肿瘤坏死因子及转化生长因子在肺间质病变发病机制中的作用

目的 了解肿瘤坏死因子(TNF)-α及转化生长因子(TGF)-β在结缔组织病相关的肺间质病变(CTD-ILD)发病过程中的作用.方法 提取患者肺组织及外周血单个核细胞(PBMCs)总mRNA,通过反转录聚合酶链反应(RT-RCR)法检测TNF-α mRNA,TGF-β mRNA相对含量;通过酶联免疫吸附试验(ELISA)法测定患者血清的TNF-α、TGF-β含量及血清纤维化指标--透明质酸(HA),并分析其与影像学类型和病理类型的关系.结果 肺组织病理改变以纤维化为主的患者肺脏组织及PBMCs中TGF-β mRNA明显升高.血清TGF-β含量及血清HA亦明显升高,而TNF-α在肺组织及PBMCs中未见明显升高.结论 肺组织和PBMCs中TGF-β mRNA、血清TGF-β及HA在肺纤维化发生中起作用,其指标的测定有助于帮助了解肺组织纤维化的程度.     

Connective tissue growth factor: A new and important player in the pathogenesis of fibrosis

Connective tissue fibrosis is the final common pathogenic process for almost all forms of chronic tissue injury. Whether caused by vascular dysfunction, inflammation, metabolic injury, trauma, or environmental agents, once initiated the fibrogenic process results in the progressive replacement of the normal tissue architecture with fibrotic lesions that eventually lead to organ compromise and failure. Fibrosis can be considered as a dysregulation in the normal tissue repair mechanism, resulting in severe tissue scarring. Fibrosis appears to be a consequence of linked processes, including the proliferation of resident fibroblast cell types, the increased production and deposition of extracellular matrix components, and the transition of fibroblasts into cells exhibiting a myofibroblast phenotype. Although transforming growth factor-beta (TGFβ) has long been regarded as a pivotal growth factor in the formation and maintenance of connective tissues and as a major driving influence in many progressive fibrotic diseases, attention has focused recently on the role of connective tissue growth factor (CTGF) in fibrosis. CTGF is selectively and rapidly induced in mesenchymally derived cells by the action of TGFβ. CTGF expression is increased in many fibrosing diseases. In addition, increasing evidence from in vivo and in vitro models of tissue remodeling and fibrosis suggest that CTGF may represent a downstream effector molecule of the profibrotic activities of TGFβ in the maintenance and repair of connective tissues and within fibrotic disease settings.     

细胞因子与间质性肺疾病的发病机制

间质性肺疾病是指以弥漫性肺泡单位慢性炎症和间质纤维化为主要病理特征的一大组疾病。多种细胞因子构成的复杂的细胞因子网络在间质性肺疾病的发病机制中发挥重要作用。Th1/Th2细胞因子在组织损伤、炎症形成、纤维化的各个阶段有不同作用。化学趋化因子在炎症组织中吸引和激活白细胞亚群,调节血管生成,促进纤维化的形成。     

IL-24: A new player in the pathogenesis of pro-inflammatory and allergic skin diseases

Interleukin (IL)-24 is a member of the IL-20 family of cytokines and is produced by various types of cells, such as CD4⁺ T cells, NK cells, mast cells, keratinocytes, bronchial epithelial cells, and myofibroblasts. Previous studies suggest that IL-24 plays an essential role in the pathogenesis of pro-inflammatory autoimmune disorders such as psoriasis, arthritis, and inflammatory bowel diseases. However, the role of IL-24 in the pathogenesis of allergic diseases has been elusive. It has already been reported that IL-24 is involved in the pathogenesis of allergic lung and skin diseases. Moreover, we have recently revealed for the first time the pivotal functions of IL-24 in IL-13–mediated skin barrier dysfunction in atopic dermatitis (AD), which is known to be a characteristic of AD caused by Th2 cytokines such as IL-4 or IL-13. In this review, we show recent advances in the basic characteristics of IL-24 and its novel functions in the pathogenesis of allergic skin inflammation, focusing on AD. A better understanding of the role of IL-24 in allergic diseases can lead to the development of new therapeutic options.     

Relationship between lung inflammation or fibrosis and frequency dependence of compliance in interstitial pulmonary diseases

In order to find a physiological parameter which discriminates between the predominance of inflammation or fibrosis, pulmonary function tests and open lung biopsy were performed on 19 patients with interstitial lung disease. Our results showed that the only test which may be useful is the dynamic lung compliance/quasi-static lung compliance (Cdyn/Cst) index. In this context, values equal or lower than 0.85 of the Cdyn/Cst index indicate that inflammation predominates, and values higher than 0.85 suggest that interstitial fibrosis is the main feature.     

Cluster phenotypes in a non-idiopathic pulmonary fibrosis fibrotic interstitial lung diseases cohort in Singapore

BackgroundNon-idiopathic pulmonary fibrosis fibrosing interstitial lung diseases (F-ILDs) may demonstrate a progressive disease trajectory similar to idiopathic pulmonary fibrosis (IPF). We aimed to identify novel F-ILD phenotypes in a multi-ethnic South-East Asian population.MethodsF-ILD subjects (n=201) were analysed using unsupervised hierarchical cluster analysis and their outcomes compared against IPF (n=86).ResultsFour clusters were identified. Cluster 1 (n=53, 26.4%) comprised older Chinese males with high body mass index (BMI) and comorbidity burden, higher baseline forced vital capacity (FVC) percentage predicted and lower diffusing capacity of the lung for carbon monoxide (DLCO) percentage predicted. They had similar mortality to IPF. Cluster 2 (n=67, 33.3%) had younger female non-smokers with low comorbidity burden, groundglass changes on high-resolution chest computed tomography (HRCT) and a positive anti-nuclear antibody (ANA) titre ≥1:160. They had lower baseline FVC and higher DLCO, low mortality and slower lung function decline. Cluster 3 (n=42, 20.9%) consisted male smokers with low comorbidity burden, emphysema on HRCT and high baseline lung function. They had low mortality and slow lung function decline. Cluster 4 (n=39, 19.4%) was the highest risk and comprised of mainly Indians with high BMI. They had the highest proportion of ischemic heart disease (IHD) and previous pulmonary tuberculosis. Subjects had the lowest baseline lung function, highest mortality, and fastest lung function decline. Survival differences across clusters remained significant following adjustment for treatment.ConclusionsWe identified four distinct F-ILD clinical phenotypes with varying disease trajectories. This demonstrates heterogeneity in F-ILD and the need for complementary approaches for classification and prognostication beyond ATS/ERS guideline diagnosis.     

Clinical analysis of autoimmune diseases associated with interstitial lung diseases initially presented with idiopathic pulmonary fibrosis

<正>Objective To describe the clinical characteristics of patients with autoimmune diseases associated interstitial lung diseases(AID-ILD) initially presented with idiopathic pulmonary fibrosis(IPF) in a tertiary Chinese hospital.Methods We conducted a retrospective analysis of 14 patients diagnosed with AID-ILD during the IPF follow-up between January 2016 and December 2021.     

Ghrelin and immunity: a young player in an old field

There is increasing evidence of the coupling of immune status to the metabolic system. The communication between the state of systemic and cellular energy balance to immune compartment is mediated via a complex array of cytokines, hormones and neuropeptides. Ghrelin, a recently described orexigenic peptide hormone, is predominantly produced by the stomach and functions as a positive regulator of the somatotropic axis and a peripheral signal of negative energy balance. Apart from its well-studied metabolic effects, ghrelin also exerts multiple regulatory effects on several other organ systems including the cardiovascular, central nervous and immune systems. Here, we summarize the growing evidence of ghrelin as a significant player in the regulation of inflammation and the immune function and the potential therapeutic targeting of ghrelin or its receptor, the growth hormone secretagogue receptor (GHS-R), in various inflammatory and cachexic disease states.     

PTEN在纤维化疾病中的作用

第10号染色体同源丢失性磷酸酶-张力蛋白基因（PTEN）作为肿瘤抑制基因，可以负性调节肿瘤细胞的生长。目前发现PTEN在纤维化疾病中也有重要的作用和意义，但其与肝纤维化的关系尚不明确，对PTEN在各器官纤维化中的作用这一问题的深入研究可能为纤维化疾病的治疗提供新的思路。本文就近年来PTEN在纤维化疾病中的作用和意义作一综述。     

Treatment in diffuse interstitial lung diseases

Diffuse interstitial lung diseases are parenchymal diseases of the lung with many various etiologies and most of which are idiopathic. The mainstays of the treatment are corticosteroids and immunosuppressants. This paper deals with the treatment of idiopathic interstitial pneumonias and sarcoidosis.     

Induced sputum in interstitial lung diseases

PURPOSE OF REVIEW: Induced sputum is a particularly useful procedure since it provides information on the cellular and molecular constituents in inflammation. Extensive work has demonstrated the application of induced sputum in the management of asthma, chronic obstructive pulmonary disease and chronic bronchitis, but less attention has been paid to its efficacy in diagnosing interstitial lung diseases. This review analyzes the applications of induced sputum in the assessment of sarcoidosis, nongranulomatous interstitial lung diseases, occupational lung diseases and other systemic diseases with or without lung involvement. RECENT FINDINGS: T cell subsets in induced sputum in combination with pulmonary function testing can serve as predictors with high specificity and sensitivity in diagnosing sarcoidosis, using multivariate logistic regression models which can be easily implemented in clinical practice. Differential cell counts in induced sputum are as useful as bronchoalveolar lavage for identifying neutrophilic inflammation in patients with nongranulomatous interstitial lung diseases (e.g. idiopathic pulmonary fibrosis) and detecting chronic rejection in bronchiolitis obliterans syndrome. Sputum analysis has also been shown to be a useful tool for diagnosing, assessing and monitoring occupational lung disorders. SUMMARY: We suggest integrating induced sputum technology to the well-established criteria for the diagnosis of interstitial lung diseases, especially when there are clinical contraindications for performing bronchoscopy or when tissue confirmation is absent for any reason.     

Viral-induced inflammation in interstitial lung diseases

Viruses have long been implicated as either causative agents or propagators of inflammation in interstitial lung diseases. To date, culture of lung tissue specimens or bronchoalveolar lavage has failed to provide evidence of viable viral organisms. Indirect evidence comes from studies reporting serologic evidence of exposure to numerous viruses in individuals with a variety of interstitial lung diseases. A link between viral infection and interstitial lung diseases also has been suggested by some studies that amplified viral DNA from lung biopsy specimens. The lack of reproducibility of some of these studies suggests that some of these findings may have been false-positive results generated by the extreme sensitivity of the molecular methods used. Furthermore, amplification of viral genomic components from tissue specimens does not necessarily imply that the virus had a direct role in causing the lung injury. There is no definitive evidence that viruses participate in the pathogenesis of idiopathic pulmonary fibrosis, sarcoidosis, and Langerhans' cell histiocytosis. It is possible that some viruses may precipitate hypersensitivity pneumonitis in predisposed individuals, and occasional cases of uncommon interstitial lung diseases have been reported to occur during the course of well-documented viral infections, indicating that, at least in some situations, viruses may be the primary cause of interstitial lung disease. The lack of definitive evidence implicating viral infection as a cause of interstitial lung diseases does not rule out a potential role of viruses as a triggering event that may be important for the development of interstitial lung disease in predisposed individuals.     

Smoking-related emphysema and interstitial lung diseases

Smoking-related illnesses contribute to a large number of deaths in the industrialized world and their treatment comprises a substantial percentage of total healthcare dollars. The most common and most well-known smoking-related illnesses include chronic obstructive pulmonary disease, bronchogenic carcinoma, and ischemic heart disease. However, the role of cigarette smoking in the pathogenesis of other lung diseases is becoming increasingly apparent. Knowledge of both the histologic and radiographic manifestations of smoking-related lung disease is important to the radiologist as imaging findings can be nonspecific. Finally, correlation of imaging and clinical information may obviate the need for open lung biopsy.     

Exhaled ethane: an in vivo biomarker of lipid peroxidation in interstitial lung diseases

BACKGROUND: Oxidative stress plays a role in the pathogenesis and progression of interstitial lung disease (ILD). Exhaled ethane is a product of lipid peroxidation that has been proposed as a biomarker of oxidative stress in vivo. OBJECTIVES: To determine whether the exhaled ethane level is elevated in patients with ILD and to compare it with other clinical parameters. METHODS: Breath samples were collected from 34 patients with ILD, including 13 with idiopathic pulmonary fibrosis (IPF), 9 patients with cryptogenic organizing pneumonia, 6 patients with collagen vascular disease-associated interstitial pneumonia, and 6 patients with pulmonary sarcoidosis. Gas samples were obtained at hospital admission and after 3 weeks. After each expired sample was concentrated using a trap-and-purge procedure, the ethane level was analyzed by gas chromatography. RESULTS: Exhaled ethane levels were elevated in ILD patients (n = 34, mean +/- SD, 8.5 +/- 8.0 pmol/dL) compared with healthy volunteers (n = 16, 2.9 +/- 1.0 pmol/dL; p < 0.001). Serial measurements revealed that increase and decrease of ethane levels were largely consistent with the clinical course. Four patients with IPF who had persistently high ethane levels died or deteriorated, whereas those with ethane levels < 5.0 pmol/dL remained stable or improved. Exhaled ethane concentrations were positively correlated with levels of lactate dehydrogenase (Spearman rank correlation coefficient [rs], 0.28, p = 0.026) and C-reactive protein (rs, 0.38, p = 0.025) and were inversely correlated with Pa(O2) (rs, - 0.40, p = 0.0026). Patients showing increased uptake on (67)Ga scintigraphy demonstrated higher ethane levels (n = 19, 7.5 +/- 5.7 pmol/dL) compared with those who did not show increased uptake on scintigraphy (n = 10, 3.0 +/- 2.4 pmol/dL; p < 0.01). CONCLUSIONS: Exhaled ethane is elevated in patients with ILD and is correlated with the clinical outcome, suggesting that it provides useful information about ongoing oxidative stress, and thereby disease activity and severity in ILD.