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

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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.