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Updated: Oct 29, 2025
Automated Measurement of Pulmonary Emphysema and Small Airway Remodeling in Cigarette Smoke-exposed Mice
Published on: January 16, 2015
Development and multimodal characterization of an elastase-induced emphysema mouse disease model for the COPD
Irene Rodríguez-Arce1, Xabier Morales2,3, Mikel Ariz2,3
1Instituto De Agrobiotecnología, CSIC (IdAB-CSIC)-Gobierno de Navarra, Mutilva, Spain.
Abstract:
Chronic obstructive pulmonary disease (COPD) patients undergo infectious exacerbations whose frequency identifies a clinically meaningful phenotype. Mouse models have been mostly used to separately study both COPD and the infectious processes, but a reliable model of the COPD frequent exacerbator phenotype is still lacking. Accordingly, we first established a model of single bacterial exacerbation by nontypeable Haemophilus influenzae (NTHi) infection on mice with emphysema-like lesions. We characterized this single exacerbation model combining both noninvasive in vivo imaging and ex vivo techniques, obtaining longitudinal information about bacterial load and the extent of the developing lesions and host responses. Bacterial load disappeared 48 hours post-infection (hpi). However, lung recovery, measured using tests of pulmonary function and the disappearance of lung inflammation as revealed by micro-computed X-ray tomography, was delayed until 3 weeks post-infection (wpi). Then, to emulate the frequent exacerbator phenotype, we performed two recurrent episodes of NTHi infection on the emphysematous murine lung. Consistent with the amplified infectious insult, bacterial load reduction was now observed 96 hpi, and lung function recovery and disappearance of lesions on anatomical lung images did not happen until 12 wpi. Finally, as a proof of principle of the use of the model, we showed that azithromycin successfully cleared the recurrent infection, confirming this macrolide utility to ameliorate infectious exacerbation. In conclusion, we present a mouse model of recurrent bacterial infection of the emphysematous lung, aimed to facilitate investigating the COPD frequent exacerbator phenotype by providing complementary, dynamic information of both infectious and inflammatory processes.
Insights
Researchers developed a new mouse model for chronic obstructive pulmonary disease (COPD) frequent exacerbations. This model simulates recurrent bacterial lung infections, aiding the study of COPD exacerbator phenotypes.
Area of Science:
- Pulmonary Medicine and Infectious Disease Research
- Animal Models for Respiratory Diseases
Background:
- Chronic obstructive pulmonary disease (COPD) patients experience frequent infectious exacerbations, a key clinical phenotype.
- Existing mouse models inadequately represent the frequent exacerbator COPD phenotype, hindering research.
- A reliable model is needed to study recurrent infections in COPD.
Purpose of the Study:
- To establish and characterize a mouse model of recurrent bacterial lung infection in emphysema.
- To investigate the dynamics of infection, inflammation, and lung function recovery after single and recurrent exacerbations.
- To validate the model's utility for testing therapeutic interventions.
Main Methods:
- Established emphysema-like lesions in mice, followed by single or recurrent nontypeable Haemophilus influenzae (NTHi) infections.
- Utilized noninvasive in vivo imaging and ex vivo techniques for longitudinal assessment of bacterial load, lesions, and host response.
- Evaluated pulmonary function and lung inflammation using micro-computed X-ray tomography.
Main Results:
- Single NTHi infection showed bacterial clearance by 48 hours post-infection, but lung recovery was delayed until 3 weeks post-infection.
- Recurrent NTHi infections resulted in prolonged bacterial presence (96 hours post-infection) and delayed lung function recovery (12 weeks post-infection).
- Azithromycin treatment successfully reduced recurrent infections, demonstrating the model's potential for therapeutic evaluation.
Conclusions:
- A novel mouse model of recurrent bacterial lung infection in emphysematous lungs was successfully developed.
- This model provides dynamic insights into infectious and inflammatory processes relevant to the COPD frequent exacerbator phenotype.
- The model facilitates the investigation of COPD exacerbations and the efficacy of treatments like azithromycin.
