Critical Care Commons^™

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.

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) …

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.

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 …

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 …

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 …

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 …

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

Faculty, Staff and Students Publications

No abstract provided.

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 …

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 …

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 …

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 …

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.

Innate Immune Cell Dysfunction And Systemic Inflammation In Children With Chronic Liver Diseases Undergoing Transplantation, Krupa R Mysore, Sunil Kannanganat, Jeremy M Schraw, Philip J Lupo, John A Goss, Kenneth D R Setchell, Farrah Kheradmand, Xian C Li, Benjamin L Shneider

Faculty, Staff and Students Publications

Advanced liver diseases (ALD) can affect immune function and compromise host defense against infections. In this study, we examined the phenotypic and functional alterations in circulating monocyte and dendritic cells (DCs) in children with ALD undergoing liver transplantation (LT). Children were stratified into 2 clusters, C1 (mild) and C2 (severe), on the basis of laboratory parameters of ALD and compared with healthy pediatric controls. Children in C2 had a significant reduction in frequencies of nonclassical monocytes and myeloid DCs. Children in C2 displayed monocyte and DC dysfunction, characterized by lower human leucocyte antigen DR expression and reduced interleukin 12 production, …

Clinical Efficacy Among Patients With Chronic Rhinosinusitis With Nasal Polyps And Clinical Features Of Obstructive Lung Disease: Post Hoc Analysis Of The Phase Iii Sinus-24 And Sinus-52 Studies, Jorge F Maspero, Claus Bachert, Fernando J Martinez, Nicola A Hanania, Benjamin Ortiz, Naimish Patel, Leda P Mannent, Amy Praestgaard, Nami Pandit-Abid, Shahid Siddiqui, Megan Hardin

Faculty, Staff and Students Publications

PURPOSE: To provide a descriptive summary of clinical efficacy and health-related quality of life (HRQoL) measures in patients with chronic rhinosinusitis with nasal polyps (CRSwNP) and clinical features of obstructive lung disease in the Phase III dupilumab studies SINUS-24 and SINUS-52 (NCT02912468, NCT02898454).

PATIENTS AND METHODS: Patients met a "broad" definition of having clinical features of obstructive lung disease with any of 3 criteria: (i) pre-bronchodilator forced expiratory volume in 1 second (FEV

RESULTS: Across both studies, 131 patients met the "broad" definition, of whom 90 also had asthma, and 115 patients met the "narrow" definition, of whom 74 had …

Lower Respiratory Illnesses In Childhood Are Associated With The Presence Of Air Trapping In Early Adulthood, Francesca Polverino, Debra A Stern, Eric M Snyder, Courtney Wheatley-Guy, Surya P Bhatt, Fernando D Martinez, Stefano Guerra, Wayne J Morgan

Faculty, Staff and Students Publications

Several factors occurring in early life, including lower respiratory tract illnesses (LRIs), are involved in determining lung structure and function in adulthood, but the effects of these factors on lung development remain largely unknown. Hereby, we evaluated the parameters from computed tomography (CT) scans performed at the age of 26 years in 39 subjects from the birth cohort of the Tucson Children's Respiratory Study (TCRS) in order to determine the relationship between early childhood factors and lung structural changes in young adult life. We found that participants with LRIs in childhood had increased air trapping at the age of 26 …

Corrigendum: Alveolar Macrophages In Lung Cancer: Opportunities And Challenges, Cheng-Yen Chang, Dominique Armstrong, David B Corry, Farrah Kheradmand

Faculty, Staff and Students Publications

In the published article, there was an error in the article title. Instead of “Alveolar Macrophages in Lung Cancer: Opportunities Challenges”, it should be “Alveolar Macrophages in Lung Cancer: Opportunities and Challenges”.

The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated.

Respiratory Function Changes As Early Signs Of Amyotrophic Lateral Sclerosis, Mario Polverino, Simone Sampaolo, Antonio Capuozzo, Marco Fasolino, Michele Aliberti, Ersilia Satta, Carlo Santoriello, James Peter Orengo, Francesca Polverino

Faculty, Staff and Students Publications

BACKGROUND: The current diagnostic criteria for amyotrophic lateral sclerosis (ALS) may remain unsatisfactory for months or years in the early disease. Pulmonary assessment has never been considered useful in the early diagnosis of ALS, and studies of pulmonary function in this patient category are lacking.

OBJECTIVES: The objective of this study was to assess the pulmonary function in subjects with unspecific symptoms of ALS in whom an ALS diagnosis cannot be reached based on the current available guidelines.

METHODS: We performed pulmonary function tests, arterial gas analysis, maximal inspiratory (MIP) and expiratory (MEP) pressure, and respiratory drive (P0.1) assessment in …

Cc16 Drives Vla-2-Dependent Splunc1 Expression, Natalie Iannuzo, Holly Welfley, Nicholas C Li, Michael D L Johnson, Joselyn Rojas-Quintero, Francesca Polverino, Stefano Guerra, Xingnan Li, Darren A Cusanovich, Paul R Langlais, Julie G Ledford

Faculty, Staff and Students Publications

RATIONALE: CC16 (Club Cell Secretory Protein) is a protein produced by club cells and other non-ciliated epithelial cells within the lungs. CC16 has been shown to protect against the development of obstructive lung diseases and attenuate pulmonary pathogen burden. Despite recent advances in understanding CC16 effects in circulation, the biological mechanisms of CC16 in pulmonary epithelial responses have not been elucidated.

OBJECTIVES: We sought to determine if CC16 deficiency impairs epithelial-driven host responses and identify novel receptors expressed within the pulmonary epithelium through which CC16 imparts activity.

METHODS: We utilized mass spectrometry and quantitative proteomics to investigate how CC16 deficiency …

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 …

Lymphangioleiomyomatosis: Circulating Levels Of Fgf23 And Pulmonary Diffusion, Anthony J Esposito, Jewel Imani, Shikshya Shrestha, Shefali Bagwe, Anthony M Lamattina, Marina Vivero, Hilary J Goldberg, Ivan O Rosas, Elizabeth P Henske, Souheil Y El-Chemaly

Faculty, Staff and Students Publications

OBJECTIVE: Lymphangioleiomyomatosis (LAM) is a rare, destructive disease of the lungs with a limited number of determinants of disease activity, which are a critical need for clinical trials. FGF23 has been implicated in several chronic pulmonary diseases. We aimed to determine the association between serum FGF23 levels and pulmonary function in a cohort of patients with LAM.

METHODS: This was a descriptive single-center study in which subjects with LAM and controls with unreported lung disease were recruited. Serum FGF23 levels were measured in all subjects. Clinical data, including pulmonary function testing, were retrospectively obtained from electronic medical records of LAM …