Effect of prolonged lipopolysaccharide exposure on lung function and health

Abstract

RationalePatients with Chronic Obstructive Pulmonary Disease often have persistent inflammation of the airways that lead to symptoms of chronic bronchitis and airway obstruction. While it is known that long term exposure to cigarette smoke can cause persistent airways inflammation, it is not clear if this is a direct result of tobacco exposure or if it is a result of chronic inflammation. We hypothesized that a recurrent and prolonged inflammatory insult would result in alterations in lung mechanics characterized by airway obstruction.Methods. To test the independent effects of recurrent and persistent lung inflammation on lung mechanics, C57Bl/6 8 week old male mice were treated weekly with PBS or lipopolysaccharide (LPS) via direct intratracheal injection. Monthly, we evaluated lung function analysis including: airway resistance and compliance, tissue damping, pressure volume loops, and forced expiratory volume using the flexiVent system.Results. Airway resistance at month 1 was 0.5543±0.017 PBS vs 0.552±0.009 cmH2O.s/mL LPS (p=0.999), month 2 0.5177±0.015 PBS vs 0.576±0.017 LPS (p=0.999), month 3 0.461± 0.03 PBS vs 0.47±0.038 cmH2O.s/mL LPS (p=0.999), month 5 0.43±0.015 PBS vs 0.468±0.026 cmH2O.s/mL LPS (p=0.999), month 6 PBS 0.408± 0.06 vs LPS 0.6465±0.18 cmH2O.s/mL (p=0.999), and month 7 PBS 0.384 ± 0.023 vs LPS 0.3498 ± 0.015 cmH2O.s/mL (p=0.999). Forced expiratory volume 0.1 (FEV 0.1) at month 1 was 0.4±0.08 PBS vs 0.803±0.107 mL LPS (p=0.999), month 2 0.2115±0.01 PBS vs 0.184±0.03 mL LPS (p=0.999), month 3 1.071±0.09 PBS vs 1.098±0.06 mL LPS (p=0.999), month 5 0.853±0.243 vs 0.756±0.21 mL LPS (p=0.999), month 6 2.671±1.06 PBS vs 1.669±0.87 mL LPS (p=0.999), month 7 0.9049±0.27 PBS vs 1.127±0.152 mL LPS (p=0.999).ConclusionIt is well known that chronic smoking can have a significant impact of lung function. Through this project we aimed to discover whether chronic inflammation alone would alter lung function. Interestingly even after weekly direct intratracheal injections of LPS there were no significant changes in lung function compared to PBS treated mice. We have shown here that chronic inflammation alone was not sufficient to alter lung function in mice, and that the decrease in lung function seen in chronic smokers is attributable to numerous factors and not inflammation alone.