Role of vitamin D in cystic fibrosis and non-cystic fibrosis bronchiectasis

Bronchiectasis is usually classified as cystic fibrosis(CF) related or CF unrelated(non-CF); the latter is not considered an orphan disease any more, even in developed countries. Irrespective of the underlying etiology, bronchiectasis is the result of interaction between host, pathogens, and environment. Vitamin D is known to be involved in a wide spectrum of significant immunomodulatory effects such as down-regulation of pro-inflammatory cytokines and chemokines. Respiratory epithelial cells constitutively express 1α-hydroxylase leading to the local transformation of the inactive 25(OH)-vitamin D to the active 1,25(OH)_2-vitamin D. The latter through its autocrine and paracrine functions up-regulates vitamin D dependent genes with important consequences in the local immunity of lungs. Despite the scarcity of direct evidence on the involvement of vitamin D deficiency states in the development of bronchiectasis in either CF or non-CF patients, it is reasonable to postulate that vitamin D may play some role in the pathogenesis of lung diseases and especially bronchiectasis. The potential contribution of vitamin D deficiency in the process of bronchiectasis is of particular clinical importance, taking into consideration the increasing prevalence of vitamin D deficiency worldwide and the significant morbidity of bronchiectasis. Given the well-established association of vitamin D deficiency with increased inflammation, and the indicative evidence for harmful consequences in lungs, it is intriguing to speculate that the administration of vitamin D supplementation could be a reasonable and cost effective supplementary therapeutic approach for children with non-CF bronchiectasis. Regarding CF patients, maybe in the future as more data become available, we have to re-evaluate our policy on the most appropriate dosage scheme for vitamin D.

The Role of Vitamin D3 Therapy in Pediatric Bronchiectasis Severity (CF versus non-CF Patients)

Objective: To determine and compare the effect of vitamin D3 supplementation on modifying the disease severity in cystic fibrosis (CF) and non-CF bronchiectasis pediatric patients. Methods: A randomized clinical trial evaluating the role of oral vitamin D3 supplementation for six months, was performed in forty patients with CF and non-CF bronchiectasis under the age of 18 years with vitamin D deficiency or insufficiency. The primary outcome was to reach the sufficient Vitamin D level, the secondary outcome was to reevaluate bronchiectasis severity by following up the frequency, severity of pulmonary exacerbations and lung function after vitamin D3 supplementation. Results: Forty patients completed the trial. The percentage of improvement of vitamin D level after vitamin D3 supplementation for six months was significantly higher in CF (88.3%) than non-CF bronchiectasis patients (59.82%) (P = 0.03). Additionally, moderate to severe pulmonary exacerbations significantly decreased by more than 60%, 45% (P = 0.001, 0.005) and frequent exacerbations decreased by 15%, 10% (P = 0.327, 0.490), while the forced expiratory volume in 1 (FEV1) significantly increased by 17% and 15% in non CF bronchiectasis and CF patients respectively (p < 0.001). Conclusions: Vitamin D3 therapy was effective in decreasing the frequency and severity of pulmonary exacerbations and preserving lung function. Thereby, improving the disease severity even more in non-CF bronchiectasis than CF patients.

中性粒细胞胞外陷阱在慢性气道炎症性疾病中作用的研究进展

中性粒细胞胞外陷阱(NETs)是由DNA和抗菌蛋白组成的大型网状结构,能够结合病原体,防止微生物传播并降解细菌毒力因子。然而NETs组成蛋白如蛋白酶、抗菌蛋白、组蛋白和DNA过度释放也会导致组织损伤、黏膜纤毛清除受损和炎症增加。许多研究已将气道NETs形成与慢性气道炎症性疾病中疾病严重程度增加、急性加重次数增加和整体疾病恶化结局联系起来。本文将综述NETs在肺囊性纤维化、慢性阻塞性肺疾病、哮喘和支气管扩张慢性气道炎症性疾病中的作用。

长期大环内酯类抗生素治疗非囊性纤维化支气管扩张症疗效与风险的系统评价和Meta分析

目的评估长期大环内酯类抗生素治疗非囊性纤维化支气管扩张症的疗效与风险。方法分别检索中国知网、万方数据、中国生物医学网、维普网、PubMed、Embase、Cochrane Library及Web of Science数据库中已发表的关于长期大环内酯类抗生素治疗非囊性纤维化支气管扩张症疗效与风险的随机对照研究。主要结局指标为急性发作频率、24 h痰量改变、炎症指标改变、菌群分布变化与菌群耐药变化。结果共纳入11项随机对照试验,长期大环内酯类抗生素治疗显著降低非囊性纤维化支气管扩张症的急性加重频率,包括至少发生一次急性加重人数(RR=0.63,95%CI:0.46~0.86,P=0.004)和人均急性加重次数(MD=-1.29,95%CI:-1.72~-0.86,P<0.00001)以及降低24 h痰量(MD=-8.10,95%CI:-12.62~-3.58,P=0.0004)。亚组分析显示,3个月以上大环内酯类抗生素治疗可有效降低成年患者急性加重频率。在3个月以下疗程亚组、红霉素治疗亚组以及儿童患者亚组中,大环内酯类抗生素未显著降低急性加重频率。患者种族差异未对治疗效果产生明显影响。基线水平常见痰菌种类及数量、治疗结束后的痰菌种类及数量、治疗结束后痰菌的增加和清除率指标在大环内酯类抗生素治疗组和对照组之间的差异均无统计学意义,但大环内酯类抗生素治疗组的痰菌耐药率显著增加。结论3个月以上大环内酯类抗生素治疗可以显著降低成人非囊性纤维化支气管扩张症患者的急性加重频率,减少24 h痰量。长期大环内酯类抗生素治疗对非囊性纤维化支气管扩张症患者痰菌分布及变化无显著影响,但有提高耐大环内酯类抗生素细菌比例的风险。

吸入性抗菌药物在囊性纤维化长期管理中的应用

吸入性抗菌药物治疗可以提高靶点浓度和优化药动学/药效学指标,同时减少全身性暴露,在国外已用于囊性纤维化(cysticfibrosis,CF)、非CF支气管扩张以及呼吸机相关性肺炎的治疗研究。铜绿假单胞菌(Pseudomonas aeruginosa,Pa)是CF常见病原菌,可引起肺疾病的急性加重、肺功能加速恶化和降低生存率,首选治疗为吸入性抗菌药物。目前,我国尚没有吸入性抗菌药物制剂上市,影响了CF的临床治疗和管理。妥布霉素注射液的说明书中有记载气道局部用法,其雾化吸入用于治疗CF合并Pa感染在国内已有应用经验,国外也对妥布霉素注射液的有效性和安全性有了初步的研究,提示其可能成为现阶段我国药物可及的一种可接受的、暂时的替代。随着我国报道的CF病例逐年增多,吸入性抗菌药物在CF长期管理中的重要性应该得到重视。

支气管扩张严重程度指数和FACED评分对支气管扩张症严重性评估的比较研究

目的比较支气管扩张严重程度指数(bronchiectasis severity index, BSI)和FACED评分在评价我国非囊性支气管扩张症(non–cystic fibrosis bronchiectasis, NCFB)患者严重程度分级方面的差异。方法选取2015年1月至2020年3月清华大学附属北京清华长庚医院确诊的NCFB患者41例,根据患者BSI及FACED评分分别定义其严重程度级别,并应用IBM SPSS 26.0软件分析结果。结果根据BSI评分,轻度13例(31.7%)、中度13例(31.7%)、重度15例(36.6%)。根据FACED评分,轻度21例(51.2%)、中度14例(34.1%)、重度6例(14.6%)。二者在评价严重程度分级方面差异有统计学意义(P<0.001),具备中等强度一致性(一致率63.4%,Cohen’s Kappa=0.459, 95%CI:0.259~0.659,P<0.001)。结论与FACED评分相比,BSI评分下的NCFB患者严重程度倾向性更高,这可能与BSI评分系统中增加了既往住院史、急性加重史、其他病原体定植以及BMI等影响因素有关。

长期低剂量大环内酯类药物在支气管扩张症中的应用及安全性

支气管扩张症是支气管树的病理性、永久性扩张。作为我国的常见病,由于患者认识不足、不重视,症状常见易误诊漏诊、缺乏简单准确的普查手段等原因,我国的支扩患病率被远远低估。目前研究认为,大环内酯类药物作为广谱抗生素,不仅有抗菌作用,还有抗炎和免疫调节功能。多项大型临床试验证实,长期低剂量大环内酯类药物在治疗支扩患者时,有减少急性发作次数、延缓肺功能下降、减少痰量及清除痰菌、提高生活质量等作用。大环内酯类药物的长期使用会带来细菌耐药和菌群失调等风险,其较为常见的不良反应器官为消化系统,其次为皮肤、循环系统,用药期间医生应密切观察患者的临床表现,确保用药安全。大环内酯类药物治疗支扩的潜能不容小觑,其对支扩患者的临床应用价值尚有很多问题急需解决。本文对长期低剂量大环内酯类药物在成人支气管扩张症中的应用指征及安全性作一综述。

与三种呼吸系统疾病关联的男性不育症

男性不育症是一种复杂的临床综合征,任何干扰男性生殖功能的疾病都可能导致男性不育症,这使临床实践中男性不育症病因诊断变得复杂。呼吸系统上皮纤毛与男性精子鞭毛之间存在相似的超微解剖结构,纤毛和鞭毛功能障碍将影响呼吸道黏膜清除功能和精子运动。另外,某些遗传缺陷也可同时导致呼吸系统和男性生殖系统的异常。这类影响男性生育的呼吸系统疾病主要包括原发性纤毛运动障碍、囊性纤维化和Young综合征,介绍这三种疾病的主要临床特点及研究进展,并分析其呼吸系统与生殖系统临床表现之间的异同,以助于加强对这类疾病的认识。对于严重弱精子症患者,临床医生应常规询问呼吸系统病史,对于反复呼吸道感染的患者同样应关注他们的生育问题。

1-磷酸鞘氨醇与肺部疾病的研究进展

1-磷酸鞘氨醇(sphingosine-1-phosphate,S1P)是一种具有生物活性的细胞膜的重要组成部分以及鞘脂类代谢产物之一。S1P也是调节细胞内外多种生物学功能的重要信号分子,通过与5种G蛋白偶联受体亚型结合(即S1PR1-S1PR5)产生不同的生物学功能,包括调节细胞增殖、存活、凋亡、炎症诱导及血管再生等。近年来研究表明S1P及其S1PR/SPHK对肺部疾病的发生发展起着重要的作用,尤其对支气管哮喘、肺纤维化、肺炎、支气管扩张、慢性阻塞性肺病(chronic obstructive pulmonary disease,COPD)以及肺癌的发生发展起着关键的作用,这或许为肺部疾病的治疗提供一个新途径。

Imaging evaluation of hemoptysis in children

Hemoptysis is an uncommon but distressing symptom in children. It poses a diagnostic challenge as it is difficult to elicit a clear history and perform thorough physical examination in a child. The cause of hemoptysis in children can vary with the child's age. It can range from infection, milk protein allergy and congenital heart disease in early childhood, to vasculitis, bronchial tumor and bronchiectasis in older children. Acute lower respiratory tract infections are the most common cause of pediatric hemoptysis. The objective of imaging is to identify the source of bleeding, underlying primary cause, and serve as a roadmap for invasive procedures. Hemoptysis originates primarily from the bronchial arteries. The imaging modalities available for the diagnostic evaluation of hemoptysis include chest radiography, multi-detector computed tomography(MDCT), magnetic resonance imaging(MRI) and catheter angiography. Chest radiography is the initial screening tool. It can help in lateralizing the bleeding with high degree of accuracy and can detect several parenchymal and pleural abnormalities. However, it may be normal in up to 30% cases. MDCT is a rapid, non-invasive multiplanar imaging modality. It aids in evaluation of hemoptysis by depiction of underlying disease, assessment of consequences of hemorrhage and provides panoramic view of the thoracic vasculature. The various structures which need to be assessed carefully include the pulmonary parenchyma, tracheobronchial tree, pulmonary arteries, bronchial arteries and non-bronchial systemic arteries. Since the use of MDCT entails radiation exposure, optimal low dose protocols should be used so as to keep radiation dose as low as reasonably achievable. MRI and catheter angiography have limited application.

儿童囊性纤维化1例并临床分析

目的提高呼吸专科医生对囊性纤维化的认识。方法昆山市中西医结合医院2016年12月收治1例自幼有临床表现的囊性纤维化病人,回顾并分析其诊断治疗经过,复习相关文献总结其临床特征、鉴别诊断要点及最新治疗进展。结果囊性纤维化起病年龄较早,病人自幼年起即反复出现呼吸系统症状,但确诊时间晚,对治疗及预后产生一定影响。结论应提高对囊性纤维化的识别,对于发病年龄早、合并支气管扩张、反复肺部感染的患儿应重视囊性纤维化的筛查。

黏蛋白5B在肺部疾病中的研究进展

气道黏液层对气道产生保护性作用,但其过度分泌会使机体产生疾病。目前气道黏液高分泌的产生机制尚不明确,黏液蛋白是一种黏液层的关键成分,其中黏蛋白5B的表达与多种肺部疾病的发生及发展有密切联系。黏蛋白5B的表达会对黏液纤毛清除产生明显影响,它的缺失会造成气道中黏液的积聚,最终导致由多种细菌引起的慢性感染。因此,黏蛋白5B有望成为气道黏液高分泌治疗的一个靶点,对其研究会为肺部疾病的发生、发展及治疗提供新的理论依据。

Relationship between chronic rhinosinusitis and lower airway diseases: An extensive review

Signifcant links between allergic rhinitis and asthma have been reported, and the united airway disease hypothesis is supported by numerous findings in epidemiologic, physiologic, pathologic, and immunologic studies. The impact of allergic rhinitis on asthma has been esta-blished. On the other hand, the relationship between chronic rhinosinusitis and lung diseases has been under investigation. Chronic rhinosinusitis is a common disease, and the high prevalence of chronic rhinosinusitis in some kinds of lung diseases has been reported. Recent studies suggest that the treatment of chronic rhinosinusitis has beneficial effects in the management of asthma. Here, we present an overview of the current research on the relationship between chronic rhinosinusitis and lower airway diseases including asthma, chronic obstructive pul-monary disease, cystic fibrosis, diffuse panbronchiolitis, primary ciliary dyskinesia, idiopathic bronchiectasis, and allergic bronchopulmonary aspergillosis.

特发性肺间质纤维化1例并文献复习

特发性肺间质纤维化(IPF)是临床少见疾病,其常容易被误诊为支气管扩张、肺炎及其他间质性肺病。IPF诊断困难,预后不佳,既往缺乏有效的治疗药物,曾被称为“不是癌症的‘癌症’”,抗纤维化药物的出现使该病近年来成为研究的热点。本文回顾性分析珠海市中西医结合医院收治的1例83岁IPF女性患者的病例资料,并进行相关文献复习。

成人囊性纤维化1例并文献复习

目的报告1例成人囊性纤维化患者的诊断及治疗过程并文献复习,以提高临床医生对此种罕见疾病的认识,实现早期诊断、规范治疗和管理。方法回顾性分析2022年4月9日山东省千佛山医院呼吸与危重症医学科收治的以支气管扩张并咯血为主要表现的1例囊性纤维化患者的临床资料。分别以“囊性纤维化”“Cystic Fibrosis”AND“Case Reports”为关键词检索中国知网、万方数据知识服务平台、PubMed数据库中相关文献,进行分析与总结。结果患者,女,24岁,因“反复咳嗽、咳痰,活动耐力下降20余年,咯血6年”就诊,根据患者支气管扩张并咯血、反复肺部感染、胃肠动力不足、电解质紊乱等临床症状及影像学改变,结合基因检测提示c.320C>A:p.A107D纯合变异,诊断为囊性纤维化。结论国人囊性纤维化发病率低,临床医师需要提高其病因及临床表现的认识,当患者出现气道、消化腺、消化道、汗腺等多处黏液流变学改变时,需考虑囊性纤维化,建议行基因检测,早期诊断并及时治疗,有助于改善预后。

儿童肺康复应用进展

肺康复是对慢性呼吸道疾病患者多学科、综合的干预, 内容包括运动训练、行为改变及自我管理等, 旨在改善慢性呼吸道疾病患者的身心状况, 促进健康行为的长期坚持。肺康复在成人慢性呼吸系统疾病, 如慢性阻塞性肺病中已广泛应用, 在儿童呼吸相关疾病中也有应用。不同疾病肺康复策略有所不同, 肺康复方案应根据患儿基础疾病进行个体化选择。现就运动训练肺康复在儿童支气管哮喘、囊性纤维化、支气管扩张症、支气管肺发育不良、闭塞性细支气管炎、神经肌肉疾病并呼吸问题、重症肺炎中的应用进行综述。

环丙沙星治疗非囊性纤维化支气管扩张症有效性及安全性的Meta分析

目的系统评价环丙沙星治疗非囊性纤维化支气管扩张症的疗效和安全性。方法计算机检索PubMed、EMbase、The Cochrane Library、CBM、VIP、CNKI和WanFang Data数据库,搜集关于环丙沙星治疗非囊性纤维化支气管扩张症的随机对照试验(RCT),检索时限均从建库至2018年8月。由2位研究员独立筛选文献、提取资料并评价纳入研究的偏倚风险后,采用RevMan 5.3软件进行Meta分析。结果最终纳入9个RCT,共1 666例患者。Meta分析结果显示,稳定期治疗时,环丙沙星组的呼吸道细菌根除率[RR=4.34,95%CI(2.04,9.23),P=0.000 1]、急性加重情况再发生率[RR=0.81,95%CI(0.71,0.93),P=0.002]和痰液细菌负荷量[MD=–4.08,95%CI(–6.29,–1.87),P=0.000 3]均优于对照组。此外,两组在临床有效率和不良反应方面差异无统计学意义。结论环丙沙星治疗可有效降低稳定期非囊性纤维化支气管扩张症患者的急性加重情况再发生率、痰液细菌负荷量,更好地根除呼吸道细菌。但受纳入研究的数量和质量限制,上述结论尚需要开展更多研究予以验证。

大环内酯类药物非抗菌作用及其在支气管扩张症治疗中的应用研究进展

大环内酯类药物具有抑制炎症反应、减少气道黏液分泌、降低病原体载量等非抗菌作用。儿童支气管扩张症严重影响患儿生存质量和生长发育,目前尚无特效治疗,感染、慢性气道炎症、黏液纤毛清除作用受损参与其发生发展,大环内酯类药物的非抗菌作用可在这些环节发挥作用。该文就大环内酯类药物的非抗菌作用在儿童囊性纤维化、非囊性纤维化支气管扩张症、原发性纤毛运动障碍治疗中的有效性、安全性等应用研究的进展进行综述,供临床实践参考。

非囊性纤维化支气管扩张症的最新进展

支气管扩张症是气道多种病原菌清除不良与反复感染引起的慢性炎症与支气管壁破坏，导致气道永久性扩张。非囊性纤维化支气管扩张症（non—cystic fibrosis bronchiectasis，NCFB）是一种临床低估的疾病，诊断时要注意其基础病因，但大多数病因不清楚。治疗要强调个体化并注意随访，临床评价常用的：亡具是莱斯特咳嗽问卷与痰液颜色。要对细菌定植进行定期评价。NCFB的治疗研究很少，长期应用抗生素可改善临床症状，但不降低急性加重发生率，也不改善肺功能。有严重感染或出血危险性的1或2叶严重损害的患者可考虑手术治疗。本文重点为NCFB，指出了其处理及肺移植治疗，进一步研究其病理生理学机制与探索新的治疗方法是非常必要的。

微生物感染及定植在非囊性纤维化支气管扩张症中的研究进展

呼吸道微生物感染及定植被认为是非囊性纤维化支气管扩张症发病的主要原因。以往认为非囊性纤维化支气管扩张症患者的呼吸道感染大多局限于极少数典型病原体，如铜绿假单胞菌、流感嗜血杆菌；然而，近年来已经有越来越多的研究认识到新兴潜在病原体所造成的感染。肺微生物组学研究的兴起，为探讨不同核心菌群及其交互作用，及其对该疾病加重及免疫功能的影响，提供了更广阔的研究前景。