弥漫性泛细支气管炎和慢性鼻窦炎的相关性研究进展

弥漫性泛细支气管炎（DPB）是一种呼吸性细支气管区域的慢性炎症性疾病,主要发病于东亚地区,多合并或既往有慢性鼻窦炎,属于鼻窦支气管综合征（SBS）的一种,遗传可能是DPB发病及其与慢性鼻窦炎有相关性的基础,其中最引人注目的是有关人类白细胞抗原（HLA）的研究,该文就DPB与HLA及慢性鼻窦炎的相关性作一综述。     

滤泡性细支气管炎研究进展

滤泡性细支气管炎是一个组织病理学诊断,以细支气管壁伴有生发中心的淋巴样滤泡增生为特征.常与慢性感染和炎症性气道疾病,例如囊性纤维化、支气管扩张、慢性误吸、结缔组织疾病、包括获得性免疫缺陷综合征在内的免疫缺陷综合征有一定的相关性.在胸部影像学主要表现为两肺小结节或网状阴影,伴有胸腔内淋巴结肿大,结节和毛玻璃样影可以两肺弥漫性分布,主要位于支气管血管周围.结合临床表现和影像学表现可以用于滤泡性细支气管炎的诊断.治疗缺乏特效治疗手段,一般预后较好.     

滤泡性细支气管炎研究进展

滤泡性细支气管炎是一个组织病理学诊断,以细支气管壁伴有生发中心的淋巴样滤泡增生为特征.常与慢性感染和炎症性气道疾病,例如囊性纤维化、支气管扩张、慢性误吸、结缔组织疾病、包括获得性免疫缺陷综合征在内的免疫缺陷综合征有一定的相关性.在胸部影像学主要表现为两肺小结节或网状阴影,伴有胸腔内淋巴结肿大,结节和毛玻璃样影可以两肺弥漫性分布,主要位于支气管血管周围.结合临床表现和影像学表现可以用于滤泡性细支气管炎的诊断.治疗缺乏特效治疗手段,一般预后较好.     

弥漫性泛细支气管炎(附一例报告)

弥漫性泛细支气管炎（ＤＰＢ）是一种常见病,是下呼吸道渐进性病变,发展较缓慢。其特点为慢性气流阻塞、细支气管炎、细支气管扩张及副鼻窦感染,多为化脓菌的重复感染。以往认为ＤＰＢ主要发生在日本,１９７６年国内曾有报告［１］,但未引起关注,直到１９９６年才再度引起重视,至今文献已报告的１８例［２,３］,发现本病在中国并非少见。以往诊断的病例皆有长期误诊过程,因为ＤＰＢ的很多临床症状易与ＣＯＰＤ、支气管扩张以及慢性间质性肺疾病相混淆。因之需要加强对ＤＰＢ的认识,提高诊断率。我院收治一例,报告如下：患者,男…     

弥漫性泛细支气管炎的诊治

目的探讨弥漫性泛细支气管炎（DPB）的临床特点及诊断方法。方法举例确诊为DPB患者的临床资料,并结合文献复习。结果DPB是一种以两肺弥漫性呼吸性细支气管及其周围的慢性炎症为特征的独立性疾病,临床表现为慢性咳嗽、咳痰、活动后呼吸困难,常合并铜绿假单胞菌感染和慢性鼻窦炎;胸部高分辨CT（HRCT）有助于诊断弥漫性泛细支气管炎,早期诊断及时给予大环内酯类药物规范化治疗,本病预后良好。结论对长期慢性咳嗽、咳痰,合并有慢性鼻窦炎病史的患者。应高度怀疑本病可能,应用小剂量红霉素或其他大环内酯类抗菌药物长期治疗,效果良好。     

类风湿性关节炎伴弥漫性泛细支气管炎1例报告并文献复习

弥漫性泛细支气管炎(DPB)是弥漫性存在于两肺呼吸性细支气管区域的一种慢性炎症为特征的独立性疾病。近年来,多有文献报道。常被误诊为支气管扩张,慢性支气管炎等,而贻误治疗。本文结合我院2012年以来收治的1例类风湿性关节炎伴弥漫性泛细支气管炎病例进行总结,提高对本病的认识。     

弥漫性泛细支气管炎及其治疗进展

弥漫性泛细支气管炎（diffuse panbronchiolitis，DPB）是一种弥漫存在于两肺呼吸性细支气管区域的慢性炎症为特征，引起严重呼吸障碍的疾患。由于炎症病变弥漫性地分布并累及呼吸性细支气管壁的全层，故称之为弥漫性泛细支气管炎。主要症状为慢性咳嗽、咳痰、活动时气短。由于进行性慢性气道感染，常引起呼吸衰竭，多数预后不良，但随着红霉素疗法的应用，DPB的预后有了划时代的变化。笔者复习了有关文献，对本病及其治疗进展综述如下：     

易误诊为哮喘的疾病

支气管哮喘（简称哮喘）是一种慢性气道炎症性疾病,由于其症状缺乏特异性,因此临床上容易误诊.哮喘的主要病理生理学特征包括如下几个方面：（1）气流受限,但可经支气管舒张剂治疗而逆转;（2）气道对各种刺激的高反应性;（3）气流受限呈周期性或发作性.这些是哮喘患者症状的基础,当其急性发作时,都会出现不同程度的气流受限,因此其主要临床表现是喘息、气急、胸闷、咳嗽[1-2].但这些症状并非哮喘所独有,任何能引起气流受限、缺氧的疾病均可出现类似症状.根据近年文献报道,易被误诊为哮喘的疾病主要包括慢性阻塞性肺疾病、嗜酸粒细胞性支气管炎、变应性肉芽肿性血管炎、大气道病变（包括复发性多软骨炎、肺支气管淀粉样变、气管支气管软化、气管肿瘤）、支气管内膜结核、过度通气综合征等.     

润肺口服液对慢性支气管炎大鼠支气管TNF-α、ICAM-1蛋白及IL-8表达的影响

目的研究中药复方润肺口服液对慢性支气管炎（CB，CB）支气管肿瘤坏死因子（TNF-α）、细胞间黏附分子-1（ICAM-1）及白介素-8（IL-8）表达的影响，探讨其治疗CB的疗效机制。方法雄性Wistar大鼠随机分为假手术组、慢性支气管炎组、慢性支气管炎氢化可的松治疗组及慢性支气管炎润肺口服液治疗组，每组8只。大鼠慢性支气管炎模型通过熏香烟加气管内注入低剂量脂多糖制成，利用免疫组织化学观察各组大鼠支气管TNF-α、ICAM-1蛋白及IL-8的表达情况。结果熏香烟加气管内低剂量脂多糖注射可复制出较理想的慢性支气管炎模型，假手术组支气管上皮内可见TNF-α、ICAM-1蛋白及IL-8弱阳性表达；慢性支气管炎组支气管TNF-α、ICAM-1蛋白及IL-8在支气管上皮细胞、支气管周围的淋巴滤泡炎性细胞和肺泡间质细胞中可见强阳性表达；半定量图像分析显示，慢性支气管炎组TNF-α、ICAM-1蛋白及IL-8的表达明显强于假手术组（P〈0．05），慢性支气管炎润肺口服液治疗组的表达则明显弱于支气管炎组（P〈0．05）。结论润肺口服液通过下调支气管上皮细胞中TNF-α、ICAM-1蛋白及IL-8的表达，从而减轻气道炎症反应是其治疗慢性支气管炎的机制之一。     

Kartagener's综合征伴泛细支气管炎临床病理分析

目的探讨Kartagener’s综合征(KS)合并泛细支气管炎的临床病理学特征。方法分析8例Kartagener’s综合征合并泛细支气管炎患者的临床资料和组织形态特点。结果Kart-agener’s综合征是一种罕见的遗传性疾病,它的特点是支气管扩张症、副鼻窦炎以及内脏转位。以呼吸道为首发症状,常合并弥漫性泛细支气管炎(DPB)。病理形态特点为终末细支气管和呼吸性细支气管管壁增厚,慢性炎细胞浸润。其中2例透射电镜检查1例为纤毛的内侧臂缺失,1例纤毛畸形,融合成团。结论Kartagener’s综合征合并泛细支气管炎值得引起临床注意,影像及肺活检有助于对本病的诊断。     

Microscopic polyangiitis associated with sinobronchial syndrome.

A woman with a long history of chronic bronchitis and chronic sinusitis, i.e., sinobronchial syndrome, was admitted with a fever. Radiologically, there were areas of longstanding consolidation in both lungs, with areas of active inflammation demonstrated by gallium-67 scintigraphy. Antineutrophil cytoplasmic antibody specific for myeloperoxidase was highly positive. Pulmonary hemorrhage and hematuria occurred 2 weeks after admission and responded to steroid therapy. However, the patient died of pneumonia. An autopsy revealed systemic necrotizing vasculitis affecting multiple organs, consistent with microscopic polyangiitis. The vasculitis might have been caused by the chronic inflammation in the lungs associated with sinobronchial syndrome.     

Sinobronchial allergic mycosis: the SAM syndrome

We contend that the presence of concomitant allergic fungal sinusitis (AFS) and allergic bronchopulmonary mycosis in the same patient represents an expression of the same process of fungal hypersensitivity in the upper and lower airways. We have termed this process the SAM syndrome, an acronym for sinobronchial allergic mycosis. Diagnostic criteria have been established for the SAM syndrome, and the clinical characteristics of one previously unreported and four previously reported patients have been tabulated. Patients with the SAM syndrome have chronic sinusitis involving multiple sinuses, asthma, immediate cutaneous reactivity to fungal allergens, peripheral eosinophilia, and radiographic evidence of bronchiectasis. Total serum IgE levels are usually elevated as well. A variety of chest radiographic abnormalities may occur, ranging from mass lesions to diffuse pulmonary infiltrates and even normal findings on chest radiographs. Patients present for an evaluation of either sinus or lung disease and, at that time, demonstrate no clinical features that distinguish them from patients with isolated sinus or lung disease. All patients reported to date have had clinical responses to therapy with corticosteroids. We postulate that SAM is underdiagnosed in patients with AFS, a disease recently reported from medical centers in the southeastern and western United States. Moreover, since our patient had a mutation in the cystic fibrosis transmembrane conductor regulator (CFTR) gene, we further hypothesize that CFTR gene mutations may play an important role in the pathogenesis of the SAM syndrome.     

Genetic predisposition to diffuse panbronchiolitis

Diffuse panbronchiolitis is characterized by chronic inflammation in respiratory bronchioles and sinobronchial infection. The pathophysiology accompanying the persistent bacterial infection is noteworthy for the accumulation of lymphocytes and foamy macrophages around the small airways, for mucus hypersecretion, and for the number of neutrophils in the large airways. Until the establishment of long-term macrolide therapy, the prognosis was generally poor. Case studies of diffuse panbronchiolitis in East Asians, including Japanese, Koreans and Chinese, have frequently been reported, and genetic predisposition to the disease has been assumed in Asians. Immunogenetic studies revealed a strong association with human leukocyte antigen (HLA)-B54 in Japanese, whereas an association with HLA-A11 was reported in Koreans. These findings imply that a major susceptibility gene may be located between the HLA-A and HLA-B loci on the short arm of human chromosome 6. We have recently cloned novel mucin-like genes in this candidate region. In addition to accumulated knowledge of classical HLA genes and mucin genes, further analysis of newly identified genes may provide insights into the pathogenesis of the disease.     

Bronchiectasis with normal paranasal sinus roentgenogram

Bronchiectasis has come to be considered as a type of sinobronchial syndrome in Japan, but there exist some cases without chronic sinusitis. We studied the clinical features of 14 cases of bronchiectasis with definitely normal paranasal sinus roentgenogram, diagnosed during the past ten years. There were eleven middle-aged women and three men. Ten patients (71%) complained of hemoptysis, one (7%) of dry cough, one (7%) of productive cough, and the two (14%) had no complaint. In seven patients (50%) CT and bronchography showed localized cylindrical bronchiectasis in the right middle lobe and/or left upper lobe lingular division. They were considered to be middle lobe lingular syndrome. Three patients (22%) with localized varicose or cystic bronchiectasis had a history of pneumonia or pertussis in their infancy, so their bronchiectasis were considered secondary to infantile bronchopulmonary disease. Two patients (14%) had diffuse cystic bronchiectasis and were almost asymptomatic. They might be cases congenital bronchiectasis or Williams-Campbell syndrome. Pulmonary function tests were normal in most of the cases and sputum culture revealed no cases of persistent bacterial infection. These clinical features are quite different from those of bronchiectasis reported as sinobronchial syndrome, in which chronic productive cough, poor pulmonary function, persistent bacterial infection, etc. are significant. So we conclude that there are two distinct groups in bronchiectasis.     

Effect of macrolides on the expression of human leukocyte antigen-DR and costimulatory molecules on cultured human mononuclear cells

Although the clinical effectiveness of long-term low-dose administration of macrolides for diffuse pan-bronchiolitis, sinobronchial syndrome, chronic sinusitis and otitis media with effusion has been well documented, the mechanism of action remains to be determined. To clarify the effect of macrolides on the initiation of immune responses, we investigated changes in the expression levels of human leukocyte antigen (HLA)-DR, a major histocompatibility complex class II antigen, and of costimulatory molecules, such as CD54, CD80 and CD86, on monocytes following administration of macrolides. The expression of HLA-DR, CD54, CD80 and CD86 on cultured human peripheral mononuclear cells following stimulation by interferon (IFN)-γ and lipopolysaccharides (LPS) was analyzed using flow cytometry in the presence and absence of macrolides. The macrolides tested inhibited the expression of CD54, CD80 and CD86 on cultured monocytes following stimulation by IFN-γ and LPS, while the expression of HLA-DR on monocytes was not affected. Suppression of CD80 expression was the most significant among the costimulatory molecules tested and occurred in a dose-dependent manner. These results suggest that macrolides may downregulate the expression levels of costimulatory molecules, such as CD80, and may normalize the hyperimmune responses that may be responsible for the chronic intractable inflammation.     

Diffuse panbronchiolitis

Diffuse panbronchiolitis (DPB) was first distinguished from chronic obstructive pulmonary diseases in the early 1960s and recorded as a new clinicopathologic entity. This disease affects East Asians for the major part, and is characterized by chronic sinobronchial infection together with diffuse bilateral micronodular pulmonary lesions consisting of inflammatory cells. The prognosis at an advanced stage would often be bleak, where superinfection with Pseudomonas aeruginosa had occurred. Beginning with an initial success of erythromycin therapy, considerable improvement has been achieved in the prognosis of this disease. Simple bactericidal activity of macrolides is not a determinant factor for the clinical effect. An in-depth study, together with its pathogenesis, has been performed to clarify the underlying mechanism. Inhibitions of excessive mucus and water secretion from airway epithelium, neutrophil accumulation in the large airway, lymphocyte and macrophage accumulation around the small airway, and modulation of bacterial virulence have so far been proposed as possible mechanisms.     

Diffuse Panbronchiolitis

Diffuse panbronchiolitis (DPB) is characterized by chronic sinobronchial infection and diffuse bilateral micronodular pulmonary lesions consisting of inflammatory cells. Studies on disease etiology point to a genetic predisposition unique to Asians. Early therapy for DPB was largely symptomatic. The advent of macrolide antibiotics, including erythromycin, roxithromycin and clarithromycin, has strikingly changed disease prognosis.Low-dose, long-term macrolide therapy for DPB originated from detailed observations of response to therapy in a single patient. The bactericidal activity of macrolides, particularly erythromycin, is not a significant factor for their clinical efficacy in DPB. Firstly, irrespective of bacterial clearance, clinical improvement is observed in patients treated with erythromycin. Secondly, even in cases with bacterial superinfection with Pseudomonas aeruginosa resistant to macrolides, treatment has proved effective. Thirdly, the recommended dosage of macrolides produces peak levels in tissue that are below the minimum inhibitory concentrations for major pathogenic bacteria that colonize the airway.In the last two decades, the possible mechanism underlying the effectiveness of macrolide therapy has been extensively studied. The proposed mechanism of action includes inhibition of excessive mucus and water secretion from the airway epithelium, inhibition of neutrophil accumulation in the large airway, inhibition of lymphocyte and macrophage accumulation around the small airway, and modulation of bacterial virulence. The great success of macrolide therapy in diffuse panbronchiolitis may extend its application to the treatment of other chronic inflammatory disorders. If the anti-inflammatory activity of macrolides is independent of their bactericidal effect, new anti-inflammatory macrolides without antimicrobial activity should be developed to minimize emergence of macrolide-resistant micro-organisms.     

Diffuse panbronchiolitis: role of macrolides in therapy

Diffuse panbronchiolitis (DPB) is characterized by chronic sinobronchial infection and diffuse bilateral micronodular pulmonary lesions consisting of inflammatory cells. Studies on disease etiology point to a genetic predisposition unique to Asians. Early therapy for DPB was largely symptomatic. The advent of macrolide antibiotics, including erythromycin, roxithromycin and clarithromycin, has strikingly changed disease prognosis. Low-dose, long-term macrolide therapy for DPB originated from detailed observations of response to therapy in a single patient. The bactericidal activity of macrolides, particularly erythromycin, is not a significant factor for their clinical efficacy in DPB. Firstly, irrespective of bacterial clearance, clinical improvement is observed in patients treated with erythromycin. Secondly, even in cases with bacterial superinfection with Pseudomonas aeruginosa resistant to macrolides, treatment has proved effective. Thirdly, the recommended dosage of macrolides produces peak levels in tissue that are below the minimum inhibitory concentrations for major pathogenic bacteria that colonize the airway. In the last two decades, the possible mechanism underlying the effectiveness of macrolide therapy has been extensively studied. The proposed mechanism of action includes inhibition of excessive mucus and water secretion from the airway epithelium, inhibition of neutrophil accumulation in the large airway, inhibition of lymphocyte and macrophage accumulation around the small airway, and modulation of bacterial virulence. The great success of macrolide therapy in diffuse panbronchiolitis may extend its application to the treatment of other chronic inflammatory disorders. If the anti-inflammatory activity of macrolides is independent of their bactericidal effect, new anti-inflammatory macrolides without antimicrobial activity should be developed to minimize emergence of macrolide-resistant micro-organisms.     

Deterioration of Asthma in a Patient With Diffuse Panbronchiolitis (DPB) After Macrolide Therapy

Diffuse panbronchiolitis (DPB), an important cause of progressive obstructive lung disease in the Far East, is a distinctive sinobronchial syndrome with characteristic radiologic and histologic features. Asthma is a chronic inflammatory disease characterized by airway narrowing. The major inflammatory cells involved in the pathogenesis of asthma are type 2 helper T (Th2) cells, eosinophils, and mast cells. The authors’ patient was diagnosed with DPB and asthma. Although macrolide therapy led to the disappearance of the radiologic abnormalities indicating centrilobular nodular lesions, the respiratory symptoms and pulmonary function worsened. Administration of inhaled corticosteroids improved the respiratory symptoms and pulmonary function. To the authors’ knowledge, no case of DPB with asthma has been reported in the English-language literature.