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Interventional low-dose azithromycin attenuates cigarette smoke-induced emphysema and lung inflammation in mice.
Physiol Rep. 2020 Jul; 8(13):e14419.PR

Abstract

Cigarette smoke (CS)-induced emphysema is an important contributor to chronic obstructive pulmonary disease (COPD). We have shown the efficacy of azithromycin in reducing airway inflammation in COPD and in reducing exacerbations in severe asthma; however, the effects of long-term azithromycin on emphysema development have not been shown. We employed live animal imaging to monitor emphysema-like development and the effects of interventional azithromycin treatment in CS-exposed mice. BALB/c mice (female, 10 weeks; n = 10) were exposed to CS for 1 hr twice daily, 5 days/week, and for 12 weeks (CS). Half were cotreated with low-dose azithromycin during weeks 7-12 (CS + Azi; 0.2 mg kg-1 day-1). Microcomputed tomography (CT) and magnetic resonance imaging (MRI) scans were acquired longitudinally. Histological examinations were performed post mortem (mean linear intercept (Lm) and leukocyte infiltration). CS increased median Lm (CS: 42.45 µm versus control: 34.7 µm; p = .0317), this was recovered in CS + Azi mice (33.03 µm). Average CT values were reduced in CS mice (CS: -399.5 Hounsfield units (HU) versus control: -384.9 HU; p = .0286) but not in CS + Azi mice (-377.3 HU). CT values negatively correlated with Lm (r = -.7972; p = .0029) and T2 -weighted MRI (r = -.6434; p = .0278). MRI also showed significant CS-induced inflammatory changes that were attenuated by azithromycin in the lungs, and positively correlated with Lm (r = .7622; p = .0055) and inflammatory foci counts (r = .6503; p = .0257). Monitoring of emphysema development is possible via micro-CT and MRI. Interventional azithromycin treatment in CS-exposed mice attenuated the development of pulmonary emphysema-like changes.

Authors+Show Affiliations

Department of Thoracic Medicine, Royal Adelaide Hospital, Adelaide, SA, Australia. Adelaide Medical School, University of Adelaide, Adelaide, SA, Australia. Department of Immunology and Pathology, Monash University, Melbourne, VIC, Australia.Department of Thoracic Medicine, Royal Adelaide Hospital, Adelaide, SA, Australia. Adelaide Medical School, University of Adelaide, Adelaide, SA, Australia.Preclinical, Imaging and Research Laboratories (PIRL), South Australian Health and Medical Research Institute (SAHMRI), Adelaide, SA, Australia. Sydney School of Veterinary Science, Faculty of Science, University of Sydney, Sydney, NSW, Australia.Department of Thoracic Medicine, Royal Adelaide Hospital, Adelaide, SA, Australia. Adelaide Medical School, University of Adelaide, Adelaide, SA, Australia.Department of Thoracic Medicine, Royal Adelaide Hospital, Adelaide, SA, Australia. Centre for Cancer Biology, University of South Australia and SA Pathology, Adelaide, SA, Australia.Department of Thoracic Medicine, Royal Adelaide Hospital, Adelaide, SA, Australia. Adelaide Medical School, University of Adelaide, Adelaide, SA, Australia.Adelaide Medical School, University of Adelaide, Adelaide, SA, Australia.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32652854

Citation

Macowan, Matthew G., et al. "Interventional Low-dose Azithromycin Attenuates Cigarette Smoke-induced Emphysema and Lung Inflammation in Mice." Physiological Reports, vol. 8, no. 13, 2020, pp. e14419.
Macowan MG, Liu H, Keller MD, et al. Interventional low-dose azithromycin attenuates cigarette smoke-induced emphysema and lung inflammation in mice. Physiol Rep. 2020;8(13):e14419.
Macowan, M. G., Liu, H., Keller, M. D., Ween, M., Hamon, R., Tran, H. B., & Hodge, S. (2020). Interventional low-dose azithromycin attenuates cigarette smoke-induced emphysema and lung inflammation in mice. Physiological Reports, 8(13), e14419. https://doi.org/10.14814/phy2.14419
Macowan MG, et al. Interventional Low-dose Azithromycin Attenuates Cigarette Smoke-induced Emphysema and Lung Inflammation in Mice. Physiol Rep. 2020;8(13):e14419. PubMed PMID: 32652854.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Interventional low-dose azithromycin attenuates cigarette smoke-induced emphysema and lung inflammation in mice. AU - Macowan,Matthew G, AU - Liu,Hong, AU - Keller,Marianne D, AU - Ween,Miranda, AU - Hamon,Rhys, AU - Tran,Hai B, AU - Hodge,Sandra, PY - 2020/01/09/received PY - 2020/03/17/revised PY - 2020/03/18/accepted PY - 2020/7/12/entrez PY - 2020/7/12/pubmed PY - 2020/7/12/medline KW - COPD KW - chronic obstructive pulmonary disease KW - emphysema KW - in vivo imaging KW - magnetic resonance imaging KW - micro-CT KW - mouse model SP - e14419 EP - e14419 JF - Physiological reports JO - Physiol Rep VL - 8 IS - 13 N2 - Cigarette smoke (CS)-induced emphysema is an important contributor to chronic obstructive pulmonary disease (COPD). We have shown the efficacy of azithromycin in reducing airway inflammation in COPD and in reducing exacerbations in severe asthma; however, the effects of long-term azithromycin on emphysema development have not been shown. We employed live animal imaging to monitor emphysema-like development and the effects of interventional azithromycin treatment in CS-exposed mice. BALB/c mice (female, 10 weeks; n = 10) were exposed to CS for 1 hr twice daily, 5 days/week, and for 12 weeks (CS). Half were cotreated with low-dose azithromycin during weeks 7-12 (CS + Azi; 0.2 mg kg-1 day-1). Microcomputed tomography (CT) and magnetic resonance imaging (MRI) scans were acquired longitudinally. Histological examinations were performed post mortem (mean linear intercept (Lm) and leukocyte infiltration). CS increased median Lm (CS: 42.45 µm versus control: 34.7 µm; p = .0317), this was recovered in CS + Azi mice (33.03 µm). Average CT values were reduced in CS mice (CS: -399.5 Hounsfield units (HU) versus control: -384.9 HU; p = .0286) but not in CS + Azi mice (-377.3 HU). CT values negatively correlated with Lm (r = -.7972; p = .0029) and T2 -weighted MRI (r = -.6434; p = .0278). MRI also showed significant CS-induced inflammatory changes that were attenuated by azithromycin in the lungs, and positively correlated with Lm (r = .7622; p = .0055) and inflammatory foci counts (r = .6503; p = .0257). Monitoring of emphysema development is possible via micro-CT and MRI. Interventional azithromycin treatment in CS-exposed mice attenuated the development of pulmonary emphysema-like changes. SN - 2051-817X UR - https://www.unboundmedicine.com/medline/citation/32652854/Interventional_low-dose_azithromycin_attenuates_cigarette_smoke-induced_emphysema_and_lung_inflammation_in_mice L2 - https://doi.org/10.14814/phy2.14419 DB - PRIME DP - Unbound Medicine ER -
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