ASTHMA AND FATTY ACID IMBALANCE: IS THE OMEGA-3 SUPPLEMENT BENEFICIAL IN ASTHMA?

Introduction . Asthma is a chronic airway inflammatory disease with the characteristic of eosinophilic infiltration, mucus hypersecretion, and airway hyper-responsiveness (AHR). Lipid mediators are one of mediators that were suggested to be involved in asthma pathophysiology. Then, the pro-inflammatory mediators initiate inflammation while proresolving mediators are produced at later stage in the resolution phase to bring back the cellular homeostasis. Pro-resolving mediators can be produced from omega-3 (n-3), one of the essential fatty acid needed from food. Method . This research is a literature review based on some sources like books and journals with the same topic. Result & Analysis . The relation between diet, especially fatty acid, and the risk of lung inflammatory process, such as asthma has long been suggested. The metabolites of fatty acids and the fatty acid itself become decisive factors in regulating the persistence and resolution of bronchopulmonary inflammation in asthma. The high concentration of n-3 in vitro decreases production of pro-inflammatory prostaglandins, cytokines, and ROS that play critical roles in inflammatory process. Discussion . Since asthma is known to be mainly caused by an inflammatory process, it has been hypothesized that high intake of n-3 fatty acid may be beneficial in prevention and management of asthma.


INTRODUCTION
Asthma is a chronic airway inflammatory disease with the characteristic of eosinophilic infiltration, mucus hypersecretion, and airway hyperresponsiveness (AHR) (Wendell, Baffi and Holguin, 2014;Mims, 2015;Monga et al., 2020). The dominant diagnostic of asthma includes airway inflammation and airway remodeling (Kytikova et al., 2019;Monga et al., 2020).The studies on asthmatic patients suggested that airway inflammation plays a central role in the pathophysiology of asthma (Luster and Tager, 2004). The inflammation causes reversible airway obstruction identified by intermittent wheezing and shortness of breath (Luster and Tager, 2004;Serhan, 2014) that related to bronchospasm in response to infection, allergen, or pollutant exposure (Serhan, 2014). The asthmatic inflammation causes airways to undergo remodeling that contributes to impaired physiology (Yang et al., 2021).
There are some pathological changes found in asthmatic airway, including mucous cell metaplasia and regions of epithelial loss, subepithelial influx of myofibroblasts and collagen deposition resulting in basement membrane thickening, and angiogenesis (Vos et al., 2012;Dharmage, Perret and Custovic, 2019 (Serhan, Yacoubian and Yang, 2008;Adams et al., 2018).

RESEARCH METHOD
This research is a literature review that conducted to evaluate the state of knowledge on a particular topic. It can be used to create research agendas, identify gaps in research, or simply discuss a particular matter. Literature reviews can also be useful if the aim is to engage in theory development (Snyder, 2019).

RESULTS
The results of the review from 31 journals are then compiled based on mapping the data to explain: 1) lipid mediators as proinflammatory and pro-resolving mediators in asthma, 2) fatty acid role in asthma pathophysiology, 3) omega-3 role in asthma. People with asthma tend to have increased level of these eicosanoids in their airways when compared to normal population (Mickleborough et al., 2006).  (Mickleborough, Ionescu and Rundell, 2004).   (Mickleborough, Ionescu and Rundell, 2004;Mickleborough et al., 2006;Adams et al., 2018). Therefore, the elevated level of 15-F2t-isoP may reflect the inflammation due to infection, acute exposure to allergens or oxidants that trigger asthma such as pollutants or tobacco smoke (Adams et al., 2018).

Omega-3 role in asthma
Omega-3 (n-3) has been a considerable as therapeutic potential interest for various inflammatory diseases, including rheumatoid arthritis, inflammatory bowel disease, and asthma.
N-3 such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are categorized as the polyunsaturated fatty acids (PUFA) (Mickleborough, Ionescu and Rundell, 2004;Mickleborough et al., 2006). N-3 fatty acids that mostly contained in fish oil have been known to have beneficial roles in health and organ function, it competes with AA as substrates for eicosanoids formation, such as LTs and PGs. The high concentration of n-3 in vitro decreases production of pro-inflammatory prostaglandins, cytokines, and ROS that plays the critical roles in inflammatory process. Besides that, n-3 has also appeared to have additional anti-inflammatory effects through direct action on neutrophil and monocyte production of inflammatory mediators and chemotactic responses (Serhan et al., 2000;Hamid and Tulic, 2009).
Since asthma is known to be mainly caused by an inflammatory process, it has been hypothesized that high intake of n-3 fatty acid may be beneficial to prevent asthma. In recent years, several studies identified that EPA and DHA (major n-3 fatty acids) are precursors to the activation of novel enzymatic pathways during resolution phase. These newly identified pathways possess potent actions in controlling the resolution phase of inflammation (Villani et al., 1998).
It is believed that major lipid of fish oil, C20:5 acts on preventing the conversion of AA to proinflammatory eicosanoids (PGs and LTs) and serving alternate substrate that produces 5-series LTs that are less potent (Brannan et al., 2015;Diamant et al., 2019) -Glaser et al., 2011).Another study on the effect of n-6:n-3 ratio to inflammation process suggested that decreasing n-6:n-3 ratio is correlated with reductions in inflammatory cytokines (Arm et al., 1988). Then, a study on patients with mild asthma suggested that supplementation of fish oil inhibits the production of eicosanoids, such as LTB4 and LTB5 but doesn't significantly change the severity of asthma.

CONCLUSION
There is accumulating evidence about the effect of diet and nutrition to the clinical manifestation of asthma. Since asthma is mainly caused by inflammation of the airway, the diet rich in precursor of anti-inflammatory mediator has been suggested to bring beneficial outcome.
Several studies found that n-3, a fatty acid that is commonly contained in fish oil improve clinical manifestation in asthma by reducing the airway inflammation, and the supplementation of fish oil might be beneficial in asthma.