The role of pulmonary function testing in pulmonary fibrosis

Interstitial lung diseases are characterized by disruption of the distal pulmonary parenchyma. The clinical history manifestations, cough and dyspnea, and physical exam manifestations, inspiratory crackles, are nonspecific. Pulmonary function testing aids in the evaluation and management of patients with interstitial lung disease although the pattern of abnormality is nonspecific. Pulmonary function testing can provide an estimate of histologic severity but not a definitive quantification of histologic fibrosis or inflammation. Pulmonary function tests can provide a baseline estimation of prognosis and be used to monitor disease progression or response to therapy. The forced vital capacity and diffusion capacity are the most valuable serial measurements, but further data are required to examine composite scoring and exercise gas exchange.     

Prognostic value of clinical exercise testing in idiopathic pulmonary fibrosis

Current guidelines for referring patients with idiopathic pulmonary fibrosis (IPF) for lung transplantation, based on resting parameters, are insufficient to predict 3-year mortality. The aim of this study was to determine the prognostic value of cardio-pulmonary exercise testing (CPET) in patients with IPF. A multicentre retrospective study of 3-year outcome was made on 63 adult patients with IPF who underwent CPET with blood gas analysis. Demographic data, resting pulmonary function and CPET parameters were collected to perform a univariate survival analysis. To estimate prognosis at 3 years, a multivariate logistic regression analysis by Kaplan-Meier curves and log-rank tests was performed. Forty-four patients (70%) were alive without lung transplant at the end of the 3-year follow-up: 19 patients (30%) were dead (n=14) or transplanted (n=5). Univariate analysis indicated that: at rest lower TLC, FVC, DLCO and PaCO(2), higher alveolo-arterial gradient for oxygen [P(A-a)O(2)] and pH; at ventilatory threshold (VT) higher VE/VO(2) and VE/VCO(2) and at peak exercise higher VE/VO(2) and VE/VCO(2), higher pH and ΔP(A-a)O(2)/ΔVO(2) (mmHg/L), lower VO(2) peak, PaO(2) and VO(2)/FC were associated with a significantly lower survival at 3 years. The multivariate logistic regression analysis showed that CPT (<65%) and VE/VO(2) at VT (>45) were independently associated with a lower survival at 3 years. Restriction and hyperventilation at ventilatory threshold are major prognostic factors in the course of IPF. CPET with blood gas analysis may have a prognostic value in these patients and initial evaluation of these parameters can help to predict disease progression.     

Prognostic value of circulating KL-6 in idiopathic pulmonary fibrosis

OBJECTIVE: Circulating levels of KL-6, a high MW glycoprotein (MUC1 mucin), are elevated in a majority of patients with a number of interstitial lung diseases, including idiopathic pulmonary fibrosis (IPF). However, KL-6 levels vary from patient to patient. The aim of the present study was to determine whether the serum KL-6 level at the time of diagnosis predicts prognosis in IPF. METHODS: The relationship between clinical variables and prognosis in 27 patients with IPF were analysed retrospectively. The diagnosis was made by histological examination (n = 16) or on clinical findings including high-resolution CT scanning (n = 11). All patients were followed up for at least 3 years. Variables such as age, FVC%, PaO(2) at rest, initial LDH level, C-reactive protein and KL-6 were used for analysis. RESULTS: At the cut-off level determined by receiver operating characteristic curves, LDH and KL-6 showed a significant correlation with the patient's prognosis by univariate analysis. However, multivariate analysis revealed that only KL-6 was a predictor of prognosis. The patients were categorized by their serum KL-6 levels (as above or below the cut-off level of 1000 U/mL) and their survival estimated using the Kaplan-Meier method. The difference in median survival between the two groups was significant. The median survival of patients with low KL-6 was more than 36 months, whereas that of patients with high KL-6 was only 18 months. CONCLUSION: These results suggest that initial evaluation of serum KL-6 level can predict survival in patients with IPF.     

The role of collagenases in experimental pulmonary fibrosis

Matrix metalloproteinases (MMPs) expression plays a critical role in extracellular matrix deposition. Although several pieces of evidence have so far indicated that gelatinase contributes to the development of pulmonary fibrosis, the role of collagenase remains uncertain. In this study, we attempted to determine the role of collagenase using a bleomycin-induced pulmonary fibrosis model. Bleomycin was instilled into mice intratracheally. Bronchoalveolar lavage fluid (BAL) specimens were analyzed for gelatin and casein zymography, as well as by immunoblotting. The histology of the lungs and hydroxyproline contents were also assessed. MMPs inhibitor, CGS27023A, was simultaneously orally administered. Collagenases were induced in BAL fluids after bleomycin administration based on the data of zymography and immunohistochemistry. The co-administration of MMPs inhibitor, CGS27023A, with bleomycin resulted in worsening pulmonary fibrosis with inhibition of collagenase. The worsening of pulmonary fibrosis was mainly induced by CGS27023A administration in the late phase of bleomycin-induced pulmonary fibrosis development, but not in the early phase. The present data indicated that collagenase plays an anti-fibrotic role in the bleomycin-induced pulmonary fibrosis model. Collagenase has a greater effect on fibrosis phase than inflammatory phase in the bleomycin-induced pulmonary fibrosis in the mice.     

Prognostic scoring systems for clinical course and survival in idiopathic pulmonary fibrosis

Idiopathic pulmonary fibrosis (IPF) is the most common and rapidly fatal among idiopathic interstitial pneumonias. Its clinical course is variable. A significant fraction of the population of patients display a slow disease course and can remain stable for years, while other patients show a rapid progressive course and may die within few months from diagnosis. For these reasons estimating prognosis of IPF patients is extremely difficult and has important clinical repercussions on optimal patients management including patients referral for lung transplantation. Several studies have tried to address this key point in the course of the two last decades analyzing different clinical, functional, radiological and biological variables. The purpose of this review is to assess relevant studies published on this subject and to examine the variety of prognostic predictors proposed along with staging systems.     

线粒体DNA在肺纤维化发病机制中的作用

线粒体DNA是体内重要的遗传物质之一,参与编码13种蛋白质,易被活性氧所损伤。近年的研究发现,线粒体DNA损伤可导致线粒体功能障碍,与肺上皮细胞凋亡和肺纤维化的发病关系密切。维持线粒体DNA的完整性可能为治疗肺纤维化提供新的靶点。本文现对线粒体DNA在肺纤维化中的作用及其损伤修复机制的研究进展作简要概述,旨在为临床提供参考。     

Prognostic factors and causes of death in Korean patients with idiopathic pulmonary fibrosis

The purpose of this study was to investigate the prognostic factors at initial presentation and the causes of death in Korean patients with idiopathic pulmonary fibrosis (IPF), which might be different report wise, in comparison to the western countries. A retrospective review of 88 patients (mean 60.3 years, 69 male) was carried out and they were diagnosed as IPF positive. After diagnosis, the survival rate was 57% and 41% for third and fifth year, respectively (mean follow-up 39.1 months). Mortality was closely correlated with severe dyspnea at presentation (Hazard Ratio [HR], 2.6 per grade; p=0.015), lower initial forced vital capacity (HR, 1.7 per 10% predicted; p=0.004) and lower initial diffusing capacity of the lung (HR, 1.5 per 10% predicted; p=0.033). Treatment with specific drugs was ineffective against the survival when compared with symptomatic supportive care. Thirty-four patients (68%) died of worsened respiratory failure, seven (14%) died of infection and only one patient showed cardiovascular death. In conclusion, our study suggests that the severity of dyspnea and lung function tests at the time of diagnosis are the predictive factors for the survival of patients with IPF. In comparison to the reports from western countries, we observed that respiratory failure and pulmonary infection were more frequent causes of death, while cardiovascular death was rare in Korean patients with IPF.     

特发性肺纤维化急性加重患者预后危险因素及意义

目的分析特发性肺纤维化急性加重(AE-IPF)患者住院期间预后的危险因素。 方法选择2013年1月至2020年12月于首都医科大学大兴教学医院呼吸内科确诊为AE-IPF的住院患者99例为对象,采用单因素分析及多因素非条件Logistic回归分析住院期间预后的危险因素。以回归分析有统计学意义指标的中位数为截点值(Cutoff值)分别分组,计算组间生存率。 结果单因素分析显示,AE-IPF患者住院期间预后危险因素包括：1年内因AE住院次数(P＝0.001)、体温(P＝0.005)、血D-二聚体(P＝0.012)、血白蛋白(P＝0.006)、血乳酸脱氢酶(P＝0.001)、氧合指数(P＝0.002)与AE-IPF患者住院期间死亡相关。多因素Logistic回归分析显示,体温(OR＝22.158,P＝0.042)、1年内因AE住院次数(OR＝2.474,P＝0.011)、血白蛋白(OR＝0.819,P＝0.026)、血乳酸脱氢酶(OR＝1.011,P＝0.049)为AE-IPF患者住院期间预后的危险因素。以体温、血乳酸脱氢酶中位数为截点值分别分组,绘制Kaplan-Meier曲线,组间生存率比较P<0.05。 结论1年内因AE住院次数、体温、血白蛋白及血乳酸脱氢酶,是AE-IPF患者住院期间预后的危险因素。体温、血乳酸脱氢酶对AE-IPF患者住院期间预后有预测意义。     

The role of oxygen radicals in bleomycin-induced pulmonary fibrosis]

A model of pulmonary fibrosis in rat has been developed using intratracheal administration of bleomycin (BLM) A5 (5mg/kg). Histopathologic features and total lung collagen were studied. We found that type I pneumocytes detached, basement membrane denuded and endothelia edema were the earliest changes in BLM induced pulmonary fibrosis. Serum MDA (an index of lipid peroxidation) level in rats receiving intratracheal bleomycin were increased at earlier time after bleomycin administration. Meanwhile, MDA level in the lung homogenate was elevated too. Our results indicated that the injured type I pneumocytes and endothelia caused by oxygen radicles are the fundamental damages in bleomycin-induced pulmonary fibrosis.     

三种细胞因子表达在特发性肺纤维化中的作用

目的 观察血小板衍生的生长因子（ＰＤＧＦ）、ＡＡ、ＢＢ及转化生长因子（ＴＧＦ）β在特发性肺间质纤维化（ＩＰＦ）支气管灌洗细胞及开胞肺活检标本的蛋白及基因表达，探索其在ＩＰＦ发病中的作用。方法 用免疫组化方法检测７例ＩＰＦ患支气管灌洗细胞ＰＤＧＦ，ＴＧＦ－β蛋白和基因的表达。结果 在肺间质纤维化患支气管灌洗细胞中，ＰＤＧＦ－ＡＡ，ＰＤＧＦ－ＢＢ〉ＴＧＦ－β均定位于肺泡巨噬细胞。三种不同的细胞因子     

Prognostic role of biomarkers and right ventricular dysfunction in pulmonary embolism

Pulmonary embolism is morbidity and mortality remain high. The short-term prognosis of pulmonary embolism depends on haemodynamic status and underlying disease massive pulmonary embolism, defined as pulmonary embolism that is associated with systemic hypotension which increases up to 50% in hospital mortality. However, the in-hospital mortality of patients with normal blood pressure pulmonary embolism has been reported to vary from 3 to 15%. Right ventricular dysfunction showed by echocardiography or computerized tomography and elevated cardiac enzymes have been used to determine mortality in these patients with pulmonary embolism. In this article; we reviewed the prognostic value of right ventricular dysfunction as evaluated by echocardiography or spiral computerized tomography, and the prognostic value of increased levels of cardiac markers in patients with pulmonary embolism.     

The role of eosinophils in asthma

During recent years it has become apparent that the eosinophil may represent a powerful effector cell in the pathogenesis of asthma, particularly in the late asthmatic response. It can be stimulated by a number of stimuli among which PAF appears to be one of the most effective. The eosinophil is a source for a variety of proinflammatory and toxic products with profound effects in the lungs and airways. These eosinophil products mimic some of the features of asthma and the strong association of the eosinophil with asthma has led to the suggestion that asthma would be better classified as “chronic desquamating eosinophilic bronchitis.” Although the evidence known to date is persuasive many questions still remain unanswered and await further investigation. Future therapeutic approaches in asthma may aim at interrupting the mechanisms leading to eosinophil bronchial accumulation and activation.