Dynamic characteristics of sequential acute exacerbations and risk windows in AECOPD rats induced by cigarette-smoke and exposure to Klebsiella pneumoniae

Abstract

The risk-window (RW) of chronic obstructive pulmonary disease (COPD) is a period after an acute exacerbation (AE) but before the following stable phase, in which exacerbations are easy to relapse. We established a sequential COPD-AE-RW rat model by cigarette-smoke and bacterial exposures in the first 8 weeks, and was challenged with Klebsiella pneumonia to mimic an AE on Day 1 of week 9, and found that body temperature, white blood cell, neutrophils, serum amyloid A (SAA) and C-reactive protein (CRP) increased in AECOPD rats 24 hours after challenge, and declined in 3 ~ 6 days, while lung function declined in 48 hours, and recovered in 7 ~ 16 days. When sacrificed, pulmonary FEV100 and FEV300 decreased, while elevated BALF neutrophils and marked airway inflammation, remodeling and emphysema were observed. Sequential COPD-AE-RW rat model was established successfully and AE phase lasts for approximately 5 ~ 7 days, followed by a 10-day around risk-window.