Pulmonology Commons^™

Tlr7 Promotes Smoke-Induced Experimental Lung Damage Through The Activity Of Mast Cell Tryptase, Gang Liu, Tatt Jhong Haw, Malcolm R Starkey, Ashleigh M Philp, Stelios Pavlidis, Christina Nalkurthi, Prema M Nair, Henry M Gomez, Irwan Hanish, Alan Cy Hsu, Elinor Hortle, Sophie Pickles, Joselyn Rojas-Quintero, Raul San Jose Estepar, Jacqueline E Marshall, Richard Y Kim, Adam M Collison, Joerg Mattes, Sobia Idrees, Alen Faiz, Nicole G Hansbro, Ryutaro Fukui, Yusuke Murakami, Hong Sheng Cheng, Nguan Soon Tan, Sanjay H Chotirmall, Jay C Horvat, Paul S Foster, Brian Gg Oliver, Francesca Polverino, Antonio Ieni, Francesco Monaco, Gaetano Caramori, Sukhwinder S Sohal, Ken R Bracke, Peter A Wark, Ian M Adcock, Kensuke Miyake, Don D Sin, Philip M Hansbro

Faculty, Staff and Students Publications

Toll-like receptor 7 (TLR7) is known for eliciting immunity against single-stranded RNA viruses, and is increased in both human and cigarette smoke (CS)-induced, experimental chronic obstructive pulmonary disease (COPD). Here we show that the severity of CS-induced emphysema and COPD is reduced in TLR7-deficient mice, while inhalation of imiquimod, a TLR7-agonist, induces emphysema without CS exposure. This imiquimod-induced emphysema is reduced in mice deficient in mast cell protease-6, or when wild-type mice are treated with the mast cell stabilizer, cromolyn. Furthermore, therapeutic treatment with anti-TLR7 monoclonal antibody suppresses CS-induced emphysema, experimental COPD and accumulation of pulmonary mast cells in mice. …

Ten Steps Toward Improving In-Hospital Cardiac Arrest Quality Of Care And Outcomes, Brahmajee K. Nallamothu, Robert Greif, Theresa Anderson, Huba Atiq, Thomaz Bittencourt Couto, Julie Considine, Allan R De Caen, Therese Djärv, Ann Doll, Matthew J. Douma

Department of Anaesthesia

No abstract provided.

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 …

Plasma Metabolomics And Quantitative Interstitial Abnormalities In Ever-Smokers, Bina Choi, Raúl San José Estépar, Suneeta Godbole, Jeffrey L Curtis, Jennifer M Wang, Rubén San José Estépar, Ivan O Rosas, Jared R Mayers, Brian D Hobbs, Craig P Hersh, Samuel Y Ash, Meilan K Han, Russell P Bowler, Kathleen A Stringer, George R Washko, Wassim W Labaki

Faculty, Staff and Students Publications

BACKGROUND: Quantitative interstitial abnormalities (QIA) are an automated computed tomography (CT) finding of early parenchymal lung disease, associated with worse lung function, reduced exercise capacity, increased respiratory symptoms, and death. The metabolomic perturbations associated with QIA are not well known. We sought to identify plasma metabolites associated with QIA in smokers. We also sought to identify shared and differentiating metabolomics features between QIA and emphysema, another smoking-related advanced radiographic abnormality.

METHODS: In 928 former and current smokers in the Genetic Epidemiology of COPD cohort, we measured QIA and emphysema using an automated local density histogram method and generated metabolite profiles …

Incidence And Risk Factors For Pneumonitis Associated With Checkpoint Inhibitors In Advanced Non-Small Cell Lung Cancer: A Single Center Experience, Mehmet Altan, Felipe Soto, Linda L Zhong, Fechukwu O Akhmedzhanov, Nathaniel R Wilson, Abdulrazzak Zarifa, Aya A Albittar, Vincent Yang, Jeff Lewis, Waree Rinsurongkawong, J Jack Lee, Vadeerat Rinsurongkawong, Jianjun Zhang, Don L Gibbons, Ara A Vaporciyan, Kristofer Jennings, Fareed Khawaja, Saadia A Faiz, Vickie R Shannon, Girish Shroff, Myrna C B Godoy, Naval G Daver, Saumil Gandhi, Tito R Mendoza, Aung Naing, Carrie Daniel-Macdougall, John V Heymach, Ajay Sheshadri

Faculty, Staff and Student Publications

INTRODUCTION: Immune checkpoint inhibitor (ICI) pneumonitis causes substantial morbidity and mortality. Estimates of real-world incidence and reported risk factors vary substantially.

METHODS: We conducted a retrospective review of 419 patients with advanced non-small cell lung cancer (NSCLC) who were treated with anti-PD-(L)1 with or without anti-CTLA-4 therapy. Clinical, imaging, and microbiological data were evaluated by multidisciplinary adjudication teams. The primary outcome of interest was grade ≥2 (CTCAEv5) pneumonitis. Clinicopathologic variables, tobacco use, cancer therapies, and preexisting lung disease were assessed for univariate effects using Cox proportional hazards models. We created multivariate Cox proportional hazards models to assess risk factors for …

Inflammatory Activity Of Epithelial Stem Cell Variants From Cystic Fibrosis Lungs Is Not Resolved By Cftr Modulators, Shan Wang, Suchan Niroula, Ashley Hoffman, Melika Khorrami, Melina Khorrami, Feng Yuan, Grace N Gasser, Soon Choi, Bovey Liu, Justin Li, Mark L Metersky, Matthew Vincent, Christopher P Crum, Richard C Boucher, Harry Karmouty-Quintana, Howard J Huang, Ajay Sheshadri, Burton F Dickey, Kalpaj R Parekh, John F Engelhardt, Frank D Mckeon, Wa Xian

Faculty, Staff and Student Publications

Rationale

CFTR (cystic fibrosis transmembrane conductance regulator) modulator drugs restore function to mutant channels in patients with cystic fibrosis (CF) and lead to improvements in body mass index and lung function. Although it is anticipated that early childhood treatment with CFTR modulators will significantly delay or even prevent the onset of advanced lung disease, lung neutrophils and inflammatory cytokines remain high in patients with CF with established lung disease despite modulator therapy, underscoring the need to identify and ultimately target the sources of this inflammation in CF lungs.

Objectives

To determine whether CF lungs, like chronic obstructive pulmonary disease (COPD) …

Does Chronic Obstructive Pulmonary Disease Originate From Different Cell Types?, Yohannes Tesfaigzi, Jeffrey L Curtis, Irina Petrache, Francesca Polverino, Farrah Kheradmand, Ian M Adcock, Stephen I Rennard

Faculty, Staff and Students Publications

The onset of chronic obstructive pulmonary disease (COPD) is heterogeneous, and current approaches to define distinct disease phenotypes are lacking. In addition to clinical methodologies, subtyping COPD has also been challenged by the reliance on human lung samples from late-stage diseases. Different COPD phenotypes may be initiated from the susceptibility of different cell types to cigarette smoke, environmental pollution, and infections at early stages that ultimately converge at later stages in airway remodeling and destruction of the alveoli when the disease is diagnosed. This perspective provides discussion points on how studies to date define different cell types of the lung …

Individual- And Neighborhood-Level Characteristics Of Lung Cancer Screening Participants Undergoing Telemedicine Shared Decision Making, Christine S. Shusted, Hee-Soon Juon, Brooke Ruane, Brian M. Till, Charnita Zeigler-Johnson, Russell K. Mcintire, Tyler Grenda, Olugbenga Okusanya, Nathaniel R. Evans, Gregory C. Kane, Julie Barta

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

BACKGROUND: Although lung cancer screening (LCS) for high-risk individuals reduces lung cancer mortality in clinical trial settings, many questions remain about how to implement high-quality LCS in real-world programs. With the increasing use of telemedicine in healthcare, studies examining this approach in the context of LCS are urgently needed. We aimed to identify sociodemographic and other factors associated with screening completion among individuals undergoing telemedicine Shared Decision Making (SDM) for LCS.

METHODS: This retrospective study examined patients who completed Shared Decision Making (SDM) via telemedicine between May 4, 2020 - March 18, 2021 in a centralized LCS program. Individuals were …

Further Refinement Of The Differentially Methylated Distant Lung-Specific Foxf1 Enhancer In A Neonate With Alveolar Capillary Dysplasia, Przemyslaw Szafranski, Rijutha P Garimella, Haresh Mani, Ryan Hartman, Gail Deutsch, Alan Silk, Alan Benheim, Paweł Stankiewicz

Faculty, Staff and Students Publications

Heterozygous SNVs or CNV deletions involving the FOXF1 gene, or its distant enhancer, are causative for 80-90% of cases of alveolar capillary dysplasia with misalignment of pulmonary veins. Recently, we proposed bimodal structure and parental functional dimorphism of the lung-specific FOXF1 enhancer, with Unit 1 having higher activity on the paternal chr16 and Unit 2 on the maternal chr16. Here, we describe a novel unusually sized pathogenic de novo copy-number variant deletion involving a portion of the FOXF1 enhancer on maternal chr16 that implies narrowing Unit 2 to an essential ~ 9-kb segment. Using a restrictase-based assay, we found that …

Heritable Traits And Lung Cancer Risk: A Two-Sample Mendelian Randomization Study, Rowland W Pettit, Jinyoung Byun, Younghun Han, Quinn T Ostrom, Cristian Coarfa, Melissa L Bondy, Christopher I Amos

Faculty, Staff and Students Publications

INTRODUCTION: Lung cancer is a complex polygenic disorder. Analysis with Mendelian randomization (MR) allows for genetically predicted risks to be estimated between exposures and outcomes.

METHODS: We analyzed 345 heritable traits from the United Kingdom Biobank and estimated their associated effects on lung cancer outcomes using two sample MR. In addition to estimating effects with overall lung cancer, adenocarcinoma, small cell lung cancer, and squamous cell lung cancers, we performed conditional effect modeling with multivariate MR (MVMR) and the traits of alcohol use, smoking initiation, average pre-tax income, and educational attainment.

RESULTS: Univariate MR provided evidence for increased age at …

Bronchopulmonary Dysplasia – Associated Pulmonary Hypertension: An Updated Review, Ahmed El-Saie, Nidhy P Varghese, Melissa K Webb, Natalie Villafranco, Bheru Gandhi, Milenka Cuevas Guaman, Binoy Shivanna

Faculty, Staff and Students Publications

Bronchopulmonary dysplasia (BPD) is the leading cause of chronic lung disease in infants and the commonest complication of prematurity. Advances in respiratory and overall neonatal care have increased the survival of extremely low gestational age newborns, leading to the continued high incidence of BPD. Pulmonary hypertension (PH) represents the severe form of the pulmonary vascular disease associated with BPD, and affects almost one-third of infants with moderate to severe BPD. PH responds suboptimally to pulmonary vasodilators and increases morbidity and mortality in BPD infants. An up-to-date knowledge of the pathogenesis, pathophysiology, diagnosis, treatment, and outcomes of BPD-PH can be helpful …

Molecular Insights Using Spatial Transcriptomics Of The Distal Lung In Congenital Diaphragmatic Hernia, Krithika Lingappan, Oluyinka O Olutoye, Abiud Cantu, Manuel Eliezer Cantu Gutierrez, Nahir Cortes-Santiago, J D Hammond, Jamie Gilley, Joselyn Rojas Quintero, Hui Li, Francesca Polverino, Jason P Gleghorn, Sundeep G Keswani

Faculty, Staff and Students Publications

Abnormal pulmonary vascular development and function in congenital diaphragmatic hernia (CDH) is a significant factor leading to pulmonary hypertension. The lung is a very heterogenous organ and has marked cellular diversity that is differentially responsive to injury and therapeutic agents. Spatial transcriptomics provides the unmatched capability of discerning the differences in the transcriptional signature of these distinct cell subpopulations in the lung with regional specificity. We hypothesized that the distal lung parenchyma (selected as a region of interest) would show a distinct transcriptomic profile in the CDH lung compared with control (normal lung). We subjected lung sections obtained from male …

The Pre-Adaptation Of A Stroke-Specific Self-Management Program Among Older Adults, Timothy Reistetter, Kimberly Hreha, Julianna M Dean, Monique R Pappadis, Rachel R Deer, Chih-Ying Li, Ickpyo Hong, Annalisa Na, Sara Nowakowski, Hashem M Shaltoni, Suresh K Bhavnani

Faculty, Staff and Students Publications

Objectives:

Managing multimorbidity as aging stroke patients is complex; standard self-management programs necessitate adaptations. We used visual analytics to examine complex relationships among aging stroke survivors’ comorbidities. These findings informed pre-adaptation of a component of the Chronic Disease Self-Management Program.

Methods:

Secondary analysis of 2013–2014 Medicare claims with stroke as an index condition, hospital readmission within 90 days (n=42,938), and 72 comorbidities. Visual analytics identified patient subgroups and co-occurring comorbidities. Guided by the framework for reporting adaptations and modifications to evidence-based interventions (FRAME), an interdisciplinary team developed vignettes that highlighted multimorbidity to customize the self-management program.

Results:

There were five …

Obesity Paradox Or Hypoxia Preconditioning: How Obstructive Sleep Apnea Modifies The Obesity-Mi Relationship, Amir Sharafkhaneh, Ritwick Agrawal, Vijay Nambi, Ahmed Bahammam, Javad Razjouyan

Faculty, Staff and Students Publications

OBJECTIVES: The objective of this study was to evaluate the interaction between obesity and obstructive sleep apnea on acute MI in hospital mortality.

METHODS: This retrospective cohort study utilized Veterans Health Administration data from years 1999-2020. Participants were categorized according to their body mass index (BMI) to non-obese (BMI

RESULTS: Among 72,036 veterans with acute-MI hospitalization, individuals with obesity and obstructive sleep apnea (OB-SA) had the lowest in-hospital mortality rate (1.0%) compared to those without obesity and obstructive sleep apnea (nOB-nSA, 2.8%), with obesity but without obstructive sleep apnea (OB-nSA, 2.4%), and with obesity and obstructive sleep apnea (nOB-SA, 1.4%). …

Heterogenous Lung Inflammation Ct Patterns Distinguish Pneumonia And Immune Checkpoint Inhibitor Pneumonitis And Complement Blood Biomarkers In Acute Myeloid Leukemia: Proof Of Concept, Muhammad Aminu, Naval Daver, Myrna C B Godoy, Girish Shroff, Carol Wu, Luis F Torre-Sada, Alberto Goizueta, Vickie R Shannon, Saadia A Faiz, Mehmet Altan, Guillermo Garcia-Manero, Hagop Kantarjian, Farhad Ravandi-Kashani, Tapan Kadia, Marina Konopleva, Courtney Dinardo, Sherry Pierce, Aung Naing, Sang T Kim, Dimitrios P Kontoyiannis, Fareed Khawaja, Caroline Chung, Jia Wu, Ajay Sheshadri

Faculty, Staff and Student Publications

BACKGROUND: Immune checkpoint inhibitors (ICI) may cause pneumonitis, resulting in potentially fatal lung inflammation. However, distinguishing pneumonitis from pneumonia is time-consuming and challenging. To fill this gap, we build an image-based tool, and further evaluate it clinically alongside relevant blood biomarkers.

MATERIALS AND METHODS: We studied CT images from 97 patients with pneumonia and 29 patients with pneumonitis from acute myeloid leukemia treated with ICIs. We developed a CT-derived signature using a habitat imaging algorithm, whereby infected lungs are segregated into clusters ("habitats"). We validated the model and compared it with a clinical-blood model to determine whether imaging can add …

Associations Between Telomere Attrition, Genetic Variants In Telomere Maintenance Genes, And Non-Small Cell Lung Cancer Risk In The Jammu And Kashmir Population Of North India, Gh Rasool Bhat, Rajeshwer Singh Jamwal, Itty Sethi, Amrita Bhat, Ruchi Shah, Sonali Verma, Minerva Sharma, Hana Q Sadida, Sara K Al-Marzooqi, Tariq Masoodi, Sameer Mirza, Mohammad Haris, Muzafar A Macha, Ammira S Alshabeeb Akil, Ajaz A Bhat, Rakesh Kumar

Faculty, Staff and Student Publications

BACKGROUND: Telomeres are repetitive DNA sequences located at the ends of chromosomes, playing a vital role in maintaining chromosomal integrity and stability. Dysregulation of telomeres has been implicated in the development of various cancers, including non-small cell lung cancer (NSCLC), which is the most common type of lung cancer. Genetic variations within telomere maintenance genes may influence the risk of developing NSCLC. The present study aimed to evaluate the genetic associations of select variants within telomere maintenance genes in a population from Jammu and Kashmir, North India, and to investigate the relationship between telomere length and NSCLC risk.

METHODS: We …

Shp2 Promotes Sarcoidosis Severity By Inhibiting Skp2-Targeted Ubiquitination Of Tbet In Cd8+ T Cells, Sherly I Celada, Clarice X Lim, Alexandre F Carisey, Scott A Ochsner, Carlos F Arce Deza, Praveen Rexie, Fernando Poli De Frias, Rafael Cardenas-Castillo, Francesca Polverino, Markus Hengstschläger, Konstantin Tsoyi, Neil J Mckenna, Farrah Kheradmand, Thomas Weichhart, Ivan O Rosas, Luc Van Kaer, Lindsay J Celada

Faculty, Staff and Students Publications

Sarcoidosis is an interstitial lung disease (ILD) characterized by IFNγ and TBET dysregulation. Although one-third of patients progress from granulomatous inflammation to severe lung damage, the molecular mechanisms underlying this process remain unclear. Here, we report that pharmacological inhibition of phosphorylated SH2 containing protein tyrosine phosphatase-2 (pSHP2), a facilitator of aberrant IFNγ levels, decreases large granuloma formation and macrophage infiltration in the lungs of mice with sarcoidosis-like disease. Positive treatment outcomes were dependent on the effective enhancement of TBET ubiquitination within CD8+ T cells. Mechanistically, our findings identified a previously unknown post-translational modification (PTM) pathway in which the E3 F-box …

Design Of A Phase Iii, Double-Blind, Randomised, Placebo-Controlled Trial Of Bi 1015550 In Patients With Progressive Pulmonary Fibrosis (Fibroneer-Ild), Toby M Maher, Shervin Assassi, Arata Azuma, Vincent Cottin, Anna-Maria Hoffmann-Vold, Michael Kreuter, Justin M Oldham, Luca Richeldi, Claudia Valenzuela, Marlies S Wijsenbeek, Carl Coeck, Christina Schlecker, Florian Voss, Daniel Wachtlin, Fernando J Martinez

Faculty, Staff and Student Publications

INTRODUCTION: Progressive pulmonary fibrosis (PPF) includes any diagnosis of progressive fibrotic interstitial lung disease (ILD) other than idiopathic pulmonary fibrosis (IPF). However, disease progression appears comparable between PPF and IPF, suggesting a similar underlying pathology relating to pulmonary fibrosis. Following positive results in a phase II study in IPF, this phase III study will investigate the efficacy and safety of BI 1015550 in patients with PPF (FIBRONEER-ILD).

METHODS AND ANALYSIS: In this phase III, double-blind, placebo-controlled trial, patients are being randomised 1:1:1 to receive BI 1015550 (9 mg or 18 mg) or placebo twice daily over at least 52 weeks, …

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 …

Interstitial Lung Abnormalities After Hospitalization For Covid-19 In Patients With Cancer: A Prospective Cohort Study, Sungryong Noh, Christopher Bertini, Isabel Mira-Avendano, Maryam Kaous, Bela Patel, Saadia A Faiz, Vickie R Shannon, Diwakar D Balachandran, Lara Bashoura, Roberto Adachi, Scott E Evans, Burton Dickey, Carol Wu, Girish S Shroff, Joanna-Grace Manzano, Bruno Granwehr, Shannon Holloway, Kodwo Dickson, Alyssa Mohammed, Mayoora Muthu, Hui Song, Caroline Chung, Jia Wu, Lyndon Lee, Ying Jiang, Fareed Khawaja, Ajay Sheshadri

Faculty, Staff and Student Publications

INTRODUCTION: Survivors of SARS-CoV-2 pneumonia often develop persistent respiratory symptom and interstitial lung abnormalities (ILAs) after infection. Risk factors for ILA development and duration of ILA persistence after SARS-CoV-2 infection are not well described in immunocompromised hosts, such as cancer patients.

METHODS: We conducted a prospective cohort study of 95 patients at a major cancer center and 45 patients at a tertiary referral center. We collected clinical and radiographic data during the index hospitalization for COVID-19 pneumonia and measured pneumonia severity using a semi-quantitative radiographic score, the Radiologic Severity Index (RSI). Patients were evaluated in post-COVID-19 clinics at 3 and …

From Pre-Copd To Copd: A Simple, Low Cost And Easy To Implement (Slim) Risk Calculator, Miguel J Divo, Congjian Liu, Francesca Polverino, Peter J Castaldi, Bartolome R Celli, Yohannes Tesfaigzi

Faculty, Staff and Students Publications

BACKGROUND: The lifetime risk of developing clinical COPD among smokers ranges from 13% to 22%. Identifying at-risk individuals who will develop overt disease in a reasonable timeframe may allow for early intervention. We hypothesised that readily available clinical and physiological variables could help identify ever-smokers at higher risk of developing chronic airflow limitation (CAL).

METHODS: Among 2273 Lovelace Smokers' Cohort (LSC) participants, we included 677 (mean age 54 years) with normal spirometry at baseline and a minimum of three spirometries, each 1 year apart. Repeated spirometric measurements were used to determine incident CAL. Using logistic regression, demographics, anthropometrics, smoking history, …

Revisiting The Use Of Antibiotics To Prevent Copd Exacerbation: Is Doxycycline The Answer?, Muhammad Adrish, Nicola A Hanania

Faculty, Staff and Students Publications

No abstract provided.

Approach To Non-Type 2 Asthma, Muhammad Adrish, Praveen Akuthota

Faculty, Staff and Students Publications

No abstract provided.

Early Detection Of Lung Cancer Using Artificial Intelligence-Enhanced Optical Nanosensing Of Chromatin Alterations In Field Carcinogenesis, Ali Daneshkhah, Sravya Prabhala, Parvathi Viswanathan, Hariharan Subramanian, Jianan Lin, Andrew S Chang, Ankit Bharat, Hemant Kumar Roy, Vadim Backman

Faculty, Staff and Students Publications

Supranucleosomal chromatin structure, including chromatin domain conformation, is involved in the regulation of gene expression and its dysregulation has been associated with carcinogenesis. Prior studies have shown that cells in the buccal mucosa carry a molecular signature of lung cancer among the cigarette-smoking population, the phenomenon known as field carcinogenesis or field of injury. Thus, we hypothesized that chromatin structural changes in buccal mucosa can be predictive of lung cancer. However, the small size of the chromatin chain (approximately 20 nm) folded into chromatin packing domains, themselves typically below 300 nm in diameter, preclude the detection of alterations in intradomain …

Racial And Ethnic Disparities In Antifibrotic Therapy In Idiopathic Pulmonary Fibrosis, Joy Zhao, Joseph Fares, Gautam George, Arlene Maheu, Giorgos Loizidis, Jesse Roman, Daniel Kramer, Michael Li, Ross Summer

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

BACKGROUND AND OBJECTIVE: Racial disparities have been documented in care of many respiratory diseases but little is known about the impact of race on the treatment of interstitial lung diseases. The purpose of this study was to determine how race and ethnicity influence treatment of idiopathic pulmonary fibrosis.

METHODS: Adults with idiopathic pulmonary fibrosis (>18 years) were identified using TriNetX database and paired-wised comparisons were performed for antifibrotic treatment among White, Black, Hispanic and Asian patients. Mortality of treated and untreated IPF patients was compared after propensity score matching for age, sex, nicotine dependence, oxygen dependence and predicted FVC. …

Pathologist-Initiated Reflex Testing For Biomarkers In Non-Small-Cell Lung Cancer: Expert Consensus On The Rationale And Considerations For Implementation, J R Gosney, L Paz-Ares, P Jänne, K M Kerr, N B Leighl, M D Lozano, U Malapelle, T Mok, B S Sheffield, A Tufman, I I Wistuba, S Peters

Faculty, Staff and Student Publications

Biomarker tests in lung cancer have been traditionally ordered by the treating oncologist upon confirmation of an appropriate pathological diagnosis. The delay this introduces prolongs yet further what is already a complex, multi-stage, pre-treatment pathway and delays the start of first-line systemic treatment, which is crucially informed by the results of such analysis. Reflex testing, in which the responsibility for testing for an agreed range of biomarkers lies with the pathologist, has been shown to standardise and expedite the process. Twelve experts discussed the rationale and considerations for implementing reflex testing as standard clinical practice.

Clinical Outcomes Associated With Overestimation Of Oxygen Saturation By Pulse Oximetry In Patients Hospitalized With Covid-19, Ashraf Fawzy, Tianshi David Wu, Kunbo Wang, Kenneth E Sands, Arielle M Fisher, Shanna A Arnold Egloff, Jeffrey D Dellavolpe, Theodore J Iwashyna, Yanxun Xu, Brian T Garibaldi

Faculty, Staff and Students Publications

IMPORTANCE: Many pulse oximeters have been shown to overestimate oxygen saturation in persons of color, and this phenomenon has potential clinical implications. The relationship between overestimation of oxygen saturation with timing of COVID-19 medication delivery and clinical outcomes remains unknown.

OBJECTIVE: To investigate the association between overestimation of oxygen saturation by pulse oximetry and delay in administration of COVID-19 therapy, hospital length of stay, risk of hospital readmission, and in-hospital mortality.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study included patients hospitalized for COVID-19 at 186 acute care facilities in the US with at least 1 functional arterial oxygen saturation (SaO2) …

Blunted Adaptive Immune Responses And Acute Exacerbations Of Copd: Breaking The Code, Ken R Bracke, Francesca Polverino

Faculty, Staff and Students Publications

No abstract provided.

Leveraging Omics To Predict Chronic Obstructive Pulmonary Disease Exacerbations: The "Immunome", Francesca Polverino, Ravi Kalhan

Faculty, Staff and Students Publications

No abstract provided.

Disparities In Antifibrotic Medication Utilization Among Veterans With Idiopathic Pulmonary Fibrosis, Bhavika Kaul, Joyce S Lee, Laura A Petersen, Charles Mcculloch, Ivan O Rosas, Venkata D Bandi, Ning Zhang, Alison M Dedent, Harold R Collard, Mary A Whooley

Faculty, Staff and Students Publications

BACKGROUND: Two antifibrotic medications, pirfenidone and nintedanib, are approved for the treatment of idiopathic pulmonary fibrosis (IPF). Little is known about their real-world adoption.

RESEARCH QUESTION: What are the real-world antifibrotic utilization rates and factors associated with uptake among a national cohort of veterans with IPF?

STUDY DESIGN AND METHODS: This study identified veterans with IPF who received care either provided by the Veterans Affairs (VA) Healthcare System or non-VA care paid for by the VA. Patients who had filled at least one antifibrotic prescription through the VA pharmacy or Medicare Part D between October 15, 2014, and December 31, …