Clinical Characteristics and Management Strategies for Adult Obese Asthma Patients

References

• Asthma data, statistics and surveillance; 2021. Available from: http://www.cdc.gov/asthma/most_recent_data/htm. Accessed January 9, 2022.
   Google Scholar
• AsthmaStats- asthma and obesity. Available from: https://www.cdc.gov/asthma/asthma_stats/percentage_people_asthma_obese.pdf. Accessed January 17, 2022.
   Google Scholar
• Mohan A, Grace J, Wang BR, Lugogo N. The effects of obesity in asthma. Curr Allergy Asthma Rep. 2019;19(49). doi:10.1007/s11882-019-0877-z
   PubMed Web of Science ®Google Scholar
• Miethe S, Katsonova K, Karaulov A, Renz H. Obesity and asthma. J Allergy Clin Immunol. 2020;146:685–693. doi:10.1016/j.jaci.2020.08.011
   PubMed Web of Science ®Google Scholar
• Peters U, Dixon AE, Forno E. Obesity and asthma. J Allergy Clin Immunol. 2018;141:1169–1179. doi:10.1016/j.jaci.2018.02.004
   PubMed Web of Science ®Google Scholar
• Garcia-Rio F, Alvarez-Puebla MJ, Esteba-Gorgojo I. Barranco P and olaguibel jm. obesity and asthma: key clinical questions. J Allergy Clin Immunol. 2019;29(4):262–271.
   Google Scholar
• Beuther DA, Sutherland ER. Overweight, obesity and incident asthma: a meta-analysis of prospective epidemiologic studies. Am J Respir Crit Care Med. 2007;175:661–666. doi:10.1164/rccm.200611-1717OC
   PubMed Web of Science ®Google Scholar
• Wenzel SE. Asthma phenotypes: the evolution from clinical to molecular to clinical approaches. Nat Med. 2012;18:716–725. doi:10.1038/nm.2678
   PubMed Web of Science ®Google Scholar
• Dixon AE, Poynter ME. Mechanisms of asthma in obesity. Pleiotropic aspects of obesity produce distinct asthma phenotypes. Am J Respir Cell Mol Biol. 2016;54:601–608. doi:10.1165/rcmb.2016-0017PS
   PubMed Web of Science ®Google Scholar
• Scott HA, Wood LG, Gibson PG. Role of obesity in asthma: mechanisms and management strategies. Curr Allergy Asthma Rep. 2017;17(53). doi:10.1007/s11882-017-0719-9
   PubMed Web of Science ®Google Scholar
• Khalid F, Holguin F. A review of obesity and asthma across the life span. J Asthma. 2018;55(12):1286–1300. doi:10.1080/02770903.2018.1424187
   PubMed Web of Science ®Google Scholar
• Haldar P, Pavord ID, Shaw DE, et al. Cluster analysis and clinical asthma phenotypes. Am J Respir Crit Care Med. 2008;178(3):218–224. doi:10.1164/rccm.200711-1754OC
   PubMed Web of Science ®Google Scholar
• Moore WC, Meyers DA, Wenzel SE, et al. Identification of asthma phenotypes using cluster analysis in the severe asthma research program. Am J Respir Crit Care Med. 2010;181(4):315–323. doi:10.1164/rccm.200906-0896OC
   PubMed Web of Science ®Google Scholar
• Holguin F, Bleecker ER, Busse WW, et al. Obesity and asthma, an association modified by age of asthma onset. J Allergy Clin Immunol. 2011;127(6):1486–1493. doi:10.1016/j.jaci.2011.03.036
   PubMed Web of Science ®Google Scholar
• Scott HA, Gibson PG, Garg ML, Wood LG. Airway inflammation is augmented by obesity and fatty acids in asthma. Eur Respir J. 2011;38(3):594–602. doi:10.1183/09031936.00139810
   PubMed Web of Science ®Google Scholar
• Sutherland TJ, Cowan JO, Young S, et al. The association between obesity and asthma: interactions between systemic and airway inflammation. Am J Respir Crit Care Med. 2008;178(5):469–475. doi:10.1164/rccm.200802-301OC
   PubMed Web of Science ®Google Scholar
• Sutherland ER, Goleva E, King TS, et al. Cluster analysis of obesity and asthma phenotypes. PLoS One. 2012;7(5):e36631. doi:10.1371/journal.pone.0036631
   PubMed Web of Science ®Google Scholar
• Jones RL, Nzekwu -M-MU. The effects of body mass index on lung volumes. Chest. 2006;130:827–833. doi:10.1378/chest.130.3.827
   PubMed Web of Science ®Google Scholar
• Biring MS, Lewis MI, Liu JT, Mohsenifar Z. Pulmonary physiologic changes of morbid obesity. Am J Med Sci. 1999;318:293–297. doi:10.1016/S0002-9629(15)40641-X
   PubMed Web of Science ®Google Scholar
• Ding DJ, Martin JG, Macklem PT. Effects of lung volume on maximal methacholine-induced bronchoconstriction in normal humans. J Appl Physiol. 1987;62:1324–1330. doi:10.1152/jappl.1987.62.3.1324
   PubMed Web of Science ®Google Scholar
• Sin DD, Sutherland ER. Obesity and the lung: 4. Obesity and asthma. Thorax. 2008;63:1018–1023. doi:10.1136/thx.2007.086819
   PubMed Web of Science ®Google Scholar
• Sideleva O, Suratt BT, Black KE, et al. Obesity and asthma: an inflammatory disease of adipose tissue not the airway. Am J Respir Crit Care Med. 2012;186:598–605. doi:10.1164/rccm.201203-0573OC
   PubMed Web of Science ®Google Scholar
• Peters U, Hernandez P, Dechman G, Ellsmere J, Maksym G. Early detection of changes in lung mechanics with oscillometry following bariatric surgery in severe obesity. Appl Physiol Nutr Metab. 2016;41(5):538–547. PMID: 27109263. doi:10.1139/apnm-2015-0473
   PubMed Web of Science ®Google Scholar
• Bates JH, Dixon AE. Potential role of the airway wall in the asthma of obesity. J Appl Physiol. 2015;118:36–41. doi:10.1152/japplphysiol.00684.2014
   PubMed Web of Science ®Google Scholar
• Yalcin HC, Perry SF, Ghadiali SN. Influence of airway diameter and cell confluence on epithelial cell injury in an in vitro model of airway reopening. J Appl Physiol. 2007;103:1796–1807. doi:10.1152/japplphysiol.00164.2007
   PubMed Web of Science ®Google Scholar
• Brazzale DJ, Pretto JJ, Schachter LM. Optimizing respiratory function assessments to elucidate the impact of obesity on respiratory health. Respirology. 2015;20:715–721. doi:10.1111/resp.12563
   PubMed Web of Science ®Google Scholar
• Acosta JR, Douagi I, Andersson DP, et al. Increased fat cell size: a major phenotype of subcutaneous white adipose tissue in non-obese individuals with type 2 diabetes. Diabetologia. 2016;59:560–570. doi:10.1007/s00125-015-3810-6
   PubMed Web of Science ®Google Scholar
• Dixon AE, Pratley RE, Forgione PM, et al. Effects of obesity and bariatric surgery on airway hyperresponsiveness, asthma control, and inflammation. J Allergy Clin Immunol. 2011;128:508–515.e1,2. doi:10.1016/j.jaci.2011.06.009
   PubMed Web of Science ®Google Scholar
• McLaughlin T, Liu LF, Lamendola C, et al. T-cell profile in adipose tissue is associated with insulin resistance and systemic inflammation in humans. Arterioscler Thromb Vasc Biol. 2014;34:2632–2636. doi:10.1161/ATVBAHA.114.304636
   PubMed Web of Science ®Google Scholar
• Desai D, Newby C, Symon FA, et al. Elevated sputum interleukin-5 and submucosal eosinophilia in obese individuals with severe asthma. Am J Respir Crit Care Med. 2013;188:657–663. doi:10.1164/rccm.201208-1470OC
   PubMed Web of Science ®Google Scholar
• van der Wiel E, Ten Hacken NH, van den Berge M, Timens W, Reddel HK, Postma DS. Eosinophilic inflammation in subjects with mild-to-moderate asthma with and without obesity: disparity between sputum and biopsies. Am J Respir Crit Care Med. 2014;189:1281–1284. doi:10.1164/rccm.201310-1841LE
   PubMed Web of Science ®Google Scholar
• van Veen IH, Ten Brinke A, Sterk PJ, Rabe KF, Bel EH. Airway inflammation in obese and nonobese patients with difficult-to-treat asthma. Allergy. 2008;63:570–574. doi:10.1111/j.1398-9995.2007.01597.x
   PubMed Web of Science ®Google Scholar
• Lessard A, Turcotte H, Cormier Y, Boulet LP. Obesity and asthma: a specific phenotype? Chest. 2008;134:317–323. doi:10.1378/chest.07-2959
   PubMed Web of Science ®Google Scholar
• Marijsse GS, Seys SF, Schelpe AS, et al. Obese individuals with asthma preferentially have a high IL-5/IL-17A/IL-25 sputum inflammatory pattern. Am J Respir Crit Care Med. 2014;189:1284–1285. doi:10.1164/rccm.201311-2011LE
   PubMed Web of Science ®Google Scholar
• Ge XN, Greenberg Y, Hosseinkhani MR, et al. High-fat diet promotes lung fibrosis and attenuates airway eosinophilia after exposure to cockroach allergen in mice. Exp Lung Res. 2013;39:365–378. doi:10.3109/01902148.2013.829537
   PubMed Web of Science ®Google Scholar
• Calixto MC, Lintomen L, Schenka A, Saad MJ, Zanesco A, Antunes E. Obesity enhances eosinophilic inflammation in a murine model of allergic asthma. Br J Pharmacol. 2010;159:617–625. doi:10.1111/j.1476-5381.2009.00560.x
   PubMed Web of Science ®Google Scholar
• Lintomen L, Calixto MC, Schenka A, Antunes E. Allergen-induced bone marrow eosinophilopoiesis and airways eosinophilic inflammation in leptin-deficient ob/ob mice. Obesity. 2012;20:1959–1965. doi:10.1038/oby.2012.93
   PubMed Web of Science ®Google Scholar
• Shore SA, Schwartzman IN, Mellema MS, Flynt L, Imrich A, Johnston RA. Effect of leptin on allergic airway responses in mice. J Allergy Clin Immunol. 2005;115:103–109. doi:10.1016/j.jaci.2004.10.007
   PubMed Web of Science ®Google Scholar
• Jeong KY, Lee J, Li C. Juvenile obesity aggravates disease severity in a rat model of atopic dermatitis. Allergy Asthma Immunol Res. 2015;7:69–75. doi:10.4168/aair.2015.7.1.69
   PubMed Web of Science ®Google Scholar
• Zheng H, Zhang X, Castillo EF, Luo Y, Liu M, Yang XO. Leptin enhances TH2 and ILC2 responses in allergic airway disease. J Biol Chem. 2016;291(42):22043–22052. PMID: 27566543; PMCID: PMC5063987. doi:10.1074/jbc.M116.743187
   PubMed Web of Science ®Google Scholar
• Hasenkrug KJ. The leptin connection: regulatory T cells and autoimmunity. Immunity. 2007;26(2):143–145. doi:10.1016/j.immuni.2007.02.002
   PubMed Web of Science ®Google Scholar
• Masaki T, Chiba S, Tatsukawa H, et al. Adiponectin protects LPS-induced liver injury through modulation of TNF-alpha in KK-Ay obese mice. Hepatology. 2004;40:177–184. doi:10.1002/hep.20282
   PubMed Web of Science ®Google Scholar
• Kumada M, Kihara S, Ouchi N, et al. Adiponectin specifically increased tissue inhibitor of metalloproteinase-1 through interleukin-10 expression in human macrophages. Circulation. 2004;109:2046–2049. doi:10.1161/01.CIR.0000127953.98131.ED
   PubMed Web of Science ®Google Scholar
• Shore SA, Terry RD, Flynt L, Xu A, Hug C. Adiponectin attenuates allergen-induced airway inflammation and hyperresponsiveness in mice. J Allergy Clin Immunol. 2006;118:389–395. doi:10.1016/j.jaci.2006.04.021
   PubMed Web of Science ®Google Scholar
• Kanneganti TD, Dixit VD. Immunological complications of obesity. Nat Immunol. 2012;13:707–712. doi:10.1038/ni.2343
   PubMed Web of Science ®Google Scholar
• Fantuzzi G. Adipose tissue, adipokines, and inflammation. J Allergy Clin Immunol. 2005;115:911–919. doi:10.1016/j.jaci.2005.02.023
   PubMed Web of Science ®Google Scholar
• Sharma N, Akkoyunlu M, Rabin RL. Macrophages-common culprit in obesity and asthma. Allergy. 2018;73(6):1196–1205. PMID: 29178573. doi:10.1111/all.13369
   PubMed Web of Science ®Google Scholar
• Periyalil HA, Wood LG, Scott HA, Jensen ME, Gibson PG. Macrophage activation, age and sex effects of immunometabolism in obese asthma. Eur Respir J. 2014;45:388–395. doi:10.1183/09031936.00080514
   PubMed Web of Science ®Google Scholar
• Fernandez-Boyanapalli R, Goleva E, Kolakowski C, et al. Obesity impairs apoptotic cell clearance in asthma. J Allergy Clin Immunol. 2013;131:1041–1047. doi:10.1016/j.jaci.2012.09.028
   PubMed Web of Science ®Google Scholar
• Kim HY, Lee HJ, Chang YJ, et al. Interleukin-17-producing innate lymphoid cells and the NLRP3 inflammasome facilitate obesity-associated airway hyperreactivity. Nat Med. 2014;20:54–61. doi:10.1038/nm.3423
   PubMed Web of Science ®Google Scholar
• Sumarac-Dumanovic M, Stevanovic D, Ljubic A, et al. Increased activity of interleukin-23/interleukin-17 proinflammatory axis in obese women. Intl J Obesity. 2009;33:151–156. doi:10.1038/ijo.2008.216
   PubMed Web of Science ®Google Scholar
• Telenga ED, Tideman SW, Kerstjens HAM, et al. Obesity in asthma: more neutrophilic inflammation as a possible explanation for a reduced treatment response. Allergy. 2012;67(8):1060–1068. doi:10.1111/j.1398-9995.2012.02855.x
   PubMed Web of Science ®Google Scholar
• Chen J-H, Qin L, Shi -Y-Y, et al. IL- 17 protein levels in both induced sputum and plasma are increased in stable but not acute asthma individuals with obesity. Respir med. 2016;121:48–58. doi:10.1016/j.rmed.2016.10.018
   PubMed Web of Science ®Google Scholar
• Umetsu DT. Mechanisms by which obesity impacts upon asthma. Thorax. 2017;72(2):174–177. PMID: 27672120. doi:10.1136/thoraxjnl-2016-209130
   PubMed Web of Science ®Google Scholar
• Halwani R, Sultana A, Vazquez-Tello A, Jamhawi A, Al-Masri AA, Al-Muhsen S. Th-17 regulatory cytokines IL-21, IL-23, and IL-6 enhance neutrophil production of IL-17 cytokines during asthma. J Asthma. 2017;54:893–904. doi:10.1080/02770903.2017.1283696
   PubMed Web of Science ®Google Scholar
• Chen Y, Tian J, Tian X, et al. Adipose tissue dendritic cells enhances inflammation by prompting the generation of Th17 cells. PLoS One. 2014;9(3):e92450. PMID: 24642966; PMCID: PMC3958510. doi:10.1371/journal.pone.0092450
   PubMed Web of Science ®Google Scholar
• Bullens DMA, Truyen E, Coteur L, et al. IL-17 mRNA in sputum of asthmatic patients: linking T cell driven inflammation and granulocytic influx? Respir Res. 2006;7:135. doi:10.1186/1465-9921-7-135
   PubMed Web of Science ®Google Scholar
• Farahi N, Paige E, Balla J, et al. Neutrophil-mediated IL-6 receptor trans-signaling and the risk of chronic obstructive pulmonary disease and asthma. Hum Mol Genet. 2017;26:1584–1596. doi:10.1093/hmg/ddx053
   PubMed Web of Science ®Google Scholar
• Peters MC, McGrath KW, Hawkins GA; National Heart, Lung, and Blood Institute Severe Asthma Research Program. Plasma interleukin-6 concentrations, metabolic dysfunction, and asthma severity: a cross-sectional analysis of two cohorts. Lancet Respir Med. 2016:574–584. PMID: 27283230; PMCID: PMC5007068. doi:10.1016/S2213-2600(16)30048-0
   PubMed Web of Science ®Google Scholar
• Lin YL, Chen SH, Wang JY. Critical role of IL-6 in dendritic cell-induced allergic inflammation of asthma. J Mol Med (Berl). 2016;94(1):51–59. PMID: 26232935. doi:10.1007/s00109-015-1325-8
   PubMed Web of Science ®Google Scholar
• Jevnikar Z, Östling J, Ax E, et al. Epithelial IL-6 trans-signaling defines a new asthma phenotype with increased airway inflammation. J Allergy Clin Immunol. 2019;143:577–590. doi:10.1016/j.jaci.2018.05.026
   PubMed Web of Science ®Google Scholar
• Berry MA, Hargadon B, Shelley M, et al. Evidence of a role of tumor necrosis factor α in refractory asthma. N Engl J Med. 2006;354:697–708. doi:10.1056/NEJMoa050580
   PubMed Web of Science ®Google Scholar
• Manni ML, Trudeau JB, Scheller EV, et al. The complex relationship between inflammation and lung function in severe asthma. Mucosal Immunol. 2014;7:1186–1198. doi:10.1038/mi.2014.8
   PubMed Web of Science ®Google Scholar
• Kips JC, Tavernier J, Pauwels RA. Tumor necrosis factor causes bronchial hyperresponsiveness in rats. Am Rev Respir Dis. 1992;145(2 Pt 1):332–336. PMID: 1736737. doi:10.1164/ajrccm/145.2_Pt_1.332
   PubMed Web of Science ®Google Scholar
• Cai Y, Cao YX, Lu SM, Xu CB, Cardell LO. Infliximab alleviates inflammation and ex vivo airway hyperreactivity in asthmatic E3 rats. Int Immunol. 2011;23(7):443–451. PMID: 21677048. doi:10.1093/intimm/dxr032
   PubMed Web of Science ®Google Scholar
• Kim JY, Sohn JH, Lee JH, Park JW. Obesity increases airway hyperresponsiveness via the TNF-a pathway and treating obesity induces recovery. PLoS One. 2015;10:e0116540. doi:10.1371/journal.pone.0116540
   PubMed Web of Science ®Google Scholar
• Hurrell BP, Galle-Treger L, Jahani PS, et al. TNFR2 signaling enhances ILC2 survival, function, and induction of airway hyperreactivity. Cell Rep. 2019;29(13):4509–4524.e5. PMID: 31875557; PMCID: PMC6940205. doi:10.1016/j.celrep.2019.11.102
   PubMed Web of Science ®Google Scholar
• Lugogo N, Francisco D, Addison KJ, et al. Obese asthmatic patients have decreased surfactant protein A levels: mechanisms and implications. J Allergy Clin Immunol. 2018;141(3):918–926.e3. PMID: 28624607; PMCID: PMC5732097. doi:10.1016/j.jaci.2017.05.028
   PubMed Web of Science ®Google Scholar
• Gilmour JS, Coutinho AE, Cailhier JF, et al. Local amplification of glucocorticoids by 11 beta-hydroxysteroid dehydrogenase type 1 promotes macrophage phagocytosis of apoptotic leukocytes. J Immunol. 2006;176:7605–7611. doi:10.4049/jimmunol.176.12.7605
   PubMed Web of Science ®Google Scholar
• Freire-de-lima CG, Xiao YQ, Gardai SJ, Bratton DL, Schiemann WP, Henson PM. Apoptotic cells, through transforming growth factor-beta, coordinately induce anti-inflammatory and suppress pro-inflammatory eicosanoid and NO synthesis in murine macrophages. J Biol Chem. 2006;281:38376–38384. doi:10.1074/jbc.M605146200
   PubMed Web of Science ®Google Scholar
• Grace J, Mohan A, Lugogo NL. Obesity and adult asthma: diagnostic and management challenges. Curr Opin Pulm Med. 2019;25(1):44–50. PMID: 30394901. doi:10.1097/MCP.0000000000000531
   PubMed Web of Science ®Google Scholar
• Mathews JA, Krishnamoorthy N, Kasahara DI, et al. IL-33 drives augmented responses to ozone in obese mice. Environ Health Perspect. 2017;125(2):246–253. doi:10.1289/EHP272
   PubMed Web of Science ®Google Scholar
• Bhatraju NK, Agrawal A. Mitochondrial dysfunction linking obesity and asthma. Ann Am Thorac Soc. 2017;14(Supplement_5):S368–S373. PMID: 29161084. doi:10.1513/AnnalsATS.201701-042AW
   PubMed Web of Science ®Google Scholar
• Cheng Z, Almeida FA. Mitochondrial alteration in type 2 diabetes and obesity: an epigenetic link. Cell Cycle. 2014;13:890–897. doi:10.4161/cc.28189
   PubMed Web of Science ®Google Scholar
• Koves TR, Ussher JR, Noland RC, et al. Mitochondrial overload and incomplete fatty acid oxidation contribute to skeletal muscle insulin resistance. Cell Metab. 2008;7:45–56. doi:10.1016/j.cmet.2007.10.013
   PubMed Web of Science ®Google Scholar
• Stuhlinger MC, Stanger O. Asymmetric dimethyl-L-arginine (ADMA): a possible link between homocyst(e)ine and endothelial dysfunction. Curr Drug Metab. 2005;6:3–14. doi:10.2174/1389200052997393
   PubMed Web of Science ®Google Scholar
• Bayarri MA, Milara J, Estornut C, Cortijo J. Nitric oxide system and bronchial epithelium: more than a barrier. Front Physiol. 2021;12:687381. PMID: 34276407; PMCID: PMC8279772. doi:10.3389/fphys.2021.687381
   PubMed Web of Science ®Google Scholar
• Holguin F, Comhair SAA, Hazen SL, et al. An association between L-arginine/asymmetric dimethyl arginine balance, obesity, and the age of asthma onset phenotype. Am J Respir Crit Care Med. 2013;187:153–159. doi:10.1164/rccm.201207-1270OC
   PubMed Web of Science ®Google Scholar
• Grasemann H, Holguin F. Oxidative stress and obesity-related asthma. Paediatr Respir Rev. 2021;37:18–21. PMID: 32660723. doi:10.1016/j.prrv.2020.05.004
   PubMed Web of Science ®Google Scholar
• Konra´ Dova´ V, Copova´ C, Sukova´ B, Houstĕk J. Ultrastructure of the bronchial epithelium in three children with asthma. Pediatr Pulmonol. 1985;1:182–187. doi:10.1002/ppul.1950010403
   PubMedGoogle Scholar
• Mabalirajan U, Dinda AK, Kumar S, et al. Mitochondrial structural changes and dysfunction are associated with experimental allergic asthma. J Immunol. 2008;181:3540–3548. doi:10.4049/jimmunol.181.5.3540
   PubMed Web of Science ®Google Scholar
• Aguilera-Aguirre L, Bacsi A, Saavedra-Molina A, Kurosky A, Sur S, Boldogh I. Mitochondrial dysfunction increases allergic airway inflammation. J Immunol. 2009;183:5379–5387. doi:10.4049/jimmunol.0900228
   PubMed Web of Science ®Google Scholar
• Ahmad T, Kumar M, Mabalirajan U, et al. Hypoxia response in asthma: differential modulation on inflammation and epithelial injury. Am J Respir Cell Mol Biol. 2012;47:1–10. doi:10.1165/rcmb.2011-0203OC
   PubMed Web of Science ®Google Scholar
• Winnica D, Corey C, Mullett S, et al. Bioenergetic differences in the airway epithelium of lean versus obese asthmatics are driven by nitric oxide and reflected in circulating platelets. Antioxid Redox Signal. 2019;31(10):673–686. doi:10.1089/ars.2018.7627
   PubMed Web of Science ®Google Scholar
• Komakula S, Khatri S, Mermis J, et al. Body mass index is associated with reduced exhaled nitric oxide and higher exhaled 8-isoprostanes in asthmatics. Respir Res. 2007;16(8):32. doi:10.1186/1465-9921-8-32
   Web of Science ®Google Scholar
• Aldakheel FM, Thomas PS, Bourke JE, Matheson MC, Dharmage SC, Lowe AJ. Relationships between adult asthma and oxidative stress markers and pH in exhaled breath condensate: a systematic review. Allergy. 2016;71(6):741–757. doi:10.1111/all.12865
   PubMed Web of Science ®Google Scholar
• Mabalirajan U, Rehman R, Ahmad T, et al. Linoleic acid metabolite drives severe asthma by causing airway epithelial injury. Sci Rep. 2013;3(1). doi:10.1038/srep01349
   Web of Science ®Google Scholar
• Holguin F, Khatri S, Serpil E, Powers RW, Trudeau J, Wenzel SE. Reduced L-arginine/ADMA as a potential mechanism to explain increased symptom severity and reduced atopy in late onset obese asthmatics. Am J Respit Crit Care Med. 2012;185:A2197.
   Google Scholar
• Brown SD, Baxter KM, Stephenson ST, Esper AM, Brown LA, Fitzpatrick AM. Airway TGF-β1 and oxidant stress in children with severe asthma: association with airflow limitation. J Allergy Clin Immunol. 2012;129(2):388–96, 396.e1–8. PMID: 22206775; PMCID: PMC3268912. doi:10.1016/j.jaci.2011.11.037
   Web of Science ®Google Scholar
• Holguin F. Arginine and nitric oxide pathways in obesity-associated asthma. J Allergy (Cairo). 2013;2013:714595. PMID: 23710196; PMCID: PMC3654368. doi:10.1155/2013/714595
   PubMedGoogle Scholar
• Wu W, Bang S, Bleecker ER, et al. Multiview cluster analysis identifies variable corticosteroid response phenotypes in severe asthma. Am J Respir Crit Care Med. 2019;199(11):1358–1367. doi:10.1164/rccm.201808-1543OC
   PubMed Web of Science ®Google Scholar
• Barnes PJ, Adcock IM. Glucocorticoid resistance in inflammatory diseases. Lancet. 2009;373(9678):1905–1917. doi:10.1016/S0140-6736(09)60326-3
   PubMed Web of Science ®Google Scholar
• Lu KD, Breysse PN, Diette GB, et al. Being overweight increases susceptibility to indoor pollutants among urban children with asthma. J Allergy Clin Immunol. 2013;131:1017–1023, 1023.e1–1023.e3. doi:10.1016/j.jaci.2012.12.1570
   Web of Science ®Google Scholar
• Alexeeff SE, Litonjua AA, Suh H, Sparrow D, Vokonas PS, Schwartz J. Ozone exposure and lung function: effect modified by obesity and airways hyperresponsiveness in the VA normative aging study. Chest. 2007;132:1890–1897. doi:10.1378/chest.07-1126
   PubMed Web of Science ®Google Scholar
• Arrieta MC, Finlay B. The intestinal microbiota and allergic asthma. J Infect. 2014;69(Suppl 1):S53e5. doi:10.1016/j.jinf.2014.07.015
   Web of Science ®Google Scholar
• Ygenetiuan Y, Ran N, Xiong L, et al. Obesity-related asthma: immune regulation and potential targeted therapies. J Immunol Res. 2018;2018:1943497. PMID: 30050954; PMCID: PMC6046139. doi:10.1155/2018/1943497
   PubMed Web of Science ®Google Scholar
• Ley RE. Obesity and the human microbiome. Curr Opin Gastroenterol. 2010;26:5–11. doi:10.1097/MOG.0b013e328333d751
   PubMed Web of Science ®Google Scholar
• Tavares da Silva S, Araújo Dos Santos C, Bressan J. Intestinal microbiota; relevance to obesity and modulation by prebiotics and probiotics. Nutricion Hospitalaria. 2013;28(4):1039–1048. doi:10.3305/nh.2013.28.4.6525
   PubMed Web of Science ®Google Scholar
• Ley RE, Turnbaugh PJ, Klein S, Gordon JI. Microbial ecology: human gut microbes associated with obesity. Nature. 2006;444:1022–1023. doi:10.1038/4441022a
   PubMed Web of Science ®Google Scholar
• Catrysse L, van Loo G. Inflammation and the metabolic syndrome: the tissue-specific functions of NF-κB. Trends Cell Biol. 2017;27(6):417–429. doi:10.1016/j.tcb.2017.01.006
   PubMed Web of Science ®Google Scholar
• Cani PD, Bibiloni R, Knauf C, et al. Changes in gut microbiota control metabolic endotoxemia-induced inflammation in high-fat diet-induced obesity and diabetes in mice. Diabetes. 2008;57(6):1470–1481. PMID: 18305141. doi:10.2337/db07-1403
   PubMed Web of Science ®Google Scholar
• Tremaroli V, Backhed F. Functional interactions between the gut microbiota and host metabolism. Nature. 2012;489:242–249. doi:10.1038/nature11552
   PubMed Web of Science ®Google Scholar
• Trompette A, Gollwitzer ES, Yadava K, et al. Gut microbiota metabolism of dietary fiber influences allergic airway disease and hematopoiesis. Nat Med. 2014;20:159–166. doi:10.1038/nm.3444
   PubMed Web of Science ®Google Scholar
• Cho Y, Shore SA. Obesity, asthma, and the microbiome. Physiology. 2016;31(2):108–116. PMID: 26889016; PMCID: PMC4888975. doi:10.1152/physiol.00045.2015
   PubMed Web of Science ®Google Scholar
• Smith PM, Howitt MR, Panikov N, et al. The microbial metabolites, short-chain fatty acids, regulate colonic Treg cell homeostasis. Science. 2013;341(6145):569–573. PMID: 23828891; PMCID: PMC3807819. doi:10.1126/science.1241165
   PubMed Web of Science ®Google Scholar
• Vinolo MA, Rodrigues HG, Hatanaka E, Sato FT, Sampaio SC, Curi R. Suppressive effect of short-chain fatty acids on production of proinflammatory mediators by neutrophils. J Nutr Biochem. 2011;22(9):849–855. doi:10.1016/j.jnutbio.2010.07.009
   PubMed Web of Science ®Google Scholar
• Manni ML, Heinrich VA, Buchan GJ, et al. Nitroalkene fatty acids modulate bile acid metabolism and lung function in obese asthma. Sci Rep. 2021;11(1):17788. PMID: 34493738; PMCID: PMC8423735. doi:10.1038/s41598-021-96471-9
   PubMed Web of Science ®Google Scholar
• Miyamoto M, Prause O, Sjostrand M, Laan M, Lotvall J, Linden A. Endogenous IL-17 as a mediator of neutrophil recruitment caused by endotoxin exposure in mouse airways. J Immunol. 2003;170:4665–4672. doi:10.4049/jimmunol.170.9.4665
   PubMed Web of Science ®Google Scholar
• Michalovich D, Rodriguez-Perez N, Smolinska S, et al. Obesity and disease severity magnify disturbed microbiome-immune interactions in asthma patients. Nat Commun;2019. 1–14. doi:10.1038/s41467-018-07882-8
   PubMed Web of Science ®Google Scholar
• Huang YJ, Nariya S, Harris JM, et al. The airway microbiome in patients with severe asthma: associations with disease features and severity. J Allergy Clin Immunol. 2015;136:874e84. doi:10.1016/j.jaci.2015.05.044
   Web of Science ®Google Scholar
• Wood LG, Garg ML, Gibson PG. A high-fat challenge increases airway inflammation and impairs bronchodilator recovery in asthma. J Allergy Clin Immunol. 2011;127:1133–1140. doi:10.1016/j.jaci.2011.01.036
   PubMed Web of Science ®Google Scholar
• Soutar A, Seaton A, Brown K. Bronchial reactivity and dietary antioxidants. Thorax. 1997;52:166–170. doi:10.1136/thx.52.2.166
   PubMed Web of Science ®Google Scholar
• Kien CL, Bunn JY, Fukagawa NK, et al. Lipidomic evidence that lowering the typical dietary palmitate to oleate ratio in humans decreases the leukocyte production of proinflammatory cytokines and muscle expression of redox-sensitive genes. J Nutr Biochem. 2015;26:1599–1606. doi:10.1016/j.jnutbio.2015.07.014
   PubMed Web of Science ®Google Scholar
• Singh VP, Aggarwal R, Singh S, et al. Metabolic syndrome is associated with increased oxo-nitrative stress and asthma-like changes in lungs. PLoS One. 2015;10:e0129850. doi:10.1371/journal.pone.0129850
   PubMed Web of Science ®Google Scholar
• Tashiro H, Shore SA. Obesity and severe asthma. Allergol Int. 2019;68(2):135–142. PMID: 30509734; PMCID: PMC6540088. doi:10.1016/j.alit.2018.10.004
   PubMed Web of Science ®Google Scholar
• Wood LG, Li Q, Scott HA, et al. Saturated fatty acids, obesity, and the nucleotide oligomerization domain-like receptor protein 3 (NLRP3) inflammasome in asthmatic patients. J Allergy Clin Immunol. 2019;143:305e15. doi:10.1016/j.jaci.2018.04.037
   Web of Science ®Google Scholar
• Wood LG, Garg ML, Smart JM, Scott HA, Barker D, Gibson P. Manipulating antioxidant intake in asthma: a randomized controlled trial. Am J Clin Nutr. 2012;96:534–543. doi:10.3945/ajcn.111.032623
   PubMed Web of Science ®Google Scholar
• Wood LG, Garg ML, Powell H, Gibson PG. Lycopene-rich treatments modify noneosinophilic airway inflammation in asthma: proof of concept. Free Radic res. 2008;42:94–102. doi:10.1080/10715760701767307
   PubMed Web of Science ®Google Scholar
• Pereira-Santos M, Costa PR, Assis AM, Santos CA, Santos DB. Obesity and vitamin D deficiency: a systematic review and meta-analysis. Obes Rev. 2015;16:341e9. doi:10.1111/obr.12239
   Web of Science ®Google Scholar
• Martineau AR, MacLaughlin BD, Hooper RL, et al. Double-blind randomised placebo-controlled trial of bolus-dose vitamin D3 supplementation in adults with asthma (ViDiAs). Thorax. 2015;70:451e7.
   Web of Science ®Google Scholar
• Aydin M, Koca C, Ozol D, et al. Interaction of metabolic syndrome with asthma in postmenopausal women: role of adipokines. Inflammation. 2013;36:1232–1238. doi:10.1007/s10753-013-9660-9
   PubMed Web of Science ®Google Scholar
• van Huisstede A, Cabezas MC, Birnie E, et al. Systemic inflammation and lung function impairment in morbidly obese subjects with the metabolic syndrome. J Obes. 2013;2013:131349. PMID: 23509614; PMCID: PMC3595660. doi:10.1155/2013/131349
   PubMedGoogle Scholar
• Forno E, Han -Y-Y, Muzumdar RH, Celedón JC. Insulin resistance, metabolic syndrome, and lung function in US adolescents with and without asthma. J Allergy Clin Immunol. 2015;136(2):304–311.e8. doi:10.1016/j.jaci.2015.01.010
   PubMed Web of Science ®Google Scholar
• Forno E, Zhang P, Nouraie M, et al. The impact of bariatric surgery on asthma control differs among obese individuals with reported prior or current asthma, with or without metabolic syndrome. PLoS One. 2019;14(4):e0214730. doi:10.1371/journal.pone.0214730
   PubMed Web of Science ®Google Scholar
• Nie Z, Jacoby DB, Fryer AD. Hyperinsulinemia potentiates airway responsiveness to parasympathetic nerve stimulation in obese rats. Am J Respir Cell Mol Biol. 2014;51:251–261. doi:10.1165/rcmb.2013-0452OC
   PubMed Web of Science ®Google Scholar
• Leiria LO, Arantes-Costa FM, Calixto MC, et al. Increased airway reactivity and hyperinsulinemia in obese mice are linked by ERK signaling in brain stem cholinergic neurons. Cell Rep. 2015;11:934–943. doi:10.1016/j.celrep.2015.04.012
   PubMed Web of Science ®Google Scholar
• Thomsen SF, Ulrik CS, Kyvik KO, et al. Association between obesity and asthma in a twin cohort. Allergy. 2007;62(10):1199–1204. PMID: 17845591. doi:10.1111/j.1398-9995.2007.01480.x
   PubMed Web of Science ®Google Scholar
• Murphy A, Tantisira KG, Soto-Quirós ME, et al. PRKCA: a positional candidate gene for body mass index and asthma. Am J Hum Genet. 2009;85(1):87–96. PMID: 19576566; PMCID: PMC2706964. doi:10.1016/j.ajhg.2009.06.011
   PubMed Web of Science ®Google Scholar
• Castro-Giner F, Kogevinas M, Imboden M, et al. Joint effect of obesity and TNFA variability on asthma: two international cohort studies. Eur Respir J. 2009;33:1003–1009. PMID: 19196817. doi:10.1183/09031936.00140608
   PubMed Web of Science ®Google Scholar
• González JR, Cáceres A, Esko T, et al. A common 16p11.2 inversion underlies the joint susceptibility to asthma and obesity. Am J Hum Genet. 2014;94(3):361–372. PMID: 24560518; PMCID: PMC3951940. doi:10.1016/j.ajhg.2014.01.015
   PubMed Web of Science ®Google Scholar
• Cloutier MM, Baptist AP, Blake KV; Expert Panel Working Group of the National Heart L, Blood Institute a, coordinated National Asthma E. Focused updates to the asthma management guidelines: a report from the national asthma education and prevention program coordinating committee expert panel working group. J Allergy Clin Immunol. 2020;146(6):1217–1270. doi:10.1016/j.jaci.2020.10.003
   PubMed Web of Science ®Google Scholar
• Peerboom S, Graff S, Seidel L, et al. Predictors of a good response to inhaled corticosteroids in obesity-associated asthma. Biochem Pharmacol. 2020;179:113994. doi:10.1016/j.bcp.2020.113994
   PubMed Web of Science ®Google Scholar
• Tashiro H, Takahashi K, Sadamatsu H, et al. Biomarkers for overweight in adult-onset asthma. J Asthma Allergy. 2020;13:409–414. doi:10.2147/JAA.S276371
   PubMed Web of Science ®Google Scholar
• Camargo CA Jr, Boulet LP, Sutherland ER, et al. Body mass index and response to asthma therapy: fluticasone propionate/salmeterol versus montelukast. J Asthma. 2010;47(1):76–82. doi:10.3109/02770900903338494
   PubMed Web of Science ®Google Scholar
• Thompson CA, Eslick SR, Berthon BS, Wood LG. Asthma medication use in obese and healthy weight asthma: systematic review/meta-analysis. Eur Respir J. 2021;57(3):2000612. doi:10.1183/13993003.00612-2020
   PubMed Web of Science ®Google Scholar
• Luthe SK, Hirayama A, Goto T, Faridi MK, Camargo CA Jr, Hasegawa K. Association between obesity and acute severity among patients hospitalized for asthma exacerbation. J Allergy Clin Immunol Pract. 2018;6(6):1936–1941 e4. doi:10.1016/j.jaip.2018.02.001
   PubMed Web of Science ®Google Scholar
• Ilmarinen P, Vahatalo I, Tuomisto LE, Niemela O, Kankaanranta H. Long-term adherence to inhaled corticosteroids in clinical phenotypes of adult-onset asthma. J Allergy Clin Immunol Pract. 2021;9(9):3503–3505 e3. doi:10.1016/j.jaip.2021.04.057
   PubMed Web of Science ®Google Scholar
• Lefaudeux D, De Meulder B, Loza MJ, et al. U-BIOPRED clinical adult asthma clusters linked to a subset of sputum omics. J Allergy Clin Immunol. 2017;139(6):1797–1807. doi:10.1016/j.jaci.2016.08.048
   PubMed Web of Science ®Google Scholar
• Sutherland ER, Lehman EB, Teodorescu M, Wechsler ME, National Heart L. Blood Institute’s Asthma Clinical Research N. Body mass index and phenotype in subjects with mild-to-moderate persistent asthma. J Allergy Clin Immunol. 2009;123(6):1328–34 e1. doi:10.1016/j.jaci.2009.04.005
   PubMed Web of Science ®Google Scholar
• Peters-Golden M, Swern A, Bird SS, Hustad CM, Grant E, Edelman JM. Influence of body mass index on the response to asthma controller agents. Eur Respir J. 2006;27(3):495–503. doi:10.1183/09031936.06.00077205
   PubMed Web of Science ®Google Scholar
• Boulet LP, Franssen E. Influence of obesity on response to fluticasone with or without salmeterol in moderate asthma. Respir Med. 2007;101(11):2240–2247. doi:10.1016/j.rmed.2007.06.031
   PubMed Web of Science ®Google Scholar
• Sutherland ER, Goleva E, Strand M, Beuther DA, Leung DY. Body mass and glucocorticoid response in asthma. Am J Respir Crit Care Med. 2008;178(7):682–687. doi:10.1164/rccm.200801-076OC
   PubMed Web of Science ®Google Scholar
• Al Heialy S, Gaudet M, Ramakrishnan RK, et al. Contribution of IL-17 in steroid hyporesponsiveness in obese asthmatics through dysregulation of glucocorticoid receptors alpha and beta. Front Immunol. 2020;11:1724. doi:10.3389/fimmu.2020.01724
   PubMed Web of Science ®Google Scholar
• Demarche SF, Schleich FN, Henket MA, Paulus VA, Van Hees TJ, Louis RE. Effectiveness of inhaled corticosteroids in real life on clinical outcomes, sputum cells and systemic inflammation in asthmatics: a retrospective cohort study in a secondary care centre. BMJ Open. 2017;7(11):e018186. doi:10.1136/bmjopen-2017-018186
   PubMed Web of Science ®Google Scholar
• Yadav UC, Srivastava SK. Cysteinyl leukotrienes (CysLTs): role in obesity-induced asthma. Curr Mol Med. 2015;15(7):598–605. doi:10.2174/1566524015666150831130954
   PubMed Web of Science ®Google Scholar
• Farzan S, Khan S, Elera C, Tsang J, Akerman M, DeVoti J. Effectiveness of montelukast in overweight and obese atopic asthmatics. Ann Allergy Asthma Immunol. 2017;119(2):189–190. doi:10.1016/j.anai.2017.05.024
   PubMed Web of Science ®Google Scholar
• Sutherland ER, Camargo CA Jr, Busse WW, et al. Comparative effect of body mass index on response to asthma controller therapy. Allergy Asthma Proc. 2010;31(1):20–25. doi:10.2500/aap.2010.31.3307
   PubMed Web of Science ®Google Scholar
• Menzies-Gow A, Corren J, Bourdin A, et al. Tezepelumab in adults and adolescents with severe, uncontrolled asthma. N Engl J Med. 2021;384(19):1800–1809. PMID: 33979488. doi:10.1056/NEJMoa2034975
   PubMed Web of Science ®Google Scholar
• Sposato B, Scalese M, Milanese M, et al. Factors reducing omalizumab response in severe asthma. Eur J Intern Med. 2018;52:78–85. doi:10.1016/j.ejim.2018.01.026
   PubMed Web of Science ®Google Scholar
• Busse WW, Paggiaro P, Muñoz X, et al. Impact of baseline patient characteristics on dupilumab efficacy in type 2 asthma. Eur Respir J. 2021;58:2004605. doi:10.1183/13993003.04605-2020
   PubMed Web of Science ®Google Scholar
• Gibson PG, Prazma CM, Chupp GL, et al. Mepolizumab improves clinical outcomes in patients with severe asthma and comorbid conditions. Respir Res. 2021;22:171. doi:10.1186/s12931-021-01746-4
   PubMed Web of Science ®Google Scholar
• Li X, Song Y, Ma X. Lactobacillus plantarum and Lactobacillus fermentum alone or in combination regulate intestinal flora composition and systemic immunity to alleviate obesity syndrome in high-fat diet rat. Int J Food Sci Technol. 2018;53(1):137–146. doi:10.1111/ijfs.13567
   Web of Science ®Google Scholar
• Saeed MA, Gribben KC, Alam M, Lyden ER, Hanson CK, LeVan TD. Association of dietary fiber on asthma, respiratory symptoms, and inflammation in the adult national health and nutrition examination survey population. Ann Am Thorac Soc. 2020;17(9):1062–1068. PMID: 32369709. doi:10.1513/AnnalsATS.201910-776OC
   PubMed Web of Science ®Google Scholar
• Gutkowski P, Madalinski K, Grek M, Dmenska H, Syczewska M, Michalkiewicz J. Effect of orally administered probiotic strains “Lactobacillus” and “Bifidobacterium” in children with atopic asthma. Central-Eur J Immunol. 2010;35:233–238.
   Web of Science ®Google Scholar
• Huang CF, Chie WC, Wang IJ. Efficacy of lactobacillus administration in school-age children with asthma: a randomized, placebo-controlled trial. Nutrients. 2018;10(11):1678. PMID: 30400588; PMCID: PMC6265750. doi:10.3390/nu10111678
   PubMed Web of Science ®Google Scholar
• Chen YS, Jan RL, Lin YL, Chen HH, Wang JY. Randomized placebo-controlled trial of lactobacillus on asthmatic children with allergic rhinitis. Pediatr Pulmonol. 2010;45(11):1111–1120. PMID: 20658483. doi:10.1002/ppul.21296
   PubMed Web of Science ®Google Scholar
• Holguin F, Grasemann H, Sharma S, et al. L-Citrulline increases nitric oxide and improves control in obese asthmatics. JCI Insight. 2019;4(24):e131733. PMID: 31714895; PMCID: PMC6975256. doi:10.1172/jci.insight.131733
   PubMed Web of Science ®Google Scholar
• Stoodley I, Williams L, Thompson C, Scott H, Wood L. Evidence for lifestyle interventions in asthma. Breathe. 2019;15(2):e50–e61. doi:10.1183/20734735.0019-2019
   Web of Science ®Google Scholar
• Pakhale S, Baron J, Dent R, Vandemheen K, Aaron SD. Effects of weight loss on airway responsiveness in obese adults with asthma: does weight loss lead to reversibility of asthma? Chest. 2015;147:1582e90. doi:10.1378/chest.14-3105
   Web of Science ®Google Scholar
• Özbey Ü, Balaban S, Sözener ZÇ, Uçar A, Mungan D, Mısırlıgil Z. The effects of diet-induced weight loss on asthma control and quality of life in obese adults with asthma: a randomized controlled trial. J Asthma. 2020;57(6):618–626. doi:10.1080/02770903.2019.1590594
   PubMed Web of Science ®Google Scholar
• Freitas PD, Silva AG, Ferreira PG, et al. Exercise improves physical activity and comorbidities in obese adults with asthma. Med Sci Sports Exerc. 2018;50(7):1367–1376. doi:10.1249/MSS.0000000000001574
   PubMed Web of Science ®Google Scholar
• Lim R. Bariatric procedures for the management of severe obesity: descriptions. In: Post TW, editor. UpToDate. UpToDate; 2021.
   Google Scholar
• Upala S, Thavaraputta S, Sanguankeo A. Improvement in pulmonary function in asthmatic patients after bariatric surgery: a systematic review and meta-analysis. Surg Obes Relat Dis. 2019;15(5):794–803. doi:10.1016/j.soard.2018.12.018
   PubMed Web of Science ®Google Scholar
• Hossain N, Arhi C, Borg CM. Is bariatric surgery better than nonsurgical weight loss for improving asthma control? a systematic review. Obes Surg. 2021;31(4):1810–1832. doi:10.1007/s11695-021-05255-7
   PubMed Web of Science ®Google Scholar
• Nyenhuis SM, Dixon AE, Ma J. Impact of lifestyle interventions targeting healthy diet, physical activity, and weight loss on asthma in adults: what is the evidence? J Allergy Clin Immunol Pract. 2018;6(3):751–763. doi:10.1016/j.jaip.2017.10.026
   PubMed Web of Science ®Google Scholar