Respiratory Tract Diseases Commons^™

Bayesian Reanalysis Of Early Remdesivir For The Treatment Of Covid-19 In Outpatients With High Risk Of Progression To Severe Disease, Mazin Abdelghany, Fang Yu, Stephen I. Rennard, Yeongjin Gwon

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: Though Bayesian methods are flexible, intuitive, and readily incorporated into clinical decision-making, with particular utility when prior information is available, they remain underutilized in the analysis of clinical trials.

METHODS: In PINETREE, a Phase 3 randomized controlled trial (RCT) of remdesivir (RDV) for the treatment of outpatients with COVID-19 at high risk of severe disease, the primary outcome of COVID-19-related hospitalization or all-cause death was reanalyzed using a range of reference and data-driven priors. Posterior probability distributions were used to calculate the probability that the estimated hazard ratio (HR) was below a range of clinically meaningful specified thresholds and …

Chronic Rhinosinusitis Is A Risk Factor For Interstitial Lung Disease In Sjogren’S Syndrome, Brian Schonewald, Christopher Xie, Andrew Engel, Ross Summer, Giorgos Loizidis

Division of Pulmonary, Allergy, and Critical Care Medicine Faculty Papers

BACKGROUND: Interstitial lung disease (ILD) is a leading cause of morbidity and mortality in Sjögren's syndrome (SS), but its risk factors remain unclear. Although SS affects both the upper and lower respiratory epithelium, it is unknown whether this occurs simultaneously or separately. In other autoimmune conditions-such as eosinophilic granulomatosis with polyangiitis and granulomatosis with polyangiitis-upper airway disease precedes lower lung involvement by months or even years. We hypothesized that chronic rhinosinusitis (CRS), as an upper airway disease, may be a risk factor for ILD in SS.

METHODS: We analyzed the TriNetX Research Network database to compare incident ILD in SS …

Periprocedural Results And Right Ventricular Outcomes Of Computer Assisted Vacuum Thrombectomy Treatment Of Acute Pulmonary Embolism: Interim Analysis Of 300 Patients From The Strike-Pe Study, John M. Moriarty, Brian J. Schiro, Suhail Y. Dohad, Houman Tamaddon, Hugh C. Davis, David M. Shavelle, George S. Chrysant, Elias A. Iliadis, David J. Dexter, Juan J. Ciampi Dopazo, Andrew Holden, Frances M. West, Brent Keeling, Andrew S. P. Sharp, Ido Weinberg

Division of Pulmonary, Allergy, and Critical Care Medicine Faculty Papers

BACKGROUND: Pulmonary embolism (PE) can be a life-threatening condition. Endovascular treatment is emerging as a promising treatment to restore hemodynamic stability and reverse right ventricular (RV) dysfunction in PE; however, more studies are needed to elucidate the effects on the right ventricle after endovascular treatment. This analysis reports the effects of computer assisted vacuum thrombectomy on RV function.

METHODS: Eligible patients for the single-arm, prospective, international, multicenter STRIKE-PE (A Prospective, Multicenter Study of the Indigo Aspiration System Seeking to Evaluate the Long-Term Safety and Outcomes of Treating Pulmonary Embolism) cohort study are adults with acute PE with symptoms for ≤14 …

Beyond Smoking: A Geospatial Investigation Of Factors Associated With Lung And Bronchus Cancer Risk In Pennsylvania, Tesla D. Dubois, Daniel Wiese, Kevin A. Henry, Shannon M. Lynch

Kimmel Cancer Center Faculty Papers

INTRODUCTION: While smoking is the leading cause of lung and bronchus cancer (LBC), additional exposures have been implicated and may explain the rise in LBC among never-smokers. To better understand the spatial distribution of LBC incidence and associated risk factors, this study aims to identify geographic areas with significantly elevated incidence rates in Pennsylvania and investigate the potential underlying risk factors.

METHODS: Using cancer registry data aggregated to the census tract level, spatial scan statistics were applied to detect areas of higher-than-expected LBC incidence across the state. Associations were then tested between census tract inclusion in a high-incidence area and …

Neovascular Pruning By Ido1 Inhibitors Can Potentiate Immunogenic Cytotoxicity Of Ischemia-Targeted Agents To Synergistically Enhance Anti-Pd-1 Responsiveness, Shih-Chun Shen, Souvik Dey, James B. Duhadaway, Erika Sutanto-Ward, Maurice T. Hampton, Serguei V. Kozlov, George C. Prendergast, Alexander J. Muller

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

BACKGROUND: Strategies for deploying indoleamine 2,3-dioxygenase 1 (IDO1)-targeted therapies for use against cancer have focused on IDO1's role in promoting peripheral immune tolerance that shields tumors from effector T cells. However, preclinical investigation of both primary and metastatic tumor development in the lungs has uncovered a previously unappreciated role for IDO1 in directing a counterregulatory response to interferon (IFN)-γ that realigns the local inflammatory environment to promote tumor neovascularization. Understanding how to therapeutically leverage the ability of IDO1 inhibitors to subvert inflammatory neovascularization within the tumor microenvironment has potential ramifications for future clinical development of these compounds.

METHODS: Pulmonary metastases …

Complement Activity And Autophagy Are Dysregulated In The Lungs Of Patients With Nonresolvable Covid-19 Requiring Lung Transplantation, Pooja Shivshankar, Stacey L Mueller-Ortiz, Aleksey Y Domozhirov, Weizhen Bi, Scott D Collum, Marie-Francoise Doursout, Manish Patel, Isabella N Lefebvre, Bindu Akkanti, Simon Yau, Howard J Huang, Rahat Hussain, Harry Karmouty-Quintana

Faculty, Staff and Student Publications

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-induced coronavirus disease 2019 (COVID-19) pandemic has challenged the current understanding of the complement cascade mechanisms of host immune responses during infection-induced nonresolvable lung disease. While the complement system is involved in opsonization and phagocytosis of the invading pathogens, uncontrolled complement activation also leads to aberrant autophagic response and tissue damage. Our recent study revealed unique pathologic and fibrotic signature genes associated with epithelial bronchiolization in the lung tissues of patients with nonresolvable COVID-19 (NR-COVID-19) requiring lung transplantation. However, there is a knowledge gap if complement components are modulated to contribute to tissue …

A Qualitative Assessment Of Changes In Occupational Exposures Among Healthcare Facility Workers, David Gimeno Ruiz De Porras, Jenil Patel, Sadie Conway, Lisa Pompeii, Laura E Mitchell, Arch Carson, Lawrence W Whitehead, Inkyu Han, Jan-Paul Zock, Paul K Henneberger, Riddhi Patel, Joy De Los Reyes, George L Delclos

Faculty, Staff and Student Publications

Adult-onset asthma, notably prevalent among healthcare professionals, especially nurses, is often attributed to occupational factors such as exposure to cleaning agents. Studies consistently underscore the substantial role of such exposure in work-related asthma among hospital staff. We aimed to (a) identify and characterize current practices in cleaning and aerosolized medication administration; (b) assess changes in practices since a similar 2003 study of Texas healthcare workers; and (c) identify factors contributing to diverse exposures within healthcare job categories. We conducted focus groups with 38 participants in 6 healthcare settings, analyzing current practices, changes since 2003, and factors contributing to exposure diversity. …

Patient-Reported Outcomes: Comparing Functional Avoidance And Standard Thoracic Radiation Therapy In Lung Cancer, Spencer Poiset, Joseph Lombardo, Edward Castillo, Richard Castillo, Bernard Jones, Moyed Miften, Brian Kavanagh, Adam Dicker, Cullen Boyle, Nicole Simone, Benjamin Movsas, Inga Grills, Chad Rusthoven, Yevgeniy Vinogradskiy, Lydia Wilson

Department of Radiation Oncology Faculty Papers

PURPOSE: Novel methods generate functional images using image processing techniques combined with four-dimensional computed tomography (4DCT) data (4DCT-ventilation). 4DCT-ventilation was implemented in a phase II, multicenter functional avoidance clinical trial. The work compares functional avoidance patient-reported outcomes (PROs) against historical standards.

METHODS: Patients with locally advanced lung cancer undergoing curative-intent chemoradiation were accrued. 4DCT-ventilation imaging was generated and functional avoidance treatment plans created reduced dose to functional lung. PRO instruments included Functional Assessment of Cancer Therapy Lung questionnaire and accompanying subscales (including the Trial Outcome Index [TOI]), EuroQol-5 Dimension (EQ-5D), and EQ-Visual Analog Scale (EQ-VAS). The average change from baseline …

Predictors For Spontaneous Pleurodesis In Patients With Indwelling Pleural Catheters For Malignant Pleural Effusion: A Safety Net Hospital Experience, Saad Farooq, Sabiha Armin, Jordan E Killingsworth, Akriti Agrawal, Adishwar Rao, Rosa M Estrada-Y-Martin, Sujith V Cherian

Faculty, Staff and Student Publications

Background: Malignant pleural effusion (MPE) affects approximately 150,000 patients in the United States each year and usually signifies advanced-stage cancer. The optimal treatment remains a challenge but indwelling pleural catheters (IPC) offer several advantages and may help achieve spontaneous pleurodesis (SP) in some patients.

Objectives: We aim to investigate the predictors of SP among patients with MPE, particularly in a resource-limited community-based safety net hospital.

Design: This is a retrospective cohort study done at a community-based safety net hospital.

Methods: Adults diagnosed with or suspected of having MPE between January 2015 and December 2023 who underwent IPC placement were included. …

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 …

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 …

Safety And Feasibility Of Third-Party Cytotoxic T Lymphocytes For High-Risk Patients With Covid-19, Dolores Grosso, John L. Wagner, Allyson O'Connor, Kaitlyn Keck, Yanping Huang, Zi-Xuan Wang, Hilary Mehler, Benjamin Leiby, Phyllis Flomenberg, Usama Gergis, Neda Nikbakht, Michael Morris, Julie Karp, Alexis R. Peedin, Neal Flomenberg

COVID-19 Papers, Posters, and Presentations

Cytotoxic T lymphocytes (CTLs) destroy virally infected cells and are critical for the elimination of viral infections such as those caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Delayed and dysfunctional adaptive immune responses to SARS-CoV-2 are associated with poor outcomes. Treatment with allogeneic SARS-CoV-2-specific CTLs may enhance cellular immunity in high-risk patients providing a safe, direct mechanism of treatment. Thirty high-risk ambulatory patients with COVID-19 were enrolled in a phase 1 trial assessing the safety of third party, SARS-CoV-2-specific CTLs. Twelve interventional patients, 6 of whom were immunocompromised, matched the HLA-A∗02:01 restriction of the CTLs and received …

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.

Polygenic And Transcriptional Risk Scores Identify Chronic Obstructive Pulmonary Disease Subtypes In The Copdgene And Eclipse Cohort Studies, Matthew Moll, Julian Hecker, John Platig, Jingzhou Zhang, Auyon J. Ghosh, Katherine A. Pratte, Rui-Sheng Wang, Davin Hill, Iain R. Konigsberg, Joe W. Chiles, Craig P. Hersh, Peter J. Castaldi, Kimberly Glass, Jennifer G. Dy, Don D. Sin, Ruth Tal-Singer, Majd Mouded, Stephen I. Rennard, Gary P. Anderson, Gregory L. Kinney, Russell P. Bowler, Jeffrey L. Curtis, Merry-Lynn Mcdonald, Edwin K. Silverman, Brian D. Hobbs, Michael H. Cho

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: Genetic variants and gene expression predict risk of chronic obstructive pulmonary disease (COPD), but their effect on COPD heterogeneity is unclear. We aimed to define high-risk COPD subtypes using genetics (polygenic risk score, PRS) and blood gene expression (transcriptional risk score, TRS) and assess differences in clinical and molecular characteristics.

METHODS: We defined high-risk groups based on PRS and TRS quantiles by maximising differences in protein biomarkers in a COPDGene training set and identified these groups in COPDGene and ECLIPSE test sets. We tested multivariable associations of subgroups with clinical outcomes and compared protein-protein interaction networks and drug repurposing …

Treatment Of High- And Intermediate-High-Risk Pulmonary Embolism By The Pulmonary Embolism Response Team: Focus On Catheter-Directed Therapies, Arkadiusz Pietrasik, Paweł Kurzyna, Piotr Szwed, Karolina Jasińska-Gniadzik, Aleksandra Gąsecka, Szymona Darocha, Dariusz Zieliński, Łukasz Szarpak, Janusz Kochman, Marcin Grabowski, Grzegorz Opolski, Adam Torbicki, Marcin Kurzyna

Faculty, Staff and Students Publications

BACKGROUND: Multidisciplinary Pulmonary Embolism Response Teams (PERTs) were established to individualize the treatment of high-risk (HR) and intermediate-high-risk (IHR) pulmonary embolism (PE) patients, which pose a challenge in clinical practice.

METHODS: We retrospectively collected the data of all HR and IHR acute PE patients consulted by PERT CELZAT between September 2017 and October 2022. The patient population was divided into four different treatment methods: anticoagulation alone (AC), systemic thrombolysis (ST), surgical embolectomy (SE), and catheter-directed therapies (CDTx). Baseline clinical characteristics, risk stratification, PE severity parameters, and treatment outcomes were compared between the four groups.

RESULTS: Of the 110 patients with …

Association Between Duration Of Smoking Abstinence Before Non-Small-Cell Lung Cancer Diagnosis And Survival: A Retrospective, Pooled Analysis Of Cohort Studies, Aline F Fares, Yao Li, Mei Jiang, M Catherine Brown, Andrew C L Lam, Reenika Aggarwal, Sabine Schmid, Natasha B Leighl, Frances A Shepherd, Zhichao Wang, Nancy Diao, Angela S Wenzlaff, Juntao Xie, Takashi Kohno, Neil E Caporaso, Curtis Harris, Hongxia Ma, Matthew J Barnett, Leticia Ferro Leal, G Fernandez-Tardon, Mónica Pérez-Ríos, Michael P A Davies, Fiona Taylor, Ben Schöttker, Paul Brennan, David Zaridze, Ivana Holcatova, Jolanta Lissowska, Beata Świątkowska, Dana Mates, Milan Savic, Hermann Brenner, Angeline Andrew, Angela Cox, John K Field, Alberto Ruano-Ravina, Sanjay S Shete, Adonina Tardon, Ying Wang, Loic Le Marchand, Rui Manuel Reis, Matthew B Schabath, Chu Chen, Hongbing Shen, Brid M Ryan, Maria Teresa Landi, Kouya Shiraishi, Jie Zhang, Ann G Schwartz, Ming S Tsao, David C Christiani, Ping Yang, Rayjean J Hung, Wei Xu, Geoffrey Liu

Faculty, Staff and Student Publications

BACKGROUND: The association between duration of smoking abstinence before non-small-cell lung cancer (NSCLC) diagnosis and subsequent survival can influence public health messaging delivered in lung-cancer screening. We aimed to assess whether the duration of smoking abstinence before diagnosis of NSCLC is associated with improved survival.

METHODS: In this retrospective, pooled analysis of cohort studies, we used 26 cohorts participating in Clinical Outcomes Studies of the International Lung Cancer Consortium (COS-ILCCO) at 23 hospitals. 16 (62%) were from North America, six (23%) were from Europe, three (12%) were from Asia, and one (4%) was from South America. Patients enrolled were diagnosed …

Intravenous Aviptadil And Remdesivir For Treatment Of Covid-19-Associated Hypoxaemic Respiratory Failure In The Usa (Tesico): A Randomised, Placebo-Controlled Trial, Samuel M Brown, Christina E Barkauskas, Birgit Grund, Shweta Sharma, Andrew N Phillips, Lindsay Leither, Ithan D Peltan, Michael Lanspa, Daniel L Gilstrap, Ahmad Mourad, Kathleen Lane, Jeremy R Beitler, Alexis L Serra, Ivan Garcia, Eyad Almasri, Mohamed Fayed, Kinsley Hubel, Estelle S Harris, Elizabeth A Middleton, Macy A G Barrios, Kusum S Mathews, Neha N Goel, Samuel Acquah, Jarrod Mosier, Cameron Hypes, Elizabeth Salvagio Campbell, Akram Khan, Catherine L Hough, Jennifer G Wilson, Joseph E Levitt, Abhijit Duggal, Siddharth Dugar, Andrew J Goodwin, Charles Terry, Peter Chen, Sam Torbati, Nithya Iyer, Uriel S Sandkovsky, Nicholas J Johnson, Bryce R H Robinson, Michael A Matthay, Neil R Aggarwal, Ivor S Douglas, Jonathan D Casey, Manuel Hache-Marliere, J Georges Youssef, William Nkemdirim, Brad Leshnower, Omar Awan, Sonal Pannu, Darragh Shane O'Mahony, Prasad Manian, J W Awori Hayanga, Glenn W Wortmann, Bruno M Tomazini, Robert F Miller, Jens-Ulrik Jensen, Daniel D Murray, Nina A Bickell, Jigna Zatakia, Sarah Burris, Elizabeth S Higgs, Ven Natarajan, Robin L Dewar, Adam Schechner, Nayon Kang, Alejandro Arenas-Pinto, Fleur Hudson, Adit A Ginde, Wesley H Self, Angela J Rogers, Cathryn F Oldmixon, Haley Morin, Adriana Sanchez, Amy C Weintrob, Alexandre Biasi Cavalcanti, Anne Davis-Karim, Nicole Engen, Eileen Denning, B Taylor Thompson, Annetine C Gelijns, Virginia Kan, Victoria J Davey, Jens D Lundgren, Abdel G Babiker, James D Neaton, H Clifford Lane

Faculty, Staff and Student Publications

BACKGROUND: There is a clinical need for therapeutics for COVID-19 patients with acute hypoxemic respiratory failure whose 60-day mortality remains at 30-50%. Aviptadil, a lung-protective neuropeptide, and remdesivir, a nucleotide prodrug of an adenosine analog, were compared with placebo among patients with COVID-19 acute hypoxaemic respiratory failure.

METHODS: TESICO was a randomised trial of aviptadil and remdesivir versus placebo at 28 sites in the USA. Hospitalised adult patients were eligible for the study if they had acute hypoxaemic respiratory failure due to confirmed SARS-CoV-2 infection and were within 4 days of the onset of respiratory failure. Participants could be randomly …

Abatacept, Cenicriviroc, Or Infliximab For Treatment Of Adults Hospitalized With Covid-19 Pneumonia: A Randomized Clinical Trial, Jane A O'Halloran, Emily R Ko, Kevin J Anstrom, Eyal Kedar, Matthew W Mccarthy, Reynold A Panettieri, Martin Maillo, Patricia Segura Nunez, Anne M Lachiewicz, Cynthia Gonzalez, P Brian Smith, Sabina Mendivil-Tuchia De Tai, Akram Khan, Alfredo J Mena Lora, Matthias Salathe, Gerardo Capo, Daniel Rodríguez Gonzalez, Thomas F Patterson, Christopher Palma, Horacio Ariza, Maria Patelli Lima, John Blamoun, Esteban C Nannini, Eduardo Sprinz, Analia Mykietiuk, Radica Alicic, Adriana M Rauseo, Cameron R Wolfe, Britta Witting, Jennifer P Wang, Luis Parra-Rodriguez, Tatyana Der, Kate Willsey, Jun Wen, Adam Silverstein, Sean M O'Brien, Hussein R Al-Khalidi, Michael A Maldonado, Richard Melsheimer, William G Ferguson, Steven E Mcnulty, Pearl Zakroysky, Susan Halabi, Daniel K Benjamin, Sandra Butler, Jane C Atkinson, Stacey J Adam, Soju Chang, Lisa Lavange, Michael Proschan, Samuel A Bozzette, William G Powderly, Activ-1 Im Study Group Members

Faculty, Staff and Student Publications

IMPORTANCE: Immune dysregulation contributes to poorer outcomes in COVID-19.

OBJECTIVE: To investigate whether abatacept, cenicriviroc, or infliximab provides benefit when added to standard care for COVID-19 pneumonia.

DESIGN, SETTING, AND PARTICIPANTS: Randomized, double-masked, placebo-controlled clinical trial using a master protocol to investigate immunomodulators added to standard care for treatment of participants hospitalized with COVID-19 pneumonia. The results of 3 substudies are reported from 95 hospitals at 85 clinical research sites in the US and Latin America. Hospitalized patients 18 years or older with confirmed SARS-CoV-2 infection within 14 days and evidence of pulmonary involvement underwent randomization between October 2020 and …

Higher Dose Corticosteroids In Patients Admitted To Hospital With Covid-19 Who Are Hypoxic But Not Requiring Ventilatory Support (Recovery): A Randomised, Controlled, Open-Label, Platform Trial, Recovery Collaborative Group

Faculty, Staff and Student Publications

BACKGROUND: Low-dose corticosteroids have been shown to reduce mortality for patients with COVID-19 requiring oxygen or ventilatory support (non-invasive mechanical ventilation, invasive mechanical ventilation, or extracorporeal membrane oxygenation). We evaluated the use of a higher dose of corticosteroids in this patient group.

METHODS: This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]) is assessing multiple possible treatments in patients hospitalised for COVID-19. Eligible and consenting adult patients with clinical evidence of hypoxia (ie, receiving oxygen or with oxygen saturation

FINDINGS: Between May 25, 2021, and May 13, 2022, 1272 patients with COVID-19 and hypoxia receiving no oxygen …

In-Hospital Mortality Risk Stratification In Children Aged Under 5 Years With Pneumonia With Or Without Pulse Oximetry: A Secondary Analysis Of The Pneumonia Research Partnership To Assess Who Recommendations (Prepare) Dataset, Shubhada Hooli, Carina King, Eric D Mccollum, Tim Colbourn, Norman Lufesi, Charles Mwansambo, Christopher J Gregory, Somsak Thamthitiwat, Clare Cutland, Shabir Ahmed Madhi, Marta C Nunes, Bradford D Gessner, Tabish Hazir, Joseph L Mathew, Emmanuel Addo-Yobo, Noel Chisaka, Mumtaz Hassan, Patricia L Hibberd, Prakash Jeena, Juan M Lozano, William B Macleod, Archana Patel, Donald M Thea, Ngoc Tuong Vy Nguyen, Syed Ma Zaman, Raul O Ruvinsky, Marilla Lucero, Cissy B Kartasasmita, Claudia Turner, Rai Asghar, Salem Banajeh, Imran Iqbal, Irene Maulen-Radovan, Greta Mino-Leon, Samir K Saha, Mathuram Santosham, Sunit Singhi, Shally Awasthi, Ashish Bavdekar, Monidarin Chou, Pagbajabyn Nymadawa, Jean-William Pape, Glaucia Paranhos-Baccala, Valentina Sanchez Picot, Mala Rakoto-Andrianarivelo, Vanessa Rouzier, Graciela Russomando, Mariam Sylla, Philippe Vanhems, Jianwei Wang, Sudha Basnet, Tor A Strand, Mark I Neuman, Luis Martinez Arroyo, Marcela Echavarria, Shinjini Bhatnagar, Nitya Wadhwa, Rakesh Lodha, Satinder Aneja, Angela Gentile, Mandeep Chadha, Siddhivinayak Hirve, Kerry-Ann F O'Grady, Alexey W Clara, Chris A Rees, Harry Campbell, Harish Nair, Jennifer Falconer, Linda J Williams, Margaret Horne, Shamim A Qazi, Yasir Bin Nisar, Pneumonia Research Partnership To Assess Who Recommendations (Prepare) Study Group

Faculty, Staff and Students Publications

OBJECTIVES: We determined the pulse oximetry benefit in pediatric pneumonia mortality risk stratification and chest-indrawing pneumonia in-hospital mortality risk factors.

METHODS: We report the characteristics and in-hospital pneumonia-related mortality of children aged 2-59 months who were included in the Pneumonia Research Partnership to Assess WHO Recommendations dataset. We developed multivariable logistic regression models of chest-indrawing pneumonia to identify mortality risk factors.

RESULTS: Among 285,839 children, 164,244 (57.5%) from hospital-based studies were included. Pneumonia case fatality risk (CFR) without pulse oximetry measurement was higher than with measurement (5.8%, 95% confidence interval [CI] 5.6-5.9% vs 2.1%, 95% CI 1.9-2.4%). One in five …

Assembling A Global Database Of Child Pneumonia Studies To Inform Who Pneumonia Management Algorithm: Methodology And Applications, Helena Martin, Jennifer Falconer, Emmanuel Addo-Yobo, Satinder Aneja, Luis Martinez Arroyo, Rai Asghar, Shally Awasthi, Salem Banajeh, Abdul Bari, Sudha Basnet, Ashish Bavdekar, Nita Bhandari, Shinjini Bhatnagar, Zulfiqar A Bhutta, Abdullah Brooks, Mandeep Chadha, Noel Chisaka, Monidarin Chou, Alexey W Clara, Tim Colbourn, Clare Cutland, Valérie D'Acremont, Marcela Echavarria, Angela Gentile, Brad Gessner, Christopher J Gregory, Tabish Hazir, Patricia L Hibberd, Siddhivinayak Hirve, Shubhada Hooli, Imran Iqbal, Prakash Jeena, Cissy B Kartasasmita, Carina King, Romina Libster, Rakesh Lodha, Juan M Lozano, Marilla Lucero, Norman Lufesi, William B Macleod, Shabir Ahmed Madhi, Joseph L Mathew, Irene Maulen-Radovan, Eric D Mccollum, Greta Mino, Charles Mwansambo, Mark I Neuman, Ngoc Tuong Vy Nguyen, Marta C Nunes, Pagbajabyn Nymadawa, Kerry-Ann F O'Grady, Jean-William Pape, Glaucia Paranhos-Baccala, Archana Patel, Valentina Sanchez Picot, Mala Rakoto-Andrianarivelo, Zeba Rasmussen, Vanessa Rouzier, Graciela Russomando, Raul O Ruvinsky, Salim Sadruddin, Samir K Saha, Mathuram Santosham, Sunit Singhi, Sajid Soofi, Tor A Strand, Mariam Sylla, Somsak Thamthitiwat, Donald M Thea, Claudia Turner, Philippe Vanhems, Nitya Wadhwa, Jianwei Wang, Syed Ma Zaman, Harry Campbell, Harish Nair, Shamim Ahmad Qazi, Yasir Bin Nisar, World Health Organization Pneumonia Research Partnership To Assess Who Recommendation (Prepare) Study Group

Faculty, Staff and Students Publications

BACKGROUND: The existing World Health Organization (WHO) pneumonia case management guidelines rely on clinical symptoms and signs for identifying, classifying, and treating pneumonia in children up to 5 years old. We aimed to collate an individual patient-level data set from large, high-quality pre-existing studies on pneumonia in children to identify a set of signs and symptoms with greater validity in the diagnosis, prognosis, and possible treatment of childhood pneumonia for the improvement of current pneumonia case management guidelines.

METHODS: Using data from a published systematic review and expert knowledge, we identified studies meeting our eligibility criteria and invited investigators to …

Relationships Of Serum Cc16 Levels With Smoking Status And Lung Function In Copd, Kelli C. Gribben, Jill A. Poole, Amy J. Nelson, Paraskevi A. Farazi, Christopher S. Wichman, Art J. Heires, Debra J. Romberger, Tricia D. Levan

Journal Articles: Pulmonary & Critical Care Med

Background: The club cell secretory protein (CC16) has anti-inflammatory and antioxidant effects, and low CC16 serum levels have been associated with both risk and progression of COPD, yet the interaction between smoking and CC16 on lung function outcomes remains unknown.

Methods: Utilizing cross-sectional data on United States veterans, CC16 serum concentrations were measured by ELISA and log transformed for analyses. Spirometry was conducted and COPD status was defined by post-bronchodilator FEV₁/FVC ratio < 0.7. Smoking measures were self-reported on questionnaire. Multivariable logistic and linear regression were employed to examine associations between CC16 levels and COPD, and lung function with adjustment for covariates. Unadjusted Pearson correlations described relationships between CC16 level and lung function measures, pack-years smoked, and years since smoking cessation.

Results: The study population (N = 351) was mostly male, white, with an average age over 60 years. An interaction between CC16 and smoking status on …

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 …

Transient Ascaris Suum Larval Migration Induces Intractable Chronic Pulmonary Disease And Anemia In Mice, Yifan Wu, Evan Li, Morgan Knight, Grace Adeniyi-Ipadeola, Li-Zhen Song, Alan R Burns, Ana Clara Gazzinelli-Guimaraes, Ricardo Fujiwara, Maria Elena Bottazzi, Jill E Weatherhead

Faculty, Staff and Students Publications

Ascariasis is one of the most common infections in the world and associated with significant global morbidity. Ascaris larval migration through the host's lungs is essential for larval development but leads to an exaggerated type-2 host immune response manifesting clinically as acute allergic airway disease. However, whether Ascaris larval migration can subsequently lead to chronic lung diseases remains unknown. Here, we demonstrate that a single episode of Ascaris larval migration through the host lungs induces a chronic pulmonary syndrome of type-2 inflammatory pathology and emphysema accompanied by pulmonary hemorrhage and chronic anemia in a mouse model. Our results reveal that …

Predicting Lymph Node Metastasis In Non-Small Cell Lung Cancer: Prospective External And Temporal Validation Of The Hal And Homer Models, Gabriela Martinez-Zayas, Francisco A Almeida, Lonny Yarmus, Daniel Steinfort, Donald R Lazarus, Michael J Simoff, Timothy Saettele, Septimiu Murgu, Tarek Dammad, D Kevin Duong, Lakshmi Mudambi, Joshua J Filner, Sofia Molina, Carlos Aravena, Jeffrey Thiboutot, Asha Bonney, Adriana M Rueda, Labib G Debiane, D Kyle Hogarth, Harmeet Bedi, Mark Deffebach, Ala-Eddin S Sagar, Joseph Cicenia, Diana H Yu, Avi Cohen, Laura Frye, Horiana B Grosu, Thomas Gildea, David Feller-Kopman, Roberto F Casal, Michael Machuzak, Muhammad H Arain, Sonali Sethi, George A Eapen, Louis Lam, Carlos A Jimenez, Manuel Ribeiro, Laila Z Noor, Atul Mehta, Juhee Song, Humberto Choi, Junsheng Ma, Liang Li, David E Ost

Faculty, Staff and Students Publications

BACKGROUND: Two models, the Help with the Assessment of Adenopathy in Lung cancer (HAL) and Help with Oncologic Mediastinal Evaluation for Radiation (HOMER), were recently developed to estimate the probability of nodal disease in patients with non-small cell lung cancer (NSCLC) as determined by endobronchial ultrasound-transbronchial needle aspiration (EBUS-TBNA). The objective of this study was to prospectively externally validate both models at multiple centers.

RESEARCH QUESTION: Are the HAL and HOMER models valid across multiple centers?

STUDY DESIGN AND METHODS: This multicenter prospective observational cohort study enrolled consecutive patients with PET-CT clinical-radiographic stages T1-3, N0-3, M0 NSCLC undergoing EBUS-TBNA staging. …

Tocilizumab In Hospitalized Patients With Severe Covid-19 Pneumonia, Ivan O Rosas, Norbert Bräu, Michael Waters, Ronaldo C Go, Bradley D Hunter, Sanjay Bhagani, Daniel Skiest, Mariam S Aziz, Nichola Cooper, Ivor S Douglas, Sinisa Savic, Taryn Youngstein, Lorenzo Del Sorbo, Antonio Cubillo Gracian, David J De La Zerda, Andrew Ustianowski, Min Bao, Sophie Dimonaco, Emily Graham, Balpreet Matharu, Helen Spotswood, Larry Tsai, Atul Malhotra

Faculty, Staff and Students Publications

BACKGROUND: Coronavirus disease 2019 (Covid-19) is associated with immune dysregulation and hyperinflammation, including elevated interleukin-6 levels. The use of tocilizumab, a monoclonal antibody against the interleukin-6 receptor, has resulted in better outcomes in patients with severe Covid-19 pneumonia in case reports and retrospective observational cohort studies. Data are needed from randomized, placebo-controlled trials.

METHODS: In this phase 3 trial, we randomly assigned patients who were hospitalized with severe Covid-19 pneumonia in a 2:1 ratio receive a single intravenous infusion of tocilizumab (at a dose of 8 mg per kilogram of body weight) or placebo. Approximately one quarter of the participants …

Latent Traits Of Lung Tissue Patterns In Former Smokers Derived By Dual Channel Deep Learning In Computed Tomography Images, Frank Li, Jiwoong Choi, Chunrui Zou, John D. Newell, Alejandro P. Comellas, Chang Hyun Lee, Hongseok Ko, R. Graham Barr, Eugene R. Bleecker, Christopher B. Cooper, Fereidoun Abtin, Igor Barjaktarevic, David Couper, Meilan Han, Nadia N. Hansel, Richard E. Kanner, Robert Paine, Ella A. Kazerooni, Fernando J. Martinez, Wanda O'Neal, Stephen I. Rennard, Benjamin M. Smith, Prescott G. Woodruff, Eric A. Hoffman, Ching-Long Lin

Journal Articles: Pulmonary & Critical Care Med

Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease and the traditional variables extracted from computed tomography (CT) images may not be sufficient to describe all the topological features of lung tissues in COPD patients. We employed an unsupervised three-dimensional (3D) convolutional autoencoder (CAE)-feature constructor (FC) deep learning network to learn from CT data and derive tissue pattern-clusters jointly. We then applied exploratory factor analysis (EFA) to discover the unobserved latent traits (factors) among pattern-clusters. CT images at total lung capacity (TLC) and residual volume (RV) of 541 former smokers and 59 healthy non-smokers from the cohort of the SubPopulations …

Occupational Health Practices Among Dental Care Professionals Before And During The Covid-19 Pandemic, Sean Banaee, Denise M. Claiborne, Muge Akpinar-Elci

Community & Environmental Health Faculty Publications

BACKGROUND: The COVID-19 pandemic has posed a substantial burden on dental care professionals. While dentistry is known as one of the most exposed and high-risk professions, dental care professionals are indeed at even greater risk.

OBJECTIVE: The aim of this study was to assess knowledge, attitudes, occupational health practices, personal protective equipment usage, and mental stressors during COVID-19 pandemic among dental care professionals.

METHODS: A cross-sectional study was conducted among dental care professionals who were subscribers to a dental hygiene journal using a self-administered online survey (n = 1047 respondents). Cross-tabulations were performed to determine differences in the responses to …

Losartan Rescues Inflammation-Related Mucociliary Dysfunction In Relevant Models Of Cystic Fibrosis, Michael D Kim, Nathalie Baumlin, Makoto Yoshida, Deepika Polineni, Sebastian F Salathe, Joseph K David, Charles A Peloquin, Adam Wanner, John S Dennis, Juliette Sailland, Philip Whitney, Frank T Horrigan, Juan R Sabater, William M Abraham, Matthias Salathe

Faculty, Staff and Students Publications

Rationale: Despite therapeutic progress in treating cystic fibrosis (CF) airway disease, airway inflammation with associated mucociliary dysfunction remains largely unaddressed. Inflammation reduces the activity of apically expressed large-conductance Ca²⁺-activated and voltage-dependent K⁺ (BK) channels, critical for mucociliary function in the absence of CFTR (CF transmembrane conductance regulator).

Objectives: To test losartan as an antiinflammatory therapy in CF using CF human bronchial epithelial cells and an ovine model of CF-like airway disease.

Methods: Losartan’s antiinflammatory effectiveness to rescue BK activity and thus mucociliary function was tested in vitro using primary, fully redifferentiated human airway epithelial cells homozygous for …

Current Smoking With Or Without Chronic Bronchitis Is Independently Associated With Goblet Cell Hyperplasia In Healthy Smokers And Copd Subjects, Victor Kim, Stephanie Jeong, Huaqing Zhao, Mehmet Kesimer, Richard C. Boucher, J. Michael Wells, Stephanie A. Christenson, Meilan K. Han, Mark Dransfield, Robert Paine, Christopher B. Cooper, Igor Barjaktarevic, Russell Bowler, Jeffrey L. Curtis, Robert J. Kaner, Sarah L. O'Beirne, Wanda K. O'Neal, Stephen I. Rennard, Fernando J. Martinez, Prescott G. Woodruff

Journal Articles: Pulmonary & Critical Care Med

COPD, chronic bronchitis (CB) and active smoking have all been associated with goblet cell hyperplasia (GCH) in small studies. Active smoking is strongly associated with CB, but there is a disconnect between CB clinical symptoms and pathology. Chronic cough and sputum production poorly correlate with the presence of GCH or COPD. We hypothesized that the primary determinant of GCH in ever smokers with or without airflow obstruction is active smoking. Goblet Cell Density (GCD) was measured in 71 current or former smokers [32 subjects without COPD and 39 COPD subjects]. Endobronchial mucosal biopsies were stained with Periodic Acid Schiff-Alcian Blue, …