原发性纤毛运动障碍1例及文献复习

目的 提高对原发性纤毛运动障碍(PCD)临床与病理特点的认识.方法 分析我院收治的1例PCD患者的临床资料及诊治经过,并复习相关文献.结果 患者临床表现为慢性咳嗽、咯痰、喘息;胸部CT表现为双肺弥漫的小结节改变并伴局部支气管扩张;经纤维支气管镜肺活检电镜病理表现为纤毛结构异常,动力臂缺失.其表现符合PCD.结论 PCD是由纤毛功能和(或)结构缺陷导致的一种常染色体隐性遗传病,容易误诊,其诊断依赖于纤毛超微结构检测.目前尚无标准治疗方案,以对症治疗为主.

Abstract：

Objective To improve the understanding of clinical and pathological characteristics of primary ciliary dyskinesia (PCD). Methods A case diagnosed with PCD was reported,and the related literatures were reviewed. Results The patient had cough,expectoration,and dyspnea. Chest CT scan showed diffuse nodules and local bronchieclasis. Transbronchial lung biopsy was done and transmission electron microscopy showed ciliary abnormalities and absence of dynein arms. Those findings were consistent with PCD. Conclusions PCD is an inherited disease characterised by functional and/or structural congenital abnormalities of cilia,and is often misdiagnosed. The diagnosis of PCD relies on the analysis of cilium ultrastructure. There is no specific therapy for PCD,and symptomatic treatment is recommended.     

原发性纤毛运动障碍一例

<正>原发性纤毛运动障碍或称原发性纤毛不动综合征(primary ciliary dyskinesia,PCD)一种罕见的纤毛运动障碍的遗传性疾病,是第一个与纤毛运动障碍有关的人类疾病~([1])。最近发现了超过40个与PCD有关的基因,每个基因都有许多致病突变,而不同的突变导致不同的临床和病理模式,从而对PCD的诊断造成挑战~([2-3])。本院呼吸科于2014年6月收治一例PCD患者,现报道如下。     

原发性不动纤毛综合征四例并文献复习

目的 提高对原发性不动纤毛综合征的认识和诊断水平.方法 对2007年1月至2009年8月北京协和医院经电镜证实存在纤毛超微结构异常的4例原发性不动纤毛综合征(PCD)的临床资料进行分析,并进行相关的文献复习.结果 4例PCD中男性1例,女性3例;发病年龄0～10岁,确诊年龄15～53岁.临床表现:4例均有咳嗽、咳痰,鼻窦炎、喘息各3例,内脏反位2例,不育和不孕、中耳炎各1例;实验室检查:4例中低氧血症3例,阻塞性通气功能障碍伴有弥散功能减低2例,肺功能正常2例;胸部高分辨率CT示支气管扩张4例,双肺弥漫分布的微结节影3例,肺部斑片状影2例;电镜下可见动力臂缺失4例,纤毛稀少2例,微管排列异常或中央微管移位2例.结论 不合并内脏反位的PCD易被漏诊.对幼年发病,胸部影像学表现为弥漫支气管扩张或弥漫树枝出芽征样微结节的患者,需要鉴别PCD.可通过电镜观察纤毛超微结构以明确诊断.     

原发性纤毛运动障碍综合征1例及文献综述

原发性纤毛运动障碍(PCD)是由纤毛结构缺陷导致的一种疾病,属常染色体隐形遗传病,国外报道发病率约1∶30000～1∶60000,中国资料少,流行病学尚不清楚。现将我院收治确诊的1例PCD患者的临床资料报道如下,并结合相关报道对该病进行文献复习。     

成人特发性淋巴细胞性间质性肺炎三例并文献复习

目的 通过分析特发性淋巴细胞性间质性肺炎(LIP)的临床、影像、病理特征,探讨其诊断方法、治疗措施,提高临床工作者对其的认识.方法 回顾性分析3例经肺活检证实的特发性LIP患者的临床表现、胸部X线和CT、病理资料及诊治过程,并文献复习.结果 特发性LIP患者的主要临床表现为干咳、呼吸困难,常伴有高球蛋白血症;胸部影像学改变主要是双肺弥漫分布的小结节影和小囊肿;病理特征是以多克隆淋巴细胞尤其是B淋巴细胞浸润为主的弥漫性间质性炎症.主要治疗手段是糖皮质激素联合细胞毒药物,治疗反应良好.结论 LIP临床、影像和病理表现有一定特征性;最可靠的诊断方法为临床-影像-病理诊断;糖皮质激素和细胞毒药物联合治疗效果良好.     

慢性支气管炎患者支气管上皮获得性纤毛缺陷

慢性支气管炎(慢支)患者呼吸道粘液量的明显增加及其流变学特性的改变,以致平衡遭到破坏.同时,纤毛数量的减少及功能降低也有重要作用.作者研究旨在观察慢支患者纤毛超微结构的改变。患者和方法:对30(男25,女5)例可疑支气管肺疾病患者进行经纤维支气管镜肺活检(内镜)。根据临床及内镜的表现分为3组:①对照组(8例):临床及内镜均无急、慢性支气管炎证据者,平均年龄58.1±13.6岁.②内镜慢支组(8例):内镜具有慢支表现而无临床症状者,平均年龄68.5±11.9岁。③临床慢支组(14例):内镜及临床均证实为慢支者,平均年龄65.8±10.1岁。内镜检查时至少从每例患者右主支气管取2块组织,立即固定、切片、染色、用光学显微镜和透射电镜观察。采用随机的方法至少观察300根纤毛,包括纤毛     

中国原发性纤毛运动障碍患儿纤毛超微结构及基因分析

目的探讨中国原发性纤毛运动障碍(PCD)患儿纤毛超微结构及基因变异特点。方法搜集重庆医科大学附属儿童医院呼吸中心2018年11月至2021年5月经支气管黏膜活检纤毛透射电子显微镜检查及第二代全外显子trio家系测序的8例PCD患儿资料, 在国内外数据库PubMed、中国知网、维普、万方进行文献检索, 检索时间为自数据库建库起至2021年9月, 结合相关报道完善纤毛活检及基因检测的中国PCD患儿资料, 总结其基因突变和纤毛结构的关系。结果 8例患儿确诊中位年龄为6.25岁, 其中男6例, 女2例, 大多有慢性咳嗽、慢性鼻-鼻窦炎、支气管扩张, 伴全内脏转位2例。支气管纤毛透射电子显微镜结果示支气管黏膜纤毛内、外动力臂(IDA+ODA)缺陷5例, IDA缺陷1例, 纤毛数量减少1例, 正常1例。完善基因分析, 共检测出致病基因突变10个, 其中DNAH5检测到新发致病突变1个:c.11029-2A>T(剪切突变)。通过文献复习并结合本文病例, 共纳入80例同时完善了纤毛活检及基因检测的中国PCD患儿, 其中DNAH5、DNAH11、HYDIN基因为中国患儿常见突变基因, ODA缺陷(...     

香烟烟雾致COPD模型大鼠气道纤毛结构变化的评价

目的 应用气道纤毛超微结构的综合评价方法,观察香烟烟雾暴露对COPD大鼠气道纤毛结构的影响.方法 Wister大鼠,随机分为对照组(5只)、香烟暴露组(5只),香烟暴露组通过45 d被动吸烟建立COPD大鼠模型,利用光镜观察肺组织病理学变化,电镜观察纤毛超微结构改变,免疫荧光标记技术观察纤毛超微结构中微管蛋白变化.结果 香烟暴露组大鼠的纤毛荧光强度为(53.46±13.28),低于对照组(120.00±26.86)(P＜0.05).香烟暴露组纤毛膜水疱数为(7.36±2.38)个高于对照组(O.66±1.21)个(P＜0.05).结论 被动吸烟导致COPD大鼠气道纤毛结构异常,表现为纤毛膜水疱数增加、纤毛荧光强度减低.     

多发性肌炎/皮肌炎合并肺间质性病变的临床特征

目的 回顾分析病理确诊的多发性肌炎/皮肌炎肺受累患者的临床、影像和病理学特征,以提高临床诊断水平.方法 1980年1月至2006年10月在北京协和医院住院,经病理确诊的多发性肌炎/皮肌炎肺受累患者共26例,其中6例进行尸检,5例行开胸肺活检或经胸腔镜肺活检,15例行经皮肺活检,进行临床、影像和病理学及预后综合分析.结果 26例患者的中位年龄为48岁(19～65岁),男10例,女16例.胸部X线主要表现为磨玻璃样变,双肺斑片状阴影和网格影.病理表现为弥漫性肺泡损伤(DAD)5例;淋巴细胞间质性肺炎2例;非特异性间质性肺炎(NSIP)富细胞型6例,混合型8例;机化性肺炎4例;普通型间质性肺炎(UIP)1例.所有患者均接受了泼尼松+环磷酰胺的治疗.中位随诊时间为15个月(6～108个月),中位生存期为21个月(1～253个月).26例患者中18例病情改善或稳定,8例死亡,其中5例病理表现为DAD,2例为NSIP混合型,1例为UIP.结论 多发性肌炎/皮肌炎肺受累患者的胸部CT及病理表现多样,病理诊断为DAD者预后差.     

肺透明细胞癌1例并文献复习

目的 分析肺透明细胞癌的临床特征、影像学表现及病理诊断要点.方法 报告1例经肺活检病理确诊的肺透明细胞癌病例,并结合文献资料对该病的临床特征、影像学表现及病理诊断要点进行分析.结果 本例患者为女性,45岁,以反复咳嗽2个月为首发症状,胸部CT示两肺多发结节灶合并肺门及纵隔淋巴结肿大,胸腔镜下肺活检病理确诊为原发性肺透明细胞癌.近20年国内外文献报道肺透明细胞癌病例仅27例,其中男性18例,女性9例,平均年龄(55±11)岁.临床表现主要为咳嗽(16/27)、胸痛(12/27)、咯血(10/27).影像学表现以周围型单发结节或团块影多见(22/27),病灶直径0.5～11 cm.该病罕见,属大细胞癌的变异型;确诊多依赖开胸肺组织病理活检,免疫组织化学染色有助于鉴别.结论 肺透明细胞癌的临床表现无特异性;影像学表现以肺部单发结节或团块影多见,亦可为两肺多发和弥漫型;确诊依赖肺组织病理活检,免疫组织化学染色有助于鉴别.     

Ultrastructural ciliary defects in children with recurrent infections of the lower respiratory tract

One hundred fifty-four children with recurrent or chronic infections of the lower respiratory tract compatible with the diagnosis of primary ciliary dyskinesia (PCD) were evaluated for the presence of ultrastructural ciliary abnormalities. Studies were performed on multiple samples of respiratory mucosa obtained by nasal and bronchial brushing. Twenty-eight children showed ultrastructural ciliary defects compatible with the diagnosis of PCD: Twenty-four presented dynein arm deficiency (either as isolated defect or in association with microtubular abnormalities), two had ciliary aplasia, and two showed microtubular abnormalities. Eleven patients with PCD had situs viscerum inversus, bronchiectasis, and chronic sinusitis (Kartagener's syndrome); one child with Kartagener's syndrome had normal ciliary structure. The appearance of respiratory symptoms within the first month of life, the colonization by Haemophilus influenzae, and a history of recurrent rhinitis and otitis were characteristically present in children with PCD. The clinical status of those patients who reached adolescence was, in our experience, remarkably good. An early diagnosis with adequate prevention and therapy of respiratory infections may have an important role in minimizing irreversible lung damage.     

Dyskinésie ciliaire primitive

Primary ciliary dyskinesia (PCD, MIM 242650) is an inherited respiratory disease caused by functional and ultrastructural abnormalities of respiratory cilia. This disorder, which affects 1 in 16,000 individuals, is usually transmitted as an autosomal recessive trait. In half the cases, PCD is associated with situs inversus (Kartagener syndrome). PCD is characterized by impaired mucociliary clearance resulting from a lack of ciliary motion, which is responsible for recurrent respiratory infections. The most frequent and first identified ciliary defect involves the dynein arms. The genetic heterogeneity underlying PCD is extremely important, and only three genes have as yet been identified in a few PCD patients with absence of outer dynein arms. The main clinical symptoms, at pulmonary and ENT levels, the abnormalities of ciliary structure and function, and the molecular basis of PCD will be reported in this review.     

Nasal ciliary ultrastructure and function in patients with primary ciliary dyskinesia compared with that in normal subjects and in subjects with various respiratory diseases

In an attempt to establish the relevance of ciliary ultrastructure to the pathophysiologic aspects of respiratory tract disease, we compared quantitatively the ultrastructure and function of cilia from healthy subjects (atopic and nonatopic nonsmokers, asymptomatic smokers) and patients with a variety of respiratory diseases (cystic fibrosis, chronic rhinitis, bronchiectasis associated with hypogammaglobulinemia, chronic bronchitis) with cilia from patients with primary ciliary dyskinesia (PCD). In healthy subjects and patients with non-PCD respiratory disease, approximately 5% of the cilia evaluated had ultrastructural abnormalities. Ciliary beat frequency was significantly higher in the chronic rhinitis group (15.3 +/- 1.2 Hz) than in the other non-PCD groups, which were within the normal range (12.5 +/- 1.7 Hz), and in all non-PCD cases ciliary wave form was normal. In each of these groups, normal mucociliary transport had been previously demonstrated. By contrast, in patients with PCD, the proportion of cilia with ultrastructural abnormalities was significantly greater than in the normal subjects and those with non-PCD respiratory disease (p less than 0.0001). In addition, beat frequency was significantly reduced, ciliary wave form was grossly abnormal, and pulmonary and nasal mucociliary transport were virtually absent. These findings demonstrate the relevance of ciliary ultrastructural abnormalities to altered ciliary function and lend support to the primary role of the demonstrated abnormalities in the respiratory tract disease of PCD.     

Pulmonary radioaerosol mucociliary clearance in diagnosis of primary ciliary dyskinesia

BACKGROUND: Methods relying on nasal ciliary motility for the diagnosis of primary ciliary dyskinesia (PCD) are often hampered by secondary ciliary dyskinesia. A functional test for pulmonary mucociliary clearance, which is not influenced by secondary nasal ciliary defects, would be a valuable tool in a PCD workup. METHODS: The diagnostic validity and repeatability of a pulmonary radioaerosol mucociliary clearance (PRMC) test for the diagnosis of PCD was assessed in the following three sequentially performed substudies: (1) a preliminary cross-sectional study of PRMC in patients with known PCD; (2) a prospective blinded trial of patients referred for suspicion of PCD; and (3) an implementation study of PRMC as a routine method used in a PCD workup. PRMC was studied after (99m)Tc-albumin colloid aerosol inhalation, and the results were compared to (1) the results of nasal ciliary motility studies, (2) ciliary ultrastructure, and (3) the final clinical diagnosis. The repeatability of PRMC was assessed in 14 patients. RESULTS: A total of 95 patients, 5 to 74 years of age, were included in the study (57 patients in whom PCD was diagnosed, 26 non-PCD patients, and 12 patients referred for PCD workup without a conclusive workup result). In substudy 1, 14 of 15 patients with known PCD showed impaired PRMC; the results were inconclusive in 1 patient. In substudy 2, among 59 patients referred for PCD workup PRMC test results, compared to nasal ciliary motility, showed a sensitivity of 88% and a specificity of 100%. In substudy 3, among 21 patients referred for PCD investigation who were included in a routine PCD workup after PRMC implementation, 71% of PRMC test results were in alignment with nasal ciliary motility. Repeatability of interpretation was seen in 13 of 14 cases. A conclusive PRMC after only one test was found in 81 of 95 patients (85%). CONCLUSION: PRMC is a noninvasive functional test for total tracheobronchial mucociliary clearance with a high sensitivity and specificity for PCD, a high rate of conclusive results after only one test and a further ability to separate PCD from focal pulmonary mucociliary defects.     

Primary ciliary dyskinesia: diagnostic and phenotypic features

Primary ciliary dyskinesia (PCD) is a genetic disease characterized by abnormalities in ciliary structure/function. We hypothesized that the major clinical and biologic phenotypic markers of the disease could be evaluated by studying a cohort of subjects suspected of having PCD. Of 110 subjects evaluated, PCD was diagnosed in 78 subjects using a combination of compatible clinical features coupled with tests of ciliary ultrastructure and function. Chronic rhinitis/sinusitis (n = 78; 100%), recurrent otitis media (n = 74; 95%), neonatal respiratory symptoms (n = 57; 73%), and situs inversus (n = 43; 55%) are strong phenotypic markers of the disease. Mucoid Pseudomonas aeruginosa (n = 12; 15%) and nontuberculous mycobacteria (n = 8; 10%) were present in older (> 30 years) patients with PCD. All subjects had defects in ciliary structure, 66% in the outer dynein arm. Nasal nitric oxide production was very low in PCD (nl/minute; 19 +/- 17 vs. 376 +/- 124 in normal control subjects). Rigorous clinical and ciliary phenotyping and measures of nasal nitric oxide are useful for the diagnosis of PCD. An increased awareness of the clinical presentation and diagnostic criteria for PCD will help lead to better diagnosis and care for this orphan disease.     

The emerging genetics of primary ciliary dyskinesia

Primary ciliary dyskinesia (PCD) is an autosomal recessive, rare, genetically heterogeneous condition characterized by oto-sino-pulmonary disease together with situs abnormalities (Kartagener syndrome) owing to abnormal ciliary structure and function. Most patients are currently diagnosed with PCD based on the presence of defective ciliary ultrastructure. However, diagnosis often remains challenging due to variability in the clinical phenotype and ciliary ultrastructural changes. Some patients with PCD have normal ciliary ultrastructure, which further confounds the diagnosis. A genetic test for PCD exists but is of limited value because it investigates only a limited number of mutations in only two genes. The genetics of PCD is complicated owing to the complexity of axonemal structure that is highly conserved through evolution, which is comprised of multiple proteins. Identifying a PCD-causing gene is challenging due to locus and allelic heterogeneity. Despite genetic heterogeneity, multiple tools have been used, and there are 11 known PCD-causing genes. All of these genes combined explain approximately 50% of PCD cases; hence, more genes need to be identified. This review briefly describes the current knowledge regarding the genetics of PCD and focuses on the methodologies used to identify novel PCD-causing genes, including a candidate gene approach using model organisms, next-generation massively parallel sequencing techniques, and the use of genetically isolated populations. In conclusion, we demonstrate the multipronged approach that is necessary to circumvent challenges due to genetic heterogeneity to uncover genetic causes of PCD.     

Inherited factors in diffuse bronchiectasis in the adult: a prospective study.

To evaluate the prevalence of inherited respiratory ciliary structure and underlying mucus abnormalities in the diffuse bronchiectasis syndrome, we investigated 53 subjects comprising 38 patients with diffuse bronchiectasis confirmed by high-resolution thoracic computed tomography, ten with chronic bronchitis and no diffuse bronchiectasis and five healthy nonsmoking control subjects. The clinical history was determined by means of a standardized questionnaire. Axonemal abnormalities of respiratory cilia were evaluated on bronchial or nasal mucosa samples by transmission electron microscopy (structure) and stroboscopic observation (function). Cystic fibrosis (CF) and Young's syndrome were detected by means of the sweat test and semen analysis when male infertility was suspected. Among the 38 patients with diffuse bronchiectasis, a primary ciliary dyskinesia (PCD) was detected in five (13%) with a high proportion (range: 55-100%) of cilia showing axonemal ultrastructural abnormalities always involving the dynein arms. The prevalence of this inherited condition was higher in North African (36%) than in European patients (4%) (p less than 0.01). After exclusion of the five patients with PCD, the patients with diffuse bronchiectasis showed axonemal ultrastructural abnormalities similar to those with chronic bronchitis. The diagnosis of underlying mucus disorders was based on two types of criterion, i.e. for CF, sweat chloride levels greater than 80 mmol.l-1, or the combination of diagnostic criteria proposed by Stern et al. Respectively, five (three Young's syndrome and two CF) and seven (one Young's syndrome and six CF) cases of inherited mucus disorders were suspected. Our results showed that PCD was highly prevalent among the adult North African patients with diffuse bronchiectasis but relatively rare in the Europeans.     

Primäre ziliäre Dyskinesie

Primary ciliary dyskinesia (PCD) is a rare autosomal recessive disorder with defective structure or function of normally motile cilia, leading to chronic upper and lower respiratory tract infections, fertility problems and organ site abnormalities. The PCD is a genetically heterogeneous condition entailing a broad range of different disease variants. Diagnosing these different PCD phenotypes requires a combined approach using complementary methods for detection of defects of ciliary function, ultrastructure and composition as well as low nasal nitric oxide values and biallelic genetic mutations. To date, mutations in 31 different genes have been linked to PCD permitting a genetic diagnosis in approximately 60?% of cases. Due to the lack of adequate trials evidence-based knowledge on the epidemiology, disease course and management of PCD is currently lacking. An international PCD registry has been developed to overcome these limitations (www.pcdregistry.eu) and is currently recruiting patients. Current treatment regimens have to rely on expert opinions and on experience gained from other respiratory diseases. The management of PCD includes surveillance of pulmonary function, culturing upper and lower airway secretions and diagnostic imaging. Daily airway clearance techniques as well as prompt antibiotic treatment of infections are the cornerstones of PCD treatment regimens.     

Primary ciliary dyskinesia and humoral immunodeficiency – Is there a missing link?

BackgroundPrimary ciliary dyskinesia (PCD) and humoral mmunodeficiency (HID) are both rare disorders which cause recurrent upper and lower respiratory tract infections.ObjectiveTo examine the concurrence of PCD and HID in a patient cohort with known PCD.MethodsRetrospective review of the patient files.ResultsWe describe 11 patients of a cohort of 168 patients with PCD (6.5%) with a combination of PCD and some form of HID. The patients all presented with typical clinical symptoms for PCD, however the role of the concomitant immunological abnormalities is not clear.ConclusionPCD and HID coincided in 6.5% of the patients. We suggest that a common pathophysiological pathway results in both disorders.