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COPD 2016: COPD是一种加速衰老的疾病吗?威廉·麦克尼_英国爱丁堡大学

摘要

衰老与组织的进行性退化有关，这对重要器官的结构和功能有负面影响，是大多数慢性疾病最重要的已知危险因素之一。越来越明显的是，许多慢性炎症性疾病代表着衰老过程的加速。慢性肺病是多种日益常见的使人衰弱的疾病的一个重要组成部分，这些疾病是发病和死亡的主要原因，特别是在老年人中。肺正在老化，有人认为慢性阻塞性肺病(COPD)是肺部加速老化的一种情况，衰老可以在COPD与其许多肺外效应和合并症之间提供机械联系。本报告将介绍衰老的生理变化和机制，特别强调衰老对肺的影响，以及它们如何与COPD的发展及其主要肺外表现相关。随着年龄的增长，肺功能逐渐恶化，导致呼吸短促的风险增加，老年人慢性肺部疾病的患病率增加。年龄增长与FEV1逐渐减少约20ml /年有关，FEV1 / FVC比值减少，残余容积增加，总肺活量保留。肺功能的这些变化会导致低氧水平和由于胸壁顺应性降低、肺的弹性后坐力和肌肉力量降低而降低的二氧化碳清除能力。呼吸。这些肺功能随年龄的变化与COPD的变化相似。 Changes in pulmonary physiology with age are associated with structural changes in the lung involving alveolar enlargement, resulting in a decrease in the area available for gas exchange. However, this alveolar enlargement is different from that which occurs in COPD, since there is no destruction of the alveolar walls in the aging lung, as occurs in emphysema in COPD. Since the classic epidemiological studies of Fletcher and Peto, it has been considered that, in smokers of sensitive cigarettes who develop COPD, there is an accelerated decrease in lung function with the age of 50 to 100 ml of FEV1 / year. However, it is clear from recent studies that there is marked individual variability in the decline in FEV1 in subjects with COPD and that the development of the persistent airflow limitation characteristic of COPD is not always the result. result of an accelerated decrease in FEV1 but may be due, for example, to suboptimal lung growth during childhood. Thus, accelerated pulmonary aging may not be a pathogenic mechanism in all people with COPD. The incidence of COPD increases dramatically with age. The rate of newly diagnosed COPD in patients has increased from approximately 200 cases per 10,000 patients under the age of 45 to 1,200 cases per 10,000 patients aged 45 years or older. The greatest increase occurs in patients aged 65 to 74 years. Aging has been thought to result from the accumulation of genetic damage and DNA repair defects. Oxidative stress is recognized as a mechanism for DNA damage from premature aging in the free radical theory of aging. Increased oxidative stress is known to occur in the lungs of COPD patients, as shown by the increased presence of oxidative stress biomarkers. Smokers and COPD patients also have increased evidence of oxidative DNA damage in the lungs, as shown by an increase in the concentration of 8-hydroxy-2-deoxyguanosine in the peripheral lung and type II pneumocytes. In addition, there is an increase in the number of double stranded DNA breaks, as shown by an increase in foci of phosphorylated histone 2AX in pulmonary endothelial cells, which also express an increase in p16 (a marker of cellular senescence). There is also evidence of a failed repair of DNA strand rupture in COPD. This imbalance between oxygen-induced DNA damage and COPD repair can lead to increased cellular senescence, although the pathogenic link to DNA damage in COPD may be more linked to the increased risk of lung cancer. William MacNee

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