Effects of Oxidative Stress on Airway Epithelium Permeability in Asthma and Potential Implications for Patients with Comorbid Obesity

References

• Michaeloudes C, Abubakar-Waziri H, Lakhdar R, et al. Molecular mechanisms of oxidative stress in asthma. Mol Aspects Med. 2022;85:101026. doi:10.1016/j.mam.2021.101026
   PubMed Web of Science ®Google Scholar
• van der Vliet A, Janssen-Heininger YMW, Anathy V. Oxidative stress in chronic lung disease: from mitochondrial dysfunction to dysregulated redox signaling. Mol Aspects Med. 2018;63:59–69. doi:10.1016/j.mam.2018.08.001
   PubMed Web of Science ®Google Scholar
• Betteridge DJ. What is oxidative stress? Metabolism. 2000;49(2Suppl 1):3–8. doi:10.1016/s0026-0495(00)80077-3
   PubMed Web of Science ®Google Scholar
• Sahiner UM, Birben E, Erzurum S, Sackesen C, Kalayci O. Oxidative stress in asthma: part of the puzzle. Pediatr Allergy Immunol. 2018;29(8):789–800. doi:10.1111/pai.12965
   PubMed Web of Science ®Google Scholar
• Liu Z, Ren Z, Zhang J, et al. Role of ROS and nutritional antioxidants in human diseases. Front Physiol. 2018;9:477. doi:10.3389/fphys.2018.00477
   PubMed Web of Science ®Google Scholar
• CDC. Most recent national asthma data. Available from: https://www.cdc.gov/asthma/most_recent_national_asthma_data.htm. Accessed October 25, 2022.
   Google Scholar
• Su X, Ren Y, Li M, Zhao X, Kong L, Kang J. Prevalence of comorbidities in asthma and nonasthma patients: a meta-analysis. Medicine. 2016;95(22):e3459. doi:10.1097/MD.0000000000003459
   PubMed Web of Science ®Google Scholar
• Chapman DG, Irvin CG. Mechanisms of airway hyper-responsiveness in asthma: the past, present and yet to come. Clin Exp Allergy. 2015;45(4):706–719. doi:10.1111/cea.12506
   PubMed Web of Science ®Google Scholar
• Tan HT, Hagner S, Ruchti F, et al. Tight junction, mucin, and inflammasome-related molecules are differentially expressed in eosinophilic, mixed, and neutrophilic experimental asthma in mice. Allergy. 2019;74(2):294–307. doi:10.1111/all.13619
   PubMed Web of Science ®Google Scholar
• Hinks TSC, Levine SJ, Brusselle GG. Treatment options in type-2 low asthma. Eur Respir J. 2021;57(1):2000528. doi:10.1183/13993003.00528-2020
   PubMed Web of Science ®Google Scholar
• Ricciardolo FLM, Sprio AE, Baroso A, et al. Characterization of T2-low and T2-high asthma phenotypes in real-life. Biomedicines. 2021;9(11):1684. doi:10.3390/biomedicines9111684
   PubMed Web of Science ®Google Scholar
• Yaghoubi M, Adibi A, Safari A, FitzGerald JM, Sadatsafavi M. The projected economic and health burden of uncontrolled asthma in the United States. Am J Respir Crit Care Med. 2019;200(9):1102–1112. doi:10.1164/rccm.201901-0016OC
   PubMed Web of Science ®Google Scholar
• Guilbert TW, Garris C, Jhingran P, et al. Asthma that is not well-controlled is associated with increased healthcare utilization and decreased quality of life. J Asthma. 2011;48(2):126–132. doi:10.3109/02770903.2010.535879
   PubMed Web of Science ®Google Scholar
• NHLBI Obesity Education Initiative Expert Panel on the Identification E, and Treatment of Obesity in Adults (US). Clinical Guidelines on the Identification, Evaluation, and Treatment of Overweight and Obesity in Adults. National Heart, Lung, and Blood Institute; 1998:98–4083.
   Google Scholar
• Fernandez-Sanchez A, Madrigal-Santillan E, Bautista M, et al. Inflammation, oxidative stress, and obesity. Int J Mol Sci. 2011;12(5):3117–3132. doi:10.3390/ijms12053117
   PubMed Web of Science ®Google Scholar
• Furukawa S, Fujita T, Shimabukuro M, et al. Increased oxidative stress in obesity and its impact on metabolic syndrome. J Clin Invest. 2004;114(12):1752–1761. doi:10.1172/JCI21625
   PubMed Web of Science ®Google Scholar
• Beltowski J, Wojcicka G, Jamroz A. Leptin decreases plasma paraoxonase 1 (PON1) activity and induces oxidative stress: the possible novel mechanism for proatherogenic effect of chronic hyperleptinemia. Atherosclerosis. 2003;170(1):21–29. doi:10.1016/s0021-9150(03)00236-3
   PubMed Web of Science ®Google Scholar
• Cinkajzlova A, Mraz M, Haluzik M. Adipose tissue immune cells in obesity, type 2 diabetes mellitus and cardiovascular diseases. J Endocrinol. 2021;252(1):R1–R22. doi:10.1530/JOE-21-0159
   PubMed Web of Science ®Google Scholar
• Liu R, Nikolajczyk BS. Tissue immune cells fuel obesity-associated inflammation in adipose tissue and beyond. Front Immunol. 2019;10:1587. doi:10.3389/fimmu.2019.01587
   PubMed Web of Science ®Google Scholar
• Kawai T, Autieri MV, Scalia R. Adipose tissue inflammation and metabolic dysfunction in obesity. Am J Physiol Cell Physiol. 2021;320(3):C375–C391. doi:10.1152/ajpcell.00379.2020
   PubMed Web of Science ®Google Scholar
• Ouchi N, Parker JL, Lugus JJ, Walsh K. Adipokines in inflammation and metabolic disease. Nat Rev Immunol. 2011;11(2):85–97. doi:10.1038/nri2921
   PubMed Web of Science ®Google Scholar
• McGarry ME, Castellanos E, Thakur N, et al. Obesity and bronchodilator response in black and Hispanic children and adolescents with asthma. Chest. 2015;147(6):1591–1598. doi:10.1378/chest.14-2689
   PubMed Web of Science ®Google Scholar
• Farah CS, Kermode JA, Downie SR, et al. Obesity is a determinant of asthma control independent of inflammation and lung mechanics. Chest. 2011;140(3):659–666. doi:10.1378/chest.11-0027
   PubMed Web of Science ®Google Scholar
• Taylor B, Mannino D, Brown C, Crocker D, Twum-Baah N, Holguin F. Body mass index and asthma severity in the national asthma survey. Thorax. 2008;63(1):14–20. doi:10.1136/thx.2007.082784
   PubMed Web of Science ®Google Scholar
• Scott HA, Gibson PG, Garg ML, et al. Dietary restriction and exercise improve airway inflammation and clinical outcomes in overweight and obese asthma: a randomized trial. Clin Exp Allergy. 2013;43(1):36–49. doi:10.1111/cea.12004
   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;8:32. doi:10.1186/1465-9921-8-32
   PubMed Web of Science ®Google Scholar
• Shore SA, Rivera-Sanchez YM, Schwartzman IN, Johnston RA. Responses to ozone are increased in obese mice. J Appl Physiol. 2003;95(3):938–945. doi:10.1152/japplphysiol.00336.2003
   PubMed Web of Science ®Google Scholar
• Finkelstein EA, Khavjou OA, Thompson H, et al. Obesity and severe obesity forecasts through 2030. Am J Prev Med. 2012;42(6):563–570. doi:10.1016/j.amepre.2011.10.026
   PubMed Web of Science ®Google Scholar
• CDC. Asthma and obesity. Available from: https://www.cdc.gov/asthma/asthma_stats/asthma_obesity.htm. Accessed October 25, 2022.
   Google Scholar
• Holguin F. Oxidative stress in airway diseases. Ann Am Thorac Soc. 2013;10(Supplement):S150–S157. doi:10.1513/AnnalsATS.201305-116AW
   PubMedGoogle Scholar
• David WH, Riches TRM. Overview of innate lung immunity and inflammation. In: Lung Innate Immunity and Inflammation Methods in Molecular Biology. Vol. 1809. Springer; 2018.
   Google Scholar
• Crystal RG, Randell SH, Engelhardt JF, Voynow J, Sunday ME. Airway epithelial cells: current concepts and challenges. Proc Am Thorac Soc. 2008;5(7):772–777. doi:10.1513/pats.200805-041HR
   PubMedGoogle Scholar
• Wang SZ, Rosenberger CL, Bao YX, Stark JM, Harrod KS. Clara cell secretory protein modulates lung inflammatory and immune responses to respiratory syncytial virus infection. J Immunol. 2003;171(2):1051–1060. doi:10.1183/13993003.00528-2020
   PubMed Web of Science ®Google Scholar
• Hiemstra PS, McCray PB Jr, Bals R. The innate immune function of airway epithelial cells in inflammatory lung disease. Eur Respir J. 2015;45(4):1150–1162. doi:10.1183/09031936.00141514
   PubMed Web of Science ®Google Scholar
• Campbell HK, Maiers JL, DeMali KA. Interplay between tight junctions & adherens junctions. Exp Cell Res. 2017;358(1):39–44. doi:10.1016/j.yexcr.2017.03.061
   PubMed Web of Science ®Google Scholar
• Schlingmann B, Molina SA, Koval M. Claudins: gatekeepers of lung epithelial function. Semin Cell Dev Biol. 2015;42:47. doi:10.1016/J.SEMCDB.2015.04.009
   PubMed Web of Science ®Google Scholar
• Loxham M, Davies DE. Phenotypic and genetic aspects of epithelial barrier function in asthmatic patients. J Allergy Clin Immunol. 2017;139(6):1736–1751. doi:10.1016/j.jaci.2017.04.005
   PubMed Web of Science ®Google Scholar
• Coyne CB, Vanhook MK, Gambling TM, Carson JL, Boucher RC, Johnson LG. Regulation of airway tight junctions by proinflammatory cytokines. Mol Biol Cell. 2002;13(9):3218–3234. doi:10.1091/mbc.e02-03-0134
   PubMed Web of Science ®Google Scholar
• Yuksel H, Ocalan M, Yilmaz O. E-cadherin: an important functional molecule at respiratory barrier between defence and dysfunction. Front Physiol. 2021;12:720227. doi:10.3389/fphys.2021.720227
   PubMed Web of Science ®Google Scholar
• Erle DJ, Sheppard D. The cell biology of asthma. J Cell Biol. 2014;205(5):621–631. doi:10.1083/jcb.201401050
   PubMed Web of Science ®Google Scholar
• Gon Y, Hashimoto S. Role of airway epithelial barrier dysfunction in pathogenesis of asthma. Allergol Int. 2018;67(1):12–17. doi:10.1016/j.alit.2017.08.011
   PubMed Web of Science ®Google Scholar
• Hough KP, Curtiss ML, Blain TJ, et al. Airway remodeling in asthma. Front Med. 2020;7:191. doi:10.3389/fmed.2020.00191
   PubMed Web of Science ®Google Scholar
• Bergeron C, Tulic MK, Hamid Q. Airway remodelling in asthma: from benchside to clinical practice. Can Respir J. 2010;17(4):e85–e93. doi:10.1155/2010/318029
   PubMed Web of Science ®Google Scholar
• Xiao C, Puddicombe SM, Field S, et al. Defective epithelial barrier function in asthma. J Allergy Clin Immunol. 2011;128(3):549–612. doi:10.1016/j.jaci.2011.05.038
   PubMed Web of Science ®Google Scholar
• Wedes SH, Khatri SB, Zhang R, et al. Noninvasive markers of airway inflammation in asthma. Clin Transl Sci. 2009;2(2):112–117. doi:10.1111/j.1752-8062.2009.00095.x
   PubMed Web of Science ®Google Scholar
• Nadeem A, Chhabra SK, Masood A, Raj HG. Increased oxidative stress and altered levels of antioxidants in asthma. J Allergy Clin Immunol. 2003;111(1):72–78. doi:10.1067/mai.2003.17
   PubMed Web of Science ®Google Scholar
• Zhao JJ, Shimizu Y, Dobashi K, et al. The relationship between oxidative stress and acid stress in adult patients with mild asthma. J Investig Allergol Clin Immunol. 2008;18(1):41–45.
   PubMed Web of Science ®Google Scholar
• Ganas K, Loukides S, Papatheodorou G, Panagou P, Kalogeropoulos N. Total nitrite/nitrate in expired breath condensate of patients with asthma. Respir Med. 2001;95(8):649–654. doi:10.1053/rmed.2001.1117
   PubMed Web of Science ®Google Scholar
• Svensson S, Olin AC, Larstad M, Ljungkvist G, Toren K. Determination of hydrogen peroxide in exhaled breath condensate by flow injection analysis with fluorescence detection. J Chromatogr B Analyt Technol Biomed Life Sci. 2004;809(2):199–203. doi:10.1016/j.jchromb.2004.06.027
   PubMed Web of Science ®Google Scholar
• Bayram H, Rusznak C, Khair OA, Sapsford RJ, Abdelaziz MM. Effect of ozone and nitrogen dioxide on the permeability of bronchial epithelial cell cultures of non-asthmatic and asthmatic subjects. Clin Exp Allergy. 2002;32(9):1285–1292. doi:10.1046/j.1365-2745.2002.01435.x
   PubMed Web of Science ®Google Scholar
• Que LG, Stiles JV, Sundy JS, Foster WM. Pulmonary function, bronchial reactivity, and epithelial permeability are response phenotypes to ozone and develop differentially in healthy humans. J Appl Physiol. 2011;111(3):679–687. doi:10.1152/japplphysiol.00337.2011
   PubMed Web of Science ®Google Scholar
• Kehrl HR, Vincent LM, Kowalsky RJ, et al. Ozone exposure increases respiratory epithelial permeability in humans. Am Rev Respir Dis. 1987;135(5):1124–1128. doi:10.1164/arrd.1987.135.5.1124
   PubMedGoogle Scholar
• Del Donno M, Chetta A, Foresi A, Olivieri D, Gavaruzzi G, Ugolotti G. Lung epithelial permeability and bronchial responsiveness in subjects with stable asthma. Chest. 1997;111(5):1255–1260. doi:10.1378/chest.111.5.1255
   PubMed Web of Science ®Google Scholar
• Elwood RK, Kennedy S, Belzberg A, Hogg JC, Pare PD. Respiratory mucosal permeability in asthma. Am Rev Respir Dis. 1983;128(3):523–527. doi:10.1164/arrd.1983.128.3.523
   PubMed Web of Science ®Google Scholar
• Georas S, Ransom N, Hillman S, et al. The leaky lung test: a pilot study using inhaled mannitol to measure airway barrier function in asthma. J Asthma. 2019;56(12):1257–1265. doi:10.1080/02770903.2018.1536145
   PubMed Web of Science ®Google Scholar
• Liu J, Chen X, Dou M, et al. Particulate matter disrupts airway epithelial barrier via oxidative stress to promote Pseudomonas aeruginosa infection. J Thorac Dis. 2019;11(6):2617–2627. doi:10.21037/jtd.2019.05.77
   PubMed Web of Science ®Google Scholar
• Kim BG, Lee PH, Lee SH, Park CS, Jang AS. Impact of ozone on claudins and tight junctions in the lungs. Environ Toxicol. 2018;33(7):798–806. doi:10.1002/tox.22566
   PubMed Web of Science ®Google Scholar
• Michaudel C, Mackowiak C, Maillet I, et al. Ozone exposure induces respiratory barrier biphasic injury and inflammation controlled by IL-33. J Allergy Clin Immunol. 2018;142(3):942–958. doi:10.1016/j.jaci.2017.11.044
   PubMed Web of Science ®Google Scholar
• Georas SN, Rezaee F. Epithelial barrier function: at the front line of asthma immunology and allergic airway inflammation. J Allergy Clin Immunol. 2014;134(3):509–520. doi:10.1016/j.jaci.2014.05.049
   PubMed Web of Science ®Google Scholar
• Grasemann H, Holguin F. Oxidative stress and obesity-related asthma. Paediatr Respir Rev. 2021;37:18–21. doi:10.1016/j.prrv.2020.05.004
   PubMed Web of Science ®Google Scholar
• Wells SM, Holian A. Asymmetric dimethylarginine induces oxidative and nitrosative stress in murine lung epithelial cells. Am J Respir Cell Mol Biol. 2007;36(5):520–528. doi:10.1165/rcmb.2006-0302SM
   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
• Devarajan A, Bourquard N, Hama S, et al. Paraoxonase 2 deficiency alters mitochondrial function and exacerbates the development of atherosclerosis. Antioxid Redox Signal. 2011;14(3):341–351. doi:10.1089/ars.2010.3430
   PubMed Web of Science ®Google Scholar
• Winnica DE, Monzon A, Ye S, et al. Airway epithelial paraoxonase-2 in obese asthma. PLoS One. 2022;17(3):e0261504. doi:10.1371/journal.pone.0261504
   PubMed Web of Science ®Google Scholar
• Schiffers C, Reynaert NL, Wouters EFM, van der Vliet A. Redox dysregulation in aging and COPD: role of NOX enzymes and implications for antioxidant strategies. Antioxidants. 2021;10(11):1799. doi:10.3390/antiox10111799
   Web of Science ®Google Scholar
• Comstock AT, Ganesan S, Chattoraj A, et al. Rhinovirus-induced barrier dysfunction in polarized airway epithelial cells is mediated by NADPH oxidase 1. J Virol. 2011;85(13):6795–6808. doi:10.1128/JVI.02074-10
   PubMed Web of Science ®Google Scholar
• Sajjan U, Wang Q, Zhao Y, Gruenert DC, Hershenson MB. Rhinovirus disrupts the barrier function of polarized airway epithelial cells. Am J Respir Crit Care Med. 2008;178(12):1271–1281. doi:10.1164/rccm.200801-136OC
   PubMed Web of Science ®Google Scholar
• Singh D, McCann KL, Imani F. MAPK and heat shock protein 27 activation are associated with respiratory syncytial virus induction of human bronchial epithelial monolayer disruption. Am J Physiol Lung Cell Mol Physiol. 2007;293(2):L436–L445. doi:10.1152/ajplung.00097.2007
   PubMed Web of Science ®Google Scholar
• Corne JM, Marshall C, Smith S, et al. Frequency, severity, and duration of rhinovirus infections in asthmatic and non-asthmatic individuals: a longitudinal cohort study. Lancet. 2002;359(9309):831–834. doi:10.1016/S0140-6736(02)07953-9
   PubMed Web of Science ®Google Scholar
• Nicholson KG, Kent J, Ireland DC. Respiratory viruses and exacerbations of asthma in adults. BMJ. 1993;307(6910):982–986. doi:10.1136/bmj.307.6910.982
   PubMed Web of Science ®Google Scholar
• Tang M, Henderson RJ, Holbrook JT, et al. Does obesity increase respiratory tract infections in patients with asthma? J Allergy Clin Immunol Pract. 2019;7(3):954–961e6. doi:10.1016/j.jaip.2018.09.033
   PubMed Web of Science ®Google Scholar
• Spannhake EW, Reddy SP, Jacoby DB, Yu XY, Saatian B, Tian J. Synergism between rhinovirus infection and oxidant pollutant exposure enhances airway epithelial cell cytokine production. Environ Health Perspect. 2002;110(7):665–670. doi:10.1289/ehp.02110665
   PubMed Web of Science ®Google Scholar
• Le Dréan G, Haure-Mirande V, Ferrier L, et al. Visceral adipose tissue and leptin increase colonic epithelial tight junction permeability via a RhoA-ROCK-dependent pathway. FASEB J. 2014;28(3):1059–1070. doi:10.1096/fj.13-234203
   PubMed Web of Science ®Google Scholar
• Fain JN. Release of interleukins and other inflammatory cytokines by human adipose tissue is enhanced in obesity and primarily due to the nonfat cells. Vitam Horm. 2006;74:443–477. doi:10.1016/S0083-6729(06
   PubMed Web of Science ®Google Scholar
• Maslov LN, Naryzhnaya NV, Boshchenko AA, Popov SV, Ivanov VV, Oeltgen PR. Is oxidative stress of adipocytes a cause or a consequence of the metabolic syndrome? J Clin Transl Endocrinol. 2019;15:1–5. doi:10.1016/j.jcte.2018.11.001
   PubMedGoogle Scholar
• Monickaraj F, Aravind S, Nandhini P, et al. Accelerated fat cell aging links oxidative stress and insulin resistance in adipocytes. J Biosci. 2013;38(1):113–122. doi:10.1007/s12038-012-9289-0
   PubMed Web of Science ®Google Scholar
• Berry MA, Hargadon B, Shelley M, et al. Evidence of a role of tumor necrosis factor alpha in refractory asthma. N Engl J Med. 2006;354(7):697–708. doi:10.1056/NEJMoa050580
   PubMed Web of Science ®Google Scholar
• Broide DH, Lotz M, Cuomo AJ, Coburn DA, Federman EC, Wasserman SI. Cytokines in symptomatic asthma airways. J Allergy Clin Immunol. 1992;89(5):958–967. doi:10.1016/0091-6749(92)90218-q
   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(5):1186–1198. doi:10.1038/mi.2014.8
   PubMed Web of Science ®Google Scholar
• Holgate ST, Noonan M, Chanez P, et al. Efficacy and safety of etanercept in moderate-to-severe asthma: a randomised, controlled trial. Eur Respir J. 2011;37(6):1352–1359. doi:10.1183/09031936.00063510
   PubMed Web of Science ®Google Scholar
• Taille C, Poulet C, Marchand-Adam S, et al. Monoclonal anti-TNF-alpha antibodies for severe steroid-dependent asthma: a case series. Open Respir Med J. 2013;7:21–25. doi:10.2174/1874306401307010021
   PubMedGoogle Scholar
• Hardyman MA, Wilkinson E, Martin E, et al. TNF-alpha-mediated bronchial barrier disruption and regulation by src-family kinase activation. J Allergy Clin Immunol. 2013;132(3):665–675 e8. doi:10.1016/j.jaci.2013.03.005
   PubMed Web of Science ®Google Scholar
• Huang S, Dudez T, Scerri I, et al. Defective activation of c-Src in cystic fibrosis airway epithelial cells results in loss of tumor necrosis factor-alpha-induced gap junction regulation. J Biol Chem. 2003;278(10):8326–8332. doi:10.1074/jbc.M208264200
   PubMed Web of Science ®Google Scholar
• Tashiro H, Shore SA. Obesity and severe asthma. Allergol Int. 2019;68(2):135–142. doi:10.1016/j.alit.2018.10.004
   PubMed Web of Science ®Google Scholar
• Marini M, Avoni E, Hollemborg J, Mattoli S. Cytokine mRNA profile and cell activation in bronchoalveolar lavage fluid from nonatopic patients with symptomatic asthma. Chest. 1992;102(3):661–669. doi:10.1378/chest.102.3.661
   PubMed Web of Science ®Google Scholar
• Virchow JC Jr, Kroegel C, Walker C, Matthys H. Inflammatory determinants of asthma severity: mediator and cellular changes in bronchoalveolar lavage fluid of patients with severe asthma. J Allergy Clin Immunol. 1996;98(5 Pt 2):S27–S33; discussion S33–S40. doi:10.1016/S0091-6749(96)70014-3
   Web of Science ®Google Scholar
• Peters MC, McGrath KW, Hawkins GA, et al. Plasma interleukin-6 concentrations, metabolic dysfunction, and asthma severity: a cross-sectional analysis of two cohorts. Lancet Respir Med. 2016;4(7):574–584. doi:10.1016/S2213-2600(16)30048-0
   PubMed Web of Science ®Google Scholar
• Jevnikar Z, Ostling 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(2):577–590. doi:10.1016/j.jaci.2018.05.026
   PubMed Web of Science ®Google Scholar
• Callaghan PJ, Rybakovsky E, Ferrick B, Thomas S, Mullin JM. Retinoic acid improves baseline barrier function and attenuates TNF-alpha-induced barrier leak in human bronchial epithelial cell culture model, 16HBE 14o. PLoS One. 2020;15(12):e0242536. doi:10.1371/journal.pone.0242536
   PubMed Web of Science ®Google Scholar
• Al-Sadi R, Ye D, Boivin M, et al. Interleukin-6 modulation of intestinal epithelial tight junction permeability is mediated by JNK pathway activation of claudin-2 gene. PLoS One. 2014;9(3):e85345. doi:10.1371/journal.pone.0085345
   PubMed Web of Science ®Google Scholar
• Suzuki T, Yoshinaga N, Tanabe S. Interleukin-6 (IL-6) regulates claudin-2 expression and tight junction permeability in intestinal epithelium. J Biol Chem. 2011;286(36):31263–31271. doi:10.1074/jbc.M111.238147
   PubMed Web of Science ®Google Scholar
• Al-Sadi RM, Ma TY. IL-1beta causes an increase in intestinal epithelial tight junction permeability. J Immunol. 2007;178(7):4641–4649. doi:10.4049/jimmunol.178.7.4641
   PubMed Web of Science ®Google Scholar
• Genser L, Aguanno D, Soula HA, et al. Increased jejunal permeability in human obesity is revealed by a lipid challenge and is linked to inflammation and type 2 diabetes. J Pathol. 2018;246(2):217–230. doi:10.1002/path.5134
   PubMed Web of Science ®Google Scholar
• Shore SA. Obesity, airway hyperresponsiveness, and inflammation. J Appl Physiol. 2010;108(3):735–743. doi:10.1152/japplphysiol.00749.2009
   PubMed Web of Science ®Google Scholar
• Ahmad R, Rah B, Bastola D, Dhawan P, Singh AB. Obesity-induces organ and tissue specific tight junction restructuring and barrier deregulation by claudin switching. Sci Rep. 2017;7(1):5125. doi:10.1038/s41598-017-04989-8
   PubMedGoogle Scholar
• Suzuki T, Hara H. Dietary fat and bile juice, but not obesity, are responsible for the increase in small intestinal permeability induced through the suppression of tight junction protein expression in LETO and OLETF rats. Nutr Metab. 2010;7(1):19. doi:10.1186/1743-7075-7-19
   Google Scholar
• Marseglia L, Manti S, D’Angelo G, et al. Oxidative stress in obesity: a critical component in human diseases. Int J Mol Sci. 2014;16(1):378–400. doi:10.3390/ijms16010378
   PubMed Web of Science ®Google Scholar
• Iikuni N, Lam QL, Lu L, Matarese G, La Cava A. Leptin and inflammation. Curr Immunol Rev. 2008;4(2):70–79. doi:10.2174/157339508784325046
   PubMedGoogle Scholar
• Bruno A, Pace E, Chanez P, et al. Leptin and leptin receptor expression in asthma. J Allergy Clin Immunol. 2009;124(2):230–7, 237 e1–4. doi:10.1016/j.jaci.2009.04.032
   Web of Science ®Google Scholar
• Holguin F, Rojas M, Hart CM. The peroxisome proliferator activated receptor gamma (PPARgamma) ligand rosiglitazone modulates bronchoalveolar lavage levels of leptin, adiponectin, and inflammatory cytokines in lean and obese mice. Lung. 2007;185(6):367–372. doi:10.1007/s00408-007-9035-9
   PubMed Web of Science ®Google Scholar
• Holguin F, Fitzpatrick A. Obesity, asthma, and oxidative stress. J Appl Physiol. 2010;108(3):754–759. doi:10.1152/japplphysiol.00702.2009
   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(1):103–109. doi:10.1016/j.jaci.2004.10.007
   PubMed Web of Science ®Google Scholar
• Brun P, Castagliuolo I, Di Leo V, et al. Increased intestinal permeability in obese mice: new evidence in the pathogenesis of nonalcoholic steatohepatitis. Am J Physiol Gastrointest Liver Physiol. 2007;292(2):G518–G525. doi:10.1152/ajpgi.00024.2006
   PubMed Web of Science ®Google Scholar
• Zhang Y, Saradna A, Ratan R, et al. RhoA/Rho-kinases in asthma: from pathogenesis to therapeutic targets. Clin Transl Immunol. 2020;9(5):e01134. doi:10.1002/cti2.1134
   PubMed Web of Science ®Google Scholar
• Castro M, King TS, Kunselman SJ, et al. Effect of vitamin D3 on asthma treatment failures in adults with symptomatic asthma and lower vitamin D levels: the VIDA randomized clinical trial. JAMA. 2014;311(20):2083–2091. doi:10.1001/jama.2014.5052
   PubMed Web of Science ®Google Scholar
• Johnson O, Gerald LB, Harvey J, et al. An online weight loss intervention for people with obesity and poorly controlled asthma. J Allergy Clin Immunol Pract. 2022;10(6):1577–1586 e3. doi:10.1016/j.jaip.2022.02.040
   PubMed Web of Science ®Google Scholar
• Hinnen D. Glucagon-like peptide 1 receptor agonists for type 2 diabetes. diabetes spectr. 2017;30(3):202–210. doi:10.2337/ds16-0026
   PubMedGoogle Scholar
• Foer D, Beeler PE, Cui J, Karlson EW, Bates DW, Cahill KN. Asthma exacerbations in patients with type 2 diabetes and asthma on glucagon-like peptide-1 receptor agonists. Am J Respir Crit Care Med. 2021;203(7):831–840. doi:10.1164/rccm.202004-0993OC
   PubMed Web of Science ®Google Scholar
• Rogliani P, Calzetta L, Capuani B, et al. Glucagon-like peptide 1 receptor: a novel pharmacological target for treating human bronchial hyperresponsiveness. Am J Respir Cell Mol Biol. 2016;55(6):804–814. doi:10.1165/rcmb.2015-0311OC
   PubMed Web of Science ®Google Scholar
• Danielewicz H. What the genetic background of individuals with asthma and obesity can reveal: is beta2-adrenergic receptor gene polymorphism important? Pediatr Allergy Immunol Pulmonol. 2014;27(3):104–110. doi:10.1089/ped.2014.0360
   PubMed Web of Science ®Google Scholar
• Cazzola M, Page CP, Rogliani P, Matera MG. Beta 2-agonist therapy in lung disease. Am J Respir Crit Care Med. 2013;187(7):690–696. doi:10.1164/rccm.201209-1739PP
   PubMed Web of Science ®Google Scholar
• Dixon AE, Que LG, Kalhan R, et al. Roflumilast may increase risk of exacerbations when used to treat poorly controlled asthma in people with obesity. Ann Am Thorac Soc. 2023;20(2):206–214. doi:10.1513/AnnalsATS.202204-368OC
   PubMed Web of Science ®Google Scholar
• Chandrasekaran R, Bruno SR, Mark ZF, et al. Mitoquinone mesylate attenuates pathological features of lean and obese allergic asthma in mice. Am J Physiol Lung Cell Mol Physiol. 2023;324(2):L141–L153. doi:10.1152/ajplung.00249.2022
   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). doi:10.1172/jci.insight.131733
   Web of Science ®Google Scholar
• Sweerus K, Lachowicz-Scroggins M, Gordon E, et al. Claudin-18 deficiency is associated with airway epithelial barrier dysfunction and asthma. J Allergy Clin Immunol. 2017;139(1):72–81e1. doi:10.1016/j.jaci.2016.02.035
   PubMed Web of Science ®Google Scholar
• Saatian B, Rezaee F, Desando S, et al. Interleukin-4 and interleukin-13 cause barrier dysfunction in human airway epithelial cells. Tissue Barriers. 2013;1(2):e24333. doi:10.4161/tisb.24333
   PubMedGoogle Scholar
• Heijink IH, van Oosterhout A, Kapus A. Epidermal growth factor receptor signalling contributes to house dust mite-induced epithelial barrier dysfunction. Eur Respir J. 2010;36(5):1016–1026. doi:10.1183/09031936.00125809
   PubMed Web of Science ®Google Scholar
• Trautmann A, Kruger K, Akdis M, et al. Apoptosis and loss of adhesion of bronchial epithelial cells in asthma. Int Arch Allergy Immunol. 2005;138(2):142–150. doi:10.1159/000088436
   PubMed Web of Science ®Google Scholar
• Petecchia L, Sabatini F, Usai C, Caci E, Varesio L, Rossi GA. Cytokines induce tight junction disassembly in airway cells via an EGFR-dependent MAPK/ERK1/2-pathway. Lab Invest. 2012;92(8):1140–1148. doi:10.1038/labinvest.2012.67
   PubMed Web of Science ®Google Scholar
• Post S, Nawijn MC, Hackett TL, et al. The composition of house dust mite is critical for mucosal barrier dysfunction and allergic sensitisation. Thorax. 2012;67(6):488–495. doi:10.1136/thoraxjnl-2011-200606
   PubMed Web of Science ®Google Scholar
• Wan H, Winton HL, Soeller C, et al. Der p 1 facilitates transepithelial allergen delivery by disruption of tight junctions. J Clin Invest. 1999;104(1):123–133. doi:10.1172/JCI5844
   PubMed Web of Science ®Google Scholar