The Inflammatory Roles of n-3 and n-6 Polyunsaturated Fatty Acids in COPD: Clinical Implications and Underlying Mechanisms

Chronic obstructive pulmonary disease (COPD) ranks among the leading causes of global mortality, with chronic inflammation as its primary pathogenic mechanism. Developing effective therapeutic strategies to attenuate this inflammatory response is crucial for reducing the prevalence, mortality, and overall burden of COPD. Polyunsaturated fatty acids (PUFAs) are recognized for their role in modulating inflammation and may influence inflammation-driven diseases. This narrative review evaluates observational and interventional studies on PUFAs in COPD and explores their potential mechanisms in modulating inflammation. The synthesis of the literature reveals limited and inconsistent evidence linking PUFAs to COPD. Robust data are lacking to conclusively demonstrate the biological benefits and clinical efficacy of n-3 PUFAs in COPD. Therefore, we systematically assess current research and recommends extensive and rigorous future clinical trials. Furthermore, PUFAs and their derivatives play roles in initiating and resolving inflammation in COPD through direct involvement, macrophage polarization regulation, and effects on membrane biophysics and signal transduction. Despite the current inconclusive evidence, we emphasize the necessity for intensified clinical trials and drug development efforts targeting PUFAs in COPD to develop new therapeutic strategies.