Pulmonology Commons^™

Defining The Genetic Landscape Of Idiopathic Pulmonary Fibrosis: Role Of Common And Rare Variants, Benjamin J Moss, Ivan O Rosas

Faculty, Staff and Students Publications

No abstract provided.

Obstructive Sleep Apnea Modulates Clinical Outcomes Post-Acute Myocardial Infarction: A Large Longitudinal Veterans’ Dataset Report, Ritwick Agrawal, Amir Sharafkhaneh, Vijay Nambi, Ahmed Bahammam, Javad Razjouyan

Faculty, Staff and Students Publications

BACKGROUND: While the longer-term Obstructive Sleep apnea (OSA)-related intermittent hypoxia (IH) leads to various comorbidities, it has become increasingly evident that OSA confers protective advantages during and after acute myocardial infarction (AMI). We hypothesized in patients who were admitted with acute MI, the presence of OSA is associated with lower in-hospital mortality compared to those without a prior diagnosis of OSA.

METHODS: In this nationwide retrospective study utilizing Veterans Health Administration records, we included patients hospitalized for MI with a history of sleep disorders from 1999 to 2020. We divided patients into two cohorts: those with OSA and those without …

Genetic Susceptibility To Chronic Obstructive Pulmonary Disease And Idiopathic Pulmonary Fibrosis: The Missing Link?, Francesca Polverino

Faculty, Staff and Students Publications

No abstract provided.

Cloning A Profibrotic Stem Cell Variant In Idiopathic Pulmonary Fibrosis, Shan Wang, Wei Rao, Ashley Hoffman, Jennifer Lin, Justin Li, Tao Lin, Audrey-Ann Liew, Matthew Vincent, Tinne C J Mertens, Harry Karmouty-Quintana, Christopher P Crum, Mark L Metersky, David A Schwartz, Peter J A Davies, Clifford Stephan, Soma S K Jyothula, Ajay Sheshadri, Erik Eddie Suarez, Howard J Huang, John F Engelhardt, Burton F Dickey, Kalpaj R Parekh, Frank D Mckeon, Wa Xian

Faculty, Staff and Student Publications

Idiopathic pulmonary fibrosis (IPF) is a progressive, irreversible, and rapidly fatal interstitial lung disease marked by the replacement of lung alveoli with dense fibrotic matrices. Although the mechanisms initiating IPF remain unclear, rare and common alleles of genes expressed in lung epithelia, combined with aging, contribute to the risk for this condition. Consistently, single-cell RNA sequencing (scRNA-seq) studies have identified lung basal cell heterogeneity in IPF that might be pathogenic. We used single-cell cloning technologies to generate "libraries" of basal stem cells from the distal lungs of 16 patients with IPF and 10 controls. We identified a major stem cell …

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

Faculty, Staff and Student Publications

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

Update On The Role Of Feno In Asthma Management, Neveda Murugesan, Damini Saxena, Arundhati Dileep, Muhammad Adrish, Nicola A Hanania

Faculty, Staff and Students Publications

Asthma is a heterogenous disorder characterized by presence of different phenotypes and endotypes. Up to 10% of the individuals suffer from severe asthma and are at increased risk of morbidity and mortality. Fractional exhaled nitric oxide (FeNO) is a cost-effective, point of care biomarker that is used to detect type 2 airway inflammation. Guidelines have proposed to measure FeNO as an adjunct to diagnostic evaluation in individuals with suspected asthma and to monitor airway inflammation. FeNO has lower sensitivity, suggesting that it may not be a good biomarker to rule out asthma. FeNO may also be used to predict response …

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

Faculty, Staff and Student Publications

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

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

Faculty, Staff and Student Publications

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

Emt-Activated Secretory And Endocytic Vesicular Trafficking Programs Underlie A Vulnerability To Pi4k2a Antagonism In Lung Cancer, Xiaochao Tan, Guan-Yu Xiao, Shike Wang, Lei Shi, Yanbin Zhao, Xin Liu, Jiang Yu, William K Russell, Chad J Creighton, Jonathan M Kurie

Faculty, Staff and Students Publications

Hypersecretory malignant cells underlie therapeutic resistance, metastasis, and poor clinical outcomes. However, the molecular basis for malignant hypersecretion remains obscure. Here, we showed that epithelial-mesenchymal transition (EMT) initiates exocytic and endocytic vesicular trafficking programs in lung cancer. The EMT-activating transcription factor zinc finger E-box-binding homeobox 1 (ZEB1) executed a PI4KIIIβ-to-PI4KIIα (PI4K2A) dependency switch that drove PI4P synthesis in the Golgi and endosomes. EMT enhanced the vulnerability of lung cancer cells to PI4K2A small-molecule antagonists. PI4K2A formed a MYOIIA-containing protein complex that facilitated secretory vesicle biogenesis in the Golgi, thereby establishing a hypersecretory state involving osteopontin (SPP1) and other prometastatic ligands. …

Preventable Tacrolimus Toxicity, Brooke Parker, Jessica Sterner, John Mele, Laura Dewald, Cassidy Johnston

Articles, Abstracts, and Reports

No abstract provided.

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

Faculty, Staff and Student Publications

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

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

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

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 …

Lung Volume Reduction In Copd: Scope Or Surgery, Francesca Polverino, Frank Sciurba

Faculty, Staff and Students Publications

No abstract provided.

Community-Based Approach To Assess Obstructive Respiratory Diseases And Risk In Urban African American Churches, Lorriane A Odhiambo, Ezinne Anaba, Peggy C Stephens, Vinay K Cheruvu, Melissa D Zullo

Faculty, Staff and Student Publications

Asthma, and chronic obstructive pulmonary disease (COPD) are significant health problems that have disparate effects on many Americans. Misdiagnosis and underdiagnosis are common and lead to ineffective treatment and management. This study assessed the feasibility of applying a two-step case-finding technique to identify both COPD and adult asthma cases in urban African American churches. We established a community-based partnership, administered a cross-sectional survey in step one of the case-finding technique and performed spirometry testing in step two. A total of 219 surveys were completed. Provider-diagnosed asthma and COPD were reported in 26% (50/193) and 9.6% (18/187) of the sample. Probable …

The Indirect Influence Of ‘Invisible’ Support On Pulmonary Function Among Adults With Chronic Obstructive Pulmonary Disease, Aliza A Panjwani, Joel Erblich, Tracey A Revenson, Hoda J Badr, Alex D Federman, Juan P Wisnivesky

Faculty, Staff and Students Publications

Individuals living with chronic obstructive pulmonary disease (COPD) often require support from family or friends. We examined whether invisible support - support that is provided but goes unnoticed - is related to pulmonary function, and whether this association is mediated by depressive symptoms and illness perceptions. Sixty-six dyads of individuals with COPD and their informal caregivers reported on receipt and provision of support, respectively. Those with COPD completed measures of depressive symptoms, illness perceptions and pulmonary function. Although invisible support was not directly related to pulmonary function, mediation analyses revealed a combined indirect effect through lower depressive symptoms and less …

Giant Cell Arteritis In An Elderly Female With Pulmonary Tuberculosis, Ashwin Parchani, Ashish Baweja, Harnoor Singh, Yatharth Malik, Vinod Gupta, Minakshi Dhar, Monika Pathania

Faculty, Staff and Student Publications

Giant cell arteritis (GCA) is a type of systemic vasculitis that primarily affects people over the age of 50 and affects the medium to large arteries. GCA's clinical manifestations can be varied and non-specific, similar to those observed in atherosclerosis. Here, the authors present a case of an elderly woman with pulmonary tuberculosis with GCA masquerading as atherosclerosis.

Cardiopulmonary Outcomes In Covid-19 Patients Discharged From A Tertiary Care Center: A Prospective Study, Lakshmi Prasanna Vaishnavi Kattamuri, Vibhav Sharma, Radhika Sarda, Kunal Sharma, Anuj Ajayababu, Gaurav Gupta, Surabhi Vyas, Shivam Pandey, Arvind Kumar, Naveet Wig, Rajiv Narang, Sanjeev Sinha

Faculty, Staff and Student Publications

To determine the cardiopulmonary changes in the survivors of acute COVID-19 infection at 3-6 month and 6-12 month. We followed up 53 patients out of which 28 (52%) had mild COVID-19 and 25 (48%) had severe COVID-19. The first follow-up was between 3 month after diagnosis up to 6 month and second follow-up between 6 and 12 month from the date of diagnosis of acute COVID-19. They were monitored using vital parameters, pulmonary function tests, echocardiography and a chest computed tomography (CT) scan. We found improvement in diffusing capacity for carbon monoxide (DLCO) with a median of 52% of predicted …

Cc16 Augmentation Reduces Exaggerated Copd-Like Disease In Cc16-Deficient Mice, Joselyn Rojas-Quintero, Maria Eugenia Laucho-Contreras, Xiaoyun Wang, Quynh-Anh Fucci, Patrick R Burkett, Se-Jin Kim, Duo Zhang, Yohannes Tesfaigzi, Yuhong Li, Abhiram R Bhashyam, Zhang Li, Haider Khamas, Bartolome Celli, Aprile L Pilon, Francesca Polverino, Caroline A Owen

Faculty, Staff and Students Publications

Low Club Cell 16 kDa protein (CC16) plasma levels are linked to accelerated lung function decline in patients with chronic obstructive pulmonary disease (COPD). Cigarette smoke-exposed (CS-exposed) Cc16-/- mice have exaggerated COPD-like disease associated with increased NF-κB activation in their lungs. It is unclear whether CC16 augmentation can reverse exaggerated COPD in CS-exposed Cc16-/- mice and whether increased NF-κB activation contributes to the exaggerated COPD in CS-exposed Cc16-/- lungs. CS-exposed WT and Cc16-/- mice were treated with recombinant human CC16 (rhCC16) or an NF-κB inhibitor versus vehicle beginning at the midpoint of the exposures. COPD-like disease and NF-κB activation were …

Gender Disparities In The Diagnosis Of Sleep Disordered Breathing, Kenna Haile, Nesrine Ibrahim, Safwan Badr, Apala Vaishnav

Medical Student Research Symposium

Introduction: Current diagnostic guidelines for sleep disordered breathing (SDB) require that apneas and hypopneas be accompanied by a 4% desaturation for it to constitute a respiratory event (AHI-Accepted). However, the American Academy of Sleep Medicine recommends expanding the diagnostic criteria to include apneas and hypopneas accompanied by a 3% desaturation or a cortical arousal for diagnosis (AHI-Recommended). We hypothesized that a clinical sample of both men and women would demonstrate that women are more likely to be misdiagnosed using the accepted criteria compared to the recommended criteria.

Methods: The clinical sample consisted of all patients receiving a PSG at the …

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

Faculty, Staff and Student Publications

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

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