Pulmonology Commons^™

Randomized, Double-Blinded, Placebo-Controlled Trial Of Allogeneic Cord Blood T-Regulatory Cells For Treatment Of Covid-19 Ards, Douglas E Gladstone, Franco D'Alessio, Christopher Howard, Mi-Ae Lyu, Jason R Mock, Kevin W Gibbs, Darryl Abrams, Meixian Huang, Ke Zeng, James P Herlihy, Sergio T Castillo, Roland Bassett, Tara Sadeghi, Simrit Parmar, Christopher R Flowers, Siddhartha Mukherjee, David Schoenfeld, Peter F Thall, Arthur S Slutsky

Faculty, Staff and Students Publications

No abstract provided.

Professionalism And Moral Injury In A Capitalist Healthcare System, James Peter Meza Md, Phd, Kassem Soufan Md, Michael Francis Do, Abbass Berjaoui Md

Clinical Research in Practice: The Journal of Team Hippocrates

Professionalism cautions against profit while capitalism exists for profit. This case is a structural analysis of capitalism in a clinical setting that reveals physicians to be simultaneously wage laborers and professionals. Capitalism generates profit. Professionalism views profit as a conflict of interest that erodes trust in the doctor-patient relationship. Managing these conflicting values causes moral injury for physicians, which is a driver of physician burnout.

Calculating Differences In Surrogate Lung Perfusion Measurements Between Smokers And Nonsmokers As A Biomarker To Assess Their Potentials For Developing Chronic Obstructive Pulmonary Disease, A Prakash, A Nowacki, Y K. Liu, J Cisneros-Paz, Girish Nair, E Castillo

Conference Presentation Abstracts

Purpose: COPD (chronic obstructive pulmonary disease) is a collection of lung diseases that complicates breathing and causes irreversible lung damage. Given that it is a progressive disease, early detection is crucial for managing its symptoms. We recently developed a method for calculating pulmonary blood mass change (PBMC) apparent on paired inhale/exhale non-contrast computed tomography (CT) scans as a quantitative surrogate for lung perfusion. Our long term objective is to develop a PBMC biomarker for predicting COPD progression. As a first step, we hypothesize that PBMC is significantly lower for non-COPD smokers versus non-COPD non-smokers. Methods: CT scans from 77 healthy …

Plasma Extracellular Vesicle Proteins As Promising Noninvasive Biomarkers For Diagnosis Of Idiopathic Pulmonary Fibrosis, Raju S R Adduri, Kai Cai, Karen Velasco-Alzate, Ravikiran Vasireddy, Jeffrey W Miller, Sergio Poli De Frías, Fernando Poli De Frías, Yasushi Horimasu, Hiroshi Iwamoto, Noboru Hattori, Yingze Zhang, Kevin F Gibson, Anoop K Pal, Zhe Chen, Daniela Nicastro, Li Li, Sujith Cherian, Lynette M Sholl, Sreerama Shetty, Harrison Ndetan, Anthony H Maeda, Maria A Planchart Ferretto, Gary M Hunninghake, David A Schwartz, Daniel J Kass, Ivan O Rosas, Nagarjun V Konduru

Faculty, Staff and Students Publications

High-resolution computed tomography (HRCT) imaging is critical for diagnostic evaluation of Idiopathic Pulmonary Fibrosis (IPF). However, several other interstitial lung diseases (ILDs) often exhibit radiologic pattern similar to IPF on HRCT making the diagnosis of the disease difficult. Therefore, biomarkers that distinguish IPF from other ILDs can be a valuable aid in diagnosis. Using mass spectrometry, we performed proteomic analysis of plasma extracellular vesicles (EVs) in patients diagnosed with IPF, chronic hypersensitivity pneumonitis, nonspecific interstitial pneumonitis, and healthy subjects. A five-protein signature was identified by lasso regression and was validated in an independent cohort using ELISA. The five-protein signature derived …

High-Resolution Transcriptomic And Epigenetic Profiling Identifies Novel Regulators Of Copd, Uwe Schwartz, Maria Llamazares Prada, Stephanie T Pohl, Mandy Richter, Raluca Tamas, Michael Schuler, Corinna Keller, Vedrana Mijosek, Thomas Muley, Marc A Schneider, Karsten Quast, Joschka Hey, Claus P Heußel, Arne Warth, Hauke Winter, Özdemirhan Serçin, Harry Karmouty-Quintana, Soma Sk Jyothula, Manish K Patel, Felix Herth, Ina Koch, Giuseppe Petrosino, Alexandru Titimeaua, Balca R Mardin, Dieter Weichenhan, Tomasz P Jurkowski, Charles D Imbusch, Benedikt Brors, Vladimir Benes, Birgit Jung, David Wyatt, Heiko F Stahl, Christoph Plass, Renata Z Jurkowska

Faculty, Staff and Student Publications

Patients with chronic obstructive pulmonary disease (COPD) are still waiting for curative treatments. Considering its environmental cause, we hypothesized that COPD will be associated with altered epigenetic signaling in lung cells. We generated genome-wide DNA methylation maps at single CpG resolution of primary human lung fibroblasts (HLFs) across COPD stages. We show that the epigenetic landscape is changed early in COPD, with DNA methylation changes occurring predominantly in regulatory regions. RNA sequencing of matched fibroblasts demonstrated dysregulation of genes involved in proliferation, DNA repair, and extracellular matrix organization. Data integration identified 110 candidate regulators of disease phenotypes that were linked …

Quantifying Disease Progression In Copd Patients By Forecasting Pft Scores Using Extracted Features From Non-Contrast Ct, A T. Luong, C J. Herrera, E Young, Y K. Liu, A Nowacki, J Cisneros-Paz, Girish Nair, E Castillo

Conference Presentation Abstracts

Purpose: Currently there is no validated method for quantifying risk of disease progression in chronic obstructive pulmonary disease (COPD). We aim to address this by predicting whether a patient will worsen using a machine learning model trained on basic patient information, current pulmonary function values, FEV1 and FVC, and extracted features from a non-contrast CT scan. Disease severity is characterized by these pulmonary function values, and by extension disease progression can be determined by the change in these values between future timepoints. Methods: XGBoost, a popular classification library that utilizes gradient boosted trees, was used to define an ensemble model …

Quantifying Disease Progression In Copd Patients By Forecasting Pft Scores Using Extracted Features From Non-Contrast Ct, A T. Luong, C J. Herrera, E Young, Y K. Liu, A Nowacki, J Cisneros-Paz, Girish Nair, E Castillo

Conference Presentation Abstracts

Purpose: Currently there is no validated method for quantifying risk of disease progression in chronic obstructive pulmonary disease (COPD). We aim to address this by predicting whether a patient will worsen using a machine learning model trained on basic patient information, current pulmonary function values, FEV1 and FVC, and extracted features from a non-contrast CT scan. Disease severity is characterized by these pulmonary function values, and by extension disease progression can be determined by the change in these values between future timepoints. Methods: XGBoost, a popular classification library that utilizes gradient boosted trees, was used to define an ensemble model …

Prognostic Value Of Severe Acute Respiratory Syndrome Coronavirus-2 Viral Load And Antibodies In Patients Hospitalized With Covid-19, Rebecca N Bauer, Anastasia Teterina, Haridha Shivram, Jacqueline Mcbride, Carrie M Rosenberger, Fang Cai, Min Bao, Larry Tsai, Oliver Gordon, Ivan T Lee, Jeffrey J Wallin, Danielle Porter, Kavita Juneja, Gregory Camus, Ivan O Rosas, Steffen Wildum

Faculty, Staff and Students Publications

Observational studies have identified the potential prognostic value for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) viral load and anti-SARS-CoV-2 antibodies in coronavirus disease 2019 (COVID-19). However, viral load in nasopharyngeal (NP) swabs produced inconsistent results in prognostic analyses, and the prognostic value of viral load or antibodies has not been confirmed in large clinical trials. COVACTA and REMDACTA were double-blind, randomized, controlled trials with a combined enrollment of 1078 patients hospitalized with COVID-19 treated with tocilizumab or placebo in COVACTA or tocilizumab plus remdesivir or placebo plus remdesivir in REMDACTA. We assessed the potential prognostic value of NP and serum …

Evaluating The Accuracy And Quality Of The Information On Pulmonary Rehabilitation Videos Shared On Youtube Amidst The Covid-19 Pandemic, Payaum Fotovat-Ahmadi, Bilal M. Ali, Bhavinkumar Dalal

Posters

YouTube is a visual library that is growing at incredible pace, especially with the rise of COVID-19 pandemic. Pulmonary rehabilitation refers to the rehabilitation treatment of patients with chronic pulmonary diseases. YouTube has made it possible to practice remote rehabilitation, the effectiveness of which have been proven non-inferior to traditional approaches.

Impact Of Structured Reporting Template On The Quality Of Hrct Radiology Reports For Interstitial Lung Disease, Han G. Ngo, Girish B. Nair, Sayf Al-Katib

Posters

This QI study compared the completeness of HRCT radiology reports before and after the implementation of a disease-specific structured reporting template for suspected cases of interstitial lung disease (ILD).

Evaluation Of Phenobarbital In The Treatment Of Alcohol Withdrawal In The Intensive Care Unit, Sienna J. Ringgenberg, Vishal K. Patel

Posters

Alcohol withdrawal syndrome (AWS) is typically managed using the Clinical Institute Withdrawal Assessment (CIWA) protocol which includes benzodiazepines, supportive care, and close clinical monitoring. Alternatives to benzodiazepines such as phenobarbital provide several advantages including less frequent dosing, longer tapering off of doses, and additional glutamate inhibition. The purpose of this study is to evaluate the effectiveness and potential benefit to using phenobarbital in addition to CIWA protocol in the treatment of AWS at Beaumont, Royal Oak.

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.

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

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 …

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 …

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 …

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

Faculty, Staff and Students Publications

No abstract provided.

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 …

Electrical Stimulation To Regain Lower Extremity Muscle Perfusion And Endurance In Patients With Post-Acute Sequelae Of Sars Cov-2: A Randomized Controlled Trial, Alejandro Zulbaran-Rojas, Myeounggon Lee, Rasha O Bara, Areli Flores-Camargo, Gil Spitz, M G Finco, Amir Behzad Bagheri, Dipaben Modi, Fidaa Shaib, Bijan Najafi

Faculty, Staff and Students Publications

Muscle deconditioning and impaired vascular function in the lower extremities (LE) are among the long‐term symptoms experienced by COVID‐19 patients with a history of severe illness. These symptoms are part of the post‐acute sequelae of Sars‐CoV‐2 (PASC) and currently lack evidence‐based treatment. To investigate the efficacy of lower extremity electrical stimulation (E‐Stim) in addressing PASC‐related muscle deconditioning, we conducted a double‐blinded randomized controlled trial. Eighteen (n = 18) patients with LE muscle deconditioning were randomly assigned to either the intervention (IG) or the control (CG) group, resulting in 36 LE being assessed. Both groups received daily 1 h E‐Stim …

Asthma And Cardiovascular Disease: A Bidirectional Association?, Muhammad Adrish, Nicola A Hanania

Faculty, Staff and Students Publications

No abstract provided.

Association Of Glucose-6-Phosphate Dehydrogenase Deficiency With Outcomes In Us Veterans With Covid-19, Sarah H Elsea, Javad Razjouyan, Kyung Min Lee, Julie A Lynch, Sharyl Martini, Lavannya M Pandit

Faculty, Staff and Students Publications

IMPORTANCE: The underlying biological risk factors for severe outcome due to SAR-CoV-2 infection are not well defined.

OBJECTIVE: To determine the association between glucose-6-phosphate dehydrogenase (G6PD) deficiency and severity of COVID-19.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study included analysis of 24 700 veterans with G6PD enzyme testing prior to January 1, 2020, obtained through the US Veterans Health Administration national databases. These veterans were cross-referenced with the Veterans Administration COVID-19 Shared Data Resource for SARS-CoV-2 testing from February 15, 2020, to January 1, 2021. The final study population consisted of 4811 veterans who tested positive for SARS-CoV-2. Statistical …

Mortality Patterns Associated With Central Sleep Apnea Among Veterans: A Large, Retrospective, Longitudinal Report, Ritwick Agrawal, Amir Sharafkhaneh, Daniel J Gottlieb, Sara Nowakowski, Javad Razjouyan

Faculty, Staff and Students Publications

Rationale

Central sleep apnea (CSA) is associated with high mortality. Current knowledge stems from studies with limited sample size (fewer than 100 subjects) and in homogeneous populations such as heart failure (HF).

Objectives

To address this knowledge gap, we compared the mortality pattern and time to death between the CSA and obstructive sleep apnea (OSA) patients in the large Veterans Health Administration patient population using the big data analytic approach.

Methods

This is a retrospective study using national Veterans Health Administration electronic medical records from October 1, 1999, through September 30, 2020. We grouped the patients with underlying sleep disorders …

Inflammatory Biomarkers Differ Among Hospitalized Veterans Infected With Alpha, Delta, And Omicron Sars-Cov-2 Variants, Catherine Park, Shahriar Tavakoli-Tabasi, Amir Sharafkhaneh, Benjamin J Seligman, Bret Hicken, Christopher I Amos, Andrew Chou, Javad Razjouyan

Faculty, Staff and Students Publications

Mortality due to COVID-19 has been correlated with laboratory markers of inflammation, such as C-reactive protein (CRP). The lower mortality during Omicron variant infections could be explained by variant-specific immune responses or host factors, such as vaccination status. We hypothesized that infections due to Omicron variant cause less inflammation compared to Alpha and Delta, correlating with lower mortality. This was a retrospective cohort study of veterans hospitalized for COVID-19 at the Veterans Health Administration. We compared inflammatory markers among patients hospitalized during Omicron infection with those of Alpha and Delta. We reported the adjusted odds ratio (aOR) of the first …

Pulse Oximetry: Why Oxygen Saturation Is Still Not A Part Of Standard Pediatric Guidelines In Low-And-Middle-Income Countries (Lmics), Maheen Sheikh, Huzaifa Ahmad, Romesa Ibrahim, Muhammad Imran Nisar, Fyezah Jehan

Department of Paediatrics and Child Health

Background: With the high frequency of acute respiratory infections in children worldwide, particularly so in low-resource countries, the development of effective diagnostic support is crucial. While pulse oximetry has been found to be an acceptable method of hypoxemia detection, improving clinical decision making and efficient referral, many healthcare set ups in low- and middle-income countries have not been able to implement pulse oximetry into their practice.
Main body: A review of past pulse oximetry implementation attempts in low- and middle-income countries proposes the barriers and potential solutions for complete integration in the healthcare systems. The addition of pulse oximetry into …

Dynamic Errors In Pulse Oximetry Preclude Use Of Correction Factor, Ashraf Fawzy, Valeria S M Valbuena, Christopher F Chesley, Tianshi David Wu, Theodore J Iwashyna

Faculty, Staff and Students Publications

No abstract provided.

Recurrent Cyanotic Spells In An Octogenarian, Chin Tong Kwok, Chun Kit Wong

Journal of the Hong Kong College of Cardiology

We report rare case of an octogenarian who, after years of diagnostic delay, was found to have a patent foramen ovale, and due to an ascending aortic aneurysm that anatomically facilitated right-to-left shunt, presenting with life-threatening cyanotic attacks. The characteristic orthodeoxia-platypnea syndrome and high alveolar arterial gradient hint to the diagnosis. She was eventually treated successfully with urgent percutaneous PFO closure. Routine ordering of a transthoracic echocardiogram, without agitated saline injection under provocation maneuvers, may not be sufficient to rule out shunts.

Diagnosis Of Amyotrophic Lateral Sclerosis By Respiratory Function Test, Francesca Polverino, Simone Sampaolo, Antonio Capuozzo, Marco Fasolino, Michele Aliberti, Ersilia Satta, Carlo Santoriello, Mario Polverino

Faculty, Staff and Students Publications

The diagnostic criterion for amyotrophic lateral sclerosis (ALS) based on the findings of concomitant clinical and electrophysiological evidence of upper and lower motor neuron involvement may remain unsatisfied for months and in some patients, even for years in the early stage of the disease. Since respiratory involvement is an onset symptom of ALS in only 1-3% of patients, pulmonary assessment has never been considered useful in the early diagnosis of ALS. However, studies on pulmonary function are lacking, especially in those early stages where neurologic tests are also inconclusive. In contrast to the scarcity of data in the early stages, …

Progressive Interstitial Lung Disease In Relatives Of Patients With Pulmonary Fibrosis, Jonathan A Rose, Maria A Planchart Ferretto, Anthony H Maeda, Maria F Perez Garcia, Nikkola E Carmichael, Swati Gulati, Mary B Rice, Hilary J Goldberg, Rachel K Putman, Hiroto Hatabu, Benjamin A Raby, Ivan O Rosas, Gary M Hunninghake

Faculty, Staff and Students Publications

No abstract provided.

Peptidylarginine Deiminase 2 Citrullinates Mzb1 And Promotes The Secretion Of Igm And Iga, Benjamin Geary, Bo Sun, Ronak R Tilvawala, Leonard Barasa, Konstantin Tsoyi, Ivan O Rosas, Paul R Thompson, I-Cheng Ho

Faculty, Staff and Students Publications

INTRODUCTION: MZB1 is an endoplasmic reticulum residential protein preferentially expressed in plasma cells, marginal zone and B1 B cells. Recent studies on murine B cells show that it interacts with the tail piece of IgM and IgA heavy chain and promotes the secretion of these two classes of immunoglobulin. However, its role in primary human B cells has yet to be determined and how its function is regulated is still unknown. The conversion of peptidylarginine to peptidylcitrulline, also known as citrullination, by peptidylarginine deiminases (PADs) can critically influence the function of proteins in immune cells, such as neutrophils and T …

Distinct Temporal Trajectories And Risk Factors For Post-Acute Sequelae Of Sars-Cov-2 Infection, Chen Chen, Sairam Parthasarathy, Jacqueline M Leung, Michelle J Wu, Katherine A Drake, Vanessa K Ridaura, Howard C Zisser, William A Conrad, Victor F Tapson, James N Moy, Christopher R Defilippi, Ivan O Rosas, Bellur S Prabhakar, Mujeeb Basit, Mirella Salvatore, Jerry A Krishnan, Charles C Kim

Faculty, Staff and Students Publications

BACKGROUND: The understanding of Post-acute sequelae of SARS-CoV-2 infection (PASC) can be improved by longitudinal assessment of symptoms encompassing the acute illness period. To gain insight into the various disease trajectories of PASC, we assessed symptom evolution and clinical factors associated with the development of PASC over 3 months, starting with the acute illness period.

METHODS: We conducted a prospective cohort study to identify parameters associated with PASC. We performed cluster and case control analyses of clinical data, including symptomatology collected over 3 months following infection.

RESULTS: We identified three phenotypic clusters associated with PASC that could be characterized as …