@article {Keir185, author = {Holly Rachael Keir and Hollian Richardson and Amy Gilmour and Daniela Alferes De Lima and Abirami Veluchamy and Chandani Hennayake and Merete B Long and Diane Cassidy and Amelia Shoemark and James D Chalmers}, title = {The Cathelicidin LL-37 and microbial dysbiosis in COPD patients receiving inhaled corticosteroids}, volume = {8}, number = {suppl 8}, elocation-id = {185}, year = {2022}, doi = {10.1183/23120541.LSC-2022.185}, publisher = {European Respiratory Society}, abstract = {Introduction: Recent studies have suggested that suppression of the antimicrobial peptide LL-37 results in increased bacterial load and expansion of Streptococcus in murine models of COPD. We investigated the relationship between LL-37, bacterial load and airway inflammation in patients with COPD.Methods: Stable patients with moderate to severe COPD, a blood eosinophil count \<300cell/ul and receiving inhaled corticosteroid (ICS) therapy were enrolled. The microbiome was characterised by 16S rRNA sequencing and qPCR in sputum. Sputum LL-37 levels was measured by ELISA.Results: 76 patients with COPD were enrolled, mean age 69.3, 51.2\% male, 32.5\% current smokers, mean CAT score of 20.6. The microbiome was heterogenous, with the majority of sequences identified as Proteobacteria or Firmicutes phyla. LL-37 concentrations ranged from 0.01-290.0ng/mL. Higher LL-37 was associated with elevated sputum bacterial load (16S copies/ml, r=0.34 95\% CI 0.12-0.54,p=0.0024) and was negatively associated with microbiome diversity (Shannon diversity index p\<0.0001 and Chao index p\<0.0001). Patients were divided into tertiles of LL-37 concentrations, with the highest tertile showing altered beta-diversity (PERMANOVA p\<0.0001). Random Forest analysis showed high sputum LL-37 levels associated with Haemophilus, while low LL-37 levels were associated with Streptococcus and commensal taxa such as Rothia. LL-37 showed a strong linear correlation with neutrophil extracellular traps, elastase and CXCL8 suggesting neutrophils as a likely source.Conclusion: Elevated LL-37 is associated with higher bacterial load, neutrophilic inflammation and microbial dysbiosis in patients with COPD using regular ICS.FootnotesCite this article as ERJ Open Research 2022; 8: Suppl. 8, 185.This article was presented at the 2022 ERS Lung Science Conference, in session {\textquotedblleft}Poster Session 2{\textquotedblright}.This is an ERS Lung Science Conference abstract. No full-text version is available. Further material to accompany this abstract may be available at www.ers-education.org (ERS member access only).}, URL = {https://openres.ersjournals.com/content/8/suppl_8/185}, eprint = {https://openres.ersjournals.com/content}, journal = {ERJ Open Research} }