• Title/Summary/Keyword: IPF (idiopathic pulmonary fibrosis)

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Therapeutic potential of targeting kinase inhibition in patients with idiopathic pulmonary fibrosis

  • Kim, Suji;Lim, Jae Hyang;Woo, Chang-Hoon
    • Journal of Yeungnam Medical Science
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    • 제37권4호
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    • pp.269-276
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    • 2020
  • Fibrosis is characterized by excessive accumulation of extracellular matrix components. The fibrotic process ultimately leads to organ dysfunction and failure in chronic inflammatory and metabolic diseases such as pulmonary fibrosis, advanced kidney disease, and liver cirrhosis. Idiopathic pulmonary fibrosis (IPF) is a common form of progressive and chronic interstitial lung disease of unknown etiology. Pathophysiologically, the parenchyma of the lung alveoli, interstitium, and capillary endothelium becomes scarred and stiff, which makes breathing difficult because the lungs have to work harder to transfer oxygen and carbon dioxide between the alveolar space and bloodstream. The transforming growth factor beta (TGF-β) signaling pathway plays an important role in the pathogenesis of pulmonary fibrosis and scarring of the lung tissue. Recent clinical trials focused on the development of pharmacological agents that either directly or indirectly target kinases for the treatment of IPF. Therefore, to develop therapeutic targets for pulmonary fibrosis, it is essential to understand the key factors involved in the pathogenesis of pulmonary fibrosis and the underlying signaling pathway. The objective of this review is to discuss the role of kinase signaling cascades in the regulation of either TGF-β-dependent or other signaling pathways, including Rho-associated coiled-coil kinase, c-jun N-terminal kinase, extracellular signal-regulated kinase 5, and p90 ribosomal S6 kinase pathways, and potential therapeutic targets in IPF.

Recent Advances in Idiopathic Pulmonary Fibrosis

  • Park, Sanghoon;Lee, Eun Joo
    • Tuberculosis and Respiratory Diseases
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    • 제74권1호
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    • pp.1-6
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    • 2013
  • The concept on idiopathic pulmonary fibrosis (IPF) pathogenesis has progressed from chronic inflammation to aberrant wounding healing and even more to the current paradigms of a multifactorial and heterogeneous disease process. Despite the growth of clinical trials for IPF, most of the results, including N-acetylcysteine combination, warfarin, and bosentan, were disappointing. On the other hand, there have been a number of important developments; the foremost is the licensing of pirfenidone in Europe and Asia. In this article, we briefly review the recent knowledge of pathogenesis of IPF. We also summarize the recent clinical trials regarding the management of IPF.

Therapeutic Use of Stem Cell Transplantation for Cell Replacement or Cytoprotective Effect of Microvesicle Released from Mesenchymal Stem Cell

  • Choi, Moonhwan;Ban, Taehyun;Rhim, Taiyoun
    • Molecules and Cells
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    • 제37권2호
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    • pp.133-139
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    • 2014
  • Idiopathic pulmonary fibrosis (IPF) is the most common and severe type of idiopathic interstitial pneumonias (IIP), and which is currently no method was developed to restore normal structure and function. There are several reports on therapeutic effects of adult stem cell transplantations in animal models of pulmonary fibrosis. However, little is known about how mesenchymal stem cell (MSC) can repair the IPF. In this study, we try to provide the evidence to show that transplanted mesenchymal stem cells directly replace fibrosis with normal lung cells using IPF model mice. As results, transplanted MSC successfully integrated and differentiated into type II lung cell which express surfactant protein. In the other hand, we examine the therapeutic effects of microvesicle treatment, which were released from mesenchymal stem cells. Though the therapeutic effects of MV treatment is less than that of MSC treatment, MV treat-ment meaningfully reduced the symptom of IPF, such as collagen deposition and inflammation. These data suggest that stem cell transplantation may be an effective strategy for the treatment of pulmonary fibrosis via replacement and cytoprotective effect of microvesicle released from MSCs.

Diagnostic Approaches for Idiopathic Pulmonary Fibrosis

  • Jae Ha Lee;Jin Woo Song
    • Tuberculosis and Respiratory Diseases
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    • 제87권1호
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    • pp.40-51
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    • 2024
  • Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, fibrosing interstitial pneumonia with a very poor prognosis. Accurate diagnosis of IPF is essential for good outcomes but remains a major medical challenge due to variability in clinical presentation and the shortcomings of existing diagnostic tests. Medical history collection is the first and most important step in the IPF diagnosis process; the clinical probability of IPF is high if the suspected patient is 60 years or older, male, and has a history of cigarette smoking. Systemic assessment for connective tissue disease is essential in the initial evaluation of patients with suspected IPF to identify potential causes of interstitial lung disease (ILD). Radiologic examination using high-resolution computed tomography plays a pivotal role in the evaluation of patients with ILD, and prone and expiratory computed tomography images can be considered. If additional tests such as surgical lung biopsy or transbronchial lung cryobiopsy are needed, transbronchial lung cryobiopsy should be considered as an alternative to surgical lung biopsy in medical centers with experience performing this procedure. Diagnosis through multidisciplinary discussion (MDD) is strongly recommended as MDD has become the cornerstone for diagnosis of IPF, and the scope of MDD has expanded to monitoring of disease progression and suggestion of appropriate treatment options.

간질성 폐질환 (Interstitial Lung Disease)

  • 정만표
    • Tuberculosis and Respiratory Diseases
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    • 제71권3호
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    • pp.163-171
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    • 2011
  • Recently published articles on interstitial lung disease (ILD) have focused on the accurate diagnosis of idiopathic pulmonary fibrosis (IPF), serum biomarkers, acute exacerbation of IPF, the prognostic factors of ILD and the trial of new treatment. In particular, reports on the serum biomarkers such as CC-chemokine ligand 18, surfactant protein, circulating fibrocytes, and acute exacerbation of IPF are sufficient to be mentioned here. Pirfenidone therapy is the most important trial for the treatment of IPF. Other newer treatment trials such as interferon-gamma, sildenafil and imatinib have been reported to be unsuccessful. On the other hand, the sirolimus trial for lymphangioleiomyomatosis is promising. Combined pulmonary fibrosis and emphysema and IgG4-related disease are established to be the new disease entities of ILD.

Searching for Novel Candidate Small Molecules for Ameliorating Idiopathic Pulmonary Fibrosis: a Narrative Review

  • Kyung-il Kim;Rajib Hossain;Xin Li;Hyun Jae Lee;Choong Jae Lee
    • Biomolecules & Therapeutics
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    • 제31권5호
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    • pp.484-495
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    • 2023
  • Idiopathic pulmonary fibrosis (IPF) can be defined as a progressive chronic pulmonary disease showing scarring in the lung parenchyma, thereby resulting in increase in mortality and decrease in the quality of life. The pathophysiologic mechanism of fibrosis in IPF is still unclear. Repetitive microinjuries to alveolar epithelium with genetical predisposition and an abnormal restorative reaction accompanied by excessive deposition of collagens are involved in the pathogenesis. Although the two FDA-approved drugs, pirfenidone and nintedanib, are under use for retarding the decline in lung function of patients suffered from IPF, they are not able to improve the survival rate or quality of life. Therefore, a novel therapeutic agent acting on the major steps of the pathogenesis of disease and/or, at least, managing the clinical symptoms of IPF should be developed for the effective regulation of this incurable disease. In the present review, we tried to find a potential of managing the clinical symptoms of IPF by natural products derived from medicinal plants used for controlling the pulmonary inflammatory diseases in traditional Asian medicine. A multitude of natural products have been reported to exert an antifibrotic effect in vitro and in vivo through acting on the epithelial-mesenchymal transition pathway, transforming growth factor (TGF)- β-induced intracellular signaling, and the deposition of extracellular matrix. However, clinical antifibrotic efficacy of these natural products on IPF have not been elucidated yet. Thus, those effects should be proven by further examinations including the randomized clinical trials, in order to develop the ideal and optimal candidate for the therapeutics of IPF.

Annual Change in Pulmonary Function and Clinical Characteristics of Combined Pulmonary Fibrosis and Emphysema and Idiopathic Pulmonary Fibrosis: Over a 3-Year Follow-up

  • Kim, Yu Jin;Shin, Seong Hyun;Park, Jeong-Woong;Kyung, Sun Young;Kang, Shin Myung;Lee, Sang-Pyo;Sung, Yon Mi;Kim, Yoon Kyung;Jeong, Sung Hwan
    • Tuberculosis and Respiratory Diseases
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    • 제77권1호
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    • pp.18-23
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    • 2014
  • Background: Combined pulmonary fibrosis and emphysema (CPFE) have different pulmonary function tests (PFTs) and outcomes than idiopathic pulmonary fibrosis (IPF). The intention of this study was to identify unknown differences between CPFE and IPF by a retrospective comparison of clinical data including baseline and annual changes in pulmonary function, comorbidities, laboratory findings, clinical characteristics and cause of hospitalization. Methods: This study retrospectively enrolled patients with CPFE and IPF who had undergone PFTs once or several times per year during a follow-up period of three years. Baseline clinical characteristics and the annual changes in the pulmonary function during the follow-up period were compared between 26 with CPFE and 42 patients with IPF. Results: The baseline ratio of forced expiratory volume in one second to forced vital capacity ($FEV_1$/FVC%) in patients with CPFE was lower than that in patients with IPF ($78.6{\pm}1.7$ vs. $82.9{\pm}1.1$, p=0.041). The annual decrease in $FEV_1$/FVC in the CPFE was significantly higher than in the IPF. The annual decreases in diffusion capacity of carbon monoxide and FVC showed no significant differences between the two groups. The symptom durations of cough and sputum were in the CPFE significantly lower than in the IPF. The serum erythrocyte sedimentation rate level at the acute stage was significantly higher than in the IPF. There were no significant differences in the hospitalization rate and pneumonia was the most common cause of hospitalization in both study groups. Conclusion: The annual decrease of $FEV_1$/FVC was in patients with CPFE significantly higher than in the patients with IPF.

Clinical Predictors of Survival in Idiopathic Pulmonary Fibrosis

  • Kim, Ji Hye;Lee, Jin Hwa;Ryu, Yon Ju;Chang, Jung Hyun
    • Tuberculosis and Respiratory Diseases
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    • 제73권3호
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    • pp.162-168
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    • 2012
  • Background: Idiopathic pulmonary fibrosis (IPF) is a progressive disease. Effective treatment is not currently available and the prognosis is poor. The aim of our study was to identify clinical predictors of survival in patients with IPF. Methods: By using medical record database of a university hospital, we reviewed the records of patients who had been diagnosed as having IPF from January 1996 through December 2007. Results: Among 89 patients considered as having interstitial lung disease (ILD) on computed tomography (CT) of the chest, 22 were excluded because of the diagnosis of other ILDs or connective tissue disease, and finally, 67 met the criteria of IPF. The mean age at the diagnosis of IPF was 70 years (range, 41~87 years) and 43 (64%) were male. The mean survival time following the diagnosis of IPF was 40 months (range, 0~179 months). Among them, 28 cases were diagnosed as the progressive state of IPF on the follow-up CT examination, and the mean duration between diagnosis of IPF and progression was 31 months. Multivariate analysis using Cox regression model revealed that body mass index (BMI) less than 18.5 $kg/m^2$ (p=0.030; hazard ratio [HR], 12.085; 95% confidence interval [CI], 1.277~114.331) and CT progression before 36 months from the diagnosis of IPF (p=0.042; HR, 13.564; 95% CI, 1.101~167.166) were independently associated with mortality. Conclusion: Since low BMI at the diagnosis of IPF and progression on follow-up CT were associated with poor prognosis, IPF patients with low BMI and/or progression before 36 months following the diagnosis should be closely monitored.

The Clinical Assessment of Protease-Activated Receptor-2 Expression in Inflammatory Cells from Peripheral Blood and Bronchoalveolar Lavage Fluid in Idiopathic Pulmonary Fibrosis

  • Park, Young Sik;Yoo, Chul-Gyu
    • Tuberculosis and Respiratory Diseases
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    • 제74권6호
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    • pp.264-268
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    • 2013
  • Background: Idiopathic pulmonary fibrosis (IPF) is a lethal pulmonary fibrotic disease. In general, the exaggerated activation of the coagulation cascade has been observed during initiation or maintenance of the fibrotic disease. In our recent study, immunohistochemical expression of protease-activated receptor-2 (PAR-2), which plays a key role in coagulation cascade, was observed in surgical specimen of IPF patients, and associated with poor clinical outcome. The aim of this study was to evaluate the overexpression of PAR-2 in inflammatory cells from peripheral blood and bronchoalveolar lavage fluid in IPF patients. Methods: From May 2011 to March 2012, IPF patients and controls were enrolled in Seoul National University Hospital. Peripheral blood and bronchoalveolar lavage fluid were collected for analysis of PAR-2 expression. Flow cytometry and reverse transcription polymerase chain reaction were used for PAR-2 receptor and mRNA assessment. Results: Twelve IPF patients and 14 controls were included in this study. Among them, flow cytometry analysis was conducted from 26 peripheral blood (patient group, 11; control group, 13) and 7 bronchoalveolar lavage fluid (patient group, 5; control group, 2). The expression of PAR-2 receptor was not different between patient and control groups (p=0.074). Among all 24 population, PAR-2 mRNA assessment was performed in 19 persons (patient group, 10; control group, 9). The mRNA expression of PAR-2 was not significant different (p=0.633). Conclusion: In IPF patients, PAR-2 receptor and mRNA expression were not different from control group.

황기가 C57BL/6J 생쥐의 Bleomycin유발 폐섬유화에 미치는 영향 (The Effects of Astragali Radix on Bleomycin-induced Lung Fibrosis)

  • 이경희;정희재;정승기;윤유식;이형구
    • 대한한의학회지
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    • 제25권2호
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    • pp.41-50
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    • 2004
  • Backgrounds & Objectives: Many acute and chronic lung disorders with variable degrees of pulmonary inflammation and fibrosis are collectively referred to as interstitial lung diseases. Idiopathic pulmonary fibrosis (IPF) is one of several idiopathic interstitial pneumonias with the pathogenesis unclear. Astragali Radix is known to inhibit the Th2 immune response. The effects of Astragali Radix on bleomycin-induced lung fibrosis were evaluated. Materials and Methods: Astragali Radix extract was daily given to the normal rats, control (bleomycin) and treated (bleomycin and Astragali Radix extract, 24.0 mg/10g body weight) rats for 14 days. After 14 days, we observed the change of total leukocyte count and percentage, IFN-gamma and IL-4 in BALF (Bronchoalveolar lavage fluid), and of semiquantitative histological index (SHI). Results: Compared to the control group, Astragali Radix decreased total leukocyte count (p<0.05), lymphocyte (p<0.05), neutrophil (no significance) percentage, SHI (p<0.05), IFN-gamma and IL-4 (p<0.05). Otherwise, macrophage percentage was increased (p<0.01). Conclusion: This study showed that Astragali Radix reduced the incidence of inflammatory cells and cytokines and prevented the fibrosis of tissue in bleomycin-induced lung fibrosis rats.

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