Pediatric Asthma: Comparison
Please note this is a comparison between Version 2 by Lily Guo and Version 1 by Maria Michelle Papamichael.

Asthma in children remains a significant public health challenge affecting 5–20% of children in Europe and is associated with increased morbidity and societal healthcare costs. 

  • asthma
  • asthma phenotypes
  • metabolomics
  • biomarkers
  • pediatric
Please wait, diff process is still running!

References

  1. GINA. Pocket guide for Asthma Management and Prevention (For Adults and Children older than 5 years). In Global Initiative for Asthma; Global Initiative for Asthma: Fontana-on-Geneva Lake, WI, USA, 2019; Available online: (accessed on 15 March 2021).
  2. Beasley, R.; Semprini, A.; Mitchell, E.A. Risk factors for asthma: Is prevention possible? Lancet 2015, 386, 1075–1085.
  3. Asher, I.; Pearce, N. Global burden of asthma among children. Int. J. Tuberc. Lung Dis. 2014, 18, 1269–1278.
  4. Katsardis, C.V.; Alexandraki, S.; Paraskakis, E. Chapter 2: Spirometry in children 6-16 years old. In Paediatric Pulmonary Function Testing Indications and Interpretation; Katsardis, C., Koumbourlis, A., Anthracopoulos, M., Paraskakis, E., Eds.; NOVA Biomedical: New York, NY, USA, 2015; pp. 15–42.
  5. Frima, E.-S.; Theodorakopoulos, I.; Gidaris, D.; Karantaglis, N.; Chatziparasidis, G.; Plotas, P.; Anthracopoulos, M.; Fouzas, S. Lung Function Variability in Children and Adolescents With and Without Asthma (LUV Study): Protocol for a Prospective, Nonrandomized, Clinical Trial. JMIR Res. Protoc. 2020, 9, e20350.
  6. Wang, T.J.; Larson, M.G.; Vasan, R.S.; Cheng, S.; Rhee, E.P.; McCabe, E.; Lewis, G.D.; Fox, C.S.; Jacques, P.F.; Fernandez, C.; et al. Metabolite profiles and the risk of developing diabetes. Nat. Med. 2011, 17, 448–453.
  7. Wang, T.J.; Gona, P.; Larson, M.G.; Tofler, G.H.; Levy, D.; Newton-Cheh, C.; Jacques, P.F.; Rifai, N.; Selhub, J.; Robins, S.J.; et al. Multiple Biomarkers for the Prediction of First Major Cardiovascular Events and Death. N. Engl. J. Med. 2006, 355, 2631–2639.
  8. Tsoukalas, D.; Fragoulakis, V.; Sarandi, E.; Docea, A.O.; Papakonstaninou, E.; Tsilimidos, G.; Anamaterou, C.; Fragkiadaki, P.; Aschner, M.; Tsatsakis, A.; et al. Targeted Metabolomic Analysis of Serum Fatty Acids for the Prediction of Autoimmune Diseases. Front. Mol. Biosci. 2019, 6, 120.
  9. Tsoukalas, D.; Fragoulakis, V.; Papakonstantinou, E.; Antonaki, M.; Vozikis, A.; Tsatsakis, A.; Buga, A.M.; Mitroi, M.; Calina, D. Prediction of Autoimmune Diseases by Targeted Metabolomic Assay of Urinary Organic Acids. Metabolites 2020, 10, 502.
  10. Johnson, C.H.; Ivanisevic, J.; Siuzdak, G. Metabolomics: Beyond biomarkers and towards mechanisms. Nat. Rev. Mol. Cell Biol. 2016, 17, 451–459.
  11. Sarandi, E.; Thanasoula, M.; Anamaterou, C.; Papakonstantinou, E.; Geraci, F.; Papamichael, M.M.; Itsiopoulos, C.; Tsoukalas, D. Metabolic profiling of organic and fatty acids in chronic and autoimmune diseases. Adv. Appl. Microbiol. 2021, 101, 169–229.
  12. Kelly, R.S.; Dahlin, A.; McGeachie, M.J.; Qiu, W.; Sordillo, J.; Wan, E.S.; Wu, A.C.; Lasky-Su, J. Asthma Metabolomics and the Potential for Integrative Omics in Research and the Clinic. Chest 2017, 151, 262–277.
  13. Dunn, W.B.; Broadhurst, D.I.; Atherton, H.J.; Goodacre, R.; Griffin, J.L. Systems level studies of mammalian metabolomes: The roles of mass spectrometry and nuclear magnetic resonance spectroscopy. Chem. Soc. Rev. 2011, 40, 387–426.
  14. Roberts, L.D.; Souza, A.L.; Gerszten, R.E.; Clish, C.B. Targeted Metabolomics. Curr. Protoc. Mol. Biol. 2012, 98, 30–32.
  15. Fitzpatrick, A.M.; Park, Y.; Brown, L.A.S.; Jones, D.P. Children with severe asthma have unique oxidative stress-associated metabolomic profiles. J. Allergy Clin. Immunol. 2014, 133, 258.e8–261.e8.
  16. Mattarucchi, E.; Baraldi, E.; Guillou, C. Metabolomics applied to urine samples in childhood asthma; Differentiation between asthma phenotypes and identification of relevant metabolites. Biomed. Chromatogr. 2011, 26, 89–94.
  17. Van De Kant, K.D.G.; Van Berkel, J.J.B.N.; Jöbsis, Q.; Passos, V.L.; Klaassen, E.M.M.; Van Der Sande, L.; Van Schayck, O.C.P.; De Jongste, J.C.; Van Schooten, F.J.; Derks, E.; et al. Exhaled breath profiling in diagnosing wheezy preschool children. Eur. Respir. J. 2012, 41, 183–188.
  18. Blume, C.; Davies, D.E. In vitro and ex vivo models of human asthma. Eur. J. Pharm. Biopharm. 2013, 84, 394–400.
  19. Carraro, S.; Bozzetto, S.; Giordano, G.; El Mazloum, D.; Stocchero, M.; Pirillo, P.; Zanconato, S.; Baraldi, E. Wheezing preschool children with early-onset asthma reveal a specific metabolomic profile. Pediatr. Allergy Immunol. 2018, 29, 375–382.
  20. Turi, K.N.; Romick-Rosendale, L.; Gebretsadik, T.; Watanabe, M.; Brunwasser, S.; Anderson, L.J.; Moore, M.L.; Larkin, E.K.; Peebles, R.S.; Hartert, T.V. Using urine metabolomics to understand the pathogenesis of infant respiratory syncytial virus (RSV) infection and its role in childhood wheezing. Metabolomics 2018, 14, 135.
  21. Chiu, C.-Y.; Cheng, M.-L.; Chiang, M.-H.; Wang, C.-J.; Tsai, M.-H.; Lin, G. Metabolomic Analysis Reveals Distinct Profiles in the Plasma and Urine Associated with IgE Reactions in Childhood Asthma. J. Clin. Med. 2020, 9, 887.
  22. Saude, E.J.; Skappak, C.D.; Regush, S.; Cook, K.; Ben-Zvi, A.; Becker, A.; Moqbel, R.; Sykes, B.D.; Rowe, B.H.; Adamko, D.J. Metabolomic profiling of asthma: Diagnostic utility of urine nuclear magnetic resonance spectroscopy. J. Allergy Clin. Immunol. 2011, 127, 757.e6–764.e6.
  23. Papamichael, M.M.; Katsardis, C.; Erbas, B.; Itsiopoulos, C.; Tsoukalas, D.; Katsardis, C. Urinary organic acids as biomarkers in the assessment of pulmonary function in children with asthma. Nutr. Res. 2019, 61, 31–40.
  24. Barlotta, A.; Pirillo, P.; Stocchero, M.; Donato, F.; Giordano, G.; Bont, L.; Zanconato, S.; Carraro, S.; Baraldi, E. Metabolomic Profiling of Infants With Recurrent Wheezing After Bronchiolitis. J. Infect. Dis. 2018, 219, 1216–1223.
  25. Carraro, S.; Baraldi, E.; Giordano, G.; Pirillo, P.; Stocchero, M.; Houben, M.; Bont, L. Metabolomic Profile of Amniotic Fluid and Wheezing in the First Year of Life—A Healthy Birth Cohort Study. J. Pediatr. 2018, 196, 264.e4–269.e4.
  26. Tao, J.-L.; Chen, Y.-Z.; Dai, Q.-G.; Tian, M.; Wang, S.-C.; Shan, J.-J.; Ji, J.-J.; Lin, L.-L.; Li, W.-W.; Yuan, B. Urine metabolic profiles in paediatric asthma. Respirology 2019, 24, 572–581.
  27. Chawes, B.L.; Giordano, G.; Pirillo, P.; Rago, D.; Rasmussen, M.A.; Stokholm, J.; Bønnelykke, K.; Bisgaard, H.; Baraldi, E. Neonatal Urine Metabolic Profiling and Development of Childhood Asthma. Metabolites 2019, 9, 185.
  28. Kelly, R.S.; Virkud, Y.; Giorgio, R.; Celedón, J.C.; Weiss, S.T.; Lasky-Su, J. Metabolomic profiling of lung function in Costa-Rican children with asthma. Biochim. Biophys. Acta Mol. Basis Dis. 2017, 1863, 1590–1595.
  29. Chang, C.; Guo, Z.-G.; He, B.; Yao, W.-Z. Metabolic alterations in the sera of Chinese patients with mild persistent asthma: A GC-MS-based metabolomics analysis. Acta Pharmacol. Sin. 2015, 36, 1356–1366.
  30. Aragonés, J.; Fraisl, P.; Baes, M.; Carmeliet, P. Oxygen Sensors at the Crossroad of Metabolism. Cell Metab. 2009, 9, 11–22.
  31. Ho, W.E.; Xu, Y.-J.; Xu, F.; Cheng, C.; Peh, H.Y.; Tannenbaum, S.R.; Wong, W.S.F.; Ong, C.N. Metabolomics Reveals Altered Metabolic Pathways in Experimental Asthma. Am. J. Respir. Cell Mol. Biol. 2013, 48, 204–211.
  32. Jung, J.; Kim, S.-H.; Lee, H.-S.; Choi, G.S.; Jung, Y.-S.; Ryu, D.H.; Park, H.-S.; Hwang, G.-S. Serum metabolomics reveals pathways and biomarkers associated with asthma pathogenesis. Clin. Exp. Allergy 2013, 43, 425–433.
  33. Infantino, V.; Iacobazzi, V.; Menga, A.; Avantaggiati, M.L.; Palmieri, F. A key role of the mitochondrial citrate carrier (SLC25A1) in TNFα- and IFNγ-triggered inflammation. Biochim. Biophys. Acta Bioenerg. 2014, 1839, 1217–1225.
  34. Lampropoulou, V.; Sergushichev, A.; Bambouskova, M.; Nair, S.; Vincent, E.E.; Loginicheva, E.; Cervantes-Barragan, L.; Ma, X.; Huang, S.C.-C.; Griss, T.; et al. Itaconate Links Inhibition of Succinate Dehydrogenase with Macrophage Metabolic Remodeling and Regulation of Inflammation. Cell Metab. 2016, 24, 158–166.
  35. Litwack, G. Pantothenic Acid in Chapter 20—Vitamins and Nutrition. In Human Biochemistry; Litwack, G., Ed.; Academic Press: Boston, MA, USA, 2018; pp. 645–680.
  36. Nelson, D.; Cox, M.L. Principles of Biochemistry; W.H Freeman & Co Ltd.: New York, NY, USA, 2017.
  37. Martínez-Reyes, I.; Chandel, N.S. Mitochondrial TCA cycle metabolites control physiology and disease. Nat. Commun. 2020, 11, 1–11.
  38. Hettling, H.; Van Beek, J.H.G.M. Analyzing the Functional Properties of the Creatine Kinase System with Multiscale “Sloppy” Modeling. PLoS Comput. Biol. 2011, 7, e1002130.
  39. Upadhyay, D.; Dave, S.T.C. Rhabdomyolysis in Acute Severe Asthma: A Case Report and Literature Review. Int. J. Asthma Allergy Immunol. 2001, 2, 1–4. Available online: (accessed on 15 March 2021).
  40. Demos, M.A.; Gitin, E.L.; Kagen, L.J. Exercise myoglobinemia and acute exertional rhabdomyolysis. Arch. Intern. Med. 1974, 134, 669–673.
  41. Ahmad, T.; Kumar, M.; Mabalirajan, U.; Pattnaik, B.; Aggarwal, S.; Singh, R.; Singh, S.; Mukerji, M.; Ghosh, B.; Agrawal, A. Hypoxia Response in Asthma. Am. J. Respir. Cell Mol. Biol. 2012, 47, 1–10.
  42. Chiu, C.-Y.; Lin, G.; Cheng, M.-L.; Chiang, M.-H.; Tsai, M.-H.; Su, K.-W.; Hua, M.-C.; Liao, S.-L.; Lai, S.-H.; Yao, T.-C.; et al. Longitudinal urinary metabolomic profiling reveals metabolites for asthma development in early childhood. Pediatr. Allergy Immunol. 2018, 29, 496–503.
  43. Comhair, S.A.A.; McDunn, J.; Bennett, C.; Fettig, J.; Erzurum, S.C.; Kalhan, S.C.; Fetig, J. Metabolomic Endotype of Asthma. J. Immunol. 2015, 195, 643–650.
  44. Gebicki, J.; Sysa-Jedrzejowska, A.; Adamus, J.; Woźniacka, A.; Rybak, M.; Zielonka, J. 1-Methylnicotinamide: A potent anti-inflammatory agent of vitamin origin. Pol. J. Pharmacol. 2003, 55, 109–112.
  45. Biedroń, R.; Ciszek, M.; Tokarczyk, M.; Bobek, M.; Kurnyta, M.; Słomińska, E.M.; Smolenski, R.T.; Marcinkiewicz, J. 1-Methylnicotinamide and nicotinamide: Two related anti-inflammatory agents that differentially affect the functions of activated macrophages. Arch. Immunol. Ther. Exp. 2008, 56, 127–134.
  46. Oka, T.; Itoi, T.; Terada, N.; Nakanishi, H.; Taguchi, R.; Hamaoka, K. Change in the Membranous Lipid Composition Accelerates Lipid Peroxidation in Young Rat Hearts Subjected to 2 Weeks of Hypoxia Followed by Hyperoxia. Circ. J. 2008, 72, 1359–1366.
  47. Pauly, D.F.; Pepine, C.J. The role of carnitine in myocardial dysfunction. Am. J. Kidney Dis. 2003, 41, S35–S43.
  48. Baker, P.R.S.; Cramer, S.D.; Kennedy, M.; Assimos, D.G.; Holmes, R.P. Glycolate and glyoxylate metabolism in HepG2 cells. Am. J. Physiol. Physiol. 2004, 287, C1359–C1365.
  49. Kalapos, M. Possible physiological roles of acetone metabolism in humans. Med. Hypotheses 1999, 53, 236–242.
  50. Simpson, A.J.; Horne, S.; Sharp, P.; Sharps, R.; Kippelen, P. Effect of Creatine Supplementation on the Airways of Youth Elite Soccer Players. Med. Sci. Sports Exerc. 2019, 51, 1582–1590.
  51. Ferreira, S.C.; Toledo, A.C.; Hage, M.; Santos, A.B.G.; Medeiros, M.C.R.; Martins, M.A.; Carvalho, C.; Dolhnikoff, M.; Vieira, R.P. Creatine Activates Airway Epithelium in Asthma. Endoscopy 2010, 31, 906–912.
  52. Takeda, M.; Kiyatake, I.; Koide, H.; Jung, K.Y.; Endou, H. Biosynthesis of Guanidinoacetic Acid in Isolated Renal Tubules. Clin. Chem. Lab. Med. 1992, 30, 325–331.
  53. Strapková, A.; Antošová, M. Glutamate receptors and the airways hyperreactivity. Gen. Physiol. Biophys. 2012, 31, 93–100.
  54. Cruzat, V.; Rogero, M.M.; Keane, K.N.; Curi, R.; Newsholme, P. Glutamine: Metabolism and Immune Function, Supplementation and Clinical Translation. Nutrients 2018, 10, 1564.
  55. Atzei, A.; Atzori, L.; Moretti, C.; Barberini, L.; Noto, A.; Ottonello, G.; Pusceddu, E.; Fanos, V. Metabolomics in paediatric respiratory diseases and bronchiolitis. J. Matern. Neonatal. Med. 2011, 24, 59–62.
  56. Stewart, C.J.; Hasegawa, K.; Wong, B.M.C.; Ajami, N.J.; Petrosino, J.F.; Piedra, P.A.; Espinola, M.J.A.; Tierney, M.C.N.; Camargo, J.C.A.; Mansbach, J.M. Respiratory Syncytial Virus and Rhinovirus Bronchiolitis Are Associated With Distinct Metabolic Pathways. J. Infect. Dis. 2017, 217, 1160–1169.
  57. Wang, L.; Tang, Y.; Liu, S.; Mao, S.; Ling, Y.; Liu, D.; He, X.; Wang, X. Metabonomic Profiling of Serum and Urine by 1H NMR-Based Spectroscopy Discriminates Patients with Chronic Obstructive Pulmonary Disease and Healthy Individuals. PLoS ONE 2013, 8, e65675.
  58. Kassel, D.B.; Martin, M.; Schall, W.; Sweeley, C.C. Urinary metabolites ofL-threonine in type 1 diabetes determined by combined gas chromatography/chemical ionization mass spectrometry. J. Mass Spectrom. 1986, 13, 535–540.
  59. Sanchez Jimenez, J.; Herrero Espinet, F.J.; Mengibar Garrido, J.M.; Roca Antonio, J.; Penos Mayor, S.; Penas Boira, M.D.M.; Roca Comas, A.; Ballester Martinez, A. Asthma and insulin resistance in obese children and adolescents. Pediatr. Allergy Immunol. 2014, 25, 699–705.
  60. NCBI. PubChem Compound Summary for Creatinine. USA: National Center for Biotechnology Information. 2020. Available online: (accessed on 7 January 2021).
  61. Atzori, L. 1H NMR-based metabolomic analysis of urine from preterm and term neonates. Front. Biosci. 2011, 3, 1005–1012.
  62. Rodríguez, M.M.; Gómez, A.H.; Abitbol, C.L.; Chandar, J.J.; Duara, S.; Zilleruelo, G.E. Histomorphometric Analysis of Postnatal Glomerulogenesis in Extremely Preterm Infants. Pediatr. Dev. Pathol. 2004, 7, 17–25.
  63. Aguirre, M.; Oliveros, R.; Vallo, A. Long-term renal follow-up of extremely low birth weight infants. Pediatr. Nephrol. 2005, 20, 579–584.
  64. Licari, A.; Fuchs, D.; Marseglia, G.; Ciprandi, G. Tryptophan metabolic pathway and neopterin in asthmatic children in clinical practice. Ital. J. Pediatr. 2019, 45, 1–4.
  65. Wedes, S.H.; Wu, W.; Comhair, S.A.; McDowell, K.M.; DiDonato, J.A.; Erzurum, S.C.; Hazen, S.L. Urinary Bromotyrosine Measures Asthma Control and Predicts Asthma Exacerbations in Children. J. Pediatr. 2011, 159, 248.e1–255.e1.
  66. Richard, D.M.; Dawes, M.A.; Mathias, C.W.; Acheson, A.; Hill-Kapturczak, N.; Dougherty, D.M. L-Tryptophan: Basic Metabolic Functions, Behavioral Research and Therapeutic Indications. Int. J. Tryptophan Res. 2009, 2, IJTR.S2129–IJTR.S2160.
  67. Kepert, I.; Fonseca, J.; Müller, C.; Milger, K.; Hochwind, K.; Kostric, M.; Fedoseeva, M.; Ohnmacht, C.; Dehmel, S.; Nathan, P.; et al. D-tryptophan from probiotic bacteria influences the gut microbiome and allergic airway disease. J. Allergy Clin. Immunol. 2017, 139, 1525–1535.
  68. Van Der Sluijs, K.F.; Van De Pol, M.A.; Kulik, W.; Dijkhuis, A.; Smids, B.S.; Van Eijk, H.W.; Karlas, J.A.; Molenkamp, R.; Wolthers, K.C.; Johnston, S.L.; et al. Systemic tryptophan and kynurenine catabolite levels relate to severity of rhinovirus-induced asthma exacerbation: A prospective study with a parallel-group design. Thorax 2013, 68, 1122–1130.
  69. Tan, P.; Bharath, A. Manipulation of indoleamine 2,3 dioxygenase; a novel therapeutic target for treatment of diseases. Expert Opin. Ther. Targets 2009, 13, 987–1012.
  70. Gostner, J.M.; Becker, K.; Kofler, H.; Strasser, B.; Fuchs, D. Tryptophan Metabolism in Allergic Disorders. Int. Arch. Allergy Immunol. 2016, 169, 203–215.
  71. Ünüvar, S.; Erge, D.; Kılıçarslan, B.; Bağ, H.G.G.; Çatal, F.; Girgin, G.; Baydar, T. Neopterin Levels and Indoleamine 2,3-Dioxygenase Activity as Biomarkers of Immune System Activation and Childhood Allergic Diseases. Ann. Lab. Med. 2019, 39, 284–290.
  72. Sackesen, C.; Ercan, H.; Dizdar, E.; Soyer, O.; Gumus, P.; Tosun, B.N.; Büyüktuncer, Z.; Karabulut, E.; Besler, T.; Kalayci, O. A comprehensive evaluation of the enzymatic and nonenzymatic antioxidant systems in childhood asthma. J. Allergy Clin. Immunol. 2008, 122, 78–85.
  73. Noto, A.; Fanos, V.; Barberini, L.; Grapov, D.; Fattuoni, C.; Zaffanello, M.; Casanova, A.; Fenu, G.; De Giacomo, A.; De Angelis, M.; et al. The urinary metabolomics profile of an Italian autistic children population and their unaffected siblings. J. Matern. Neonat. Med. 2014, 27, 46–52.
  74. Barnes, M.A.; Carson, M.J.; Nair, M.G. Non-traditional cytokines: How catecholamines and adipokines influence macrophages in immunity, metabolism and the central nervous system. Cytokine 2015, 72, 210–219.
  75. Arreola, R.; Becerril-Villanueva, E.; Cruz-Fuentes, C.; Velasco-Velázquez, M.A.; Garcés-Alvarez, M.E.; Hurtado-Alvarado, G.; Quintero-Fabian, S.; Pavón, L. Immunomodulatory Effects Mediated by Serotonin. J. Immunol. Res. 2015, 2015, 1–21.
  76. Park, Y.H.; Fitzpatrick, A.M.; Medriano, C.A.; Jones, D.P. High-resolution metabolomics to identify urine biomarkers in corticosteroid-resistant asthmatic children. J. Allergy Clin. Immunol. 2017, 139, 1518.e4–1524.e4.
  77. NCBI. PubChem Compound Summary for CID 4740700, 3-Phenylpropionate; National Center for Biotechnology Information, National Library of Medicine: Bethesda, MD, USA, 2021. Available online: (accessed on 18 March 2021).
  78. MacPherson, J.C.; Comhair, S.A.A.; Erzurum, S.C.; Klein, D.F.; Lipscomb, M.F.; Kavuru, M.S.; Samoszuk, M.K.; Hazen, S.L. Eosinophils Are a Major Source of Nitric Oxide-Derived Oxidants in Severe Asthma: Characterization of Pathways Available to Eosinophils for Generating Reactive Nitrogen Species. J. Immunol. 2001, 166, 5763–5772.
  79. Wu, W.; Samoszuk, M.K.; Comhair, S.A.A.; Thomassen, M.J.; Farver, C.F.; Dweik, R.A.; Kavuru, M.S.; Erzurum, S.C.; Hazen, S.L. Eosinophils generate brominating oxidants in allergen-induced asthma. J. Clin. Investig. 2000, 105, 1455–1463.
  80. HMDB. Methyl-Imidazole Acetic Acid; Human Metabolome Database: Edmonton, AB, Canada, 2021. Available online: (accessed on 18 March 2021).
  81. Yamauchi, K.; Ogasawara, M. The Role of Histamine in the Pathophysiology of Asthma and the Clinical Efficacy of Antihistamines in Asthma Therapy. Int. J. Mol. Sci. 2019, 20, 1733.
  82. Neumann, D. Role of the Histamine H4-Receptor in Bronchial Asthma. Organotypic Model. Drug Dev. 2016, 241, 347–359.
  83. Çakmak, A.; Zeyrek, D.; Atas, A.; Çelik, H.; Aksoy, N.; Erel, O. Serum prolidase activity and oxidative status in patients with bronchial asthma. J. Clin. Lab. Anal. 2009, 23, 132–138.
  84. Nishitani, S.; Matsumura, T.; Fujitani, S.; Sonaka, I.; Miura, Y.; Yagasaki, K. Leucine promotes glucose uptake in skeletal muscles of rats. Biochem. Biophys. Res. Commun. 2002, 299, 693–696.
  85. Liu, H.; Liu, R.; Xiong, Y.; Li, X.; Wang, X.; Ma, Y.; Guo, H.; Hao, L.; Yao, P.; Liu, L.; et al. Leucine facilitates the insulin-stimulated glucose uptake and insulin signaling in skeletal muscle cells: Involving mTORC1 and mTORC2. Amino Acids 2014, 46, 1971–1979.
  86. D’Antona, G.; Ragni, M.; Cardile, A.; Tedesco, L.; Dossena, M.; Bruttini, F.; Caliaro, F.; Corsetti, G.; Bottinelli, R.; Carruba, M.O.; et al. Branched-Chain Amino Acid Supplementation Promotes Survival and Supports Cardiac and Skeletal Muscle Mitochondrial Biogenesis in Middle-Aged Mice. Cell Metab. 2010, 12, 362–372.
  87. Nakamura, I.; Ochiai, K.; Imai, Y.; Moriyasu, F.; Imawari, M. Restoration of innate host defense responses by oral supplementation of branched-chain amino acids in decompensated cirrhotic patients. Hepatol. Res. 2007, 37, 1062–1067.
  88. Calder, P.C. Branched-Chain Amino Acids and Immunity. J. Nutr. 2006, 136, 288S–293S.
  89. Lara, A.; Khatri, S.B.; Wang, Z.; Comhair, S.A.A.; Xu, W.; Dweik, R.A.; Bodine, M.; Levison, B.S.; Hammel, J.; Bleecker, E.; et al. Alterations of the Arginine Metabolome in Asthma. Am. J. Respir. Crit. Care Med. 2008, 178, 673–681.
  90. Morris, C.R.; Poljakovic, M.; Lavrisha, L.; Machado, L.; Kuypers, F.A.; Morris, S.M. Decreased Arginine Bioavailability and Increased Serum Arginase Activity in Asthma. Am. J. Respir. Crit. Care Med. 2004, 170, 148–153.
  91. Ripps, H.; Shen, W. Review: Taurine: A “very essential” amino acid. Mol. Vis. 2012, 18, 2673–2686.
  92. Mahmoud, A.M.; Ali, M.M. Methyl Donor Micronutrients that Modify DNA Methylation and Cancer Outcome. Nutrients 2019, 11, 608.
  93. Zhang, J.; Zheng, Y.G. SAM/SAH Analogs as Versatile Tools for SAM-Dependent Methyltransferases. ACS Chem. Biol. 2016, 11, 583–597.
  94. Su, X.; Wellen, K.E.; Rabinowitz, J.D. Metabolic control of methylation and acetylation. Curr. Opin. Chem. Biol. 2016, 30, 52–60.
  95. Martino, D.; Prescott, S. Epigenetics and Prenatal Influences on Asthma and Allergic Airways Disease. Chest 2011, 139, 640–647.
  96. Locasale, J.W. Serine, glycine and one-carbon units: Cancer metabolism in full circle. Nat. Rev. Cancer 2013, 13, 572–583.
  97. Brosnan, M.E.; Brosnan, J.T. Formate: The Neglected Member of One-Carbon Metabolism. Annu. Rev. Nutr. 2016, 36, 369–388.
  98. Sinha, A.; Desiraju, K.; Aggarwal, K.; Kutum, R.; Roy, S.; Lodha, R.; Kabra, S.K.; Ghosh, B.; Sethi, T.; Agrawal, A. Exhaled breath condensate metabolome clusters for endotype discovery in asthma. J. Transl. Med. 2017, 15, 1–9.
  99. Niculescu, M.D.; Zeisel, S.H. Diet, Methyl Donors and DNA Methylation: Interactions between Dietary Folate, Methionine and Choline. J. Nutr. 2002, 132, 2333S–2335S.
  100. Boisvert, F.-M.; Richard, S. Arginine Methylation Regulates the Cytokine Response. Mol. Cell 2004, 15, 492–494.
  101. Schwartz, D.A. Epigenetics and Environmental Lung Disease. Proc. Am. Thorac. Soc. 2010, 7, 123–125.
  102. Yu, M.; Cui, F.-X.; Jia, H.-M.; Zhou, C.; Yang, Y.; Zhang, H.-W.; Ding, G.; Zou, Z.-M. Aberrant purine metabolism in allergic asthma revealed by plasma metabolomics. J. Pharm. Biomed. Anal. 2016, 120, 181–189.
  103. Li, L.; Wan, C.; Wen, F. An unexpected role for serum uric acid as a biomarker for severity of asthma exacerbation. Asian Pac. J. Allergy Immunol. 2013, 32, 93–99.
  104. Abdulnaby, N.K.; Sayed, A.O.; Shalaby, N.M. Predictive value of serum uric acid in hospitalized adolescents and adults with acute asthma. Ther. Clin. Risk Manag. 2016, 12, 1701–1708.
  105. Kool, M.; Willart, M.A.; Van Nimwegen, M.; Bergen, I.; Pouliot, P.; Virchow, J.C.; Rogers, N.; Osorio, F.; Sousa, C.R.E.; Hammad, H.; et al. An unexpected role for uric acid as an inducer of T helper 2 cell immunity to inhaled antigens and inflammatory mediator of allergic asthma. Immunity 2011, 34, 527–540.
  106. Spicuzza, L.; Di Maria, G.; Polosa, R. Adenosine in the airways: Implications and applications. Eur. J. Pharmacol. 2006, 533, 77–88.
  107. Driver, A.G.; Kukoly, C.A.; Ali, S.; Mustafa, S.J. Adenosine in bronchoalveolar lavage fluid in asthma. Am. Rev. Respir. Dis. 1993, 148, 91–97.
  108. Huszár, É.; Vass, G.; Vizi, É.; Csoma, Z.; Barát, E.; Világos, G.M.; Herjavecz, I.; Horváth, I. Adenosine in exhaled breath condensate in healthy volunteers and in patients with asthma. Eur. Respir. J. 2002, 20, 1393–1398.
  109. Carraro, S.; Giordano, G.; Reniero, F.; Carpi, D.; Stocchero, M.; Sterk, P.; Baraldi, E. Asthma severity in childhood and metabolomic profiling of breath condensate. Allergy 2012, 68, 110–117.
  110. Brown, R.A.; Spina, D.; Page, C.P. Adenosine receptors and asthma. Br. J. Pharmacol. 2008, 153, S446–S456.
  111. HMDB. N-Methyladenosine; Human Metabolome Database: Edmonton, AB, Canada, 2021. Available online: (accessed on 15 March 2021).
  112. HMDB. Hypoxanthine; Human Metabolome Database: Edmonton, AB, Canada, 2021. Available online: (accessed on 15 March 2021).
  113. Lee, M.-Y.; Lee, N.-H.; Jung, D.; Lee, J.-A.; Seo, C.-S.; Lee, H.; Kim, J.-H.; Shin, H.-K. Protective effects of allantoin against ovalbumin (OVA)-induced lung inflammation in a murine model of asthma. Int. Immunopharmacol. 2010, 10, 474–480.
  114. Pan, L.; Han, P.; Ma, S.; Peng, R.; Wang, C.; Kong, W.; Cong, L.; Fu, J.; Zhang, Z.; Yu, H.; et al. Abnormal metabolism of gut microbiota reveals the possible molecular mechanism of nephropathy induced by hyperuricemia. Acta Pharm. Sin. B 2020, 10, 249–261.
  115. Calder, P.C. Omega-3 polyunsaturated fatty acids and inflammatory processes: Nutrition or pharmacology? Br. J. Clin. Pharmacol. 2013, 75, 645–662.
  116. Ferraro, V.A.; Carraro, S.; Pirillo, P.; Gucciardi, A.; Poloniato, G.; Stocchero, M.; Giordano, G.; Zanconato, S.; Baraldi, E. Breathomics in Asthmatic Children Treated with Inhaled Corticosteroids. Metabolites 2020, 10, 390.
  117. Reinke, S.N.; Gallart-Ayala, H.; Gómez, C.; Checa, A.; Fauland, A.; Naz, S.; Kamleh, M.A.; Djukanović, R.; Hinks, T.S.; Wheelock, C.E. Metabolomics analysis identifies different metabotypes of asthma severity. Eur. Respir. J. 2017, 49, 1601740.
  118. Comhair, S.A.A.; Bochenek, G.; Baicker-McKee, S.; Wang, Z.; Stachura, T.; Sanak, M.; Hammel, J.P.; Hazen, S.L.; Erzurum, S.C.; Nizankowska-Mogilnicka, E. The utility of biomarkers in diagnosis of aspirin exacerbated respiratory disease. Respir. Res. 2018, 19, 210.
  119. Miyata, J.; Fukunaga, K.; Kawashima, Y.; Ohara, O.; Kawana, A.; Asano, K.; Arita, M. Dysregulated metabolism of polyunsaturated fatty acids in eosinophilic allergic diseases. Prostaglandins Other Lipid Mediat. 2020, 150, 106477.
  120. Sanak, M. Eicosanoid Mediators in the Airway Inflammation of Asthmatic Patients: What is New? Allergy Asthma Immunol. Res. 2016, 8, 481–490.
  121. Montuschi, P.; Barnes, P.J. Exhaled leukotrienes and prostaglandins in asthma. J. Allergy Clin. Immunol. 2002, 109, 615–620.
  122. Wang, Z.-J.; Liang, C.-L.; Li, G.-M.; Yu, C.-Y.; Yin, M. Stearic acid protects primary cultured cortical neurons against oxidative stress. Acta Pharmacol. Sin. 2007, 28, 315–326.
  123. Ellwood, P.; Asher, M.I.; García-Marcos, L.; Williams, H.; Keil, U.; Robertson, C.; Nagel, G.; the ISAAC Phase III Study Group. Do fast foods cause asthma, rhinoconjunctivitis and eczema? Global findings from the International Study of Asthma and Allergies in Childhood (ISAAC) Phase Three. Thorax 2013, 68, 351–360.
  124. Nagel, G.; Weinmayr, G.; Kleiner, A.; Garcia-Marcos, L.; Strachan, D.P.; the ISAAC Phase Two Study Group. Effect of diet on asthma and allergic sensitisation in the International Study on Allergies and Asthma in Childhood (ISAAC) Phase Two. Thorax 2010, 65, 516–522.
  125. Calder, P.C.; Kremmyda, L.-S.; Vlachava, M.; Noakes, P.S.; Miles, E.A. Is there a role for fatty acids in early life programming of the immune system? Proc. Nutr. Soc. 2010, 69, 373–380.
  126. Papamichael, M.M.; Shrestha, S.K.; Itsiopoulos, C.; Erbas, B. The role of fish intake on asthma in children: A meta-analysis of observational studies. Pediatr. Allergy Immunol. 2018, 29, 350–360.
  127. Biong, A.S.; Berstad, P.; Pedersen, J.I. Biomarkers for intake of dairy fat and dairy products. Eur. J. Lipid Sci. Technol. 2006, 108, 827–834.
  128. Lordan, R.; Zabetakis, I. Invited review: The anti-inflammatory properties of dairy lipids. J. Dairy Sci. 2017, 100, 4197–4212.
  129. La Marca, G.; Rizzo, C. Analysis of organic acids and acylglycines for the diagnosis of related inborn errors of metabolism by GC- and HPLC-MS. In Metabolic Profiling, Methods in Molecular Biology; Metz, T.O., Ed.; Springer: Berlin, Germany, 2011; pp. 73–98.
  130. HMDB. 3-Hydroxytetradecanedioic Acid; Human Metabolome Database: Edmonton, AB, Canada, 2021. Available online: (accessed on 15 March 2021).
  131. Kumps, A.; Duez, P.; Mardens, Y. Metabolic, nutritional, iatrogenic, and artifactual sources of urinary organic acids: A comprehensive table. Clin. Chem. 2002, 48, 708–717.
  132. Quinn, K.D.; Schedel, M.; Nkrumah-Elie, Y.; Joetham, A.; Armstrong, M.; Cruickshank-Quinn, C.; Reisdorph, N.; Gelfand, E.W. Dysregulation of metabolic pathways in a mouse model of allergic asthma. Allergy 2017, 72, 1327–1337.
  133. Yoder, M.; Zhuge, Y.; Yuan, Y.; Holian, O.; Kuo, S.; Van Breemen, R.; Thomas, L.L.; Lum, H. Bioactive Lysophosphatidylcholine 16:0 and 18:0 Are Elevated in Lungs of Asthmatic Subjects. Allergy Asthma Immunol. Res. 2014, 6, 61–65.
  134. Tracey, T.J.; Steyn, F.J.; Wolvetang, E.J.; Ngo, S.T. Neuronal Lipid Metabolism: Multiple Pathways Driving Functional Outcomes in Health and Disease. Front. Mol. Neurosci. 2018, 11, 10.
  135. Ono, J.G.; Worgall, T.S.; Worgall, S. Airway reactivity and sphingolipids—Implications for childhood asthma. Mol. Cell. Pediatr. 2015, 2, 1–6.
  136. Mishra, V.; Banga, J.; Silveyra, P. Oxidative stress and cellular pathways of asthma and inflammation: Therapeutic strategies and pharmacological targets. Pharmacol. Ther. 2018, 181, 169–182.
  137. Niwa, T. Indoxyl Sulfate Is a Nephro-Vascular Toxin. J. Ren. Nutr. 2010, 20, S2–S6.
  138. Zduńska, K.; Dana, A.; Kolodziejczak, A.; Rotsztejn, H. Antioxidant Properties of Ferulic Acid and Its Possible Application. Ski. Pharmacol. Physiol. 2018, 31, 332–336.
  139. Pujos-Guillot, E.; Hubert, J.; Martin, J.-F.; Lyan, B.; Quintana, M.; Claude, S.; Chabanas, B.; Rothwell, J.A.; Bennetau-Pelissero, C.; Scalbert, A.; et al. Mass Spectrometry-based Metabolomics for the Discovery of Biomarkers of Fruit and Vegetable Intake: Citrus Fruit as a Case Study. J. Proteome Res. 2013, 12, 1645–1659.
  140. Motta, A.; Paris, D.; D’Amato, M.; Melck, D.; Calabrese, C.; Vitale, C.; Stanziola, A.A.; Corso, G.; Sofia, M.; Maniscalco, M. NMR Metabolomic Analysis of Exhaled Breath Condensate of Asthmatic Patients at Two Different Temperatures. J. Proteome Res. 2014, 13, 6107–6120.
  141. Albert, E.; Walker, J.; Thiesen, A.; Churchill, T.; Madsen, K. cis-Urocanic Acid Attenuates Acute Dextran Sodium Sulphate-Induced Intestinal Inflammation. PLoS ONE 2010, 5, e13676.
  142. Dawson, H.D.; Collins, G.; Pyle, R.; Key, M.; Weeraratna, A.; Deep-Dixit, V.; Nadal, C.N.; Taub, D.D. Direct and indirect effects of retinoic acid on human Th2 cytokine and chemokine expression by human T lymphocytes. BMC Immunol. 2006, 7, 27.
  143. Druilhe, A.; Zahm, J.-M.; Benayoun, L.; El Mehdi, D.; Grandsaigne, M.; Dombret, M.-C.; Mosnier, I.; Feger, B.; Depondt, J.; Aubier, M.; et al. Epithelium Expression and Function of Retinoid Receptors in Asthma. Am. J. Respir. Cell Mol. Biol. 2008, 38, 276–282.
  144. Schuster, G.U.; Kenyon, N.J.; Stephensen, C.B. Vitamin A Deficiency Decreases and High Dietary Vitamin A Increases Disease Severity in the Mouse Model of Asthma. J. Immunol. 2008, 180, 1834–1842.
  145. Arora, P.; Kumar, V.; Batra, S. Vitamin A status in children with asthma. Pediatr. Allergy Immunol. 2002, 13, 223–226.
  146. Jat, K.R.; Khairwa, A. Vitamin D and asthma in children: A systematic review and meta-analysis of observational studies. Lung India 2017, 34, 355–363.
  147. Brehm, J.M.; Schuemann, B.; Fuhlbrigge, A.L.; Hollis, B.W.; Strunk, R.C.; Zeiger, R.S.; Weiss, S.T.; Litonjua, A.A. Serum vitamin D levels and severe asthma exacerbations in the Childhood Asthma Management Program study. J. Allergy Clin. Immunol. 2010, 126, 52.e5–58.e5.
  148. Chinellato, I.; Piazza, M.; Sandri, M.; Peroni, D.G.; Cardinale, F.; Piacentini, G.L.; Boner, A.L. Serum vitamin D levels and exercise-induced bronchoconstriction in children with asthma. Eur. Respir. J. 2010, 37, 1366–1370.
  149. Uysalol, M.; Mutlu, L.C.; Saracoglu, G.V.; Karasu, E.; Guzel, S.; Kayaoglu, S.; Uzel, N. Childhood asthma and vitamin D deficiency in Turkey: Is there cause and effect relationship between them? Ital. J. Pediatr. 2013, 39, 78.
  150. Chinellato, I.; Piazza, M.; Sandri, M.; Peroni, D.; Piacentini, G.; Boner, A.L. Vitamin D Serum Levels and Markers of Asthma Control in Italian Children. J. Pediatr. 2011, 158, 437–441.
  151. Gupta, A.; Sjoukes, A.; Richards, D.; Banya, W.; Hawrylowicz, C.; Bush, A.; Saglani, S. Relationship between Serum Vitamin D, Disease Severity, and Airway Remodeling in Children with Asthma. Am. J. Respir. Crit. Care Med. 2011, 184, 1342–1349.
  152. Papamichael, M.M.; Itsiopoulos, C.; Lambert, K.; Katsardis, C.; Tsoukalas, D.; Erbas, B. Sufficient vitamin D status positively modified ventilatory function in asthmatic children following a Mediterranean diet enriched with fatty fish intervention study. Nutr. Res. 2020, 82, 99–109.
  153. Hall, S.C.; Agrawal, D.K. Vitamin D and Bronchial Asthma: An Overview of Data From the Past 5 Years. Clin. Ther. 2017, 39, 917–929.
  154. Fitzpatrick, A.M.; Jones, D.P.; Brown, L.A.S. Glutathione Redox Control of Asthma: From Molecular Mechanisms to Therapeutic Opportunities. Antioxid. Redox Signal. 2012, 17, 375–408.
  155. Holguin, F. Oxidative Stress in Airway Diseases. Ann. Am. Thorac. Soc. 2013, 10, S150–S157.
  156. Husain, Q.; Ahmad, A.; Shameem, M. Relation of oxidant-antioxidant imbalance with disease progression in patients with asthma. Ann. Thorac. Med. 2012, 7, 226–232.
  157. Fitzpatrick, A.M.; Teague, W.G.; Holguin, F.; Yeh, M.; Brown, L.A.S. Airway glutathione homeostasis is altered in children with severe asthma: Evidence for oxidant stress. J. Allergy Clin. Immunol. 2009, 123, 146.e8–152.e8.
  158. Ueda, N.; Tsuboi, K.; Uyama, T. Enzymological studies on the biosynthesis of N-acylethanolamines. Biochim. Biophys. Acta Mol. Cell Biol. Lipids 2010, 1801, 1274–1285.
  159. Berdyshev, E.V.; Schmid, P.C.; Krebsbach, R.J.; Hillard, C.J.; Huang, C.; Chen, N.; Dong, Z.; Schmid, H.H.O. Cannabinoid-receptor-independent cell signalling by N-acylethanolamines. Biochem. J. 2001, 360, 67–75.
  160. Duncan, R.S.; Chapman, K.D.; Koulen, P. The neuroprotective properties of palmitoylethanolamine against oxidative stress in a neuronal cell line. Mol. Neurodegener. 2009, 4, 50.
  161. Boots, A.W.; Van Berkel, J.J.B.N.; Dallinga, J.W.; Smolinska, A.; Wouters, E.F.; Van Schooten, F.J. The versatile use of exhaled volatile organic compounds in human health and disease. J. Breath Res. 2012, 6, 027108.
  162. Smolinska, A.; Klaassen, E.M.M.; Dallinga, J.W.; Van De Kant, K.D.G.; Jobsis, Q.; Moonen, E.J.C.; Van Schayck, O.C.P.; Dompeling, E.; Van Schooten, F.J. Profiling of Volatile Organic Compounds in Exhaled Breath As a Strategy to Find Early Predictive Signatures of Asthma in Children. PLoS ONE 2014, 9, e95668.
  163. Klaassen, E.M.M.; Van De Kant, K.D.G.; Jöbsis, Q.; Van Schayck, O.C.P.; Smolinska, A.; Dallinga, J.W.; Van Schooten, F.J.; Hartog, G.J.M.D.; De Jongste, J.C.; Rijkers, G.T.; et al. Exhaled Biomarkers and Gene Expression at Preschool Age Improve Asthma Prediction at 6 Years of Age. Am. J. Respir. Crit. Care Med. 2015, 191, 201–207.
  164. Dallinga, J.W.; Robroeks, C.M.H.H.T.; Van Berkel, J.J.B.N.; Moonen, E.J.C.; Godschalk, R.W.L.; Jöbsis, Q.; Dompeling, E.; Wouters, E.F.M.; Van Schooten, F.J. Volatile organic compounds in exhaled breath as a diagnostic tool for asthma in children. Clin. Exp. Allergy 2009, 40, 68–76.
  165. Caldeira, M.; Perestrelo, R.; Barros, A.; Bilelo, M.; Morête, A.; Câmara, J.; Rocha, S. Allergic asthma exhaled breath metabolome: A challenge for comprehensive two-dimensional gas chromatography. J. Chromatogr. A 2012, 1254, 87–97.
  166. Loureiro, C.C.; Duarte, I.F.; Gomes, J.; Carrola, J.; Barros, A.; Gil, A.M.; Bousquet, J.; Bom, A.T.; Rocha, S.M. Urinary metabolomic changes as a predictive biomarker of asthma exacerbation. J. Allergy Clin. Immunol. 2014, 133, 261.e5–263.e5.
  167. Paredi, P.; Kharitonov, S.A.; Barnes, P.J. Analysis of Expired Air for Oxidation Products. Am. J. Respir. Crit. Care Med. 2002, 166, S31–S37.
  168. Gahleitner, F.; Guallar-Hoyas, C.; Beardsmore, C.S.; Pandya, H.C.; Thomas, C.P. Metabolomics pilot study to identify volatile organic compound markers of childhood asthma in exhaled breath. Bioanalysis 2013, 5, 2239–2247.
  169. Chau-Etchepare, F.; Hoerger, J.L.; Kuhn, B.T.; Zeki, A.A.; Haczku, A.; Louie, S.; Kenyon, N.J.; Davis, C.E.; Schivo, M. Viruses and non-allergen environmental triggers in asthma. J. Investig. Med. 2019, 67, 1029–1041.
  170. NCBI. PubChem Compound Summary for 4-Isopropyl-1-Methylcyclohexane-1-Hydroperoxide; National Center for Biotechnology: Bethesda, MD, USA, 2020. Available online: (accessed on 15 March 2021).
  171. Elliott, L.; Longnecker, M.P.; Kissling, G.E.; London, S.J. Volatile Organic Compounds and Pulmonary Function in the Third NationalHealth and Nutrition Examination Survey, 1988–1994. Environ. Health Perspect. 2006, 114, 1210–1214.
  172. Guarneri, F.; Barbuzza, O.; Vaccaro, M.; Galtieri, G. Allergic contact dermatitis and asthma caused by limonene in a labourer handling citrus fruits. Contact Dermat. 2008, 58, 315–316.
  173. Rumchev, K.; Spickett, J.; Bulsara, M.; Phillips, M.; Stick, S. Association of domestic exposure to volatile organic compounds with asthma in young children. Thorax 2004, 59, 746–751.
  174. Arrieta, M.-C.; Stiemsma, L.T.; Dimitriu, P.A.; Thorson, L.; Russell, S.; Yurist-Doutsch, S.; Kuzeljevic, B.; Gold, M.J.; Britton, H.M.; Lefebvre, D.L.; et al. Early infancy microbial and metabolic alterations affect risk of childhood asthma. Sci. Transl. Med. 2015, 7, 307ra152.
  175. Joyce, S.A.; Gahan, C.G. Disease-Associated Changes in Bile Acid Profiles and Links to Altered Gut Microbiota. Dig. Dis. 2017, 35, 169–177.
  176. Menon, R.; Jones, J.; Gunst, P.R.; Kacerovsky, M.; Fortunato, S.J.; Saade, G.R.; Basraon, S. Amniotic Fluid Metabolomic Analysis in Spontaneous Preterm Birth. Reprod. Sci. 2014, 21, 791–803.
  177. Viaene, L.; Thijs, L.; Jin, Y.; Liu, Y.; Gu, Y.; Meijers, B.; Claes, K.; Staessen, J.A.; Evenepoel, P. Heritability and Clinical Determinants of Serum Indoxyl Sulfate and p-Cresyl Sulfate, Candidate Biomarkers of the Human Microbiome Enterotype. PLoS ONE 2014, 9, e79682.
  178. Nakada, E.M.; Bhakta, N.R.; Korwin-Mihavics, B.R.; Kumar, A.; Chamberlain, N.; Bruno, S.R.; Chapman, D.G.; Hoffman, S.M.; Daphtary, N.; Aliyeva, M.; et al. Conjugated bile acids attenuate allergen-induced airway inflammation and hyperresposiveness by inhibiting UPR transducers. JCI Insight 2019, 4.
  179. Shaik, F.B.; Panati, K.; Narasimha, V.R.; Narala, V.R. Chenodeoxycholic acid attenuates ovalbumin-induced airway inflammation in murine model of asthma by inhibiting the T H 2 cytokines. Biochem. Biophys. Res. Commun. 2015, 463, 600–605.
  180. Frati, F.; Salvatori, C.; Incorvaia, C.; Bellucci, A.; Di Cara, G.; Marcucci, F.; Esposito, S. The Role of the Microbiome in Asthma: The Gut–Lung Axis. Int. J. Mol. Sci. 2018, 20, 123.
  181. Abrahamsson, T.; Jakobsson, H.E.; Andersson, A.F.; Björkstén, B.; Engstrand, L.; Jenmalm, M.C. Low gut microbiota diversity in early infancy precedes asthma at school age. Clin. Exp. Allergy 2014, 44, 842–850.
  182. Martinez, F.D.; Guerra, S. Early Origins of Asthma. Role of Microbial Dysbiosis and Metabolic Dysfunction. Am. J. Respir. Crit. Care Med. 2018, 197, 573–579.
  183. Zhang, L.S.; Davies, S.S. Microbial metabolism of dietary components to bioactive metabolites: Opportunities for new therapeutic interventions. Genome Med. 2016, 8, 1–18.
  184. Juge, N.; Tailford, L.; Owen, C.D. Sialidases from gut bacteria: A mini-review. Biochem. Soc. Trans. 2016, 44, 166–175.
  185. Holmes, E.; Li, J.V.; Athanasiou, T.; Ashrafian, H.; Nicholson, J.K. Understanding the role of gut microbiome-host metabolic signal disruption in health and disease. Trends Microbiol. 2011, 19, 349–359.
  186. Kelly, R.S.; Sordillo, J.E.; Lasky-Su, J.; Dahlin, A.; Perng, W.; Rifas-Shiman, S.L.; Weiss, S.T.; Gold, D.R.; Litonjua, A.A.; Hivert, M.-F.; et al. Plasma metabolite profiles in children with current asthma. Clin. Exp. Allergy 2018, 48, 1297–1304.
  187. Kannisto, S.; Laatikainen, A.; Taivainen, A.; Savolainen, K.; Tukiainen, H.; Voutilainen, R. Serum dehydroepiandrosterone sulfate concentration as an indicator of adrenocortical suppression during inhaled steroid therapy in adult asthmatic patients. Eur. J. Endocrinol. 2004, 150, 687–690.
  188. Chawes, B.L.; Stokholm, J.; Bønnelykke, K.; Brix, S.; Bisgaard, H.F. Neonates with reduced neonatal lung function have systemic low-grade inflammation. J. Allergy Clin. Immunol. 2015, 135, 1450.e1–1456.e1.
  189. U.S. Department of Health and Human Services. Chapter 3: Chemistry and toxicology of cigarette smoke and biomarkers of exposure and harm. In How Tobacco Smoke Causes Disease: The Biology and Behavioral Basis for Smoking-Attributable Disease: A Report of the Surgeon; Office on Smoking and Health, National Center for Chronic Disease Prevention and Health Promotion, US Department of Health and Human Services Centers for Disease Control and Prevention: Atlanta, GA, USA, 2010; pp. 27–102. Available online: (accessed on 7 January 2021).
More
Video Production Service