The Korean Journal of Internal Medicine Vol. 29, No. 5 (Suppl. 1)
WCIM 2014 SEOUL KOREA 411
Slide Session
OS-005 DILD
Clinical Characteristics of Rituximab-Induced Interstitial Lung Disease
Jee Min Kim1, Jong Sun Park1, Se Joong Kim1, Yeon Joo Lee1, Yeong-Jae Cho1, Ho Il Yoon1, Jae Ho Lee1, Choon-Taek Lee1
Seoul National University Bundang Hospital, Korea1
Background: Rituximab, monoclonal antibody to CD20, has been a cornerstone in the treatment of lymphoma and many connective tissue diseases. Although rituximab has been safely used for over 15years, rituximab-induced interstitial lung disease(R-ILD) is not infrequent and can be fatal in real clinical practice. We investigated clinical char- acteristics and risk factors for R-ILD.
Methods: We identifi ed patients who received rituximab as either monotherapy or part of combination therapy between March, 2003 and March, 2014 in Seoul National University Bundang Hospital. We retrospectively reviewed demographics, laboratory, and clinical course of patients with R-ILD.
Results: Of 509 patients who received rituximab, 37 patients were compatible with R-ILD, with incidence being 7%. Most common clinical presentations were fever (51%) and dyspnea (48%), but about 12% were clinically asymptomatic except newly appeared bilateral gound-glass opacities in chest CT. The mean number of cycles of rituximab before disease onset was four (4.18th±0.57), and their bronchoalveolar lavage showed lymphocyte-dominant cellular components (58.84%±16.63). 5 patients died for respiratory failure even after steroid therapy. There were no statistically sig- nifi cant differences between patients with R-ILD and without R-ILD in terms of age, sex, disease status or extent, cumulative rituximab dose, underlying comorbidities, presence of pulmonary involvement of lymphoma.
Conclusions: R-ILD might not be as rare as previously reported. Because some of the patients may be fatal, R-ILD should be promptly suspected if patients present respira- tory symptoms or their radiologic imaging shows any changes.
OS-006 DILD
Pulmonary Alveolar Proteinosis in Korea for 20 Years from 1993 to 2013
Joo Han Song1, Korean Interstitial Lung Diseases Research Group2, Kyung Soo Chung1, Song Yee Kim1, Eun Young Kim1, Ji Ye Jung1, Young Ae Kang1, Young Sam Kim1, Se Kyu Kim1, Joon Chang1, Moo Suk Park1
Division of Pulmonology, Department of Internal Medicine, Institute of Chest Diseases, Severance Hospital, Yonsei University College of Medicine, Korea1, Korean Interstitial Lung Diseases Research Group, Korea2 Background: Pulmonary alveolar proteinosis (PAP) is a rare disease characterized by abnormal accumulation of lipoproteinaceous material within the alveoli. This study aims to compare clinical and laboratory features and therapeutic approach of PAP over the years.
Methods: A total of 78 patients with PAP from 13 university hospitals registered in Korean Interstitial Lung Disease Research Group were included in this study. The patients were divided into two groups, based on the year of diagnosis: group A with patients diagnosed from 1993 to 2007 (n= 41) and group B diagnosed from 2008 to 2013 (n = 37). We compared group A and B using the data on demographics, smoking status, diagnostic methods, symptom at presentation, pulmonary function tests, and occupation and exposed dusts.
Results: The median age at diagnosis was 41 years (range, 15-81) in group A and 48 years (range, 15-68) in group B (p=0.349). Male to female ratio was similar. In recent years, less number of patients received BAL and/or TBLB (90.2% vs 75.7%; p=0.085), while surgical lung biopsy (SLB) was performed in similar numbers (43.9% vs 45.9%;
p=0.856). Although not significant, the incidence of PAP in never smoker was in- creased after 2008. A history of dust exposure was seen in 43.6% (39.0% vs. 48.6%;
p=0.392). Thirty-five (44.9%) patients underwent whole lung lavage (WLL), which was used less in recent years (58.5% vs. 29.7%; p=0.011). Oxygenation (PaO2: n=23, p=0.016; DLco: n=13, p=0.089) markedly improved after WLL. Anti-GM CSF antibody treatment was used for 1 patient in group A (2.4%) and 3 patients in group B (8.1%;
p=0.341). Overall survival was 96% (n=75).
Conclusions: PAP is increasing in Korea. Dust exposure seems an important predisposing factor. WLL is a safe procedure and yields dramatic improvements in oxygenation in PAP.
OS-007 DILD
Bleomycin-Induced Pulmonary Fibrosis Is Improved by Inhibition of Endoplasmic Reticulum Stress in Mice
Yong Chul Lee1, So Ri Kim1, Kyung Bae Lee1, Yang Keun Rhee1, Heung Bum Lee1, Seoung Ju Park1, Yeong Hun Choe1, Seung Yong Park1
Chonbuk National University Hospital, Korea1
Background: Pulmonary fi brosis occurs in a wide variety of illnesses, including sys- temic disorders as well as primary lung diseases. Fibrotic changes can also appear as sequelae to insults by a diverse group of infectious, environmental, and therapeutic exposures. It is one of the devastating diseases, however, there are very few thera- peutic options. Therefore, the understanding the pathogenic mechanisms implicated in the process of fi brosis is important. Recently, one potential emerging mechanism for pulmonary fi brotic changes involves the endoplasmic reticulum (ER), the organelle responsible for protein folding, maturation, quality control, and traffi cking. However, to date, there is little information on which molecular mechanisms related to ER stress induces fi brotic changes in the lung.
Methods: In this study, we used a murine model of bleomycin-inducd lung fi brosis to evaluate the therapeutic potential of ER stress inhibitor on pulmonary fi brosis and to investigate the molecular action mechanisms.
Results: These results showed that the increased the expression of ER stress markers and the protein levels of unfolded-protein response (UPR)-related markers in lung tissues, increased numbers of airway infl ammatory cells, airway hyperresponsiveness, and increased levels of pro-infl ammatory cytokines, TGF-ß1, and increased nuclear translocation of NF-κB. In addition, the bloemycin-inhaled mice developed features of pulmonary fi brotic changes, including thickening of the peribronchial smooth muscle layer, subepithelial collagen deposition, and increased airway mucus production. Ad- ministration of 4-PBA reduced the pathophysiological symptoms of pulmonary fi brosis, increased NF-κB activation, pro-infl ammatory cytokines, and TGF-ß1 in lungs as well as the increased expression of ER stress markers and the protein levels of UPR-related markers after bleomycin inhalation.
Conclusions: These results indicate that inhibition of ER stress may attenuate pulmo- nary fi brotic changes through the regulation of NF-κB pathway leading to increase pro-fi brotic cytokines.
OS-008 DILD
Mitochondrial ROS Are Required for Bleomycin- Induced Pulmonary Fibrosis in Mice
So Ri Kim1, Yong Chul Lee1, Kyung Bae Lee1, Soon Ha Kim2, Yang Keun Rhee1, Heung Bum Lee1, Seoung Ju Park1, Yeong Hun Choe1, Seung Yong Park1
Chonbuk National University Hospital, Korea1, LG Life Sciences Ltd., Korea2
Background: Mitochondrial oxidative damage has been recognized as being involved in many diseases and in the aging process. Fibrotic changes appear as sequelae to insults by a diverse group of infectious, environmental, and therapeutic exposures.
Therefore, this pathologic process can be involved in common pathway to fi nal stage of various pulmonary disroders including senile pulmonary illness.
Methods: To date, bloemycin-inhlaed animal model represents as a relatively well established experimental tool for pulmonary fi brotic chages. In this study, using this animal model we investgated the role of mitochondrial ROS in the pathogenesis of bleomycin-induced lung infl ammation and fi brosis and the related mechanisms.
Results: These results showed that the increased the gneeration of mitochondrial ROS in inflammatory cells and lung tissues, increased numbers of airway inflammatory cells, airway hyperresponsiveness, and increased levels of pro-infl ammatory cytokines, TGF-ß1, and increased nuclear translocation of NF-κB. In addition, the bloemycin-in- haled mice developed features of pulmonary fi brotic changes, including thickening of the peribronchial smooth muscle layer, subepithelial collagen deposition, and increased airway mucus production. Administration of NecroX compounds including NecroX-5 and -7 reduced the pathophysiological symptoms of pulmonary fibrosis, increased NF-κB activation, Th2 cytokines, and TGF-ß1 in lungs as well as the increased gener- ation of mitochondrial ROS in lung after bleomycin inhalation.
Conclusions: These results indicate that reduction of mitochondrial ROS may attenu- ate pulmonary fi brotic changes through the regulation of NF-κB pathway, providing the therapeutic potential of NecroX compounds as an anti-fi brotic agent.
