Pulmonology Commons^™

Shaping The Future Of Respiratory Care: A Look Into The Next Decade And Strategic Recommendations By The European Forum For Research And Education In Allergy And Airways Diseases, Xander Bertels, Glenis K. Scadding, Vibeke Backer, Susanne Lou, Wytske J. Fokkens, Peter J. Barnes, Manuel Bernal Sprekelsen, Leif Bjermer, Michael Blaiss, Elena Borzova, Marie-Charlotte Brüggen, Guy G. Brusselle, Lars Olaf Cardell, Diego M. Conti, Marjolein Cornet, Eugenio De Corso, Bernard De Groeve, Ratko Djukanovic, Adam T. Fox, Mina Gaga, Philippe Gevaert, Peter Gibson, Claudia L. Gray, Joseph Han, Liam Heaney, Enrico Heffler, Hans Jürgen Hoffmann, Claire Hopkins, Daniel Jackson, Outi Jauhola, Milos Jesenak, Pål Johansen, Ekaterina Khaleva, Basile Landis, Stella Lee, Valerie Lund, Mika Mäkelä, Marinda Mcdonald, Erik Melén, Joaquim Mullol, Antonio Nieto-García, Ian Pavord, Anju Peters, David Price, Santiago Quirce, Dermot Ryan, Pernilla Sahlstrand-Johnson, Sophie Scheire, Peter Schmid-Grendelmeier, Sven Schneider, Brent A. Senior, Catherine M.E. Shire, Peter K. Smith, Zsolt Szépfalusi, M. Thijs A. Teeling, Michael E. Wechsler, Philippe Houssiau, Klaus F. Rabe, Peter W. Hellings, José Luis Castro

Department of Otolaryngology (ENT) Faculty Publications

Chronic respiratory diseases (CRDs) remain 1 of the leading causes of preventable morbidity and disability worldwide, affecting up to one-third of the total Western population in 2025. Recognizing the substantial burden of inflammatory airway diseases such as asthma, COPD, chronic rhinosinusitis, and respiratory allergy, the European Forum for Research and Education in Allergy and Airway Diseases (EUFOREA) organized the symposium “Shaping the Future of Respiratory Care” in April 2025 in Brussels, Belgium, at the occasion of the 10-year jubilee. Featuring keynote speakers from the World Health Organization and EUFOREA, this initiative had the following aims: (1) promoting dialogue on translating …

Hsp90 Inhibitor, At13387 Mitigates Chronic Lung Injury In Pre-Pubertal Mice: A Therapeutic Axis In Bronchopulmonary Dysplasia, Pavel A. Solopov, Christiana Dimitropoulou, John D. Catravas, Ruben M. L. Colunga Biancatelli

Bioelectrics Publications

Exposure to hydrochloric acid (HCl) can provoke severe chronic pulmonary injury. Children are particularly vulnerable due to their smaller airways, higher respiratory rate, and stronger inflammatory response; yet no countermeasures exist for HCl-induced chronic lung injury in the pediatric population. We have previously demonstrated the involvement of HSP90 during HCl-induced lung injury in pre-pubertal (p24) mice, who develop stronger persistent inflammation with higher NLRP3 inflammasome activation, but less pulmonary fibrosis compared to adults. Here, we tested the hypothesis that post-treatment with the second-generation HSP90 inhibitor AT13387 (Onalespib), administered subcutaneously beginning 24 h after HCl instillation, would prevent HCl-induced chronic lung …

Revisiting Nasal Polyp Scoring In Clinical Trials: Interpretive Variability And The Need For Standardization, Leigh J. Sowerby, Babak Pourmomenarabi, Antonino Maniaci, Olivia Ginty, Joseph Khristian Han

Department of Otolaryngology (ENT) Faculty Publications

[Introduction] Borish et al. provided an excellent review highlighting methodological variability among the six pivotal Phase III trials [1]. One critical yet overlooked issue is the inconsistent application of the endoscopic nasal polyp score (NPS), a primary outcome measure in all trials.

A Diagnostic Dilemma Due To A Large Chiari Network, Kyle Admire, Xian Qiao

Cardiovascular Research Symposium

INTRODUCTION: Chiari networks are reticulated networks of fibers that result from incomplete reabsorption of the right valve of the sinus venosus. While the true clinical significance of these is currently unknown, there are associations with dysrhythmias, paradoxical emboli, and thrombi formation. Here, we describe a large, incidentally found Chiari network which encompasses most of the right atrium.

CASE: A 42-year-old female with a past medical history of obesity (BMI 58) and well-controlled asthma presented to the emergency department in respiratory distress with hypercapnia and hypoxemia. Computed tomography (CT) with angiography of the chest was performed and did not show a …

Investigating Extracellualr Vesicles Role In The Pathogenesis Of Acute Lung Injury, Ruben Manuel Luciano Colunga Biancatelli, Pavel Solopov, Tierney Day, Anca Dobrian, John D. Catravas

Cardiovascular Research Symposium

Background: Extracellular vesicles (EVs) are small lipid-bound particles containing proteins and RNAs, whose role in intercellular communication and signaling is critical for homeostasis or inflammatory responses. Patients with acute lung injury display changes in EVs number, cargo content and signature compared to healthy individuals.

Hypothesis: We have hypothesized that EVs may play a role in the pathogenesis of acute lung, by transferring harmful mediators of inflammation and disrupting recipient cells homeostasis.

Methods: C57BL/6j mice (8-10 weeks old, 25g BW) were intratracheally instilled with 50µL of 5*1010- 11 EVs isolated from Human Lung Microvascular Endothelial cells (HLMVEC) exposed to 1 µg …

Cannabinoid-2 Receptor Activation Attenuates Sulfur Mustard Analog 2-Chloroethyl-Ethyl-Sulfide-Induced Acute Lung Injury In Mice, Gregory Nicholson, Nicholas Richards, Janette Lockett, My Boi Ly, Raj V. Nair, Woong-Ki Kim, K. Yaragudri Vinod, Nagaraja Nagre

Department of Biomedical and Translational Sciences Faculty Publications

Background: Exposure to sulfur mustard (SM; 2,2′-dichlorodiethyl sulfide) causes toxicity in the human body, particularly the lungs. The molecular mechanisms of SM-induced lung damage are elusive, and no effective treatments exist. This study explores the anti-inflammatory potential of cannabinoid receptor 2 (CB2R) activation in mitigating acute lung injury (ALI) and inflammation induced by 2-chloroethyl ethyl sulfide (CEES), a structural analog of SM. Methods: C57BL/6J mice were exposed to CEES via intratracheal administration to model ALI. CB2R activation was achieved through the intraperitoneal administration of HU308, a selective synthetic agonist. ALI and inflammation were evaluated at 48 h post-exposure to CEES. …

Large-Bore Mechanical Thrombectomy Versus Catheter-Directed Thrombolysis In The Management Of Intermediate-Risk Pulmonary Embolism: Primary Results Of The Peerless Randomized Controlled Trial, Wissam A. Jaber, Carin F. Gonsalves Md, Stefan Stortecky, Samuel Horr, Ripal T. Gandhi, Keith Pereira, Jay Giri, Sameer J. Khandhar, Khawaja Afzal Ammar, David M. Lasorda, Brian Stegman, Lucas Busch, David J. Dexter, Ezana M. Azene, Nikhil Daga, Fakhir Elmasri, Chandra R. Kunavarapu, Mark E. Rea, Joseph S. Rossi, Joseph Campbell, Jonathan Lindquist, Adam Raskin, Jason C. Smith, Thomas M. Tamlyn, Gabriel A. Hernandez, Parth Rali, Torrey R. Schmidt, Jeffrey T. Bruckel, Juan C. Camacho, Jun Li, Samy Selim, Catalin Toma, Sukhdeep Singh Basra, Brian A. Bergmark, Bhavraj Khalsa, David M. Zlotnick, Jordan Castle, David J. O'Connor, C. Michael Gibson, For The Peerless Committees And Investigators

Department Surgery Faculty Publications

BACKGROUND: There are a lack of randomized controlled trial data comparing outcomes of different catheter-based interventions for intermediate-risk pulmonary embolism.

METHODS: PEERLESS is a prospective, multicenter, randomized controlled trial that enrolled 550 patients with intermediate-risk pulmonary embolism with right ventricular dilatation and additional clinical risk factors randomized 1:1 to treatment with large-bore mechanical thrombectomy (LBMT) or catheter-directed thrombolysis (CDT). The primary end point was a hierarchal win ratio composite of the following (assessed at the sooner of hospital discharge or 7 days after the procedure): (1) all-cause mortality, (2) intracranial hemorrhage, (3) major bleeding, (4) clinical deterioration and/or escalation …

Patient-Self Inflicted Lung Injury (P-Sili): An Insight Into The Pathophysiology Of Lung Injury And Management, Himanshu Deshwal, Ahmed Elkhapery, Rudra Ramanathan, Deepak Nair, Isha Singh, Ankur Sinha, Rishik Vashisht, Vikramjit Mukherjee

Department of Medicine Faculty Publications

Acute respiratory distress syndrome (ARDS) is a heterogeneous group of disease entities that are associated with acute hypoxic respiratory failure and significant morbidity and mortality. With a better understanding and phenotyping of lung injury, novel pathophysiologic mechanisms demonstrate the impact of a patient’s excessive spontaneous breathing effort on perpetuating lung injury. Patient self-inflicted lung injury (P-SILI) is a recently identified phenomenon that delves into the impact of spontaneous breathing on respiratory mechanics in patients with lung injury. While the studies are hypothesis-generating and have been demonstrated in animal and human studies, further clinical trials are needed to identify its impact …

A Case Displaying The Importance Of Jak1 And Jak2 Gene Transcription In Antifungal Defense Against Coccidioidomycosis, Jennifer K. Priessnitz, Taylor Colore, Nelson Nicolasora

Department of Medicine Faculty Publications

This case report explores the consequences of ruxolitinib via inhibition janus kinase 1 (JAK1) and JAK2 pathways in the context of fungal defense in a patient diagnosed with pulmonary coccidioidomycosis during ruxolitinib therapy for polycythemia vera. The patient experienced a relapse of pulmonary coccidioidomycosis after antifungal treatment was discontinued while continuing ruxolitinib use. This case illustrates the heightened risk of discontinuing antifungal therapy in endemic regions, emphasizing the critical need for continued monitoring. Furthermore, this case underscores the vital role of the JAK1 and JAK2 signaling cascade, particularly the interferon-gamma (INF-γ)-JAK1 and JAK2-signal transducer and activator of transcription 1 (STAT) …

Kvx-053, A Protein Tyrosine Phosphatase 4a3 Inhibitor, Ameliorates Sars-Cov-2 Spike Protein Subunit 1 - Induced Acute Lung Injury In Mice, Pavel A. Solopov, Ruben Manuel Luciano Colunga Biancatelli, Tierney Day, Betsy Gregory, Elizabeth R. Sharlow, John S. Lazo, John D. Catravas

Bioelectrics Publications

The Acute Respiratory Distress Syndrome (ARDS), often preceded by acute lung injury (ALI), is characterized by the accumulation of inflammatory fluid in the lung alveoli, leaky alveolar epithelium and endothelium, and overexpression of pro-inflammatory cytokines. This progression from ALI to ARDS is a major contributor to the high mortality observed in COVID-19 patients. The Spike protein of SARS-CoV-2 binds to lung ACE2 and, in addition to facilitating viral cell entry, it plays an important role in the development of ALI and ARDS, especially in the later phases of COVID-19 as well as long COVID. Protein tyrosine phosphatase (PTP) 4A3 is …

A Novel Non-Rodent Animal Model Of Hydrochloric Acid-Induced Acute And Chronic Lung Injury, Pavel A. Solopov, Ruben Manuel Luciano Biancatelli, Tierney Day, Christiana Dimitropoulou, John D. Catravas

Bioelectrics Publications

Hydrochloric acid is one of the most prevalent and hazardous chemicals. Accidental spills occur in industrial plants or during transportation. Exposure to HCl can induce severe health impairment, including acute and chronic pulmonary diseases. We have previously described the molecular, structural, and functional aspects of the development of chronic lung injury and pulmonary fibrosis caused by intratracheal instillation of HCl in mice. Although mouse models of human disease have many advantages, rodents are evolutionary far from human and exhibit significant anatomical and physiological differences. Genetic and anatomic similarities between rabbits and humans are significantly higher. Rabbit models of HCl-induced lung …

Hsp90 Inhibitors Modulate Sars-Cov-2 Spike Protein Subunit 1-Induced Human Pulmonary Microvascular Endothelial Activation And Barrier Dysfunction, Ruben Manuel Luciano Colunga Biancatelli, Pavel Solopov, Betsy W. Gregory, Yara Khodour, John D. Catravas

Bioelectrics Publications

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has caused more than 5 million deaths worldwide. Multiple reports indicate that the endothelium is involved during SARS-Cov-2-related disease (COVID-19). Indeed, COVID-19 patients display increased thrombophilia with arterial and venous embolism and lung microcapillary thrombotic disease as major determinants of deaths. The pathophysiology of endothelial dysfunction in COVID-19 is not completely understood. We have investigated the role of subunit 1 of the SARS-CoV-2 spike protein (S1SP) in eliciting endothelial barrier dysfunction, characterized dose and time relationships, and tested the hypothesis that heat shock protein 90 (HSP90) inhibitors would prevent and repair such injury. S1SP …

Pulmonary Capillary Recruitment And Distention In Mammalian Lungs: Species Similarities, David Langleben, Benjamin D. Fox, Stylianos E. Orfanos, Michele Giovinazzo, John D. Catravas

Bioelectrics Publications

Pulmonary arterial pressure rises minimally during exercise. The pulmonary microcirculation accommodates increasing blood flow via recruitment of pulmonary capillaries and, at higher flows, by distention of already perfused capillaries. The flow transition range between recruitment and distention has not been studied or compared across mammalian species, including humans. We hypothesised that the range would be similar. Functional pulmonary capillary surface area (FCSA) can be estimated using validated metabolic techniques. We reviewed data from previous studies in three mammalian species (perfused rabbit lungs and dog lung lobes, and exercising humans) and generated blood flow-FCSA curves over a range of flows. We …

The Heat Shock Protein 90 Inhibitor, At13387, Protects The Alveolo-Capillary Barrier And Prevents Hci-Induced Chronic Lung Injury And Pulmonary Fibrosis, Ruben M.L. Colunga Biancatelli, Pavel Solopov, Christiana Dimitropoulou, Betsy Gregory, Tierney Day, John D. Catravas

Bioelectrics Publications

Hydrochloric acid (HCl) exposure causes asthma-like conditions, reactive airways dysfunction syndrome, and pulmonary fibrosis. Heat Shock Protein 90 (HSP90) is a molecular chaperone that regulates multiple cellular processes. HSP90 inhibitors are undergoing clinical trials for cancer and are also being studied in various pre-clinical settings for their anti-inflammatory and anti-fibrotic effects. Here we investigated the ability of the heat shock protein 90 (HSP90) inhibitor AT13387 to prevent chronic lung injury induced by exposure to HCl in vivo and its protective role in the endothelial barrier in vitro. We instilled C57Bl/6J mice with 0.1N HCl (2 µL/g body weight, intratracheally) and …

The Paradox Of Pulmonary Vascular Resistance: Restoration Of Pulmonary Capillary Recruitment As A Sine Qua Non For True Therapeutic Success In Pulmonary Arterial Hypertension, David Langleben, Stylianos E. Orfanos, Benjamin D. Fox, Nathan Messas, Michele Giovinazzo, John D. Catravas

Bioelectrics Publications

Exercise-induced increases in pulmonary blood flow normally increase pulmonary arterial pressure only minimally, largely due to a reserve of pulmonary capillaries that are available for recruitment to carry the flow. In pulmonary arterial hypertension, due to precapillary arteriolar obstruction, such recruitment is greatly reduced. In exercising pulmonary arterial hypertension patients, pulmonary arterial pressure remains high and may even increase further. Current pulmonary arterial hypertension therapies, acting principally as vasodilators, decrease calculated pulmonary vascular resistance by increasing pulmonary blood flow but have a minimal effect in lowering pulmonary arterial pressure and do not restore significant capillary recruitment. Novel pulmonary arterial hypertension …

Activation Of Cannabinoid-2 Receptor Protects Against Pseudomonas Aeruginosa Induced Acute Lung Injury And Inflammation, Nagaraja Nagre, Gregory Nicholson, Xiaofei Cong, Janette Lockett, Andrew C. Pearson, Vincent Chan, Woong-Ki Kim, K. Yaragudri Vinod, John D. Catravas

Bioelectrics Publications

Background

Bacterial pneumonia is a major risk factor for acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Pseudomonas aeruginosa (PA), an opportunistic pathogen with an increasing resistance acquired against multiple drugs, is one of the main causative agents of ALI and ARDS in diverse clinical settings. Given the anti-inflammatory role of the cannabinoid-2 receptor (CB2R), the effect of CB2R activation in the regulation of PA-induced ALI and inflammation was tested in a mouse model as an alternative to conventional antibiotic therapy.

Methods

In order to activate CB2R, a selective synthetic agonist, JWH133, was administered intraperitoneally (i.p.) to C57BL/6J …

Observations Of Delayed Changes In Respiratory Function Among Allergy Clinic Patients Exposed To Wildfire Smoke, James Blando, Michael Allen, Hadiza Galadima, Timothy Tolson, Muge Akpinar-Elci, Mariana Szklo-Coxe

Community & Environmental Health Faculty Publications

Wildfires have increased in frequency and magnitude and pose a significant public health challenge. The principal objective of this study was to assess the impact of wildfire smoke on respiratory peak flow performance of patients exposed to two different wildfire events. This longitudinal study utilized an observational approach and a cohort study design with a patient-level clinical dataset from a local outpatient allergy clinic (n = 842). Meteorological data from a local weather station served as a proxy for smoke exposure because air quality measurements were not available. This study found that there were decreases in respiratory peak flow among …

The Hsp90 Inhibitor, Auy-922, Protects And Repairs Human Lung Microvascular Endothelial Cells From Hydrochloric Acid-Induced Endothelial Barrier Dysfunction, Ruben M.L. Colunga Biancatelli, Pavel Solopov, Betsy Gregory, John D. Catravas

Bioelectrics Publications

Exposure to hydrochloric acid (HCl) leads acutely to asthma-like symptoms, acute respiratory distress syndrome (ARDS), including compromised alveolo-capillary barrier, and respiratory failure. To better understand the direct effects of HCl on pulmonary endothelial function, we studied the characteristics of HCl-induced endothelial barrier dysfunction in primary cultures of human lung microvascular endothelial cells (HLMVEC), defined the involved molecular pathways, and tested the potentially beneficial effects of Heat Shock Protein 90 (HSP90) inhibitors. HCl impaired barrier function in a time- and concentration-dependent manner and was associated with activation of Protein Kinase B (AKT), Ras homolog family member A (RhoA) and myosin light …

Dietary Phytoestrogens Ameliorate Hydrochloric Acid-Induced Chronic Lung Injury And Pulmonary Fibrosis In Mice, Pavel Solopov, Ruben Manuel Luciano Colunga Biancatelli, Christiana Dimitropoulou, John D. Catravas

Bioelectrics Publications

We previously reported that female mice exhibit protection against chemically induced pulmonary fibrosis and suggested a potential role of estrogen. Phytoestrogens act, at least in part, via stimulation of estrogen receptors; furthermore, compared to residents of Western countries, residents of East Asian countries consume higher amounts of phytoestrogens and exhibit lower rates of pulmonary fibrosis. Therefore, we tested the hypothesis that dietary phytoestrogens ameliorate the severity of experimentally induced pulmonary fibrosis. Male mice placed on either regular soybean diet or phytoestrogen-free diet were instilled with 0.1 N HCl to provoke pulmonary fibrosis. Thirty days later, lung mechanics were measured as …

Age-Dependent Chronic Lung Injury And Pulmonary Fibrosis Following Single Exposure To Hydrochloric Acid, Ruben M.L. Colunga Biancatelli, Pavel Solopov, Christiana Dimitropoulou, John D. Catravas

Bioelectrics Publications

Exposure to hydrochloric acid (HCl) represents a threat to public health. Children may inhale higher doses and develop greater injury because of their smaller airways and faster respiratory rate. We have developed a mouse model of pediatric exposure to HCl by intratracheally instilling p24 mice (mice 24 days old; 8–10 g) with 2 µL/g 0.1 N HCl, and compared the profile of lung injury to that in HCl-instilled adults (10 weeks old; 25–30 g) and their age-matched saline controls. After 30 days, alveolar inflammation was observed with increased proteinosis and mononuclear cells in the bronchoalveolar lavage fluid (BALF) in both …

Longitudinal Association Of Sleep-Disordered Breathing And Nondipping Of Nocturnal Blood Pressure In The Wisconsin Sleep Cohort Study, Khin Mae Hla, Terry Young, Laurel Finn, Paul E. Peppard, Mariana Szklo-Coxe, Maryan Stubbs

Community & Environmental Health Faculty Publications

Study objectives: The association of sleep-disordered breathing (SDB) and blunting of normal nocturnal lowering of blood pressure (BP) (nondipping) has only been examined cross-sectionally. The purpose of this study is to investigate whether SDB is prospectively associated with nondipping.

Methods: The longitudinal association between SDB and incident nondipping was examined in a subsample of 328 adults enrolled in the Wisconsin Sleep Cohort Study who completed 2 or more 24-hour ambulatory BP studies over an average of 7.2 years of follow-up. SDB identified by baseline in-laboratory polysomnography was defined by apnea-hypopnea index (AHI) categories. Systolic and diastolic nondipping was defined by …

Quantitative Respirator Fit Testing: Probed Facepiece Versus Probed Cartridge, Sonya Melissa Seward

Community & Environmental Health Theses & Dissertations

This study was performed to determine if there is a quantifiable difference between quantitative fit testing using a probed facepiece and a probed cartridge. Four subjects were tested on four different respirators. The respirators used were MSA & 3M full and half face respirator. Each subject performed each method five times per respirator. The results indicated no correlation between the two fit testing methods overall. However, a moderate correlation was found between the MSA respirators and the two methods. This study found many variables which influence fit testing. These include the type of respirator used (brand and facepiece), the probe …