Pub Date : 2019-09-28DOI: 10.1183/13993003.congress-2019.pa4706
K. Gashynova, V. Rodionova, O. Karasyova, O. Shaulska, O. Khmel
{"title":"Matrix metalloproteinases, as markers of the severity of idiopathic pulmonary fibrosis","authors":"K. Gashynova, V. Rodionova, O. Karasyova, O. Shaulska, O. Khmel","doi":"10.1183/13993003.congress-2019.pa4706","DOIUrl":"https://doi.org/10.1183/13993003.congress-2019.pa4706","url":null,"abstract":"","PeriodicalId":13242,"journal":{"name":"Idiopathic interstitial pneumonias","volume":"5 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74500120","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-09-28DOI: 10.1183/13993003.congress-2019.pa1293
Gwanghee Lee, Sang-Uk Kang, Jeong-Hyun Ryou, Jongwon Lim, Yong-Hee Lee
Idiopathic Pulmonary Fibrosis (IPF) is a progressive, irreversible and fatal lung disease with unmet medical needs. Autotaxin (ATX) is an extracellular enzyme involved in the generation of lysophosphatidic acid (LPA). Preclinical and clinical data have suggested the ATX – LPA – LPA receptor (LPAR) axis plays a pivotal role in the pathogenesis and the progression of IPF. BBT-877 is an orally available small molecule inhibitor against ATX. In ex vivo enzymatic assays using human plasma, IC50 of BBT-877 was measured 6.5 – 6.9 nM (LPA 18:2) whereas that of GLPG1690 was measured 75 – 132 nM. To determine in vivo anti-fibrotic efficacy of BBT-877, bleomycin was intranasally administrated in mice at day 0, and BBT-877 was administrated orally twice a day from day 7 to 21. The BBT-877 treatment showed anti-fibrotic efficacy as revealed by significantly reduced body weight loss, lung weight and Ashcroft score as well as collagen content compared to the vehicle-treated group. During phase 1 clinical trial with 80 healthy volunteers, in which 50 – 800 mg (SAD) and 200 – 800 mg QD or 100 – 200 mg BID for two weeks (MAD) doses were administrated, only mild adverse events were noted. Pharmacokinetic analysis revealed the dose-proportional increase in systemic exposure with elimination half-life of 12hr. The decrease of plasma LPA level was maintained at 80% or higher for 24hr when 400 mg BBT-877 was administrated. Taken together, nonclinical data suggest BBT-877 is a potent, selective, and potentially best-in-class ATX inhibitor. Phase 1 clinical data demonstrate BBT-877 is a safe and well-tolerated drug with excellent pharmacokinetic-pharmacodynamic profiles.
{"title":"Late Breaking Abstract - BBT-877, a Potent Autotaxin Inhibitor in Clinical Development to Treat Idiopathic Pulmonary Fibrosis","authors":"Gwanghee Lee, Sang-Uk Kang, Jeong-Hyun Ryou, Jongwon Lim, Yong-Hee Lee","doi":"10.1183/13993003.congress-2019.pa1293","DOIUrl":"https://doi.org/10.1183/13993003.congress-2019.pa1293","url":null,"abstract":"Idiopathic Pulmonary Fibrosis (IPF) is a progressive, irreversible and fatal lung disease with unmet medical needs. Autotaxin (ATX) is an extracellular enzyme involved in the generation of lysophosphatidic acid (LPA). Preclinical and clinical data have suggested the ATX – LPA – LPA receptor (LPAR) axis plays a pivotal role in the pathogenesis and the progression of IPF. BBT-877 is an orally available small molecule inhibitor against ATX. In ex vivo enzymatic assays using human plasma, IC50 of BBT-877 was measured 6.5 – 6.9 nM (LPA 18:2) whereas that of GLPG1690 was measured 75 – 132 nM. To determine in vivo anti-fibrotic efficacy of BBT-877, bleomycin was intranasally administrated in mice at day 0, and BBT-877 was administrated orally twice a day from day 7 to 21. The BBT-877 treatment showed anti-fibrotic efficacy as revealed by significantly reduced body weight loss, lung weight and Ashcroft score as well as collagen content compared to the vehicle-treated group. During phase 1 clinical trial with 80 healthy volunteers, in which 50 – 800 mg (SAD) and 200 – 800 mg QD or 100 – 200 mg BID for two weeks (MAD) doses were administrated, only mild adverse events were noted. Pharmacokinetic analysis revealed the dose-proportional increase in systemic exposure with elimination half-life of 12hr. The decrease of plasma LPA level was maintained at 80% or higher for 24hr when 400 mg BBT-877 was administrated. Taken together, nonclinical data suggest BBT-877 is a potent, selective, and potentially best-in-class ATX inhibitor. Phase 1 clinical data demonstrate BBT-877 is a safe and well-tolerated drug with excellent pharmacokinetic-pharmacodynamic profiles.","PeriodicalId":13242,"journal":{"name":"Idiopathic interstitial pneumonias","volume":"78 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80289693","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-09-28DOI: 10.1183/13993003.congress-2019.pa1284
R. Felix, A. L. C. Bovolato, P. D. Leão, M. Golim, W. Teodoro, A. Fabro, E. Deffune, V. Capelozzi
{"title":"Pulmonary fibrosis modulation by mesenchymal stem cells and conditioned medium","authors":"R. Felix, A. L. C. Bovolato, P. D. Leão, M. Golim, W. Teodoro, A. Fabro, E. Deffune, V. Capelozzi","doi":"10.1183/13993003.congress-2019.pa1284","DOIUrl":"https://doi.org/10.1183/13993003.congress-2019.pa1284","url":null,"abstract":"","PeriodicalId":13242,"journal":{"name":"Idiopathic interstitial pneumonias","volume":"8 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81799056","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-09-28DOI: 10.1183/13993003.congress-2019.pa1291
J. Katzen, A. Venosa, Y. Tomer, Meghan C. Kopp, Michael Morely, A. Diwadkar, E. Morrisey, B. Himes, S. Mulugeta, M. Beers
{"title":"Interstitial lung disease related surfactant protein-C mutations alter the transcriptome and progenitor cell function of alveolar epithelial cells in mice","authors":"J. Katzen, A. Venosa, Y. Tomer, Meghan C. Kopp, Michael Morely, A. Diwadkar, E. Morrisey, B. Himes, S. Mulugeta, M. Beers","doi":"10.1183/13993003.congress-2019.pa1291","DOIUrl":"https://doi.org/10.1183/13993003.congress-2019.pa1291","url":null,"abstract":"","PeriodicalId":13242,"journal":{"name":"Idiopathic interstitial pneumonias","volume":"26 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81845881","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-09-28DOI: 10.1183/13993003.congress-2019.pa1313
K. Akaike, K. Saruwatari, S. Oda, S. Hamada, Y. Tomita, S. Saeki, H. Ichiyasu, K. Fujii, S. Shiraishi, T. Sakagami
Background: Acute exacerbation (AE) of interstitial pneumonia disease (ILD) in lung cancer (LC) patients with ILD could be one of the lethal adverse effect related to chemotherapy. The purpose of this study was to determine if the result of 18F-FDG PET/CT before chemotherapy could predict onset of chemotherapy-related AE-ILD in LC patients with ILD. Methods: Between April 2006 and March 2018, 33 patients with LC and ILD performed 18F-FDG PET/CT and treated with chemotherapy in Kumamoto University Hospital. The SUVmax of interstitial lesion was measured to quantify the background ILD activity. A prediction model chemotherapy-related AE of ILD was developed using a logistic regression and ROC curve analysis. Results: Among 33 patients, 7 experienced AE of ILD (AE group) and 26 did not (non-AE group), the SUVmax of contralateral interstitial lesion in AE group was significantly higher than that in non-AE group (median SUVmax 2.22 vs. 1.80, P = 0.041). An univariable logistic regression analysis showed that the SUVmax of contralateral interstitial lesion had potential to be associated with chemotherapy-related AE of ILD (odds ratio, 8.683; 95% confidence interval [CI], 0.88–85.83; P = 0.064). The AUC of the SUVmax for predicting chemotherapy-related AE of ILD was 0.780 (95% CI: 0.579-0.982, P = 0.025). The optimal cut-off value for SUVmax was 2.005. Sensitivity and specificity value for this cut-off point were 0.857 and 0.769, respectively. Conclusions: The SUVmax of contralateral interstitial lesion in 18F-FDG PET/CT might be useful to predict chemotherapy-related AE of ILD in LC with ILD.
背景:肺癌(LC)间质性肺炎(ILD)患者急性加重(AE)可能是化疗相关的致死性不良反应之一。本研究的目的是确定化疗前18F-FDG PET/CT结果是否可以预测LC合并ILD患者化疗相关AE-ILD的发病。方法:2006年4月至2018年3月，33例LC和ILD患者在熊本大学医院进行了18F-FDG PET/CT检查并接受了化疗。测量间质病变的SUVmax以量化背景ILD活性。采用logistic回归和ROC曲线分析建立了化疗相关AE的预测模型。结果:33例患者中，有7例发生了ILD的AE (AE组)，26例未发生AE(非AE组)，AE组对侧间质病变SUVmax显著高于非AE组(中位SUVmax 2.22 vs. 1.80, P = 0.041)。单变量logistic回归分析显示，对侧间质病变SUVmax可能与化疗相关的ILD AE相关(优势比8.683;95%置信区间[CI]， 0.88-85.83;P = 0.064)。SUVmax预测ILD化疗相关AE的AUC为0.780 (95% CI: 0.579 ~ 0.982, P = 0.025)。SUVmax的最佳临界值为2.005。该分界点的敏感性和特异性分别为0.857和0.769。结论:18F-FDG PET/CT对侧间质病变SUVmax可用于预测LC合并ILD患者化疗相关AE。
{"title":"Predictive value of 18F-FDG PET/CT for chemotherapy-related acute exacerbation of interstitial lung disease in lung cancer patients with interstitial lung disease","authors":"K. Akaike, K. Saruwatari, S. Oda, S. Hamada, Y. Tomita, S. Saeki, H. Ichiyasu, K. Fujii, S. Shiraishi, T. Sakagami","doi":"10.1183/13993003.congress-2019.pa1313","DOIUrl":"https://doi.org/10.1183/13993003.congress-2019.pa1313","url":null,"abstract":"Background: Acute exacerbation (AE) of interstitial pneumonia disease (ILD) in lung cancer (LC) patients with ILD could be one of the lethal adverse effect related to chemotherapy. The purpose of this study was to determine if the result of 18F-FDG PET/CT before chemotherapy could predict onset of chemotherapy-related AE-ILD in LC patients with ILD. Methods: Between April 2006 and March 2018, 33 patients with LC and ILD performed 18F-FDG PET/CT and treated with chemotherapy in Kumamoto University Hospital. The SUVmax of interstitial lesion was measured to quantify the background ILD activity. A prediction model chemotherapy-related AE of ILD was developed using a logistic regression and ROC curve analysis. Results: Among 33 patients, 7 experienced AE of ILD (AE group) and 26 did not (non-AE group), the SUVmax of contralateral interstitial lesion in AE group was significantly higher than that in non-AE group (median SUVmax 2.22 vs. 1.80, P = 0.041). An univariable logistic regression analysis showed that the SUVmax of contralateral interstitial lesion had potential to be associated with chemotherapy-related AE of ILD (odds ratio, 8.683; 95% confidence interval [CI], 0.88–85.83; P = 0.064). The AUC of the SUVmax for predicting chemotherapy-related AE of ILD was 0.780 (95% CI: 0.579-0.982, P = 0.025). The optimal cut-off value for SUVmax was 2.005. Sensitivity and specificity value for this cut-off point were 0.857 and 0.769, respectively. Conclusions: The SUVmax of contralateral interstitial lesion in 18F-FDG PET/CT might be useful to predict chemotherapy-related AE of ILD in LC with ILD.","PeriodicalId":13242,"journal":{"name":"Idiopathic interstitial pneumonias","volume":"95 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85471504","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-09-28DOI: 10.1183/13993003.congress-2019.pa1333
J. Swigris, S. Nathan, R. Tighe, Sunny Nagra, C. Rabe, Douglas O. Kelkhoff, Thomas Switzer, N. Kolatkar, P. Belloni, J. Golden
{"title":"STARMAP: an observational study to assess disease-relevant outcomes using home-monitoring devices in patients with idiopathic pulmonary fibrosis (IPF)","authors":"J. Swigris, S. Nathan, R. Tighe, Sunny Nagra, C. Rabe, Douglas O. Kelkhoff, Thomas Switzer, N. Kolatkar, P. Belloni, J. Golden","doi":"10.1183/13993003.congress-2019.pa1333","DOIUrl":"https://doi.org/10.1183/13993003.congress-2019.pa1333","url":null,"abstract":"","PeriodicalId":13242,"journal":{"name":"Idiopathic interstitial pneumonias","volume":"148 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76952271","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-09-28DOI: 10.1183/13993003.congress-2019.rct1886
L. Troy, C. Grainge, T. Corte, J. Williamson, M. Vallely, W. Cooper, A. Mahar, J. Myers, Simon Lai, Ellie Mulyadi, P. Torzillo, M. Phillips, H. Jo, Susanne E Webster, Qi Lin, J. Rhodes, M. Salamonsen, J. Wrobel, B. Harris, G. Don, P. Wu, B. Ng, C. Oldmeadow, G. Raghu, E. Lau, Coldice Investigators
Transbronchial lung cryobiopsy (TBLC) is a novel technique for sampling lung tissue for interstitial lung disease (ILD) diagnosis. Despite increasing use, the diagnostic accuracy of TBLC compared to surgical lung biopsy (SLB) remains unclear. Methods: We conducted a prospective, multicenter study investigating agreement between TBLC and SLB. ILD patients referred for lung biopsy after central screening underwent sequential TLBC and SLB, under one anesthetic. Blinded analysis of samples was conducted by 3 pathologists, individually and by consensus. At multidisciplinary discussion (MDD), deidentified cases were discussed twice with either TBLC or SLB along with clinical and radiology data, in random non-consecutive order. Primary endpoints were agreement of TBLC and SLB for 1) “definite/probable usual interstitial pneumonia (UIP)”, “indeterminate for UIP” and “alternative diagnosis” histopathologic patterns; and for 2) MDD diagnoses. Concordance and kappa values were calculated. Results: 65 patients (30 males; age 66±9yrs; FVC 84±14%; DLCO 63±13%) were enrolled. TBLC (7.1±1.9mm) and SLB samples (47±15mm) were taken from two separate ipsilateral lobes. Histopathological agreement between TBLC and SLB was 70.8%, weighted κ 0.70 (95%CI 0.55-0.86); agreement at MDD was 76.9%, κ 0.62 (95%CI 0.47-0.78). For TBLC with high/definite diagnostic confidence at MDD (39/65, 60% cases), 94.9% were concordant with SLB diagnoses. In the 26 with low-confidence/unclassifiable TBLC diagnoses, SLB reclassified only 6 to alternative high/definite MDD diagnoses. Conclusion: High agreement between TBLC and SLB for pathologic and MDD diagnoses support the clinical utility of TBLC in ILD diagnostic algorithms.
{"title":"Late Breaking Abstract - Transbronchial lung cryobiopsy for interstitial lung disease diagnosis: results of the COLDICE Study","authors":"L. Troy, C. Grainge, T. Corte, J. Williamson, M. Vallely, W. Cooper, A. Mahar, J. Myers, Simon Lai, Ellie Mulyadi, P. Torzillo, M. Phillips, H. Jo, Susanne E Webster, Qi Lin, J. Rhodes, M. Salamonsen, J. Wrobel, B. Harris, G. Don, P. Wu, B. Ng, C. Oldmeadow, G. Raghu, E. Lau, Coldice Investigators","doi":"10.1183/13993003.congress-2019.rct1886","DOIUrl":"https://doi.org/10.1183/13993003.congress-2019.rct1886","url":null,"abstract":"Transbronchial lung cryobiopsy (TBLC) is a novel technique for sampling lung tissue for interstitial lung disease (ILD) diagnosis. Despite increasing use, the diagnostic accuracy of TBLC compared to surgical lung biopsy (SLB) remains unclear. Methods: We conducted a prospective, multicenter study investigating agreement between TBLC and SLB. ILD patients referred for lung biopsy after central screening underwent sequential TLBC and SLB, under one anesthetic. Blinded analysis of samples was conducted by 3 pathologists, individually and by consensus. At multidisciplinary discussion (MDD), deidentified cases were discussed twice with either TBLC or SLB along with clinical and radiology data, in random non-consecutive order. Primary endpoints were agreement of TBLC and SLB for 1) “definite/probable usual interstitial pneumonia (UIP)”, “indeterminate for UIP” and “alternative diagnosis” histopathologic patterns; and for 2) MDD diagnoses. Concordance and kappa values were calculated. Results: 65 patients (30 males; age 66±9yrs; FVC 84±14%; DLCO 63±13%) were enrolled. TBLC (7.1±1.9mm) and SLB samples (47±15mm) were taken from two separate ipsilateral lobes. Histopathological agreement between TBLC and SLB was 70.8%, weighted κ 0.70 (95%CI 0.55-0.86); agreement at MDD was 76.9%, κ 0.62 (95%CI 0.47-0.78). For TBLC with high/definite diagnostic confidence at MDD (39/65, 60% cases), 94.9% were concordant with SLB diagnoses. In the 26 with low-confidence/unclassifiable TBLC diagnoses, SLB reclassified only 6 to alternative high/definite MDD diagnoses. Conclusion: High agreement between TBLC and SLB for pathologic and MDD diagnoses support the clinical utility of TBLC in ILD diagnostic algorithms.","PeriodicalId":13242,"journal":{"name":"Idiopathic interstitial pneumonias","volume":"60 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77117128","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-09-28DOI: 10.1183/13993003.congress-2019.pa1724
N. Hoyer, T. Prior, E. Bendstrup, T. Wilcke, S. Shaker
{"title":"Risk factors for diagnostic delay in a prospective IPF-cohort","authors":"N. Hoyer, T. Prior, E. Bendstrup, T. Wilcke, S. Shaker","doi":"10.1183/13993003.congress-2019.pa1724","DOIUrl":"https://doi.org/10.1183/13993003.congress-2019.pa1724","url":null,"abstract":"","PeriodicalId":13242,"journal":{"name":"Idiopathic interstitial pneumonias","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85528810","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-09-28DOI: 10.1183/13993003.congress-2019.pa1727
Ivonne M. Raats ten Cate, C. V. Moorsel, A. Meer, P. Zanen, J. Grutters
{"title":"Efficacy of switching antifibrotic therapy in idiopathic pulmonary fibrosis: real life data","authors":"Ivonne M. Raats ten Cate, C. V. Moorsel, A. Meer, P. Zanen, J. Grutters","doi":"10.1183/13993003.congress-2019.pa1727","DOIUrl":"https://doi.org/10.1183/13993003.congress-2019.pa1727","url":null,"abstract":"","PeriodicalId":13242,"journal":{"name":"Idiopathic interstitial pneumonias","volume":"128 4 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78947618","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-09-28DOI: 10.1183/13993003.congress-2019.pa4704
Takumi Yoshikawa, M. Otsuka, Kimiyuki Ikeda, Yuki Mori, Yasuaki Umeda, Hirotaka Nishikiori, Satsuki Miyajima, Mamoru Takahashi, K. Kuronuma, H. Chiba, Hiroki Takahashi
Background: Serum surfactant protein (SP)-A, SP-D, and KL-6 are prognostic biomarkers of patients with idiopathic pulmonary fibrosis (IPF), however, the relationship with the therapeutic effect of antifibrotic drugs has not been investigated. Aim: To clarify whether serum SP-A, SP-D and KL-6 are therapeutic predictive markers of pirfenidone and nintedanib in patients with IPF. Methods: We retrospectively investigated patients with IPF who started pirfenidone or nintedanib between January 2014 and June 2018 at our hospital. The change in clinical parameters and serum SP-A, SP-D and KL-6 levels were evaluated. Patients with a > 10% decline in forced vital capacity (FVC) or a > 15% decline in diffusing capacity of the lung for carbon monoxide (DLco) from baseline to 6 months were classified as a deterioration group and the other was classified as an effective group. Results: Forty-nine patients were included (pirfenidone; 23, nintedanib; 26). Thirty-two patients were the effective group and 17 patients were the deterioration group. In the effective group, the change in serum SP-A, SP-D, and KL-6 from baseline to 3 and/or 6 months significantly decreased compared with the deterioration group. The change in serum SP-A and SP-D showed significant negative correlations with the change in %FVC and %DLCO. According to the logistic regression analysis, the decrease in SP-A from baseline to 3 months was a predictor of the effect at 6 months (odd’ ratio 0.88). Conclusions: Change in SP-A, SP-D and KL-6 represent the therapeutic effect of antifibrotic drugs. These may be therapeutic predictive biomarkers of antifibrotic drugs.
{"title":"Change in serum surfactant protein (SP)-A, SP-D and KL-6 predict the therapeutic effect of antifibrotic drugs in IPF","authors":"Takumi Yoshikawa, M. Otsuka, Kimiyuki Ikeda, Yuki Mori, Yasuaki Umeda, Hirotaka Nishikiori, Satsuki Miyajima, Mamoru Takahashi, K. Kuronuma, H. Chiba, Hiroki Takahashi","doi":"10.1183/13993003.congress-2019.pa4704","DOIUrl":"https://doi.org/10.1183/13993003.congress-2019.pa4704","url":null,"abstract":"Background: Serum surfactant protein (SP)-A, SP-D, and KL-6 are prognostic biomarkers of patients with idiopathic pulmonary fibrosis (IPF), however, the relationship with the therapeutic effect of antifibrotic drugs has not been investigated. Aim: To clarify whether serum SP-A, SP-D and KL-6 are therapeutic predictive markers of pirfenidone and nintedanib in patients with IPF. Methods: We retrospectively investigated patients with IPF who started pirfenidone or nintedanib between January 2014 and June 2018 at our hospital. The change in clinical parameters and serum SP-A, SP-D and KL-6 levels were evaluated. Patients with a > 10% decline in forced vital capacity (FVC) or a > 15% decline in diffusing capacity of the lung for carbon monoxide (DLco) from baseline to 6 months were classified as a deterioration group and the other was classified as an effective group. Results: Forty-nine patients were included (pirfenidone; 23, nintedanib; 26). Thirty-two patients were the effective group and 17 patients were the deterioration group. In the effective group, the change in serum SP-A, SP-D, and KL-6 from baseline to 3 and/or 6 months significantly decreased compared with the deterioration group. The change in serum SP-A and SP-D showed significant negative correlations with the change in %FVC and %DLCO. According to the logistic regression analysis, the decrease in SP-A from baseline to 3 months was a predictor of the effect at 6 months (odd’ ratio 0.88). Conclusions: Change in SP-A, SP-D and KL-6 represent the therapeutic effect of antifibrotic drugs. These may be therapeutic predictive biomarkers of antifibrotic drugs.","PeriodicalId":13242,"journal":{"name":"Idiopathic interstitial pneumonias","volume":"54 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87148519","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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