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  1. Article ; Online: Kidney-lung cross talk during ARDS: mitochondrial DAMPs join the conversation.

    Varon, Jack / Englert, Joshua A

    American journal of physiology. Lung cellular and molecular physiology

    2021  Volume 320, Issue 5, Page(s) L819–L820

    MeSH term(s) Alarmins/metabolism ; Humans ; Kidney/physiopathology ; Lung/physiopathology ; Mitochondria/metabolism ; Mitochondria/pathology ; Respiratory Distress Syndrome/metabolism ; Respiratory Distress Syndrome/pathology
    Chemical Substances Alarmins
    Language English
    Publishing date 2021-03-10
    Publishing country United States
    Document type Editorial
    ZDB-ID 1013184-x
    ISSN 1522-1504 ; 1040-0605
    ISSN (online) 1522-1504
    ISSN 1040-0605
    DOI 10.1152/ajplung.00093.2021
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  2. Article ; Online: Pulmonary drug delivery for acute respiratory distress syndrome.

    Fei, Qinqin / Bentley, Ian / Ghadiali, Samir N / Englert, Joshua A

    Pulmonary pharmacology & therapeutics

    2023  Volume 79, Page(s) 102196

    Abstract: The acute respiratory distress syndrome (ARDS) is a life-threatening condition that causes respiratory failure. Despite numerous clinical trials, there are no molecularly targeted pharmacologic therapies to prevent or treat ARDS. Drug delivery during ... ...

    Abstract The acute respiratory distress syndrome (ARDS) is a life-threatening condition that causes respiratory failure. Despite numerous clinical trials, there are no molecularly targeted pharmacologic therapies to prevent or treat ARDS. Drug delivery during ARDS is challenging due to the heterogenous nature of lung injury and occlusion of lung units by edema fluid and inflammation. Pulmonary drug delivery during ARDS offers several potential advantages including limiting the off-target and off-organ effects and directly targeting the damaged and inflamed lung regions. In this review we summarize recent ARDS clinical trials using both systemic and pulmonary drug delivery. We then discuss the advantages of pulmonary drug delivery and potential challenges to its implementation. Finally, we discuss the use of nanoparticle drug delivery and surfactant-based drug carriers as potential strategies for delivering therapeutics to the injured lung in ARDS.
    MeSH term(s) Humans ; Lung ; Respiratory Distress Syndrome/drug therapy ; Drug Delivery Systems ; Pulmonary Surfactants/therapeutic use ; Drug Carriers
    Chemical Substances Pulmonary Surfactants ; Drug Carriers
    Language English
    Publishing date 2023-01-20
    Publishing country England
    Document type Journal Article ; Review ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 1399707-5
    ISSN 1522-9629 ; 1094-5539
    ISSN (online) 1522-9629
    ISSN 1094-5539
    DOI 10.1016/j.pupt.2023.102196
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  3. Article: Magnetic Resonance Elastography and Computational Modeling Identify Heterogeneous Lung Biomechanical Properties during Cystic Fibrosis.

    Cho, Youjin / Fakhouri, Faisal / Ballinger, Megan N / Englert, Joshua A / Hayes, Don / Kolipaka, Arunark / Ghadiali, Samir N

    Research square

    2024  

    Abstract: The lung is a dynamic mechanical organ and several pulmonary disorders are characterized by heterogeneous changes in the lung's local mechanical properties (i.e. stiffness). These alterations lead to abnormal lung tissue deformation (i.e. strain) which ... ...

    Abstract The lung is a dynamic mechanical organ and several pulmonary disorders are characterized by heterogeneous changes in the lung's local mechanical properties (i.e. stiffness). These alterations lead to abnormal lung tissue deformation (i.e. strain) which have been shown to promote disease progression. Although heterogenous mechanical properties may be important biomarkers of disease, there is currently no non-invasive way to measure these properties for clinical diagnostic purposes. In this study, we use a magnetic resonance elastography technique to measure heterogenous distributions of the lung's shear stiffness in healthy adults and in people with Cystic Fibrosis. Additionally, computational finite element models which directly incorporate the measured heterogenous mechanical properties were developed to assess the effects on lung tissue deformation. Results indicate that consolidated lung regions in people with Cystic Fibrosis exhibited increased shear stiffness and reduced spatial heterogeneity compared to surrounding non-consolidated regions. Accounting for heterogenous lung stiffness in healthy adults did not change the globally averaged strain magnitude obtained in computational models. However, computational models that used heterogenous stiffness measurements predicted significantly more variability in local strain and higher spatial strain gradients. Finally, computational models predicted lower strain variability and spatial strain gradients in consolidated lung regions compared to non-consolidated regions. These results indicate that spatial variability in shear stiffness alters local strain and strain gradient magnitudes in people with Cystic Fibrosis. This imaged-based modeling technique therefore represents a clinically viable way to non-invasively assess lung mechanics during both health and disease.
    Language English
    Publishing date 2024-03-21
    Publishing country United States
    Document type Preprint
    DOI 10.21203/rs.3.rs-4125891/v1
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  4. Article: A Micro-scale Humanized Ventilator-on-a-Chip to Examine the Injurious Effects of Mechanical Ventilation.

    Gabela-Zuniga, Basia / Shukla, Vasudha C / Bobba, Christopher / Higuita-Castro, Natalia / Powell, Heather M / Englert, Joshua A / Ghadiali, Samir N

    bioRxiv : the preprint server for biology

    2024  

    Abstract: Patients with compromised respiratory function frequently require mechanical ventilation to survive. Unfortunately, non-uniform ventilation of injured lungs generates complex mechanical forces that lead to ventilator induced lung injury (VILI). Although ... ...

    Abstract Patients with compromised respiratory function frequently require mechanical ventilation to survive. Unfortunately, non-uniform ventilation of injured lungs generates complex mechanical forces that lead to ventilator induced lung injury (VILI). Although investigators have developed lung-on-a-chip systems to simulate normal respiration, modeling the complex mechanics of VILI as well as the subsequent recovery phase is a challenge. Here we present a novel humanized in vitro ventilator-on-a-chip (VOC) model of the lung microenvironment that simulates the different types of injurious forces generated in the lung during mechanical ventilation. We used transepithelial/endothelial electrical resistance (TEER) measurements to investigate how individual and simultaneous application of the different mechanical forces alters real-time changes in barrier integrity during and after injury. We find that compressive stress (i.e. barotrauma) does not significantly alter barrier integrity while over-distention (20% cyclic radial strain, volutrauma) results in decreased barrier integrity that quickly recovers upon removal of mechanical stress. Conversely, surface tension forces generated during airway reopening (atelectrauma), result in a rapid loss of barrier integrity with a delayed recovery relative to volutrauma. Simultaneous application of cyclic stretching (volutrauma) and airway reopening (atelectrauma), indicate that the surface tension forces associated with reopening fluid-occluded lung regions is the primary driver of barrier disruption. Thus, our novel VOC system can monitor the effects of different types of injurious forces on barrier disruption and recovery in real-time and can be used to identify the biomechanical mechanisms of VILI.
    Language English
    Publishing date 2024-03-01
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2024.02.26.582200
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  5. Article ; Online: Cancer Is an Independent Risk Factor for Acute Respiratory Distress Syndrome in Critically Ill Patients: A Single Center Retrospective Cohort Study.

    Ho, Kevin / Gordon, Joshua / Litzenberg, Kevin T / Exline, Matthew C / Englert, Joshua A / Herman, Derrick D

    Journal of intensive care medicine

    2021  Volume 37, Issue 3, Page(s) 385–392

    Abstract: Background: Acute Respiratory Distress Syndrome (ARDS) is a frequent cause of respiratory failure in intensive care unit (ICU) patients and results in significant morbidity and mortality. ARDS often develops as a result of a local or systemic ... ...

    Abstract Background: Acute Respiratory Distress Syndrome (ARDS) is a frequent cause of respiratory failure in intensive care unit (ICU) patients and results in significant morbidity and mortality. ARDS often develops as a result of a local or systemic inflammatory insult. Cancer can lead to systemic inflammation but whether cancer is an independent risk factor for developing ARDS is unknown. We hypothesized that critically ill cancer patients admitted to the ICU were at increased risk for the diagnosis of ARDS.
    Methods: Retrospective cohort study of critically ill patients admitted between July 2017 and December 2018 at an academic medical center in Columbus, Ohio. The primary outcome was the association of patients with malignancy and the diagnosis of ARDS in a multivariable logistic regression model with covariables selected a priori informed through the construction of a directed acyclic graph.
    Results: 412 ARDS cases were identified with 166 of those patients having active cancer. There was an association between cancer and ARDS, with an odds ratio (OR) of 1.55 (95% CI 1.26-1.92,
    Conclusion: In this single center retrospective cohort study, cancer was found to be an independent risk factor for the diagnosis of ARDS in critically ill patients. To our knowledge, we are the first report an independent association between cancer and ARDS in critically ill patients.
    MeSH term(s) Critical Illness ; Humans ; Intensive Care Units ; Neoplasms/complications ; Respiratory Distress Syndrome/epidemiology ; Respiratory Distress Syndrome/etiology ; Retrospective Studies ; Risk Factors
    Language English
    Publishing date 2021-03-29
    Publishing country United States
    Document type Journal Article
    ZDB-ID 632828-3
    ISSN 1525-1489 ; 0885-0666
    ISSN (online) 1525-1489
    ISSN 0885-0666
    DOI 10.1177/08850666211005422
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    Zs.A 2158: Show issues Location:
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  6. Article ; Online: Steroids and β-Agonists in Acute Respiratory Distress Syndrome: Timing Is Everything.

    Englert, Joshua A / Crouser, Elliott D

    Critical care medicine

    2017  Volume 45, Issue 5, Page(s) 914–915

    MeSH term(s) Adrenal Cortex Hormones ; Humans ; Immunosuppressive Agents ; Respiration, Artificial ; Respiratory Distress Syndrome, Adult
    Chemical Substances Adrenal Cortex Hormones ; Immunosuppressive Agents
    Language English
    Publishing date 2017-04-12
    Publishing country United States
    Document type Editorial ; Comment
    ZDB-ID 197890-1
    ISSN 1530-0293 ; 0090-3493
    ISSN (online) 1530-0293
    ISSN 0090-3493
    DOI 10.1097/CCM.0000000000002385
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    Zs.A 1261: Show issues Location:
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  7. Article ; Online: Unhinging the machinery of sepsis: An unexpected role for vascular smooth muscle.

    Englert, Joshua A / Christman, John W / Ballinger, Megan N

    Journal of leukocyte biology

    2018  Volume 104, Issue 4, Page(s) 661–663

    MeSH term(s) Humans ; Muscle, Smooth, Vascular ; Sepsis ; Transgenes
    Language English
    Publishing date 2018-08-22
    Publishing country United States
    Document type Editorial ; Comment
    ZDB-ID 605722-6
    ISSN 1938-3673 ; 0741-5400
    ISSN (online) 1938-3673
    ISSN 0741-5400
    DOI 10.1002/JLB.CE0618-236R
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    Zs.A 603: Show issues Location:
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  8. Article ; Online: Integrating molecular pathogenesis and clinical translation in sepsis-induced acute respiratory distress syndrome.

    Englert, Joshua A / Bobba, Christopher / Baron, Rebecca M

    JCI insight

    2019  Volume 4, Issue 2

    Abstract: Sepsis-induced acute respiratory distress syndrome (ARDS) has high morbidity and mortality and arises after lung infection or infection at extrapulmonary sites. An aberrant host response to infection leads to disruption of the pulmonary alveolar- ... ...

    Abstract Sepsis-induced acute respiratory distress syndrome (ARDS) has high morbidity and mortality and arises after lung infection or infection at extrapulmonary sites. An aberrant host response to infection leads to disruption of the pulmonary alveolar-capillary barrier, resulting in lung injury characterized by hypoxemia, inflammation, and noncardiogenic pulmonary edema. Despite increased understanding of the molecular biology underlying sepsis-induced ARDS, there are no targeted pharmacologic therapies for this devastating condition. Here, we review the molecular underpinnings of sepsis-induced ARDS with a focus on relevant clinical and translational studies that point toward novel therapeutic strategies.
    Language English
    Publishing date 2019-01-24
    Publishing country United States
    Document type Journal Article ; Review
    ISSN 2379-3708
    ISSN (online) 2379-3708
    DOI 10.1172/jci.insight.124061
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  9. Article ; Online: PRMT5 in T Cells Drives Th17 Responses, Mixed Granulocytic Inflammation, and Severe Allergic Airway Inflammation.

    Lewis, Brandon W / Amici, Stephanie A / Kim, Hye-Young / Shalosky, Emily M / Khan, Aiman Q / Walum, Joshua / Gowdy, Kymberly M / Englert, Joshua A / Porter, Ned A / Grayson, Mitchell H / Britt, Rodney D / Guerau-de-Arellano, Mireia

    Journal of immunology (Baltimore, Md. : 1950)

    2022  Volume 208, Issue 7, Page(s) 1525–1533

    Abstract: Severe asthma is characterized by steroid insensitivity and poor symptom control and is responsible for most asthma-related hospital costs. Therapeutic options remain limited, in part due to limited understanding of mechanisms driving severe asthma. ... ...

    Abstract Severe asthma is characterized by steroid insensitivity and poor symptom control and is responsible for most asthma-related hospital costs. Therapeutic options remain limited, in part due to limited understanding of mechanisms driving severe asthma. Increased arginine methylation, catalyzed by protein arginine methyltransferases (PRMTs), is increased in human asthmatic lungs. In this study, we show that PRMT5 drives allergic airway inflammation in a mouse model reproducing multiple aspects of human severe asthma. We find that PRMT5 is required in CD4
    MeSH term(s) Animals ; Asthma/metabolism ; Granulocytes/metabolism ; Hypersensitivity/metabolism ; Inflammation/metabolism ; Mice ; Th17 Cells/metabolism
    Language English
    Publishing date 2022-03-14
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 3056-9
    ISSN 1550-6606 ; 0022-1767 ; 1048-3233 ; 1047-7381
    ISSN (online) 1550-6606
    ISSN 0022-1767 ; 1048-3233 ; 1047-7381
    DOI 10.4049/jimmunol.2100994
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  10. Article ; Online: Bilateral Lung Masses and Dyspnea in a Young Woman.

    Hay, Bryan R / Shilo, Konstantin / Englert, Joshua A

    Annals of the American Thoracic Society

    2018  Volume 15, Issue 7, Page(s) 875–879

    MeSH term(s) Adult ; Biopsy ; Diagnosis, Differential ; Dyspnea/diagnosis ; Dyspnea/etiology ; Female ; Humans ; Lung/diagnostic imaging ; Sarcoidosis, Pulmonary/complications ; Sarcoidosis, Pulmonary/diagnosis ; Tomography, X-Ray Computed
    Language English
    Publishing date 2018-06-28
    Publishing country United States
    Document type Case Reports ; Journal Article
    ZDB-ID 2717461-X
    ISSN 2325-6621 ; 1943-5665 ; 2325-6621
    ISSN (online) 2325-6621 ; 1943-5665
    ISSN 2325-6621
    DOI 10.1513/AnnalsATS.201801-066CC
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