Inflammatory lung diseases (ILDs) represent a global public health crisis characterized by escalating prevalence, significant morbidity, and substantial mortality. In response to the complex immunopathogenic mechanisms driving these conditions, novel pharmacological strategies targeting resolution pathways have emerged throughout the discovery of specialized pro-resolving lipid mediator (SPM; resolvins, maresins, and protectins) dysregulation across the ILD spectra, positioning these endogenous molecules as promising therapeutic candidates for modulating maladaptive inflammation and promoting tissue repair. Over the past decade, this paradigm has catalyzed extensive translational research into SPM-based interventions as precision therapeutics for respiratory inflammation. In asthma, they reduce mucus hypersecretion, bronchial hyperreactivity, and airway inflammation, with prenatal SPM exposure potentially lowering offspring disease risk. In COPD, SPMs attenuate amyloid A-driven inflammation, normalizing cytokine/chemokine imbalances and oxidative stress and mitigating COVID-19-associated cytokine storm, enhancing survival. This review synthesizes SPMs' pharmacotherapeutic mechanisms in ILDs and evaluates current preclinical and clinical evidence.

Endocrine and Metabolic Diseases Research Center School of Medicine University of Zulia Maracaibo 4001 Venezuela

Institute of Molecular and Translational Medicine Faculty of Medicine and Dentistry Palacký University Olomouc 77900 Olomouc Czech Republic

The Research Institute of the McGill University Health Center McGill University Montreal QC H0H H9Z Canada

Universidad de la Costa Departamento de Productividad e Innovación Barranquilla 080001 Atlántico Colombia

Universidad del Zulia Facultad de Medicina Departamento de Ciencias Fisiológicas Maracaibo 4001 Venezuela

Universidad Simón Bolívar Facultad de Ciencias de la Salud Centro de Investigaciones en Ciencias de la Vida Barranquilla 080001 Atlántico Colombia

See more in PubMed

Asthma. [(accessed on 18 March 2022)]. Available online: https://www.who.int/news-room/fact-sheets/detail/asthma.

Chronic Obstructive Pulmonary Disease (COPD) [(accessed on 18 March 2022)]. Available online: https://www.who.int/news-room/fact-sheets/detail/chronic-obstructive-pulmonary-disease-(copd)

Sanders D.B., Fink A.K. Background and Epidemiology. Pediatr. Clin. N. Am. 2016;63:567–584. doi: 10.1016/j.pcl.2016.04.001. PubMed DOI PMC

COVID-19 Cases | WHO COVID-19 Dashboard. [(accessed on 1 July 2024)]. Available online: https://data.who.int/dashboards/covid19/cases.

López-Campos J.L., Tan W., Soriano J.B. Global burden of COPD. Respirol. Carlton Vic. 2016;21:14–23. doi: 10.1111/resp.12660. PubMed DOI

Loftus P.A., Wise S.K. Epidemiology and economic burden of asthma. Int. Forum Allergy Rhinol. 2015;5((Suppl. S1)):S7–S10. doi: 10.1002/alr.21547. PubMed DOI

Frey S., Stargardt T., Schneider U., Schreyögg J. The Economic Burden of Cystic Fibrosis in Germany from a Payer Perspective. PharmacoEconomics. 2019;37:1029–1039. doi: 10.1007/s40273-019-00797-2. PubMed DOI

Robles A.J., Kornblith L.Z., Hendrickson C.M., Howard B.M., Conroy A.S., Moazed F., Calfee C.S., Cohen M.J., Callcut R.A. Health care utilization and the cost of posttraumatic acute respiratory distress syndrome care. J. Trauma Acute Care Surg. 2018;85:148–154. doi: 10.1097/TA.0000000000001926. PubMed DOI PMC

Duvall M.G., Levy B.D. DHA- and EPA-derived resolvins, protectins, and maresins in airway inflammation. Eur. J. Pharmacol. 2016;785:144–155. doi: 10.1016/j.ejphar.2015.11.001. PubMed DOI PMC

Philippe R., Urbach V. Specialized Pro-Resolving Lipid Mediators in Cystic Fibrosis. Int. J. Mol. Sci. 2018;19:2865. doi: 10.3390/ijms19102865. PubMed DOI PMC

Robb C.T., Regan K.H., Dorward D.A., Rossi A.G. Key mechanisms governing resolution of lung inflammation. Semin. Immunopathol. 2016;38:425–448. doi: 10.1007/s00281-016-0560-6. PubMed DOI PMC

Kim K.H., Park T.S., Kim Y.S., Lee J.S., Oh Y.M., Lee S.D., Lee S.W. Resolvin D1 prevents smoking-induced emphysema and promotes lung tissue regeneration. Int. J. Chron. Obstruct. Pulmon. Dis. 2016;11:1119–1128. doi: 10.2147/COPD.S100198. PubMed DOI PMC

Bisgaard H., Stokholm J., Chawes B.L., Vissing N.H., Bjarnadóttir E., Schoos A.-M.M., Wolsk H.M., Pedersen T.M., Vinding R.K., Thorsteinsdóttir S., et al. Fish Oil-Derived Fatty Acids in Pregnancy and Wheeze and Asthma in Offspring. N. Engl. J. Med. 2016;375:2530–2539. doi: 10.1056/NEJMoa1503734. PubMed DOI

Atlantis E., Cochrane B. The association of dietary intake and supplementation of specific polyunsaturated fatty acids with inflammation and functional capacity in chronic obstructive pulmonary disease: A systematic review. Int. J. Evid. Based Healthc. 2016;14:53–63. doi: 10.1097/XEB.0000000000000056. PubMed DOI PMC

Keen C., Olin A.C., Eriksson S., Ekman A., Lindblad A., Basu S., Beermann C., Strandvik B. Supplementation with fatty acids influences the airway nitric oxide and inflammatory markers in patients with cystic fibrosis. J. Pediatr. Gastroenterol. Nutr. 2010;50:537–544. doi: 10.1097/MPG.0b013e3181b47967. PubMed DOI

Chiang N., Serhan C.N. Structural elucidation and physiologic functions of specialized pro-resolving mediators and their receptors. Mol. Asp. Med. 2017;58:114–129. doi: 10.1016/j.mam.2017.03.005. PubMed DOI PMC

Seki H., Fukunaga K., Arita M., Arai H., Nakanishi H., Taguchi R., Miyasho T., Takamiya R., Asano K., Ishizaka A., et al. The anti-inflammatory and proresolving mediator resolvin E1 protects mice from bacterial pneumonia and acute lung injury. J. Immunol. Baltim. Md 1950. 2010;184:836–843. doi: 10.4049/jimmunol.0901809. PubMed DOI PMC

Aoki H., Hisada T., Ishizuka T., Utsugi M., Kawata T., Shimizu Y., Okajima F., Dobashi K., Mori M. Resolvin E1 dampens airway inflammation and hyperresponsiveness in a murine model of asthma. Biochem. Biophys. Res. Commun. 2008;367:509–515. doi: 10.1016/j.bbrc.2008.01.012. PubMed DOI

Serhan C.N., Levy B.D. Resolvins in inflammation: Emergence of the pro-resolving superfamily of mediators. J. Clin. Investig. 2018;128:2657–2669. doi: 10.1172/JCI97943. PubMed DOI PMC

Serhan C.N., Chiang N., Van Dyke T.E. Resolving inflammation: Dual anti-inflammatory and pro-resolution lipid mediators. Nat. Rev. Immunol. 2008;8:349–361. doi: 10.1038/nri2294. PubMed DOI PMC

Zhang L.Y., Jia M.R., Sun T. The roles of special proresolving mediators in pain relief. Rev. Neurosci. 2018;29:645–660. doi: 10.1515/revneuro-2017-0074. PubMed DOI

Calder P.C. Polyunsaturated fatty acids and inflammatory processes: New twists in an old tale. Biochimie. 2009;91:791–795. doi: 10.1016/j.biochi.2009.01.008. PubMed DOI

Schaller M.S., Zahner G.J., Gasper W.J., Harris W.S., Conte M.S., Hills N.K., Grenon S.M. Relationship between the omega-3 index and specialized pro-resolving lipid mediators in patients with peripheral arterial disease taking fish oil supplements. J. Clin. Lipidol. 2017;11:1289–1295. doi: 10.1016/j.jacl.2017.06.011. PubMed DOI PMC

Chandrasekharan J.A., Sharma-Walia N. Lipoxins: Nature’s way to resolve inflammation. J. Inflamm. Res. 2015;8:181–192. doi: 10.2147/JIR.S90380. PubMed DOI PMC

Romano M., Cianci E., Simiele F., Recchiuti A. Lipoxins and aspirin-triggered lipoxins in resolution of inflammation. Eur. J. Pharmacol. 2015;760:49–63. doi: 10.1016/j.ejphar.2015.03.083. PubMed DOI

Chiang N., Bermudez E.A., Ridker P.M., Hurwitz S., Serhan C.N. Aspirin triggers antiinflammatory 15-epi-lipoxin A4 and inhibits thromboxane in a randomized human trial. Proc. Natl. Acad. Sci. USA. 2004;101:15178–15183. doi: 10.1073/pnas.0405445101. PubMed DOI PMC

Poorani R., Bhatt A.N., Dwarakanath B.S., Das U.N. COX-2, aspirin and metabolism of arachidonic, eicosapentaenoic and docosahexaenoic acids and their physiological and clinical significance. Eur. J. Pharmacol. 2016;785:116–132. doi: 10.1016/j.ejphar.2015.08.049. PubMed DOI

Calder P.C. Omega-3 polyunsaturated fatty acids and inflammatory processes: Nutrition or pharmacology? Br. J. Clin. Pharmacol. 2013;75:645–662. doi: 10.1111/j.1365-2125.2012.04374.x. PubMed DOI PMC

Levy B.D. Resolvins and protectins: Natural pharmacophores for resolution biology. Prostaglandins Leukot. Essent. Fat. Acids. 2010;82:327–332. doi: 10.1016/j.plefa.2010.02.003. PubMed DOI PMC

Sun Y.P., Oh S.F., Uddin J., Yang R., Gotlinger K., Campbell E., Colgan S.P., Petasis N.A., Serhan C.N. Resolvin D1 and its aspirin-triggered 17R epimer. Stereochemical assignments, anti-inflammatory properties, and enzymatic inactivation. J. Biol. Chem. 2007;282:9323–9334. doi: 10.1074/jbc.M609212200. PubMed DOI

Serhan C.N. Pro-resolving lipid mediators are leads for resolution physiology. Nature. 2014;510:92–101. doi: 10.1038/nature13479. PubMed DOI PMC

Kohli P., Levy B.D. Resolvins and protectins: Mediating solutions to inflammation. Br. J. Pharmacol. 2009;158:960–971. doi: 10.1111/j.1476-5381.2009.00290.x. PubMed DOI PMC

Jadapalli J.K., Halade G.V. Unified nexus of macrophages and maresins in cardiac reparative mechanisms. FASEB J. 2018;32:5227–5237. doi: 10.1096/fj.201800254R. PubMed DOI PMC

Tang S., Wan M., Huang W., Stanton R.C., Xu Y. Maresins: Specialized Proresolving Lipid Mediators and Their Potential Role in Inflammatory-Related Diseases. Mediat. Inflamm. 2018;2018:2380319. doi: 10.1155/2018/2380319. PubMed DOI PMC

Mas E., Croft K.D., Zahra P., Barden A., Mori T.A. Resolvins D1, D2, and other mediators of self-limited resolution of inflammation in human blood following n-3 fatty acid supplementation. Clin. Chem. 2012;58:1476–1484. doi: 10.1373/clinchem.2012.190199. PubMed DOI

Mims J.W. Asthma: Definitions and pathophysiology. Int. Forum Allergy Rhinol. 2015;5((Suppl. S1)):S2–S6. doi: 10.1002/alr.21609. PubMed DOI

Calder P.C. Marine omega-3 fatty acids and inflammatory processes: Effects, mechanisms and clinical relevance. Biochim. Biophys. Acta. 2015;1851:469–484. doi: 10.1016/j.bbalip.2014.08.010. PubMed DOI

Brüggemann T.R., Peh H.Y., Tavares L.P., Nijmeh J., Shay A.E., Rezende R.M., Lanser T.B., Serhan C.N., Levy B.D. Eosinophil Phenotypes Are Functionally Regulated by Resolvin D2 during Allergic Lung Inflammation. Am. J. Respir. Cell Mol. Biol. 2023;69:666–677. doi: 10.1165/rcmb.2023-0121OC. PubMed DOI PMC

Townsend E.A., Guadarrama A., Shi L., Roti Roti E., Denlinger L.C. P2X7 signaling influences the production of pro-resolving and pro-inflammatory lipid mediators in alveolar macrophages derived from individuals with asthma. Am. J. Physiol. Lung Cell. Mol. Physiol. 2023;325:L399–L410. doi: 10.1152/ajplung.00070.2023. PubMed DOI PMC

Serhan C.N., Krishnamoorthy S., Recchiuti A., Chiang N. Novel anti-inflammatory--pro-resolving mediators and their receptors. Curr. Top. Med. Chem. 2011;11:629–647. doi: 10.2174/1568026611109060629. PubMed DOI PMC

Dauletbaev N., Lands L.C. Could relative abundance of airway lipoxins be the clue to restore corticosteroid sensitivity in severe asthma? J. Allergy Clin. Immunol. 2016;137:1807–1808. doi: 10.1016/j.jaci.2016.02.012. PubMed DOI

Levy B.D., Lukacs N.W., Berlin A.A., Schmidt B., Guilford W.J., Serhan C.N., Parkinson J.F. Lipoxin A4 stable analogs reduce allergic airway responses via mechanisms distinct from CysLT1 receptor antagonism. FASEB J. Off. Publ. Fed. Am. Soc. Exp. Biol. 2007;21:3877–3884. doi: 10.1096/fj.07-8653com. PubMed DOI PMC

Hamid Q., Tulic M. Immunobiology of asthma. Annu. Rev. Physiol. 2009;71:489–507. doi: 10.1146/annurev.physiol.010908.163200. PubMed DOI

Barnig C., Cernadas M., Dutile S., Liu X., Perrella M.A., Kazani S., Wechsler M.E., Israel E., Levy B.D. Lipoxin A4 regulates natural killer cell and type 2 innate lymphoid cell activation in asthma. Sci. Transl. Med. 2013;5:174ra26. doi: 10.1126/scitranslmed.3004812. PubMed DOI PMC

Serhan C.N. Resolution phase of inflammation: Novel endogenous anti-inflammatory and proresolving lipid mediators and pathways. Annu. Rev. Immunol. 2007;25:101–137. doi: 10.1146/annurev.immunol.25.022106.141647. PubMed DOI

Kytikova O., Novgorodtseva T., Denisenko Y., Antonyuk M., Gvozdenko T. Pro-Resolving Lipid Mediators in the Pathophysiology of Asthma. Med. Kaunas Lith. 2019;55:284. doi: 10.3390/medicina55060284. PubMed DOI PMC

Bonnans C., Chanez P., Chavis C. Lipoxins in asthma: Potential therapeutic mediators on bronchial inflammation? Allergy. 2004;59:1027–1041. doi: 10.1111/j.1398-9995.2004.00617.x. PubMed DOI

O’Meara S.J., Rodgers K., Godson C. Lipoxins: Update and impact of endogenous pro-resolution lipid mediators. Rev. Physiol. Biochem. Pharmacol. 2008;160:47–70. doi: 10.1007/112_2006_0606. PubMed DOI

Barnig C., Levy B.D. Innate immunity is a key factor for the resolution of inflammation in asthma. Eur. Respir. Rev. Off. J. Eur. Respir. Soc. 2015;24:141–153. doi: 10.1183/09059180.00012514. PubMed DOI PMC

Yonetomi Y., Sekioka T., Kadode M., Kitamine T., Kamiya A., Matsumura N., Fujita M., Kawabata K. Leukotriene C4 induces bronchoconstriction and airway vascular hyperpermeability via the cysteinyl leukotriene receptor 2 in S-hexyl glutathione-treated guinea pigs. Eur. J. Pharmacol. 2015;754:98–104. doi: 10.1016/j.ejphar.2015.02.014. PubMed DOI

Miyata J., Arita M. Role of omega-3 fatty acids and their metabolites in asthma and allergic diseases. Allergol. Int. Off. J. Jpn. Soc. Allergol. 2015;64:27–34. doi: 10.1016/j.alit.2014.08.003. PubMed DOI

Levy B.D., Serhan C.N. Resolution of acute inflammation in the lung. Annu. Rev. Physiol. 2014;76:467–492. doi: 10.1146/annurev-physiol-021113-170408. PubMed DOI PMC

Duffney P.F., Falsetta M.L., Rackow A.R., Thatcher T.H., Phipps R.P., Sime P.J. Key roles for lipid mediators in the adaptive immune response. J. Clin. Investig. 2018;128:2724–2731. doi: 10.1172/JCI97951. PubMed DOI PMC

Tungen J.E., Gerstmann L., Vik A., De Matteis R., Colas R.A., Dalli J., Chiang N., Serhan C.N., Kalesse M., Hansen T.V. Resolving Inflammation: Synthesis, Configurational Assignment, and Biological Evaluations of RvD1n-3 DPA. Chem. Weinh. Bergstr. Ger. 2019;25:1476–1480. doi: 10.1002/chem.201806029. PubMed DOI PMC

Zambalde É.P., Teixeira M.M., Favarin D.C., de Oliveira J.R., Magalhães M.L., Cunha M.M., Silva W.C., Okuma C.H., Rodrigues V., Levy B.D., et al. The anti-inflammatory and pro-resolution effects of aspirin-triggered RvD1 (AT-RvD1) on peripheral blood mononuclear cells from patients with severe asthma. Int. Immunopharmacol. 2016;35:142–148. doi: 10.1016/j.intimp.2016.03.014. PubMed DOI

Kim N., Ramon S., Thatcher T.H., Woeller C.F., Sime P.J., Phipps R.P. Specialized proresolving mediators (SPMs) inhibit human B-cell IgE production. Eur. J. Immunol. 2016;46:81–91. doi: 10.1002/eji.201545673. PubMed DOI PMC

Buckley C.D., Gilroy D.W., Serhan C.N. Proresolving lipid mediators and mechanisms in the resolution of acute inflammation. Immunity. 2014;40:315–327. doi: 10.1016/j.immuni.2014.02.009. PubMed DOI PMC

Serhan C.N., Dalli J., Colas R.A., Winkler J.W., Chiang N. Protectins and maresins: New pro-resolving families of mediators in acute inflammation and resolution bioactive metabolome. Biochim. Biophys. Acta. 2015;1851:397–413. doi: 10.1016/j.bbalip.2014.08.006. PubMed DOI PMC

Krishnamoorthy N., Burkett P.R., Dalli J., Abdulnour R.E.E., Colas R., Ramon S., Phipps R.P., Petasis N.A., Kuchroo V.K., Serhan C.N., et al. Cutting edge: Maresin-1 engages regulatory T cells to limit type 2 innate lymphoid cell activation and promote resolution of lung inflammation. J. Immunol. Baltim. Md 1950. 2015;194:863–867. doi: 10.4049/jimmunol.1402534. PubMed DOI PMC

Lotfi R., Rezaiemanesh A., Mortazavi S.H., Karaji A.G., Salari F. Immunoresolvents in asthma and allergic diseases: Review and update. J. Cell. Physiol. 2019;234:8579–8596. doi: 10.1002/jcp.27836. PubMed DOI

Levy B.D. Resolvin D1 and Resolvin E1 Promote the Resolution of Allergic Airway Inflammation via Shared and Distinct Molecular Counter-Regulatory Pathways. Front. Immunol. 2012;3:390. doi: 10.3389/fimmu.2012.00390. PubMed DOI PMC

Qureshi H., Sharafkhaneh A., Hanania N.A. Chronic obstructive pulmonary disease exacerbations: Latest evidence and clinical implications. Ther. Adv. Chronic Dis. 2014;5:212–227. doi: 10.1177/2040622314532862. PubMed DOI PMC

May S.M., Li J.T.C. Burden of chronic obstructive pulmonary disease: Healthcare costs and beyond. Allergy Asthma Proc. 2015;36:4–10. doi: 10.2500/aap.2015.36.3812. PubMed DOI PMC

Pauwels R.A., Buist A.S., Calverley P.M., Jenkins C.R., Hurd S.S., GOLD Scientific Committee Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease NHLBI/WHO Global Initiative for Chronic Obstructive Lung Disease (GOLD) Workshop summary. Am. J. Respir. Crit. Care Med. 2001;163:1256–1276. doi: 10.1164/ajrccm.163.5.2101039. PubMed DOI

Barnes P.J. Cellular and molecular mechanisms of chronic obstructive pulmonary disease. Clin. Chest Med. 2014;35:71–86. doi: 10.1016/j.ccm.2013.10.004. PubMed DOI

Devine J.F. Chronic obstructive pulmonary disease: An overview. Am. Health Drug Benefits. 2008;1:34–42. PubMed PMC

Giudetti A.M., Cagnazzo R. Beneficial effects of n-3 PUFA on chronic airway inflammatory diseases. Prostaglandins Other Lipid Mediat. 2012;99:57–67. doi: 10.1016/j.prostaglandins.2012.09.006. PubMed DOI

Vestbo J., Hurd S.S., Agustí A.G., Jones P.W., Vogelmeier C., Anzueto A., Barnes P.J., Fabbri L.M., Martinez F.J., Nishimura M., et al. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary. Am. J. Respir. Crit. Care Med. 2013;187:347–365. doi: 10.1164/rccm.201204-0596PP. PubMed DOI

Brusselle G.G., Joos G.F., Bracke K.R. New insights into the immunology of chronic obstructive pulmonary disease. Lancet Lond. Engl. 2011;378:1015–1026. doi: 10.1016/S0140-6736(11)60988-4. PubMed DOI

Joo M.J., Au D.H., Fitzgibbon M.L., Lee T.A. Inhaled corticosteroids and risk of pneumonia in newly diagnosed COPD. Respir. Med. 2010;104:246–252. doi: 10.1016/j.rmed.2009.10.002. PubMed DOI

Invernizzi G., Ruprecht A., De Marco C., Mazza R., Nicolini G., Boffi R. Inhaled steroid/tobacco smoke particle interactions: A new light on steroid resistance. Respir. Res. 2009;10:48. doi: 10.1186/1465-9921-10-48. PubMed DOI PMC

Balode L., Strazda G., Jurka N., Kopeika U., Kislina A., Bukovskis M., Beinare M., Gardjušina V., Taivāns I. Lipoxygenase-derived arachidonic acid metabolites in chronic obstructive pulmonary disease. Med. Kaunas Lith. 2012;48:292–298. doi: 10.3390/medicina48060043. PubMed DOI

Hsiao H.M., Sapinoro R.E., Thatcher T.H., Croasdell A., Levy E.P., Fulton R.A., Olsen K.C., Pollock S.J., Serhan C.N., Phipps R.P., et al. A novel anti-inflammatory and pro-resolving role for resolvin D1 in acute cigarette smoke-induced lung inflammation. PLoS ONE. 2013;8:e58258. doi: 10.1371/journal.pone.0058258. PubMed DOI PMC

Bozinovski S., Uddin M., Vlahos R., Thompson M., McQualter J.L., Merritt A.-S., Wark P.A.B., Hutchinson A., Irving L.B., Levy B.D., et al. Serum amyloid A opposes lipoxin A4 to mediate glucocorticoid refractory lung inflammation in chronic obstructive pulmonary disease. Proc. Natl. Acad. Sci. USA. 2012;109:935–940. doi: 10.1073/pnas.1109382109. PubMed DOI PMC

Groutas W.C., Dou D., Alliston K.R. Neutrophil elastase inhibitors. Expert Opin. Ther. Pat. 2011;21:339–354. doi: 10.1517/13543776.2011.551115. PubMed DOI PMC

Stevens T., Ekholm K., Gränse M., Lindahl M., Kozma V., Jungar C., Ottosson T., Falk-Håkansson H., Churg A., Wright J.L., et al. AZD9668: Pharmacological characterization of a novel oral inhibitor of neutrophil elastase. J. Pharmacol. Exp. Ther. 2011;339:313–320. doi: 10.1124/jpet.111.182139. PubMed DOI

Guilherme R.F., Xisto D.G., Kunkel S.L., Freire-de-Lima C.G., Rocco P.R.M., Neves J.S., Fierro I.M., Canetti C., Benjamim C.F. Pulmonary antifibrotic mechanisms aspirin-triggered lipoxin A(4) synthetic analog. Am. J. Respir. Cell Mol. Biol. 2013;49:1029–1037. doi: 10.1165/rcmb.2012-0462OC. PubMed DOI PMC

Planagumà A., Pfeffer M.A., Rubin G., Croze R., Uddin M., Serhan C.N., Levy B.D. Lovastatin decreases acute mucosal inflammation via 15-epi-lipoxin A4. Mucosal Immunol. 2010;3:270–279. doi: 10.1038/mi.2009.141. PubMed DOI PMC

Croasdell A., Thatcher T.H., Kottmann R.M., Colas R.A., Dalli J., Serhan C.N., Sime P.J., Phipps R.P. Resolvins attenuate inflammation and promote resolution in cigarette smoke-exposed human macrophages. Am. J. Physiol. Lung Cell. Mol. Physiol. 2015;309:L888–L901. doi: 10.1152/ajplung.00125.2015. PubMed DOI PMC

Hsiao H.M., Thatcher T.H., Colas R.A., Serhan C.N., Phipps R.P., Sime P.J. Resolvin D1 Reduces Emphysema and Chronic Inflammation. Am. J. Pathol. 2015;185:3189–3201. doi: 10.1016/j.ajpath.2015.08.008. PubMed DOI PMC

Mitchell D.C., Schenker M.B. Protection against breathing dust: Behavior over time in Californian farmers. J. Agric. Saf. Health. 2008;14:189–203. doi: 10.13031/2013.24350. PubMed DOI

Chiurchiù V., Leuti A., Dalli J., Jacobsson A., Battistini L., Maccarrone M., Serhan C.N. Proresolving lipid mediators resolvin D1, resolvin D2, and maresin 1 are critical in modulating T cell responses. Sci. Transl. Med. 2016;8:353ra111. doi: 10.1126/scitranslmed.aaf7483. PubMed DOI PMC

Harizi H., Corcuff J.B., Gualde N. Arachidonic-acid-derived eicosanoids: Roles in biology and immunopathology. Trends Mol. Med. 2008;14:461–469. doi: 10.1016/j.molmed.2008.08.005. PubMed DOI

Noguera A., Gomez C., Faner R., Cosio B., González-Périz A., Clària J., Carvajal A., Agustí A. An investigation of the resolution of inflammation (catabasis) in COPD. Respir. Res. 2012;13:101. doi: 10.1186/1465-9921-13-101. PubMed DOI PMC

Sun S.C. The noncanonical NF-κB pathway. Immunol. Rev. 2012;246:125–140. doi: 10.1111/j.1600-065X.2011.01088.x. PubMed DOI PMC

Serhan C.N., Yang R., Martinod K., Kasuga K., Pillai P.S., Porter T.F., Oh S.F., Spite M. Maresins: Novel macrophage mediators with potent antiinflammatory and proresolving actions. J. Exp. Med. 2009;206:15–23. doi: 10.1084/jem.20081880. PubMed DOI PMC

Corriveau S., Sykes J., Stephenson A.L. Cystic fibrosis survival: The changing epidemiology. Curr. Opin. Pulm. Med. 2018;24:574–578. doi: 10.1097/MCP.0000000000000520. PubMed DOI

Naehrig S., Chao C.-M., Naehrlich L. Cystic Fibrosis. Dtsch. Arztebl. Int. 2017;114:564–574. doi: 10.3238/arztebl.2017.0564. PubMed DOI PMC

Elborn J.S. Cystic fibrosis. Lancet Lond. Engl. 2016;388:2519–2531. doi: 10.1016/S0140-6736(16)00576-6. PubMed DOI

Calella P., Valerio G., Brodlie M., Donini L.M., Siervo M. Cystic fibrosis, body composition, and health outcomes: A systematic review. Nutr. Burbank Los Angeles Cty. Calif. 2018;55–56:131–139. doi: 10.1016/j.nut.2018.03.052. PubMed DOI

Duvall M.G., Bruggemann T.R., Levy B.D. Bronchoprotective mechanisms for specialized pro-resolving mediators in the resolution of lung inflammation. Mol. Asp. Med. 2017;58:44–56. doi: 10.1016/j.mam.2017.04.003. PubMed DOI PMC

Mattoscio D., Evangelista V., De Cristofaro R., Recchiuti A., Pandolfi A., Di Silvestre S., Manarini S., Martelli N., Rocca B., Petrucci G., et al. Cystic fibrosis transmembrane conductance regulator (CFTR) expression in human platelets: Impact on mediators and mechanisms of the inflammatory response. FASEB J. Off. Publ. Fed. Am. Soc. Exp. Biol. 2010;24:3970–3980. doi: 10.1096/fj.10-159921. PubMed DOI

Ringholz F.C., Buchanan P.J., Clarke D.T., Millar R.G., McDermott M., Linnane B., Harvey B.J., McNally P., Urbach V. Reduced 15-lipoxygenase 2 and lipoxin A4/leukotriene B4 ratio in children with cystic fibrosis. Eur. Respir. J. 2014;44:394–404. doi: 10.1183/09031936.00106013. PubMed DOI

Ringholz F.C., Higgins G., Hatton A., Sassi A., Moukachar A., Fustero-Torre C., Hollenhorst M., Sermet-Gaudelus I., Harvey B.J., McNally P., et al. Resolvin D1 regulates epithelial ion transport and inflammation in cystic fibrosis airways. J. Cyst. Fibros. Off. J. Eur. Cyst. Fibros. Soc. 2018;17:607–615. doi: 10.1016/j.jcf.2017.11.017. PubMed DOI

Higgins G., Fustero Torre C., Tyrrell J., McNally P., Harvey B.J., Urbach V. Lipoxin A4 prevents tight junction disruption and delays the colonization of cystic fibrosis bronchial epithelial cells by Pseudomonas aeruginosa. Am. J. Physiol. Lung Cell. Mol. Physiol. 2016;310:L1053–L1061. doi: 10.1152/ajplung.00368.2015. PubMed DOI

Bonnans C., Mainprice B., Chanez P., Bousquet J., Urbach V. Lipoxin A4 stimulates a cytosolic Ca2+ increase in human bronchial epithelium. J. Biol. Chem. 2003;278:10879–10884. doi: 10.1074/jbc.M210294200. PubMed DOI

Verrière V., Higgins G., Al-Alawi M., Costello R.W., McNally P., Chiron R., Harvey B.J., Urbach V. Lipoxin A4 stimulates calcium-activated chloride currents and increases airway surface liquid height in normal and cystic fibrosis airway epithelia. PLoS ONE. 2012;7:e37746. doi: 10.1371/journal.pone.0037746. PubMed DOI PMC

Mayer-Hamblett N., Retsch-Bogart G., Kloster M., Accurso F., Rosenfeld M., Albers G., Black P., Brown P., Cairns A., Davis S.D., et al. Azithromycin for Early Pseudomonas Infection in Cystic Fibrosis. The OPTIMIZE Randomized Trial. Am. J. Respir. Crit. Care Med. 2018;198:1177–1187. doi: 10.1164/rccm.201802-0215OC. PubMed DOI PMC

Codagnone M., Cianci E., Lamolinara A., Mari V.C., Nespoli A., Isopi E., Mattoscio D., Arita M., Bragonzi A., Iezzi M., et al. Resolvin D1 enhances the resolution of lung inflammation caused by long-term Pseudomonas aeruginosa infection. Mucosal Immunol. 2018;11:35–49. doi: 10.1038/mi.2017.36. PubMed DOI

Karp C.L., Flick L.M., Park K.W., Softic S., Greer T.M., Keledjian R., Yang R., Uddin J., Guggino W.B., Atabani S.F., et al. Defective lipoxin-mediated anti-inflammatory activity in the cystic fibrosis airway. Nat. Immunol. 2004;5:388–392. doi: 10.1038/ni1056. PubMed DOI

Recchiuti A., Mattoscio D., Isopi E. Roles, Actions, and Therapeutic Potential of Specialized Pro-resolving Lipid Mediators for the Treatment of Inflammation in Cystic Fibrosis. Front. Pharmacol. 2019;10:252. doi: 10.3389/fphar.2019.00252. PubMed DOI PMC

Colas R.A., Dalli J., Chiang N., Vlasakov I., Sanger J.M., Riley I.R., Serhan C.N. Identification and Actions of the Maresin 1 Metabolome in Infectious Inflammation. J. Immunol. Baltim. Md 1950. 2016;197:4444–4452. doi: 10.4049/jimmunol.1600837. PubMed DOI PMC

Zaidi A.K., Singh R.B. Progress in Molecular Biology and Translational Science. Volume 202. Elsevier; Amsterdam, The Netherlands: 2024. SARS-CoV-2 variant biology and immune evasion; pp. 45–66. PubMed

Chilamakuri R., Agarwal S. COVID-19: Characteristics and Therapeutics. Cells. 2021;10:206. doi: 10.3390/cells10020206. PubMed DOI PMC

Hu B., Huang S., Yin L. The cytokine storm and COVID-19. J. Med. Virol. 2021;93:250–256. doi: 10.1002/jmv.26232. PubMed DOI PMC

Karki R., Kanneganti T.-D. Innate immunity, cytokine storm, and inflammatory cell death in COVID-19. J. Transl. Med. 2022;20:542. doi: 10.1186/s12967-022-03767-z. PubMed DOI PMC

Driscoll D.F., Bistrian B.R. Cytokine storm associated with severe COVID-19 infections: The potential mitigating role of omega-3 fatty acid triglycerides in the ICU. FASEB J. 2023;37:e23066. doi: 10.1096/fj.202300396R. PubMed DOI

Regidor P.A., De La Rosa X., Santos F.G., Rizo J.M., Gracia Banzo R., Silva R.S. Acute severe SARS COVID-19 patients produce pro-resolving lipids mediators and eicosanoids. Eur. Rev. Med. Pharmacol. Sci. 2021;25:6782–6796. doi: 10.26355/eurrev_202111_27123. PubMed DOI

Ferri G., Mucci M., Mattoscio D., Recchiuti A. Specialized pro-resolving lipid mediators and resolution of viral diseases. Prostaglandins Other Lipid Mediat. 2023;168:106762. doi: 10.1016/j.prostaglandins.2023.106762. PubMed DOI PMC

Chiang N., Serhan C.N. Specialized pro-resolving mediator network: An update on production and actions. Essays Biochem. 2020;64:443–462. doi: 10.1042/EBC20200018. PubMed DOI PMC

Pawelzik S.C., Arnardottir H., Sarajlic P., Mahdi A., Vigor C., Zurita J., Zhou B., Kolmert J., Galano J.M., Religa D., et al. Decreased oxidative stress and altered urinary oxylipidome by intravenous omega-3 fatty acid emulsion in a randomized controlled trial of older subjects hospitalized for COVID-19. Free Radic. Biol. Med. 2023;194:308–315. doi: 10.1016/j.freeradbiomed.2022.12.006. PubMed DOI PMC

Serhan C.N., Libreros S., Nshimiyimana R. E-series resolvin metabolome, biosynthesis and critical role of stereochemistry of specialized pro-resolving mediators (SPMs) in inflammation-resolution: Preparing SPMs for long COVID-19, human clinical trials, and targeted precision nutrition. Semin. Immunol. 2022;59:101597. doi: 10.1016/j.smim.2022.101597. PubMed DOI PMC

Recchiuti A., Patruno S., Mattoscio D., Isopi E., Pomilio A., Lamolinara A., Iezzi M., Pecce R., Romano M. Resolvin D1 and D2 reduce SARS-Cov-2-induced inflammation in cystic fibrosis macrophages. bioRxiv. 2020:bioRxiv 2020.08.28.255463. doi: 10.1101/2020.08.28.255463. PubMed DOI PMC

Dalli J., Serhan C.N. Pro-Resolving Mediators in Regulating and Conferring Macrophage Function. Front. Immunol. 2017;8:1400. doi: 10.3389/fimmu.2017.01400. PubMed DOI PMC

Navarini L., Vomero M., Currado D., Berardicurti O., Biaggi A., Marino A., Bearzi P., Corberi E., Rigon A., Arcarese L., et al. The specialized pro-resolving lipid mediator Protectin D1 affects macrophages differentiation and activity in Adult-onset Still’s disease and COVID-19, two hyperinflammatory diseases sharing similar transcriptomic profiles. Front. Immunol. 2023;14:1148268. doi: 10.3389/fimmu.2023.1148268. PubMed DOI PMC

Yasmeen N., Selvaraj H., Lakhawat S.S., Datta M., Sharma P.K., Jain A., Khanna R., Srinivasan J., Kumar V. Possibility of averting cytokine storm in SARS-COV 2 patients using specialized pro-resolving lipid mediators. Biochem. Pharmacol. 2023;209:115437. doi: 10.1016/j.bcp.2023.115437. PubMed DOI PMC

Morita M., Kuba K., Ichikawa A., Nakayama M., Katahira J., Iwamoto R., Watanebe T., Sakabe S., Daidoji T., Nakamura S., et al. The Lipid Mediator Protectin D1 Inhibits Influenza Virus Replication and Improves Severe Influenza. Cell. 2013;153:112–125. doi: 10.1016/j.cell.2013.02.027. PubMed DOI

Goc A., Niedzwiecki A., Rath M. Polyunsaturated ω-3 fatty acids inhibit ACE2-controlled SARS-CoV-2 binding and cellular entry. Sci. Rep. 2021;11:5207. doi: 10.1038/s41598-021-84850-1. PubMed DOI PMC

Balta M.G., Papathanasiou E., Christopoulos P.F. Specialized Pro-Resolving Mediators as Potential Regulators of Inflammatory Macrophage Responses in COVID-19. Front. Immunol. 2021;12:632238. doi: 10.3389/fimmu.2021.632238. PubMed DOI PMC

Kumar V., Yasmeen N., Chaudhary A.A., Alawam A.S., Al-Zharani M., Suliman Basher N., Harikrishnan S., Goud M.D., Pandey A., Lakhawat S.S., et al. Specialized pro-resolving lipid mediators regulate inflammatory macrophages: A paradigm shift from antibiotics to immunotherapy for mitigating COVID-19 pandemic. Front. Mol. Biosci. 2023;10:1104577. doi: 10.3389/fmolb.2023.1104577. PubMed DOI PMC

Kirsch C.M., Payan D.G., Wong M.Y., Dohlman J.G., Blake V.A., Petri M.A., Offenberger J., Goetzl E.J., Gold W.M. Effect of eicosapentaenoic acid in asthma. Clin. Allergy. 1988;18:177–187. doi: 10.1111/j.1365-2222.1988.tb02857.x. PubMed DOI

Scaglia N., Chatkin J., Chapman K.R., Ferreira I., Wagner M., Selby P., Allard J., Zamel N. The relationship between omega-3 and smoking habit: A cross-sectional study. Lipids Health Dis. 2016;15:61. doi: 10.1186/s12944-016-0220-9. PubMed DOI PMC

Novgorodtseva T.P., Denisenko Y.K., Zhukova N.V., Antonyuk M.V., Knyshova V.V., Gvozdenko T.A. Modification of the fatty acid composition of the erythrocyte membrane in patients with chronic respiratory diseases. Lipids Health Dis. 2013;12:117. doi: 10.1186/1476-511X-12-117. PubMed DOI PMC

Lawrence R., Sorrell T. Eicosapentaenoic acid in cystic fibrosis: Evidence of a pathogenetic role for leukotriene B4. Lancet Lond. Engl. 1993;342:465–469. doi: 10.1016/0140-6736(93)91594-C. PubMed DOI

Doaei S., Gholami S., Rastgoo S., Gholamalizadeh M., Bourbour F., Bagheri S.E., Samipoor F., Akbari M.E., Shadnoush M., Ghorat F., et al. The effect of omega-3 fatty acid supplementation on clinical and biochemical parameters of critically ill patients with COVID-19: A randomized clinical trial. J. Transl. Med. 2021;19:128. doi: 10.1186/s12967-021-02795-5. PubMed DOI PMC

Mazidimoradi A., Alemzadeh E., Alemzadeh E., Salehiniya H. The effect of polyunsaturated fatty acids on the severity and mortality of COVID patients: A systematic review. Life Sci. 2022;299:120489. doi: 10.1016/j.lfs.2022.120489. PubMed DOI PMC

Miyata J., Fukunaga K., Iwamoto R., Isobe Y., Niimi K., Takamiya R., Takihara T., Tomomatsu K., Suzuki Y., Oguma T., et al. Dysregulated synthesis of protectin D1 in eosinophils from patients with severe asthma. J. Allergy Clin. Immunol. 2013;131:353–360. doi: 10.1016/j.jaci.2012.07.048. PubMed DOI

Levy B.D., Bonnans C., Silverman E.S., Palmer L.J., Marigowda G., Israel E. Severe Asthma Research Program, National Heart, Lung, and Blood Institute Diminished lipoxin biosynthesis in severe asthma. Am. J. Respir. Crit. Care Med. 2005;172:824–830. doi: 10.1164/rccm.200410-1413OC. PubMed DOI PMC

Vachier I., Bonnans C., Chavis C., Farce M., Godard P., Bousquet J., Chanez P. Severe asthma is associated with a loss of LX4, an endogenous anti-inflammatory compound. J. Allergy Clin. Immunol. 2005;115:55–60. doi: 10.1016/j.jaci.2004.09.038. PubMed DOI

Kazani S., Planaguma A., Ono E., Bonini M., Zahid M., Marigowda G., Wechsler M.E., Levy B.D., Israel E. Exhaled breath condensate eicosanoid levels associate with asthma and its severity. J. Allergy Clin. Immunol. 2013;132:547–553. doi: 10.1016/j.jaci.2013.01.058. PubMed DOI PMC

Fritscher L.G., Post M., Rodrigues M.T., Silverman F., Balter M., Chapman K.R., Zamel N. Profile of eicosanoids in breath condensate in asthma and COPD. J. Breath. Res. 2012;6:026001. doi: 10.1088/1752-7155/6/2/026001. PubMed DOI

Hasan R.A., O’Brien E., Mancuso P. Lipoxin A(4) and 8-isoprostane in the exhaled breath condensate of children hospitalized for status asthmaticus. Pediatr. Crit. Care Med. J. Soc. Crit. Care Med. World Fed. Pediatr. Intensive Crit. Care Soc. 2012;13:141–145. doi: 10.1097/PCC.0b013e3182231644. PubMed DOI PMC

Tahan F., Saraymen R., Gumus H. The role of lipoxin A4 in exercise-induced bronchoconstriction in asthma. J. Asthma Off. J. Assoc. Care Asthma. 2008;45:161–164. doi: 10.1080/02770900701847068. PubMed DOI

Sanak M., Levy B.D., Clish C.B., Chiang N., Gronert K., Mastalerz L., Serhan C.N., Szczeklik A. Aspirin-tolerant asthmatics generate more lipoxins than aspirin-intolerant asthmatics. Eur. Respir. J. 2000;16:44–49. doi: 10.1034/j.1399-3003.2000.16a08.x. PubMed DOI

Celik G.E., Erkekol F.O., Misirligil Z., Melli M. Lipoxin A4 levels in asthma: Relation with disease severity and aspirin sensitivity. Clin. Exp. Allergy J. Br. Soc. Allergy Clin. Immunol. 2007;37:1494–1501. doi: 10.1111/j.1365-2222.2007.02806.x. PubMed DOI

Yamaguchi H., Higashi N., Mita H., Ono E., Komase Y., Nakagawa T., Miyazawa T., Akiyama K., Taniguchi M. Urinary concentrations of 15-epimer of lipoxin A(4) are lower in patients with aspirin-intolerant compared with aspirin-tolerant asthma. Clin. Exp. Allergy J. Br. Soc. Allergy Clin. Immunol. 2011;41:1711–1718. doi: 10.1111/j.1365-2222.2011.03839.x. PubMed DOI

Levy B.D., De Sanctis G.T., Devchand P.R., Kim E., Ackerman K., Schmidt B.A., Szczeklik W., Drazen J.M., Serhan C.N. Multi-pronged inhibition of airway hyper-responsiveness and inflammation by lipoxin A(4) Nat. Med. 2002;8:1018–1023. doi: 10.1038/nm748. PubMed DOI

Karra L., Haworth O., Priluck R., Levy B.D., Levi-Schaffer F. Lipoxin B4 promotes the resolution of allergic inflammation in the upper and lower airways of mice. Mucosal Immunol. 2015;8:852–862. doi: 10.1038/mi.2014.116. PubMed DOI PMC

Aoki H., Hisada T., Ishizuka T., Utsugi M., Ono A., Koga Y., Sunaga N., Nakakura T., Okajima F., Dobashi K., et al. Protective effect of resolvin E1 on the development of asthmatic airway inflammation. Biochem. Biophys. Res. Commun. 2010;400:128–133. doi: 10.1016/j.bbrc.2010.08.025. PubMed DOI

Flesher R.P., Herbert C., Kumar R.K. Resolvin E1 promotes resolution of inflammation in a mouse model of an acute exacerbation of allergic asthma. Clin. Sci. Lond. Engl. 1979. 2014;126:805–814. doi: 10.1042/CS20130623. PubMed DOI

Rogerio A.P., Haworth O., Croze R., Oh S.F., Uddin M., Carlo T., Pfeffer M.A., Priluck R., Serhan C.N., Levy B.D. Resolvin D1 and aspirin-triggered resolvin D1 promote resolution of allergic airways responses. J. Immunol. Baltim. Md 1950. 2012;189:1983–1991. doi: 10.4049/jimmunol.1101665. PubMed DOI PMC

Kim N., Thatcher T.H., Sime P.J., Phipps R.P. Corticosteroids inhibit anti-IgE activities of specialized proresolving mediators on B cells from asthma patients. JCI Insight. 2017;2:e88588. doi: 10.1172/jci.insight.88588. PubMed DOI PMC

Haworth O., Cernadas M., Yang R., Serhan C.N., Levy B.D. Resolvin E1 regulates interleukin 23, interferon-gamma and lipoxin A4 to promote the resolution of allergic airway inflammation. Nat. Immunol. 2008;9:873–879. doi: 10.1038/ni.1627. PubMed DOI PMC

Levy B.D., Kohli P., Gotlinger K., Haworth O., Hong S., Kazani S., Israel E., Haley K.J., Serhan C.N. Protectin D1 is generated in asthma and dampens airway inflammation and hyperresponsiveness. J. Immunol. 2007;178:496–502. doi: 10.4049/jimmunol.178.1.496. PubMed DOI PMC

Abdulnour R.E., Sham H.P., Douda D.N., Colas R.A., Dalli J., Bai Y., Ai X., Serhan C.N., Levy B.D. Aspirin-triggered resolvin D1 is produced during self-resolving gram-negative bacterial pneumonia and regulates host immune responses for the resolution of lung inflammation. Mucosal Immunol. 2016;9:1278–1287. doi: 10.1038/mi.2015.129. PubMed DOI PMC

Nordgren T.M., Bauer C.D., Heires A.J., Poole J.A., Wyatt T.A., West W.W., Romberger D.J. Maresin-1 reduces airway inflammation associated with acute and repetitive exposures to organic dust. Transl. Res. J. Lab. Clin. Med. 2015;166:57–69. doi: 10.1016/j.trsl.2015.01.001. PubMed DOI PMC

Barros R., Moreira A., Fonseca J., Delgado L., Castel-Branco M.G., Haahtela T., Lopes C., Moreira P. Dietary intake of α-linolenic acid and low ratio of n-6:n-3 PUFA are associated with decreased exhaled NO and improved asthma control. Br. J. Nutr. 2011;106:441–450. doi: 10.1017/S0007114511000328. PubMed DOI

Broadfield E.C., McKeever T.M., Whitehurst A., Lewis S.A., Lawson N., Britton J., Fogarty A. A case-control study of dietary and erythrocyte membrane fatty acids in asthma. Clin. Htmlent Glyphamp Asciiamp Exp. Allergy. 2004;34:1232–1236. doi: 10.1111/j.1365-2222.2004.02032.x. PubMed DOI

Burns J.S., Dockery D.W., Neas L.M., Schwartz J., Coull B.A., Raizenne M., Speizer F.E. Low dietary nutrient intakes and respiratory health in adolescents. Chest. 2007;132:238–245. doi: 10.1378/chest.07-0038. PubMed DOI

Kompauer I., Demmelmair H., Koletzko B., Bolte G., Linseisen J., Heinrich J. Association of fatty acids in serum phospholipids with lung function and bronchial hyperresponsiveness in adults. Eur. J. Epidemiol. 2008;23:175–190. doi: 10.1007/s10654-007-9218-y. PubMed DOI

Schwartz J., Weiss S.T. The relationship of dietary fish intake to level of pulmonary function in the first National Health and Nutrition Survey (NHANES I) Eur. Respir. J. 1994;7:1821–1824. doi: 10.1183/09031936.94.07101821. PubMed DOI

Mickleborough T.D., Lindley M.R., Ionescu A.A., Fly A.D. Protective effect of fish oil supplementation on exercise-induced bronchoconstriction in asthma. Chest. 2006;129:39–49. doi: 10.1378/chest.129.1.39. PubMed DOI

Mickleborough T.D., Murray R.L., Ionescu A.A., Lindley M.R. Fish oil supplementation reduces severity of exercise-induced bronchoconstriction in elite athletes. Am. J. Respir. Crit. Care Med. 2003;168:1181–1189. doi: 10.1164/rccm.200303-373OC. PubMed DOI

Adams S., Lopata A.L., Smuts C.M., Baatjies R., Jeebhay M.F. Relationship between Serum Omega-3 Fatty Acid and Asthma Endpoints. Int. J. Environ. Res. Public. Health. 2018;16:43. doi: 10.3390/ijerph16010043. PubMed DOI PMC

Li J., Xun P., Zamora D., Sood A., Liu K., Daviglus M., Iribarren C., Jacobs D., Shikany J.M., He K. Intakes of long-chain omega-3 (n-3) PUFAs and fish in relation to incidence of asthma among American young adults: The CARDIA study. Am. J. Clin. Nutr. 2013;97:173–178. doi: 10.3945/ajcn.112.041145. PubMed DOI PMC

Nagakura T., Matsuda S., Shichijyo K., Sugimoto H., Hata K. Dietary supplementation with fish oil rich in omega-3 polyunsaturated fatty acids in children with bronchial asthma. Eur. Respir. J. 2000;16:861–865. doi: 10.1183/09031936.00.16586100. PubMed DOI

Hodge L., Salome C.M., Hughes J.M., Liu-Brennan D., Rimmer J., Allman M., Pang D., Armour C., Woolcock A.J. Effect of dietary intake of omega-3 and omega-6 fatty acids on severity of asthma in children. Eur. Respir. J. 1998;11:361–365. doi: 10.1183/09031936.98.11020361. PubMed DOI

Arm J.P., Horton C.E., Mencia-Huerta J.M., House F., Eiser N.M., Clark T.J., Spur B.W., Lee T.H. Effect of dietary supplementation with fish oil lipids on mild asthma. Thorax. 1988;43:84–92. doi: 10.1136/thx.43.2.84. PubMed DOI PMC

Arm J.P., Horton C.E., Spur B.W., Mencia-Huerta J.M., Lee T.H. The effects of dietary supplementation with fish oil lipids on the airways response to inhaled allergen in bronchial asthma. Am. Rev. Respir. Dis. 1989;139:1395–1400. doi: 10.1164/ajrccm/139.6.1395. PubMed DOI

Okamoto M., Mitsunobu F., Ashida K., Mifune T., Hosaki Y., Tsugeno H., Harada S., Tanizaki Y. Effects of dietary supplementation with n-3 fatty acids compared with n-6 fatty acids on bronchial asthma. Intern. Med. Tokyo Jpn. 2000;39:107–111. doi: 10.2169/internalmedicine.39.107. PubMed DOI

Thien F.C., Mencia-Huerta J.M., Lee T.H. Dietary fish oil effects on seasonal hay fever and asthma in pollen-sensitive subjects. Am. Rev. Respir. Dis. 1993;147:1138–1143. doi: 10.1164/ajrccm/147.5.1138. PubMed DOI

Stenius-Aarniala B., Aro A., Hakulinen A., Ahola I., Seppälä E., Vapaatalo H. Evening primose oil and fish oil are ineffective as supplementary treatment of bronchial asthma. Ann. Allergy. 1989;62:534–537. PubMed

Emelyanov A., Fedoseev G., Krasnoschekova O., Abulimity A., Trendeleva T., Barnes P.J. Treatment of asthma with lipid extract of New Zealand green-lipped mussel: A randomised clinical trial. Eur. Respir. J. 2002;20:596–600. doi: 10.1183/09031936.02.02632001. PubMed DOI

Dry J., Vincent D. Effect of a Fish Oil Diet on Asthma: Results of a 1-Year Double-Blind Study. Int. Arch. Allergy Immunol. 1991;95:156–157. doi: 10.1159/000235421. PubMed DOI

Thien F.C., De Luca S., Woods R.K., Abramson M.J. Cochrane Review: Dietary marine fatty acids (fish oil) for asthma in adults and children. Evid.-Based Child Health Cochrane Rev. J. 2011;6:984–1012. doi: 10.1002/ebch.765. DOI

Venter C., Meyer R.W., Nwaru B.I., Roduit C., Untersmayr E., Adel-Patient K., Agache I., Agostoni C., Akdis C.A., Bischoff S.C., et al. EAACI position paper: Influence of dietary fatty acids on asthma, food allergy, and atopic dermatitis. Allergy. 2019;74:1429–1444. doi: 10.1111/all.13764. PubMed DOI

Mickleborough T.D., Vaughn C.L., Shei R.-J., Davis E.M., Wilhite D.P. Marine lipid fraction PCSO-524 (lyprinol/omega XL) of the New Zealand green lipped mussel attenuates hyperpnea-induced bronchoconstriction in asthma. Respir. Med. 2013;107:1152–1163. doi: 10.1016/j.rmed.2013.04.010. PubMed DOI

Wood L.G., Hazlewood L.C., Foster P.S., Hansbro P.M. Lyprinol reduces inflammation and improves lung function in a mouse model of allergic airways disease. Clin. Exp. Allergy J. Br. Soc. Allergy Clin. Immunol. 2010;40:1785–1793. doi: 10.1111/j.1365-2222.2010.03503.x. PubMed DOI

Masoli M., Fabian D., Holt S., Beasley R. Global Initiative for Asthma (GINA) Program The global burden of asthma: Executive summary of the GINA Dissemination Committee report. Allergy. 2004;59:469–478. doi: 10.1111/j.1398-9995.2004.00526.x. PubMed DOI

Bisgaard H., Szefler S. Prevalence of asthma-like symptoms in young children. Pediatr. Pulmonol. 2007;42:723–728. doi: 10.1002/ppul.20644. PubMed DOI

Prescott S.L., Barden A.E., Mori T.A., Dunstan J.A. Maternal fish oil supplementation in pregnancy modifies neonatal leukotriene production by cord-blood-derived neutrophils. Clin. Sci. Lond. Engl. 1979. 2007;113:409–416. doi: 10.1042/CS20070111. PubMed DOI

Dunstan J.A., Mori T.A., Barden A., Beilin L.J., Taylor A.L., Holt P.G., Prescott S.L. Maternal fish oil supplementation in pregnancy reduces interleukin-13 levels in cord blood of infants at high risk of atopy. Clin. Exp. Allergy J. Br. Soc. Allergy Clin. Immunol. 2003;33:442–448. doi: 10.1046/j.1365-2222.2003.01590.x. PubMed DOI

Krauss-Etschmann S., Hartl D., Rzehak P., Heinrich J., Shadid R., Del Carmen Ramírez-Tortosa M., Campoy C., Pardillo S., Schendel D.J., Decsi T., et al. Decreased cord blood IL-4, IL-13, and CCR4 and increased TGF-beta levels after fish oil supplementation of pregnant women. J. Allergy Clin. Immunol. 2008;121:464–470.e6. doi: 10.1016/j.jaci.2007.09.018. PubMed DOI

Blümer N., Renz H. Consumption of omega3-fatty acids during perinatal life: Role in immuno-modulation and allergy prevention. J. Perinat. Med. 2007;35((Suppl. S1)):S12–S18. doi: 10.1515/JPM.2007.031. PubMed DOI

Willers S.M., Devereux G., Craig L.C.A., McNeill G., Wijga A.H., Abou El-Magd W., Turner S.W., Helms P.J., Seaton A. Maternal food consumption during pregnancy and asthma, respiratory and atopic symptoms in 5-year-old children. Thorax. 2007;62:773–779. doi: 10.1136/thx.2006.074187. PubMed DOI PMC

Dunstan J.A., Mori T.A., Barden A., Beilin L.J., Taylor A.L., Holt P.G., Prescott S.L. Fish oil supplementation in pregnancy modifies neonatal allergen-specific immune responses and clinical outcomes in infants at high risk of atopy: A randomized, controlled trial. J. Allergy Clin. Immunol. 2003;112:1178–1184. doi: 10.1016/j.jaci.2003.09.009. PubMed DOI

Olsen S.F., Østerdal M.L., Salvig J.D., Mortensen L.M., Rytter D., Secher N.J., Henriksen T.B. Fish oil intake compared with olive oil intake in late pregnancy and asthma in the offspring: 16 y of registry-based follow-up from a randomized controlled trial. Am. J. Clin. Nutr. 2008;88:167–175. doi: 10.1093/ajcn/88.1.167. PubMed DOI

Palmer D.J., Sullivan T., Gold M.S., Prescott S.L., Heddle R., Gibson R.A., Makrides M. Effect of n-3 long chain polyunsaturated fatty acid supplementation in pregnancy on infants’ allergies in first year of life: Randomised controlled trial. BMJ. 2012;344:e184. doi: 10.1136/bmj.e184. PubMed DOI PMC

Palmer D.J., Sullivan T., Gold M.S., Prescott S.L., Heddle R., Gibson R.A., Makrides M. Randomized controlled trial of fish oil supplementation in pregnancy on childhood allergies. Allergy. 2013;68:1370–1376. doi: 10.1111/all.12233. PubMed DOI

Lumia M., Luukkainen P., Tapanainen H., Kaila M., Erkkola M., Uusitalo L., Niinistö S., Kenward M.G., Ilonen J., Simell O., et al. Dietary fatty acid composition during pregnancy and the risk of asthma in the offspring. Pediatr. Allergy Immunol. Off. Publ. Eur. Soc. Pediatr. Allergy Immunol. 2011;22:827–835. doi: 10.1111/j.1399-3038.2011.01202.x. PubMed DOI

Best K.P., Gold M., Kennedy D., Martin J., Makrides M. Omega-3 long-chain PUFA intake during pregnancy and allergic disease outcomes in the offspring: A systematic review and meta-analysis of observational studies and randomized controlled trials. Am. J. Clin. Nutr. 2016;103:128–143. doi: 10.3945/ajcn.115.111104. PubMed DOI

Hansen S., Strøm M., Maslova E., Dahl R., Hoffmann H.J., Rytter D., Bech B.H., Henriksen T.B., Granström C., Halldorsson T.I., et al. Fish oil supplementation during pregnancy and allergic respiratory disease in the adult offspring. J. Allergy Clin. Immunol. 2017;139:104–111.e4. doi: 10.1016/j.jaci.2016.02.042. PubMed DOI

Furuhjelm C., Warstedt K., Fagerås M., Fälth-Magnusson K., Larsson J., Fredriksson M., Duchén K. Allergic disease in infants up to 2 years of age in relation to plasma omega-3 fatty acids and maternal fish oil supplementation in pregnancy and lactation. Pediatr. Allergy Immunol. Off. Publ. Eur. Soc. Pediatr. Allergy Immunol. 2011;22:505–514. doi: 10.1111/j.1399-3038.2010.01096.x. PubMed DOI

Best K.P., Sullivan T., Palmer D., Gold M., Kennedy D.J., Martin J., Makrides M. Prenatal Fish Oil Supplementation and Allergy: 6-Year Follow-up of a Randomized Controlled Trial. Pediatrics. 2016;137:e20154443. doi: 10.1542/peds.2015-4443. PubMed DOI

Gunaratne A.W., Makrides M., Collins C.T. Maternal prenatal and/or postnatal n-3 long chain polyunsaturated fatty acids (LCPUFA) supplementation for preventing allergies in early childhood. Cochrane Database Syst. Rev. 2015;7:CD010085. doi: 10.1002/14651858.CD010085.pub2. PubMed DOI PMC

Rodriguez B.L., Sharp D.S., Abbott R.D., Burchfiel C.M., Masaki K., Chyou P.-H., Huang B., Yano K., Curb J.D. Fish Intake May Limit the Increase in Risk of Coronary Heart Disease Morbidity and Mortality Among Heavy Smokers: The Honolulu Heart Program. Circulation. 1996;94:952–956. doi: 10.1161/01.CIR.94.5.952. PubMed DOI

Shahar E., Folsom A.R., Melnick S.L., Tockman M.S., Comstock G.W., Gennaro V., Higgins M.W., Sorlie P.D., Ko W.J., Szklo M. Dietary n-3 polyunsaturated fatty acids and smoking-related chronic obstructive pulmonary disease. Atherosclerosis Risk in Communities Study Investigators. N. Engl. J. Med. 1994;331:228–233. doi: 10.1056/NEJM199407283310403. PubMed DOI

Leng S., Picchi M.A., Tesfaigzi Y., Wu G., Gauderman W.J., Xu F., Gilliland F.D., Belinsky S.A. Dietary nutrients associated with preservation of lung function in Hispanic and non-Hispanic white smokers from New Mexico. Int. J. Chron. Obstruct. Pulmon. Dis. 2017;12:3171–3181. doi: 10.2147/COPD.S142237. PubMed DOI PMC

Wood L.G., Attia J., McElduff P., McEvoy M., Gibson P.G. Assessment of dietary fat intake and innate immune activation as risk factors for impaired lung function. Eur. J. Clin. Nutr. 2010;64:818–825. doi: 10.1038/ejcn.2010.68. PubMed DOI

Ahmadi A., Haghighat N., Hakimrabet M., Tolide-ie H. Nutritional evaluation in chronic obstructive pulmonary disease patients. Pak. J. Biol. Sci. PJBS. 2012;15:501–505. doi: 10.3923/pjbs.2012.501.505. PubMed DOI

Broekhuizen R., Wouters E.F.M., Creutzberg E.C., Weling-Scheepers C.a.P.M., Schols A.M.W.J. Polyunsaturated fatty acids improve exercise capacity in chronic obstructive pulmonary disease. Thorax. 2005;60:376–382. doi: 10.1136/thx.2004.030858. PubMed DOI PMC

de Batlle J., Sauleda J., Balcells E., Gómez F.P., Méndez M., Rodriguez E., Barreiro E., Ferrer J.J., Romieu I., Gea J., et al. Association between Ω3 and Ω6 fatty acid intakes and serum inflammatory markers in COPD. J. Nutr. Biochem. 2012;23:817–821. doi: 10.1016/j.jnutbio.2011.04.005. PubMed DOI

Sugawara K., Takahashi H., Kasai C., Kiyokawa N., Watanabe T., Fujii S., Kashiwagura T., Honma M., Satake M., Shioya T. Effects of nutritional supplementation combined with low-intensity exercise in malnourished patients with COPD. Respir. Med. 2010;104:1883–1889. doi: 10.1016/j.rmed.2010.05.008. PubMed DOI

Sugawara K., Takahashi H., Kashiwagura T., Yamada K., Yanagida S., Homma M., Dairiki K., Sasaki H., Kawagoshi A., Satake M., et al. Effect of anti-inflammatory supplementation with whey peptide and exercise therapy in patients with COPD. Respir. Med. 2012;106:1526–1534. doi: 10.1016/j.rmed.2012.07.001. PubMed DOI

Lemoine S.C.M., Brigham E.P., Woo H., Hanson C.K., McCormack M.C., Koch A., Putcha N., Hansel N.N. Omega-3 fatty acid intake and prevalent respiratory symptoms among U.S. adults with COPD. BMC Pulm. Med. 2019;19:97. doi: 10.1186/s12890-019-0852-4. PubMed DOI PMC

National Institutes of Health National Institute on Minority Health and Health Disparities (NIMHD). The National Institute on Minority Health and Health Disparities Research Framework. NIMHD Research Framework. [(accessed on 22 August 2024)];2021 Available online: https://www.nih.gov/

Shi J., Li H., Yuan C., Luo M., Wei J., Liu X. Cigarette Smoke-Induced Acquired Dysfunction of Cystic Fibrosis Transmembrane Conductance Regulator in the Pathogenesis of Chronic Obstructive Pulmonary Disease. Oxid. Med. Cell. Longev. 2018;2018:6567578. doi: 10.1155/2018/6567578. PubMed DOI PMC

Raju S.V., Jackson P.L., Courville C.A., McNicholas C.M., Sloane P.A., Sabbatini G., Tidwell S., Tang L.P., Liu B., Fortenberry J.A., et al. Cigarette Smoke Induces Systemic Defects in Cystic Fibrosis Transmembrane Conductance Regulator Function. Am. J. Respir. Crit. Care Med. 2013;188:1321–1330. doi: 10.1164/rccm.201304-0733OC. PubMed DOI PMC

Courville C.A., Raju S.V., Liu B., Accurso F.J., Dransfield M.T., Rowe S.M. Recovery of Acquired Cystic Fibrosis Transmembrane Conductance Regulator Dysfunction after Smoking Cessation. Am. J. Respir. Crit. Care Med. 2015;192:1521–1524. doi: 10.1164/rccm.201502-0396LE. PubMed DOI PMC

Bodas M., Min T., Vij N. Critical role of CFTR-dependent lipid rafts in cigarette smoke-induced lung epithelial injury. Am. J. Physiol.-Lung Cell. Mol. Physiol. 2011;300:L811–L820. doi: 10.1152/ajplung.00408.2010. PubMed DOI PMC

Kaza N., Lin V.Y., Stanford D., Hussain S.S., Falk Libby E., Kim H., Borgonovi M., Conrath K., Mutyam V., Byzek S.A., et al. Evaluation of a novel CFTR potentiator in COPD ferrets with acquired CFTR dysfunction. Eur. Respir. J. 2022;60:2101581. doi: 10.1183/13993003.01581-2021. PubMed DOI PMC

Brown M.B., Hunt W.R., Noe J.E., Rush N.I., Schweitzer K.S., Leece T.C., Moldobaeva A., Wagner E.M., Dudek S.M., Poirier C., et al. Loss of Cystic Fibrosis Transmembrane Conductance Regulator Impairs Lung Endothelial Cell Barrier Function and Increases Susceptibility to Microvascular Damage from Cigarette Smoke. Pulm. Circ. 2014;4:260–268. doi: 10.1086/675989. PubMed DOI PMC

Carlstedt-Duke J., Brönnegård M., Strandvik B. Pathological regulation of arachidonic acid release in cystic fibrosis: The putative basic defect. Proc. Natl. Acad. Sci. USA. 1986;83:9202–9206. doi: 10.1073/pnas.83.23.9202. PubMed DOI PMC

Farrell P.M., Mischler E.H., Engle M.J., Jeannette Brown D., Lau S.-M. Fatty Acid Abnormalities in Cystic Fibrosis. Pediatr. Res. 1985;19:104–109. doi: 10.1203/00006450-198501000-00028. PubMed DOI

Andersson C., Al-Turkmani M.R., Savaille J.E., Alturkmani R., Katrangi W., Cluette-Brown J.E., Zaman M.M., Laposata M., Freedman S.D. Cell culture models demonstrate that CFTR dysfunction leads to defective fatty acid composition and metabolism. J. Lipid Res. 2008;49:1692–1700. doi: 10.1194/jlr.M700388-JLR200. PubMed DOI PMC

Guilbault C., De Sanctis J.B., Wojewodka G., Saeed Z., Lachance C., Skinner T.A.A., Vilela R.M., Kubow S., Lands L.C., Hajduch M., et al. Fenretinide Corrects Newly Found Ceramide Deficiency in Cystic Fibrosis. Am. J. Respir. Cell Mol. Biol. 2008;38:47–56. doi: 10.1165/rcmb.2007-0036OC. PubMed DOI

Guilbault C., Wojewodka G., Saeed Z., Hajduch M., Matouk E., De Sanctis J.B., Radzioch D. Cystic Fibrosis Fatty Acid Imbalance Is Linked to Ceramide Deficiency and Corrected by Fenretinide. Am. J. Respir. Cell Mol. Biol. 2009;41:100–106. doi: 10.1165/rcmb.2008-0279OC. PubMed DOI

Garić D., Dumut D.C., Shah J., De Sanctis J.B., Radzioch D. The role of essential fatty acids in cystic fibrosis and normalizing effect of fenretinide. Cell. Mol. Life Sci. 2020;77:4255–4267. doi: 10.1007/s00018-020-03530-x. PubMed DOI PMC

Garić D., De Sanctis J.B., Dumut D.C., Shah J., Peña M.J., Youssef M., Petrof B.J., Kopriva F., Hanrahan J.W., Hajduch M., et al. Fenretinide favorably affects mucins (MUC5AC/MUC5B) and fatty acid imbalance in a manner mimicking CFTR-induced correction. Biochim. Biophys. Acta BBA Mol. Cell Biol. Lipids. 2020;1865:158538. doi: 10.1016/j.bbalip.2019.158538. PubMed DOI

Centorame A., Dumut D.C., Youssef M., Ondra M., Kianicka I., Shah J., Paun R.A., Ozdian T., Hanrahan J.W., Gusev E., et al. Treatment With LAU-7b Complements CFTR Modulator Therapy by Improving Lung Physiology and Normalizing Lipid Imbalance Associated With CF Lung Disease. Front. Pharmacol. 2022;13:876842. doi: 10.3389/fphar.2022.876842. PubMed DOI PMC

Rouzer C.A., Marnett L.J. Cyclooxygenases: Structural and functional insights. J. Lipid Res. 2009;50:S29–S34. doi: 10.1194/jlr.R800042-JLR200. PubMed DOI PMC

Samuelsson B., Dahlén S.-E., Lindgren J.Å., Rouzer C.A., Serhan C.N. Leukotrienes and Lipoxins: Structures, Biosynthesis, and Biological Effects. Science. 1987;237:1171–1176. doi: 10.1126/science.2820055. PubMed DOI

Freedman S.D., Blanco P.G., Zaman M.M., Shea J.C., Ollero M., Hopper I.K., Weed D.A., Gelrud A., Regan M.M., Laposata M., et al. Association of cystic fibrosis with abnormalities in fatty acid metabolism. N. Engl. J. Med. 2004;350:560–569. doi: 10.1056/NEJMoa021218. PubMed DOI

Jeanson L., Guerrera I.C., Papon J.-F., Chhuon C., Zadigue P., Prulière-Escabasse V., Amselem S., Escudier E., Coste A., Edelman A. Proteomic analysis of nasal epithelial cells from cystic fibrosis patients. PLoS ONE. 2014;9:e108671. doi: 10.1371/journal.pone.0108671. PubMed DOI PMC

Eickmeier O., Fussbroich D., Mueller K., Serve F., Smaczny C., Zielen S., Schubert R. Pro-resolving lipid mediator Resolvin D1 serves as a marker of lung disease in cystic fibrosis. PLoS ONE. 2017;12:e0171249. doi: 10.1371/journal.pone.0171249. PubMed DOI PMC

Spite M., Norling L.V., Summers L., Yang R., Cooper D., Petasis N.A., Flower R.J., Perretti M., Serhan C.N. Resolvin D2 is a potent regulator of leukocytes and controls microbial sepsis. Nature. 2009;461:1287–1291. doi: 10.1038/nature08541. PubMed DOI PMC

Hanssens L., Thiébaut I., Lefèvre N., Malfroot A., Knoop C., Duchateau J., Casimir G. The clinical benefits of long-term supplementation with omega-3 fatty acids in cystic fibrosis patients—A pilot study. Prostaglandins Leukot. Essent. Fat. Acids. 2016;108:45–50. doi: 10.1016/j.plefa.2016.03.014. PubMed DOI

Henderson W.R., Astley S.J., McCready M.M., Kushmerick P., Casey S., Becker J.W., Ramsey B.W. Oral absorption of omega-3 fatty acids in patients with cystic fibrosis who have pancreatic insufficiency and in healthy control subjects. J. Pediatr. 1994;124:400–408. doi: 10.1016/S0022-3476(94)70362-0. PubMed DOI

Panchaud A., Sauty A., Kernen Y., Decosterd L.A., Buclin T., Boulat O., Hug C., Pilet M., Roulet M. Biological effects of a dietary omega-3 polyunsaturated fatty acids supplementation in cystic fibrosis patients: A randomized, crossover placebo-controlled trial. Clin. Nutr. Edinb. Scotl. 2006;25:418–427. doi: 10.1016/j.clnu.2005.10.011. PubMed DOI

Oliver C., Watson H. Omega-3 fatty acids for cystic fibrosis. Cochrane Database Syst. Rev. 2016:CD002201. doi: 10.1002/14651858.CD002201.pub5. PubMed DOI PMC

Watson H., Stackhouse C. Omega-3 fatty acid supplementation for cystic fibrosis. Cochrane Database Syst. Rev. 2020;4:CD002201. doi: 10.1002/14651858.CD002201.pub6. PubMed DOI PMC

Elborn J.S., Horsley A., MacGregor G., Bilton D., Grosswald R., Ahuja S., Springman E.B. Phase I Studies of Acebilustat: Biomarker Response and Safety in Patients with Cystic Fibrosis. Clin. Transl. Sci. 2017;10:28–34. doi: 10.1111/cts.12428. PubMed DOI PMC

Elborn J.S., Ahuja S., Springman E., Mershon J., Grosswald R., Rowe S.M. EMPIRE-CF: A phase II randomized placebo-controlled trial of once-daily, oral acebilustat in adult patients with cystic fibrosis—Study design and patient demographics. Contemp. Clin. Trials. 2018;72:86–94. doi: 10.1016/j.cct.2018.07.014. PubMed DOI

Zurier R.B., Sun Y.-P., George K.L., Stebulis J.A., Rossetti R.G., Skulas A., Judge E., Serhan C.N. Ajulemic acid, a synthetic cannabinoid, increases formation of the endogenous proresolving and anti-inflammatory eicosanoid, lipoxin A4. FASEB J. Off. Publ. Fed. Am. Soc. Exp. Biol. 2009;23:1503–1509. doi: 10.1096/fj.08-118323. PubMed DOI PMC

Motwani M.P., Bennett F., Norris P.C., Maini A.A., George M.J., Newson J., Henderson A., Hobbs A.J., Tepper M., White B., et al. Potent Anti-Inflammatory and Pro-Resolving Effects of Anabasum in a Human Model of Self-Resolving Acute Inflammation. Clin. Pharmacol. Ther. 2018;104:675–686. doi: 10.1002/cpt.980. PubMed DOI PMC

Springman E., Grosswald R., Philpot E., MacGregor G., Horsley A., Bilton D., Stewart J., Elborn J.S. 126 A phase 1 clinical study of CTX-4430 in cystic fibrosis patients. J. Cyst. Fibros. 2015;14:S90. doi: 10.1016/S1569-1993(15)30303-9. DOI

A double-blind, placebo-controlled phase 2 study in adults with cystic fibrosis of anabasum, a selective cannabinoid receptor type 2 agonist. Pediatr. Pulmonol. 2017;52:S214–S516. doi: 10.1002/ppul.23840. DOI

Chmiel J.F., Flume P., Downey D.G., Dozor A.J., Colombo C., Mazurek H., Sapiejka E., Rachel M., Constantine S., Conley B., et al. Safety and efficacy of lenabasum in a phase 2 randomized, placebo-controlled trial in adults with cystic fibrosis. J. Cyst. Fibros. 2021;20:78–85. doi: 10.1016/j.jcf.2020.09.008. PubMed DOI

Chmiel J.F., Elborn J.S., Constantine S., White B. WS01.5 A Phase 2 study of the safety, pharmacokinetics, and efficacy of anabasum (JBT-101) in cystic fibrosis (CF) J. Cyst. Fibros. 2017;16:1–13. doi: 10.1016/S1569-1993(17)30160-1. DOI

Cilloniz C., Pantin-Jackwood M.J., Ni C., Goodman A.G., Peng X., Proll S.C., Carter V.S., Rosenzweig E.R., Szretter K.J., Katz J.M., et al. Lethal Dissemination of H5N1 Influenza Virus Is Associated with Dysregulation of Inflammation and Lipoxin Signaling in a Mouse Model of Infection. J. Virol. 2010;84:7613–7624. doi: 10.1128/JVI.00553-10. PubMed DOI PMC

Lee C.H. Role of specialized pro-resolving lipid mediators and their receptors in virus infection: A promising therapeutic strategy for SARS-CoV-2 cytokine storm. Arch. Pharm. Res. 2021;44:84–98. doi: 10.1007/s12272-020-01299-y. PubMed DOI PMC

Louca P., Murray B., Klaser K., Graham M.S., Mazidi M., Leeming E.R., Thompson E., Bowyer R., Drew D.A., Nguyen L.H., et al. Modest effects of dietary supplements during the COVID-19 pandemic: Insights from 445 850 users of the COVID-19 Symptom Study app. BMJ Nutr. Prev. Health. 2021;4:149–157. doi: 10.1136/bmjnph-2021-000250. PubMed DOI PMC

Zapata B.R., Müller J.M., Vásquez J.E., Ravera F., Lago G., Cañón E., Castañeda D., Pradenas M., Ramírez-Santana M. Omega-3 Index and Clinical Outcomes of Severe COVID-19: Preliminary Results of a Cross-Sectional Study. Int. J. Environ. Res. Public. Health. 2021;18:7722. doi: 10.3390/ijerph18157722. PubMed DOI PMC

Berger A.A., Sherburne R., Urits I., Patel H., Eskander J. Icosapent Ethyl—A Successful Treatment for Symptomatic COVID-19 Infection. Cureus. 2020;12:e10211. doi: 10.7759/cureus.10211. PubMed DOI PMC

Hackensack Meridian Health Feasibility Pilot Clinical Trial of Omega-3 (EPA+DHA) Supplement vs. Placebo for Post-Acute Sequelae of Coronavirus-19 (COVID-19) Recovery Among Health Care Workers. [(accessed on 25 August 2024)];2024 Available online: https://clinicaltrials.gov/study/NCT05121766.

S.L.A. Pharma AG A Randomised, Double-blind, Placebo Controlled Study of Eicosapentaenoic Acid (EPA-FFA) Gastro-resistant Capsules to Treat Hospitalised Subjects With Confirmed SARS-CoV-2. [(accessed on 25 August 2024)];2021 Available online: https://clinicaltrials.gov/study/NCT04335032.

Hamad Medical Corporation Omega-3 Oil Use in COVID-19 Patients in Qatar: A Randomized Controlled Trial. [(accessed on 25 August 2024)];2021 Available online: https://clinicaltrials.gov/study/NCT04836052.