smoking cessation programme. In order to identify current smokers, a questionnaire was sent out to persons who had been on sick leave for various reasons certified by a physician for more than 2 weeks. Subjects who stated that they currently smoked more than eight cigarettes per day were invited to perform a lung function test. Results: A total of 3887 subjects performed spirometry, i.e. forced expiratory volume in 1 s and forced expirations, and among these, 674 (17.3%) had COPD according to the European Respiratory Society (ERS) consensus guidelines. Of those, 103 (17.3%) had physician‐diagnosed COPD. Productive cough was reported by 16.6% of the COPD subjects. Despite the fact that smokers were on sick leave certified by a physician, more than 80% of those with COPD had no previous diagnosis. As the COPD diagnosis cannot be based on reported symptoms, a spirometry on persons at risk must be performed. Conclusion: The awareness of COPD among primary care physicians has to increase and smokers above the age of 40, with and without respiratory symptoms, have to undergo spirometry if it is regarded important to establish the COPD diagnosis at an early stage. Please cite this paper as: Sundblad B‐M, Larsson K and Nathell L. Low awareness of COPD among physicians. The Clinical Respiratory Journal 2008; 2: 11–16.     

Chronic obstructive pulmonary disease megatrials: taking the results into office practice

Primary care specialists provide first-line care of chronic obstructive pulmonary disease (COPD), characterized by progressive, partially reversible airflow limitation induced mainly by smoking. Spirometry and questionnaires are important for COPD diagnosis, staging and prognosis. Smoking cessation, immunizations, pulmonary rehabilitation and self-management action plans comprise nonpharmacologic COPD management. The Understanding Potential Long-term Impacts on Function with Tiotropium (UPLIFT?) and Towards a Revolution in COPD Health (TORCH) megatrials provide evidence for maintenance pharmacotherapy to reduce exacerbations and improve patient symptoms and health-related quality of life. Although the primary outcomes--lung function decline (UPLIFT?) and mortality (TORCH)--were negative, long-acting bronchodilators in both trials reduced exacerbation rates and improved health status. Tiotropium added to usual care (in UPLIFT?) and salmeterol/fluticasone therapy (in TORCH) improved key patient-centered outcomes with no significant mortality risk or excess in serious cardiac adverse events associated with the study drugs. These results provide strong evidence of efficacy and acceptable safety profiles of maintenance pharmacotherapies in patient-centered outcomes and support combination drug regimens in patients with moderate to very severe COPD.     

Effect of 1-year smoking cessation on airway inflammation in COPD and asymptomatic smokers.

Smoking cessation is the only treatment in patients with chronic obstructive pulmonary disease (COPD) effective in slowing down disease progression. Its effect on airway inflammation in COPD is unknown, although cross-sectional studies suggest ongoing inflammation in ex-smokers. In order to elucidate the effect of smoking cessation on airway inflammation, 28 smokers with COPD (mean age: 55 yrs; forced expiratory volume in one second: 71% predicted) and 25 asymptomatic smokers with normal lung function (aged 50 yrs) were included in a 1-yr smoking cessation programme. Effects of smoking cessation on airway inflammation were investigated in bronchial biopsies (baseline, 12 months) and sputum samples (baseline, 2, 6 and 12 months). In the 12 candidates with COPD who successfully ceased smoking, airway inflammation persisted in bronchial biopsies, while the number of sputum neutrophils, lymphocytes, interleukin (IL)-8 and eosinophilic-cationic-protein levels significantly increased at 12 months. In the 16 asymptomatic smokers who successfully quitted, inflammation significantly reduced (i.e. number of sputum macrophages, percentage of eosinophils and IL-8 levels) or did not change. The current authors suggest that the observed persistent airway inflammation in patients with chronic obstructive pulmonary disease is related to repair of tissue damage in the airways. It remains to be elucidated whether this reflects a beneficial or detrimental effect.     

Pathogenesis of COPD. Part III. Inflammation in COPD.

Chronic obstructive pulmonary disease (COPD) is mostly caused by cigarette smoking and affects up to 25% of smokers. Air pollution and occupational exposure to dust and fumes can also induce COPD. COPD is characterised by airflow limitation that is not fully reversible and chronic inflammation of the lung. Most patients with COPD also have evidence of tissue remodelling in the smaller airways. How the different pathological features are linked remains unknown. The inflammation of the COPD lung is initially caused by cigarette smoke and the increased infiltration of immune cells into the lung, but it is not clear why the inflammation persists after smoking cessation, while other pathologies partly reverse. Furthermore, anti-inflammatory treatments are not very successful and only control the symptoms but do not cure the disease. Animal models suggest that the imbalance of proteases and antiproteases is central to the major pathologies in the COPD lung. However, this hypothesis was never fully confirmed in humans and may only explain the degenerative stage of the disease, emphysema. The role of tissue-forming cells in the pathogenesis of COPD has not been adequately studied and indicates a deregulated synthesis of growth factors and cytokines in COPD. Finally, recent studies indicate that alpha-1-antitrypsin activity plays a role in all forms of COPD.