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Article: Commentary: A Breath of Fresh Air on the Mesenchyme: Impact of Impaired Mesenchymal Development on the Pathogenesis of Bronchopulmonary Dysplasia.

White, Eric S

2016 Volume 3, Page(s) 13

Language	English
Publishing date	2016-03-31
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2775999-4
ISSN	2296-858X
ISSN	2296-858X
DOI	10.3389/fmed.2016.00013
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Article: Challenges for Clinical Drug Development in Pulmonary Fibrosis.

White, Eric S / Thomas, Matthew / Stowasser, Susanne / Tetzlaff, Kay

Frontiers in pharmacology

2022 Volume 13, Page(s) 823085

Abstract: Pulmonary fibrosis is a pathologic process associated with scarring of the lung interstitium. Interstitial lung diseases (ILDs) encompass a large and heterogenous group of disorders, a number of which are characterized by progressive pulmonary fibrosis ... ...

Abstract	Pulmonary fibrosis is a pathologic process associated with scarring of the lung interstitium. Interstitial lung diseases (ILDs) encompass a large and heterogenous group of disorders, a number of which are characterized by progressive pulmonary fibrosis that leads to respiratory failure and death. Idiopathic pulmonary fibrosis (IPF) has been described as an archetype of progressive fibrosing ILD, and the development of pirfenidone and nintedanib has been a major breakthrough in the treatment of patients with this deadly disease. Both drugs principally target scar-forming fibroblasts and have been shown to significantly slow down the accelerated decline of lung function by approximately 50%. In addition, nintedanib has been approved for patients with other progressive fibrosing ILDs and systemic sclerosis-associated ILD. However, there is still no cure for pulmonary fibrosis and no meaningful improvement of symptoms or quality of life has been shown. Advancement in research, such as the advent of single cell sequencing technology, has identified additional pathologic cell populations beyond the fibroblast which could be targeted for therapeutic purposes. The preclinical and clinical development of novel drug candidates is hampered by profound challenges such as a lack of sensitive clinical outcomes or suitable biomarkers that would provide an early indication of patient benefit. With the availability of these anti-fibrotic treatments, it has become even more difficult to demonstrate added efficacy, in particular in short-term clinical studies. Patient heterogeneity and the paucity of biomarkers of disease activity further complicate clinical development. It is conceivable that future treatment of pulmonary fibrosis will need to embrace more precision in treating the right patient at the right time, explore novel measures of efficacy, and likely combine treatment options.
Language	English
Publishing date	2022-01-31
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2587355-6
ISSN	1663-9812
ISSN	1663-9812
DOI	10.3389/fphar.2022.823085
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Article ; Online: Lung extracellular matrix and fibroblast function.

White, Eric S

Annals of the American Thoracic Society

2015 Volume 12 Suppl 1, Page(s) S30–3

Abstract: Extracellular matrix (ECM) is a tissue-specific macromolecular structure that provides physical support to tissues and is essential for normal organ function. In the lung, ECM plays an active role in shaping cell behavior both in health and disease by ... ...

Abstract	Extracellular matrix (ECM) is a tissue-specific macromolecular structure that provides physical support to tissues and is essential for normal organ function. In the lung, ECM plays an active role in shaping cell behavior both in health and disease by virtue of the contextual clues it imparts to cells. Qualities including dimensionality, molecular composition, and intrinsic stiffness all promote normal function of the lung ECM. Alterations in composition and/or modulation of stiffness of the focally injured or diseased lung ECM microenvironment plays a part in reparative processes performed by fibroblasts. Under conditions of remodeling or in disease states, inhomogeneous stiffening (or softening) of the pathologic ECM may both precede modifications in cell behavior and be a result of disease progression. The ability of ECM to stimulate further ECM production by fibroblasts and drive disease progression has potentially significant implications for mesenchymal stromal cell-based therapies; in the setting of pathologic ECM stiffness or composition, the therapeutic intent of progenitor cells may be subverted. Taken together, current data suggest that lung ECM actively contributes to health and disease; thus, mediators of cell-ECM signaling or factors that influence ECM stiffness may represent viable therapeutic targets in many lung disorders.
MeSH term(s)	Extracellular Matrix/physiology ; Fibroblasts/physiology ; Humans ; Lung/physiology ; Lung/physiopathology
Language	English
Publishing date	2015-03
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ZDB-ID	2717461-X
ISSN	2325-6621 ; 1943-5665 ; 2325-6621
ISSN (online)	2325-6621 ; 1943-5665
ISSN	2325-6621
DOI	10.1513/AnnalsATS.201406-240MG
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Article ; Online: The American Thoracic Society Research Program: Twenty Years of Driving Discovery in Respiratory Medicine.

Atabai, Kamran / Badr, M Safwan / Costello, Jack / Ridge, Karen / Rounds, Sharon / Turenne, Michelle / White, Eric S / Roman, Jesse

American journal of respiratory and critical care medicine

2024 Volume 209, Issue 9, Page(s) 1047–1048

MeSH term(s)	Humans ; Pulmonary Medicine/history ; United States ; Societies, Medical/history ; Biomedical Research/history ; History, 21st Century ; History, 20th Century
Language	English
Publishing date	2024-03-29
Publishing country	United States
Document type	Editorial ; Historical Article
ZDB-ID	1180953-x
ISSN	1535-4970 ; 0003-0805 ; 1073-449X
ISSN (online)	1535-4970
ISSN	0003-0805 ; 1073-449X
DOI	10.1164/rccm.202402-0348ED
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Article ; Online: Adoption of Antifibrotic Medications: A Closer Look at the Data.

White, Eric S / Nili, Mona / Shetty, Sharash / Leonard, Thomas B

Annals of the American Thoracic Society

2021 Volume 18, Issue 10, Page(s) 1756–1757

MeSH term(s)	Humans ; Idiopathic Pulmonary Fibrosis/drug therapy ; Pyridones
Chemical Substances	Pyridones
Language	English
Publishing date	2021-05-12
Publishing country	United States
Document type	Letter ; Research Support, Non-U.S. Gov't ; Comment
ZDB-ID	2717461-X
ISSN	2325-6621 ; 1943-5665 ; 2325-6621
ISSN (online)	2325-6621 ; 1943-5665
ISSN	2325-6621
DOI	10.1513/AnnalsATS.202103-359LE
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Article ; Online: Three dimensional fibrotic extracellular matrix directs microenvironment fiber remodeling by fibroblasts.

Nizamoglu, Mehmet / Alleblas, Frederique / Koster, Taco / Borghuis, Theo / Vonk, Judith M / Thomas, Matthew J / White, Eric S / Watson, Carolin K / Timens, Wim / El Kasmi, Karim C / Melgert, Barbro N / Heijink, Irene H / Burgess, Janette K

Acta biomaterialia

2024 Volume 177, Page(s) 118–131

Abstract: Idiopathic pulmonary fibrosis (IPF), for which effective treatments are limited, results in excessive and disorganized deposition of aberrant extracellular matrix (ECM). An altered ECM microenvironment is postulated to contribute to disease progression ... ...

Abstract	Idiopathic pulmonary fibrosis (IPF), for which effective treatments are limited, results in excessive and disorganized deposition of aberrant extracellular matrix (ECM). An altered ECM microenvironment is postulated to contribute to disease progression through inducing profibrotic behavior of lung fibroblasts, the main producers and regulators of ECM. Here, we examined this hypothesis in a 3D in vitro model system by growing primary human lung fibroblasts in ECM-derived hydrogels from non-fibrotic (control) or IPF lung tissue. Using this model, we compared how control and IPF lung-derived fibroblasts responded in control and fibrotic microenvironments in a combinatorial manner. Culture of fibroblasts in fibrotic hydrogels did not alter in the overall amount of collagen or glycosaminoglycans but did cause a drastic change in fiber organization compared to culture in control hydrogels. High-density collagen percentage was increased by control fibroblasts in IPF hydrogels at day 7, but decreased at day 14. In contrast, IPF fibroblasts only decreased the high-density collagen percentage at day 14, which was accompanied by enhanced fiber alignment in IPF hydrogels. Similarly, stiffness of fibrotic hydrogels was increased only by control fibroblasts by day 14 while those of control hydrogels were not altered by fibroblasts. These data highlight how the ECM-remodeling responses of fibroblasts are influenced by the origin of both the cells and the ECM. Moreover, by showing how the 3D microenvironment plays a crucial role in directing cells, our study paves the way in guiding future investigations examining fibrotic processes with respect to ECM remodeling responses of fibroblasts. STATEMENT OF SIGNIFICANCE: In this study, we investigated the influence of the altered extracellular matrix (ECM) in Idiopathic Pulmonary Fibrosis (IPF), using a 3D in vitro model system composed of ECM-derived hydrogels from both IPF and control lungs, seeded with human IPF and control lung fibroblasts. While our results indicated that fibrotic microenvironment did not change the overall collagen or glycosaminoglycan content, it resulted in a dramatically alteration of fiber organization and mechanical properties. Control fibroblasts responded differently from IPF fibroblasts, highlighting the unique instructive role of the fibrotic ECM and the interplay with fibroblast origin. These results underscore the importance of 3D microenvironments in guiding pro-fibrotic responses, offering potential insights for future IPF therapies as well as other fibrotic diseases and cancer.
MeSH term(s)	Humans ; Extracellular Matrix ; Idiopathic Pulmonary Fibrosis/pathology ; Lung/pathology ; Fibrosis ; Collagen ; Fibroblasts/pathology ; Hydrogels/pharmacology
Chemical Substances	Collagen (9007-34-5) ; Hydrogels
Language	English
Publishing date	2024-02-11
Publishing country	England
Document type	Journal Article
ZDB-ID	2173841-5
ISSN	1878-7568 ; 1742-7061
ISSN (online)	1878-7568
ISSN	1742-7061
DOI	10.1016/j.actbio.2024.02.008
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Article ; Online: Accessory cardiac bronchus.

White, Eric S

American journal of respiratory and critical care medicine

2011 Volume 183, Issue 6, Page(s) 825

MeSH term(s)	Bronchi/abnormalities ; Bronchography ; Bronchoscopy ; Dyspnea/etiology ; Exercise Tolerance ; Humans ; Incidental Findings ; Male ; Middle Aged ; Tomography, X-Ray Computed
Language	English
Publishing date	2011-04-06
Publishing country	United States
Document type	Case Reports ; Journal Article
ZDB-ID	1180953-x
ISSN	1535-4970 ; 0003-0805 ; 1073-449X
ISSN (online)	1535-4970
ISSN	0003-0805 ; 1073-449X
DOI	10.1164/rccm.201009-1493IM
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Article ; Online: Hypothyroidism Is Associated with Increased Mortality in Interstitial Pneumonia with Autoimmune Features.

O'Dwyer, David N / Wang, Bonnie R / Nagaraja, Vivek / Flaherty, Kevin R / Khanna, Dinesh / Murray, Susan / Mari, Pier Valerio / White, Eric S

Annals of the American Thoracic Society

2022 Volume 19, Issue 10, Page(s) 1772–1776

MeSH term(s)	Autoimmune Diseases/complications ; Humans ; Hypothyroidism/complications ; Lung ; Lung Diseases, Interstitial
Language	English
Publishing date	2022-05-18
Publishing country	United States
Document type	Letter ; Research Support, N.I.H., Extramural
ZDB-ID	2717461-X
ISSN	2325-6621 ; 1943-5665 ; 2325-6621
ISSN (online)	2325-6621 ; 1943-5665
ISSN	2325-6621
DOI	10.1513/AnnalsATS.202203-233RL
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Article ; Online: Routine Chest Radiography for the Evaluation of Pneumothorax Following Bronchoscopy.

Centonze, Christopher P / Davenport, Matthew S / White, Eric S / Kazerooni, Ella A

Academic radiology

2019 Volume 26, Issue 5, Page(s) 585–590

Abstract: Rationale and objectives: To determine the utility of routine postbronchoscopy chest radiography to detect pneumothorax.: Materials and methods: This retrospective quality improvement cohort study was approved by the Institutional Review Board. All ... ...

Abstract	Rationale and objectives: To determine the utility of routine postbronchoscopy chest radiography to detect pneumothorax. Materials and methods: This retrospective quality improvement cohort study was approved by the Institutional Review Board. All outpatients (n = 1443) who underwent protocol-driven postbronchoscopy chest radiography in one health system from January 2010 to July 2017 were identified by electronic medical record query. The prevalence of pneumothorax (with 95% confidence intervals [CI]) and clinical outcome were determined following coded review of chest radiography reports and review of the electronic medical record. The effect of smoking and lung disease on risk of pneumothorax was determined with Chi Square tests. Results: Of 1443 subjects undergoing interventional bronchoscopy, 6% (93/1443) were current smokers, 35% (505/1442) were former smokers, and 35% (540/1443) had known lung disease. Pneumothorax prevalence was 3.4% (49/1443; 95% CI: 2.6%-4.5%) following any intervention and 4.1% (42/1032; 95% CI: 3.9%-5.5%) following transbronchial intervention. In those without known pre-existing pneumothorax or a confirmed false positive diagnosis, the real overall pneumothorax rate was 2.9% (42/1443; 95% CI: 2.1%-3.9%). The risk of pneumothorax did not differ based on smoking history (p = 0.99) or history of lung disease (p = 0.19). Of 49 subjects with pneumothorax, 13 were symptomatic, and 10 had a change in management including chest tube placement (N = 2), inpatient admission (N = 3), and/or observation (N = 7). No pneumothorax-related intervention was performed in asymptomatic patients. Conclusion: Pneumothorax following interventional outpatient bronchoscopy is uncommon, usually asymptomatic, and often clinically insignificant. Asymptomatic postbronchoscopy patients are very low risk and may not need routine imaging.
MeSH term(s)	Aged ; Bronchoscopy/adverse effects ; Cohort Studies ; Female ; Humans ; Lung Diseases/complications ; Lung Diseases/diagnostic imaging ; Male ; Middle Aged ; Pneumothorax/diagnostic imaging ; Pneumothorax/etiology ; Postoperative Complications/diagnostic imaging ; Postoperative Complications/etiology ; Radiography, Thoracic ; Retrospective Studies ; Smoking/adverse effects
Language	English
Publishing date	2019-05-02
Publishing country	United States
Document type	Journal Article
ZDB-ID	1355509-1
ISSN	1878-4046 ; 1076-6332
ISSN (online)	1878-4046
ISSN	1076-6332
DOI	10.1016/j.acra.2018.11.025
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Article ; Online: Lung function trajectories in patients with idiopathic pulmonary fibrosis.

Neely, Megan L / Hellkamp, Anne S / Bender, Shaun / Todd, Jamie L / Liesching, Timothy / Luckhardt, Tracy R / Oldham, Justin M / Raj, Rishi / White, Eric S / Palmer, Scott M

Respiratory research

2023 Volume 24, Issue 1, Page(s) 209

Abstract: Background: Idiopathic pulmonary fibrosis (IPF) is a progressive fibrosing interstitial lung disease characterised by decline in lung function. We evaluated trajectories of forced vital capacity (FVC) and diffusing capacity (DLco) in a cohort of ... ...

Abstract	Background: Idiopathic pulmonary fibrosis (IPF) is a progressive fibrosing interstitial lung disease characterised by decline in lung function. We evaluated trajectories of forced vital capacity (FVC) and diffusing capacity (DLco) in a cohort of patients with IPF. Methods: Patients with IPF that was diagnosed or confirmed at the enrolling centre in the previous 6 months were enrolled into the IPF-PRO Registry between June 2014 and October 2018. Patients were followed prospectively, with lung function data collected as part of routine clinical care. Mean trajectories of FVC and DLco % predicted in all patients and in subgroups by characteristics assessed at enrolment were estimated using a joint model that accounted for factors such as disease severity and visit patterns. Results: Of 1002 patients in the registry, 941 had ≥ 1 FVC and/or DLco measurement after enrolment. The median (Q1, Q3) follow-up period was 35.1 (18.9, 47.2) months. Overall, mean estimated declines in FVC and DLco % predicted were 2.8% and 2.9% per year, respectively. There was no evidence that the mean trajectories of FVC or DLco had a non-linear relationship with time at the population level. Patients who were male, white, had a family history of ILD, were using oxygen, or had prior/current use of antifibrotic therapy at enrolment had greater rates of decline in FVC % predicted. Patients who were male or white had greater rates of decline in DLco % predicted. Conclusions: Data from the IPF-PRO Registry suggest a constant rate of decline in lung function over a prolonged period, supporting the inexorably progressive nature of IPF. A graphical abstract summarising the data in this manuscript is available at: https://www.usscicomms.com/respiratory/IPF-PRORegistry_LungFunctionTrajectories . Trial registration: NCT01915511.
MeSH term(s)	Female ; Humans ; Male ; Idiopathic Pulmonary Fibrosis/diagnosis ; Idiopathic Pulmonary Fibrosis/drug therapy ; Lung ; Oxygen ; Patient Acuity ; Registries
Chemical Substances	Oxygen (S88TT14065)
Language	English
Publishing date	2023-08-24
Publishing country	England
Document type	Clinical Study ; Journal Article
ZDB-ID	2041675-1
ISSN	1465-993X ; 1465-993X
ISSN (online)	1465-993X
ISSN	1465-993X
DOI	10.1186/s12931-023-02503-5
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