Pathogenesis of pulmonary vasculitis

Vasculitis is inflammation of blood vessels and can affect any type of vessel in any organ. Pulmonary vasculitis usually is a component of a systemic small vessel vasculitis. Three major forms of small vessel vasculitis that often affect the lungs are Wegener's granulomatosis, microscopic polyangiitis, and Churg-Strauss syndrome. These forms of vasculitis are strongly associated with antineutrophil cytoplasmic autoantibodies (ANCA) directed against enzymes contained in the primary granules of neutrophils and peroxidase-positive lysosomes of monocytes. This review discusses the evidence for a pathogenic role of ANCA. In vitro, ANCAs can activate cytokine-primed neutrophils and monocytes resulting in oxygen radical formation and release of lysosomal enzymes. In vivo, antimyeloperoxidase ANCA has been shown to induce crescentic glomerulonephritis and systemic vasculitis. Overall, the available data suggest that ANCA are indeed a pathogenic factor in the development of small-vessel vasculitis. Antiglomerular basement membrane (anti-GBM) disease also causes pulmonary vasculitis through immune attack on alveolar capillaries and glomerulonephritis through antibody mediated injury to glomerular capillaries. Thus, there is evidence that antibodies are important pathogenic factors in both ANCA disease and anti-GBM disease, however, there are also indications that T cells may play important pathogenic roles in both categories of disease as well.     

The lung in systemic vasculitis

Pulmonary vasculitis is usually caused by one of three disorders: (1) Wegener's granulomatosis (WG); (2) Churg-Strauss syndrome (CSS), or allergic angiitis and granulomatosis; or (3) a nonspecific small vessel systemic necrotizing vasculitis (SNV), or microscopic polyarteritis. WG, the most common cause of lung vasculitis, has features of a granulomatous vasculitis of the upper airway and lung and widespread small vessel vasculitis involving the kidneys and other organs. The features of pulmonary WG overlap with those of malignancy and infectious granulomatous lung disease; accurate diagnosis generally requires open lung biopsy. CSS is defined by the triad of asthma, eosinophilia, and systemic vasculitis. Easily accessible tissues should be biopsied, but the clinical features are so distinctive that tissue biopsy is not invariably required for diagnosis. CSS must be differentiated from other diseases that cause pulmonary infiltrates with eosinophilia, including infections. Nonspecific SNV causes diffuse alveolar hemorrhage due to pulmonary capillaritis. Concomitant segmental necrotizing glomerulonephritis is almost always present. Diagnosis is made by renal biopsy, compatible extrarenal features, exclusion of nonimmune causes of lung hemorrhage, and exclusion of WG to the extent possible.     

Small vessel vasculitis of the lung

The diagnosis and management of SVV remains one of the most challenging clinical scenarios encountered by a clinician. Careful attention to detail and a thorough knowledge of the specific disorders, their therapies, and complications thereof is required to optimally care for these patients. The recent completion of a number of randomized, controlled, multicenter clinical trials has greatly improved our knowledge base and ability to care for vasculitis patient. The next decade holds even more promise.     

放射性肺损伤的发病机制

放射治疗是肿瘤综合治疗的重要手段之一,肺是辐射中度敏感器官,在胸部肿瘤的放射治疗中,放射性肺损伤是常见的剂量限制因素.电离辐射损伤后各种因素参与的修复、再生过程的失控是最终导致肺纤维化的原因.氧化应激所致的自由基过度生成、炎症细胞及相关细胞因子参与的炎症反应过程是放射性肺损伤的关键因素,本文就相关研究作一综述.     

放射性肺损伤的发病机制研究进展

放射性肺损伤是胸部恶性肿瘤放射性治疗的并发症之一,病程呈进行性发展,最终引起呼吸衰竭而死亡.放射性肺损伤是由多种细胞、细胞因子及信号通路参与的疾病,本文就相关研究作一阐述.     

Pathogenesis of lung disease in cystic fibrosis

Lung disease in cystic fibrosis is primarily due to a defect in the cystic fibrosis transmembrane regulating protein (CFTR). This results in abnormal chloride transfer across epithelial membranes causing an excessively viscid mucus lining of the airways. Bacterial invasion particularly with Staphylococcus aureus, Haemophilus influenzae and Pseudomonas aeruginosa stimulates a vigorous and excessive primarily neutrophil-driven inflammatory response throughout the lungs. Products of this inflammation not only damage incoming bacteria but also the host tissue itself. Over a period of years this chronic suppurative process results in permanent ongoing lung destruction principally manifested as bilateral bronchiectasis.     

肺小血管炎的研究进展

肺小血管炎(SVVL)是原发性小血管炎累及肺脏血管的一组疾患.因本病与抗中性粒细胞胞浆抗体(ANCA)密切相关,故称为抗中性粒细胞胞浆抗体相关性小血管炎(AAVS).主要包括:韦格纳肉芽肿病(WG)、显微镜下多血管炎(MPA)、变应性肉芽肿性血管炎(CSS)[1],常可累及多个系统.肺是原发性小血管炎累及频率最高的脏器之一,据报道肺脏受累占75%,仅次于肾脏,且是造成死亡的主要原因.其临床表现复杂多变,缺乏特异性,常常被误诊为其它疾病,延误治疗.而经积极治疗,其生存率明显上升.因此有必要提高对SVVL的认识.     

病毒感染导致急性肺损伤的发病机制

病毒主要侵犯人类呼吸道,一方面在呼吸道上皮细胞和血管内皮细胞内复制,损伤肺组织,破坏气体交换屏障;另一方面,通过巨噬细胞、分叶核中性粒细胞、淋巴细胞以及内皮细胞等释放大量细胞因子,宿主免疫机制被过度激活并失控,导致急性肺损伤.     

急性出血坏死性胰腺炎肺损伤的发病机制

0 引言急性胰腺炎(AP)的研究进展较大,然而急性出血坏死性胰腺炎(AHNP)早期容易并发多器官功能衰竭(MODS),尤其是呼吸功能障碍在75%的急性胰腺炎(AP)患者中发生,临床症状从较轻的低氧血症到成人呼吸窘迫综合征(ARDS)均可出现.AHNP 相关的 ARDS 在临床表现和病理特征上均与其他原因如败血症、严重创伤所引起的 ARDS 相似,但是其发病机制还不清楚.最新的研究表明,AP 是一种全身炎症反应综合征,其发病机制复杂,与多种因素有关.近年来经大量研究,许多学者对 AP 相关肺损伤的发病机制有了较多的认识,其中包括胰酶、补体系统和激肽的作用,循     

Pathogenesis of the lung in restrictive defects of Klinefelter's syndrome.

Patients with Klinefelter's syndrome show a high incidence of restrictive lung defects, the pathogenesis of which is not clear yet. We investigated the respiratory muscle force (PImax) and lung compliance in 13 patients with Klinefelter's syndrome who had not been receiving hormonal therapy for at least one year prior to being studied. Eleven were smokers and two were nonsmokers. None showed abnormalities of the chest wall. Five had normal lung volumes and eight showed a restrictive defect (TLC < 80 percent, VC < 85 percent, FEV1/FVC percent within normal values); DCOSB and arterial blood gases were within normal limits. PImax was similar in restricted (-115.9 +/- 26.7 cm H2O) and not restricted patients (-115.4 +/- 20.3 cm H2O), all within reference values. Lung compliance, however, was significantly decreased in the four patients studied (0.13 +/- 0.08 cm H2O-1) compared with five normal control subjects (0.29 +/- 0.05 cm H2O-1). We conclude that the likely cause of the lung restriction is a decrease of compliance of the lung matrix, probably related to the absence of testosterone.     

肺部原发性小血管炎的临床表现和诊断

目的 研究肺脏受累的原发性小血管炎的临床特点和早期诊断要点，减少其误诊率。方法 对26例原发性小血管炎伴肺脏受累患者的临床资料进行回顾性分析。结果 26例中，显微镜下多血管炎(MPA)15例，韦格纳肉芽肿(WG)9例，变应性肉芽肿性血管炎(CCS)2例。抗中性粒细胞胞浆抗体(ANCA)阳性率61．5％。肺脏受累的临床表现有咯血、呼吸困难、干咳、胸痛、胸闷等，胸部X线多表现为多发斑片状或点状阴影、大片高密度阴影或团块影、结节影、网格状影，可有空洞形成。疾病早期多误诊为肺部感染、肿瘤、肺间质病变等。应用肾上腺皮质激素和环磷酰胺治疗肺部病变可明显吸收，临床危重症得以改善。结论 伴肺脏受累的原发性小血管炎临床表现复杂多样，诊断困难，误诊率高，易延误病情，须引起临床医师的重视。