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Full-Text Articles in Pulmonology

Advances In Idiopathic Pulmonary Fibrosis Diagnosis And Treatment, Hongli Liu, Jiaxi Shen, Chao He Mar 2025

Advances In Idiopathic Pulmonary Fibrosis Diagnosis And Treatment, Hongli Liu, Jiaxi Shen, Chao He

Faculty, Staff and Students Publications

Significant advances have been made in diagnosing and treating idiopathic pulmonary fibrosis (IPF) in the last decade. The incidence and prevalence of IPF are increasing, and morbidity and mortality remain high despite the two Food and Drug Administration (FDA)-approved medications, pirfenidone and nintedanib. Hence, there is an urgent need to develop new diagnostic tools and effective therapeutics to improve early, accurate diagnosis of IPF and halt or reverse the progression of fibrosis with a better safety profile. New diagnostic tools such as transbronchial cryobiopsy and genomic classifier require less tissue and generally have good safety profiles, and they have been …


Oxidative Stress Promotes Lipid-Laden Macrophage Formation Via Cyp1b1, Yin Zhu, Saugata Dutta, Yohan Han, Dooyoung Choi, Francesca Polverino, Caroline A Owen, Payaningal R Somanath, Xiaoyun Wang, Duo Zhang Feb 2025

Oxidative Stress Promotes Lipid-Laden Macrophage Formation Via Cyp1b1, Yin Zhu, Saugata Dutta, Yohan Han, Dooyoung Choi, Francesca Polverino, Caroline A Owen, Payaningal R Somanath, Xiaoyun Wang, Duo Zhang

Faculty, Staff and Students Publications

Emerging evidence suggests that lipid-laden macrophages (LLM) participate in lung damage in various clinical conditions. However, the mechanisms involved in LLM formation are not fully understood. In this study, we aimed to investigate the link between reactive oxygen species (ROS) and LLM formation. We found that ROS triggered by cigarette smoke extract (CSE) or H2O2 significantly promoted LLM formation. Given the key role of ROS in LLM formation, we further demonstrated that LLM formation is induced by various ROS-producing stimuli, including bacteria, oxidized low-density lipoprotein (OxLDL), hyperoxia, and E-cigarette vapor extract (EVE). Meanwhile, cytochrome P450 family-1 subfamily B member 1 …


Clinical Characteristics Of Patients With Copd And Comorbid Depression And Anxiety: Data From A National Multicenter Cohort Study, Jing Gennie Wang, Sonali Bose, Janet T Holbrook, Lin Nan, Michelle N Eakin, Abebaw M Yohannes, Robert A Wise, Nicola A Hanania Jan 2025

Clinical Characteristics Of Patients With Copd And Comorbid Depression And Anxiety: Data From A National Multicenter Cohort Study, Jing Gennie Wang, Sonali Bose, Janet T Holbrook, Lin Nan, Michelle N Eakin, Abebaw M Yohannes, Robert A Wise, Nicola A Hanania

Faculty, Staff and Students Publications

Background: Most studies on mental health among individuals with chronic obstructive pulmonary disease (COPD) utilize screening questionnaires, which detect psychiatric symptoms, but cannot be used to diagnose depression/anxiety disorders. We utilized the Mini-International Neuropsychiatric Interview (MINI) to identify depression/anxiety disorders meeting the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition diagnostic criteria and described associated disease burden in people with COPD.

Methods: This is a cross-sectional, secondary analysis of a multicenter study designed to evaluate anxiety questionnaires in COPD patients. Research coordinators administered both the MINI and screening questionnaires to determine participants who met diagnostic criteria for depression/anxiety …


Peripheral Extracellular Vesicles For Diagnosis And Prognosis Of Resectable Lung Cancer: The Lucex Study Protocol, Jorge Rodríguez-Sanz, Nadia Muñoz-González, José Pablo Cubero, Pablo Ordoñez, Victoria Gil, Raquel Langarita, Myriam Ruiz, Marta Forner, Marta Marín-Oto, Elisabet Vera, Pedro Baptista, Francesca Polverino, Juan Antonio Domingo, Javier García-Tirado, José María Marin, David Sanz-Rubio Jan 2025

Peripheral Extracellular Vesicles For Diagnosis And Prognosis Of Resectable Lung Cancer: The Lucex Study Protocol, Jorge Rodríguez-Sanz, Nadia Muñoz-González, José Pablo Cubero, Pablo Ordoñez, Victoria Gil, Raquel Langarita, Myriam Ruiz, Marta Forner, Marta Marín-Oto, Elisabet Vera, Pedro Baptista, Francesca Polverino, Juan Antonio Domingo, Javier García-Tirado, José María Marin, David Sanz-Rubio

Faculty, Staff and Students Publications

Background/Objectives: Lung cancer is the primary cause of cancer-related deaths. Most patients are typically diagnosed at advanced stages. Low-dose computed tomography (LDCT) has been proven to reduce lung cancer mortality, but screening programs using LDCT are associated with a high number of false positives and unnecessary thoracotomies. It is therefore imperative that a certain diagnosis is refined, especially in cases of solitary pulmonary nodules that are difficult to technically access for an accurate preoperative diagnosis. Extracellular vesicles (EVs) involved in intercellular communication may be an innovative biomarker for diagnosis and therapeutic strategies in lung cancer, regarding their ability to carry …


Advancing Narcolepsy Advocacy: Bridging Patient Narratives And Systemic Change, Ahmed Salem Bahammam, Lindsay Jesteadt, Hamza Dhafar, Amir Sharafkhaneh Jan 2025

Advancing Narcolepsy Advocacy: Bridging Patient Narratives And Systemic Change, Ahmed Salem Bahammam, Lindsay Jesteadt, Hamza Dhafar, Amir Sharafkhaneh

Faculty, Staff and Students Publications

We introduce the Stigma-to-Structure Advocacy Framework, a novel, evidence-based model designed to transform narcolepsy advocacy by systematically bridging patient narratives with structural change. Narcolepsy remains a profoundly underdiagnosed and misunderstood neurological disorder, with persistent diagnostic delays and pervasive cultural stigma undermining patient well-being and access to care. Despite recent progress in awareness and support, advocacy efforts remain fragmented and insufficiently integrated with health policy, particularly in low- and middle-income countries. This perspective advances a strategic evolution of narcolepsy advocacy through the Stigma-to-Structure Advocacy Framework, which is anchored in three pillars: narrative-driven awareness, clinical system integration, and policy activation. Drawing on …


B-Cell Immune Repertoire Sequencing In Tobacco Cigarette Smoking, Vaping, And Chronic Obstructive Pulmonary Disease In The Copdgene Cohort, Matthew Moll, Zhonghui Xu, Adel Boueiz, Min Hyung Ryu, Edwin K Silverman, Michael H Cho, Craig P Hersh, Maor Sauler, Francesca Polverino, Gregory L Kinney, Jeffrey L Curtis, Laura E Crotty-Alexander, Christopher Vollmers, Peter J Castaldi Jan 2025

B-Cell Immune Repertoire Sequencing In Tobacco Cigarette Smoking, Vaping, And Chronic Obstructive Pulmonary Disease In The Copdgene Cohort, Matthew Moll, Zhonghui Xu, Adel Boueiz, Min Hyung Ryu, Edwin K Silverman, Michael H Cho, Craig P Hersh, Maor Sauler, Francesca Polverino, Gregory L Kinney, Jeffrey L Curtis, Laura E Crotty-Alexander, Christopher Vollmers, Peter J Castaldi

Faculty, Staff and Students Publications

Rationale: Cigarette smoking (CS) impairs B-cell function and antibody production, increasing infection risk. The impact of e-cigarette use ('vaping') and combined CS and vaping ('dual-use') on B-cell activity is unclear.

Objective: To examine B-cell receptor sequencing (BCR-seq) profiles associated with CS, vaping, and dual-use.

Methods: BCR-seq was performed on blood RNA samples from 234 participants in the COPDGene study. We assessed multivariable associations of B-cell function measures (immunoglobulin heavy chain (IGH) subclass expression and usage, class-switching, V allele usage, and clonal expansion) with CS, vaping, and dual-use. We adjusted for multiple comparisons using the Benjamini-Hochberg method, identifying significant associations at …


Skewed Adaptive Immune Responses Are Involved In Alpha-1 Antitrypsin Deficiency Emphysema, Joselyn Rojas-Quintero, Scott A Ochsner, Hyun-Sung Lee, Christine Cong, Alan Waich Cohen, Adrianne S Colborg, Konstantin Tsoyi, Maria C Basil, Edward Cantu, Ivan O Rosas, Neil J Mckenna, Raúl San-José Estépar, Igor Barjaktarevic, Andrew A Wilson, Francesca Polverino Jan 2025

Skewed Adaptive Immune Responses Are Involved In Alpha-1 Antitrypsin Deficiency Emphysema, Joselyn Rojas-Quintero, Scott A Ochsner, Hyun-Sung Lee, Christine Cong, Alan Waich Cohen, Adrianne S Colborg, Konstantin Tsoyi, Maria C Basil, Edward Cantu, Ivan O Rosas, Neil J Mckenna, Raúl San-José Estépar, Igor Barjaktarevic, Andrew A Wilson, Francesca Polverino

Faculty, Staff and Students Publications

No abstract provided.


Long-Term Anti-Sars-Cov-2 Antibody Trajectories After Neutralizing Monoclonal Antibody Treatment, Elizabeth S Munroe, Greg A Grandits, Robert C Hyzy, Hallie C Prescott, Thomas W Barrett, Robin L Dewar, Nicole Engen, Anna L Goodman, Timothy J Hatlen, Helene Highbarger, Thomas L Holland, Gareth Hughes, Tomas O Jensen, Muhammad A Khan, Ioannis Kalomenidis, Nayon Kang, Sylvain Laverdure, Prasad Manian, Vidya Menon, Ravi Patel, Srikanth Ramachandruni, Tauseef Rehman, Kathryn Shaw-Saliba, Birgit Thorup Røge, David M Vock, Amy C Weintrob, Barnaby E Young, Anne P Frosch, Strive Network And Therapeutics For Inpatients With Covid-19 (Tico) Study Groups Jan 2025

Long-Term Anti-Sars-Cov-2 Antibody Trajectories After Neutralizing Monoclonal Antibody Treatment, Elizabeth S Munroe, Greg A Grandits, Robert C Hyzy, Hallie C Prescott, Thomas W Barrett, Robin L Dewar, Nicole Engen, Anna L Goodman, Timothy J Hatlen, Helene Highbarger, Thomas L Holland, Gareth Hughes, Tomas O Jensen, Muhammad A Khan, Ioannis Kalomenidis, Nayon Kang, Sylvain Laverdure, Prasad Manian, Vidya Menon, Ravi Patel, Srikanth Ramachandruni, Tauseef Rehman, Kathryn Shaw-Saliba, Birgit Thorup Røge, David M Vock, Amy C Weintrob, Barnaby E Young, Anne P Frosch, Strive Network And Therapeutics For Inpatients With Covid-19 (Tico) Study Groups

Faculty, Staff and Students Publications

Background: Neutralizing monoclonal antibodies (nMAbs) have been used to treat COVID-19 and are increasingly being used to treat other infections. However, there is concern that by neutralizing the SARS-CoV-2 virus, nMAbs may decrease the availability of antigens to the immune system, potentially impairing the endogenous polyclonal immune response and decreasing long-term immune protection.

Methods: We compared 28 and 90-day anti-SARS-CoV-2 spike protein neutralization activity and anti-SARS-CoV-2 nucleocapsid response for patients hospitalized with COVID-19 infection randomized to receive nMAbs or placebo in the large platform ACTIV-3/TICO trials. We pooled results from four trials of anti-spike nMAbs. For most tested agents, measurements …


Mice With Lymphatic Dysfunction Develop Pathogenic Lung Tertiary Lymphoid Organs That Model An Autoimmune Emphysema Phenotype Of Copd, Barbara Summers, Kihwan Kim, Anjali Trivedi, Tyler M Lu, Sean Houghton, Jade Palmer-Johnson, Joselyn Rojas-Quintero, Juan Cala-Garcia, Tania Pannellini, Francesca Polverino, Raphaël Lis, Hasina Outtz Reed Jan 2025

Mice With Lymphatic Dysfunction Develop Pathogenic Lung Tertiary Lymphoid Organs That Model An Autoimmune Emphysema Phenotype Of Copd, Barbara Summers, Kihwan Kim, Anjali Trivedi, Tyler M Lu, Sean Houghton, Jade Palmer-Johnson, Joselyn Rojas-Quintero, Juan Cala-Garcia, Tania Pannellini, Francesca Polverino, Raphaël Lis, Hasina Outtz Reed

Faculty, Staff and Students Publications

We have previously shown that mice with a loss of C-type lectin-like type II (CLEC2), which have lymphatic dysfunction due to the role of CLEC2 in platelets for maintaining separation between the venous and lymphatic system, develop lung tertiary lymphoid organ (TLO) formation and lung injury that resembles an emphysema phenotype of chronic obstructive pulmonary disease (COPD). We now sought to investigate whether and how TLOs in these mice may play a pathogenic role in lung injury that is relevant to human disease. We found that inhibiting TLO formation using an anti-CD20 antibody in CLEC2-deficient mice partially blocked the development …


Parental Report Of Indoor Air Pollution Is Associated With Respiratory Morbidities In Bronchopulmonary Dysplasia, Jessica L Rice, Joseph M Collaco, Michael C Tracy, Catherine A Sheils, Lawrence M Rhein, Antonia P Popova, Paul E Moore, Audrey N Miller, Winston M Manimtim, Khanh Lai, Jacob A Kaslow, Lystra P Hayden, Julie L Fierro, Manvi Bansal, Eric D Austin, Brianna Aoyama, Stamatia Alexiou, Gangaram Akangire, Amit Agarwal, Natalie Villafranco, Roopa Siddaiah, Joanne M Lagatta, Mehtap Haktanir Abul, A Ioana Cristea, Christopher D Baker, Steven H Abman, Sharon A Mcgrath-Morrow Dec 2024

Parental Report Of Indoor Air Pollution Is Associated With Respiratory Morbidities In Bronchopulmonary Dysplasia, Jessica L Rice, Joseph M Collaco, Michael C Tracy, Catherine A Sheils, Lawrence M Rhein, Antonia P Popova, Paul E Moore, Audrey N Miller, Winston M Manimtim, Khanh Lai, Jacob A Kaslow, Lystra P Hayden, Julie L Fierro, Manvi Bansal, Eric D Austin, Brianna Aoyama, Stamatia Alexiou, Gangaram Akangire, Amit Agarwal, Natalie Villafranco, Roopa Siddaiah, Joanne M Lagatta, Mehtap Haktanir Abul, A Ioana Cristea, Christopher D Baker, Steven H Abman, Sharon A Mcgrath-Morrow

Faculty, Staff and Students Publications

Objective: To determine the association between indoor air pollution and respiratory morbidities in children with bronchopulmonary dysplasia (BPD) recruited from the multicenter BPD Collaborative.

Study design: A cross-sectional study was performed among participants < 3 years old in the BPD Collaborative Outpatient Registry. Indoor air pollution was defined as any reported exposure to tobacco or marijuana smoke, electronic cigarette emissions, gas stoves, and/or wood stoves. Clinical data included acute care use and chronic respiratory symptoms in the past 4 weeks.

Results: A total of 1011 participants born at a mean gestational age of 26.4 ± 2.2 weeks were included. Most (66.6%) had severe BPD. More than 40% of participants were exposed to ≥1 source of indoor air pollution. The odds of reporting an emergency department visit (OR, 1.7; 95% CI, 1.18-2.45), antibiotic use (OR, 1.9; 95% CI, 1.12-3.21), or a systemic steroid course (OR, 2.18; 95% CI, …


Exploring Fibroblast Interactions On Nanocrystalline Surfaces In Physiological Environments Through A Phenomenological Lens, R D K Misra, Aladin M Boriek Dec 2024

Exploring Fibroblast Interactions On Nanocrystalline Surfaces In Physiological Environments Through A Phenomenological Lens, R D K Misra, Aladin M Boriek

Faculty, Staff and Students Publications

The cytological behaviour and functional dynamics (adhesion, spreading, synthesis of proteins) of fibroblasts when interacting with biomedical surfaces are intricately influenced by the inherent nature of surface (nanocrystalline or microcrystalline), where the nanocrystalline (NC) surface is preferred in relation to the microcrystalline (MC) surface. This preference is a direct consequence of the distinct differences in physical and chemical characteristics between NC and MC surfaces, which include crystal boundary bio-physical attributes, electron work function, surface energy, and charge carrier density. The observed variances in cytological behaviour at the interfaces of NC and MC bio-surfaces can be attributed to these fundamental differences, …


Impact Of Vitamin D On Hyperoxic Acute Lung Injury In Neonatal Mice, Thu T Tran, Jonathan Davies, Richard A Johnston, Harry Karmouty-Quintana, Huiling Li, Caroline E Crocker, Amir M Khan, Joseph L Alcorn Nov 2024

Impact Of Vitamin D On Hyperoxic Acute Lung Injury In Neonatal Mice, Thu T Tran, Jonathan Davies, Richard A Johnston, Harry Karmouty-Quintana, Huiling Li, Caroline E Crocker, Amir M Khan, Joseph L Alcorn

Faculty, Staff and Students Publications

BACKGROUND: Prolonged exposure to hyperoxia can lead to hyperoxic acute lung injury (HALI) in preterm neonates. Vitamin D (VitD) stimulates lung maturation and acts as an anti-inflammatory agent. Our objective was to determine if VitD provides a dose-dependent protective effect against HALI by reducing inflammatory cytokine expression and improving alveolarization and lung function in neonatal mice.

METHODS: C57BL/6 mouse neonates were randomized and placed in room air or hyperoxic (85% O

RESULTS: Neonatal mice treated with VitD in hyperoxic conditions had improved weight gain, reduced pulmonary edema and increased alveolar surface area compared to untreated pups in hyperoxia. No significant …


Lung Tissue Multilayer Network Analysis Uncovers The Molecular Heterogeneity Of Chronic Obstructive Pulmonary Disease, Nuria Olvera, Jon Sánchez-Valle, Iker Núñez-Carpintero, Joselyn Rojas-Quintero, Guillaume Noell, Sandra Casas-Recasens, Alen Faiz, Philip Hansbro, Angela Guirao, Rosalba Lepore, Davide Cirillo, Alvar Agustí, Francesca Polverino, Alfonso Valencia, Rosa Faner Nov 2024

Lung Tissue Multilayer Network Analysis Uncovers The Molecular Heterogeneity Of Chronic Obstructive Pulmonary Disease, Nuria Olvera, Jon Sánchez-Valle, Iker Núñez-Carpintero, Joselyn Rojas-Quintero, Guillaume Noell, Sandra Casas-Recasens, Alen Faiz, Philip Hansbro, Angela Guirao, Rosalba Lepore, Davide Cirillo, Alvar Agustí, Francesca Polverino, Alfonso Valencia, Rosa Faner

Faculty, Staff and Students Publications

Rationale: Chronic obstructive pulmonary disease (COPD) is a heterogeneous condition. Objectives: We hypothesized that the unbiased integration of different COPD lung omics using a novel multilayer approach might unravel mechanisms associated with clinical characteristics.

Methods: We profiled mRNA, microRNA and methylome in lung tissue samples from 135 former smokers with COPD. For each omic (layer), we built a patient network on the basis of molecular similarity. The three networks were used to build a multilayer network, and optimization of multiplex modularity was used to identify patient communities across the three distinct layers. Uncovered communities were related to clinical features.

Measurements …


The Complex Relationship Between Tuberculosis And Hyperglycemia, Michelle Byers, Elizabeth Guy Nov 2024

The Complex Relationship Between Tuberculosis And Hyperglycemia, Michelle Byers, Elizabeth Guy

Faculty, Staff and Students Publications

Hyperglycemia and tuberculosis are dual global pandemics. Each has a propulsive and amplifying effect on the other, and, because of this, we must consider hyperglycemia and tuberculosis together. Hyperglycemia is immunosuppressive and increases the risk of tuberculosis by threefold. It also leads to a more advanced presentation of pulmonary tuberculosis, thus increasing the likelihood of being smear positive and having cavitating lesions, and it impacts the duration and outcomes of treatment, with an increased one year mortality seen in patients with tuberculosis and diabetes. Additionally, any degree of hyperglycemia can have an impact on susceptibility to tuberculosis, and this effect …


Transcutaneous Electrical Nerve Stimulation For Fibromyalgia-Like Syndrome In Patients With Long-Covid: A Pilot Randomized Clinical Trial, Alejandro Zulbaran-Rojas, Rasha O Bara, Myeounggon Lee, Miguel Bargas-Ochoa, Tina Phan, Manuel Pacheco, Areli Flores Camargo, Syed Murtaza Kazmi, Mohammad Dehghan Rouzi, Dipaben Modi, Fidaa Shaib, Bijan Najafi Nov 2024

Transcutaneous Electrical Nerve Stimulation For Fibromyalgia-Like Syndrome In Patients With Long-Covid: A Pilot Randomized Clinical Trial, Alejandro Zulbaran-Rojas, Rasha O Bara, Myeounggon Lee, Miguel Bargas-Ochoa, Tina Phan, Manuel Pacheco, Areli Flores Camargo, Syed Murtaza Kazmi, Mohammad Dehghan Rouzi, Dipaben Modi, Fidaa Shaib, Bijan Najafi

Faculty, Staff and Students Publications

This study investigated the effect of Transcutaneous Electrical Nerve Stimulation (TENS) for fibromyalgia-like symptoms including chronic widespread musculoskeletal pain, fatigue, and/or gait impairment in twenty-five individuals with long-COVID. Participants were randomized to a high dose (intervention group, IG) or low dose (placebo group, PG) TENS device. Both groups received daily 3-5 h of TENS therapy for 4-weeks. The Brief Pain Inventory assessed functional interference from pain (BPI-I), and pain severity (BPI-S). The global fatigue index (GFI) assessed functional interference from fatigue. Wearable technology measured gait parameters during three 30-feet consecutive walking tasks. At 4-weeks, the IG exhibited a greater decrease …


Pulmonary Artery Stenting In Cancer Patients: A Single-Center Experience, Jay Gupta, Ronak Patel, Neal Patel, David Wynne, Mohammad Ghasemi-Rad Nov 2024

Pulmonary Artery Stenting In Cancer Patients: A Single-Center Experience, Jay Gupta, Ronak Patel, Neal Patel, David Wynne, Mohammad Ghasemi-Rad

Faculty, Staff and Students Publications

Endovascular stenting of the pulmonary artery treats arterial stenosis from pulmonary hypertension, congenital heart defects, or post-transplant stricture. Patients with malignant extrinsic pulmonary arterial compression, secondary to large mediastinal or pulmonary masses, often present with dyspnea, hypoxemia, and right ventricular failure. Conventional therapies like surgery, chemotherapy, and radiation are often slow and fail to promptly resolve acute symptoms. Balloon angioplasty and stenting have been explored as a rapid treatment to alleviate symptoms of external pulmonary artery compression. Despite its potential, the adoption of this procedure is limited due to risks like stent misplacement, migration, cardiac arrhythmias, and arterial rupture. This …


Access To Treatment For Chronic Obstructive Pulmonary Disease In The Americas: A Call For Action A Joint Perspective From The Brazilian Thoracic Society, Canadian Thoracic Society, Latin American Thoracic Society, And The American Thoracic Society, Francesca Polverino, Mohit Bhutani, Gustavo Zabert, Frederico Leon Arrabal Fernandes, Karen Czischke, Luiz Fernando Pereira Ferreira, Lian Szabo, Juan P Wisnivesky, Margareth Pretti Dalcolmo, Juan C Celedón Nov 2024

Access To Treatment For Chronic Obstructive Pulmonary Disease In The Americas: A Call For Action A Joint Perspective From The Brazilian Thoracic Society, Canadian Thoracic Society, Latin American Thoracic Society, And The American Thoracic Society, Francesca Polverino, Mohit Bhutani, Gustavo Zabert, Frederico Leon Arrabal Fernandes, Karen Czischke, Luiz Fernando Pereira Ferreira, Lian Szabo, Juan P Wisnivesky, Margareth Pretti Dalcolmo, Juan C Celedón

Faculty, Staff and Students Publications

Chronic obstructive pulmonary disease (COPD) is a major public health problem in the Americas (a region of the world comprising North, Central, and South America), although there is substantial variation in disease prevalence, morbidity, and mortality between and within nations. Across the Americas, COPD disproportionately affects vulnerable populations, including minoritized populations and impoverished persons, who are more likely to be exposed to risk factors such as tobacco use, air pollution, infections such as tuberculosis, and biomass smoke, but less likely to have adequate healthcare access. Management of COPD can be challenging across the Americas, with some barriers being specific to …


Personalized Copd Care: The Future Of Precision-Based Therapies, Leslie K Appleton, Nicola A Hanania, Muhammad Adrish Oct 2024

Personalized Copd Care: The Future Of Precision-Based Therapies, Leslie K Appleton, Nicola A Hanania, Muhammad Adrish

Faculty, Staff and Students Publications

Chronic obstructive pulmonary disease (COPD) is a progressive respiratory illness characterized by long-standing respiratory symptoms and airflow limitation. It is a major contributor to respiratory disease-related deaths and currently ranked as the sixth leading cause of mortality in the United States. Approved pharmacological therapies for the stable disease primarily consist of inhaled short and long-acting bronchodilators, inhaled corticosteroids, azithromycin, and roflumilast. In recent years, significant progress has been made in the management of COPD through the identification of different COPD phenotypes and endotypes, which allows for a more personalized treatment approach. While earlier studies investigating targeted therapies were less promising, …


Sdeper: A Hybrid Machine Learning And Regression Method For Cell-Type Deconvolution Of Spatial Barcoding-Based Transcriptomic Data, Yunqing Liu, Ningshan Li, Ji Qi, Gang Xu, Jiayi Zhao, Nating Wang, Xiayuan Huang, Wenhao Jiang, Huanhuan Wei, Aurélien Justet, Taylor S Adams, Robert Homer, Amei Amei, Ivan O Rosas, Naftali Kaminski, Zuoheng Wang, Xiting Yan Oct 2024

Sdeper: A Hybrid Machine Learning And Regression Method For Cell-Type Deconvolution Of Spatial Barcoding-Based Transcriptomic Data, Yunqing Liu, Ningshan Li, Ji Qi, Gang Xu, Jiayi Zhao, Nating Wang, Xiayuan Huang, Wenhao Jiang, Huanhuan Wei, Aurélien Justet, Taylor S Adams, Robert Homer, Amei Amei, Ivan O Rosas, Naftali Kaminski, Zuoheng Wang, Xiting Yan

Faculty, Staff and Students Publications

Spatial barcoding-based transcriptomic (ST) data require deconvolution for cellular-level downstream analysis. Here we present SDePER, a hybrid machine learning and regression method to deconvolve ST data using reference single-cell RNA sequencing (scRNA-seq) data. SDePER tackles platform effects between ST and scRNA-seq data, ensuring a linear relationship between them while addressing sparsity and spatial correlations in cell types across capture spots. SDePER estimates cell-type proportions, enabling enhanced resolution tissue mapping by imputing cell-type compositions and gene expressions at unmeasured locations. Applications to simulated data and four real datasets showed SDePER's superior accuracy and robustness over existing methods.


Trβ Activation Confers At2-To-At1 Cell Differentiation And Anti-Fibrosis During Lung Repair Via Klf2 And Cebpa, Xin Pan, Lan Wang, Juntang Yang, Yingge Li, Min Xu, Chenxi Liang, Lulu Liu, Zhongzheng Li, Cong Xia, Jiaojiao Pang, Mengyuan Wang, Meng Li, Saiya Guo, Peishuo Yan, Chen Ding, Ivan O Rosas, Guoying Yu Oct 2024

Trβ Activation Confers At2-To-At1 Cell Differentiation And Anti-Fibrosis During Lung Repair Via Klf2 And Cebpa, Xin Pan, Lan Wang, Juntang Yang, Yingge Li, Min Xu, Chenxi Liang, Lulu Liu, Zhongzheng Li, Cong Xia, Jiaojiao Pang, Mengyuan Wang, Meng Li, Saiya Guo, Peishuo Yan, Chen Ding, Ivan O Rosas, Guoying Yu

Faculty, Staff and Students Publications

Aberrant repair underlies the pathogenesis of pulmonary fibrosis while effective strategies to convert fibrosis to normal regeneration are scarce. Here, we found that thyroid hormone is decreased in multiple models of lung injury but is essential for lung regeneration. Moreover, thyroid hormone receptor α (TRα) promotes cell proliferation, while TRβ fuels cell maturation in lung regeneration. Using a specific TRβ agonist, sobetirome, we demonstrate that the anti-fibrotic effects of thyroid hormone mainly rely on TRβ in mice. Cellularly, TRβ activation enhances alveolar type-2 (AT2) cell differentiation into AT1 cell and constrains AT2 cell hyperplasia. Molecularly, TRβ activation directly regulates the …


Context-Aware Single-Cell Multiomics Approach Identifies Cell-Type-Specific Lung Cancer Susceptibility Genes, Erping Long, Jinhu Yin, Ju Hye Shin, Yuyan Li, Bolun Li, Alexander Kane, Harsh Patel, Xinti Sun, Cong Wang, Thong Luong, Jun Xia, Younghun Han, Jinyoung Byun, Tongwu Zhang, Wei Zhao, Maria Teresa Landi, Nathaniel Rothman, Qing Lan, Yoon Soo Chang, Fulong Yu, Christopher I Amos, Jianxin Shi, Jin Gu Lee, Eun Young Kim, Jiyeon Choi Sep 2024

Context-Aware Single-Cell Multiomics Approach Identifies Cell-Type-Specific Lung Cancer Susceptibility Genes, Erping Long, Jinhu Yin, Ju Hye Shin, Yuyan Li, Bolun Li, Alexander Kane, Harsh Patel, Xinti Sun, Cong Wang, Thong Luong, Jun Xia, Younghun Han, Jinyoung Byun, Tongwu Zhang, Wei Zhao, Maria Teresa Landi, Nathaniel Rothman, Qing Lan, Yoon Soo Chang, Fulong Yu, Christopher I Amos, Jianxin Shi, Jin Gu Lee, Eun Young Kim, Jiyeon Choi

Faculty, Staff and Students Publications

Genome-wide association studies (GWAS) identified over fifty loci associated with lung cancer risk. However, underlying mechanisms and target genes are largely unknown, as most risk-associated variants might regulate gene expression in a context-specific manner. Here, we generate a barcode-shared transcriptome and chromatin accessibility map of 117,911 human lung cells from age/sex-matched ever- and never-smokers to profile context-specific gene regulation. Identified candidate cis-regulatory elements (cCREs) are largely cell type-specific, with 37% detected in one cell type. Colocalization of lung cancer candidate causal variants (CCVs) with these cCREs combined with transcription factor footprinting prioritize the variants for 68% of the GWAS loci. …


Hyperglycemia And Venous Thromboembolism, Neha Panchagnula, William Philip Brasher Sep 2024

Hyperglycemia And Venous Thromboembolism, Neha Panchagnula, William Philip Brasher

Faculty, Staff and Students Publications

Patients with diabetes mellitus (DM) have chronically increased blood glucose and multiple physiologic alterations that place them at elevated risk for vascular disease. Traditionally, this vascular risk has mainly referred to chronic atherosclerosis and embolic arterial disease. Retrospective studies have suggested an increased risk of a pulmonary embolism (PE) and deep vein thrombosis (DVT), collectively termed venous thromboembolism (VTE), in patients with DM, but this association has been difficult to demonstrate with comorbidities such as obesity in meta-analysis. Clinical studies have demonstrated worse outcomes for patients with DM who suffer from VTE. In vitro studies show multiple physiologic abnormalities with …


Traumatic Brain Injury And Variants Of Shock Index, Sai Doppalapudi, Muhammad Adrish Sep 2024

Traumatic Brain Injury And Variants Of Shock Index, Sai Doppalapudi, Muhammad Adrish

Faculty, Staff and Students Publications

Traumatic Brain Injury is a major cause of death and long-term disability. The early identification of patients at high risk of mortality is important for both management and prognosis. Although many modified scoring systems have been developed for improving the prediction accuracy in patients with trauma, few studies have focused on prediction accuracy and application in patients with traumatic brain injury. The shock index (SI) which was first introduced in the 1960s has shown to strongly correlate degree of circulatory shock with increasing SI. In this editorial we comment on a publication by Carteri et al wherein they perform a …


Reimagining Critical Care: Trends And Shifts In 21st Century Medicine, Sai Doppalapudi, Bilal Khan, Muhammad Adrish Sep 2024

Reimagining Critical Care: Trends And Shifts In 21st Century Medicine, Sai Doppalapudi, Bilal Khan, Muhammad Adrish

Faculty, Staff and Students Publications

Critical care medicine has undergone significant evaluation in the 21st century, primarily driven by advancements in technology, changes in healthcare delivery, and a deeper understanding of disease processes. Advancements in technology have revolutionized patient monitoring, diagnosis, and treatment in the critical care setting. From minimally invasive procedures to advances imaging techniques, clinicians now have access to a wide array of tools to assess and manage critically ill patients more effectively. In this editorial we comment on the review article published by Padte S et al wherein they concisely describe the latest developments in critical care medicine.


An Interdisciplinary Consensus Approach To Pulmonary Hypertension In Developmental Lung Disease, Nidhy P Varghese, Eric D Austin, Csaba Galambos, Mary P Mullen, Delphine Yung, R Paul Guillerman, Sara O Vargas, Catherine M Avitabile, Corey A Chartan, Nahir Cortes-Santiago, Michaela Ibach, Emma O Jackson, Jill Ann Jarrell, Roberta L Keller, Usha S Krishnan, Kalyani R Patel, Jennifer Pogoriler, Elise C Whalen, Kathryn A Wikenheiser-Brokamp, Natalie M Villafranco, Rachel K Hopper, J Usha Raj, Steven H Abman Sep 2024

An Interdisciplinary Consensus Approach To Pulmonary Hypertension In Developmental Lung Disease, Nidhy P Varghese, Eric D Austin, Csaba Galambos, Mary P Mullen, Delphine Yung, R Paul Guillerman, Sara O Vargas, Catherine M Avitabile, Corey A Chartan, Nahir Cortes-Santiago, Michaela Ibach, Emma O Jackson, Jill Ann Jarrell, Roberta L Keller, Usha S Krishnan, Kalyani R Patel, Jennifer Pogoriler, Elise C Whalen, Kathryn A Wikenheiser-Brokamp, Natalie M Villafranco, Rachel K Hopper, J Usha Raj, Steven H Abman

Faculty, Staff and Students Publications

It is increasingly recognised that diverse genetic respiratory disorders present as severe pulmonary hypertension (PH) in the neonate and young infant, but many controversies and uncertainties persist regarding optimal strategies for diagnosis and management to maximise long-term outcomes. To better define the nature of PH in the setting of developmental lung disease (DEVLD), in addition to the common diagnoses of bronchopulmonary dysplasia and congenital diaphragmatic hernia, we established a multidisciplinary group of expert clinicians from stakeholder paediatric specialties to highlight current challenges and recommendations for clinical approaches, as well as counselling and support of families. In this review, we characterise …


A Novel Deep Learning Model Based On Transformer And Cross Modality Attention For Classification Of Sleep Stages, Sahar Hassanzadeh Mostafaei, Jafar Tanha, Amir Sharafkhaneh Sep 2024

A Novel Deep Learning Model Based On Transformer And Cross Modality Attention For Classification Of Sleep Stages, Sahar Hassanzadeh Mostafaei, Jafar Tanha, Amir Sharafkhaneh

Faculty, Staff and Students Publications

The classification of sleep stages is crucial for gaining insights into an individual's sleep patterns and identifying potential health issues. Employing several important physiological channels in different views, each providing a distinct perspective on sleep patterns, can have a great impact on the efficiency of the classification models. In the context of neural networks and deep learning models, transformers are very effective, especially when dealing with time series data, and have shown remarkable compatibility with sequential data analysis as physiological channels. On the other hand, cross-modality attention by integrating information from multiple views of the data enables to capture relationships …


Deployment-Related Cigarette Smoking Behaviors And Pulmonary Function Among Us Veterans, Jennifer R Maccarone, Olivia R Sterns, Andrew Timmons, Anna M Korpak, Nicholas L Smith, Karen S Nakayama, Coleen P Baird, Paul Ciminera, Farrah Kheradmand, Vincent S Fan, Jaime E Hart, Petros Koutrakis, Michael Jerrett, Ware G Kuschner, Octavian C Ioachimescu, Philippe R Montgrain, Susan P Proctor, Carrie A Redlich, Christine H Wendt, Paul D Blanc, Eric Garshick, Emily S Wan Aug 2024

Deployment-Related Cigarette Smoking Behaviors And Pulmonary Function Among Us Veterans, Jennifer R Maccarone, Olivia R Sterns, Andrew Timmons, Anna M Korpak, Nicholas L Smith, Karen S Nakayama, Coleen P Baird, Paul Ciminera, Farrah Kheradmand, Vincent S Fan, Jaime E Hart, Petros Koutrakis, Michael Jerrett, Ware G Kuschner, Octavian C Ioachimescu, Philippe R Montgrain, Susan P Proctor, Carrie A Redlich, Christine H Wendt, Paul D Blanc, Eric Garshick, Emily S Wan

Faculty, Staff and Students Publications

Introduction: The effects of smoking on lung function among post-9/11 Veterans deployed to environments with high levels of ambient particulate matter are incompletely understood.

Materials and methods: We analyzed interim data (04/2018-03/2020) from the Veterans Affairs (VA) Cooperative Studies Program #595, "Service and Health Among Deployed Veterans". Veterans with ≥1 land-based deployments enrolled at 1 of 6 regional Veterans Affairs sites completed questionnaires and spirometry. Multivariable linear regression models assessed associations between cigarette smoking (cumulative, deployment-related and non-deployment-related) with pulmonary function.

Results: Among 1,836 participants (mean age 40.7 ± 9.6, 88.6% male), 44.8% (n = 822) were ever-smokers (mean age …


Asthma And Hyperglycemia: Exploring The Interconnected Pathways, Dharani K Narendra, Sandhya Khurana Aug 2024

Asthma And Hyperglycemia: Exploring The Interconnected Pathways, Dharani K Narendra, Sandhya Khurana

Faculty, Staff and Students Publications

The interplay between asthma and glucose metabolism disorders, such as hyperglycemia, has gained increasing attention due to the potential exacerbation of asthma symptoms and severity. This review explores the complex relationship between hyperglycemia and asthma, emphasizing the pathophysiological links, the impact of glucose metabolism disorders on asthma, and the effects of asthma medications on glucose levels. Hyperglycemia, often induced by asthma treatments like corticosteroids, has been associated with an increased risk of asthma exacerbations. This review delves into the pathophysiology underlying this association, highlighting the role of insulin resistance, metabolic syndrome, and obesity in both the development and management of …


Safety Of Treating Acute Pulmonary Embolism At Home: An Individual Patient Data Meta-Analysis, Dieuwke Luijten, Delphine Douillet, Kim Luijken, Cecile Tromeur, Andrea Penaloza, Olivier Hugli, Drahomir Aujesky, Stefano Barco, Joseph R Bledsoe, Kyle E Chang, Francis Couturaud, Paul L Den Exter, Carme Font, Menno V Huisman, David Jimenez, Christopher Kabrhel, Jeffrey A Kline, Stavros Konstantinides, Thijs Van Mens, Remedios Otero, W Frank Peacock, Olivier Sanchez, William B Stubblefield, Luca Valerio, David R Vinson, Philip Wells, Maarten Van Smeden, Pierre-Marie Roy, Frederikus A Klok Aug 2024

Safety Of Treating Acute Pulmonary Embolism At Home: An Individual Patient Data Meta-Analysis, Dieuwke Luijten, Delphine Douillet, Kim Luijken, Cecile Tromeur, Andrea Penaloza, Olivier Hugli, Drahomir Aujesky, Stefano Barco, Joseph R Bledsoe, Kyle E Chang, Francis Couturaud, Paul L Den Exter, Carme Font, Menno V Huisman, David Jimenez, Christopher Kabrhel, Jeffrey A Kline, Stavros Konstantinides, Thijs Van Mens, Remedios Otero, W Frank Peacock, Olivier Sanchez, William B Stubblefield, Luca Valerio, David R Vinson, Philip Wells, Maarten Van Smeden, Pierre-Marie Roy, Frederikus A Klok

Faculty, Staff and Students Publications

BACKGROUND AND AIMS: Home treatment is considered safe in acute pulmonary embolism (PE) patients selected by a validated triage tool (e.g. simplified PE severity index score or Hestia rule), but there is uncertainty regarding the applicability in underrepresented subgroups. The aim was to evaluate the safety of home treatment by performing an individual patient-level data meta-analysis.

METHODS: Ten prospective cohort studies or randomized controlled trials were identified in a systematic search, totalling 2694 PE patients treated at home (discharged within 24 h) and identified by a predefined triage tool. The 14- and 30-day incidences of all-cause mortality and adverse events …


Inhalational Drug Devices: Revisiting The Linchpin Of Asthma Management, Damini Saxena, Neveda Murugesan, Uyioghosa D Evbayiro, Marina K Ngassa, Muhammad Adrish Aug 2024

Inhalational Drug Devices: Revisiting The Linchpin Of Asthma Management, Damini Saxena, Neveda Murugesan, Uyioghosa D Evbayiro, Marina K Ngassa, Muhammad Adrish

Faculty, Staff and Students Publications

Asthma remains a prevalent condition among all age groups globally. First-line treatment requires the delivery of medications into the distal respiratory tract via inhalers. Using appropriate inhaler techniques is a significant challenge in achieving disease control. A variety of inhalers are available for treating asthma, and selecting the appropriate inhaler type for any given patient is crucial to achieving and maintaining symptomatic control. This review will discuss the anatomy and physiology behind drug delivery via inhalers, the types of inhalers currently available for use, nebulizers, and future directions in the delivery of inhaled medications for asthma.