International Journal of COPD (Nov 2018)
Cholinergic mechanisms in an organic dust model simulating an acute exacerbation in patients with COPD
Abstract
Lena Palmberg,* Britt-Marie Sundblad,* Jie Ji, Jakob Karén, Kjell Larsson Work Environment Toxicology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden *These authors contributed equally to this work Background: Exposure in a pig barn induces airway inflammation that has similarities with the response observed in acute exacerbations in COPD. Methods: A total of 15 smokers with COPD and 15 healthy non-smokers were exposed for 2 hours in a pig barn (in vivo exposure). Symptoms were assessed, lung function measured, and blood and sputum samples taken before and after exposure. Blood neutrophils were isolated and stimulated ex vivo with dust from a pig barn and acetylcholine, and inflammatory markers were analyzed. Results: In vivo exposure caused more symptoms and greater lung function fall in COPD patients than in controls. Baseline concentrations of MMP9, TIMP1, IL6, CXCL8, in sputum and neutrophil blood count were higher in COPD patients than in controls. In vivo exposure increased MMP9, TIMP1, IL6, CXCL8, TNFα, and LTB4 in sputum and MMP9 and IL6 in blood, with no difference between the groups, and serum CRP increased more in COPD subjects. Expression of choline acetyltransferase and acetylcholinesterase on sputum and blood cells was similar in the groups and uninfluenced by in vivo exposure. Dust exposure ex vivo increased choline acetyltransferase expression in neutrophils, but the dust and acetylcholine response did not differ between the groups before and after in vivo exposure. Conclusion: COPD patients exposed in a pig barn experience symptoms similar to those in acute exacerbations and lung function deterioration that is unrelated to bronchial responsiveness. Cholinergic mechanisms are involved in the inflammatory response to dust, with no difference between COPD and non-smokers. Keywords: organic dust, airway inflammation, chronic obstructive pulmonary disease, COPD, pig barn
