Respiratory System Commons^™

Imaging-Based Clusters In Former Smokers Of The Copd Cohort Associate With Clinical Characteristics: The Subpopulations And Intermediate Outcome Measures In Copd Study (Spiromics), Babak Haghighi, Sanghun Choi, Jiwoong Choi, Eric A. Hoffman, Alejandro P. Comellas, John D. Newell, Chang Hyun Lee, R. Graham Barr, Eugene Bleecker, Christopher B. Cooper, David Couper, Mei Lan Han, Nadia N. Hansel, Richard E. Kanner, Ella A. Kazerooni, Eric A.C. Kleerup, Fernando J. Martinez, Wanda O'Neal, Robert Paine, Stephen I. Rennard, Benjamin M. Smith, Prescott G. Woodruff, Ching-Long Lin

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: Quantitative computed tomographic (QCT) imaging-based metrics enable to quantify smoking induced disease alterations and to identify imaging-based clusters for current smokers. We aimed to derive clinically meaningful sub-groups of former smokers using dimensional reduction and clustering methods to develop a new way of COPD phenotyping.

METHODS: An imaging-based cluster analysis was performed for 406 former smokers with a comprehensive set of imaging metrics including 75 imaging-based metrics. They consisted of structural and functional variables at 10 segmental and 5 lobar locations. The structural variables included lung shape, branching angle, airway-circularity, airway-wall-thickness, airway diameter; the functional variables included regional ventilation, …

Tgf-Β Induces A Heart Failure Phenotype Via Fibroblasts Exosome Signaling, Hesham Basma, Adelaide N. Johanson, Kajari Dhar, Daniel R. Anderson, Fang Qiu, Stephen I. Rennard, Brian D. Lowes

Journal Articles: Pulmonary & Critical Care Med

PURPOSE: The mechanisms for persistent and progressive loss of myocardial function in advanced heart failure (HF) remain incompletely characterized. In the current study, we sought to determine the impact of TGF-β on fibroblasts transcriptional profiles and assess if exosomes from TGF-β treated fibroblasts could induce a heart failure phenotype in co-cultured cardiomyocytes.

METHOD: Normal heart fibroblasts were treated with TGF-β with a final conc. of 2.5 ng/ml in serum free media. HF fibroblasts were also obtained from patients undergoing implantation of left ventricular assist devices. Exosomes were collected using three-step ultracentrifugation. Cardiomyocytes were co-cultured with exosomes from TGF-β-treated, HF and …

Bronchoalveolar Lavage Fluid From Copd Patients Reveals More Compounds Associated With Disease Than Matched Plasma, Eitan Halper-Stromberg, Lucas Gillenwater, Charmion Cruickshank-Quinn, Wanda Kay O'Neal, Nichole Reisdorph, Irina Petrache, Yonghua Zhuang, Wassim W. Labaki, Jeffrey L. Curtis, James Wells, Stephen I. Rennard, Katherine A. Pratte, Prescott Woodruff, Kathleen A. Stringer, Katerina Kechris, Russell P. Bowler

Journal Articles: Pulmonary & Critical Care Med

Smoking causes chronic obstructive pulmonary disease (COPD). Though recent studies identified a COPD metabolomic signature in blood, no large studies examine the metabolome in bronchoalveolar lavage (BAL) fluid, a more direct representation of lung cell metabolism. We performed untargeted liquid chromatography-mass spectrometry (LC-MS) on BAL and matched plasma from 115 subjects from the SPIROMICS cohort. Regression was performed with COPD phenotypes as the outcome and metabolites as the predictor, adjusted for clinical covariates and false discovery rate. Weighted gene co-expression network analysis (WGCNA) grouped metabolites into modules which were then associated with phenotypes. K-means clustering grouped similar subjects. We detected …

It's More Than Low Bmi: Prevalence Of Cachexia And Associated Mortality In Copd, Merry-Lynn N. Mcdonald, Emiel F.M. Wouters, Erica Rutten, Richard Casaburi, Stephen I. Rennard, David A. Lomas, Marcas Bamman, Bartolome Celli, Alvar Agusti, Ruth Tal-Singer, Craig P. Hersh, Mark Dransfield, Edwin K. Silverman

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: Cachexia is associated with increased mortality risk among chronic obstructive pulmonary disease (COPD) patients. However, low body mass index (BMI) as opposed to cachexia is often used, particularly when calculating the BODE (BMI, Obstruction, Dyspnea and Exercise) index. For this reason, we examined mortality using a consensus definition and a weight-loss definition of cachexia among COPD cases and compared two new COPD severity indices with BODE.

METHODS: In the current report, the consensus definition for cachexia incorporated weight-loss > 5% in 12-months or low BMI in addition to 3/5 of decreased muscle strength, fatigue, anorexia, low FFMI and inflammation. The …

Prospective Observational Study In Patients With Obstructive Lung Disease: Novelty Design, Helen K. Reddel, Maria Gerhardsson De Verdier, Alvar Agustí, Gary Anderson, Richard Beasley, Elisabeth H. Bel, Christer Janson, Barry Make, Richard J. Martin, Ian Pavord, David Price, Christina Keen, Asparuh Gardev, Stephen I. Rennard, Alecka Sveréus, Aruna T. Bansal, Lance Brannman, Niklas Karlsson, Javier Nuevo, Fredrik Nyberg, Simon S. Young, Jørgen Vestbo

Journal Articles: Pulmonary & Critical Care Med

Asthma and chronic obstructive pulmonary disease (COPD) have overlapping clinical features and share pathobiological mechanisms but are often considered distinct disorders. Prospective, observational studies across asthma, COPD and asthma-COPD overlap are limited. NOVELTY is a global, prospective observational 3-year study enrolling ∼12 000 patients ≥12 years of age from primary and specialist clinical practices in 19 countries (ClinicalTrials.gov identifier: NCT02760329). NOVELTY's primary objectives are to describe patient characteristics, treatment patterns and disease burden over time, and to identify phenotypes and molecular endotypes associated with differential outcomes over time in patients with a diagnosis/suspected diagnosis of asthma and/or COPD. NOVELTY …

Patients' Perceptions And Patient-Reported Outcomes In Progressive-Fibrosing Interstitial Lung Diseases, Jeffrey J. Swigris, Kevin K. Brown, Rayid Abdulqawi, Ketan Buch, Daniel F. Dilling, Dirk Koschel, Krishna Thavarajah, Rade Tomic, Yoshikazu Inoue

Internal Medicine Faculty Publications

The effects of interstitial lung disease (ILD) create a significant burden on patients, unsettling almost every domain of their lives, disrupting their physical and emotional well-being and impairing their quality of life (QoL). Because many ILDs are incurable, and there are limited reliably-effective, life-prolonging treatment options available, the focus of many therapeutic interventions has been on improving or maintaining how patients with ILD feel and function, and by extension, their QoL. Such patient-centred outcomes are best assessed by patients themselves through tools that capture their perceptions, which inherently incorporate their values and judgements. These patient-reported outcome measures (PROs) can be …

A Multicenter Study To Evaluate Pulmonary Function In Osteogenesis Imperfecta., Allison Tam, Shan Chen, Evan Schauer, Ingo Grafe, Venkata Bandi, Jay R. Shapiro, Robert D. Steiner, Peter A. Smith, Michael B. Bober, Tracy Hart, David Cuthbertson, Jeffrey Krischer, Mary Mullins, Peter H. Byers, Robert A. Sandhaus, Michaela Durigova, Francis H. Glorieux, Frank Rauch, Vernon Reid Sutton, Brendan Lee, Members Of The Brittle Bone Disorders Consortium, Eric T. Rush, Sandesh C S Nagamani

Manuscripts, Articles, Book Chapters and Other Papers

Pulmonary complications are a significant cause for morbidity and mortality in osteogenesis imperfecta (OI). However, to date, there have been few studies that have systematically evaluated pulmonary function in individuals with OI. We analyzed spirometry measurements, including forced vital capacity (FVC) and forced expiratory volume in the first second (FEV₁ ), in a large cohort of individuals with OI (n = 217) enrolled in a multicenter, observational study. We show that individuals with the more severe form of the disease, OI type III, have significantly reduced FVC and FEV₁ which do not follow the expected trends of the …

Rapid And Robust Restoration Of Breathing Long After Spinal Cord Injury, Philippa M. Warren, Stephanie C. Steiger, Thomas E. Dick, Peter M. Macfarlane, Warren J. Alilain, Jerry Silver

Spinal Cord and Brain Injury Research Center Faculty Publications

There exists an abundance of barriers that hinder functional recovery following spinal cord injury, especially at chronic stages. Here, we examine the rescue of breathing up to 1.5 years following cervical hemisection in the rat. In spite of complete hemidiaphragm paralysis, a single injection of chondroitinase ABC in the phrenic motor pool restored robust and persistent diaphragm function while improving neuromuscular junction anatomy. This treatment strategy was more effective when applied chronically than when assessed acutely after injury. The addition of intermittent hypoxia conditioning further strengthened the ventilatory response. However, in a sub-population of animals, this combination treatment caused excess …

Interfering With Dna Decondensation As A Strategy Against Mycobacteria, Enzo M. Scutigliani, Edwin R. Scholl, Anita E. Grootemaat, Sadhana Khanal, Jakub A. Kochan, Przemek M. Krawczyk, Eric A. Reits, Atefeh Garzan, Huy X. Ngo, Keith D. Green, Sylvie Garneau-Tsodikova, Jan M. Ruijter, Henk A. Van Veen, Nicole N. Van Der Wel

Pharmaceutical Sciences Faculty Publications

Tuberculosis is once again a major global threat, leading to more than 1 million deaths each year. Treatment options for tuberculosis patients are limited, expensive and characterized by severe side effects, especially in the case of multidrug-resistant forms. Uncovering novel vulnerabilities of the pathogen is crucial to generate new therapeutic strategies. Using high resolution microscopy techniques, we discovered one such vulnerability of Mycobacterium tuberculosis. We demonstrate that the DNA of M. tuberculosis can condense under stressful conditions such as starvation and antibiotic treatment. The DNA condensation is reversible and specific for viable bacteria. Based on these observations, we hypothesized …

Direct Cell-To-Cell Transmission Of Respiratory Viruses: The Fast Lanes, Nicolás P. Cifuentes-Muñoz, Rebecca Ellis Dutch, Roberto Cattaneo

Molecular and Cellular Biochemistry Faculty Publications

Virus particles protect genomes from hostile environments within and outside the host, eventually delivering these genomes to target tissues to initiate infection. Complex processes requiring significant energy and time are necessary to assemble these virus particles, but only a small portion of released virus will successfully infect new target cells (Fig 1A). While the science of virology has developed based on the isolation and purification of viral particles, it is becoming increasingly clear that direct cell-to-cell transmission of viruses and/or viral components is also highly relevant [1,2].

Direct cell-to-cell spread of infections has several advantages. The first is efficiency: genomic …

Phenotypical Characterization Of Human Rhinovirus Infections In Severely Premature Children, Geovanny F. Perez, Bassem Kurdi, Rosemary Megalaa, Krishna Pancham, Shehlanoor Huseni, Natalia Isaza, Carlos E. Rodriguez-Martinez, Dinesh Pillai, Gustavo Nino

Pediatrics Faculty Publications

Background: Human Rhinovirus (HRV) has been identified as the most common cause of acute respiratory infections and hospitalizations in premature children. It is unclear if premature children are more susceptible to HRV due to their decreased pulmonary reserve or because they have enhanced lower airway reactivity to HRV.

Methods: We conducted a retrospective analysis of the clinical respiratory presentation of all PCR-confirmed HRV infections in full-term and premature children aged ≤ 3 years in our institution. Standardized respiratory distress scores were developed to examine lower airway obstruction (i.e., wheezing, hyperinflation, and sub-costal retractions) along with markers of decreased pulmonary reserve …

Performance Anxiety And The Benefits Of Proper Breathing For Singing, Kate Zecher

Undergraduate Theses

The intent of this thesis is to help those with Music Performance Anxiety, or anxiety in general, better understand their anxiety and its causes. They can then use this knowledge to reduce or control their symptoms in order to improve their performance, whether on a stage or in a classroom. One of the main symptoms of Music Performance Anxiety is constriction of the chest. It is one of the most debilitating symptoms to singers as it causes shortness of breath. Therefore, focusing on anxiety in relation to breathing will most benefit those with Music Performance Anxiety. In addition, learning about …

Mobile Critical Care Recovery Program (M-Ccrp) For Acute Respiratory Failure Survivors: Study Protocol For A Randomized Controlled Trial, Sikandar Khan, Ashok Biju, Sophia Wang, Sujuan Gao, Omar Irfan, Amanda Harrawood, Stephanie Martinez, Anthony Perkins, Frederick W. Unverzagt, Sue Lasiter

Medical College Documents

Background: Patients admitted to intensive care units (ICU) with acute respiratory failure (ARF) face chronic complications that can impede return to normal daily function. A mobile, collaborative critical care model may enhance the recovery of ARF survivors.
Methods: The Mobile Critical Care Recovery Program (m-CCRP) study is a two arm, randomized clinical trial. We will randomize 620 patients admitted to the ICU with acute respiratory failure requiring mechanical ventilation in a 1:1 ratio to one of two arms (310 patients per arm) – m-CCRP intervention versus attention control. Those in the intervention group will meet with a care coordinator after …

Clinical Management Of Pressure Control Ventilation: An Algorithmic Method Of Patient Ventilatory Management To Address “Forgotten But Important Variables”, Lonny Ashworth, Yasuhiro Norisue, Megan Koster, Jeff Anderson, Junko Takada, Hatsuyo Ebisu

Respiratory Therapy Faculty Publications and Presentations

Pressure controlled ventilation is a common mode of ventilation used to manage both adult and pediatric populations. However, there is very little evidence that distinguishes the efficacy of pressure controlled ventilation over that of volume controlled ventilation in the adult population. This gap in the literature may be due to the absence of a consistent and systematic algorithm for managing pressure controlled ventilation. This article provides a brief overview of the applications of both pressure controlled ventilation and volume controlled ventilation and proposes an algorithmic approach to the management of patients receiving pressure controlled ventilation. This algorithmic approach highlights the …

The South Sudan: Tuberculosis, Blake Schwarz

Global Public Health

The South Sudan is a country that recently gained independence from the Sudan after a bloody twenty year civil war. They lost nearly two million lives during the war, and are now ravaged by Tuberculosis, or TB. After gaining their independence in 2011, the South Sudan has an average of 18,000 cases of TB at any time. This would consider TB in the South Sudan an endemic, as it always has a base level of TB cases that does not vary. There is medication for TB that is available to the citizens on the South Sudan, but the prescription is …

Increase In Intra-Abdominal Pressure During Airway Suctioning-Induced Cough After A Successful Spontaneous Breathing Trial Is Associated With Extubation Outcome, Lonny Ashworth

Respiratory Therapy Faculty Publications and Presentations

Background: A patient’s ability to clear secretions and protect the airway with an effective cough is an important part of the pre-extubation evaluation. An increase in intra-abdominal pressure (IAP) is important in generating the flow rate necessary for a cough. This study investigated whether an increase from baseline in IAP during a coughing episode induced by routine pre-extubation airway suctioning is associated with extubation outcome after a successful spontaneous breathing trial (SBT).

Methods: Three hundred thirty-five (335) mechanically ventilated patients who passed an SBT were enrolled. Baseline IAP and peak IAP during successive suctioning-induced coughs were measured with a fluid …

Imaging-Based Clusters In Current Smokers Of The Copd Cohort Associate With Clinical Characteristics: The Subpopulations And Intermediate Outcome Measures In Copd Study (Spiromics), Babak Haghighi, Sanghun Choi, Jiwoong Choi, Eric A. Hoffman, Alejandro P. Comellas, John D. Newell, R. Graham Barr, Eugene Bleecker, Christopher B. Cooper, David Couper, Mei Lan Han, Nadia N. Hansel, Richard E. Kanner, Ella A. Kazerooni, Eric A.C. Kleerup, Fernando J. Martinez, Wanda O'Neal, Stephen I. Rennard, Prescott G. Woodruff, Ching-Long Lin

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: Classification of COPD is usually based on the severity of airflow, which may not sensitively differentiate subpopulations. Using a multiscale imaging-based cluster analysis (MICA), we aim to identify subpopulations for current smokers with COPD.

METHODS: Among the SPIROMICS subjects, we analyzed computed tomography images at total lung capacity (TLC) and residual volume (RV) of 284 current smokers. Functional variables were derived from registration of TLC and RV images, e.g. functional small airways disease (fSAD%). Structural variables were assessed at TLC images, e.g. emphysema and airway wall thickness and diameter. We employed an unsupervised method for clustering.

RESULTS: Four clusters …

Use Of A 4-Week Up-Titration Regimen Of Roflumilast In Patients With Severe Copd, Henrik Watz, Nitin Bagul, Klaus F. Rabe, Stephen I. Rennard, Vijay Kt Alagappan, Jonas Román, Axel Facius, Peter Ma Calverley

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: The oral selective phosphodiesterase-4 inhibitor roflumilast (ROF) reduces exacerbations in patients with severe COPD. Adverse events (AEs) can cause early ROF discontinuation. Alternative dosing strategies may help patients continue their therapy.

METHODS: In this multicenter, double-blind trial, 1,321 patients with severe COPD were randomized 1:1:1 to 4 weeks' treatment with ROF 250 µg once daily (OD), 500 µg every other day (EOD), or 500 µg OD, each followed by ROF 500 µg OD for 8 weeks, plus standard therapy. The primary end point was the percentage of patients prematurely discontinuing study treatment.

RESULTS: Patients in the 250 µg OD/500 …

Towards Using A Physio-Cognitive Model In Tutoring For Psychomotor Tasks., Jong W. Kim, Chris Dancy, Robert A. Sottilare

Faculty Conference Papers and Presentations

We report our exploratory research of psychomotor task training in intelligent tutoring systems (ITSs) that are generally limited to tutoring in the desktop learning environment where the learner acquires cognitively oriented knowledge and skills. It is necessary to support computer-guided training in a psychomotor task domain that is beyond the desktop environment. In this study, we seek to extend the current capability of GIFT (Generalized Intelligent Frame-work for Tutoring) to address these psychomotor task training needs. Our ap-proach is to utilize heterogeneous sensor data to identify physical motions through acceleration data from a smartphone and to monitor respiratory activity through …

Centrilobular Emphysema And Coronary Artery Calcification: Mediation Analysis In The Spiromics Cohort, Surya P. Bhatt, Hrudaya P. Nath, Young-Il Kim, Rekha Ramachandran, Jubal R. Watts, Nina L.J. Terry, Sushil Sonavane, Swati P. Deshmane, Prescott G. Woodruff, Elizabeth C. Oelsner, Sandeep Bodduluri, Meilan K. Han, Wassim W. Labaki, J. Michael Wells, Fernando J. Martinez, R. Graham Barr, Mark T. Dransfield, Spiromics Investigators

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is associated with a two-to-five fold increase in the risk of coronary artery disease independent of shared risk factors. This association is hypothesized to be mediated by systemic inflammation but this link has not been established.

METHODS: We included 300 participants enrolled in the SPIROMICS cohort, 75 each of lifetime non-smokers, smokers without airflow obstruction, mild-moderate COPD, and severe-very severe COPD. We quantified emphysema and airway disease on computed tomography, characterized visual emphysema subtypes (centrilobular and paraseptal) and airway disease, and used the Weston visual score to quantify coronary artery calcification (CAC). We used …