Hogg James C
James Hogg iCAPTURE Centre for Cardiovascular and Pulmonary Research, University of British Columbia and St Paul's Hospital, Room 166-1081, Burrard Street, Vancouver, BC V6Z 1Y6, Canada.
Lancet. 2004;364(9435):709-21. doi: 10.1016/S0140-6736(04)16900-6.
The airflow limitation that defines chronic obstructive pulmonary disease (COPD) is the result of a prolonged time constant for lung emptying, caused by increased resistance of the small conducting airways and increased compliance of the lung as a result of emphysematous destruction. These lesions are associated with a chronic innate and adaptive inflammatory immune response of the host to a lifetime exposure to inhaled toxic gases and particles. Processes contributing to obstruction in the small conducting airways include disruption of the epithelial barrier, interference with mucociliary clearance apparatus that results in accumulation of inflammatory mucous exudates in the small airway lumen, infiltration of the airway walls by inflammatory cells, and deposition of connective tissue in the airway wall. This remodelling and repair thickens the airway walls, reduces lumen calibre, and restricts the normal increase in calibre produced by lung inflation. Emphysematous lung destruction is associated with an infiltration of the same type of inflammatory cells found in the airways. The centrilobular pattern of emphysematous destruction is most closely associated with cigarette smoking, and although it is initially focused on respiratory bronchioles, separate lesions coalesce to destroy large volumes of lung tissue. The panacinar pattern of emphysema is characterised by a more even involvement of the acinus and is associated with alpha1 antitrypsin deficiency. The technology needed to diagnose and quantitate the individual small airway and emphysema phenotypes present in people with COPD is being developed, and should prove helpful in the assessment of therapeutic interventions designed to modify the progress of either phenotype.
定义慢性阻塞性肺疾病（COPD）的气流受限是肺排空时间常数延长的结果，这是由小气道传导阻力增加以及肺气肿破坏导致的肺顺应性增加所致。这些病变与宿主对终生吸入有毒气体和颗粒的慢性先天性和适应性炎症免疫反应有关。导致小气道传导阻塞的过程包括上皮屏障破坏、干扰黏液纤毛清除装置导致炎性黏液渗出物在小气道腔内积聚、炎性细胞浸润气道壁以及结缔组织在气道壁沉积。这种重塑和修复使气道壁增厚，管腔口径减小，并限制了肺膨胀时正常的口径增加。肺气肿性肺破坏与气道中发现的相同类型炎性细胞浸润有关。小叶中心型肺气肿破坏模式与吸烟关系最为密切，虽然它最初集中在呼吸性细支气管，但独立的病变融合会破坏大量肺组织。全小叶型肺气肿的特征是腺泡受累更为均匀，与α1抗胰蛋白酶缺乏有关。目前正在开发用于诊断和量化COPD患者个体小气道和肺气肿表型的技术，这将有助于评估旨在改变任一表型进展的治疗干预措施。
