Pathogenesis of lung vasculitis

Vasculitides that affect the lung represent a diverse group of diseases with various systemic clinical manifestations, and include microscopic polyangiitis (MPA), granulomatosis with polyangiitis (GPA, formerly Wegener granulomatosis), Churg-Strauss syndrome (CSS), and anti-glomerular basement membrane (anti-GBM) disease (Goodpasture syndrome). The etiologies of these diseases remain largely unknown. Although the pathogenic mechanisms of each differ, these diseases overlap by the presence of anti-neutrophil cytoplasmic autoantibodies in the vast majority of patients with MPA and GPA, and a substantial minority of patients with CSS and anti-GBM disease. This article reviews the current understanding of the pathogenesis of these four disease entities.     

Pathology of pulmonary vasculitis

There are three major vasculitis syndromes that affect the lung: Wegener's granulomatosis (WG), Churg-Strauss syndrome (CSS), and microscopic polyangiitis (MPA). The pathology of pulmonary vasculitis is complicated because it requires correlation with clinical, laboratory, and radiological features; there is overlap in some histological features among the vasculitis syndromes; biopsies early in the course of disease or after therapy may show atypical or incomplete histological features; the differential diagnosis is complex and includes infection that should not be treated with corticosteriods or immunosupressive agents; and few pathologists have much experience with these cases. Major histological features of necrosis, granulomatous inflammation, and vasculitis characterize WG. The inflammatory consolidation consists of a mixture of neutrophils, lymphocytes, plasma cells, macrophages, giant cells, and eosinophils. Necrosis may take the form of neutrophil microabscesses or geographic necrosis. Granulomas may take several forms, including scattered or loose clusters of giant cells, palisading histiocytes or giant cells lining the border of geographic necrosis or microabscesses, and palisading microgranulomas. Sarcoidal granulomas are very rare. CSS may show eosinophilic pneumonia, allergic granulomas, and eosinophilic vasculitis. Asthmatic bronchitis may also be present. Biopsies from CSS patients are rare because this syndrome is usually diagnosed clinically. Microscopic polyangiitis demonstrates neutrophilic capillaritis and diffuse alveolar hemorrhage.     

肺血管炎的治疗

在免疫抑制疗法应用于临床之前,系统性血管炎患者的病死率达到75%,中位生存期仅为5个月。单独使用皮质激素治疗1年时能降低病死率。但随着皮质激素相关病死率和致残率的增加,5年病死率仍高达到50%。系统性血管炎治疗的突破性进展主要是环磷酰胺的应用,使5年病死率降低到12%。尽     

Pathogenesis of pulmonary infarction

Pulmonary embolism discovered at autopsy is still as prevalent as previously reported in the last three to four decades. Only a certain percentage of pulmonary emboli result in pulmonary infarction. Recently published studies have suggested that importance of the size of the occluded pulmonary artery in the occurrence of infarction. Our study of 45 autopsy subjects in which there were pulmonary emboli shows a 31 percent incidence of pulmonary artery branches of 3 mm in diameter or less, but emboli in larger arteries may show frequent extensions into their smaller distal branches without producing infarct. Pulmonary infarction also occurs more commonly in patients dying of cardiovascular or malignant diseases than it does in those dying of other diseases, and the combination of shock and congestive left heart failure appears to be the most significant hemodynamic risk factor in the development of pulmonary infarction. However, the increased risk of pulmonary infarction in patients with malignancy may not be accounted for by the existence of these two hemodynamic risk factors alone.     

Cutaneous vasculitis disclosing pulmonary tuberculosis

We report the case of a patient with leukocytoclasic vasculitis that disclosed active pulmonary tuberculosis. This patient had no signs of systemic vasculitis. The clinical course was favorable with anti-tuberculosis drugs alone. There has been no recurrence at 8 months.Vasculitis associated with tuberculosis is uncommon. The pathophysiological mechanism remains uncertain. No immunosuppressor treatment is needed and the vasculitis generally regresses with treatment of the infection.     

肺血管炎的临床与影像学特点解析

肺部血管炎包括原发性与继发性两大类.继发性血管炎包括感染性疾病、结缔组织病、恶性肿瘤和过敏性疾病所致肺血管炎.原发性血管炎的分类通常根据受累血管的大小分为大血管炎、中血管炎和小血管炎.肺部血管受累常见于原发性大血管炎[大动脉炎(Takayasu arteritis),巨细胞动脉炎(giant cell arteritis,GCA),白塞病(Behcetdisease)]和原发性抗中性粒细胞胞浆抗体(anti-neutrophil cytoplasmic antibody,ANCA)相关性小血管炎[肉芽肿性多血管炎(granulomatosis with polyangiitis,GPA),显微镜下多血管炎(microscopic polyangiitis),嗜酸性肉芽肿性多血管炎(eosinophilic granulomatosis with polyangiitis,EGPA)].原发性肺血管炎的影像学表现极具多样性,包括血管壁增厚、结节影、空洞、磨玻璃影和实变影等.原发性肺部小血管炎常导致弥漫性肺泡出血(diffuse alveolar hemorrhage,DAH).相比于胸片,胸部CT更能够显示肺血管炎的病变特征和侵及范围.肺部血管炎的诊断极具挑战性,需要通过患者的临床特征、影像学特点、实验室检查结果和组织病理学特征作出综合判断.     

慢性阻塞性肺疾病发病机制的新认识

慢性阻塞性肺疾病(chronic obstructive pulmonary diseas,COPD)是一种以气流受限为特征的疾病,患者气流受限不完全可逆,并呈进行性发展.吸烟以及大气污染是导致COPD发生的主要原因.有学者假设人体内本身就存在一套"肺结构维护体系"以维持肺内结构的完整,其中包括了抗氧化系统、抗蛋白酶系统和抗凋亡系统等的作用,除此之外研究还表明自身免疫系统与COPD发病也存在着关联.弄清这些系统的作用有助于更好地认识COPD的发病机制,也为临床治疗该疾病提供更充分的理论依据.     

Pathogenesis of chronic obstructive pulmonary disease

The current paradigm for the pathogenesis of chronic obstructive pulmonary disease is that chronic airflow limitation results from an abnormal inflammatory response to inhaled particles and gases in the lung. Airspace inflammation appears to be different in susceptible smokers and involves a predominance of CD8+ T lymphocytes, neutrophils, and macrophages. Studies have characterized inflammation in the peripheral airspaces in different stages of disease severity. Two other processes have received considerable research attention. The first is a protease-antiprotease imbalance, which has been linked to the pathogenesis of emphysema. However, the hypothesis of an increased protease burden associated with functional inhibition of antiproteases has been difficult to prove and is now considered an oversimplification. The second process, oxidative stress, has a role in many of the pathogenic processes of chronic obstructive pulmonary disease and may be one mechanism that enhances the inflammatory response. In addition, it has been proposed that the development of emphysema may involve alveolar cell loss through apoptosis. This mechanism may involve the vascular endothelial growth factor pathway and oxidative stress.     

Pathogenesis of chronic obstructive pulmonary disease

The pathogenesis of chronic obstructive pulmonary disease (COPD) encompasses a number of injurious processes, including an abnormal inflammatory response in the lungs to inhaled particles and gases. Other processes, such as failure to resolve inflammation, abnormal cell repair, apoptosis, abnormal cellular maintenance programs, extracellular matrix destruction (protease/antiprotease imbalance), and oxidative stress (oxidant/antioxidant imbalance) also have a role. The inflammatory responses to the inhalation of active and passive tobacco smoke and urban and rural air pollution are modified by genetic and epigenetic factors. The subsequent chronic inflammatory responses lead to mucus hypersecretion, airway remodeling, and alveolar destruction. This article provides an update on the cellular and molecular mechanisms of these processes in the pathogenesis of COPD.     

Pathogenesis of chronic obstructive pulmonary disease

It is currently believed that the most important factor in the pathogenesis of chronic obstructive pulmonary disease (COPD) is inflammation of the small airways caused by inhaled particles and gases. In this context, a disturbance of the physiological balance between proteases and antiproteases develops that may cause lung emphysema. Moreover, oxidative stress seems to be important, as it may enhance the inflammatory reaction. The development of emphysema may also involve a loss of alveolar cells by apoptosis. Finally, several studies have indicated that a systemic inflammation is induced by COPD that may be of relevance to the development of systemic components that are observed in COPD patients.     

Nodular pulmonary vasculitis in a twelve-year-old boy

A 12-year-old boy presented with left shoulder pain during physical exercise and complained of uncommon sweating and fatigue. Diagnostic evaluation revealed a solitary pulmonary nodule in the left upper lobe. All laboratory values were within normal limits, except for an elevated level of antineutrophil cytoplasmic antibodies directed against myeloperoxidase (p-ANCA). Surgery was performed, and pathological examination showed a localized granulomatous vasculitis. Antineutrophil cytoplasmic antibodies directed against affinity purified proteinase 3 (p-ANCA) concentrations returned to baseline within 6 months, and the patient has done well during a follow-up period of 2 years. While nodular vasculitis is known to occur in Wegener's granulomatosis, to the best of our knowledge, this case represents the first c-ANCA negative primary pulmonary vasculitis in childhood.     

Goodpasture's syndrome associated with pulmonary eosinophilic vasculitis

Lung hemorrhage and antiglomerular basement membrane (anti-GBM) antibody mediated nephritis define Goodpasture's syndrome. We present the case of a 19-year-old Caucasian woman with unique clinical findings of Goodpasture's syndrome. Our patient initially presented with leukocytoclastic vasculitis of the skin followed by the development of nephritis and lung hemorrhage. An open lung biopsy done prior to diagnosing anti-GBM antibody disease demonstrated an intense eosinophilic vasculitis. Skin vasculitis has only been rarely reported, and to our knowledge this is the first reported case of pulmonary eosinophilic vasculitis associated with Goodpasture's syndrome.