抽象
Early diagnosis and intervention is essential to prevent progressive lung damage in primary ciliary dyskinesiahttp://ow.ly/JMCE30l8YVa
Primary ciliary dyskinesia (PCD) is a chronic suppurative lung disease that is recessively inherited and has marked clinical phenotypic heterogeneity [1]。The autosomal recessive inheritance and impaired mucociliary clearance secondary to ciliary dysfunction mean the condition is often compared to cystic fibrosis both in terms of outcomes [2] and management [3]。实际上,尽管两者都是与支气管扩张相关的慢性化脓性肺部疾病,但与迄今为止,与囊性纤维化相比,PCD经常被认为是轻度和相对良性的。
This assumption is brought into question by the data presented in the article by Halbeisenet al.[4]在当前的问题中188bet体育备用网址欧洲呼吸杂志。国际PCD(IPCD)队列是一种回顾性收集的数据集,包含诊断测试结果,临床表型,生长和肺功能[5]。The iPCD Cohort contains data on over 3000 patients with a clinical phenotype of PCD from 18 countries. Reliable data for spirometry were analysed from 991 patients aged ≥6 years in the current study by Halbeisenet al.[4],并与年龄匹配的健康个体的参考值相比,并从囊性纤维化患者发表的数据。所有PCD患者,无论年龄或原籍国,肺功能低于健康控制。儿童具有最好的肺功能,随着年龄的增加而恶化。有趣的是,在6-9岁的时候,肺活量测定到患有囊性纤维化的儿童中的相似程度。然而,早期诊断和管理对肺功能结果的影响仍然不确定,因为年龄在诊断和目前肺功能之间没有显着的关系。尽管如此,早期儿童早期肺功能降低的结果与囊性纤维化的肺部功能相似,成人的降低肺功能,突出了侵略性早期管理的重要性和需求。有趣的是,而且类似于H报告的早期功能异常albeisenet al.[4[来自患有PCD和囊性纤维化的年龄匹配儿童的内核活检评估的气道病理变化还显示出类似的炎症和重塑[6],建议结构损伤也在早期和与囊性纤维化相同的程度。虽然数据突出了PCD和囊性纤维化之间的病理生理相似性,但对PCD的早期和积极治疗的需要,统一的多期式随机对照试验将为PCD中的治疗干预措施提供具体证据。最近对PCD中高渗盐水的试验已经进行,并且应该赞扬[7]但是这是一个单一的研究和动力,从而限制了关于这种干预对所选择的主要结果的影响的最终结论。令人鼓舞的是,正在进行多期形欧洲介入试验,包括儿童和成人,以评估维持氮霉素治疗在确认的PCD中的疗效[8]。这将有助于提供有关阿奇霉素抗炎和抗感染作用在改善PCD中的结果方面的作用的信息。从囊性纤维化中的试验中推断出来并在PCD中使用效果是错误的。
在目前的研究中发现了通过肺活量测量测量的特定微管超微结构缺陷和低肺功能之间的显着关系albeisenet al.[4], which is in line with a recent report that has shown a relationship between worse lung clearance index and microtubular ultrastructural defects [9]。两个报告(使用不同的肺功能措施)表明特定超微结构缺陷和肺功能之间的关系引发了有关疾病严重程度的有趣机制问题,以及由特定超微结构缺陷介导的有效粘液间隙的光谱。PCD内的标记疾病异质性被认识到[1] and may partly be explained by efficiency of ciliary function determined by specific ultrastructural defects. For now, the data relating worse lung function to microtubular defects should at least alert clinicians to the potential need for more aggressive management in these patients to try to minimise progressive decline.
结果呈现在目前的研究中albeisenet al.[4毫无疑问,展示了稀有肺病的多期协作和数据收集的优势。此类努力所需的时间和资源不小,但已经显示出显着的益处[5,10,11]。然而,作者承认研究的局限性,并包括缺乏与肺功道结构相关的信息,从成像,血管测定法和气道病原菌之间的关系,并且没有纵向数据显示相同患者的变化随着时间的推移,强调需要前瞻性地进行此类数据收集的需要[12]。The advantages of imaging techniques include the ability to visualise regional disease compared to the global abnormalities detected by spirometry. Although computed tomography (CT) imaging has been used clinically in cystic fibrosis, studies reporting changes in PCD with specific relationships between structural and functional abnormalities are lacking. However, there is some evidence of similar magnetic resonance imaging (MRI) and lung function changes in PCD and cystic fibrosis subjects with mild pulmonary disease [13]。在囊性纤维化的随机对照介入试验中鼓励包含CT成像和MRI,以便改善对囊性纤维化疾病进展的评估[14]。Given that spirometry was less impaired in young adults with PCD in the study by Halbeisenet al.[4[是否需要鼓励对PCD进行疾病进展和区域或局灶性变化来允许对结构功能关系进行调查以允许调查纵向变化。目前的研究是对不同中心收集的数据的回顾性分析,尽管包括的参数是所有客观和强大的,但在未经前瞻性未能进行最大数据采集的机会是一种耻辱。潜在和纵向数据收集,包括统一的评估和所有中心的时间点,以了解长期预后,并为基因型和表型引导的干预措施提供方向。H中发现睫状超微结构缺陷与肺功能的关系albeisenet al.[4] presents an example of how future mechanistic studies might be designed to investigate epithelial and mucociliary function in specific ultrastructural phenotypes to identify novel therapeutic interventions.
脚注
Conflict of interest: None declared.
- 收到July 19, 2018.
- Accepted2018年7月25日。
- 版权所有©ers 2018