Epidemiology of chronic obstructive pulmonary disease (COPD)

Chronic Obstructive Pulmonary Disease (COPD) is one of the leading causes of morbidity and mortality in the industrialized and the developing countries. During 1997, COPD has been estimated to be the number four cause of death after cardiovascular diseases, tumors and cerebrovascular diseases in the United States. In 2020 COPD will probably become the third leading cause of death all over the world, following the trend of increasing prevalence of lung cancer. The impact of this respiratory disease worldwide is expected to increase with a heavy economic burden on individuals and society. In the United States direct and indirect costs of COPD were estimated at about USD24 billion in 1993. Unfortunately, there are few data on health-care utilization despite the great interest in COPD among researchers. As all chronic diseases, the prevalence of COPD is strongly associated with age. Data collected in a general population sample (living in Italy) showed a progressive increase of the prevalence of chronic bronchitis and emphysema with age, both in males and in females. COPD is determined by the action of a number of various risk factors either singly or interacting among themselves in a synergistic way. Among these, the most important is cigarette smoking, ranking at the first level for developing chronic bronchitis and emphysema. Also air pollution and some occupational exposures represent risks for developing COPD. Many epidemiological studies have indicated an association between the prevalence of chronic bronchitis and a low socioeconomic status. Furthermore, in the etiology of COPD we must consider endogenous risk factors such as gender, genetic features, presence of respiratory troubles in childhood, and family history. To date, epidemiologic studies have been of great importance for the characterization of the disease at a population level, indicating possible causes and assessing its impact on the individual and on society as a whole. Unfortunately, international standards for the diagnosis of COPD are lacking, which complicates the organization of appropriate epidemiological surveys.     

Pathogenesis of the chronic obstructive pulmonary disease (COPD)

An inflammation in the bronchial wall is usually present already in an early stage of the disease. An inflammatory infiltration cause predominantly mononuclear cells in the mucous membrane and neutrophiles in the phlegm produced by airways. Also eosinophiles can participate in the inflammation. Lymphocytes distribution is different from asthma because there is mainly submucosa infiltrated in COPD. Metaplasia of goblet cells appears. Chronic bronchial obstruction characterizing COPD is induced by conjunction of small airways disease (obstructive bronchiolitis) and a destruction of pulmonary parenchyma (emphysema) which both contribute to an impairment and differ form person to person. Chronic inflammation is a cause of remodeling and narrowing of small airways. Destruction of pulmonary parenchyma and the inflammation cause loss of alveolar connection with small airways and elastic pulmonary stress decreases. Two theories try to explain COPD--a theory of imbalance between proteinases and antiproteinases and a theory of oxidation stress.     

吸入噻托溴铵对老年慢性阻塞性肺病患者肺功能与气道炎症的影响

目的评价噻托溴铵对稳定期慢性阻塞性肺病(COPD)患者肺功能和气道炎症的影响。方法 76例COPD患者随机分成吸入噻托溴铵药物组和不吸入对照组,在治疗前、治疗后第4周和第8周分别进行圣乔治生活质量问卷(SGRQ)、肺功能检查、6分钟步行距离(6 MWD)和诱导痰检测。结果 SGRQ评分中,药物组在治疗后4、8 w分别下降(7.8±0.5)分和(12.6±0.7)分,与治疗前和对照组比较均有统计学差异。FEV1、FVC、FEV1/FVC治疗前后差异无统计学意义;但药物组的IC在治疗4、8 w后上升明显,与治疗前和对照组比较均有统计学差异。6MWD中,药物组在治疗后4、8 w分别为(332.1±21.6)m和(365.3±23.5)m,与治疗前和对照组比较均有统计学差异。药物组的中性粒细胞比例在治疗4、8 w均下降,分别为(47.7±3.2)%和(42.3±2.8)%;而巨噬细胞比例相应地上升,分别为(48.3±3.7)%和(54.2±5.2)%,与治疗前和对照组比较均有统计学差异。IC、6 MWD、诱导痰中性粒细胞百分比与SGRQ评分相关性好,优于FEV1%、FVC、FEV1/FVC。结论老年COPD患者吸入噻托溴铵后呼吸困难症状减轻而常规肺功能指标无明显变化,深吸气量IC改善和诱导痰中性粒细胞比例下降明显,且与圣乔治问卷评分相关性高,不失为反映呼吸困难症状的客观指标。     

Mental disorders in chronic obstructive pulmonary disease (COPD)

Recent research using questionnaire measures has demonstrated high prevalence rates of mental disorders in chronic obstructive pulmonary disease (COPD). However, clinical interviews and clinical rather than healthy control groups have rarely been employed. The aim of the present study was to assess mental disorders in patients with COPD with advanced methodology, to identify moderating factors explaining mental co-morbidities and to compare results with a clinical control group without COPD. A standardized clinical interview (F-DIPS) and a range of questionnaires were used to assess mental disorders, perceived physical symptoms and cognitions in 20 hospitalized patients with mild-to-moderate COPD (mean FEV(1)/VC (%)=61.3). Results were compared with a hospitalized clinical control group without pulmonary dysfunction (CCG; N=20). Results showed that 55% of patients with COPD received a diagnosis of a mental disorder compared to 30% of CCG patients. All principal mental diagnoses in the COPD group were anxiety disorders (especially Panic Disorder with Agoraphobia), while CCG patients received a wider range of diagnoses (anxiety, pain, alcohol abuse). There was no systematic association between anxiety levels and respiratory function in the whole COPD group, but a positive correlation between anxiety levels and perceived physical symptoms (p<0.001) as well as negative cognitions (p<0.001 and p<0.05, respectively) for COPD patients with anxiety disorder (N=11). The present results confirm the high prevalence rate of anxiety in patients with COPD and suggest further that anxiety in COPD patients may be mediated by cognitive processes. These findings are discussed in terms of their implications for treatment.     

Tiotropium for the treatment of stable chronic obstructive pulmonary disease: a systematic review with meta-analysis

BACKGROUND: Current guidelines recommend the use of inhaled tiotropium in patients with stable chronic obstructive pulmonary disease (COPD). However, this statement is based on a relatively small number of randomized controlled trials (RCTs) and related systematic reviews. This review was undertaken to incorporate the more recent evidence available about the effectiveness of tiotropium bromide compared with placebo, iptratropium bromide or long-acting beta-agonists (LABAs), for the treatment of stable COPD patients. DATA SOURCE: Medline, EMBASE, CINAHL, and the Cochrane Controlled Trials Register (to February 2006) were searched to identify all published RCTs. We also searched bibliographies of relevant articles. RESULTS: Data from 13 RCT (6078 subjects, 80% male) showed that tiotropium reduced COPD-related exacerbations (OR=0.76; 95% CI: 0.68-0.87) and hospital admissions (OR=0.59; 95% CI: 0.47-0.73) compared with placebo. Also, tiotropium showed statistically significant improvement in lung function, including trough, average, and peak FEV(1) and FVC from baseline, compared with placebo and ipratropium. The administration of inhaled tiotropium lead to 30% reduction in COPD-related admissions (OR= 0.67; 95% CI: 0.46-0.98) compared with LABAs. Finally, increases in FEV(1) and FVC from baseline were significantly larger with tiotropium than with LABAs. CONCLUSIONS: This review clearly supports the beneficial effects of the use of tiotropium in stable moderate-to-severe COPD patients, and increases the evidence in favor of the superiority of tiotropium on LABAs.     

The role of indacaterol for chronic obstructive pulmonary disease (COPD)

Indacaterol is the first long-acting β2-agonist (LABAs) approved for the treatment of chronic obstructive pulmonary disease (COPD) that allows for once-daily (OD) administration. It is rapidly acting, with an onset of action in 5 minutes, like salbutamol and formoterol but with a sustained bronchodilator effect, that last for 24 hours, like tiotropium. In long-term clinical studies (12 weeks to 1 year) in patients with moderate to severe COPD, OD indacaterol 150 or 300 μg improved lung function (primary endpoint) significantly more than placebo, and improvements were significantly greater than twice-daily formoterol 12 μg or salmeterol 50 μg, and noninferior to OD tiotropium bromide 18 μg. Indacaterol was well tolerated at all doses and with a good overall safety profile. Cost-utility analyses show that indacaterol 150 μg has lower total costs and better outcomes than tiotropium and salmeterol. These findings suggest that indacaterol can be considered a first choice drug in the treatment of the patient with mild/moderate stable COPD. However, in people with COPD who remain symptomatic on treatment with indacaterol, adding a long-acting muscarinic antagonist (LAMA) is the preferable option. In any case, it is advisable to combine indacaterol with a OD inhaled corticosteroid (ICS), such as mometasone furoate or ciclesonide, in patients with low FEV1, and, in those patients who have many symptoms and a high risk of exacerbations, to combine it with a LAMA and a OD ICS.KEY WORDS : Long-acting β2-agonists (LABAs), indacaterol, chronic obstructive pulmonary disease (COPD), combination therapy     

噻托溴铵治疗慢性阻塞性肺疾病作用机制研究进展

噻托溴铵是一种新型长效抗胆碱类药物,是目前第一个能每日用药1次的吸人性药物,能高度选择性作用于胆碱M1和M3受体,表现出强大的支气管扩张作用,吸入一次疗效持续24 h以上.临床实验结果表明该药对中、重度慢性阻塞性肺疾病具有良好疗效,与其他常用抗胆碱能药物和β2受体激动剂相比较,噻托溴铵可显著改善肺功能、减少急性发作和改善生命质量,耐受性和安全性较好,主要不良反应为口干.     

Biomarkers of progression of chronic obstructive pulmonary disease (COPD)

Disease progression of chronic obstructive pulmonary disease (COPD) is variable, with some patients having a relatively stable course, while others suffer relentless progression leading to severe breathlessness, frequent acute exacerbations of COPD (AECOPD), respiratory failure and death. Radiological markers such as CT emphysema index, bronchiectasis and coronary artery calcification (CAC) have been linked with increased mortality in COPD patients. Molecular changes in lung tissue reflect alterations in lung pathology that occur with disease progression; however, lung tissue is not routinely accessible. Cell counts (including neutrophils) and mediators in induced sputum have been associated with lung function and risk of exacerbations. Examples of peripheral blood biological markers (biomarkers) include those associated with lung function (reduced CC-16), emphysema severity (increased adiponectin, reduced sRAGE), exacerbations and mortality [increased CRP, fibrinogen, leukocyte count, IL-6, IL-8, and tumor necrosis factor α (TNF-α)] including increased YKL-40 with mortality. Emerging approaches to discovering markers of gene-environment interaction include exhaled breath analysis [volatile organic compounds (VOCs), exhaled breath condensate], cellular and systemic responses to exposure to air pollution, alterations in the lung microbiome, and biomarkers of lung ageing such as telomere length shortening and reduced levels of sirtuins. Overcoming methodological challenges in sampling and quality control will enable more robust yet easily accessible biomarkers to be developed and qualified, in order to optimise personalised medicine in patients with COPD.     

Treatment principle of the chronic obstructive pulmonary disease (COPD) exacerbation

COPD is often accompanied with acute symptoms exacerbations. Patients in Ist stage: slide grade of COPD and IInd stage: middle grade of COPD suffer exacerbations accompanied with increased dyspnoea often together with increased cough and increased production of sputum. Patients in IIIrd stage (serious) and IVth stage (very serious) experience during exacerbations development of respiration insufficiency or its worsening and thus are usually treated in hospital. The most frequent causes of exacerbations are tracheobronchial tree infections and air pollution. The cause of approximately one third of serious exacerbations is not disclosed. Conditions which can resemble acute exacerbation are pneumonia, congestive heart failure, pneumothorax, pleural exudation, pulmonary embolism, and arrhythmia. Exacerbation treatment is symptomatic. Obstruction symptoms are treated with bronchodilatants and corticosteroids administration, hypoxemia with oxygen administration and signs of bacterial infection with antibiotics.     

One hundred years of chronic obstructive pulmonary disease (COPD)

Chronic obstructive pulmonary disease (COPD) is an increasing health problem and one of the leading causes of morbidity and mortality worldwide, but knowledge about its pathogenesis has increased substantially in recent years. The disease results from interaction between individual risk factors (like enzymatic deficiencies) and environmental exposures to noxious agents, like cigarette smoking, occupational dusts, air pollution and infections in childhood. The main mechanisms that may contribute to airflow limitation in COPD are fixed narrowing of small airways, emphysema and luminal obstruction with mucus secretions. COPD is characterised by a chronic inflammatory process in the pulmonary tissue, with a pattern different from bronchial asthma, associated with extrapulmonary effects and is considered now a complex, systemic disease. Optimal therapeutic targeting of COPD depends on a clear understanding of the precise mechanisms of these complex processes and on early and correct evaluation of disease severity. A combination of pharmacological and non-pharmacological approaches is used to treat COPD. Bronchodilators are the mainstay of COPD treatment and can be combined with inhaled corticosteroids for greater efficacy and fewer side effects. The use of LTOT for hypoxemic patients has resulted in increased survival, and expanded drug therapy options have effectively improved dyspnoea and quality of life. Recent studies have documented the benefits of pulmonary rehabilitation. In addition, non-invasive mechanical ventilation offers new alternatives for patients with acute or chronic failure.     

抗胆碱能药物治疗慢性阻塞性肺疾病作用的新进展

近年来,有关COPD相关药物的临床研究逐渐增多.支气管舒张剂是目前治疗COPD的基本药物,其中抗胆碱能药物对COPD的治疗作用是研究的热点之一.