Dynamic Characteristics of Sequential Acute Exacerbations and Risk Windows in AECOPD Rats Induced by Cigarette-Smoke and Exposure to Klebsiella pneumoniae.

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 h after challenge, and declined in 3-6 d, while lung function declined in 48 h, and recovered in 7-16 d. When sacrificed, pulmonary forced expiratory volume (FEV)100 and FEV300 decreased, while elevated bronchoalveolar lavage fluid (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 d, followed by a 10-d around risk-window.