OP1 ER STRESS PATHWAY ACTIVATION IN COPD: INSIGHTS FROM PBMC mRNA EXPRESSION STUDIES

Jia Wen Yeap1, Mei Lan Tan1, Baharudin Ibrahim2, Irfhan Ali Hyder Ali3*
1School of Pharmaceutical Sciences, Universiti Sains Malaysia, 11800 Universiti Sains Malaysia,
Pulau Pinang. Malaysia.
2Department of Clinical Pharmacy & Pharmacy Practice, Faculty of Pharmacy, University of Malaya, 50603 Kuala Lumpur, Malaysia.
3Respiratory Department, Penang General Hospital, Jalan Residensi, 10990 Pulau Pinang, Malaysia.

This study explores the activation of the ER stress pathway in COPD, triggered by factors like cigarette smoke and inflammation. Understanding these mechanisms is crucial for developing targeted therapies and improving outcomes for COPD patients. Researchers recruited 55 COPD outpatients and 55 non-COPD subjects for surveys, interviews, and blood sampling. They analyzed PBMCs to study mRNA expression of ER stress markers (BIP, CHOP, sXBP1, ATF4, ATF6, JNK). Results showed COPD patients had increased BIP (p=0.050), CHOP (p<0.001), and sXBP1 (p<0.001) expression, and decreased JNK levels (p<0.001) compared to non-COPD controls. Among COPD patients, BIP (r=0.299, p=0.035) and ATF6 (r=0.290, p=0.041) positively correlated with FEV1 (% Predicted). SABA usage correlated with ATF6 (r=0.366, p=0.006) and JNK (r=0.319, p=0.019) mRNA expression. Higher ER stress marker levels (BIP, sXBP1, ATF6) correlated with greater disease severity (CAT score). BMI showed a negative correlation with CHOP levels (r=-0.336, p<0.001). Diabetes and COVID-19 history correlated with sXBP1 levels, while employment status correlated with higher sXBP1 expression (p=0.011). Smoking habits were associated with elevated CHOP and ATF6 mRNA levels. The study concludes that elevated ER stress marker mRNA levels in COPD patients could indicate disease severity. Limitations include using PBMCs as lung proxies and age variability among participants, suggesting future research focus on age-matching controls and improving sampling strategies, especially for older COPD populations. This study sheds light on ER stress pathways in COPD, suggesting implications for disease assessment and future therapeutic strategies.