Dieulafoy's disease

一名 17 岁女性患者于 2023 年 4 月 2 日因“咯血持续 3 小时”被送入急诊科。患者在入院前 3 h 突然出现咯血，无明显诱因。咳出大约 10 mL 鲜红色血液。该发作与咳嗽、咳痰、胸闷或呼吸急促无关。患者试图通过自行服用止血药物来控制出血，但收效甚微，促使她寻求进一步的医学评估。该患者之前一直身体健康。

入院时，体格检查显示以下内容：心率 105 次/分钟，呼吸频率 30 次/分钟，血压 90/59 mmHg，血氧饱和度水平 90%（吸入氧含量为 29%）。患者总体状况不佳，右肺呼吸音减弱，双侧无外来肺音。2023 年 4 月 2 日进行的胸部计算机断层扫描 （CT） 显示双肺有高密度混浊的斑片状区域，主要在右肺，边界不清（图 1）。初步鉴别诊断包括不明原因的咯血、疑似右肺下叶肺泡出血和可能的肺部感染。进行了进一步的诊断测试，包括全血细胞计数、D-二聚体凝血功能、风湿病学检查、抗核抗体、抗肾小球基底膜抗体和肺肿瘤标志物。所有结果均在正常范围内。

两天后，进行了支气管动脉 CTA，结果显示右支气管动脉没有异常，但左支气管动脉没有清晰可见。患者拒绝接受进一步检查，包括支气管动脉血管造影和支气管镜检查。她接受了哌拉西林治疗疑似感染，并接受了依他磺酸盐和氨甲环酸止血治疗。她的病情有所好转，随后出院。

2023 年 4 月 8 日，患者出现第二次咯血发作，约 100 mL，与第一次相似。鉴于她咯血的复发性情况，考虑了支气管动脉静脉畸形或支气管腔粘膜下血管异常的可能性。病情稳定后，3 天后接受了支气管动脉栓塞术。术中观察到远端第一肋间动脉和右锁骨下动脉之间形成了动静脉瘘。右支气管动脉迂曲而扩张，将血液分配到右下叶，在远端发现肺动脉瘘管。使用微导管对异常支气管动脉进行超选择性导管插入术，证实了 BPF 的存在（图 2A）。支气管远端动脉用微球栓塞，支气管动脉主干用线圈栓塞。栓塞后血管造影显示远端支气管动脉没有进一步的可视化（图2B）。术中诊断包括支气管动脉-肺动脉瘘、咯血、肺部感染和肋间动脉-右锁骨下动脉瘘。行支气管动脉栓塞术后，患者无进一步咯血发作，出院情况稳定。然而，患者再次拒绝接受支气管镜检查。

支气管动脉血管造影术。（A） 支气管动脉血管造影显示右下肺 BPF 的形成。（B） 使用微球和线圈栓塞支气管动脉;远端支气管动脉没有进一步的可视化)(这个栓塞我觉得有问题，第一没有找到足够的血管，第二术前没有做CTA或者增强检查，可能遗漏了血管，第三，弹簧圈栓塞，值得商榷，个人不建议使用）

出院 1 个月后，患者出现严重咯血发作，咳出约 200 mL 血液，伴有呼吸衰竭和失血性休克。立即入院后，患者行气管插管和床旁支气管镜检查，发现右侧主支气管有明显出血。患者在支气管镜下接受持续气道抽血，导致出血逐渐停止。生命体征显示出稳定的趋势，导致成功脱机和拔管。随访支气管动脉血管造影未见异常。鉴于最近的咯血发作与支气管动脉-肺动脉瘘有关的可能性很低，因此有必要进一步调查。5 月 30 日，在局部麻醉下，再次进行支气管镜检查。检查显示右下叶支气管口的粘膜隆起，血管充血明显，呈淡紫色，管腔内有少量新鲜血液（图3）。考虑到当地血液供应丰富，没有进行活检或刷牙。根据支气管镜检查结果，怀疑 BDD 是咯血的原因。

2023 年 6 月 12 日，患者通过胸腔镜接受了右下叶切除术。切除的右下叶的组织病理学检查显示大而异常的血管，伴有少量淋巴细胞浸润，并在血管周围观察到肺泡出血（图4）。肺叶切除术后，患者没有进一步的咯血发作，出院时状况良好。四个月通过电话随访表明，患者的病情保持稳定。

Dieulafoy 病最早由法国医生 Dieulafoy 于 1898 年报道，最初被描述为“单纯性溃疡”。 ² 它是指由于外部因素导致动脉破裂，或由于胃肠道、胆管或支气管血管畸形导致动脉自发破裂引起的急性管腔出血。供血动脉穿透粘膜下层，而不会逐渐变细成毛细血管，保持其直径并突出到管腔中。1995 年，Sweets 等人 ³ 首次报道了 BDD，它现在被认为是隐源性大量咯血的主要原因之一。BDD 的病理特征是支气管粘膜下层异常扩张或畸形的动脉破裂，导致出血。Dieulafoy 病的临床表现是非特异性的，在这种情况下，初始症状是咯血。在年轻患者中，我们主要考虑肺结核、血管炎或肺肾综合征等原因，应该进行常规支气管镜检查。本例患者拒绝支气管镜检查，延误了诊断。保守止血治疗出院后，患者继续出现复发性咯血。随后的支气管镜检查显示右下叶支气管粘膜隆起、明显充血，与 Dieulafoy 病的支气管镜检查结果一致。最终通过右下肺叶切除术后的病理检查确诊。由于支气管动脉血管造影在诊断 BDD 方面缺乏特异性，通常仅显示支气管动脉分支的局部增加或曲折扩张，无法识别支气管镜检查期间观察到的相应部位。因此，该患者的第二次咯血发作未通过支气管动脉血管造影产生 BDD 阳性结果。在这种情况下，如果动脉造影无法确认 BDD，则需要进行支气管镜检查。支气管内超声 （EBUS） 和窄带成像 （NBI） 是 BDD 内窥镜诊断的宝贵工具。NBI 可以有效地显示粘膜血管形态和表面结构，有助于血管疾病诊断。EBUS 通过显示血流和促进识别粘膜隆起下的血管畸形，帮助阐明支气管内隆起病变的性质。 ⁴ 呼吸内窥镜检查在诊断和治疗 BDD 中也起着至关重要的作用，因为它可以在支气管动脉栓塞 （BAE） 之前定位出血的肺叶，从而在发生大量出血时协助球囊闭塞手术。(没有提供足够的血管造影图片和术前CT增强图片，没有支气管镜的超声检查，不够完美）

Research advances in Dieulafoy's disease of the bronchus (Review)

支气管diulafoy病的研究进展（综述）

Abstract

Dieulafoy's disease is characterized by abnormal submucosal arteries and results in acute luminal hemorrhage. Dieulafoy's lesions can also be found in the submucosa of the bronchus. Due to its low incidence rate and non‑specific clinical symptoms, Dieulafoy's disease is easy to overlook, but can lead to massive bleeding and high rates of mortality. Therefore, improvements in the understanding of the disease are necessary. The awareness of the disease and associated diagnostic and treatment techniques have continued to improve, and thus, an increasing number of cases of Dieulafoy's disease of the bronchus have been reported. In the present review, 74 cases of Dieulafoy's disease are summarized. New technologies such as endobronchial ultrasound, narrow‑band imaging, angiography and argon plasma treatment have been found to be increasingly applied to diagnose and treat Dieulafoy's disease of the bronchus. Therefore, the primary focus of this systematic review is to highlight advances in the diagnosis and treatment of bronchial Dieulafoy's disease.

摘要

diulafoy病以粘膜下动脉异常为特征，可导致急性腔内出血。Dieulafoy病变也见于支气管粘膜下层。由于其发病率低，临床症状无特异性，Dieulafoy病容易被忽视，但可导致大出血和高死亡率。因此，提高对该病的认识是必要的。对该病的认识以及相关的诊断和治疗技术不断提高，因此，越来越多的支气管Dieulafoy病病例被报道。本文对74例diulafoy病进行了总结。支气管超声、窄带成像、血管造影和氩等离子体治疗等新技术越来越多地应用于支气管diulafoy病的诊断和治疗。因此，本系统综述的主要重点是强调支气管Dieulafoy病的诊断和治疗进展。

1. Introduction

Dieulafoy's disease, initially described as ‘exulceratio simplex’ (1) in 1897, is an acute luminal hemorrhage caused by the rupture of a feeding artery under the actions of external factors, or spontaneous rupture owing to vascular malformations of the gastrointestinal, biliary or bronchial wall; the feeding artery does not taper to capillaries after entering the submucosa, but remains constant in diameter and protrudes from the intestinal lumen. After >100 years of revisions and improved understanding, the disease was renamed as Dieulafoy's disease.

Dieulafoy's disease of the bronchus was first described by Sweerts et al (2) in 1995, and to date, <100 cases have been reported worldwide. However, as the condition is under-recognized and frequently underdiagnosed, the actual incidence is likely to be much higher. Therefore, it is necessary to increase our awareness of Dieulafoy's disease of the bronchus, which is considered to be one of the primary causes of massive hemoptysis (3). Although the natural history, diagnosis and preferred treatment of the disease are still unclear, Dieulafoy's disease of the bronchus is believed to be caused by both congenital (2) and acquired factors (4). In previous years, the awareness of the disease and associated techniques of diagnosis and treatment have continued to improve, and novel diagnostic technologies have been increasingly applied. The present review summarizes the research advances in Dieulafoy's disease of the bronchus.

1. 介绍

diulafoy病最初在1897年被描述为“单纯溃疡病”(1)，是一种急性管腔出血，由外部因素作用下供血动脉破裂或胃肠道、胆道或支气管壁血管畸形引起的自发破裂引起；供血动脉在进入粘膜下层后不变细为毛细血管，但其直径保持不变，并从肠腔伸出。经过100多年的修订和认识的提高，这种疾病被重新命名为diulafoy病。

1995年，sweets等人(2)首次描述了支气管diulafoy病，迄今为止，全世界报告的病例不足100例。然而，由于该病未被充分认识和诊断，实际发病率可能要高得多。因此，有必要提高我们对支气管Dieulafoy病的认识，它被认为是大咯血的主要原因之一(3)。虽然该病的自然史、诊断和首选治疗尚不清楚，但认为Dieulafoy病有先天性(2)和后天因素(4)两方面的原因。对疾病的认识和相关的诊断和治疗技术不断提高，新的诊断技术得到越来越多的应用。现就支气管diulafoy病的研究进展作一综述。

2. Methods

The terms ‘bronchial OR bronchus’ AND ‘dieulafoy OR dieulafoy's’ were searched in the PubMed and Embase databases, covering the period between January 1985 and December 2019. Literature associated with a definitive diagnosis or a high suspicion of Dieulafoy's disease of the bronchus was screened, with abstracts of meetings excluded. There were no limitations on the language of the publications. A manual search was then conducted according to the reference lists of the published articles.

2. 方法

在PubMed和Embase数据库中检索了术语“支气管或支气管”和“dieulafoy或dieulafoy’s”，涵盖1985年1月至2019年12月期间。筛选与明确诊断或高度怀疑支气管diulafoy病相关的文献，排除会议摘要。出版物的语言没有任何限制。然后根据已发表文章的参考文献表进行人工检索。

3. Pathogenesis

Dieulafoy's disease of the bronchus is pathologically characterized by the rupture and bleeding of a dilated or abnormal artery in the bronchial submucosa. The dilated or abnormal artery passes through the bronchial wall next to the bronchial cavity, and is surrounded by a thin mucosal epithelial layer. Abnormal vessels predominantly branch from the bronchial artery system and rarely from the pulmonary artery (5).

The pathogenesis of bronchial Dieulafoy's disease remains to be clarified. Most researchers believe that the disease is congenital, while others believe that it is acquired or is simply an abnormality of normal blood vessels (2,4-6). The etiology and pathogenesis of Dieulafoy's disease of the bronchus may be associated with congenital abnormalities of bronchial and pulmonary arteries, chronic inflammation or injury of the airway, and is also considered to be associated with long-term heavy smoking (7). Almost half of the patients are smoking or had smoked in our study (31 of the 74 patients had a history of smoking). Parrot et al (7) reported the cases of seven patients with Dieulafoy's disease of the bronchus, all of whom were long-term heavy smokers (mean smoking capacity, 49 packs/year), which supports the aforementioned findings. Moreover, some patients had a history of tuberculosis (6 of the 74 patients developed tuberculosis), indicating a possible association with inflammatory injury in tuberculosis or stretching and dilation of the bronchial artery (7). In addition, 15 patients developed other respiratory diseases and two patients had a history of cardiovascular disease (8). These findings indicate that Dieulafoy's disease of the bronchus may be associated with a history of basic diseases, especially respiratory diseases such as tuberculosis (9-12), pneumonia (13,14) and bronchiectasis (15).

3. 发病机理

支气管溃疡病的病理特征是支气管粘膜下层扩张或异常动脉破裂和出血。扩张或异常的动脉穿过靠近支气管腔的支气管壁，并被薄粘膜上皮包围。异常血管主要来自支气管动脉系统，很少来自肺动脉(5)。

支气管Dieulafoy病的发病机制尚不清楚。大多数研究人员认为这种疾病是先天性的，而另一些人则认为它是获得性的或仅仅是正常血管的异常（2,4-6）。支气管diulafoy病的病因和发病机制可能与支气管和肺动脉的先天性异常、气道的慢性炎症或损伤有关，也被认为与长期大量吸烟有关(7)。在我们的研究中，几乎一半的患者正在吸烟或曾经吸烟（74例患者中有31例有吸烟史）。Parrot等(7)报道了7例支气管Dieulafoy病患者，均为长期重度吸烟者（平均吸烟量为49包/年），支持上述发现。此外，部分患者有结核史（74例患者中有6例发展为结核），提示可能与结核炎症损伤或支气管动脉伸展扩张有关(7)。此外，15例患者有其他呼吸系统疾病，2例患者有心血管疾病史(8)。这些结果提示支气管diulafoy病可能与基础疾病史有关。特别是呼吸道疾病，如肺结核（9-12）、肺炎（13、14）和支气管扩张（15）。

4. Incidence

In total, 74 cases of bronchial Dieulafoy's disease have been identified in the past 20 years since the first reported case in 1995 (2,4-44). Owing to the substantially low incidence of Dieulafoy's disease of the bronchus, there have been no statistical reports of its exact incidence. Among the patients reported, the youngest was 5 years old, and the oldest was 85 years old. Subjects aged 30-70 years were at a high risk, accounting for 80% of the total patients (Table I). The male-to-female incidence ratio was ~2:1 (45 male vs. 24 female patients), although the reason for the sex differences in Dieulafoy's disease of the bronchus is not clear.

4. 发病率

自1995年首次报道病例以来，在过去的20年中，总共发现了74例支气管Dieulafoy病（2,4-44）。由于支气管diulafoy病的发病率非常低，没有关于其确切发病率的统计报告。在报告的患者中，最小的为5岁，最大的为85岁。30-70岁为高危人群，占患者总数的80%（表1）。尽管支气管Dieulafoy病性别差异的原因尚不清楚，但男女发病率比为~2:1（男性45例，女性24例）。

5. Lesion site

A total of 74 cases of Dieulafoy's disease of the bronchus were summarized, including 48 in the right bronchus (19 in the right lower lobe, 12 in the right middle lobe, 9 in the right upper lobe, 5 in the right lower and middle lobes, 2 in the right middle and upper lobes, and 1 in the entire right lung), 20 in the left bronchus (11 in the left lower lobe, 1 in the left main bronchus, 7 in the left upper lobe, and 1 in the left lung), 1 in the lingula, and 6 in an unspecified location. An analysis of the reported cases revealed that Dieulafoy's disease of the bronchus commonly occurs in the right bronchus, and that patients with lesions in the right bronchus account for approximately two-thirds of the total cases. These differences may be due to the anatomical characteristics of the bronchi. The right bronchus is short and thick so that foreign bodies are more likely to enter and cause infection, one of the potential causes of Dieulafoy's disease of the bronchus. Therefore, biopsies should be performed with caution to prevent hemorrhage in patients with cryptogenic hemoptysis if a lesion (especially in the right bronchus) with similar manifestations to Dieulafoy's disease is demonstrated by bronchoscopy.

5. 病变部位

总共74例Dieulafoy支气管的疾病进行了综述,包括48个正确的支气管(19日在正确的下叶,12个正确的中部叶,9在右上叶,5对中低叶,2在合适的中、上部叶,和1在整个右肺癌),20在左支气管(11在左侧下叶,1在左主支气管,7在左肺上叶,左肺和1),1在海豆芽,6在一个不明地点。对报告病例的分析显示，支气管diulafoy病通常发生在右支气管，右支气管病变患者约占总病例的三分之二。这些差异可能是由于支气管的解剖特征。右支气管短而粗，异物更容易进入引起感染，是支气管diulafoy病的潜在病因之一。因此，如果支气管镜检查发现与diulafoy病表现相似的病变（尤其是右支气管），应谨慎进行活检，以防止隐蔽性咯血患者出血。

6. Clinical manifestations

Recurrent hemoptysis is a common symptom of Dieulafoy's disease of the bronchus. The maximum amount of hemoptysis has been reported as 2,000 ml, and is often without an obvious cause (14). A previously reported patient with Dieulafoy's disease presented with chest pain and no hemoptysis; the latter only occurred after bronchoscopic biopsy, and a definitive diagnosis was established by bronchial angiography (39). Indeed, patients with Dieulafoy's disease frequently visit the hospital with a cough (12,36), infection (12,20) or respiratory failure (33,34). In conclusion, the clinical symptoms of Dieulafoy's disease of the bronchus are non-specific. Therefore, physicians should not only pay more attention to patients with massive hemoptysis, but also focus on patients with recurrent respiratory symptoms.

6. 临床表现

反复咯血是支气管diulafoy病的常见症状。据报道，最大咯血量为2000毫升，通常没有明显的原因（14）。先前报告的Dieulafoy病患者表现为胸痛和无咯血；后者仅发生在支气管镜活检后，并通过支气管血管造影建立明确的诊断（39）。事实上，患有diulafoy病的患者经常因咳嗽（12,36）、感染（12,20）或呼吸衰竭（33,34）而就诊。总之，支气管diulafoy病的临床症状是非特异性的。因此，医生不仅要重视大咯血患者，更要关注反复出现呼吸道症状的患者。

7. Auxiliary examination

In Dieulafoy's disease of the bronchus, chest X-rays and computed tomography (CT) scans are rarely positive for symptoms other than the manifestation of an intrapulmonary hemorrhage and the original lung disease. Only a few cases of endobronchial nodules have been identified by chest CT examination (17). By contrast, multi-slice CT angiography can clearly indicate the shape and direction of bronchial pulmonary vessels, which may detect a tortuous and dilated bronchial artery (22), and may also demonstrate well-enhanced endobronchial nodules (25).

Owing to cryptogenic hemoptysis, most patients who undergo bronchoscopic examination and bronchoscopy demonstrate massive endobronchial hemorrhage, which may even be accompanied by blood clot formation (12,36). Mucosal nodular projections can be a few millimeters in diameter and height with a smooth surface (36). The lesion may also be congested and rough, with slight vascular pulsation in specific cases. Sometimes the protruding surface is coated with yellow-white exudate forming a ‘little white hat’-like shape, easily misdiagnosed as an endobronchial tumor nodule (7) (Fig. 1). The nodule may show as a neoplasm-like granulation nodule, leading to local obstruction of the bronchial lumen and causing obstructive pneumonia. If the nodule is mistaken for a neoplasm, subsequent biopsy may lead to a large hemorrhage and death by suffocation. Abnormal vessels in the submucosa can be tortuous and dilated, and with a worm-like shape (Fig. 2), sometimes with fork-like ‘twigs’. This type of case is easily mistaken for submucosal tumor infiltration, and subsequent biopsies may lead to fatal hemorrhage. As the bronchial cavity is filled with blood and blood clots, it is difficult to find a small mucosal protrusion, or the mucosal protrusion is localized below the subsegmental bronchus and thus cannot be seen by conventional bronchoscopy.

7. 辅助检查

在支气管diulafoy病中，除了肺内出血和原有肺部疾病的表现外，胸部x线和计算机断层扫描（CT）很少有阳性症状。只有少数病例通过胸部CT检查发现支气管内结节（17）。相比之下，多层螺旋CT血管造影可以清楚地显示支气管肺血管的形状和方向，可以发现弯曲和扩张的支气管动脉（22），也可以显示支气管内结节（25）。

由于隐源性咯血，大多数接受支气管镜检查和支气管镜检查的患者表现为大量支气管内出血，甚至可能伴有血凝块形成（12,36）。粘膜结节突起直径和高度可达几毫米，表面光滑（36）。病变也可能充血和粗糙，在特殊情况下有轻微的血管搏动。有时突出表面覆盖黄白色渗出物，形成“小白帽”状，易误诊为支气管内肿瘤结节(7)（图1）。结节可表现为肿瘤样肉芽结节，导致支气管腔局部阻塞，引起阻塞性肺炎。如果结节被误认为肿瘤，随后的活检可能导致大出血和窒息死亡。粘膜下层的异常血管可以扭曲和扩张，呈蠕虫状（图2），有时呈叉状“细枝”。这种类型的病例很容易被误认为粘膜下肿瘤浸润，随后的活检可能导致致命的出血。由于支气管腔内充满血液和血凝块，很难发现小的粘膜突出，或粘膜突出位于支气管亚段以下，常规支气管镜无法发现。

Figure 1 - Small nodular protrusion from the mucosa of the left lingual segment of the bronchus. Protrusion of ~3 mm in diameter and height, coated with yellow-white exudate, and forming a ‘little while hat’ (black arrow).图1 -支气管左舌段粘膜小结节状突出。直径和高度约3mm的突出物，被黄白色渗出物覆盖，形成“小帽”（黑色箭头）。

8. Diagnosis

The possibility of Dieulafoy's disease of the bronchus should be considered in patients with hemoptysis when chest X-ray and CT examinations demonstrate no obvious abnormalities other than pulmonary hemorrhage. Dieulafoy's disease of the bronchus is largely diagnosed according to the presentations of bronchoscopy, bronchial angiography and pathology of surgical or autopsy specimens. Numerous researchers consider that pathological examination of biopsies, surgical or autopsy specimens is required for a definite diagnosis. However, there are no uniform diagnostic criteria, and since pathological biopsies can lead to fatal hemorrhages, the need for pathological diagnosis remains controversial. In some cases, the diagnosis is based on the manifestations revealed by bronchoscopy and bronchial angiography (24,25,39). Endobronchial ultrasonography (EBUS) is a new diagnostic method used to detect the lesions of Dieulafoy's disease (21).

8. 诊断

咯血患者胸片及CT检查除肺出血外无明显异常时，应考虑支气管diulafoy病的可能性。支气管diulafoy病的诊断主要根据支气管镜检查、支气管血管造影和手术或尸检标本的病理表现。许多研究人员认为，病理检查活检，手术或尸检标本是明确诊断的必要条件。然而，没有统一的诊断标准，由于病理活检可能导致致命的出血，病理诊断的必要性仍然存在争议。在某些情况下，诊断是基于支气管镜检查和支气管血管造影所显示的表现（24,25,39）。支气管超声检查（EBUS）是一种新的诊断方法，用于检测Dieulafoy病的病变（21）。

Bronchoscopy

Under bronchoscopy, a mucosal protrusion a few millimeters in diameter and height is visible in the corresponding site of the bleeding bronchus. On the top of the protrusion, the mucosa turns white without a pulsating sensation; the surrounding mucosa may be normal or slightly congested. In some cases, abnormal blood vessels within the submucosa are tortuous and dilated in an earthworm-like pattern, sometimes presenting with a purple nodular shape (39). To prevent uncontrollable hemorrhage, caution must be taken during biopsy if Dieulafoy's disease is suspected (based on the results of bronchoscopy). Yang et al (26) analyzed the clinical data of 22 patients with Dieulafoy's disease, including 12 with hemorrhage during biopsy. Bleeding stopped in eight patients after local hemostasis, and in two after lobectomy of the diseased lobe; another two patients died of massive hemorrhage. The remaining 10 patients did not undergo bronchoscopic biopsy. Our previous study reported the cases of six patients, including two undergoing bronchoscopic biopsy, both of whom suffered hemorrhage; the maximum amount of hemorrhage was ~1,000 ml, and bleeding stopped in both cases after selective bronchial artery embolization (39). Since 2014, with an improvement of the understanding of Dieulafoy's disease, biopsy has been avoided for nodules suspected to be caused by Dieulafoy's disease in the trachea (23,41), which has effectively reduced the probability of massive hemorrhage in Dieulafoy's disease.

支气管镜检查

支气管镜下，在出血支气管的相应部位可见直径和高度为几毫米的粘膜突出物。在突出的顶部，粘膜变白，没有搏动感；周围粘膜可能正常或轻度充血。在一些病例中，粘膜下层的异常血管呈蚓状扭曲和扩张，有时表现为紫色结节状（39）。为了防止无法控制的出血，如果怀疑diulafoy病（基于支气管镜检查结果），活检时必须谨慎。Yang等（26）分析了22例diulafoy病患者的临床资料，其中12例活检时出血。局部止血后止血8例，切除病变肺叶后止血2例；另有两名患者死于大出血。其余10例患者未行支气管镜活检。我们之前的研究报告了6例患者，其中2例接受支气管镜活检，均出现出血；最大出血量为~ 1000 ml，选择性支气管动脉栓塞后出血停止（39）。2014年以来，随着对Dieulafoy病认识的提高，气管内疑似Dieulafoy病引起的结节避免了活检（23,41），有效降低了Dieulafoy病大出血的概率。

Bronchial angiography

As aforementioned, bronchial angiography can be used to indicate the rich blood supply to the corresponding site of the lesion. The bronchial artery is tortuous, dilated and deformed, with signs of bleeding (39).

支气管血管造影

如前所述，支气管血管造影可以显示病变相应部位的血供是否丰富。支气管动脉迂曲、扩张和变形，伴有出血的迹象（39）。

Multi-slice CT angiography of the bronchial or pulmonary artery

This technique is used to visualize an abnormal bronchial artery associated with tortuosity and dilation (22), and sometimes detects well-enhanced endobronchial nodules (25). A CT value of >100 for the enhanced lesion should be considered to indicate a vascular lesion.

支气管或肺动脉的多层螺旋CT血管造影

该技术用于观察与扭曲和扩张相关的异常支气管动脉（22），有时也能检测到良好增强的支气管内结节（25）。增强病灶的CT值为bbb100时应考虑为血管病变。

Endobronchial ultrasound

When convex probe EBUS is used to detect blood flow within a lesion, it often shows a fluid echo-free zone in submucosal lesions; the blood flow can be displayed in the color or energy Doppler mode (21). Owing to its large diameter, convex probe EBUS cannot reach the upper lobe bronchus or segmental bronchus. Alternatively, radial probe EBUS can be used to examine the lesion. However, the latter approach has no Doppler mode and thus cannot determine blood flow within the lesion. Nonetheless, radial probe EBUS can indicate an echo-free zone, which may be considered for vascular lesions in patients with hemoptysis.

支气管内超声

当使用凸探头EBUS检测病变内血流时，通常在粘膜下病变处显示流体无回声区；血流可以以彩色或能量多普勒模式显示（21）。凸探头EBUS由于其直径较大，不能到达支气管上叶或支气管节段。或者，可以使用径向探头EBUS检查病变。然而，后一种方法没有多普勒模式，因此不能确定病变内的血流。然而，放射状探头EBUS可提示无回声区，可考虑咯血患者的血管病变。

Narrow-band imaging

Wang et al (45) reported that narrow band imaging (NBI) can display endobronchial lesions such as bronchial artery-pulmonary artery fistulae. Thickened blood vessels and capillaries are tortuous and disordered in the submucosa of the lesion site. However, there have been no studies to assess the diagnostic value of NBI in Dieulafoy's disease.

Narrow-band imaging  窄带成像

Wang et al (45) reported that narrow band imaging (NBI) can display endobronchial lesions such as bronchial artery-pulmonary artery fistulae. Thickened blood vessels and capillaries are tortuous and disordered in the submucosa of the lesion site. However, there have been no studies to assess the diagnostic value of NBI in Dieulafoy's disease.
Wang 等人 （45） 报道，窄带成像 （NBI） 可以显示支气管内病变，例如支气管动脉-肺动脉瘘。增厚的血管和毛细血管在病变部位的粘膜下层迂回曲折且无序。然而，还没有研究评估 NBI 在 Dieulafoy 病中的诊断价值。

Pathological examination  病理检查

Pathology or autopsy pathology presents with arterial malformation in the bronchial submucosa. The tortuous, dilated, deformed artery forms small nodules coated with bronchial mucosa, protrudes from the bronchial lumen, and is only a few millimeters in diameter and height. In some cases, deformed blood vessels have an opening within the bronchial lumen, or the diseased bronchus is surrounded by rich blood vessels, some of which invade the bronchial wall and directly reach the submucosa (5). A diagnosis of Dieulafoy's disease depends on the results of pathological examination. However, since this can easily lead to massive bleeding, its use has been limited. Therefore, the incidence of Dieulafoy's disease may have been underestimated.
病理学或尸检病理表现为支气管粘膜下层动脉畸形。蜿蜒、扩张、变形的动脉形成涂有支气管粘膜的小结节，从支气管腔突出，直径和高度只有几毫米。在某些情况下，变形的血管在支气管腔内有一个开口，或者患病的支气管被丰富的血管包围，其中一些血管侵入支气管壁并直接到达粘膜下层 （5）。Dieulafoy 病的诊断取决于病理检查的结果。然而，由于这很容易导致大量出血，因此其使用受到限制。因此，Dieulafoy 病的发病率可能被低估了。

9. Differential diagnosis
9. 鉴别诊断

Dieulafoy's disease and endobronchial hemorrhagic lesions are primarily distinguished by differential diagnosis. Additionally, the disease must be distinguished from early endobronchial cancer to avoid misdiagnosis.
Dieulafoy 病和支气管内出血病变主要通过鉴别诊断来鉴别。此外，必须将这种疾病与早期支气管内癌区分开来，以避免误诊。

Bronchial arteriovenous malformation (46)
支气管动静脉畸形 （46）

Bronchial arteriovenous malformation can manifest as an endobronchial vascular lesion. The presence of abnormal blood vessels in the lesion can be demonstrated by EBUS or NBI, but it is difficult to distinguish via bronchoscopy. Bronchial angiography can be used to clarify the communication between the bronchial artery and the pulmonary circulation or cavernous hemangioma.
支气管动静脉畸形可表现为支气管内血管病变。病变中存在异常血管可通过 EBUS 或 NBI 证明，但很难通过支气管镜检查进行鉴别。支气管血管造影可用于阐明支气管动脉与肺循环或海绵状血管瘤之间的交通。

Bronchial artery aneurysm (47)
支气管动脉瘤 （47）

Bronchial artery aneurysm can manifest as an endobronchial vascular lesion. This condition can be distinguished from Dieulafoy's disease by bronchial angiography or multi-slide CT angiography as an aneurysm-like dilation of the bronchial artery.
支气管动脉瘤可表现为支气管内血管病变。这种情况可以通过支气管血管造影或多玻片 CT 血管造影作为支气管动脉的动脉瘤样扩张来与 Dieulafoy 病区分开来。

Lobular capillary hemangioma (48)
小叶毛细血管瘤 （48）

This condition has no typical symptoms other than hemoptysis. Intraluminal neoplasms can be seen under bronchoscopy. Ulcers and bleeding are visible on the surface and are difficult to distinguish from Dieulafoy's disease of the bronchus. The differential diagnosis primarily relies on pathological examination.
这种情况除了咯血外没有典型症状。腔内肿瘤可以在支气管镜下看到。溃疡和出血在表面可见，很难与支气管的 Dieulafoy 病区分开来。鉴别诊断主要依靠病理检查。

Tracheal capillary hemangioma (49)
气管毛细血管瘤 （49）

In general, tracheal capillary hemangioma is similar to tracheal lobular capillary hemangioma and Dieulafoy's disease of the bronchus in terms of clinical manifestations, laboratory examination results, imaging and endoscopy. The differential diagnosis primarily relies on pathological examination.
一般来说，气管毛细血管瘤在临床表现、实验室检查结果、影像学和内窥镜检查方面与气管小叶毛细血管瘤和支气管 Dieulafoy 病相似。鉴别诊断主要依靠病理检查。

Early cancer  早期癌症

If Dieulafoy's disease is suspected based on bronchoscopy, and the possibility of early cancer cannot be ruled out, NBI and EBUS may be used to determine the presence of thickened and abnormally tortuous and disordered vessels within the lesion. Fluorescence bronchoscopy preliminarily determines the malignancy of the lesion.
如果根据支气管镜检查怀疑 Dieulafoy 病，并且不能排除早期癌症的可能性，则可以使用 NBI 和 EBUS 来确定病变内是否存在增厚、异常曲折和无序的血管。荧光支气管镜检查初步确定病变的恶性肿瘤。

10. Treatment and prognosis
10. 治疗和预后

Existing methods for the treatment of Dieulafoy's disease of the bronchus include conservative internal medication, selective bronchial artery embolization (SBAE), pulmonary lobectomy and argon plasma coagulation via bronchoscopy. Currently, SBAE is the preferred surgical approach, and lobectomy of the diseased lobe is used following embolization failure or recurrent post-embolization hemoptysis. Only one case of argon plasma coagulation via bronchoscopy has been reported (24).
治疗支气管 Dieulafoy 病的现有方法包括保守内服、选择性支气管动脉栓塞 （SBAE）、肺叶切除术和通过支气管镜进行氩血浆凝固。目前，SBAE 是首选的手术方法，在栓塞失败或栓塞后咯血复发后使用病变肺叶切除术。仅报道了一例通过支气管镜检查进行氩血浆凝固的病例 （24）。

Medication  药物

As the condition presents with bleeding caused by the rupture of the bronchial or pulmonary artery, internal treatment with hemostatic agents often has poor efficacy for Dieulafoy's disease of the bronchus (39). However, for individual patients, pituitrin and thrombin may occasionally demonstrate good therapeutic effects (30).
由于该病症表现为支气管或肺动脉破裂引起的出血，因此用止血剂进行内部治疗通常对支气管 Dieulafoy 病的疗效不佳 （39）。然而，对于个体患者，垂体素和凝血酶可能偶尔表现出良好的治疗效果 （30）。

Bronchoscopic treatment  支气管镜治疗

Topical application of hemostatic drugs under bronchoscopy also has poor efficacy. To date, only Dalar et al (24) has reported the success of treating one patient with Dieulafoy's disease of the bronchus by argon plasma coagulation via bronchoscopy. However, the patient underwent no bronchial angiography or pathological diagnosis, and Dieulafoy's disease of the bronchus was diagnosed based solely on the presentations under bronchoscopy. Thus, the diagnosis of that patient remains controversial. In Dieulafoy's disease, once blood vessels rupture and bleed, the hemorrhage is fast and massive, resulting in an unclear field of view under bronchoscopy. Hence, it is our belief that bleeding from Dieulafoy's disease is not suited to dotted electrocoagulation and superficial hemostasis by argon-beam-coagulator burning, laser treatment and freezing under bronchoscopy. Nevertheless, this approach is feasible to remove blood clots that block the bronchial lumen and to clarify the bleeding site under bronchoscopy, thereby determining the lesion site for bronchial angiography or surgery. The use of a Dumon silicone stent for compression was reported in a patient with Dieulafoy's disease of the left main bronchus, and the patient was followed up for 8 months without recurrent hemorrhage (44). This study indicated that hemostasis by stent compression may be an alternative treatment option. Additionally, a bronchoscopic balloon can be used to compress the bronchus at the bleeding site to provide preparation time for SBAE. For the treatment of gastrointestinal Dieulafoy's disease, coagulant injection under digestive endoscopy can be used for hemostasis. However, no study has reported the use of this method for Dieulafoy's disease of the bronchus, thus the feasibility, safety and efficacy of the method are currently undetermined.
支气管镜检查下局部应用止血药物的疗效也很差。迄今为止，只有 Dalar 等人 （24） 报道了通过支气管镜进行氩浆凝固治疗一名支气管 Dieulafoy 病患者的成功。然而，患者没有接受支气管血管造影或病理诊断，支气管 Dieulafoy 病仅根据支气管镜检查下的表现进行诊断。因此，该患者的诊断仍然存在争议。在 Dieulafoy 病中，一旦血管破裂和出血，出血迅速而大，导致支气管镜检查下的视野不清晰。因此，我们认为 Dieulafoy 病的出血不适合通过氩束凝固器燃烧、激光治疗和支气管镜下冷冻进行点状电凝和浅表止血。尽管如此，这种方法对于去除阻塞支气管腔的血凝块和支气管镜检查下的出血部位是可行的，从而确定支气管血管造影或手术的病变部位。据报道，在一名左主支气管 Dieulafoy 病患者中使用 Dumon 硅胶支架进行压迫，并且该患者随访了 8 个月，没有复发性出血 （44）。这项研究表明，通过支架加压止血可能是一种替代治疗选择。此外，支气管镜球囊可用于压迫出血部位的支气管，为 SBAE 提供准备时间。用于治疗胃肠道 Dieulafoy 病，消化内镜下注射凝血剂可用于止血。 然而，没有研究报道该方法用于支气管的 Dieulafoy 病，因此该方法的可行性、安全性和有效性目前尚不确定。

SBAE  

The SBAE procedure is effective in most patients with Dieulafoy's disease of the bronchus; however, hemoptysis may recur after surgery. Bhatia et al (10) reported the case of one patient with recurrent hemorrhage who had undergone SBAE seven times. Patients with abnormal blood vessels from the pulmonary artery are often non-responsive to SBAE. In our previous repor (39), all six patients with Dieulafoy's disease of the bronchus underwent SBAE at the corresponding site of hemorrhage. Hemorrhage was stopped in one patient following SBAE, who then underwent a pulmonary lobectomy; the other five patients all underwent SBAE and were followed up for 1 to 5 years. Furthermore, hemoptysis was not recurrent in four of the patients, though one patient did experience relapse.
SBAE 手术对大多数支气管 Dieulafoy 病患者有效;然而，咯血可能在手术后复发。Bhatia 等人 （10） 报道了一名复发性出血患者接受了 7 次 SBAE 的病例。肺动脉血管异常的患者通常对 SBAE 无反应。在我们之前的 repor （39） 中，所有 6 名支气管 Dieulafoy 病患者都在相应的出血部位接受了 SBAE。1 例患者在 SBAE 后停止出血，然后接受肺叶切除术;其他 5 例患者均接受了 SBAE 并随访 1 至 5 年。此外，其中 4 例患者的咯血没有复发，但 1 例患者确实出现了复发。

Surgical treatment  手术治疗

In cases of SBAE failure, SBAE for hemoptysis relapse or no SBAE treatment, a lobectomy may be performed at the corresponding site of the lesion. Hemoptysis is unlikely to recur following resection of the diseased lung lobe. In a report by Yang et al (26), 13 patients underwent lobectomy of the diseased lobe; 12 did not experience recurrent hemoptysis, and one died due to hemorrhage after bronchoscopic biopsy, but not due to surgery.
在 SBAE 失败的情况下，SBAE 治疗 咯血 复发或无 SBAE 治疗，可以在 病变的相应部位。咯血不太可能复发 切除患病肺叶后。在 Yang 的一份报告中 等 （26），13 例患者接受了患病叶的肺叶切除术;12 例未出现复发性咯血，1 例因支气管镜活检后出血死亡，但未因手术死亡。

11. Conclusions  11. 结论

Dieulafoy's disease of the bronchus lacks specificity in clinical symptoms and primarily presents as massive hemoptysis, although other respiratory or cardiovascular symptoms may also occur. Due to its relative rarity, respiratory physicians currently lack sufficient awareness of Dieulafoy's disease of the bronchus, thus the disease is likely to be missed or misdiagnosed. Serious consequences may result if attention is not paid to the diagnosis and treatment process. In particular, when local protrusion changes are found in the lumen during routine bronchoscopy, physicians perform routine biopsies which can cause fatal bleeding. Therefore, to rule out the possibility of Dieulafoy's disease of the bronchus, bronchial angiography, multi-slice CT angiography, EBUS and NBI examinations must be considered for patients undergoing bronchoscopy who present with cryptogenic hemoptysis and/or smooth protrusion within the bronchial lumen resembling Dieulafoy's disease (even those who do not experience hemoptysis). Biopsy must be prohibited if bronchial angiography demonstrates: i) The presence of a bronchial artery with abnormal tortuosity and dilation, as well as rupture and bleeding at the lesion site; ii) an enhanced CT value >100 for the lesion; or iii) EBUS and NBI results of abnormal blood flow within the lesion. Caution must be taken during bronchoscopic operations, such as biopsy and brushing, to prevent asphyxial hemorrhage. At present, SBAE and pulmonary lobectomy are the primary treatment methods for Dieulafoy's disease of the bronchus, although conservative drug treatment and flexible bronchoscope argon plasma coagulation have also been successfully used. SBAE can retain part of the function of the diseased lung, but may result in relapse following treatment. Lobectomy is a radical cure for Dieulafoy's disease, although complete removal of the diseased lung may affect the patient's quality of life. Thus, clinicians must assess the advantages and disadvantages, and select the most appropriate treatment method depending on the physical manifestations of each patient.
支气管 Dieulafoy 病在临床症状中缺乏特异性，主要表现为大面积咯血，但也可能出现其他呼吸道或心血管症状。由于其相对罕见，呼吸科医生目前对支气管的 Dieulafoy 病缺乏足够的认识，因此该疾病很可能被漏诊或误诊。如果不注意诊断和治疗过程，可能会导致严重后果。特别是，当在常规支气管镜检查中发现管腔局部突出变化时，医生会进行常规活检，这可能会导致致命的出血。因此，为了排除支气管 Dieulafoy 病的可能性，对于接受支气管镜检查的患者，必须考虑支气管镜检查的患者出现隐源性咯血和/或支气管腔内光滑突出，类似于 Dieulafoy 病（即使那些没有咯血的人）。如果支气管血管造影显示：i） 支气管动脉异常迂曲和扩张，以及病变部位破裂和出血，则必须禁止活检;ii） 病变的 CT 值 >100 增强;或 iii） 病灶内异常血流的 EBUS 和 NBI 结果。在支气管镜手术（例如活检和刷牙）期间必须小心，以防止窒息性出血。目前，SBAE 和肺叶切除术是支气管 Dieulafoy 病的主要治疗方法，尽管保守药物治疗和可弯曲支气管镜氩等离子体凝固也已成功使用。SBAE 可以保留患病肺的部分功能，但可能导致治疗后复发。 肺叶切除术是 Dieulafoy 病的根治性方法，尽管完全切除患病肺可能会影响患者的生活质量。因此，临床医生必须评估优缺点，并根据每位患者的身体表现选择最合适的治疗方法。