Pulmonology Commons^™

A Nasal Inflammatory Cytokine Signature Is Associated With Early Graft-Versus-Host Disease Of The Lung After Allogeneic Hematopoietic Cell Transplantation: Proof Of Concept, Edwin J Ostrin, Nicholas L Rider, Amin M Alousi, Ehsan Irajizad, Liang Li, Qian Peng, Sang T Kim, Lara Bashoura, Muhammad H Arain, Laila Z Noor, Nikul Patel, Rohtesh Mehta, Uday R Popat, Chitra Hosing, Robert R Jenq, Gabriela Rondon, Samir M Hanash, Sophie Paczesny, Elizabeth J Shpall, Richard E Champlin, Burton F Dickey, Ajay Sheshadri

Faculty, Staff and Student Publications

Respiratory inflammation in bronchiolitis obliterans syndrome (BOS) after hematopoietic cell transplantation (HCT) is poorly understood. Clinical criteria for early-stage BOS (stage 0p) often capture HCT recipients without BOS. Measuring respiratory tract inflammation may help identify BOS, particularly early BOS. We conducted a prospective observational study in HCT recipients with new-onset BOS (n = 14), BOS stage 0p (n = 10), and recipients without lung impairment with (n = 3) or without (n = 8) chronic graft-versus-host disease and measured nasal inflammation using nasosorption at enrollment and then every 3 mo for 1 y. We divided BOS stage 0p into impairment …

Genome-Wide Association Study Of Lung Adenocarcinoma In East Asia And Comparison With A European Population, Jianxin Shi, Kouya Shiraishi, Jiyeon Choi, Keitaro Matsuo, Tzu-Yu Chen, Juncheng Dai, Rayjean J Hung, Kexin Chen, Xiao-Ou Shu, Young Tae Kim, Maria Teresa Landi, Dongxin Lin, Wei Zheng, Zhihua Yin, Baosen Zhou, Bao Song, Jiucun Wang, Wei Jie Seow, Lei Song, I-Shou Chang, Wei Hu, Li-Hsin Chien, Qiuyin Cai, Yun-Chul Hong, Hee Nam Kim, Yi-Long Wu, Maria Pik Wong, Brian Douglas Richardson, Karen M Funderburk, Shilan Li, Tongwu Zhang, Charles Breeze, Zhaoming Wang, Batel Blechter, Bryan A Bassig, Jin Hee Kim, Demetrius Albanes, Jason Y Y Wong, Min-Ho Shin, Lap Ping Chung, Yang Yang, She-Juan An, Hong Zheng, Yasushi Yatabe, Xu-Chao Zhang, Young-Chul Kim, Neil E Caporaso, Jiang Chang, James Chung Man Ho, Michiaki Kubo, Yataro Daigo, Minsun Song, Yukihide Momozawa, Yoichiro Kamatani, Masashi Kobayashi, Kenichi Okubo, Takayuki Honda, Dean H Hosgood, Hideo Kunitoh, Harsh Patel, Shun-Ichi Watanabe, Yohei Miyagi, Haruhiko Nakayama, Shingo Matsumoto, Hidehito Horinouchi, Masahiro Tsuboi, Ryuji Hamamoto, Koichi Goto, Yuichiro Ohe, Atsushi Takahashi, Akiteru Goto, Yoshihiro Minamiya, Megumi Hara, Yuichiro Nishida, Kenji Takeuchi, Kenji Wakai, Koichi Matsuda, Yoshinori Murakami, Kimihiro Shimizu, Hiroyuki Suzuki, Motonobu Saito, Yoichi Ohtaki, Kazumi Tanaka, Tangchun Wu, Fusheng Wei, Hongji Dai, Mitchell J Machiela, Jian Su, Yeul Hong Kim, In-Jae Oh, Victor Ho Fun Lee, Gee-Chen Chang, Ying-Huang Tsai, Kuan-Yu Chen, Ming-Shyan Huang, Wu-Chou Su, Yuh-Min Chen, Adeline Seow, Jae Yong Park, Sun-Seog Kweon, Kun-Chieh Chen, Yu-Tang Gao, Biyun Qian, Chen Wu, Daru Lu, Jianjun Liu, Ann G Schwartz, Richard Houlston, Margaret R Spitz, Ivan P Gorlov, Xifeng Wu, Ping Yang, Stephen Lam, Adonina Tardon, Chu Chen, Stig E Bojesen, Mattias Johansson, Angela Risch, Heike Bickeböller, Bu-Tian Ji, H-Erich Wichmann, David C Christiani, Gadi Rennert, Susanne Arnold, Paul Brennan, James Mckay, John K Field, Sanjay S Shete, Loic Le Marchand, Geoffrey Liu, Angeline Andrew, Lambertus A Kiemeney, Shan Zienolddiny-Narui, Kjell Grankvist, Mikael Johansson, Angela Cox, Fiona Taylor, Jian-Min Yuan, Philip Lazarus, Matthew B Schabath, Melinda C Aldrich, Hyo-Sung Jeon, Shih Sheng Jiang, Jae Sook Sung, Chung-Hsing Chen, Chin-Fu Hsiao, Yoo Jin Jung, Huan Guo, Zhibin Hu, Laurie Burdett, Meredith Yeager, Amy Hutchinson, Belynda Hicks, Jia Liu, Bin Zhu, Sonja I Berndt, Wei Wu, Junwen Wang, Yuqing Li, Jin Eun Choi, Kyong Hwa Park, Sook Whan Sung, Li Liu, Chang Hyun Kang, Wen-Chang Wang, Jun Xu, Peng Guan, Wen Tan, Chong-Jen Yu, Gong Yang, Alan Dart Loon Sihoe, Ying Chen, Yi Young Choi, Jun Suk Kim, Ho-Il Yoon, In Kyu Park, Ping Xu, Qincheng He, Chih-Liang Wang, Hsiao-Han Hung, Roel C H Vermeulen, Iona Cheng, Junjie Wu, Wei-Yen Lim, Fang-Yu Tsai, John K C Chan, Jihua Li, Hongyan Chen, Hsien-Chih Lin, Li Jin, Jie Liu, Norie Sawada, Taiki Yamaji, Kathleen Wyatt, Shengchao A Li, Hongxia Ma, Meng Zhu, Zhehai Wang, Sensen Cheng, Xuelian Li, Yangwu Ren, Ann Chao, Motoki Iwasaki, Junjie Zhu, Gening Jiang, Ke Fei, Guoping Wu, Chih-Yi Chen, Chien-Jen Chen, Pan-Chyr Yang, Jinming Yu, Victoria L Stevens, Joseph F Fraumeni, Nilanjan Chatterjee, Olga Y Gorlova, Chao Agnes Hsiung, Christopher I Amos, Hongbing Shen, Stephen J Chanock, Nathaniel Rothman, Takashi Kohno, Qing Lan

Faculty, Staff and Student Publications

Lung adenocarcinoma is the most common type of lung cancer. Known risk variants explain only a small fraction of lung adenocarcinoma heritability. Here, we conducted a two-stage genome-wide association study of lung adenocarcinoma of East Asian ancestry (21,658 cases and 150,676 controls; 54.5% never-smokers) and identified 12 novel susceptibility variants, bringing the total number to 28 at 25 independent loci. Transcriptome-wide association analyses together with colocalization studies using a Taiwanese lung expression quantitative trait loci dataset (n = 115) identified novel candidate genes, including FADS1 at 11q12 and ELF5 at 11p13. In a multi-ancestry meta-analysis of East Asian and European …

Toll-Like Receptors 2, 4, And 9 Modulate Promoting Effect Of Copd-Like Airway Inflammation On K-Ras-Driven Lung Cancer Through Activation Of The Myd88/Nf-ĸb Pathway In The Airway Epithelium, Walter V Velasco, Nasim Khosravi, Susana Castro-Pando, Nelly Torres-Garza, Maria T Grimaldo, Avantika Krishna, Michael J Clowers, Misha Umer, Sabah Tariq Amir, Diana Del Bosque, Soudabeh Daliri, Maria Miguelina De La Garza, Marco Ramos-Castaneda, Scott E Evans, Seyed Javad Moghaddam

Faculty, Staff and Student Publications

INTRODUCTION: Toll-like receptors (TLRs) are an extensive group of proteins involved in host defense processes that express themselves upon the increased production of endogenous damage-associated molecular patterns (DAMPs) and pathogen-associated molecular patterns (PAMPs) due to the constant contact that airway epithelium may have with pathogenic foreign antigens. We have previously shown that COPD-like airway inflammation induced by exposure to an aerosolized lysate of nontypeable

METHODS: In the present study, we have dissected the role of TLRs in this process by knocking out TLR2, 4, and 9 and analyzing how these deletions affect the promoting effect of COPD-like airway inflammation on …

Immune Cellular Patterns Of Distribution Affect Outcomes Of Patients With Non-Small Cell Lung Cancer, Edwin Roger Parra, Jiexin Zhang, Mei Jiang, Auriole Tamegnon, Renganayaki Krishna Pandurengan, Carmen Behrens, Luisa Solis, Cara Haymaker, John Victor Heymach, Cesar Moran, Jack J Lee, Don Gibbons, Ignacio Ivan Wistuba

Faculty, Staff and Student Publications

Studying the cellular geographic distribution in non-small cell lung cancer is essential to understand the roles of cell populations in this type of tumor. In this study, we characterize the spatial cellular distribution of immune cell populations using 23 makers placed in five multiplex immunofluorescence panels and their associations with clinicopathologic variables and outcomes. Our results demonstrate two cellular distribution patterns-an unmixed pattern mostly related to immunoprotective cells and a mixed pattern mostly related to immunosuppressive cells. Distance analysis shows that T-cells expressing immune checkpoints are closer to malignant cells than other cells. Combining the cellular distribution patterns with cellular …

Nuclear Export Signal Mutation Of Epidermal Growth Factor Receptor Enhances Malignant Phenotypes Of Cancer Cells, Lei Nie, Ying-Nai Wang, Jung-Mao Hsu, Junwei Hou, Yu-Yi Chu, Li-Chuan Chan, Longfei Huo, Yongkun Wei, Rong Deng, Jun Tang, Yi-Hsin Hsu, How-Wen Ko, Seung-Oe Lim, Kebin Huang, Mei-Kuang Chen, Tai-Jan Chiu, Chien-Chia Cheng, Yueh-Fu Fang, Chia-Wei Li, Aarthi Goverdhan, Hsing-Ju Wu, Cheng-Chung Lee, Wen-Ling Wang, Jennifer Hsu, Paul Chiao, Shao-Chun Wang, Mien-Chie Hung

Faculty, Staff and Student Publications

Nuclear epidermal growth factor receptor (EGFR) has been shown to be correlated with drug resistance and a poor prognosis in patients with cancer. Previously, we have identified a tripartite nuclear localization signal (NLS) within EGFR. To comprehensively determine the functions and underlying mechanism of nuclear EGFR and its clinical implications, we aimed to explore the nuclear export signal (NES) sequence of EGFR that is responsible for interacting with the exportins. We combined in silico prediction with site-directed mutagenesis approaches and identified a putative NES motif of EGFR, which is located in amino acid residues 736-749. Mutation at leucine 747 (L747) …

Development Of A Corticosteroid-Immunosuppressed Mouse Model To Study The Pathogenesis And Therapy Of Influenza-Associated Pulmonary Aspergillosis, Sebastian Wurster, Jezreel Pantaleón García, Nathaniel D Albert, Ying Jiang, Keerthi Bhoda, Vikram V Kulkarni, Yongxing Wang, Thomas J Walsh, Scott Evans, Dimitrios P Kontoyiannis

Faculty, Staff and Student Publications

Influenza-associated pulmonary aspergillosis (IAPA) is a feared complication in patients with influenza tracheobronchitis, especially those receiving corticosteroids. Herein, we established a novel IAPA mouse model with low-inoculum Aspergillus infection and compared outcomes in mice with and without cortisone acetate (CA) immunosuppression. CA was an independent predictor of increased morbidity/mortality in mice with IAPA. Early antifungal treatment with liposomal amphotericin B was pivotal to improve IAPA outcomes in CA-immunosuppressed mice, even after prior antiviral therapy with oseltamivir. In summary, our model recapitulates key clinical features of IAPA and provides a robust preclinical platform to study the pathogenesis and treatment of IAPA.

Treatment Outcomes For Rheumatoid Arthritis-Associated Interstitial Lung Disease: A Real-World, Multisite Study Of The Impact Of Immunosuppression On Pulmonary Function Trajectory, Scott M Matson, Misbah Baqir, Teng Moua, Michael Marll, Jessica Kent, Nicholas S Iannazzo, Ryan D Boente, John M Donatelli, Junqiang Dai, Francisco J Diaz, M Kristen Demoruelle, Mark B Hamblin, Susan K Mathai, Jay H Ryu, Kristen Pope, Christopher M Walker, Joyce S Lee

Faculty, Staff and Student Publications

BACKGROUND: Rheumatoid arthritis (RA)-associated interstitial lung disease (ILD) is common in patients with RA and leads to significant morbidity and mortality. No randomized, placebo-controlled data are available that support the role of immunosuppression to treat RA-associated ILD, despite being widely used in clinical practice.

RESEARCH QUESTION: How does immunosuppression impact pulmonary function trajectory in a multisite retrospective cohort of patients with RA-associated ILD?

STUDY DESIGN AND METHODS: Patients with RA who started treatment for ILD with mycophenolate, azathioprine, or rituximab were identified retrospectively from five ILD centers. Change in lung function before and after treatment was analyzed using a linear …

Disparity In Checkpoint Inhibitor Utilization Among Commercially Insured Adult Patients With Metastatic Lung Cancer, Meng Li, Kaiping Liao, Alice J Chen, Tina Cascone, Yu Shen, Qian Lu, Ya-Chen Tina Shih

Faculty, Staff and Student Publications

BACKGROUND: There is a lack of evidence from nationwide samples on the disparity of initiating immune checkpoint inhibitors (ICIs) after metastatic lung cancer diagnosis.

METHODS: We identified metastatic lung cancer patients diagnosed between 2015 and 2020 from a large, nationwide commercial claims database. We analyzed the time from metastatic lung cancer diagnosis to ICI therapy using Cox proportional hazard models. Independent variables included county-level measures (quintiles of percentage of racialized population, quintiles of percentage of population below poverty, urbanity, and density of medical oncologists) and patient characteristics (age, sex, Charlson comorbidity index, Medicare Advantage, and year of diagnosis). All tests …

Immunocompromised Host Pneumonia: Definitions And Diagnostic Criteria: An Official American Thoracic Society Workshop Report, Guang-Shing Cheng, Kristina Crothers, Stefano Aliberti, Anne Bergeron, Michael Boeckh, Jason W Chien, Catia Cilloniz, Keira Cohen, Nathan Dean, Charles S Dela Cruz, Robert P Dickson, Alexander L Greninger, Chadi A Hage, Tobias M Hohl, Steven M Holland, Barbara E Jones, Joseph Keane, Mark Metersky, Rachel Miller, Anne Puel, Julio Ramirez, Marcos I Restrepo, Ajay Sheshadri, Bashar Staitieh, Jeffrey Tarrand, Kevin L Winthrop, Richard G Wunderink, Scott E Evans

Faculty, Staff and Student Publications

Pneumonia imposes a significant clinical burden on people with immunocompromising conditions. Millions of individuals live with compromised immunity because of cytotoxic cancer treatments, biological therapies, organ transplants, inherited and acquired immunodeficiencies, and other immune disorders. Despite broad awareness among clinicians that these patients are at increased risk for developing infectious pneumonia, immunocompromised people are often excluded from pneumonia clinical guidelines and treatment trials. The absence of a widely accepted definition for immunocompromised host pneumonia is a significant knowledge gap that hampers consistent clinical care and research for infectious pneumonia in these vulnerable populations. To address this gap, the American Thoracic …

Risk Factors For Bronchiolitis Obliterans Syndrome After Initial Detection Of Pulmonary Impairment After Hematopoietic Cell Transplantation, Mansour Alkhunaizi, Badar Patel, Luis Bueno, Neel Bhan, Tahreem Ahmed, Muhammad H Arain, Rima Saliba, Gabriela Rondon, Burton F Dickey, Lara Bashoura, David E Ost, Liang Li, Shikun Wang, Elizabeth Shpall, Richard E Champlin, Rohtesh Mehta, Uday R Popat, Chitra Hosing, Amin M Alousi, Ajay Sheshadri

Faculty, Staff and Student Publications

Pulmonary chronic graft-versus-host-disease (cGVHD), or bronchiolitis obliterans syndrome (BOS), is a highly morbid complication of hematopoietic cell transplantation (HCT). The clinical significance of a single instance of pulmonary decline not meeting the criteria for BOS is unclear. We conducted a retrospective analysis in a cohort of patients who had an initial post-HCT decline in the absolute value of forced expiratory volume in 1 second (FEV1) of ≥10% or mid-expiratory flow rate of ≥25% but not meeting the criteria for BOS (pre-BOS). We examined the impact of clinical variables in patients with pre-BOS on the risk for subsequent BOS. Pre-BOS developed …

Analysis Of Immune Intratumor Heterogeneity Highlights Immunoregulatory And Coinhibitory Lymphocytes As Hallmarks Of Recurrence In Stage I Non-Small Cell Lung Cancer, Alejandro Francisco-Cruz, Pedro Rocha, Alexandre Reuben, Santhoshi N Krishnan, Priyam Das, Runzhe Chen, Kelly Quek, Jun Li, Edwin R Parra, Luisa M Solis, Souptik Barua, Mei Jiang, Rossana Lazcano, Chi-Wan Chow, Carmen Behrens, Curtis Gumb, Latasha Little, Junya Fukuoka, Neda Kalhor, Annikka Weissferdt, Humam Kadara, John V Heymach, Stephen Swisher, Boris Sepesi, Arvind Rao, Cesar Moran, Jianhua Zhang, J Jack Lee, Junya Fujimoto, P Andrew Futreal, Ignacio I Wistuba, Christine B Peterson, Jianjun Zhang

Faculty, Staff and Student Publications

Our understanding of the molecular mechanisms underlying postsurgical recurrence of non-small cell lung cancer (NSCLC) is rudimentary. Molecular and T cell repertoire intratumor heterogeneity (ITH) have been reported to be associated with postsurgical relapse; however, how ITH at the cellular level impacts survival is largely unknown. Here we report the analysis of 2880 multispectral images representing 14.2% to 27% of tumor areas from 33 patients with stage I NSCLC, including 17 cases (relapsed within 3 years after surgery) and 16 controls (without recurrence ≥5 years after surgery) using multiplex immunofluorescence. Spatial analysis was conducted to quantify the minimum distance between …

Mechanical Ventilation In Patients With Cardiogenic Pulmonary Edema: A Sub-Analysis Of The Lung Safe Study, Laura Amado-Rodríguez, Raquel Rodríguez-Garcia, Giacomo Bellani, Tài Pham, Eddy Fan, Fabiana Madotto, John G Laffey, Guillermo M Albaiceta, Lung Safe Investigators

Faculty, Staff and Student Publications

BACKGROUND: Patients with acute respiratory failure caused by cardiogenic pulmonary edema (CPE) may require mechanical ventilation that can cause further lung damage. Our aim was to determine the impact of ventilatory settings on CPE mortality.

METHODS: Patients from the LUNG SAFE cohort, a multicenter prospective cohort study of patients undergoing mechanical ventilation, were studied. Relationships between ventilatory parameters and outcomes (ICU discharge/hospital mortality) were assessed using latent mixture analysis and a marginal structural model.

RESULTS: From 4499 patients, 391 meeting CPE criteria (median age 70 [interquartile range 59-78], 40% female) were included. ICU and hospital mortality were 34% and 40%, …

Surgical Outcomes After Neoadjuvant Nivolumab Or Nivolumab With Ipilimumab In Patients With Non-Small Cell Lung Cancer, Boris Sepesi, Nicolas Zhou, William N William, Heather Y Lin, Cheuk H Leung, Annikka Weissferdt, Kyle G Mitchell, Apar Pataer, Garrett L Walsh, David C Rice, Jack A Roth, Reza J Mehran, Wayne L Hofstetter, Mara B Antonoff, Ravi Rajaram, Marcelo V Negrao, Anne S Tsao, Don L Gibbons, J Jack Lee, John V Heymach, Ara A Vaporciyan, Stephen G Swisher, Tina Cascone

Faculty, Staff and Student Publications

BACKGROUND: Surgical outcomes for non-small cell lung cancer after neoadjuvant immune checkpoint inhibitors continue to be debated. We assessed perioperative outcomes of patients treated with Nivolumab or Nivolumab plus Ipilimumab (NEOSTAR) and compared them with patients treated with chemotherapy or previously untreated patients with stage I-IIIA non-small cell lung cancer.

METHODS: Forty-four patients with stage I to IIIA non-small cell lung cancer (American Joint Committee on Cancer Staging Manual, seventh edition) were randomized to nivolumab (N; 3 mg/kg intravenously on days 1, 15, and 29; n = 23) or nivolumab with ipilimumab (NI; I, 1 mg/kg intravenously on day 1; …

Immunogenomic Profiling Of Lung Adenocarcinoma Reveals Poorly Differentiated Tumors Are Associated With An Immunogenic Tumor Microenvironment, Neal Akhave, Jiexin Zhang, Erin Bayley, Meredith Frank, Shin-Heng Chiou, Carmen Behrens, Runzhe Chen, Xin Hu, Edwin Roger Parra, Won-Chul Lee, Stephen Swisher, Luisa Solis, Annikka Weissferdt, Cesar Moran, Neda Kalhor, Jianhua Zhang, Paul Scheet, Ara A Vaporciyan, Boris Sepesi, Don L Gibbons, John V Heymach, Jack J Lee, Ignacio I Wistuba, P Andrew Futreal, Jianjun Zhang, Junya Fujimoto, Alexandre Reuben

Faculty, Staff and Student Publications

OBJECTIVES: Pathologists have routinely observed distinct histologic patterns of growth in early-stage lung adenocarcinoma (LUAD), which have been suggested to be associated with prognosis. Herein, we investigated the relationship between LUAD patterns of growth, as defined by the updated international association for the study of lung cancer (IASLC) grading criteria, and differences in the tumor immune microenvironment to identify predictors of response to immunotherapy.

METHODS: 174 resected stage I-III LUAD tumors were classified by histologic pattern of growth (i.e. solid, micropapillary, acinar, papillary, and lepidic) and then grouped as well differentiated, moderately differentiated, and poorly differentiated. Comprehensive multiplatform analysis including …

Major Pathologic Response And Prognostic Score Predict Survival In Patients With Lung Cancer Receiving Neoadjuvant Chemotherapy, Apar Pataer, Annikka Weissferdt, Arlene M Correa, Ara A Vaporciyan, Boris Sepesi, John V Heymach, Sabina Berezowska, Tina Cascone, Stephen G Swisher

Faculty, Staff and Student Publications

INTRODUCTION: Complete pathologic response (CPR) is an acceptable surrogate for survival in clinical trials but it occurs infrequently in patients with NSCLC receiving neoadjuvant chemotherapy (NCT). Therefore, we studied the impact of major pathologic response (MPR) for predicting survival of patients with NSCLC receiving NCT. We also tested a newly reported scoring system-the prognostic score (PRSC)-which combines T category, lymph node status, and MPR status.

METHODS: We analyzed CPR and MPR, defined as 0% and less than or equal to 10% viable tumor cells, respectively, in 339 patients with NSCLC with various histologic types who had been treated with NCT …

Intermediary Role Of Lung Alveolar Type 1 Cells In Epithelial Repair Upon Sendai Virus Infection, Belinda J Hernandez, Margo P Cain, Anne M Lynch, Jose R Flores, Michael J Tuvim, Burton F Dickey, Jichao Chen

Faculty, Staff and Student Publications

The lung epithelium forms the first barrier against respiratory pathogens and noxious chemicals; however, little is known about how more than 90% of this barrier, made of AT1 (alveolar type 1) cells, responds to injury. Using the Sendai virus to model natural infection in mice, we find evidence that AT1 cells have an intermediary role by persisting in areas depleted of AT2 cells, upregulating IFN responsive genes, and receding from invading airway cells. Sendai virus infection mobilizes airway cells to form alveolar SOX2+ (Sry-box 2+) clusters without differentiating into AT1 or AT2 cells. Large AT2 cell-depleted areas remain covered by …

Contributions Of Circulating Micrornas For Early Detection Of Lung Cancer, Jody Vykoukal, Johannes F Fahrmann, Nikul Patel, Masayoshi Shimizu, Edwin J Ostrin, Jennifer B Dennison, Cristina Ivan, Gary E Goodman, Mark D Thornquist, Matt J Barnett, Ziding Feng, George A Calin, Samir M Hanash

Faculty, Staff and Student Publications

There is unmet need to develop circulating biomarkers that would enable earlier interception of lung cancer when more effective treatment options are available. Here, a set of 30 miRNAs, selected from a review of the published literature were assessed for their predictive performance in identifying lung cancer cases in the pre-diagnostic setting. The 30 miRNAs were assayed using sera collected from 102 individuals diagnosed with lung cancer within one year following blood draw and 212 controls matched for age, sex, and smoking status. The additive performance of top-performing miRNA candidates in combination with a previously validated four-protein marker panel (4MP) …

Rationale And Design Of The Phase 3 Keylynk-013 Study Of Pembrolizumab With Concurrent Chemoradiotherapy Followed By Pembrolizumab With Or Without Olaparib For Limited-Stage Small-Cell Lung Cancer, Andreas Rimner, Wei-Chu Victoria Lai, Raffaele Califano, Salma K Jabbour, Charles M Rudin, Corinne Faivre-Finn, Byoung Chul Cho, Terufumi Kato, Jinming Yu, Wyatt Chafin, Li Yu, Bin Zhao, Lauren Byers

Faculty, Staff and Student Publications

Background: The current standard of care for patients with newly diagnosed limited-stage small-cell lung cancer (SCLC) is concurrent chemoradiotherapy (CCRT). The prognosis remains poor due to the aggressiveness and high risk of progression or relapse of SCLC even if an initial response is achieved. Therefore, there is an urgent unmet clinical need in this population. The multicenter, phase 3, randomized, placebo-controlled, double-blind KEYLYNK-013 study evaluates the addition of pembrolizumab to CCRT followed by pembrolizumab with or without olaparib in participants with previously untreated limited-stage SCLC. (ClinicalTrials.gov: NCT04624204).

Methods: Eligible participants aged ≥18 years with newly diagnosed, pathologically confirmed, limited-stage …

Modeling Recurrence In Idiopathic Subglottic Stenosis With Mobile Peak Expiratory Flow, Kyle Kimura, Liping Du, Lynn D Berry, Li-Ching Huang, Sheau-Chiann Chen, David O Francis, Alexander Gelbard

Faculty, Staff and Student Publications

OBJECTIVES/HYPOTHESIS: We sought to establish normative peak expiratory flow (PEF) data for patients with idiopathic subglottic stenosis (iSGS), evaluate whether immediate changes in PEF after a procedure predict long-term treatment response, and test if a decline in longitudinal PEF is associated with disease recurrence.

STUDY DESIGN: International, prospective, 3-year multicenter cohort study of 810 patients with untreated, newly diagnosed, or previously treated iSGS.

METHODS: iSGS patients consented and enrolled in the North American Airway Collaborative (NoAAC) iSGS

RESULTS: Within the NoAAC iSGS1000 cohort, 810 patients participated in a 3-year, prospective study comparing surgical treatment efficacy and 385 had appropriate PEF …

A Lung Cancer Screening Personalized Decision-Aid Improves Knowledge And Reduces Decisional Conflict Among A Diverse Population Of Smokers At An Urban Academic Medical Center, Madeline Kaufman, Nilan Schnure, Andrea Nicholson, Frank Leone, Carmen Guerra

Journal of Health Disparities Research and Practice

Introduction: Few lung cancer screening decision aids have been tested in diverse populations. The study objective was to determine whether the online decision aid www.shouldiscreen.com impacts knowledge of and decisional conflict around lung cancer screening in a diverse population.

Methods: Eligible patients had significant smoking histories, were at increased risk for lung cancer (ages 45-80, >20 pack-years, smoking within last 15 years) and had no history of prior lung cancer or screening. Data was collected and analyzed in 2017.

Results: 40 patients were enrolled: 80% were female, 62.5% black, 33% white, and 48% had a high school …

Gene Co-Expression Networks Analysis Reveal Novel Molecular Endotypes In Alpha-1 Antitrypsin Deficiency, Jen-Hwa Chu, Wenlan Zang

Yale Day of Data

Rationale:Alpha-1 antitrypsin deficiency (AATD) is a genetic condition that predisposes to early onset pulmonary emphysema and airways obstruction. The exact mechanism through which AATD leads to lung disease is incompletely understood.

Objectives: To investigate the effect of AAT genotype and augmentation therapy on bronchoalveolar lavage (BAL) and peripheral blood mononuclear cells (PBMC) transcriptome, while examining the link between gene expression profiles, and clinical features of AATD.

Methods: We performed RNA-Seq on RNA extracted from BAL and PBMC on samples obtained from 89 AATD patients enrolled in the Genomic Research in Alpha-1 Antitrypsin Deficiency and Sarcoidosis (GRADS) study. Differential …