细胞因子网络与特发性肺纤维化

特发性肺纤维化(idiopathic pulmonary fibrosis,IPF)是特发性间质性肺炎中最常见的一种类型,也是一种进展性的不可逆的快速致死性问质性肺疾病.关于IPF发病机制及治疗的研究已经有50余年,目前还没有有效的治疗方案能逆转肺纤维化.IPF的发病机制复杂,细胞因子网络是其重要机制.现已知生长因子、细胞因子、化学因子以及凋亡调节因子在肺纤维化发病机制中起重要作用.目前认为转化生长因子β是细胞因子网络的关键环节,与之相关的各种细胞因子是纤维化进程中的重要介质.本综述总结了IPF发病机制相关的细胞因子及其交互作用,通过对这些与异常损伤修复相关介质的阐述,为IPF靶向治疗提供理论依据.     

Significance of molecular biomarkers in idiopathic pulmonary fibrosis: A mini review

Idiopathic pulmonary fibrosis (IPF) is a chronic, irreversible condition with poor prognosis that is characterized by a variable clinical course in each patient, which renders it a complex disease with unknown causes. Despite the proven efficacy of novel antifibrotic therapies, including pirfenidone and nintedanib, the diagnosis and follow-up of IPF remain challenging. Hence, the identification of molecular biomarkers for early detection of IPF and to predict biologically determined individual clinical courses, has recently piqued the interest of researchers. Previous studies have demonstrated the diagnostic and prognostic efficacy of blood proteins such as KL-6, Surfactant protein (SP)-A, and SP-D, in patients with IPF. Due to their use in clinical practice in Japan, for approximately twenty years, a significant amount of data about these biomarkers has been accumulated. This paper reviews the recent literature on molecular biomarkers for IPF that have been developed in Japan as well as other potential molecular biomarkers.     

特发性肺纤维化的临床研究进展

特发性肺纤维化(IPF)是一种慢性进行性发展的并以普通性间质性肺炎为特征性病理改变的一种间质性肺疾病.新的指南中IPF定义为病因不明的疾病,但2011指南指出了IPF可能的高危因素,比如吸烟、环境及遗传因素等.IPF患者在临床症状出现后,大多死于呼吸衰竭,中位生存期只有2~5年.目前并没有药物能够明确改善患者的预后,本文强调临床检查血气分析、肺功能、凝血及血常规、6分钟步行试验、高分辨率CT对IPF的诊断意义,并通过检查了解疾病发展情况,从而对疾病做出综合评估,掌握常见的IPF并发症,做出合适的临床处理意见.     

Non-invasive biomarkers in pulmonary fibrosis

The practise of modern medicine is unthinkable without biological markers, and their adoption is now established in various clinical settings. Pulmonary fibrosis occurs in a heterogeneous group of diseases. IPF is the most frequent fibrotic lung disease and has a poor prognosis. Despite the heterogeneity in underlying diseases multiple common mechanism resulting in pulmonary fibrosis are documented. In this context, several biomarkers for pulmonary fibrosis have been described. Some substances are produced by alveolar epithelial cells such as surfactant proteins A and D, the glycoprotein Krebs von den Lungen 6 Antigen, while others are derived from macrophages such as CCL18. Most recently, increased fibrocyte counts were proposed as a marker of acute exacerbation in IPF. None of these markers is established in clinical practise so far. Studies regarding the clinical value of biomarkers in pulmonary fibrosis are hampered by the fact that fibrotic lung diseases are uncommon and variable in course. However, some markers are clearly promising, and as a spin-off the analysis of some of these in samples from recently finished pharmacological multicentric studies might give urgently needed information regarding their clinical value.     

Clinical impact of the radiological indeterminate for usual interstitial pneumonia pattern on the diagnosis of idiopathic pulmonary fibrosis

BackgroundIdiopathic pulmonary fibrosis (IPF) is a fatal lung disease associated with significant morbidity and mortality. The international clinical practice guidelines for the diagnosis of IPF have recently been revised.MethodsIn this single-center retrospective study conducted between June 2006 and March 2018, 27 patients with a newly classified indeterminate for usual interstitial pneumonia (UIP) pattern on high-resolution computed tomography (HRCT) who had undergone surgical lung biopsy were enrolled at the Japanese Red Cross Medical Center. Clinical and pathological characteristics and prognosis were retrospectively analyzed from patient records.ResultsOn the basis of multidisciplinary discussion (MDD), IPF was diagnosed in six patients (22%), unclassifiable interstitial pneumonia in 5 (19%), chronic hypersensitivity pneumonitis in 10 (37%), collagen vascular disease-associated interstitial lung disease in 5 (19%), and lymphoproliferative disorder in 1 (4%) patient. Ground-glass opacity, peribronchovascular distribution, upper or middle lobe distribution, mosaic attenuation, consolidation patterns, and honeycombing were found on HRCT. Histological UIP or probable UIP was observed in seven patients. The median survival time from the initial visit was 2770 days (92.3 months). There was a significant difference in survival time in the GAP stage and honeycombing on HRCT according to the log-rank test.ConclusionsPatients with an indeterminate for UIP pattern on HRCT were more likely to have non-IPF than IPF through pathological diagnosis and MDD. GAP stage and honeycombing on HRCT may be significant risk factors for all-cause mortality.     

气道中心性间质纤维化

气道中心性问质纤维化是新近报道的目前认为不同于现有已知任何一型的间质性肺疾病.其病因不明,性质不清,女性多见,以慢性咳嗽和缓慢进展的呼吸困难为主要症状,肺功能显示限制性通气功能障碍,支气管肺泡灌洗液有轻到中度的淋巴细胞增加,其病理特点为以膜性及呼吸性细支气管为中心的间质纤维化和细支气管上皮化生,影像学显示病变累及大气道,激素治疗效果差,预后不佳.现就气道中心性间质纤维化作一综述.     

Effects of pulmonary rehabilitation in patients with idiopathic pulmonary fibrosis

Background and objective:   Although pulmonary rehabilitation is effective for patients with COPD, its efficacy in patients with IPF is unknown. The purpose of this study was to evaluate the effects of pulmonary rehabilitation in IPF.
Methods:   Thirty patients diagnosed with IPF, according to the consensus statement, were randomly assigned to the rehabilitation group or the control group. The pulmonary rehabilitation mainly consisted of a 10-week programme of exercise training. Pulmonary function, blood gas analysis, 6MWD, dyspnoea rating with the baseline dyspnoea index and health-related quality of life score on the St George's Respiratory Questionnaire were evaluated at baseline and after the programme.
Results:   Assessment of efficacy was carried out on 13 patients who completed the programme and 15 patients in the control group. There were no significant effects of the programme on measures of pulmonary function, values of arterial blood gas analysis or dyspnoea rating. Although there were some differences in the baseline 6MWD and total health-related quality of life score which were not statistically significant, marked improvements were observed in the 6MWD (mean difference 46.3 m (95% CI: 8.3–84.4), P  < 0.05) and the total health-related quality of life score (−6.1 (95% CI: −11.7 to −0.5), P  < 0.05).
Conclusions:   Pulmonary rehabilitation improves both exercise capacity and health-related quality of life in patients with IPF.     

特发性肺纤维化急性加重的最新研究进展

特发性肺纤维化(idiopathic pulmonary fibrosis,IPF)是一种病因不明的慢性进展性纤维化型间质性肺炎,组织学表现为普通型间质性肺炎.IPF通常是缓慢进展,但部分IPF患者可以出现急剧、原因不明的临床明显恶化,称之为IPF急性加重.IPF急性加重难以预测、病死率高、缺乏有效的治疗措施.本文就近年来IPF急性加重的发病率、危险因素、病理生理、发病机制、诊断和治疗等方面的研究进展进行综述.     

Diagnostic disparity of previous and revised American Thoracic Society guidelines for idiopathic pulmonary fibrosis

BACKGROUND:A revised guideline for the diagnosis of idiopathic pulmonary fibrosis (IPF) was formulated by the American Thoracic Society (ATS) in 2011 to improve disease diagnosis and provide a simplified algorithm for clinicians. The impact of these revisions on patient classification, however, remain unclear.OBJECTIVE:To examine the concordance between diagnostic guidelines to understand how revisions impact patient classification.METHODS:A cohort of 54 patients with either suspected IPF or a working diagnosis of IPF was evaluated in a retrospective chart review, in which patient data were examined according to previous and revised ATS guidelines. Patient characteristics influencing the fulfillment of diagnostic criteria were compared using one-way ANOVA and χ² tests.RESULTS:Revised and previous guideline criteria for IPF were met in 78% and 83% of patients, respectively. Revised guidelines modified a classification based on previous guidelines in 28% of cases. Fifteen percent of patients meeting previous ATS guidelines failed to meet revised criteria due to a lack of honeycombing on high-resolution computed tomography and the absence of a surgical lung biopsy. Patients failing to meet previous and revised diagnostic criteria for IPF were younger.CONCLUSION:The revised guidelines for the diagnosis of IPF classify a substantial proportion of patients differently than the previous guidelines.     

特发性肺纤维化的综合诊断进展

特发性肺纤维化是最常见的一种特发性间质性肺炎,组织病理表现为普通型间质性肺炎,临床表现为进行性呼吸困难伴有刺激性干咳,确诊依赖于外科肺活检。但肺活检风险大、费用高,不易被患者接受。近年来研究发现综合HRCT、血清标志物、以及肺功能、支气管肺泡灌洗液等检查,可以对IPF作出早期准确的诊断。本文将从上述几个方面作一介绍。