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Research
Don Sin
University of British Columbia
Corresponding Author
ORCiD: https://orcid.org/0000-0002-0756-6643
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background;
Emphysema is a common phenotype of chronic obstructive pulmonary disease (COPD). Although resection of emphysematous tissue can improve lung mechanics, it is invasive and fraught with adverse effects. Meanwhile, radiofrequency (RF) treatment is an extracorporeal method that leads to tissue destruction and remodeling, resulting in “volume reduction” and overall improvement in lung compliance of emphysematous lungs. Whether these changes lead to improved exercise tolerance is unknown. Here, we investigated the effectiveness of RF treatment to improve the exercise capacity of mice with emphysema.
Methods;
Fifty-two mice (7 weeks of age) were used in this experiment. A bilateral emphysema model was created by intratracheally instilling porcine pancreatic elastase (PPE) (1.5U/100g body weight). RF treatment (0.5W/ g body weight) was performed extracorporeally 14 days later and mice were sacrificed after another 21 days. The exercise capacity of mice was measured using a treadmill. Treadmill runs were performed just before PPE instillation (baseline), before RF treatment and before sacrifice. Following sacrifice, lung compliance and mean linear intercept (Lm) were measured and fibrosis was assessed using a modified Ashcroft score.
Results;
There were 3 experimental groups: controls (instilled with saline, n=12), emphysema (instilled with porcine pancreatic elastase, PPE, n=11) and emphysema + treatment (instilled with PPE and given RF, n=9). At endpoint, the maximum velocity of the emphysema + treatment group was significantly higher than that of the emphysema group, indicating improved exercise tolerance (86.29% of baseline vs 61.69% of baseline, p=0.011). Histological analysis revealed a significant reduction in emphysema as denoted by Lm between the two groups (median 29.60 µm vs 35.68 µm, p=0.033). The emphysema + treatment group also demonstrated a higher prevalence of lung fibrosis (≧Grade 3) compared with the emphysema group (11.7% vs 5.4%, p<0.0001). No severe adverse events from RF were observed.
Conclusion;
RF treatment improved the exercise capacity of mice with emphysema. These data highlight the therapeutic potential of RF treatment in improving the functional status of patients with COPD.
Keywords
Radiofrequency treatment, Emphysema, COPD, Exercise capacity, Extracorporeal
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This is a list of supplementary files associated with this preprint. Click to download.
- Additionalfile1FigureS1..tif
Additional Figure 1: Figure S1. File format: TIFF Title of data: Results of the PPE dose optimization experiment. Description of data: (A) Body weight change after intratracheal instillation. The group instilled with PPE (1.5 U/ 100g body weight (BW)) showed significant body weight loss until day 7 after the instillation. (B) Maximum velocity compared to the baseline on day 14. The PPE instilled group showed a significantly greater velocity loss. (C) Mean linear intercepts were significantly larger in the PPE group. (D) Representative images (H&E staining) of the lung histology on day 14. Clear emphysema was observed in the PPE instilled group. Asterisks indicate a significant difference in the comparisons between the groups (*p<0.05, **p<0.01).
- Additionalfile2FigureS2..tif
Additional Figure 2: Figure S2. File format: TIFF Title of data: Body weight of mice over the study period. Description of data: (A): PPE-instilled mice lost body weight compared with saline controls until day 7 post-instillation. The weight loss was at maximum on day 2 and recovered by day 14. (B): RF treatment did not induce weight loss. The asterisks under each time point indicate significant differences compared to the saline control group (*p<0.05, ***p<0.001).
- Additionalfile3FigureS3..tif
Additional Figure 3: Figure S3. File format: TIFF Title of data: Maximum velocity on day14. Description of data: On day 14, the maximum velocity was measured just before the RF treatment. Therefore, the emphysema + treatment group is logically identical to the emphysema group. (A) Maximum velocity on day 14. No significant difference was observed between the control and emphysema and emphysema + treatment group. (B) A detailed comparison of the maximum velocity on day 14. No differences were observed among the 3 groups.
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This is a preprint. It has not completed peer review.
Research
Don Sin
University of British Columbia
Corresponding Author
ORCiD: https://orcid.org/0000-0002-0756-6643
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
History
CURRENT STATUS: Posted
Version 1
Posted 15 Jan, 2021
No community comments so far
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background;
Emphysema is a common phenotype of chronic obstructive pulmonary disease (COPD). Although resection of emphysematous tissue can improve lung mechanics, it is invasive and fraught with adverse effects. Meanwhile, radiofrequency (RF) treatment is an extracorporeal method that leads to tissue destruction and remodeling, resulting in “volume reduction” and overall improvement in lung compliance of emphysematous lungs. Whether these changes lead to improved exercise tolerance is unknown. Here, we investigated the effectiveness of RF treatment to improve the exercise capacity of mice with emphysema.
Methods;
Fifty-two mice (7 weeks of age) were used in this experiment. A bilateral emphysema model was created by intratracheally instilling porcine pancreatic elastase (PPE) (1.5U/100g body weight). RF treatment (0.5W/ g body weight) was performed extracorporeally 14 days later and mice were sacrificed after another 21 days. The exercise capacity of mice was measured using a treadmill. Treadmill runs were performed just before PPE instillation (baseline), before RF treatment and before sacrifice. Following sacrifice, lung compliance and mean linear intercept (Lm) were measured and fibrosis was assessed using a modified Ashcroft score.
Results;
There were 3 experimental groups: controls (instilled with saline, n=12), emphysema (instilled with porcine pancreatic elastase, PPE, n=11) and emphysema + treatment (instilled with PPE and given RF, n=9). At endpoint, the maximum velocity of the emphysema + treatment group was significantly higher than that of the emphysema group, indicating improved exercise tolerance (86.29% of baseline vs 61.69% of baseline, p=0.011). Histological analysis revealed a significant reduction in emphysema as denoted by Lm between the two groups (median 29.60 µm vs 35.68 µm, p=0.033). The emphysema + treatment group also demonstrated a higher prevalence of lung fibrosis (≧Grade 3) compared with the emphysema group (11.7% vs 5.4%, p<0.0001). No severe adverse events from RF were observed.
Conclusion;
RF treatment improved the exercise capacity of mice with emphysema. These data highlight the therapeutic potential of RF treatment in improving the functional status of patients with COPD.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
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