Schlesinger Cory, Koss Michael N
Richmond, Virginia, USA.
Treat Respir Med. 2006;5(3):193-206. doi: 10.2165/00151829-200605030-00005.
In this comprehensive review, two very closely related interstitial pneumonias are discussed: the cryptogenic form of organizing pneumonia (COP); and secondary forms of organizing pneumonia (OP), which occur in association with identifiable medical conditions. Some newer and lesser known of these associated conditions are described, most importantly post-radiation OP.Rapidly progressive, corticosteroid-resistant and poor prognostic forms of OP have been described. These types purportedly occur more frequently in secondary OP. However, OPs frequently coexist with other interstitial pneumonias, especially when associated with connective tissue diseases. Therefore, tissue sampling error or an incorrect morphologic diagnosis can be the basis for the occurrence of clinically aggressive OPs. By using the 2002 American Thoracic Society/European Respiratory Society diagnostic criteria, some pre-2002 cases reported as OP would be re-classified today.Although COP is considered to have a good prognosis and to be corticosteroid responsive, approximately 70% of patients, treated with corticosteroids, relapse even during initial treatment. Multiple and late relapses occur in about one-third of the patients. We performed a meta-analysis of second-line treatment options for corticosteroid-refractory forms of OP. Three alternative nonsteroid agents - cyclophosphamide, azathioprine, and cyclosporin - have been used in combination with corticosteroids. On careful review, in a number of cases reported as secondary OP, other histologic interstitial patterns besides OP were described. The need for second-line therapy in these patients might have been dictated by the non-organizing pneumonic component. Most of the scant number of reports come from outside the US. World experience with these is limited, but good clinical outcomes have been noted, even in patients with interstitial patterns in addition to OP.The initiation of the OP tissue response in the bronchiolar and sub-bronchiolar location may be due to the presence of bronchiolar-associated lymphoid tissue found at the bifurcations of the bronchioles. Inhaled antigens stimulate granulocyte colony stimulating factor-mediated airway inflammation, followed later by CD44-mediated clearance. Repair requires intrabronchiolar formation of granulation tissue and a favorable ratio of matrix metalloproteinase to tissue inhibitors of metalloproteinase (MMP : TIMP) within the stroma. This reparative milieu allows extracellular matrix degradation and re-synthesis to occur. MMP-expressing fibroblasts then phagocytose the collagen fibrils and microfibrils produced earlier in repair, reversing the initial fibrosis.
在这篇综述中，讨论了两种密切相关的间质性肺炎：隐源性机化性肺炎（COP）；以及与可识别的医疗状况相关的继发性机化性肺炎（OP）。文中描述了一些较新的、不太为人所知的相关状况，其中最重要的是放射性肺炎后的OP。已经描述了快速进展型、对皮质类固醇耐药型以及预后较差的OP类型。据称这些类型在继发性OP中更常见。然而，OP常与其他间质性肺炎共存，尤其是与结缔组织病相关时。因此，组织采样误差或形态学诊断错误可能是临床上侵袭性OP发生的原因。采用2002年美国胸科学会/欧洲呼吸学会的诊断标准后，一些2002年以前报告为OP的病例如今会被重新分类。尽管COP被认为预后良好且对皮质类固醇有反应，但约70%接受皮质类固醇治疗的患者即使在初始治疗期间也会复发。约三分之一的患者会出现多次复发和晚期复发。我们对皮质类固醇难治型OP的二线治疗方案进行了荟萃分析。三种替代的非甾体药物——环磷酰胺、硫唑嘌呤和环孢素——已与皮质类固醇联合使用。仔细审查后发现，在一些报告为继发性OP的病例中，除了OP外还描述了其他组织学间质性模式。这些患者对二线治疗的需求可能是由非机化性肺炎成分决定的。少数报告大多来自美国以外地区。世界各地对这些药物的经验有限，但即使是除OP外还有间质性模式的患者，也已观察到良好的临床结果。OP组织反应在细支气管和细支气管周围位置的起始可能是由于在细支气管分支处发现的支气管相关淋巴组织的存在。吸入抗原刺激粒细胞集落刺激因子介导的气道炎症，随后是CD44介导的清除。修复需要细支气管内肉芽组织的形成以及基质中基质金属蛋白酶与金属蛋白酶组织抑制剂的良好比例（MMP : TIMP）。这种修复环境允许细胞外基质降解和重新合成发生。表达MMP的成纤维细胞随后吞噬修复早期产生的胶原纤维和微纤维，逆转初始纤维化。
