Guy Cameron


PhD, Bbiomedsci(hons)

Airway and parenchymal transcriptomics in a novel model of asthma and COPD overlap


Journal article


Tu X, Kim RY, Brown AC, de Jong E, Jones-Freeman B, Ali MK, Gomez HM, Budden KF, Starkey MR, Cameron GJM, Loering S, Nguyen DH, Nair PM, Haw TJ, Alemao CA, Faiz A, Tay HL, Wark PAB, Knight DA, Foster PS, Bosco A, Horvat JC, Hansbro PM, Donovan C.
J Allergy Clin Immunol, S0091-6749(22), 2022, pp. 00706-0


Full text PubMed
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APA
X, T., RY, K., AC, B., de Jong E, B, J.-F., MK, A., … C., D. (2022). Airway and parenchymal transcriptomics in a novel model of asthma and COPD overlap. J Allergy Clin Immunol, S0091-6749(22), 00706–00700.

Chicago/Turabian
X, Tu, Kim RY, Brown AC, de Jong E, Jones-Freeman B, Ali MK, Gomez HM, et al. “Airway and Parenchymal Transcriptomics in a Novel Model of Asthma and COPD Overlap.” J Allergy Clin Immunol S0091-6749, no. 22 (2022): 00706–0.

MLA
X, Tu, et al. “Airway and Parenchymal Transcriptomics in a Novel Model of Asthma and COPD Overlap.” J Allergy Clin Immunol, vol. S0091-6749, no. 22, 2022, pp. 00706–00.


Abstract

Background: Asthma and chronic obstructive pulmonary disease (COPD) are common chronic respiratory diseases, and some patients have overlapping disease features, termed asthma-COPD overlap (ACO). Patients characterized with ACO have increased disease severity; however, the mechanisms driving this have not been widely studied.
Objectives: This study sought to characterize the phenotypic and transcriptomic features of experimental ACO in mice induced by chronic house dust mite antigen and cigarette smoke exposure.
Methods: Female BALB/c mice were chronically exposed to house dust mite antigen for 11 weeks to induce experimental asthma, cigarette smoke for 8 weeks to induce experimental COPD, or both concurrently to induce experimental ACO. Lung inflammation, structural changes, and lung function were assessed. RNA-sequencing was performed on separated airway and parenchyma lung tissues to assess transcriptional changes. Validation of a novel upstream driver SPI1 in experimental ACO was assessed using the pharmacological SPI1 inhibitor, DB2313.
Results: Experimental ACO recapitulated features of both asthma and COPD, with mixed pulmonary eosinophilic/neutrophilic inflammation, small airway collagen deposition, and increased airway hyperresponsiveness. Transcriptomic analysis identified common and distinct dysregulated gene clusters in airway and parenchyma samples in experimental asthma, COPD, and ACO. Upstream driver analysis revealed increased expression of the transcription factor Spi1. Pharmacological inhibition of SPI1 using DB2313, reduced airway remodeling and airway hyperresponsiveness in experimental ACO.
Conclusions: A new experimental model of ACO featuring chronic dual exposures to house dust mite and cigarette smoke mimics key disease features observed in patients with ACO and revealed novel disease mechanisms, including upregulation of SPI1, that are amenable to therapy.


Keywords: Asthma COPD overlap; SPI1; cigarette smoke; house dust mite; transcriptomics.
Copyright © 2022 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.