TY - JOUR T1 - Reduced neutrophil elastase inhibitor elafin and elevated TGFβ<sub>1</sub> are linked to inflammatory response in sputum of CF patients with Pseudomonas aeruginosa JF - ERJ Open Research JO - erjor DO - 10.1183/23120541.00636-2020 SP - 00636-2020 AU - Jan C. Thomassen AU - Tobias Trojan AU - Maxine Walz AU - Christina Vohlen AU - Gregor Fink AU - Ernst Rietschel AU - Miguel A. Alejandre Alcazar AU - Silke van Koningsbruggen-Rietschel Y1 - 2021/01/01 UR - http://openres.ersjournals.com/content/early/2021/04/22/23120541.00636-2020.abstract N2 - Research question Pulmonary disease progression in patients with cystic fibrosis (CF) is characterized by inflammation and fibrosis, and aggravated by Pseudomonas aeruginosa (Pa). We investigated the impact of Pa specifically 1) on protease/antiprotease balance and 2) inflammation, as well as 3) the link of both parameters to clinical parameters of CF-patients.Methods TGFβ1, IL1β, IL8, neutrophil elastase (NE) and elastase inhibitor elafin were measured (ELISA assays), and gene expression of the NF-ĸB pathway was assessed (RT-PCR) in the sputum of 60 CF-patients with a minimum age of 5 years. Spirometry was assessed according to ATS guidelines.Results 1) NE was markedly increased in Pa-positive sputum, whereas elafin was significantly decreased. 2) Increased IL1β/IL8 were associated with both Pa infection and reduced FEV1, as well as sputum TGFβ1 was elevated in Pa-infected CF-patients and linked to an impaired lung function. 3) Moreover, gene expression of NF-ĸB signaling components was increased in sputum of Pa-infected patients; these findings were positively correlated with IL8.Conclusion Our study links Pa infection to an imbalance of NE and NE-inhibitor elafin and increased inflammatory mediators. Moreover, our data demonstrate an association between high TGFβ1 sputum levels and a progress in chronic lung inflammation and pulmonary fibrosis in CF. Controlling the excessive airway inflammation by inhibition of NE and TGFβ1 might be promising therapeutic strategies in future CF therapy and a possible complement to CFTR-modulators.FootnotesThis manuscript has recently been accepted for publication in the ERJ Open Research. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJOR online. Please open or download the PDF to view this article.Conflict of interest: Dr. Thomassen has nothing to disclose.Conflict of interest: Dr. Trojan has nothing to disclose.Conflict of interest: Dr. Walz has nothing to disclose.Conflict of interest: Dr. Vohlen has nothing to disclose.Conflict of interest: Dr. Fink has nothing to disclose.Conflict of interest: Dr. Rietschel has nothing to disclose.Conflict of interest: Dr. Alejandre Alcazar has nothing to disclose.Conflict of interest: Dr. van Koningsbruggen-Rietschel has nothing to disclose. ER -