Sleep Medicine Commons^™

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.

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, …

Photoplethysmography-New Applications For An Old Technology: A Sleep Technology Review, Scott Ryals, Ambrose Chiang, Sharon Schutte-Rodin, Arvind Chandrakantan, Nitun Verma, Steven Holfinger, Fariha Abbasi-Feinberg, Anuja Bandyopadhyay, Kelly Baron, Sumit Bhargava, Ken He, Joseph Kern, Jennifer Miller, Ruchir Patel, Dulip Ratnasoma, Maryann C Deak

Faculty, Staff and Students Publications

Education is integral to the American Academy of Sleep Medicine (AASM) mission. The AASM Emerging Technology Committee identified an important and evolving piece of technology that is present in many of the consumer and clinical technologies that we review on the AASM #SleepTechnology (https://aasm.org/consumer-clinical-sleep-technology/) resource—photoplethysmography. As more patients with sleep tracking devices ask clinicians to view their data, it is important for sleep providers to have a general understanding of the technology, its sensors, how it works, targeted users, evidence for the claimed uses, and its strengths and weaknesses. The focus in this review is photoplethysmography—a sensor type …

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 …

Suspected Interstitial Lung Disease In Copdgene Study, Jonathan A Rose, Aravind A Menon, Takuya Hino, Akinori Hata, Mizuki Nishino, David A Lynch, Ivan O Rosas, Souheil El-Chemaly, Benjamin A Raby, Samuel Y Ash, Bina Choi, George R Washko, Edwin K Silverman, Michael H Cho, Hiroto Hatabu, Rachel K Putman, Gary M Hunninghake

Faculty, Staff and Students Publications

Rationale

Although interstitial lung abnormalities (ILA), specific patterns of incidentally-detected abnormal density on computed tomography, have been associated with abnormal lung function and increased mortality, it is unclear if a subset with incidental interstitial lung disease (ILD) accounts for these adverse consequences.

Objectives

To define the prevalence and risk factors of suspected ILD and assess outcomes.

Methods

Suspected ILD was evaluated in the COPDGene (Chronic Obstructive Pulmonary Disease Genetic Epidemiology) study, defined as ILA and at least one additional criterion: definite fibrosis on computed tomography, FVC less than 80% predicted, or DL_CO less than 70% predicted. Multivariable linear, longitudinal, …

A Rare Case Of Isolated Thoracic Al-Amyloidoma Causing Complete Atelectasis Of The Right Lung, Smruti Rath, Nicholas Joseph Dcunha, Neel Bhan, Bettye Cox, Muhammad Adrish

Faculty, Staff and Students Publications

Tumoral amyloidosis, or amyloidoma, is a benign, but rare form of amyloidosis that has been reported with a favorable prognosis following surgical resection in some case reports. We present a case of acute on chronic respiratory failure secondary to extensive growth of a thoracic amyloidoma causing atelectasis of the right lung. Our case patient had greater morbidity due to late presentation and extensive disease at diagnosis, precluding any surgical intervention. Radiation therapy and medical management were unsuccessful in reducing disease burden. Early diagnosis and detection are pivotal to improving survival in patients with isolated thoracic amyloidoma.

Quantitative Interstitial Abnormality Progression And Outcomes In The Genetic Epidemiology Of Copd And Pittsburgh Lung Screening Study Cohorts, Bina Choi, Najma Adan, Tracy J Doyle, Ruben San José Estépar, Rola Harmouche, Stephen M Humphries, Matthew Moll, Michael H Cho, Rachel K Putman, Gary M Hunninghake, Ravi Kalhan, Gabrielle Y Liu, Alejandro A Diaz, Stefanie E Mason, Farbod N Rahaghi, Carrie L Pistenmaa, Nicholas Enzer, Clare Poynton, Gonzalo Vegas Sánchez-Ferrero, James C Ross, David A Lynch, Fernando J Martinez, Meilan K Han, Russell P Bowler, David O Wilson, Ivan O Rosas, George R Washko, Raúl San José Estépar, Samuel Y Ash, Copdgene Study And Pittsburgh Lung Screening Study Investigators

Faculty, Staff and Students Publications

BACKGROUND: The risk factors and clinical outcomes of quantitative interstitial abnormality progression over time have not been characterized.

RESEARCH QUESTIONS: What are the associations of quantitative interstitial abnormality progression with lung function, exercise capacity, and mortality? What are the demographic and genetic risk factors for quantitative interstitial abnormality progression?

STUDY DESIGN AND METHODS: Quantitative interstitial abnormality progression between visits 1 and 2 was assessed from 4,635 participants in the Genetic Epidemiology of COPD (COPDGene) cohort and 1,307 participants in the Pittsburgh Lung Screening Study (PLuSS) cohort. We used multivariable linear regression to determine the risk factors for progression and the …

Trib3 Mediates Fibroblast Activation And Fibrosis Though Interaction With Atf4 In Ipf, Lan Wang, Wenyu Zhao, Cong Xia, Zhongzheng Li, Weiming Zhao, Kai Xu, Ningdan Wang, Hui Lian, Ivan O Rosas, Guoying Yu

Faculty, Staff and Students Publications

Idiopathic pulmonary fibrosis (IPF) is a fatal interstitial lung disease characterized by fibroblast activation, excessive deposition of extracellular matrix, and progressive scarring; the pathogenesis remains elusive. The present study explored the role of Tribbles pseudokinase 3 (TRIB3), a well-known stress and metabolic sensor, in IPF. TRIB3 is down-regulated in the lungs of IPF patients in comparison to control subjects. Deficiency of TRIB3 markedly inhibited A549 epithelial cells’ proliferation and migration, significantly reducing wound healing. Conversely, overexpression of TRIB3 promoted A549 cell proliferation and transmigration while it inhibited its apoptosis. Meanwhile, overexpressed TRIB3 inhibited fibroblast activation and decreased ECM …

A Narrative Review Of Sex And Gender Differences In Sleep Disordered Breathing: Gaps And Opportunities, Margaret Bublitz, Nour Adra, Leen Hijazi, Fidaa Shaib, Hrayr Attarian, Ghada Bourjeily

Faculty, Staff and Students Publications

Introduction: Sleep disordered breathing (SDB) is a common condition, associated with multiple comorbidities including cardiovascular and metabolic disease. It has been previously established that SDB is more prevalent in men than women, shifting the literature's focus away from the latter population. As such, underdiagnosis, and thus undertreatment, of SDB in women exists.

Methods: To establish the differences in prevalence, clinical presentation, and pathophysiology of SDB between the two sexes, a narrative review of the current literature was performed.

Results: Rates of SDB are higher among men, likely driven by differences in symptom presentation between men and women, with women presenting …

Understanding Post-Covid-19 Interstitial Lung Disease (Ild): A New Fibroinflammatory Disease Entity, Puja Mehta, Ivan O Rosas, Mervyn Singer

Faculty, Staff and Students Publications

Immunomodulation and immunity from vaccination and natural infection have reduced mortality from coronavirus disease 2019 (COVID-19). However, there are ongoing concerns regarding emerging variants and residual pulmonary sequelae in survivors, given that the lungs are the principal site for the triumvirate of infection, inflammation and injury. The initial waves of acute, severe COVID-19 were profoundly inflammatory, usually manifest as organising pneumonia ± acute respiratory distress syndrome (ARDS). The extent of the fibrogenic potential of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and the modifiability of the pathogenic processes and disease course are unclear. Interestingly patients can develop ‘post-COVID interstitial lung disease’ …

Development Of A Novel Mouse Model Of Menopause-Associated Asthma, William P Pederson, Laurie M Ellerman, Estevan C Sandoval, Scott Boitano, Jennifer B Frye, Kristian P Doyle, Heddwen L Brooks, Francesca Polverino, Julie G Ledford

Faculty, Staff and Students Publications

No abstract provided.

Choosing And Switching Biological Agents In Severe Asthma, Muhammad Adrish, Nicola A Hanania

Faculty, Staff and Students Publications

No abstract provided.

Obesity And Asthma: A Focused Review, Rubabin Tooba, Tianshi David Wu

Faculty, Staff and Students Publications

No abstract provided.