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  1. Article ; Online: The Honoring Our PACT Act: An Improved Commitment to Veterans' Health.

    Richmond, Bradley W / Miller, Robert F

    Annals of the American Thoracic Society

    2022  Volume 20, Issue 4, Page(s) 508–509

    MeSH term(s) Humans ; United States ; Veterans ; Veterans Health ; United States Department of Veterans Affairs
    Language English
    Publishing date 2022-11-15
    Publishing country United States
    Document type Journal Article ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 2717461-X
    ISSN 2325-6621 ; 1943-5665 ; 2325-6621
    ISSN (online) 2325-6621 ; 1943-5665
    ISSN 2325-6621
    DOI 10.1513/AnnalsATS.202208-718VP
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    Zs.A 5828: Show issues Location:
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  2. Article ; Online: An update in club cell biology and its potential relevance to chronic obstructive pulmonary disease.

    Blackburn, Jessica B / Li, Ngan Fung / Bartlett, Nathan W / Richmond, Bradley W

    American journal of physiology. Lung cellular and molecular physiology

    2023  Volume 324, Issue 5, Page(s) L652–L665

    Abstract: Club cells are found in human small airways where they play an important role in immune defense, xenobiotic metabolism, and repair after injury. Over the past few years, data from single-cell RNA sequencing (scRNA-seq) studies has generated new insights ... ...

    Abstract Club cells are found in human small airways where they play an important role in immune defense, xenobiotic metabolism, and repair after injury. Over the past few years, data from single-cell RNA sequencing (scRNA-seq) studies has generated new insights into club cell heterogeneity and function. In this review, we integrate findings from scRNA-seq experiments with earlier in vitro, in vivo, and microscopy studies and highlight the many ways club cells contribute to airway homeostasis. We then discuss evidence for loss of club cells or club cell products in the airways of patients with chronic obstructive pulmonary disease (COPD) and discuss potential mechanisms through which this might occur.
    MeSH term(s) Humans ; Pulmonary Disease, Chronic Obstructive/metabolism ; Bronchioles/metabolism ; Epithelial Cells/metabolism
    Language English
    Publishing date 2023-03-21
    Publishing country United States
    Document type Journal Article ; Review ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 1013184-x
    ISSN 1522-1504 ; 1040-0605
    ISSN (online) 1522-1504
    ISSN 1040-0605
    DOI 10.1152/ajplung.00192.2022
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  3. Article ; Online: Adding Insult to Injury: Does COVID-19 Promote Acute Respiratory Distress Syndrome by Inhibiting Surfactant?

    Richmond, Bradley W / Dela Cruz, Charles S

    American journal of respiratory and critical care medicine

    2022  Volume 207, Issue 1, Page(s) 5–6

    MeSH term(s) Humans ; Infant, Newborn ; Pulmonary Surfactants/therapeutic use ; Surface-Active Agents ; COVID-19 ; Respiratory Distress Syndrome/drug therapy ; Respiratory Distress Syndrome, Newborn/drug therapy ; Immunoglobulin A
    Chemical Substances Pulmonary Surfactants ; Surface-Active Agents ; Immunoglobulin A
    Language English
    Publishing date 2022-08-18
    Publishing country United States
    Document type Editorial ; Research Support, U.S. Gov't, Non-P.H.S. ; Comment
    ZDB-ID 1180953-x
    ISSN 1535-4970 ; 0003-0805 ; 1073-449X
    ISSN (online) 1535-4970
    ISSN 0003-0805 ; 1073-449X
    DOI 10.1164/rccm.202208-1549ED
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  4. Article ; Online: Integrating Clinical and Air Quality Data to Improve Prediction of COPD Exacerbations.

    Ratcliff, Grace E / Matheny, Michael E / Brown, Jeremiah R / Sullivan, Iben / Richmond, Bradley W / Paulin, Laura M / Conger, Adrienne K / Davis, Sharon E

    AMIA ... Annual Symposium proceedings. AMIA Symposium

    2024  Volume 2023, Page(s) 1209–1217

    Abstract: Several studies have found associations between air pollution and respiratory disease outcomes. However, there is minimal prognostic research exploring whether integrating air quality into clinical prediction models can improve accuracy and utility. In ... ...

    Abstract Several studies have found associations between air pollution and respiratory disease outcomes. However, there is minimal prognostic research exploring whether integrating air quality into clinical prediction models can improve accuracy and utility. In this study, we built models using both logistic regression and random forests to determine the benefits of including air quality data with meteorological and clinical data in prediction of COPD exacerbations requiring medical care. Logistic models were not improved by inclusion of air quality. However, the net benefit curves of random forest models showed greater clinical utility with the addition of air quality data. These models demonstrate a practical and relatively low-cost way to include environmental information into clinical prediction tools to improve the clinical utility of COPD prediction. Findings could be used to provide population level health warnings as well as individual-patient risk assessments.
    MeSH term(s) Humans ; Disease Progression ; Pulmonary Disease, Chronic Obstructive/diagnosis ; Air Pollution/adverse effects ; Risk Assessment ; Data Accuracy
    Language English
    Publishing date 2024-01-11
    Publishing country United States
    Document type Journal Article
    ISSN 1942-597X
    ISSN (online) 1942-597X
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  5. Article: Vaping-induced diffuse alveolar hemorrhage.

    Edmonds, Peter J / Copeland, Carla / Conger, Adrienne / Richmond, Bradley W

    Respiratory medicine case reports

    2020  Volume 29, Page(s) 100996

    Abstract: There are growing reports of adverse health effects from e-cigarette use or vaping. The U.S. Centers for Disease Control and Prevention has reported 2409 cases and 52 deaths associated with e-cigarette use as of December 10, 2019. Vaping has been ... ...

    Abstract There are growing reports of adverse health effects from e-cigarette use or vaping. The U.S. Centers for Disease Control and Prevention has reported 2409 cases and 52 deaths associated with e-cigarette use as of December 10, 2019. Vaping has been associated with acute eosinophilic pneumonia, organizing pneumonia, lipoid pneumonia, diffuse alveolar damage, acute respiratory distress syndrome, hypersensitivity pneumonia, and giant cell interstitial pneumonitis. Here we present a case of vaping-associated diffuse alveolar hemorrhage.
    Language English
    Publishing date 2020-01-07
    Publishing country England
    Document type Case Reports
    ZDB-ID 2666110-X
    ISSN 2213-0071
    ISSN 2213-0071
    DOI 10.1016/j.rmcr.2020.100996
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  6. Article ; Online: Pulmonary Vascular Disease in Veterans with Post-Deployment Respiratory Syndrome.

    Gutor, Sergey S / Richmond, Bradley W / Agrawal, Vineet / Brittain, Evan L / Shaver, Ciara M / Wu, Pingsheng / Boyle, Taryn K / Mallugari, Ravinder R / Douglas, Katrina / Piana, Robert N / Johnson, Joyce E / Miller, Robert F / Newman, John H / Blackwell, Timothy S / Polosukhin, Vasiliy V

    Cardiovascular pathology : the official journal of the Society for Cardiovascular Pathology

    2024  , Page(s) 107640

    Abstract: Exertional dyspnea has been documented in U.S. military personnel after deployment to Iraq and Afghanistan. We studied whether continued exertional dyspnea in this patient population is associated with pulmonary vascular disease (PVD). We performed ... ...

    Abstract Exertional dyspnea has been documented in U.S. military personnel after deployment to Iraq and Afghanistan. We studied whether continued exertional dyspnea in this patient population is associated with pulmonary vascular disease (PVD). We performed detailed histomorphometry of pulmonary vasculature in 52 Veterans with biopsy-proven post-deployment respiratory syndrome (PDRS) and then recruited five of these same Veterans with continued exertional dyspnea to undergo a follow-up clinical evaluation, including symptom questionnaire, pulmonary function testing, surface echocardiography, and right heart catheterization (RHC). Morphometric evaluation of pulmonary arteries showed significantly increased intima and media thicknesses, along with collagen deposition (fibrosis), in Veterans with PDRS compared to non-diseased (ND) controls. In addition, pulmonary veins in PDRS showed increased intima and adventitia thicknesses with prominent collagen deposition compared to controls. Of the five Veterans involved in our clinical follow-up study, three had borderline or overt right ventricle (RV) enlargement by echocardiography and evidence of pulmonary hypertension (PH) on RHC. Together, our studies suggest that PVD with predominant venular fibrosis is common in PDRS and development of pulmonary hypertension may explain exertional dyspnea and exercise limitation in some Veterans with PDRS.
    Language English
    Publishing date 2024-04-09
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1134600-0
    ISSN 1879-1336 ; 1054-8807
    ISSN (online) 1879-1336
    ISSN 1054-8807
    DOI 10.1016/j.carpath.2024.107640
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    Zs.A 3572: Show issues Location:
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  7. Article ; Online: Repetitive sulfur dioxide exposure in mice models post-deployment respiratory syndrome.

    Gutor, Sergey S / Salinas, Rodrigo I / Nichols, David S / Bazzano, Julia M R / Han, Wei / Gokey, Jason J / Vasiukov, Georgii / West, James D / Newcomb, Dawn C / Dikalova, Anna E / Richmond, Bradley W / Dikalov, Sergey I / Blackwell, Timothy S / Polosukhin, Vasiliy V

    American journal of physiology. Lung cellular and molecular physiology

    2024  Volume 326, Issue 5, Page(s) L539–L550

    Abstract: Soldiers deployed to Iraq and Afghanistan have a higher prevalence of respiratory symptoms than nondeployed military personnel and some have been shown to have a constellation of findings on lung biopsy termed post-deployment respiratory syndrome (PDRS). ...

    Abstract Soldiers deployed to Iraq and Afghanistan have a higher prevalence of respiratory symptoms than nondeployed military personnel and some have been shown to have a constellation of findings on lung biopsy termed post-deployment respiratory syndrome (PDRS). Since many of the subjects in this cohort reported exposure to sulfur dioxide (SO
    MeSH term(s) Animals ; Sulfur Dioxide ; Mice ; Disease Models, Animal ; Mice, Inbred C57BL ; Superoxide Dismutase/metabolism ; Superoxide Dismutase/genetics ; Lung/pathology ; Lung/drug effects ; Lung/metabolism ; Male ; Hypertension, Pulmonary/pathology ; Hypertension, Pulmonary/chemically induced ; Hypertension, Pulmonary/metabolism ; Mice, Transgenic ; Vascular Remodeling/drug effects ; Sirtuin 3/metabolism ; Sirtuin 3/genetics ; Endothelial Cells/pathology ; Endothelial Cells/metabolism ; Endothelial Cells/drug effects
    Chemical Substances Sulfur Dioxide (0UZA3422Q4) ; Superoxide Dismutase (EC 1.15.1.1) ; superoxide dismutase 2 (EC 1.15.1.1) ; Sirtuin 3 (EC 3.5.1.-)
    Language English
    Publishing date 2024-02-27
    Publishing country United States
    Document type Journal Article ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 1013184-x
    ISSN 1522-1504 ; 1040-0605
    ISSN (online) 1522-1504
    ISSN 1040-0605
    DOI 10.1152/ajplung.00239.2023
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    Uc I Zs.89: Show issues Location:
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  8. Article ; Online: Quantifying ventilation by X-ray velocimetry in healthy adults.

    Siddharthan, Trishul / Grealis, Kyle / Kirkness, Jason P / Ötvös, Tamás / Stefanovski, Darko / Tombleson, Alex / Dalzell, Molly / Gonzalez, Ernesto / Nakrani, Kinjal Bhatt / Wenger, David / Lester, Michael G / Richmond, Bradley W / Fouras, Andreas / Punjabi, Naresh M

    Respiratory research

    2023  Volume 24, Issue 1, Page(s) 215

    Abstract: Rationale: X-ray velocimetry (XV) has been utilized in preclinical models to assess lung motion and regional ventilation, though no studies have compared XV-derived physiologic parameters to measures derived through conventional means.: Objectives: ... ...

    Abstract Rationale: X-ray velocimetry (XV) has been utilized in preclinical models to assess lung motion and regional ventilation, though no studies have compared XV-derived physiologic parameters to measures derived through conventional means.
    Objectives: To assess agreement between XV-analysis of fluoroscopic lung images and pitot tube flowmeter measures of ventilation.
    Methods: XV- and pitot tube-derived ventilatory parameters were compared during tidal breathing and with bilevel-assisted breathing. Levels of agreement were assessed using the Bland-Altman analysis. Mixed models were used to characterize the association between XV- and pitot tube-derived values and optimize XV-derived values for higher ventilatory volumes.
    Measurements and main results: Twenty-four healthy volunteers were assessed during tidal breathing and 11 were reassessed with increased minute ventilation with bilevel-assisted breathing. No clinically significant differences were observed between the two methods for respiratory rate (average Δ: 0.58; 95% limits of agreement: -1.55, 2.71) or duty cycle (average Δ: 0.02; 95% limits of agreement: 0.01, 0.03). Tidal volumes and flow rates measured using XV were lower than those measured using the pitot tube flowmeter, particularly at the higher volume ranges with bilevel-assisted breathing. Under these conditions, a mixed-model based adjustment was applied to the XV-derived values of tidal volume and flow rate to obtain closer agreement with the pitot tube-derived values.
    Conclusion: Radiographically obtained measures of ventilation with XV demonstrate a high degree of correlation with parameters of ventilation. If the accuracy of XV were also confirmed for assessing the regional distribution of ventilation, it would provide information that goes beyond the scope of conventional pulmonary function tests or static radiographic assessments.
    MeSH term(s) Adult ; Humans ; X-Rays ; Respiration ; Radiography ; Tidal Volume ; Lung/diagnostic imaging
    Language English
    Publishing date 2023-08-30
    Publishing country England
    Document type Journal Article
    ZDB-ID 2041675-1
    ISSN 1465-993X ; 1465-993X
    ISSN (online) 1465-993X
    ISSN 1465-993X
    DOI 10.1186/s12931-023-02517-z
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  9. Article ; Online: Identification of a distal enhancer regulating hedgehog interacting protein gene in human lung epithelial cells.

    Guo, Feng / Zhang, Li / Yu, Yuzhen / Gong, Lu / Tao, Shiyue / Werder, Rhiannon B / Mishra, Shreya / Zhou, Yihan / Anamika, Wardatul Jannat / Lao, Taotao / Inuzuka, Hiroyuki / Zhang, Yihan / Pham, Betty / Liu, Tao / Tufenkjian, Tiffany S / Richmond, Bradley W / Wei, Wenyi / Mou, Hongmei / Wilson, Andrew A /
    Hu, Ming / Chen, Wei / Zhou, Xiaobo

    EBioMedicine

    2024  Volume 101, Page(s) 105026

    Abstract: Background: An intergenic region at chromosome 4q31 is one of the most significant regions associated with COPD susceptibility and lung function in GWAS. In this region, the implicated causal gene HHIP has a unique epithelial expression pattern in adult ...

    Abstract Background: An intergenic region at chromosome 4q31 is one of the most significant regions associated with COPD susceptibility and lung function in GWAS. In this region, the implicated causal gene HHIP has a unique epithelial expression pattern in adult human lungs, in contrast to dominant expression in fibroblasts in murine lungs. However, the mechanism underlying the species-dependent cell type-specific regulation of HHIP remains largely unknown.
    Methods: We employed snATAC-seq analysis to identify open chromatin regions within the COPD GWAS region in various human lung cell types. ChIP-quantitative PCR, reporter assays, chromatin conformation capture assays and Hi-C assays were conducted to characterize the regulatory element in this region. CRISPR/Cas9-editing was performed in BEAS-2B cells to generate single colonies with stable knockout of the regulatory element. RT-PCR and Western blot assays were used to evaluate expression of HHIP and epithelial-mesenchymal transition (EMT)-related marker genes.
    Findings: We identified a distal enhancer within the COPD 4q31 GWAS locus that regulates HHIP transcription at baseline and after TGFβ treatment in a SMAD3-dependent, but Hedgehog-independent manner in human bronchial epithelial cells. The distal enhancer also maintains chromatin topological domains near 4q31 locus and HHIP gene. Reduced HHIP expression led to increased EMT induced by TGFβ in human bronchial epithelial cells.
    Interpretation: A distal enhancer regulates HHIP expression both under homeostatic condition and upon TGFβ treatment in human bronchial epithelial cells. The interaction between HHIP and TGFβ signalling possibly contributes to COPD pathogenesis.
    Funding: Supported by NIH grants R01HL127200, R01HL148667 and R01HL162783 (to X. Z).
    MeSH term(s) Adult ; Humans ; Animals ; Mice ; Hedgehog Proteins/metabolism ; Pulmonary Disease, Chronic Obstructive/metabolism ; Lung/pathology ; Epithelial Cells/metabolism ; Chromatin/genetics ; Chromatin/metabolism ; Transforming Growth Factor beta/metabolism
    Chemical Substances Hedgehog Proteins ; Chromatin ; Transforming Growth Factor beta
    Language English
    Publishing date 2024-02-27
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 2851331-9
    ISSN 2352-3964
    ISSN (online) 2352-3964
    DOI 10.1016/j.ebiom.2024.105026
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    Zs.A 7090: Show issues Location:
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  10. Article ; Online: Activation of mTOR signaling in adult lung microvascular progenitor cells accelerates lung aging.

    Mason, Emma C / Menon, Swapna / Schneider, Benjamin R / Gaskill, Christa F / Dawson, Maggie M / Moore, Camille M / Armstrong, Laura Craig / Cho, Okyong / Richmond, Bradley W / Kropski, Jonathan A / West, James D / Geraghty, Patrick / Gomperts, Brigitte N / Ess, Kevin C / Gally, Fabienne / Majka, Susan M

    The Journal of clinical investigation

    2023  Volume 133, Issue 24

    Abstract: Reactivation and dysregulation of the mTOR signaling pathway are a hallmark of aging and chronic lung disease; however, the impact on microvascular progenitor cells (MVPCs), capillary angiostasis, and tissue homeostasis is unknown. While the existence of ...

    Abstract Reactivation and dysregulation of the mTOR signaling pathway are a hallmark of aging and chronic lung disease; however, the impact on microvascular progenitor cells (MVPCs), capillary angiostasis, and tissue homeostasis is unknown. While the existence of an adult lung vascular progenitor has long been hypothesized, these studies show that Abcg2 enriches for a population of angiogenic tissue-resident MVPCs present in both adult mouse and human lungs using functional, lineage, and transcriptomic analyses. These studies link human and mouse MVPC-specific mTORC1 activation to decreased stemness, angiogenic potential, and disruption of p53 and Wnt pathways, with consequent loss of alveolar-capillary structure and function. Following mTOR activation, these MVPCs adapt a unique transcriptome signature and emerge as a venous subpopulation in the angiodiverse microvascular endothelial subclusters. Thus, our findings support a significant role for mTOR in the maintenance of MVPC function and microvascular niche homeostasis as well as a cell-based mechanism driving loss of tissue structure underlying lung aging and the development of emphysema.
    MeSH term(s) Mice ; Humans ; Animals ; Lung/metabolism ; TOR Serine-Threonine Kinases/genetics ; TOR Serine-Threonine Kinases/metabolism ; Stem Cells/metabolism ; Wnt Signaling Pathway ; Aging/genetics
    Chemical Substances TOR Serine-Threonine Kinases (EC 2.7.11.1)
    Language English
    Publishing date 2023-12-15
    Publishing country United States
    Document type Journal Article
    ZDB-ID 3067-3
    ISSN 1558-8238 ; 0021-9738
    ISSN (online) 1558-8238
    ISSN 0021-9738
    DOI 10.1172/JCI171430
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