Pulmonology Commons^™

Prognostic Significance Of Micropapillary Pattern And Risk Factors In Patients With Resected Stage I Lung Adenocarcinoma And Possible Benefit Of Adjuvant Therapy: A Real-World Multicenter Study, Jianjie Li, Yujia Chi, Bo Jia, Qiwen Zheng, Minghan Yuan, Jianjun Zhang, Aishen Zhou, Wei Sun, Yue Yang, Jun Zhao, Tongtong An, Yuyan Wang, Minglei Zhuo, Xue Yang, Hanxiao Chen, Jingjing Wang, Xiaoyu Zhai, Yidi Tai, Yuling He, Lingdong Kong, Xumeng Ji, Yiliang Liu, Nan Wu, Ken Onodera, Paul Van Schil, Mathew Thomas, Fan Yang, Ziping Wang

Faculty, Staff and Student Publications

Background: Micropapillary (MP) pattern has been identified as a negative prognostic factor in patients with lung adenocarcinoma, but it has not been recognized as a high-risk factor for patients with stage IB lung adenocarcinoma treated with adjuvant chemotherapy. This multicenter cohort study aimed to evaluate the prognostic value of histological subtypes for stage I lung adenocarcinoma and to determine the relative survival benefit of adjuvant chemotherapy for subgroups based on MP pattern.

Methods: This retrospective study included 412 patients with stage I lung adenocarcinoma [according the eighth edition of the tumor-node-metastasis (TNM) classification] with MP pattern who underwent complete surgical …

Delta-Like Ligand 3 (Dll3) Landscape In Pulmonary And Extra-Pulmonary Neuroendocrine Neoplasms, Alejandra G Serrano, Pedro Rocha, Cibelle Freitas Lima, Allison Stewart, Bingnan Zhang, Lixia Diao, Junya Fujimoto, Robert J Cardnell, Wei Lu, Khaja Khan, Beate Sable, Aaron R Ellison, Ignacio I Wistuba, Kyle F Concannon, Daniel M Halperin, Czerniak Bogdan, Kanishka Sircar, Miao Zhang, Kasey Cargill, Qi Wang, Ana Aparicio, Alexander Lazar, Sharia Hernandez, Jeannelyn Estrella, Preetha Ramalingam, Adel El-Naggar, Neda Kalhor, Carl M Gay, Lauren Averett Byers, Luisa M Solis Soto

Faculty, Staff and Student Publications

Delta-like Ligand 3 (DLL3) targeting therapies are promising in small cell lung cancer (SCLC) treatment. However, DLL3 expression in SCLC and other neuroendocrine neoplasms (NEN) is heterogeneous and not well characterized. We describe the landscape of DLL3 at the mRNA and protein levels across SCLC, large cell neuroendocrine carcinoma (LCNEC), and non-small cell lung cancer. Additionally, we explore its expression in extra-pulmonary NEN (EP-NEN) using a standardized DLL3 IHC assay. DLL3 expression is enriched in SCLC, LCNEC along with combined histology lung cancers. Moreover, we find a wide range of DLL3 expression in high-grade EP-NEN. We describe heterogenous DLL3 expression …

Multiregional Transcriptomic Profiling Provides Improved Prognostic Insight In Localized Non-Small Cell Lung Cancer, Chenyang Li, Thinh T Nguyen, Jian-Rong Li, Xingzhi Song, Junya Fujimoto, Latasha Little, Curtis Gumb, Chi-Wan B Chow, Ignacio I Wistuba, Andrew P Futreal, Jianhua Zhang, Shawna M Hubert, John V Heymach, Jia Wu, Christopher I Amos, Jianjun Zhang, Chao Cheng

Faculty, Staff and Student Publications

Lung Cancer remains the leading cause of cancer deaths in the USA and worldwide. Non-small cell lung cancer (NSCLC) harbors high transcriptomic intratumor heterogeneity (RNA-ITH) that limits the reproducibility of expression-based prognostic models. In this study, we used multiregional RNA-seq data (880 tumor samples from 350 individuals) from both public (TRACERx) and internal (MDAMPLC) cohorts to investigate the effect of RNA-ITH on prognosis in localized NSCLC at the gene, signature, and tumor microenvironment levels. At the gene level, the maximal expression of hazardous genes (expression negatively associated with survival) but the minimal expression of protective genes (expression positively associated with …

Multi-Ancestry Gwas Meta-Analyses Of Lung Cancer Reveal Susceptibility Loci And Elucidate Smoking-Independent Genetic Risk, Bryan R Gorman, Sun-Gou Ji, Michael Francis, Anoop K Sendamarai, Yunling Shi, Poornima Devineni, Uma Saxena, Elizabeth Partan, Andrea K Devito, Jinyoung Byun, Younghun Han, Xiangjun Xiao, Don D Sin, Wim Timens, Jennifer Moser, Sumitra Muralidhar, Rachel Ramoni, Rayjean J Hung, James D Mckay, Yohan Bossé, Ryan Sun, Christopher I Amos, Va Million Veteran Program, Saiju Pyarajan

Faculty, Staff and Student Publications

Lung cancer remains the leading cause of cancer mortality, despite declining smoking rates. Previous lung cancer GWAS have identified numerous loci, but separating the genetic risks of lung cancer and smoking behavioral susceptibility remains challenging. Here, we perform multi-ancestry GWAS meta-analyses of lung cancer using the Million Veteran Program cohort (approximately 95% male cases) and a previous study of European-ancestry individuals, jointly comprising 42,102 cases and 181,270 controls, followed by replication in an independent cohort of 19,404 cases and 17,378 controls. We then carry out conditional meta-analyses on cigarettes per day and identify two novel, replicated loci, including the 19p13.11 …

Pparγ/Etv2 Axis Regulates Endothelial-To-Mesenchymal Transition In Pulmonary Hypertension, Dong Hun Lee, Minseong Kim, Sarah S Chang, Raham Lee, Andrew J Jang, Juyoung Kim, Jing Ma, Michael J Passineau, Raymond L Benza, Harry Karmouty-Quintana, Wilbur A Lam, Benjamin T Kopp, Roy L Sutliff, C Michael Hart, Changwon Park, Bum-Yong Kang

Faculty, Staff and Student Publications

Endothelial-to-mesenchymal transition (EndoMT) plays an important role in pulmonary hypertension (PH) but the molecular mechanisms regulating EndoMT remain to be defined. We demonstrate that the axis of the transcription factors PPARγ (Peroxisome Proliferator-Activated Receptor gamma) and ETV2 (ETS variant 2) play important roles in the pathogenesis of PH. Decreased levels of the expression of PPARγ and ETV2 along with reduced endothelial and increased EndoMT markers are consistently observed in lungs and pulmonary artery endothelial cells (PAECs) of idiopathic pulmonary arterial hypertension patients, in hypoxia-exposed mouse lungs, human PAECs, and in induced-EndoMT cells. Etv2 +/- mice spontaneously developed PH and right …

Persistent Microbial Infections And Idiopathic Pulmonary Fibrosis – An Insight Into Non-Typeable Haemophilus Influenza Pathogenesis, Dong Hun Lee, Minseong Kim, Sarah S Chang, Raham Lee, Andrew J Jang, Juyoung Kim, Jing Ma, Michael J Passineau, Raymond L Benza, Harry Karmouty-Quintana, Wilbur A Lam, Benjamin T Kopp, Roy L Sutliff, C Michael Hart, Changwon Park, Bum-Yong Kang

Faculty, Staff and Student Publications

Endothelial-to-mesenchymal transition (EndoMT) plays an important role in pulmonary hypertension (PH) but the molecular mechanisms regulating EndoMT remain to be defined. We demonstrate that the axis of the transcription factors PPARγ (Peroxisome Proliferator-Activated Receptor gamma) and ETV2 (ETS variant 2) play important roles in the pathogenesis of PH. Decreased levels of the expression of PPARγ and ETV2 along with reduced endothelial and increased EndoMT markers are consistently observed in lungs and pulmonary artery endothelial cells (PAECs) of idiopathic pulmonary arterial hypertension patients, in hypoxia-exposed mouse lungs, human PAECs, and in induced-EndoMT cells. Etv2 +/- mice spontaneously developed PH and right …

Molecular Landscape Of Erbb2 Alterations In 3000 Advanced Nsclc Patients, Lingzhi Hong, Sonia Patel, Leylah M Drusbosky, Yuanyuan Xiong, Rongrong Chen, Ruixuan Geng, Simon Heeke, Monique Nilsson, Jia Wu, John V Heymach, Yingyi Wang, Jianjun Zhang, Xiuning Le

Faculty, Staff and Student Publications

ERBB2 (HER2) represents a newly recognized actionable oncogenic driver in non-small cell lung cancer (NSCLC), with approved targeted therapy available. Understanding the landscape of ERBB2 alterations and co-occurring mutations is essential for guiding treatment decisions. We conducted an analysis involving 3000 NSCLC patients with all types of ERBB2 alterations, drawn from two extensive retrospective cohorts: 1281 from Geneplus (Chinese) and 1719 from Guardant360 (the United States, US). The incidence of all types of ERBB2 alterations was found to be 5.6% in the Chinese group and 5.2% in the US group. In both cohorts, among oncogenic alterations of ERBB2, exon 20 …

Premalignant Progression In The Lung: Knowledge Gaps And Novel Opportunities For Interception Of Non-Small Cell Lung Cancer An Official American Thoracic Society Research Statement, Seyed Javad Moghaddam, Rajkumar Savai, Ramin Salehi-Rad, Shreoshi Sengupta, Michael N Kammer, Pierre Massion, Jennifer E Beane, Edwin J Ostrin, Carmen Priolo, Meredith A Tennis, Laura P Stabile, Alison K Bauer, Catherine R Sears, Eva Szabo, M Patricia Rivera, Charles A Powell, Humam Kadara, Brendan J Jenkins, Steven M Dubinett, A Mcgarry Houghton, Carla F Kim, Robert L Keith

Faculty, Staff and Student Publications

Rationale: Despite significant advances in precision treatments and immunotherapy, lung cancer is the most common cause of cancer death worldwide. To reduce incidence and improve survival rates, a deeper understanding of lung premalignancy and the multistep process of tumorigenesis is essential, allowing timely and effective intervention before cancer development. Objectives: To summarize existing information, identify knowledge gaps, formulate research questions, prioritize potential research topics, and propose strategies for future investigations into the premalignant progression in the lung. Methods: An international multidisciplinary team of basic, translational, and clinical scientists reviewed available data to develop and refine research questions pertaining to the …

Overcoming Egfr-Tki Resistance By Targeting The Tumor Microenvironment, Jinsong Zhang, Natalie Vokes, Man Li, Jiachen Xu, Hua Bai, Jie Wang, Zhijie Wang, Jianjun Zhang

Faculty, Staff and Student Publications

Targeted therapy has ushered in a new era of precision medicine for non-small cell lung cancer (NSCLC). Currently, epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) stand as the recommended first-line therapy for advanced NSCLC harboring sensitive EGFR mutations. Nevertheless, most patients inevitably confront the challenge of drug resistance. This phenomenon arises not solely from intrinsic alterations within cancer cells but also from the intricate dynamics of the tumor microenvironment and the complex interactions that occur between cancer cells and their immediate surroundings. This review consolidates the current knowledge regarding EGFR-TKI resistance mechanisms, with a specific emphasis on unraveling the …

Inhibition Of Ulk1/2 And Kras G12c Controls Tumor Growth In Preclinical Models Of Lung Cancer, Phaedra C Ghazi, Kayla T O'Toole, Sanjana Srinivas Boggaram, Michael T Scherzer, Mark R Silvis, Yun Zhang, Madhumita Bogdan, Bryan D Smith, Guillermina Lozano, Daniel L Flynn, Eric L Snyder, Conan G Kinsey, Martin Mcmahon

Faculty, Staff and Student Publications

Mutational activation of KRAS occurs commonly in lung carcinogenesis and, with the recent U.S. Food and Drug Administration approval of covalent inhibitors of KRASG12C such as sotorasib or adagrasib, KRAS oncoproteins are important pharmacological targets in non-small cell lung cancer (NSCLC). However, not all KRASG12C-driven NSCLCs respond to these inhibitors, and the emergence of drug resistance in those patients who do respond can be rapid and pleiotropic. Hence, based on a backbone of covalent inhibition of KRASG12C, efforts are underway to develop effective combination therapies. Here, we report that the inhibition of KRASG12C signaling increases autophagy in KRASG12C-expressing lung cancer …

Lung Cell Transplantation For Pulmonary Fibrosis, Irit Milman Krentsis, Yangxi Zheng, Chava Rosen, Sarah Y Shin, Christa Blagdon, Einav Shoshan, Yuan Qi, Jing Wang, Sandeep K Yadav, Esther Bachar Lustig, Elias Shetzen, Burton F Dickey, Harry Karmouty-Quintana, Yair Reisner

Faculty, Staff and Student Publications

Idiopathic pulmonary fibrosis is a major cause of death with few treatment options. Here, we demonstrate the therapeutic efficacy for lung fibrosis of adult lung cell transplantation using a single-cell suspension of the entire lung in two distinct mouse systems: bleomycin treatment and mice lacking telomeric repeat-binding factor 1 expression in alveolar type 2 (AT2) cells (SPC-Cre TRF1fl/fl), spontaneously developing fibrosis. In both models, the progression of fibrosis was associated with reduced levels of host lung progenitors, enabling engraftment of donor progenitors without any additional conditioning, in contrast to our previous studies. Two months after transplantation, engrafted progenitors …

Translational Modeling-Based Evidence For Enhanced Efficacy Of Standard-Of-Care Drugs In Combination With Anti-Microrna-155 In Non-Small-Cell Lung Cancer, Prashant Dogra, Vrushaly Shinglot, Javier Ruiz-Ramírez, Joseph Cave, Joseph D Butner, Carmine Schiavone, Dan G Duda, Ahmed O Kaseb, Caroline Chung, Eugene J Koay, Vittorio Cristini, Bulent Ozpolat, George A Calin, Zhihui Wang

Faculty, Staff and Student Publications

BACKGROUND: Elevated microRNA-155 (miR-155) expression in non-small-cell lung cancer (NSCLC) promotes cisplatin resistance and negatively impacts treatment outcomes. However, miR-155 can also boost anti-tumor immunity by suppressing PD-L1 expression. Therapeutic targeting of miR-155 through its antagonist, anti-miR-155, has proven challenging due to its dual molecular effects.

METHODS: We developed a multiscale mechanistic model, calibrated with in vivo data and then extrapolated to humans, to investigate the therapeutic effects of nanoparticle-delivered anti-miR-155 in NSCLC, alone or in combination with standard-of-care drugs.

RESULTS: Model simulations and analyses of the clinical scenario revealed that monotherapy with anti-miR-155 at a dose of 2.5 mg/kg …

A Comparison Of Tracheal Intubation Using Direct Laryngoscope And Video Laryngoscope In The Sellick And Trendelenburg Position With That Using Direct Laryngoscope In The Supine Sniffing Position: A Randomized Controlled Trial, Yun-Jeong Chae, Jung-Yoon Moon, Min-Gyu Lee, Han-Bum Joe

Faculty, Staff and Student Publications

Background: Tracheal intubation in the Sellick and Trendelenburg position (ST position) can prevent pulmonary aspiration but increase the difficulty of tracheal intubation. We compared tracheal intubation using video and direct laryngoscopy in the ST position with direct laryngoscopy in the supine sniffing position to evaluate the overall intubation performance. Methods: One hundred and twenty patients were randomly assigned to three groups: direct laryngoscope in the supine sniffing position (control), direct laryngoscope in the ST position (ST direct), and video laryngoscope in the ST position (ST video). The primary outcome was the intubation time; secondary outcomes included the first …

Epigenome-Wide Association Study Of Lung Cancer Among Never Smokers In Two Prospective Cohorts In Shanghai, China, Mohammad L Rahman, Charles E Breeze, Xiao-Ou Shu, Jason Y Y Wong, Batel Blechter, Andres Cardenas, Xuting Wang, Bu-Tian Ji, Wei Hu, Qiuyin Cai, H Dean Hosgood, Gong Yang, Jianxin Shi, Jirong Long, Yu-Tang Gao, Douglas A Bell, Wei Zheng, Nathaniel Rothman, Qing Lan

Faculty, Staff and Student Publications

BACKGROUND: The aetiology of lung cancer among individuals who never smoked remains elusive, despite 15% of lung cancer cases in men and 53% in women worldwide being unrelated to smoking. Epigenetic alterations, particularly DNA methylation (DNAm) changes, have emerged as potential drivers. Yet, few prospective epigenome-wide association studies (EWAS), primarily focusing on peripheral blood DNAm with limited representation of never smokers, have been conducted.

METHODS: We conducted a nested case-control study of 80 never-smoking incident lung cancer cases and 83 never-smoking controls within the Shanghai Women's Health Study and Shanghai Men's Health Study. DNAm was measured in prediagnostic oral rinse …

The Calcineurin-Nfatc Pathway Modulates The Lipid Mediators In Bal Fluid Extracellular Vesicles, Thereby Regulating Microvascular Endothelial Cell Barrier Function, Manjula Karpurapu, Yunjuan Nie, Sangwoon Chung, Jiasheng Yan, Patrick Dougherty, Sonal Pannu, Jon Wisler, Ryan Harkless, Narasimham Parinandi, Evgeny Berdyshev, Dehua Pei, John W Christman

Faculty, Staff and Student Publications

Extracellular vesicles mediate intercellular communication by transporting biologically active macromolecules. Our prior studies have demonstrated that the nuclear factor of activated T cell cytoplasmic member 3 (NFATc3) is activated in mouse pulmonary macrophages in response to lipopolysaccharide (LPS). Inhibition of NFATc3 activation by a novel cell-permeable calcineurin peptide inhibitor CNI103 mitigated the development of acute lung injury (ALI) in LPS-treated mice. Although pro-inflammatory lipid mediators are known contributors to lung inflammation and injury, it remains unclear whether the calcineurin-NFATc pathway regulates extracellular vesicle (EV) lipid content and if this content contributes to ALI pathogenesis. In this study, EVs from mouse …

High All-Cause Mortality And Increasing Proportion Of Older Adults With Tuberculosis In Texas, 2008–2020, Belinda A Medrano, Miryoung Lee, Gretchen Gemeinhardt, Lana Yamba, Blanca I Restrepo

Faculty, Staff and Student Publications

Pulmonary tuberculosis (PTB) elimination efforts must consider the global growth of the ageing population. Here we used TB surveillance data from Texas, United States (2008-2020; total n = 10656) to identify unique characteristics and outcomes in older adults (OA, ≥65 years) with PTB, compared to young adults (YA, 18-39 years) or middle-aged adults (40-64 years). We found that the proportion of OA with PTB increased from 15% in 2008 to 24% in 2020 (trend p < 0.05). Diabetes was highly prevalent in OA (32%) but not associated with adverse outcomes. Death was 13-fold higher in OA compared to YA and was 7% at the time of diagnosis which suggests diagnostic delays. However, once TB was suspected, we found no differences in culture, smear, or nucleic acid detection of mycobacteria (although less lung cavitations) in OA. During treatment, OA had less drug-resistant TB, few adverse reactions and adhered with TB treatment. We recommend training healthcare workers to 'think TB' in OA, for prompt treatment initiation to diminish deaths. Furthermore, OA should be added as a priority group to the latent TB treatment guidelines by the World Health Organization, to prevent TB disease in this highly vulnerable group.

Ras G-Domains Allosterically Contribute To The Recognition Of Lipid Headgroups And Acyl Chains, Neha Arora, Huanwen Mu, Hong Liang, Wenting Zhao, Yong Zhou

Faculty, Staff and Student Publications

Mutant RAS are major contributors to cancer and signal primarily from nanoclusters on the plasma membrane (PM). Their C-terminal membrane anchors are main features of membrane association. However, the same RAS isoform bound to different guanine nucleotides spatially segregate. Different RAS nanoclusters all enrich a phospholipid, phosphatidylserine (PS). These findings suggest more complex membrane interactions. Our electron microscopy-spatial analysis shows that wild-types, G12V mutants, and membrane anchors of isoforms HRAS, KRAS4A, and KRAS4B prefer distinct PS species. Mechanistically, reorientation of KRAS4B G-domain exposes distinct residues, such as Arg 135 in orientation state 1 (OS1) and Arg 73/Arg 102 in OS2, …

Age At Lung Cancer Diagnosis In Females Versus Males Who Never Smoke By Race And Ethnicity, Batel Blechter, Jason Y Y Wong, Li-Hsin Chien, Kouya Shiraishi, Xiao-Ou Shu, Qiuyin Cai, Wei Zheng, Bu-Tian Ji, Wei Hu, Mohammad L Rahman, Hsin-Fang Jiang, Fang-Yu Tsai, Wen-Yi Huang, Yu-Tang Gao, Xijing Han, Mark D Steinwandel, Gong Yang, Yihe G Daida, Su-Ying Liang, Scarlett L Gomez, Mindy C Derouen, W Ryan Diver, Ananya G Reddy, Alpa V Patel, Loïc Le Marchand, Christopher Haiman, Takashi Kohno, Iona Cheng, I-Shou Chang, Chao Agnes Hsiung, Nathaniel Rothman, Qing Lan

Faculty, Staff and Student Publications

BACKGROUND: We characterized age at diagnosis and estimated sex differences for lung cancer and its histological subtypes among individuals who never smoke.

METHODS: We analyzed the distribution of age at lung cancer diagnosis in 33,793 individuals across 8 cohort studies and two national registries from East Asia, the United States (US) and the United Kingdom (UK). Student's t-tests were used to assess the study population differences (Δ years) in age at diagnosis comparing females and males who never smoke across subgroups defined by race/ethnicity, geographic location, and histological subtypes.

RESULTS: We found that among Chinese individuals diagnosed with lung cancer …

Pulmonary Endobronchial Hamartoma Presenting With Post-Obstructive Pneumonia, Diane S Habib, Pushan Jani, Bihong Zhao, Elakiya Anjali Jayaraman, Ramesh Kesavan

Faculty, Staff and Student Publications

Pulmonary hamartomas (PH) are rare but are the most common benign tumors found in the lungs. They are slow-growing and are usually found incidentally on chest imaging during the sixth decade of life. Approximately 10% of pulmonary hamartomas are endobronchial. Rarely, pulmonary hamartomas can cause a spectrum of pulmonary symptoms depending on their size and location. We present a case of endobronchial hamartoma causing airway obstruction and recurrent post-obstructive pneumonia.

Advancing Primary Ciliary Dyskinesia Diagnosis Through High-Speed Video Microscopy Analysis, Wilfredo De Jesús-Rojas, Zachary J Demetriou, José Muñiz-Hernández, Gabriel Rosario-Ortiz, Frances M Quiñones, Marcos J Ramos-Benitez, Ricardo A Mosquera

Faculty, Staff and Student Publications

Primary ciliary dyskinesia (PCD) is an inherited disorder that impairs motile cilia, essential for respiratory health, with a reported prevalence of 1 in 16,309 within Hispanic populations. Despite 70% of Puerto Rican patients having the RSPH4A [c.921+3_921+6del (intronic)] founder mutation, the characterization of the ciliary dysfunction remains unidentified due to the unavailability of advanced diagnostic modalities like High-Speed Video Microscopy Analysis (HSVA). Our study implemented HSVA for the first time on the island as a tool to better diagnose and characterize the RSPH4A [c.921+3_921+6del (intronic)] founder mutation in Puerto Rican patients. By applying HSVA, we analyzed the ciliary beat frequency …

Detection Of Acute Brain Injury In Intensive Care Unit Patients On Ecmo Support Using Ultra-Low-Field Portable Mri: A Retrospective Analysis Compared To Head Ct, Sung-Min Cho, Shivalika Khanduja, Jiah Kim, Jin Kook Kang, Jessica Briscoe, Lori R Arlinghaus, Kha Dinh, Bo Soo Kim, Haris I Sair, Audrey-Carelle N Wandji, Elena Moreno, Glenda Torres, Jose Gavito-Higuera, Huimahn A Choi, John Pitts, Aaron M Gusdon, Glenn J Whitman

Faculty, Staff and Student Publications

Early detection of acute brain injury (ABI) is critical to intensive care unit (ICU) patient management and intervention to decrease major complications. Head CT (HCT) is the standard of care for the assessment of ABI in ICU patients; however, it has limited sensitivity compared to MRI. We retrospectively compared the ability of ultra-low-field portable MR (ULF-pMR) and head HCT, acquired within 24 h of each other, to detect ABI in ICU patients supported on extracorporeal membrane oxygenation (ECMO). A total of 17 adult patients (median age 55 years; 47% male) were included in the analysis. Of the 17 patients assessed, …

Omics-Based Profiles And Biomarkers Of Respiratory Infections: Are We There Yet?, Jezreel Pantaleon Garcia, Scott E Evans

Faculty, Staff and Student Publications

Descriptive omics-based clinical research provides valuable early steps in understanding host immune responses to respiratory pathogens in our global efforts to mitigate the impacts of severe respiratory infections with rapidly evolving technologies https://bit.ly/4bjJsvL

An Atlas Of Epithelial Cell States And Plasticity In Lung Adenocarcinoma, Guangchun Han, Ansam Sinjab, Zahraa Rahal, Anne M Lynch, Warapen Treekitkarnmongkol, Yuejiang Liu, Alejandra G Serrano, Jiping Feng, Ke Liang, Khaja Khan, Wei Lu, Sharia D Hernandez, Yunhe Liu, Xuanye Cao, Enyu Dai, Guangsheng Pei, Jian Hu, Camille Abaya, Lorena I Gomez-Bolanos, Fuduan Peng, Minyue Chen, Edwin R Parra, Tina Cascone, Boris Sepesi, Seyed Javad Moghaddam, Paul Scheet, Marcelo V Negrao, John V Heymach, Mingyao Li, Steven M Dubinett, Christopher S Stevenson, Avrum E Spira, Junya Fujimoto, Luisa M Solis, Ignacio I Wistuba, Jichao Chen, Linghua Wang, Humam Kadara

Faculty, Staff and Student Publications

Understanding the cellular processes that underlie early lung adenocarcinoma (LUAD) development is needed to devise intervention strategies1. Here we studied 246,102 single epithelial cells from 16 early-stage LUADs and 47 matched normal lung samples. Epithelial cells comprised diverse normal and cancer cell states, and diversity among cancer cells was strongly linked to LUAD-specific oncogenic drivers. KRAS mutant cancer cells showed distinct transcriptional features, reduced differentiation and low levels of aneuploidy. Non-malignant areas surrounding human LUAD samples were enriched with alveolar intermediate cells that displayed elevated KRT8 expression (termed KRT8+ alveolar intermediate cells (KACs) here), reduced differentiation, increased plasticity and driver …

Biomarker-Directed Targeted Therapy Plus Durvalumab In Advanced Non-Small-Cell Lung Cancer: A Phase 2 Umbrella Trial, Benjamin Besse, Elvire Pons-Tostivint, Keunchil Park, Sylvia Hartl, Patrick M Forde, Maximilian J Hochmair, Mark M Awad, Michael Thomas, Glenwood Goss, Paul Wheatley-Price, Frances A Shepherd, Marie Florescu, Parneet Cheema, Quincy S C Chu, Sang-We Kim, Daniel Morgensztern, Melissa L Johnson, Sophie Cousin, Dong-Wan Kim, Mor T Moskovitz, David Vicente, Boaz Aronson, Rosalind Hobson, Helen J Ambrose, Sajan Khosla, Avinash Reddy, Deanna L Russell, Mohamed Reda Keddar, James P Conway, J Carl Barrett, Emma Dean, Rakesh Kumar, Marlene Dressman, Philip J Jewsbury, Sonia Iyer, Simon T Barry, Jan Cosaert, John V Heymach

Faculty, Staff and Student Publications

For patients with non-small-cell lung cancer (NSCLC) tumors without currently targetable molecular alterations, standard-of-care treatment is immunotherapy with anti-PD-(L)1 checkpoint inhibitors, alone or with platinum-doublet therapy. However, not all patients derive durable benefit and resistance to immune checkpoint blockade is common. Understanding mechanisms of resistance—which can include defects in DNA damage response and repair pathways, alterations or functional mutations in STK11/LKB1, alterations in antigen-presentation pathways, and immunosuppressive cellular subsets within the tumor microenvironment—and developing effective therapies to overcome them, remains an unmet need. Here the phase 2 umbrella HUDSON study evaluated rational combination regimens for advanced NSCLC following failure …

Association Of Socioeconomic Factors And Severity Of Bronchiolitis Hospitalizations, Raymond Parlar-Chun, Zoabe Hafeez

Faculty, Staff and Student Publications

It is unclear if socioeconomic status (SES) factors influence severity of illness of patients hospitalized with bronchiolitis. This study was conducted to identify SES factors including the Center for Disease Control and Prevention’s Social Vulnerability Composite Index (SVI), estimated income, proportion of minority, proportion of living below poverty, insurance status, and number of household members associated with length of stay (LOS) and intensive care unit admission. Infants hospitalized at a tertiary care urban center for bronchiolitis were identified using International Classification of Diseases codes. Federal information processing system codes were identified from home address and paired with SVI and 2018 …

Development And Validation Of A Nomogram For Predicting Pulmonary Infection In Patients Receiving Immunosuppressive Drugs, Chuxuan Luo, Yue Zhang, Jiajie Zhang, Chen Jin, Xiaolan Ye, Yan Ren, Huajuan Shen, Maosheng Chen, Yiwen Li, Qiang He, Guangbiao Xu, Lina Shao

Faculty, Staff and Student Publications

Objective: Pulmonary infection (PI), a severe complication of immunosuppressive therapy, affects patients' prognosis. As part of this study, we aimed to construct a pulmonary infection prediction (PIP) model and validate it in patients receiving immunosuppressive drugs (ISDs). Methods: Totally, 7,977 patients being treated with ISDs were randomised 7:3 to the developing (n = 5,583) versus validation datasets (n = 2,394). Our predictive nomogram was established using the least absolute shrinkage and selection operator (LASSO) and multivariate COX regression analyses. With the use of the concordance index (C-index) and calibration curve, the prediction performance of the final model was …

Prioritizing Clinically Significant Lung Cancer Somatic Mutations For Targeted Therapy Through Efficient Ngs Data Filtering System, Jinlian Wang, Hui Li, Hongfang Liu

Faculty, Staff and Student Publications

In the realm of lung cancer treatment, where genetic heterogeneity presents formidable challenges, precision oncology demands an exacting approach to identify and hierarchically sort clinically significant somatic mutations. Current Next-Generation Sequencing (NGS) data filtering pipelines, while utilizing various external databases for mutation screening, often fall short in comprehensive integration and flexibility needed to keep pace with the evolving landscape of clinical data. Our study introduces a sophisticated NGS data filtering system, which not only aggregates but effectively synergizes diverse data sources, encompassing genetic variants, gene functions, clinical evidence, and an extensive body of literature. This system is distinguished by a …

Survivorship, Outcomes, And Risk Factors For Conversion To Total Hip Arthroplasty After Revision Hip Arthroscopic Surgery In Obese Patients: Results At A Minimum 5-Year Follow-Up, Peng Li, Jie Luo, Zilong Zheng, Lu Meng, Anqi Zhang, Wei Cao, Xiaomei Gong

Faculty, Staff and Student Publications

OBJECTIVE: A high number of Non-Small Cell Lung Cancer (NSCLC) patients with brain metastasis who have not had surgery often have a negative outlook. Radiotherapy remains a most common and effective method. Nomograms were developed to forecast the cancer-specific survival (CSS) and overall survival (OS) in NSCLC individuals with nonoperative brain metastases who underwent radiotherapy.

METHODS: Information was gathered from the Surveillance, Epidemiology, and End Results (SEER) database about patients diagnosed with NSCLC who had brain metastases not suitable for surgery. Nomograms were created and tested using multivariate Cox regression models to forecast CSS and OS at intervals of 1, …

An Efficacy And Safety Evaluation Of Montelukast + Fluticasone Propionate Vs Fluticasone Propionate In The Treatment Of Cough Variant Asthma In Children: A Meta-Analysis, Zhengbo Wei, Sheng Li

Faculty, Staff and Student Publications

PURPOSE: This study aimed to evaluate the efficacy and safety of montelukast (Mon) + fluticasone propionate (Flu) versus Flu in the treatment of cough variant asthma (CVA) in children.

METHODS: Eligible documents were selected from various databases. Weighted mean difference (WMD) and 95% confidence interval (CI) were used to evaluate continuous variables, and categorical variables were evaluated using risk ratio (RR) and 95% CI. Heterogeneity analysis was performed using Cochran's Q test and I

RESULTS: Nine studies were included, and Flu + Mon was found to significantly improve the total effective rate and reduce cough recurrence compared to Flu. The …

Inflammation In The Tumor-Adjacent Lung As A Predictor Of Clinical Outcome In Lung Adenocarcinoma, Igor Dolgalev, Hua Zhou, Nina Murrell, Hortense Le, Theodore Sakellaropoulos, Nicolas Coudray, Kelsey Zhu, Varshini Vasudevaraja, Anna Yeaton, Chandra Goparaju, Yonghua Li, Imran Sulaiman, Jun-Chieh J Tsay, Peter Meyn, Hussein Mohamed, Iris Sydney, Tomoe Shiomi, Sitharam Ramaswami, Navneet Narula, Ruth Kulicke, Fred P Davis, Nicolas Stransky, Gromoslaw A Smolen, Wei-Yi Cheng, James Cai, Salman Punekar, Vamsidhar Velcheti, Daniel H Sterman, J T Poirier, Ben Neel, Kwok-Kin Wong, Luis Chiriboga, Adriana Heguy, Thales Papagiannakopoulos, Bettina Nadorp, Matija Snuderl, Leopoldo N Segal, Andre L Moreira, Harvey I Pass, Aristotelis Tsirigos

Faculty, Staff and Student Publications

Approximately 30% of early-stage lung adenocarcinoma patients present with disease progression after successful surgical resection. Despite efforts of mapping the genetic landscape, there has been limited success in discovering predictive biomarkers of disease outcomes. Here we performed a systematic multi-omic assessment of 143 tumors and matched tumor-adjacent, histologically-normal lung tissue with long-term patient follow-up. Through histologic, mutational, and transcriptomic profiling of tumor and adjacent-normal tissue, we identified an inflammatory gene signature in tumor-adjacent tissue as the strongest clinical predictor of disease progression. Single-cell transcriptomic analysis demonstrated the progression-associated inflammatory signature was expressed in both immune and non-immune cells, and cell …