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Current Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

Review Article

An Emerging Role for Exhaled Nitric Oxide in Guiding Biological Treatment in Severe Asthma

Author(s): Giovanni Rolla, Enrico Heffler, Stefano Pizzimenti, Alain Michils and Andrei Malinovschi*

Volume 27, Issue 42, 2020

Page: [7159 - 7167] Pages: 9

DOI: 10.2174/0929867327666200713184659

Price: $65

Abstract

Asthma is a heterogeneous disease with regard to the inflammatory pathways activated. In recent years, biologic drugs (monoclonal antibodies) directed towards specific components of type 2 inflammation have been approved for the treatment of severe asthma. Phenotyping of patients with severe asthma and evaluation of biomarkers have been recommended to help identify patients who are candidates for treatment with biologics and to monitor treatment responses.

Fractional exhaled Nitric Oxide (FeNO) is a biomarker of type 2 inflammation in asthma, signaling activation of Interleukin (IL)-4/IL-13 pathway. FeNO could be useful to assess treatment response or identify candidates for a specific drug that acts on type 2 inflammation mechanisms linked to Nitric Oxide (NO) production, such as the IL-4/IL-13 pathway or upstream processes.

The value of FeNO as a biomarker predictive of responses to the biologics available for treating severe asthma is discussed based on the published studies at the moment of the review.

Keywords: FeNO, biological treatment, severe asthma, dupilumab, omalizumab, benralizumab, reslizumab, mepolizumab.

[1]
Global initiative for asthma difficult-to-treat and severe asthma guidelines. Available at: http://www.goldcopd.org/guidelines-global-strategy-for-diagnosis-management.html (Accessed Date: 15th October, 2020).
[2]
Pavord, I.D.; Mathieson, N.; Scowcroft, A.; Pedersini, R.; Isherwood, G.; Price, D. The impact of poor asthma control among asthma patients treated with inhaled corticosteroids plus long-acting β2-agonists in the United Kingdom: a cross-sectional analysis. NPJ Prim. Care Respir. Med., 2017, 27(1), 17.
[http://dx.doi.org/10.1038/s41533-017-0014-1] [PMID: 28270657]
[3]
Chung, K.F.; Wenzel, S.E.; Brozek, J.L.; Bush, A.; Castro, M.; Sterk, P.J.; Adcock, I.M.; Bateman, E.D.; Bel, E.H.; Bleecker, E.R.; Boulet, L.P.; Brightling, C.; Chanez, P.; Dahlen, S.E.; Djukanovic, R.; Frey, U.; Gaga, M.; Gibson, P.; Hamid, Q.; Jajour, N.N.; Mauad, T.; Sorkness, R.L.; Teague, W.G. International ERS/ATS guidelines on defini-tion, evaluation and treatment of severe asthma. Eur. Respir. J., 2014, 43(2), 343-373.
[http://dx.doi.org/10.1183/09031936.00202013] [PMID: 24337046]
[4]
O’Neill, S.; Sweeney, J.; Patterson, C.C.; Menzies-Gow, A.; Niven, R.; Mansur, A.H.; Bucknall, C.; Chaudhuri, R.; Thomson, N.C.; Brightling, C.E.; O’Neill, C.; Heaney, L.G. British thoracic society difficult asthma network. The cost of treating severe refractory asthma in the UK: an economic analysis from the British Thoracic Society Difficult Asthma Registry. Thorax, 2015, 70(4), 376-378.
[http://dx.doi.org/10.1136/thoraxjnl-2013-204114] [PMID: 24917087]
[5]
Pavord, I.D.; Beasley, R.; Agusti, A.; Anderson, G.P.; Bel, E.; Brusselle, G.; Cullinan, P.; Custovic, A.; Ducharme, F.M.; Fahy, J.V.; Frey, U.; Gibson, P.; Heaney, L.G.; Holt, P.G.; Humbert, M.; Lloyd, C.M.; Marks, G.; Martinez, F.D.; Sly, P.D.; von Mutius, E.; Wenzel, S.; Zar, H.J.; Bush, A. After asthma: redefining airways diseases. Lancet, 2018, 391(10118), 350-400.
[http://dx.doi.org/10.1016/S0140-6736(17)30879-6 ] [PMID: 28911920]
[6]
Busse, W.W. Biological treatments for severe asthma: a major advance in asthma care. Allergol. Int., 2019, 68(2), 158-166.
[http://dx.doi.org/10.1016/j.alit.2019.01.004 ] [PMID: 30792118]
[7]
Spahn, J.D.; Malka, J.; Szefler, S.J. Current application of exhaled nitric oxide in clinical practice. J. Allergy Clin. Immunol., 2016, 138(5), 1296-1298.
[http://dx.doi.org/10.1016/j.jaci.2016.09.002] [PMID: 27664377]
[8]
Suresh, V.; Mih, J.D.; George, S.C. Measurement of IL-13-induced iNOS-derived gas phase nitric oxide in human bronchial epithelial cells. Am. J. Respir. Cell Mol. Biol., 2007, 37(1), 97-104.
[http://dx.doi.org/10.1165/rcmb.2006-0419OC] [PMID: 17347445]
[9]
van Rensen, E.L.; Straathof, K.C.; Veselic-Charvat, M.A.; Zwinderman, A.H.; Bel, E.H.; Sterk, P.J. Effect of inhaled steroids on airway hyperresponsiveness, sputum eosinophils, and exhaled nitric oxide levels in patients with asthma. Thorax, 1999, 54(5), 403-408.
[http://dx.doi.org/10.1136/thx.54.5.403] [PMID: 10212103]
[10]
Petsky, H.L.; Cates, C.J.; Kew, K.M.; Chang, A.B. Tailoring asthma treatment on eosinophilic markers (exhaled nitric oxide or sputum eosinophils): a systematic review and meta-analysis. Thorax, 2018, 73(12), 1110-1119.
[http://dx.doi.org/10.1136/thoraxjnl-2018-211540] [PMID: 29858277]
[11]
Al-Shamkhi, N.; Alving, K.; Dahlen, S.E.; Hedlin, G.; Mid-delveld, R.; Bjerg, A.; Ekerljung, L.; Olin, A.C.; Sommar, J.; Forsberg, B.; Janson, C.; Malinovschi, A. Important non-disease-related determinants of exhaled nitric oxide levels in mild asthma - results from the Swedish GA(2) LEN study. Clin. Exp. Allergy, 2016, 46(9), 1185-1193.
[http://dx.doi.org/10.1111/cea.12749] [PMID: 27138350]
[12]
Dweik, R.A.; Boggs, P.B.; Erzurum, S.C.; Irvin, C.G.; Leigh, M.W.; Lundberg, J.O.; Olin, A-C.; Plummer, A.L.; Taylor, D.R. American thoracic society committee on interpretation of exhaled nitric oxide levels (FENO) for clinical applications. An official ATS clinical practice guideline: interpretation of exhaled nitric oxide levels (FENO) for clinical applications. Am. J. Respir. Crit. Care Med., 2011, 184(5), 602-615.
[http://dx.doi.org/10.1164/rccm.9120-11ST] [PMID: 21885636]
[13]
Haccuria, A.; Michils, A.; Michiels, S.; Van Muylem, A. Exhaled nitric oxide: a biomarker integrating both lung function and airway inflammation changes. J. Allergy Clin. Immunol., 2014, 134(3), 554-559.
[http://dx.doi.org/10.1016/j.jaci.2013.12.1070] [PMID: 24522091]
[14]
McNicholl, D.M.; Stevenson, M.; McGarvey, L.P.; Heaney, L.G. The utility of fractional exhaled nitric oxide suppression in the identification of nonadherence in difficult asthma. Am. J. Respir. Crit. Care Med., 2012, 186(11), 1102-1108.
[http://dx.doi.org/10.1164/rccm.201204-0587OC] [PMID: 23024023]
[15]
Heaney, L.G.; Busby, J.; Bradding, P.; Chaudhuri, R.; Man-sur, A.H.; Niven, R.; Pavord, I.D.; Lindsay, J.T.; Costello, R.W. Medical research council UK refractory asthma strati-fication programme (RASP-UK). Remotely monitored ther-apy and nitric oxide suppression identifies nonadherence in severe asthma. Am. J. Respir. Crit. Care Med., 2019, 199(4), 454-464.
[http://dx.doi.org/10.1164/rccm.201806-1182OC] [PMID: 30339770]
[16]
National Institute for Health and Care Excellence Guideline. Asthma: diagnosis, monitoring and chronic asthma management.
[PMID: 32755129]
[17]
Kuo, C.R.; Spears, M.; Haughney, J.; Smith, A.; Miller, J.; Bradshaw, T.; Murray, L.; Williamson, P.; Lipworth, B. Scottish consensus statement on the role of FeNO in adult asthma. Respir. Med., 2019, 155, 54-57.
[http://dx.doi.org/10.1016/j.rmed.2019.07.010] [PMID: 31299469]
[18]
FDA files genentech’s supplemental biologics license application of Xolair® (omalizumab) for pediatric allergic asthma. Available at: https://www.gene.com/media/press-releases/14620/2016-03-01/fda-files-genentechs-supplemental-biolog (Accessed Date: 15th October, 2020)
[19]
MacDonald, K.M.; Kavati, A.; Ortiz, B.; Alhossan, A.; Lee, C.S.; Abraham, I. Short- and long-term real-world effective-ness of omalizumab in severe allergic asthma: systematic review of 42 studies published 2008-2018. Expert Rev. Clin. Immunol., 2019, 15(5), 553-569.
[http://dx.doi.org/10.1080/1744666X.2019.1574571] [PMID: 30763137]
[20]
Braunstahl, G.J.; Chen, C.W.; Maykut, R.; Georgiou, P.; Peachey, G.; Bruce, J. The eXpeRience registry: the ‘real-world’ effectiveness of omalizumab in allergic asthma. Respir. Med., 2013, 107(8), 1141-1151.
[http://dx.doi.org/10.1016/j.rmed.2013.04.017] [PMID: 23721684]
[21]
Barnes, N.; Menzies-Gow, A.; Mansur, A.H.; Spencer, D.; Percival, F.; Radwan, A.; Niven, R. Effectiveness of omali-zumab in severe allergic asthma: a retrospective UK real-world study. J. Asthma, 2013, 50(5), 529-536.
[http://dx.doi.org/10.3109/02770903.2013.790419] [PMID: 23574000]
[22]
Hanania, N.A.; Wenzel, S.; Rosén, K.; Hsieh, H.J.; Mo-sesova, S.; Choy, D.F.; Lal, P.; Arron, J.R.; Harris, J.M.; Busse, W. Exploring the effects of omalizumab in allergic asthma: an analysis of biomarkers in the EXTRA study. Am. J. Respir. Crit. Care Med., 2013, 187(8), 804-811.
[http://dx.doi.org/10.1164/rccm.201208-1414OC] [PMID: 23471469]
[23]
Solidoro, P.; Patrucco, F.; de Blasio, F.; Brussino, L.; Bel-locchia, M.; Dassetto, D.; Pivetta, E.; Riccio, A.; Heffler, E.; Canonica, W.; Rolla, G.; Bucca, C. Predictors of reversible airway obstruction with omalizumab in severe asthma: a real-life study. Ther. Adv. Respir. Dis., 2019, 131753466619841274
[http://dx.doi.org/10.1177/1753466619841274] [PMID: 31002021]
[24]
Brooks, E.A.; Massanari, M.; Hanania, N.A.; Weiner, D.J. Cost-effectiveness of fractional exhaled nitric oxide (FeNO) measurement in predicting response to omalizumab in asthma. Clinicoecon. Outcomes Res., 2019, 11, 301-307.
[http://dx.doi.org/10.2147/CEOR.S177207] [PMID: 31114270]
[25]
Haldar, P.; Brightling, C.E.; Hargadon, B.; Gupta, S.; Mon-teiro, W.; Sousa, A.; Marshall, R.P.; Bradding, P.; Green, R.H.; Wardlaw, A.J.; Pavord, I.D. Mepolizumab and exac-erbations of refractory eosinophilic asthma. N. Engl. J. Med., 2009, 360(10), 973-984.
[http://dx.doi.org/10.1056/NEJMoa0808991] [PMID: 19264686]
[26]
Corren, J.; Weinstein, S.; Janka, L.; Zangrilli, J.; Garin, M. Phase 3 study of reslizumab in patients with poorly controlled asthma: effects across a broad range of eosinophil counts. Chest, 2016, 150(4), 799-810.
[http://dx.doi.org/10.1016/j.chest.2016.03.018] [PMID: 27018175]
[27]
FitzGerald, J.M.; Bleecker, E.R.; Nair, P.; Korn, S.; Ohta, K.; Lommatzsch, M.; Ferguson, G.T.; Busse, W.W.; Barker, P.; Sproule, S.; Gilmartin, G.; Werkström, V.; Aurivillius, M.; Goldman, M. CALIMA study investigators Benralizumab, an anti-interleukin-5 receptor α monoclonal antibody, as add-on treatment for patients with severe, uncontrolled, eosinophilic asthma (CALIMA): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet, 2016, 388(10056), 2128-2141.
[http://dx.doi.org/10.1016/S0140-6736(16)31322-8] [PMID: 27609406]
[28]
Laviolette, M.; Gossage, D.L.; Gauvreau, G.; Leigh, R.; Olivenstein, R.; Katial, R.; Busse, W.W.; Wenzel, S.; Wu, Y.; Datta, V.; Kolbeck, R.; Molfino, N.A. Effects of benral-izumab on airway eosinophils in asthmatic patients with sputum eosinophilia. J. Allergy Clin. Immunol., 2013, 132(5), 1086-1096.e5.
[http://dx.doi.org/10.1016/j.jaci.2013.05.020 ] [PMID: 23866823]
[29]
Walsh, G.M.; Hartnell, A.; Wardlaw, A.J.; Kurihara, K.; Sanderson, C.J.; Kay, A.B. IL-5 enhances the in vitro adhe-sion of human eosinophils, but not neutrophils, in a leucocyte integrin (CD11/18)-dependent manner. Immunology, 1990, 71(2), 258-265.
[PMID: 2228026]
[30]
Malinovschi, A.; Fonseca, J.A.; Jacinto, T.; Alving, K.; Janson, C. Exhaled nitric oxide levels and blood eosinophil counts independently associate with wheeze and asthma events in national health and nutrition examination survey subjects. J. Allergy Clin. Immunol., 2013, 132(4), 821-827.
[http://dx.doi.org/10.1016/j.jaci.2013.06.007] [PMID: 23890753]
[31]
Pavord, I.D.; Bafadhel, M. Exhaled nitric oxide and blood eosinophilia: independent markers of preventable risk. J. Allergy Clin. Immunol., 2013, 132(4), 828-829.
[http://dx.doi.org/10.1016/j.jaci.2013.07.045] [PMID: 24001802]
[32]
Jatakanon, A.; Lim, S.; Kharitonov, S.A.; Chung, K.F.; Barnes, P.J. Correlation between exhaled nitric oxide, sputum eosinophils, and methacholine responsiveness in patients with mild asthma. Thorax, 1998, 53(2), 91-95.
[http://dx.doi.org/10.1136/thx.53.2.91] [PMID: 9624291]
[33]
Schleich, F.N.; Seidel, L.; Sele, J.; Manise, M.; Quaedvlieg, V.; Michils, A.; Louis, R. Exhaled nitric oxide thresholds associated with a sputum eosinophil count ≥3% in a cohort of unselected patients with asthma. Thorax, 2010, 65(12), 1039-1044.
[http://dx.doi.org/10.1136/thx.2009.124925] [PMID: 20671307]
[34]
Pavord, I.D.; Korn, S.; Howarth, P.; Bleecker, E.R.; Buhl, R.; Keene, O.N.; Ortega, H.; Chanez, P. Mepolizumab for severe eosinophilic asthma (DREAM): a multicentre, double-blind, placebo-controlled trial. Lancet, 2012, 380(9842), 651-659.
[http://dx.doi.org/10.1016/S0140-6736(12)60988-X] [PMID: 22901886]
[35]
Castro, M.; Wenzel, S.E.; Bleecker, E.R.; Pizzichini, E.; Kuna, P.; Busse, W.W.; Gossage, D.L.; Ward, C.K.; Wu, Y.; Wang, B.; Khatry, D.B.; van der Merwe, R.; Kolbeck, R.; Molfino, N.A.; Raible, D.G. Benralizumab, an anti-interleukin 5 receptor α monoclonal antibody, versus placebo for uncontrolled eosinophilic asthma: a phase 2b randomised dose-ranging study. Lancet Respir. Med., 2014, 2(11), 879-890.
[http://dx.doi.org/10.1016/S2213-2600(14)70201-2] [PMID: 25306557]
[36]
Bleecker, E.R.; Wechsler, M.E.; FitzGerald, J.M.; Menzies-Gow, A.; Wu, Y.; Hirsch, I.; Goldman, M.; Newbold, P.; Zangrilli, J.G. Baseline patient factors impact on the clinical efficacy of benralizumab for severe asthma. Eur. Respir. J., 2018, 52(4)1800936
[http://dx.doi.org/10.1183/13993003.00936-2018] [PMID: 30139780]
[37]
Pelaia, G.; Vatrella, A.; Maselli, R. The potential of biologics for the treatment of asthma. Nat. Rev. Drug Discov., 2012, 11(12), 958-972.
[http://dx.doi.org/10.1038/nrd3792] [PMID: 23197041]
[38]
May, R.D.; Monk, P.D.; Cohen, E.S.; Manuel, D.; Dempsey, F.; Davis, N.H.; Dodd, A.J.; Corkill, D.J.; Woods, J. Jober-ty-Candotti, C.; Conroy, L.A.; Koentgen, F.; Martin, E.C.; Wilson, R.; Brennan, N.; Powell, J.; Anderson, I.K. Preclin-ical development of CAT-354, an IL-13 neutralizing antibody, for the treatment of severe uncontrolled asthma. Br. J. Pharmacol., 2012, 166(1), 177-193.
[http://dx.doi.org/10.1111/j.1476-5381.2011.01659.x] [PMID: 21895629]
[39]
Agrawal, S.; Townley, R.G. Role of periostin, FENO, IL-13, lebrikzumab, other IL-13 antagonist and dual IL-4/IL-13 an-tagonist in asthma. Expert Opin. Biol. Ther., 2014, 14(2), 165-181.
[http://dx.doi.org/10.1517/14712598.2014.859673] [PMID: 24283478]
[40]
Corren, J.; Lemanske, R.F.; Hanania, N.A.; Korenblat, P.E.; Parsey, M.V.; Arron, J.R.; Harris, J.M.; Scheerens, H.; Wu, L.C.; Su, Z.; Mosesova, S.; Eisner, M.D.; Bohen, S.P.; Mat-thews, J.G. Lebrikizumab treatment in adults with asthma. N. Engl. J. Med., 2011, 365(12), 1088-1098.
[http://dx.doi.org/10.1056/NEJMoa1106469] [PMID: 21812663]
[41]
Russell, R.J.; Chachi, L.; FitzGerald, J.M.; Backer, V.; Olivenstein, R.; Titlestad, I.L.; Ulrik, C.S.; Harrison, T.; Singh, D.; Chaudhuri, R.; Leaker, B.; McGarvey, L.; Sid-diqui, S.; Wang, M.; Braddock, M.; Nordenmark, L.H.; Co-hen, D.; Parikh, H.; Colice, G.; Brightling, C.E. MESOS study investigators Effect of tralokinumab, an interleukin-13 neutralising monoclonal antibody, on eosinophilic airway inflammation in uncontrolled moderate-to-severe asthma (MESOS): a multicentre, double-blind, randomised, placebo-controlled phase 2 trial. Lancet Respir. Med., 2018, 6(7), 499-510.
[http://dx.doi.org/10.1016/S2213-2600(18)30201-7] [PMID: 29793857]
[42]
Hanania, N.A.; Noonan, M.; Corren, J.; Korenblat, P.; Zheng, Y.; Fischer, S.K.; Cheu, M.; Putnam, W.S.; Murray, E.; Scheerens, H.; Holweg, C.T.J.; Maciuca, R.; Gray, S.; Doyle, R.; McClintock, D.; Olsson, J.; Matthews, J.G.; Yen, K. Lebrikizumab in moderate-to-severe asthma: pooled data from two randomised placebo-controlled studies. Thorax, 2015, 70(8), 748-756.
[http://dx.doi.org/10.1136/thoraxjnl-2014-206719] [PMID: 26001563]
[43]
Hanania, N.A.; Korenblat, P.; Chapman, K.R.; Bateman, E.D.; Kopecky, P.; Paggiaro, P.; Yokoyama, A.; Olsson, J.; Gray, S.; Holweg, C.T.; Eisner, M.; Asare, C.; Fischer, S.K.; Peng, K.; Putnam, W.S.; Matthews, J.G. Efficacy and safety of lebrikizumab in patients with uncontrolled asthma (LA-VOLTA I and LAVOLTA II): replicate, phase 3, random-ised, double-blind, placebo-controlled trials. Lancet Respir. Med., 2016, 4(10), 781-796.
[http://dx.doi.org/10.1016/S2213-2600(16)30265-X] [PMID: 27616196]
[44]
Panettieri, R.A. Jr.; Sjöbring, U.; Péterffy, A.; Wessman, P.; Bowen, K.; Piper, E.; Colice, G.; Brightling, C.E. Traloki-numab for severe, uncontrolled asthma (STRATOS 1 and STRATOS 2): two randomised, double-blind, placebo-controlled, phase 3 clinical trials. Lancet Respir. Med., 2018, 6(7), 511-525.
[http://dx.doi.org/10.1016/S2213-2600(18)30184-X] [PMID: 29792288]
[45]
Santini, G.; Mores, N.; Malerba, M.; Mondino, C.; Anzivino, R.; Macis, G.; Montuschi, P. Dupilumab for the treatment of asthma. Expert Opin. Investig. Drugs, 2017, 26(3), 357-366.
[http://dx.doi.org/10.1080/13543784.2017.1282458] [PMID: 28085503]
[46]
Wenzel, S.; Ford, L.; Pearlman, D.; Spector, S.; Sher, L.; Skobieranda, F.; Wang, L.; Kirkesseli, S.; Rocklin, R.; Bock, B.; Hamilton, J.; Ming, J.E.; Radin, A.; Stahl, N.; Yancopoulos, G.D.; Graham, N.; Pirozzi, G. Dupilumab in persistent asthma with elevated eosinophil levels. N. Engl. J. Med., 2013, 368(26), 2455-2466.
[http://dx.doi.org/10.1056/NEJMoa1304048] [PMID: 23688323]
[47]
Wenzel, S.; Castro, M.; Corren, J.; Maspero, J.; Wang, L.; Zhang, B.; Pirozzi, G.; Sutherland, E.R.; Evans, R.R.; Joish, V.N.; Eckert, L.; Graham, N.M.H.; Stahl, N.; Yancopoulos, G.D.; Louis-Tisserand, M.; Teper, A. Dupilumab efficacy and safety in adults with uncontrolled persistent asthma de-spite use of medium-to-high-dose inhaled corticosteroids plus a long-acting β2 agonist: a randomised double-blind placebo-controlled pivotal phase 2b dose-ranging trial. Lancet, 2016, 388(10039), 31-44.
[http://dx.doi.org/10.1016/S0140-6736(16)30307-5] [PMID: 27130691]
[48]
Castro, M.; Corren, J.; Pavord, I.D.; Maspero, J.; Wenzel, S.; Rabe, K.F.; Busse, W.W.; Ford, L.; Sher, L.; FitzGerald, J.M.; Katelaris, C.; Tohda, Y.; Zhang, B.; Staudinger, H.; Pirozzi, G.; Amin, N.; Ruddy, M.; Akinlade, B.; Khan, A.; Chao, J.; Martincova, R.; Graham, N.M.H.; Hamilton, J.D.; Swanson, B.N.; Stahl, N.; Yancopoulos, G.D.; Teper, A. Dupilumab efficacy and safety in moderate-to-severe uncon-trolled asthma. N. Engl. J. Med., 2018, 378(26), 2486-2496.
[http://dx.doi.org/10.1056/NEJMoa1804092] [PMID: 29782217]
[49]
Rabe, K.F.; Nair, P.; Brusselle, G.; Maspero, J.F.; Castro, M.; Sher, L.; Zhu, H.; Hamilton, J.D.; Swanson, B.N.; Khan, A.; Chao, J.; Staudinger, H.; Pirozzi, G.; Antoni, C.; Amin, N.; Ruddy, M.; Akinlade, B.; Graham, N.M.H.; Stahl, N.; Yancopoulos, G.D.; Teper, A. Efficacy and safety of dupilumab in glucocorticoid-dependent severe asthma. N. Engl. J. Med., 2018, 378(26), 2475-2485.
[http://dx.doi.org/10.1056/NEJMoa1804093] [PMID: 29782224]
[50]
European Medicines Agency Available at: https://www.ema. europa.eu/en/documents/smop/chmp-post-authorisation-summary-positive-opinion-dupixent-ii-12_en.pdf (Accessed Date: 15th October, 2020).
[51]
Verstraete, K.; Peelman, F.; Braun, H.; Lopez, J.; Van Rompaey, D.; Dansercoer, A.; Vandenberghe, I.; Pauwels, K.; Tavernier, J.; Lambrecht, B.N.; Hammad, H.; De Winter, H.; Beyaert, R.; Lippens, G.; Savvides, S.N. Structure and antagonism of the receptor complex mediated by human TSLP in allergy and asthma. Nat. Commun., 2017, 8, 14937.
[http://dx.doi.org/10.1038/ncomms14937] [PMID: 28368013]
[52]
Corren, J.; Parnes, J.R.; Wang, L.; Mo, M.; Roseti, S.L.; Griffiths, J.M.; van der Merwe, R. Tezepelumab in adults with uncontrolled asthma. N. Engl. J. Med., 2017, 377(10), 936-946.
[http://dx.doi.org/10.1056/NEJMoa1704064] [PMID: 28877011]
[53]
Gauvreau, G.M.; O’Byrne, P.M.; Boulet, L-P.; Wang, Y.; Cockcroft, D.; Bigler, J.; FitzGerald, J.M.; Boedigheimer, M.; Davis, B.E.; Dias, C.; Gorski, K.S.; Smith, L.; Bautista, E.; Comeau, M.R.; Leigh, R.; Parnes, J.R. Effects of an anti-TSLP antibody on allergen-induced asthmatic responses. N. Engl. J. Med., 2014, 370(22), 2102-2110.
[http://dx.doi.org/10.1056/NEJMoa1402895] [PMID: 24846652]
[54]
Lawrence, M.G.; Steinke, J.W.; Borish, L. Cytokine-targeting biologics for allergic diseases. Ann. Allergy Asthma Immunol., 2018, 120(4), 376-381.
[http://dx.doi.org/10.1016/j.anai.2018.01.009] [PMID: 29410215]
[55]
Chinthrajah, S.; Cao, S.; Liu, C.; Lyu, S.C.; Sindher, S.B.; Long, A.; Sampath, V.; Petroni, D.; Londei, M.; Nadeau, K.C. Phase 2a randomized, placebo-controlled study of anti-IL-33 in peanut allergy. JCI Insight, 2019, 4(22)131347
[http://dx.doi.org/10.1172/jci.insight.131347] [PMID: 31723064]
[56]
Mogensen, I.; James, A.; Malinovschi, A. Systemic and breath biomarkers for asthma: an update. Curr. Opin. Allergy Clin. Immunol., 2020, 20(1), 71-79.
[http://dx.doi.org/10.1097/ACI.0000000000000599] [PMID: 31652141]

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