Sleep Medicine Commons^™

Predicting Weaning Failure From Invasive Mechanical Ventilation: The Promise And Pitfalls Of Clinical Prediction Scores, Maneesh Gaddam, Dedeepya Gullapalli, Zayaan A Adrish, Arnav Y Reddy, Muhammad Adrish

Faculty, Staff and Students Publications

Prediction of weaning success from invasive mechanical ventilation remains a challenge in everyday clinical practice. Several prediction scores have been developed to guide success during spontaneous breathing trials to help with weaning decisions. These scores aim to provide a structured framework to support clinical judgment. However, their effectiveness varies across patient populations, and their predictive accuracy remains inconsistent. In this review, we aim to identify the strengths and limitations of commonly used clinical prediction tools in assessing readiness for ventilator liberation. While scores such as the Rapid Shallow Breathing Index and the Integrative Weaning Index are widely adopted, their sensitivity …

Mechano-Signal Transduction Pathways Of The Diaphragmatic Muscle And Role Of Cytoskeleton, Junaith S Mohamed, Patricia S Pardo, Aladin M Boriek

Faculty, Staff and Students Publications

Mechanotransduction, also referred to as mechano-signal transduction, is a biophysical process wherein cells perceive and respond to mechanical stimuli by converting them into biochemical signals that initiate specific cellular responses. This mechanism is fundamental to the development and growth, and proper functioning of mechanically active tissues, such as the diaphragm-a respiratory muscle vital for breathing in mammals. In vivo, the diaphragm is subjected to transdiaphragmatic pressure, and therefore, its muscle fibers are subjected to mechanical forces not only in the direction of the muscle fibers but also in the direction transverse to the fibers. Previous research conducted in our laboratory …

Established And Emerging Asthma Biomarkers With A Focus On Biologic Trials: A Narrative Review, Philip F Lavere, Kaitlin M Phillips, Nicola A Hanania, Muhammad Adrish

Faculty, Staff and Students Publications

Chronic airway inflammation with variable airflow obstruction is clinical asthma, and it arises from distinct molecular and pathological mechanisms called endotypes. Biomarkers allow for precise endotype characterization and have been used in clinical trials to design, monitor, and evaluate outcomes for asthma biologic therapies. This review will highlight the central and evolving role of biomarkers for past, present, and future asthma, with a focus on regulatory-approved biologic therapies and emerging biomarkers. Established biomarkers, including serum immunoglobulin E (IgE), blood eosinophils, the fraction of exhaled nitric oxide (FeNO), and serum periostin, helped elucidate the complex pathophysiology of the eosinophilic type 2 …

Molecular Maestro In The Lung: The Sphingolipid Rheostat, Joselyn Rojas-Quintero, Francesca Polverino

Faculty, Staff and Students Publications

No abstract provided.

The Resilience Of The Human Lungs: Evolution, Smoke, And Disease, Joan B Soriano, Francesca Polverino

Faculty, Staff and Students Publications

No abstract provided.

Machine Learning Assisted Immune Profiling Of Copd Identifies A Unique Emphysema Subtype Independent Of Gold Stage, Natalie Bordag, Katharina Jandl, Ayu Hutami Syarif, Jürgen Gindlhuber, Diana Schnoegl, Ayse Ceren Mutgan, Vasile Foris, Konrad Hoetzenecker, Panja Maria Boehm, Robab Breyer-Kohansal, Katarina Zeder, Gregor Gorkiewicz, Francesca Polverino, Slaven Crnkovic, Grazyna Kwapiszewska, Leigh Matthew Marsh

Faculty, Staff and Students Publications

Chronic obstructive pulmonary disease (COPD) is a severe, progressive, and heterogeneous disease with a poor outcome. Inflammation plays a central role in disease pathogenesis; however, the interplay between immune changes and disease heterogeneity has been difficult to unravel. We performed a multilevel immunoinflammatory characterization of patients with COPD using flow cytometry, cytokine profiling, single-cell, or spatial transcriptomics in combination with machine learning algorithms. Our cross-cohort analysis demonstrated shared skewing of immune profiles in COPD lungs toward adaptive immune cells. We furthermore identified a subgroup of patients with COPD with a distinct immune profile, characterized by increased antigen-presenting cells, mast cells, …

Sensing The Stiffness: Cellular Mechano-Sensing At The Implant Interface, Patricia S Pardo, Delia Danila, Raja Devesh Kumar Misra, Aladin M Boriek

Faculty, Staff and Students Publications

In this perspective, we highlight the relevance of the FA-Hippo signaling pathway and its regulation of the Yes-associated protein (YAP) and the transcriptional coactivator with a PDZ-binding domain (TAZ) as main players in the process of implants integration. The modulation and responses of YAP/TAZ triggered by substrate and ECM stiffness are of particular interest in the construction of materials used for medical implants. YAP/TAZ nuclear localization and activity respond to the substrate stiffness by several mechanisms that involve the canonical and non-canonical Hippo signaling and independently of the Hippo cascade. YAP/TAZ regulate the expression of genes involved in several mechanisms …

Assessment Of Functioning Using The Whodas 20 Among People With Myasthenia Gravis-Associated Disability: A Nationwide Follow-Up Study, Jia-Pei Hong, Chih-Hong Lee, Chien Tai Hong, Lung Chan, Chen-Chih Chung, Prangthip Charoenpong, Hou-Chang Chiu, Tsan-Hon Liou

Faculty, Staff and Students Publications

Background: Advancements in treatment have increased the life expectancy of patients with Myasthenia Gravis (MG), yet the understanding of functional changes in these individuals remains limited. In our study, we explored the functional abilities of individuals with MG using the World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0).

Methods: This observational study analyzed data from 286 patients with MG, acquired from the Data Bank of Persons with Disabilities (TDPD) in Taiwan between July 11, 2012, and December 31, 2021. Participants were diagnosed with MG after the acute phase. The functional disability outcome was assessed using the WHODAS 2.0. Due …

Figo Position Statement: Gamete Donations, Laurie Henry, Aris Antsaklis, Dov Feldberg, Jaideep Malhotra, Suchitra Pandit, Carlos Salazar, Alex Vidaeff, Rafal Zadykowicz, M Louise Hull, Nikhil Purandare

Faculty, Staff and Students Publications

Gamete donation has become a crucial part of Assisted Reproductive Technologies (ARTs), providing hope to individuals, including those who may have no other option for parenthood. This process comes with a wide range of ethical, medical, and legal challenges that need to be carefully addressed to protect the well-being and rights of all parties involved: donors, recipients, and offspring. Navigating these complexities requires strict ethical standards, robust regulatory frameworks, and international collaboration. By standardizing these, the field of gamete donation can continue to develop while ensuring that all parties are well informed and safeguarded. This paper explores the ethical concerns …

Military Inhalational Exposures Outside The Theater Of Conflict And Chronic Respiratory Symptoms, Reza Hosseini, Eric Garshick, Martin D Slade, Andrew Timmons, Anna M Korpak, Nicholas L Smith, Karen S Nakayama, Coleen P Baird, Paul Ciminera, Farrah Kheradmand, Vincent S Fan, Jaime E Hart, Petros Koutrakis, Ware Glenn Kuschner, Octavian C Ioachimescu, Michael Jerrett, Philippe R Montgrain, Susan P Proctor, Christine H Wendt, Cherry Wongtrakool, Emily S Wan, Paul D Blanc, Carrie A Redlich

Faculty, Staff and Students Publications

Importance: Deployment to Afghanistan and Southwest Asia has been associated with adverse respiratory health outcomes. However, the impact of inhalational exposures (eg, vapor, dust, gas, fumes), which are known correlates of reduced lung function and future chronic lung disease, during military service time outside this deployment period has not been assessed.

Objective: To assess military inhalational exposures during nonwartime routine activities and their associations with chronic respiratory symptoms.

Design, setting, and participants: This cross-sectional study used data from the US Department of Veterans Affairs Service and Health Among Deployed Veterans study. US veterans who served between October 7, 2001, and …

Combined Anterior Palatoplasty With Barbed Suspension Pharyngoplasty In The Treatment Of Obstructive Sleep Apnea, Patheemon Thanachaikun, Natamon Charakorn

Chulalongkorn Medical Journal

Background: Surgery is a treatment option for obstructive sleep apnea (OSA) patients for whom positive airway pressure therapy is not chosen. Various palatal surgical techniques have been developed. However, the medical literature has limited accounts concerning the use of combination of these techniques to improved outcomes.

Objective: The aim of this study is to assess the efficacy of a combined anterior palatoplasty (AP) and barbed suspension pharyngoplasty (BSP) in treating adult OSA.

Methods: Data of OSA patients who underwent the combined AP with BSP between July 2020 to May 2024 were retrospectively reviewed. The surgical outcomes, including apnea-hypopnea index (AHI), …

Regulation Of Myogenesis By Mechanomir-200c/Foxo3 Axis, Junaith S Mohamed, Aladin M Boriek

Faculty, Staff and Students Publications

Cyclic mechanical stretch has been shown to inhibit myoblast differentiation while promoting proliferation. However, the underlying molecular mechanisms are not well understood. Here, we report that mechanical stretch inhibits the differentiation of mouse primary myoblasts by promoting the cell cycle program and by inhibiting the expression of the myogenic regulator MyoD. Stretch alters the miRNA expression profile as evidenced by miRNA microarray analysis. We identified miR-200c as one of the highly downregulated mechanosensitive miRNAs (mechanomiRs) whose expression level was increased during differentiation. This suggests that mechanomiRs-200c is a myogenic miRNA. Overexpression of mechanomiR-200c revoked the effect of stretch on myoblast …

Scoring Large Muscle Movements In Pediatric Sleep Studies: An Educational Module For Sleep Technologists, Shauna Michelle Vandoren, David G. Ingram

Posters

Introduction Restless Sleep Disorder (RSD) has recently been recognized as a distinct sleep disorder, with Large Muscle Movement (LMM) scoring being a crucial component of its diagnostic criteria. This project aimed to develop and implement an online educational module to enhance the knowledge and skills of sleep technologists to accurately score LMMs. Methods We constructed an online learning module that included training on the identification and scoring of LMMs in pediatric sleep studies. The module consisted of a 10-question pre-assessment, the educational content (which explained the background of RSD diagnosis, the role of LMMs in diagnostic criteria, and current scoring …

When Macroglossia Is Not Beckwith-Wiedemann: A Case Of An Infant With Congenital Central Hypoventilation Syndrome, Shauna Michelle Vandoren, Samira Naime

Posters

Introduction Congenital central hypoventilation syndrome (CCHS) is a rare genetic disorder caused by the mutation of the paired-like homeobox 2B (PHOX2B) gene that leads to alveolar hypoventilation during sleep and at times while awake. The majority of patients with CCHS have polyalanine repeat mutations (PARM) whereas 10% have non-PARM (NPARM). Of those with NPARM, less than 1% are caused by whole gene deletion. NPARM is associated with more severe phenotypes; however, some may have variable penetrance causing variable presentation within families. Report of case(s) Our patient is a 4-month-old infant born at 32 weeks in an outside hospital and transferred …

Protein Biomarkers Of Interstitial Lung Abnormalities In Relatives Of Patients With Pulmonary Fibrosis, Jonathan A Rose, Mark P Steele, Esteban J Kosak Lopez, Gisli Thor Axelsson, Andrea G Galecio Chao, Alan Waich, Katie Regan, Swati Gulati, Anthony H Maeda, Sharmin Sultana, Claire Cutting, Ann-Marcia C Tukpah, Andrew J Synn, Mary B Rice, Hilary J Goldberg, Joyce S Lee, David A Lynch, Rachel K Putman, Hiroto Hatabu, Benjamin A Raby, David A Schwartz, Ivan O Rosas, Gary M Hunninghake

Faculty, Staff and Students Publications

Rationale: First-degree relatives of patients with pulmonary fibrosis (referred to here as relatives) are at high risk for interstitial lung abnormalities (ILA), highlighting the need for biomarkers for risk prediction. We aimed to identify blood proteins associated with and predictive of ILA among relatives of patients with pulmonary fibrosis.

Methods: Relatives enrolled in two independent cohorts had protein levels measured using an aptamer-based proteomic platform. ILA were assessed with computed tomography scans as per Fleischner Society recommendations. Protein associations with ILA were assessed using regression. Significant proteins were used with clinical variables to detect ILA.

Results: Of 237 relatives from …

Targeting S1pr2 In Sepsis, One Fragmented Mitochondrion At A Time, Chao He, Jennifer L Larson-Casey

Faculty, Staff and Students Publications

No abstract provided.

Airway Immune Signatures In Severe And Fatal Infection With Covid-19, Naresh Doni Jayavelu, Jing Jing Qi, Slim Fourati, Farrah Kheradmand, Charles R Langelier, Lauren I R Ehrlich, Joann Diray-Arce, Annmarie Hoch, Monica Kraft, Patrice M Becker, Matthew C Altman, Ruth R Montgomery

Faculty, Staff and Students Publications

No abstract provided.

Secreted Phosphoprotein 1 In Lung Diseases, Hongli Liu, Cristian Coarfa, Arzoo N Charania, Jennifer L Larson-Casey, Ivan O Rosas, Chao He

Faculty, Staff and Students Publications

Secreted phosphoprotein 1 (SPP1), also known as osteopontin (OPN) or early T lymphocyte activation protein 1 (ETA-1), is a multifunctional protein involved in numerous biological processes, including immune modulation, stress response, and tissue remodeling. The role of SPP1 in interstitial lung diseases (ILDs) has become an area of increasing interest, given its elevated expression in various ILDs such as idiopathic pulmonary fibrosis (IPF), connective tissue disease-associated ILD (CTD-ILD), and pneumoconiosis, especially with recent data derived from single-cell RNA sequencing. In addition to ILDs, SPP1 has been implicated in infectious granulomatous lung diseases, lung and pleural malignancies, airway diseases, and COVID-19. …

The Perk/Atf4 Pathway Is Required For Metabolic Reprogramming And Progressive Lung Fibrosis, Jyotsana Pandey, Jennifer L Larson-Casey, Mallikarjun H Patil, Chao He, Nisarat Pinthong, A Brent Carter

Faculty, Staff and Students Publications

Asbestosis is a prototypical type of fibrosis that is progressive and does not resolve. ER stress is increased in multiple cell types that contribute to fibrosis; however, the mechanism(s) by which ER stress in lung macrophages contributes to fibrosis is poorly understood. Here, we show that ER stress resulted in protein kinase RNA-like ER kinase (PERK; Eif2ak3) activation in humans with asbestosis. Similar results were seen in asbestos-injured mice. Mice harboring a conditional deletion of Eif2ak3 were protected from fibrosis. Lung macrophages from asbestosis individuals had evidence of metabolic reprogramming to fatty acid oxidation (FAO). Eif2ak3fl/fl mice had increased oxygen …

The Joint Association Of Diet Quality And Sleep Regularity With Incident Cardiovascular Disease In The Multi-Ethnic Study Of Atherosclerosis, Kaitlin S Potts, Claire Veldkamp, Alexis C Wood, Erin D Michos, Raymond Noordam, Tianyi Huang, Susan Redline, Heming Wang

Children’s Nutrition Research Center Staff Publications

Background/objectives: Diet quality and sleep regularity both influence cardiovascular disease (CVD) risk and may influence each other, but there is scarce evidence for their joint or interacting associations in relation to CVD. We assessed these associations in the Multi-Ethnic Study of Atherosclerosis (MESA).

Methods: Participants free of CVD with valid diet and sleep measures in 2010-2013 were included and followed through 2020 for detection of incident CVD (188 events detected over 8.8 years among 1782 participants; 55% women). Sleep timing and duration regularity were assessed via the intra-individual SD of sleep onset time and duration across 5- to 7-day actigraphy. …

Single Center Comparison Of Home Sleep Apnea Testing Based On Respiratory Polygraphy Vs. Peripheral Arterial Tonometry, Stephen F. White, Md, Praneet C. Kaki, Bs, Henry C. Ideker, Md, Ritu G. Grewal, Md

Health Equity and Quality Improvement (HEQI) Summit

Introduction

• Home sleep apnea testing (HSAT) is an accessible option for diagnosing obstructive sleep apnea (OSA) in patients with high pre- test probability of moderate to severe OSA
• Cardio-respiratory polygraphy (RP) has traditionally been utilized and involves wearing a nasal airflow cannula, pulse oximeter, and respiratory effort belt with actigraphy
• Peripheral arterial tonometry (PAT)-based testing is a newer technology that involves wearing a disposable smartwatch-sized computer on the wrist, sensor on the finger and sensor on the chest and has been validated for HSAT
• PAT-based HSAT has been increasingly utilized due to perceived ease of use, improved patient comfort, and …

A Retrospective Study Of Pulmonary Function Tests In Bronchiectasis: An Infectious Disease Of The Respiratory System, Vinod Mutkule, Mahesh Shinde, Vidya Bapmare, Sangramsingh Dixit, Atharva Sharma, Kshitij Sarwey, Yogeshwari Patil, Sanket Jethlia, Aayushi Dwivedi, Disha Pardeshi, Anmol Rai, Kunal Shah, Vidhi Kalwar

The University of Louisville Journal of Respiratory Infections

Introduction: Bronchiectasis, currently being recognized worldwide, is an abnormal dilatation of the bronchi and bronchioles brought on by recurrent cycles of inflammation and airway infection. Impaired pulmonary function has a predictive significance in bronchiectasis. When treating patients with suspected or confirmed respiratory diseases, pulmonary function tests (PFT) are useful examinations. Very few studies have been done on PFTs in bronchiectasis. The main aim of this study is to study PFTs in bronchiectasis.

Method: This is a retrospective observational study done on 50 patients over two years at the tertiary care center. The previous records of patients were collected from the …

Comparative Analysis Of Drug-Induced Sleep Endoscopy With Positive Airway Pressure And Therapeutic Continuous Positive Airway Pressure In The Treatment Of Obstructive Sleep Apnea, Elliott M. Sina, Nicole Molin, Praneet C. Kaki, Henry Ideker, Stephen White, Maurits Boon, Colin Huntley

Department of Otolaryngology - Head and Neck Surgery Faculty Papers

No abstract provided.

Let-7 Restrains An Epigenetic Circuit In At2 Cells To Prevent Fibrogenic Intermediates In Pulmonary Fibrosis, Matthew J Seasock, Md Shafiquzzaman, Maria E Ruiz-Echartea, Rupa S Kanchi, Brandon T Tran, Lukas M Simon, Matthew D Meyer, Phillip A Erice, Shivani L Lotlikar, Stephanie C Wenlock, Scott A Ochsner, Anton Enright, Alex F Carisey, Freddy Romero, Ivan O Rosas, Katherine Y King, Neil J Mckenna, Cristian Coarfa, Antony Rodriguez

Faculty, Staff and Students Publications

MicroRNA-mediated post-transcriptional regulation of lung alveolar type 2 (AT2) and AT1 cell differentiation remains understudied. Here, we demonstrate that the let-7 miRNA family plays a homeostatic role in AT2 quiescence by preventing the uncontrolled accumulation of AT2 transitional cells and promoting AT1 differentiation. Using mouse and organoid models, we show that genetic ablation of let-7a1/let-7f1/let-7d cluster (let-7afd) in AT2 cells prevents AT1 differentiation and leads to KRT8 transitional cell accumulation in progressive pulmonary fibrosis. Integration of AGO2-eCLIP with RNA-sequencing identified direct let-7 targets within an oncogene feed-forward regulatory network, including BACH1/EZH2/MYC, which drives an aberrant fibrotic cascade. Additional CUT&RUN-sequencing analyses …

Integrating Positive Psychology And Spirituality To Foster Meaning And Well-Being In Older Adults, Crystal Morris

Adultspan Journal

This perspective article explores the integration of positive psychology interventions (PPIs) and spirituality in therapy to foster meaning and well-being in older adults. It highlights exercises such as the positive introduction, positive legacy, character strengths, mindfulness, mindful-based yoga, and a manifestation prayer journaling. The interventions presented are tools to support older adults that may experience depression, difficult life transitions, and the search for renewed meaning. Therapists who integrate PPIs and spirituality into therapy can promote a holistic, non-pathological approach to treatment.

Gut Dysbiosis Patterns In Cvid Patients With Noninfectious Complications Observed In A Germ-Free Mouse Model Through Fecal Microbiota Transplantation, Joud Hajjar, Anita Y Voigt, Margaret E Conner, Alton G Swennes, Stephanie Fowler, Chadi Calarge, Danielle D Mendonca, Dominique Armstrong, Chen-Yen Chang, Jolan E Walter, Manish J Butte, Tor Savidge, Julia Oh, Farrah Kheradmand, Joseph F Petrosino

Faculty, Staff and Students Publications

Patients with common variable immunodeficiency (CVID) who develop noninfectious complications (NIC) have worse clinical outcomes than those with infections only (INF). While gut microbiome aberrations have been linked to NIC, reductionist animal models that accurately recapitulate CVID are lacking. Our aim in this study was to uncover potential microbiome roles in the development of NIC in CVID. We performed whole-genome shotgun sequencing on fecal samples from CVID patients with NIC, INF, and their household controls. We also performed fecal microbiota transplants from CVID patients to germ-free mice. We found potentially pathogenic microbes

Outcomes Of Left Atrial Appendage Occlusion In Patients With Obstructive Sleep Apnea: A Comprehensive National Study, Tony Elias, Fady Beshara, Daniel Basta, Mena Elmalh, Matthew Ebrahim, Taha Syed, Olga Sarah, Abdallah Hussein

Rowan-Virtua Research Day

We sought to explore a sample of the inpatient population with OSA with AF who underwent LAAO.

Investigating Sleep Quality In Post-Stroke Delirium: A Scoping Review, Shay Greco, Bethany C. Young

Rowan-Virtua Research Day

Background: Delirium affects approximately 59% of hospitalized patients with intracerebral hemorrhage and is associated with poor outcomes. Sleep-wake cycle disturbances are hypothesized to contribute to delirium development, particularly in neurointensive care settings where frequent sleep interruptions occur.

Methods: We conducted a scoping review of literature published between 2014-2024 using PubMed, CINAHL, Embase, and Cochrane databases. Studies were included if they observed sleep in adult stroke populations.

Results: Four observational studies (2018-2023) met inclusion criteria, with sample sizes ranging from 20-112 participants. All studies included patients with ICH. All studies reported associations between poor sleep in patients with ICH and delirium …

A Broad Examination Of Sleep Issues In Pediatric Multiple Sclerosis And Other Conditions, Chaithanya Annaluru

Rowan-Virtua Research Day

Background: Poor sleep hygiene can lead to serious health consequences, including the development of health disorders and the worsening of chronic illnesses. Poor sleep quality or duration has been linked to neurocognitive changes such as inattention and lower IQ scores. Sleep disorders are especially prevalent among pediatric patients with neurologic and neuropsychiatric conditions; for example, children with epilepsy and ADHD exhibit higher rates of parasomnias, while patients with multiple sclerosis (MS) experience REM sleep behavior disorder and insomnia more often than the general population. Additionally, co-existing obstructive sleep apnea (OSA) and epilepsy can worsen seizure control, and uncontrolled epilepsy can …

Case Report: Hypercapnia's Hidden Dance: Myoclonus In A Patient With Co2 Retention, Kelsey Murray

Rowan-Virtua Research Day

Myoclonic jerking is a neurologic phenomenon characterized by sudden, involuntary muscle contractions. While often associated with neurological conditions, myoclonic jerking can also be observed in patients with significant carbon dioxide retention. This case report highlights the presentation of myoclonic jerking in a 77-year-old male with a history of sleep apnea and obesity, who presented to the emergency department with hypoxia and elevated carbon dioxide levels. Despite the lack of neurological deficits, the patient experienced intermittent myoclonic jerks of his hands, which were attributed to CO2 retention. The report underscores the importance of recognizing myoclonic jerking as a potential sign of …