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Causal Relationship Between Methotrexate and Chronic Obstructive Pulmonary Disease: A Study Based on Network
Ying-Xing Xiang1,2,3, Fang-Shu Zou1,2,3, Mei-Feng Shi1,2,3
1State Key Laboratory of Traditional Chinese Medicine Syndrome, The First Clinical Medical College of Guangzhou University of Chinese Medicine, Guangzhou, People's Republic of China.
Summary
Methotrexate (MTX) use is associated with an increased risk of chronic obstructive pulmonary disease (COPD). This study used network toxicology and Mendelian randomization to confirm this link, suggesting further research into the connection between MTX and COPD development.
Area of Science:
- Pharmacology and Toxicology
- Epidemiology
- Pulmonary Medicine
Background:
- Methotrexate (MTX) has been suggested to influence chronic obstructive pulmonary disease (COPD), but a clear causal link is lacking.
- Understanding the relationship between MTX and COPD is crucial for patient management and treatment strategies.
Purpose of the Study:
- To investigate the potential causal association between methotrexate (MTX) usage and the risk of developing chronic obstructive pulmonary disease (COPD).
- To explore the underlying mechanisms and epidemiological evidence linking MTX and COPD.
Main Methods:
- Employed a multi-dimensional research strategy combining network toxicology and Mendelian randomization (MR) analysis.
- Network toxicology predicted MTX action targets and metabolic pathways.
- MR analysis assessed the macro-epidemiological association between MTX and COPD risk.
Main Results:
- Network toxicology identified multiple pathways and metabolic routes through which MTX may affect COPD onset, with significant protein binding interactions (e.g., HIF1A, EP300, NFKB1).
- Mendelian randomization analysis revealed a significant positive correlation between MTX usage and COPD.
- The findings indicate a potential causal link between MTX and increased COPD risk.
Conclusions:
- The study suggests a notable association between methotrexate (MTX) use and an elevated risk of chronic obstructive pulmonary disease (COPD).
- These findings provide novel insights for future in-depth research on the MTX-COPD relationship.
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