• Tuberculosis and Respiratory Diseases
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• v.87 no.2
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• pp.123-133
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• 2024

Interstitial lung diseases (ILDs) are a diverse collection of lung disorders sharing similar features, such as inflammation and fibrosis. The diagnosis and management of ILD require a multidisciplinary approach using clinical, radiological, and pathological evaluation. Progressive pulmonary fibrosis (PPF) is a distinct form of progressive and fibrotic disease, occurring in ILD cases other than in idiopathic pulmonary fibrosis (IPF). It is defined based on clinical symptoms, lung function, and chest imaging, regardless of the underlying condition. The progression to PPF must be monitored through a combination of pulmonary function tests (forced vital capacity [FVC] and diffusing capacity of the lung for carbon monoxide), an assessment of symptoms, and computed tomography scans, with regular follow-up. Although the precise mechanisms of PPF remain unclear, there is evidence of shared pathogenetic mechanisms with IPF, contributing to similar disease behavior and worse prognosis compared to non-PPF ILD. Pharmacological treatment of PPF includes immunomodulatory agents to reduce inflammation and the use of antifibrotics to target progressive fibrosis. Nintedanib, a known antifibrotic agent, was found to be effective in slowing IPF progression and reducing the annual rate of decline in FVC among patients with PPF compared to placebos. Nonpharmacological treatment, including pulmonary rehabilitation, supplemental oxygen therapy, and vaccination, also play important roles in the management of PPF, leading to comprehensive care for patients with ILD. Although there is currently no cure for PPF, there are treatments that can help slow the progression of the disease and improve quality of life.

• Journal of Radiopharmaceuticals and Molecular Probes
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• v.8 no.2
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• pp.103-111
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• 2022

Idiopathic pulmonary fibrosis (IPF) is a progressive disease caused by some risk factors, including smoking, viral infection, toxic substances, and radiation, that decline lung function of fresh oxygen and blood delivery throughout the body. Patients with pulmonary fibrosis have suffered from breathing and cough and the average survival rate is only 3 years after diagnosis. Therefore, it is significant to diagnose IPF and start treatment in enough time. Usually, lung biopsy is available to diagnose localized pulmonary fibrotic sites directly. However, it is insufficient to visualize whole lung tissue, and also it has a risk of infection for patients. In the clinic, medical imaging systems can diagnose pulmonary fibrosis non-invasively without infection. In this review, we introduce current medical imaging systems used to diagnose pulmonary fibrosis, including CT, MRI, and nuclear medicine. Further, we introduce several molecular imaging probes targeting specific biomarkers which are expressed in pulmonary fibrosis. Through this paper, it is expected that it would be helpful to understand the latest knowledge and research trends on pulmonary fibrosis diagnostic imaging.

• Journal of Yeungnam Medical Science
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• v.37 no.4
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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.

• Tuberculosis and Respiratory Diseases
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• v.83 no.2
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• pp.107-115
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• 2020

Aging is often viewed as a progressive decline in fitness due to cumulative deleterious alterations of biological functions in the living system. Recently, our understanding of the molecular mechanisms underlying aging biology has significantly advanced. Interestingly, many of the pivotal molecular features of aging biology are also found to contribute to the pathogenesis of chronic lung disorders such as chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis, for which advanced age is the most crucial risk factor. Thus, an enhanced understanding of how molecular features of aging biology are intertwined with the pathobiology of these aging-related lung disorders has paramount significance and may provide an opportunity for the development of novel therapeutics for these major unmet medical needs. To serve the purpose of integrating molecular understanding of aging biology with pulmonary medicine, in this review, recent findings obtained from the studies of aging-associated lung disorders are summarized and interpreted through the perspective of molecular biology of aging.

• Tuberculosis and Respiratory Diseases
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• v.83 no.3
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• pp.195-200
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• 2020

The disease concept of interstitial lung disease with idiopathic pulmonary fibrosis at its core has been relied on for many years depending on morphological classification. The separation of non-specific interstitial pneumonia with a relatively good prognosis from usual interstitial pneumonia is also based on the perception that morphology enables predict the prognosis. Beginning with dust-exposed lungs, initially, interstitial pneumonia is classified by anatomical pathology. Diagnostic imaging has dramatically improved the diagnostic technology for surviving patients through the introduction of high-resolution computed tomography scan. And now, with the introduction of therapeutics, the direction of diagnosis is turning. It can be broadly classified into to make known the importance of early diagnosis, and to understand the importance of predicting the speed of progression/deterioration of pathological conditions. For this reason, the insight of "early lesions" has been discussed. There are reports that the presence or absence of interstitial lung abnormalities affects the prognosis. Searching for a biomarker is another prognostic indicator search. However, as is the case with many chronic diseases, pathological conditions that progress linearly are extremely rare. Rather, it progresses while changing in response to environmental factors. In interstitial lung disease, deterioration of respiratory functions most closely reflect prognosis. Treatment is determined by combining dynamic indicators as faithful indicators of restrictive impairments. Reconsidering the history being classified under the disease concept, the need to reorganize treatment targets based on common pathological phenotype is under discussed. What is the disease concept? That aspect changes with the discussion of improving prognosis.

• Tuberculosis and Respiratory Diseases
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• v.87 no.1
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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.

• Tuberculosis and Respiratory Diseases
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• v.82 no.2
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• pp.102-117
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• 2019

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive fibrosing interstitial pneumonia, which presents with a progressive worsening dyspnea, and thus a poor outcome. The members of the Korean Academy of Tuberculosis and Respiratory Diseases as well as the participating members of the Korea Interstitial Lung Disease Study Group drafted this clinical practice guideline for IPF management. This guideline includes a wide range of topics, including the epidemiology, pathogenesis, risk factors, clinical features, diagnosis, treatment, prognosis, and acute exacerbation of IPF in Korea. Additionally, we suggested the PICO for the use of pirfenidone and nintendanib and for lung transplantation for the treatment of patients with IPF through a systemic literature review using experts' help in conducting a meta-analysis. We recommend this guideline to physicians, other health care professionals, and government personnel in Korea, to facilitate the treatment of patients with IPF.

• Biomolecules & Therapeutics
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• v.31 no.5
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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.

• Tuberculosis and Respiratory Diseases
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• v.73 no.3
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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.

• Tuberculosis and Respiratory Diseases
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• v.79 no.4
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• pp.257-266
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• 2016

Background: Idiopathic pulmonary fibrosis is a common interstitial lung disease; it is a chronic, progressive, and fatal lung disease of unknown etiology. Over the last two decades, knowledge about the underlying mechanisms of pulmonary fibrosis has improved markedly and facilitated the identification of potential targets for novel therapies. However, despite the large number of antifibrotic drugs being described in experimental pre-clinical studies, the translation of these findings into clinical practices has not been accomplished yet. NADH:quinone oxidoreductase 1 (NQO1) is a homodimeric enzyme that catalyzes the oxidation of NADH to $NAD^+$ by various quinones and thereby elevates the intracellular $NAD^+$ levels. In this study, we examined the effect of increase in cellular $NAD^+$ levels on bleomycin-induced lung fibrosis in mice. Methods: C57BL/6 mice were treated with intratracheal instillation of bleomycin. The mice were orally administered with ${\beta}$-lapachone from 3 days before exposure to bleomycin to 1-3 weeks after exposure to bleomycin. Bronchoalveolar lavage fluid (BALF) was collected for analyzing the infiltration of immune cells. In vitro, A549 cells were treated with transforming growth factor ${\beta}1$ (TGF-${\beta}1$) and ${\beta}$-lapachone to analyze the extracellular matrix (ECM) and epithelial-mesenchymal transition (EMT). Results: ${\beta}$-Lapachone strongly attenuated bleomycin-induced lung inflammation and fibrosis, characterized by histological staining, infiltrated immune cells in BALF, inflammatory cytokines, fibrotic score, and TGF-${\beta}1$, ${\alpha}$-smooth muscle actin accumulation. In addition, ${\beta}$-lapachone showed a protective role in TGF-${\beta}1$-induced ECM expression and EMT in A549 cells. Conclusion: Our results suggest that ${\beta}$-lapachone can protect against bleomycin-induced lung inflammation and fibrosis in mice and TGF-${\beta}1$-induced EMT in vitro, by elevating the $NAD^+$/NADH ratio through NQO1 activation.