Novel Biological Therapies in Severe Asthma: Targeting the Right Trait

Author(s): Gilda Varricchi*, Giancarlo Marone, Giuseppe Spadaro, Michele Russo, Francescopaolo Granata, Arturo Genovese, Gianni Marone*.

Journal Name: Current Medicinal Chemistry

Volume 26 , Issue 16 , 2019

  Journal Home
Translate in Chinese

Abstract:

Asthma is a heterogeneous disease characterized by chronic airway inflammation that results in a wide spectrum of clinical manifestations. Patients with severe asthma represent a substantial share of consumption of healthcare resources and hospitalization. Moreover, these patients are at risk of increased morbidity and mortality. Recently, several phenotypes and endotypes of asthma have been identified. The identification of specific subtypes of asthma is fundamental for optimizing the clinical benefit of novel treatments. Although in most patients the disease can be controlled by some combination of pharmacologic agents, in some 5-10% of patients the disease remains uncontrolled. Several monoclonal antibodies (mAbs) targeting pathogenetic molecules (e.g., IgE, IL-5, IL- 5Rα, IL-4, IL-13, TSLP) are currently available or under development for the treatment of different forms of severe type 2 asthma. The identification of diagnostic and predictive biomarkers (e.g., IgE, blood eosinophil count, FeNO, periostin, etc.) has revolutioned the field of targeted therapy in severe asthma. Monoclonal antibodies targeting Th2-driven inflammation are generally safe in adult patients with moderate-to-severe asthma. The long-term safety of these biologics is a relevant issue that should be addressed. Unfortunately, little is known about non-type 2 asthma. Further studies are needed to identify biomarkers to guide targeted therapies of different forms of non-type 2 asthma.

Keywords: Asthma, benralizumab, IL-4, IL-13, omalizumab, mepolizumab, reslizumab, tezepelumab.

[1]
2017 GINA Report. Global Strategy for Asthma Management and Prevention, 2017 [last access: September ] 2017.
[2]
Bateman, E.D.; Hurd, S.S.; Barnes, P.J.; Bousquet, J.; Drazen, J.M.; FitzGerald, J.M.; Gibson, P.; Ohta, K.; O’Byrne, P.; Pedersen, S.E.; Pizzichini, E.; Sullivan, S.D.; Wenzel, S.E.; Zar, H.J. Global strategy for asthma management and prevention: GINA executive summary. Eur. Respir. J., 2008, 31(1), 143-178. [http://dx.doi.org/10.1183/09031936.00138707]. [PMID: 18166595].
[3]
Martinez, F.D.; Vercelli, D. Asthma. Lancet, 2013, 382(9901), 1360-1372. [http://dx.doi.org/10.1016/S0140-6736(13)61536-6]. [PMID: 24041942].
[4]
Holgate, S.T.; Wenzel, S.; Postma, D.S.; Weiss, S.T.; Renz, H.; Sly, P.D. Asthma. Nat. Rev. Dis. Primers, 2015, 1, 15025. [http://dx.doi.org/10.1038/nrdp.2015.25]. [PMID: 27189668].
[5]
Custovic, A. To what extent is allergen exposure a risk factor for the development of allergic disease? Clin. Exp. Allergy, 2015, 45(1), 54-62. [http://dx.doi.org/10.1111/cea.12450]. [PMID: 25381695].
[6]
Porsbjerg, C.; Lange, P.; Ulrik, C.S. Lung function impairment increases with age of diagnosis in adult onset asthma. Respir. Med., 2015, 109(7), 821-827. [http://dx.doi.org/10.1016/j.rmed.2015.04.012]. [PMID: 25962648].
[7]
To, T.; Stanojevic, S.; Moores, G.; Gershon, A.S.; Bateman, E.D.; Cruz, A.A.; Boulet, L.P. Global asthma prevalence in adults: findings from the cross-sectional world health survey. BMC Public Health, 2012, 12, 204. [http://dx.doi.org/10.1186/1471-2458-12-204]. [PMID: 22429515].
[8]
von Bülow, A.; Kriegbaum, M.; Backer, V.; Porsbjerg, C. The prevalence of severe asthma and low asthma control among Danish adults. J. Allergy Clin. Immunol. Pract., 2014, 2(6), 759-767. [http://dx.doi.org/10.1016/j.jaip.2014.05.005]. [PMID: 25439368].
[9]
Ebmeier, S.; Thayabaran, D.; Braithwaite, I.; Bénamara, C.; Weatherall, M.; Beasley, R. Trends in international asthma mortality: analysis of data from the WHO Mortality Database from 46 countries (1993-2012). Lancet, 2017, 390(10098), 935-945. [http://dx.doi.org/10.1016/S0140-6736(17)31448-4]. [PMID: 28797514].
[10]
Israel, E.; Reddel, H.K. Severe and Difficult-to-Treat Asthma in Adults. N. Engl. J. Med., 2017, 377(10), 965-976. [http://dx.doi.org/10.1056/NEJMra1608969]. [PMID: 28877019].
[11]
Carrascosa, J.M.; Rivera, N.; Garcia-Doval, I.; Carretero, G.; Vanaclocha, F.; Daudén, E.; Gómez-García, F.J.; De-la-Cueva-Dobao, P.; Herrera-Ceballos, E.; Belinchón, I.; Alsina, M.; Sánchez-Carazo, J.L.; Ferrán, M.; Lopez-Estebaranz, J.L.; Pérez-Zafrilla, B.; Llamas, M.; Rivera, R.; Ferrándiz, C. Does the treatment ladder for systemic therapy in moderate to severe psoriasis only go up? The percentage of patients with severe psoriasis on biologics increases over time. Actas Dermosifiliogr., 2015, 106(8), 638-643. [http://dx.doi.org/10.1016/j.adengl.2015.04.019]. [PMID: 26141003].
[12]
Chachi, L.; Abbasian, M.; Gavrila, A.; Alzahrani, A.; Tliba, O.; Bradding, P.; Wardlaw, A.J.; Brightling, C.; Amrani, Y. Protein phosphatase 5 mediates corticosteroid insensitivity in airway smooth muscle in patients with severe asthma. Allergy, 2017, 72(1), 126-136. [http://dx.doi.org/10.1111/all.13003]. [PMID: 27501780].
[13]
Kim, R.Y.; Horvat, J.C.; Pinkerton, J.W.; Starkey, M.R.; Essilfie, A.T.; Mayall, J.R.; Nair, P.M.; Hansbro, N.G.; Jones, B.; Haw, T.J.; Sunkara, K.P.; Nguyen, T.H.; Jarnicki, A.G.; Keely, S.; Mattes, J.; Adcock, I.M.; Foster, P.S.; Hansbro, P.M. MicroRNA-21 drives severe, steroid-insensitive experimental asthma by amplifying phosphoinositide 3-kinase-mediated suppression of histone deacetylase 2. J. Allergy Clin. Immunol., 2017, 139(2), 519-532. [http://dx.doi.org/10.1016/j.jaci.2016.04.038]. [PMID: 27448447].
[14]
Hekking, P.P.; Wener, R.R.; Amelink, M.; Zwinderman, A.H.; Bouvy, M.L.; Bel, E.H. The prevalence of severe refractory asthma. J. Allergy Clin. Immunol., 2015, 135(4), 896-902. [http://dx.doi.org/10.1016/j.jaci.2014.08.042]. [PMID: 25441637].
[15]
Hansen, C.L.; Baelum, J.; Skadhauge, L.; Thomsen, G.; Omland, Ø.; Thilsing, T.; Dahl, S.; Sigsgaard, T.; Sherson, D. Consequences of asthma on job absenteeism and job retention. Scand. J. Public Health, 2012, 40(4), 377-384. [http://dx.doi.org/10.1177/1403494812449079]. [PMID: 22786923].
[16]
Serra-Batlles, J.; Plaza, V.; Morejón, E.; Comella, A.; Brugués, J. Costs of asthma according to the degree of severity. Eur. Respir. J., 1998, 12(6), 1322-1326. [http://dx.doi.org/10.1183/09031936.98.12061322]. [PMID: 9877485].
[17]
Sullivan, S.D.; Rasouliyan, L.; Russo, P.A.; Kamath, T.; Chipps, B.E. Extent, patterns, and burden of uncontrolled disease in severe or difficult-to-treat asthma. Allergy, 2007, 62(2), 126-133. [http://dx.doi.org/10.1111/j.1398-9995.2006.01254.x]. [PMID: 17298420].
[18]
Guilbert, T.W.; Garris, C.; Jhingran, P.; Bonafede, M.; Tomaszewski, K.J.; Bonus, T.; Hahn, R.M.; Schatz, M. Asthma that is not well-controlled is associated with increased healthcare utilization and decreased quality of life. J. Asthma, 2011, 48(2), 126-132. [http://dx.doi.org/10.3109/02770903.2010.535879]. [PMID: 21128880].
[19]
Gold, L.S.; Yeung, K.; Smith, N.; Allen-Ramey, F.C.; Nathan, R.A.; Sullivan, S.D. Asthma control, cost and race: results from a national survey. J. Asthma, 2013, 50(7), 783-790. [http://dx.doi.org/10.3109/02770903.2013.795589]. [PMID: 23638955].
[20]
Lambrecht, B.N.; Hammad, H. The immunology of asthma. Nat. Immunol., 2015, 16(1), 45-56. [http://dx.doi.org/10.1038/ni.3049]. [PMID: 25521684].
[21]
Fahy, J.V. Type 2 inflammation in asthma--present in most, absent in many. Nat. Rev. Immunol., 2015, 15(1), 57-65. [http://dx.doi.org/10.1038/nri3786]. [PMID: 25534623].
[22]
Wu, W.; Bleecker, E.; Moore, W.; Busse, W.W.; Castro, M.; Chung, K.F.; Calhoun, W.J.; Erzurum, S.; Gaston, B.; Israel, E.; Curran-Everett, D.; Wenzel, S.E. Unsupervised phenotyping of Severe Asthma Research Program participants using expanded lung data. J. Allergy Clin. Immunol., 2014, 133(5), 1280-1288. [http://dx.doi.org/10.1016/j.jaci.2013.11.042]. [PMID: 24589344].
[23]
Wenzel, S.E. Asthma phenotypes: the evolution from clinical to molecular approaches. Nat. Med., 2012, 18(5), 716-725. [http://dx.doi.org/10.1038/nm.2678]. [PMID: 22561835].
[24]
Marone, G.; Triggiani, M.; de Paulis, A. Mast cells and basophils: friends as well as foes in bronchial asthma? Trends Immunol., 2005, 26(1), 25-31. [http://dx.doi.org/10.1016/j.it.2004.10.010]. [PMID: 15629406].
[25]
Ray, A.; Oriss, T.B.; Wenzel, S.E. Emerging molecular phenotypes of asthma. Am. J. Physiol. Lung Cell. Mol. Physiol., 2015, 308(2), L130-L140. [http://dx.doi.org/10.1152/ajplung.00070.2014]. [PMID: 25326577].
[26]
Moore, W.C.; Bleecker, E.R.; Curran-Everett, D.; Erzurum, S.C.; Ameredes, B.T.; Bacharier, L.; Calhoun, W.J.; Castro, M.; Chung, K.F.; Clark, M.P.; Dweik, R.A.; Fitzpatrick, A.M.; Gaston, B.; Hew, M.; Hussain, I.; Jarjour, N.N.; Israel, E.; Levy, B.D.; Murphy, J.R.; Peters, S.P.; Teague, W.G.; Meyers, D.A.; Busse, W.W.; Wenzel, S.E. Characterization of the severe asthma phenotype by the National Heart, Lung, and Blood Institute’s Severe Asthma Research Program. J. Allergy Clin. Immunol., 2007, 119(2), 405-413. [http://dx.doi.org/10.1016/j.jaci.2006.11.639]. [PMID: 17291857].
[27]
Haldar, P.; Pavord, I.D.; Shaw, D.E.; Berry, M.A.; Thomas, M.; Brightling, C.E.; Wardlaw, A.J.; Green, R.H. Cluster analysis and clinical asthma phenotypes. Am. J. Respir. Crit. Care Med., 2008, 178(3), 218-224. [http://dx.doi.org/10.1164/rccm.200711-1754OC]. [PMID: 18480428].
[28]
Hinks, T.S.; Brown, T.; Lau, L.C.; Rupani, H.; Barber, C.; Elliott, S.; Ward, J.A.; Ono, J.; Ohta, S.; Izuhara, K.; Djukanović, R.; Kurukulaaratchy, R.J.; Chauhan, A.; Howarth, P.H. Multidimensional endotyping in patients with severe asthma reveals inflammatory heterogeneity in matrix metalloproteinases and chitinase 3-like protein 1. J. Allergy Clin. Immunol., 2016, 138(1), 61-75. [http://dx.doi.org/10.1016/j.jaci.2015.11.020]. [PMID: 26851968].
[29]
Agache, I.; Sugita, K.; Morita, H.; Akdis, M.; Akdis, C.A. The complex type 2 endotype in allergy and asthma: from laboratory to bedside. Curr. Allergy Asthma Rep., 2015, 15(6), 29. [http://dx.doi.org/10.1007/s11882-015-0529-x]. [PMID: 26141574].
[30]
Lötvall, J.; Akdis, C.A.; Bacharier, L.B.; Bjermer, L.; Casale, T.B.; Custovic, A.; Lemanske, R.F., Jr; Wardlaw, A.J.; Wenzel, S.E.; Greenberger, P.A. Asthma endotypes: a new approach to classification of disease entities within the asthma syndrome. J. Allergy Clin. Immunol., 2011, 127(2), 355-360. [http://dx.doi.org/10.1016/j.jaci.2010.11.037]. [PMID: 21281866].
[31]
Varricchi, G.; Bagnasco, D.; Borriello, F.; Heffler, E.; Canonica, G.W. Interleukin-5 pathway inhibition in the treatment of eosinophilic respiratory disorders: evidence and unmet needs. Curr. Opin. Allergy Clin. Immunol., 2016, 16(2), 186-200. [http://dx.doi.org/10.1097/ACI.0000000000000251]. [PMID: 26859368].
[32]
Varricchi, G.; Senna, G.; Loffredo, S.; Bagnasco, D.; Ferrando, M.; Canonica, G.W. Reslizumab and eosinophilic asthma: One step closer to precision medicine? Front. Immunol., 2017, 8, 242. [http://dx.doi.org/10.3389/fimmu.2017.00242]. [PMID: 28344579].
[33]
Bagnasco, D.; Ferrando, M.; Caminati, M.; Bragantini, A.; Puggioni, F.; Varricchi, G.; Passalacqua, G.; Canonica, G.W. Targeting interleukin-5 or interleukin-5Rα: Safety considerations. Drug Saf., 2017, 40(7), 559-570. [http://dx.doi.org/10.1007/s40264-017-0522-5]. [PMID: 28321782].
[34]
Baird, B.; Shopes, R.J.; Oi, V.T.; Erickson, J.; Kane, P.; Holowka, D. Interaction of IgE with its high-affinity receptor. Structural basis and requirements for effective cross-linking. Int. Arch. Allergy Appl. Immunol., 1989, 88(1-2), 23-28. [http://dx.doi.org/10.1159/000234742]. [PMID: 2523358].
[35]
Saini, S.S.; MacGlashan, D.W., Jr; Sterbinsky, S.A.; Togias, A.; Adelman, D.C.; Lichtenstein, L.M.; Bochner, B.S. Down-regulation of human basophil IgE and FC epsilon RI alpha surface densities and mediator release by anti-IgE-infusions is reversible in vitro and in vivo. J. Immunol., 1999, 162(9), 5624-5630. [PMID: 10228046].
[36]
MacGlashan, D. W., Jr; Savage, J. H.; Wood, R. A.; Saini, S. S. Suppression of the basophil response to allergen during treatment with omalizumab is dependent on 2 competing factors. J. Allergy Clin. Immunol, 2012, 130, 1130- 1135- e5. [http://dx.doi.org/10.1016/j.jaci.2012.05.038] [PMID: 22800400]
[37]
MacGlashan, D.W., Jr; Bochner, B.S.; Adelman, D.C.; Jardieu, P.M.; Togias, A.; McKenzie-White, J.; Sterbinsky, S.A.; Hamilton, R.G.; Lichtenstein, L.M. Down-regulation of Fc(epsilon)RI expression on human basophils during in vivo treatment of atopic patients with anti-IgE antibody. J. Immunol., 1997, 158(3), 1438-1445. [PMID: 9013989].
[38]
Beck, L.A.; Marcotte, G.V.; MacGlashan, D.; Togias, A.; Saini, S. Omalizumab-induced reductions in mast cell Fce psilon RI expression and function. J. Allergy Clin. Immunol., 2004, 114(3), 527-530. [http://dx.doi.org/10.1016/j.jaci.2004.06.032]. [PMID: 15356552].
[39]
Noga, O.; Hanf, G.; Brachmann, I.; Klucken, A.C.; Kleine-Tebbe, J.; Rosseau, S.; Kunkel, G.; Suttorp, N.; Seybold, J. Effect of omalizumab treatment on peripheral eosinophil and T-lymphocyte function in patients with allergic asthma. J. Allergy Clin. Immunol., 2006, 117(6), 1493-1499. [http://dx.doi.org/10.1016/j.jaci.2006.02.028]. [PMID: 16751018].
[40]
Serrano-Candelas, E.; Martinez-Aranguren, R.; Valero, A.; Bartra, J.; Gastaminza, G.; Goikoetxea, M.J.; Martín, M.; Ferrer, M. Comparable actions of omalizumab on mast cells and basophils. Clin. Exp. Allergy, 2016, 46(1), 92-102. [http://dx.doi.org/10.1111/cea.12668]. [PMID: 26509363].
[41]
Detoraki, A.; Di Capua, L.; Varricchi, G.; Genovese, A.; Marone, G.; Spadaro, G. Omalizumab in patients with eosinophilic granulomatosis with polyangiitis: a 36-month follow-up study. J. Asthma, 2016, 53(2), 201-206. [http://dx.doi.org/10.3109/02770903.2015.1081700]. [PMID: 26377630].
[42]
Detoraki, A.; Varricchi, G.; Genovese, A.; Marone, G.; Spadaro, G. The role of omalizumab in patients with eosinophilic granulomatosis with polyangiitis (Churg-Strauss): Comment on the Article by Jachiet et al. Arthritis Rheumatol., 2017, 69(4), 868-870. [http://dx.doi.org/10.1002/art.40012]. [PMID: 27992689].
[43]
Cazzola, M.; Camiciottoli, G.; Bonavia, M.; Gulotta, C.; Ravazzi, A.; Alessandrini, A.; Caiaffa, M.F.; Berra, A.; Schino, P.; Di Napoli, P.L.; Maselli, R.; Pelaia, G.; Bucchioni, E.; Paggiaro, P.L.; Macchia, L. Italian real-life experience of omalizumab. Respir. Med., 2010, 104(10), 1410-1416. [http://dx.doi.org/10.1016/j.rmed.2010.04.013]. [PMID: 20483574].
[44]
Rottem, M. Omalizumab reduces corticosteroid use in patients with severe allergic asthma: real-life experience in Israel. J. Asthma, 2012, 49(1), 78-82. [http://dx.doi.org/10.3109/02770903.2011.637598]. [PMID: 22149205].
[45]
Vennera, Mdel. C.; Pérez De Llano, L.; Bardagí, S.; Ausin, P.; Sanjuas, C.; González, H.; Gullón, J.A.; Martínez-Moragón, E.; Carretero, J.A.; Vera, E.; Medina, J.F.; Alvarez, F.J.; Entrenas, L.M.; Padilla, A.; Irigaray, R.; Picado, C. Omalizumab therapy in severe asthma: experience from the Spanish registry--some new approaches. J. Asthma, 2012, 49(4), 416-422. [http://dx.doi.org/10.3109/02770903.2012.668255]. [PMID: 22443408].
[46]
Sweeney, J.; Brightling, C.E.; Menzies-Gow, A.; Niven, R.; Patterson, C.C.; Heaney, L.G. Clinical management and outcome of refractory asthma in the UK from the British Thoracic Society Difficult Asthma Registry. Thorax, 2012, 67(8), 754-756. [http://dx.doi.org/10.1136/thoraxjnl-2012-201869]. [PMID: 22581823].
[47]
Schumann, C.; Kropf, C.; Wibmer, T.; Rüdiger, S.; Stoiber, K.M.; Thielen, A.; Rottbauer, W.; Kroegel, C. Omalizumab in patients with severe asthma: the XCLUSIVE study. Clin. Respir. J., 2012, 6(4), 215-227. [http://dx.doi.org/10.1111/j.1752-699X.2011.00263.x]. [PMID: 21740532].
[48]
Grimaldi-Bensouda, L.; Zureik, M.; Aubier, M.; Humbert, M.; Levy, J.; Benichou, J.; Molimard, M.; Abenhaim, L. Does omalizumab make a difference to the real-life treatment of asthma exacerbations?: Results from a large cohort patients with severe uncontrolled asthma. Chest, 2013, 143(2), 398-405. [http://dx.doi.org/10.1378/chest.12-1372]. [PMID: 23505637].
[49]
Barnes, N.; Menzies-Gow, A.; Mansur, A.H.; Spencer, D.; Percival, F.; Radwan, A.; Niven, R. Effectiveness of omalizumab 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].
[50]
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].
[51]
Korn, S.; Schumann, C.; Kropf, C.; Stoiber, K.; Thielen, A.; Taube, C.; Buhl, R. Effectiveness of omalizumab in patients 50 years and older with severe persistent allergic asthma. Ann. Allergy Asthma Immunol., 2010, 105(4), 313-319. [http://dx.doi.org/10.1016/j.anai.2010.07.007]. [PMID: 20934632].
[52]
Bousquet, J.; Siergiejko, Z.; Swiebocka, E.; Humbert, M.; Rabe, K.F.; Smith, N.; Leo, J.; Peckitt, C.; Maykut, R.; Peachey, G. Persistency of response to omalizumab therapy in severe allergic (IgE-mediated) asthma. Allergy, 2011, 66(5), 671-678. [http://dx.doi.org/10.1111/j.1398-9995.2010.02522.x]. [PMID: 21255035].
[53]
Rubin, A.S.; Souza-Machado, A.; Andradre-Lima, M.; Ferreira, F.; Honda, A.; Matozo, T.M. Effect of omalizumab as add-on therapy on asthma-related quality of life in severe allergic asthma: a Brazilian study (QUALITX). J. Asthma, 2012, 49(3), 288-293. [http://dx.doi.org/10.3109/02770903.2012.660297]. [PMID: 22356355].
[54]
Holgate, S.T.; Chuchalin, A.G.; Hébert, J.; Lötvall, J.; Persson, G.B.; Chung, K.F.; Bousquet, J.; Kerstjens, H.A.; Fox, H.; Thirlwell, J.; Cioppa, G.D. Efficacy and safety of a recombinant anti-immunoglobulin E antibody (omalizumab) in severe allergic asthma. Clin. Exp. Allergy, 2004, 34(4), 632-638. [http://dx.doi.org/10.1111/j.1365-2222.2004.1916.x]. [PMID: 15080818].
[55]
Busse, W.; Corren, J.; Lanier, B.Q.; McAlary, M.; Fowler-Taylor, A.; Cioppa, G.D.; van As, A.; Gupta, N. Omalizumab, anti-IgE recombinant humanized monoclonal antibody, for the treatment of severe allergic asthma. J. Allergy Clin. Immunol., 2001, 108(2), 184-190. [http://dx.doi.org/10.1067/mai.2001.117880]. [PMID: 11496232].
[56]
Vashisht, P.; Casale, T. Omalizumab for treatment of allergic rhinitis. Expert Opin. Biol. Ther., 2013, 13(6), 933-945. [http://dx.doi.org/10.1517/14712598.2013.795943]. [PMID: 23621175].
[57]
Abraham, I.; Alhossan, A.; Lee, C.S.; Kutbi, H.; MacDonald, K. ‘Real-life’ effectiveness studies of omalizumab in adult patients with severe allergic asthma: systematic review. Allergy, 2016, 71(5), 593-610. [http://dx.doi.org/10.1111/all.12815]. [PMID: 26644231].
[58]
Hochhaus, G.; Brookman, L.; Fox, H.; Johnson, C.; Matthews, J.; Ren, S.; Deniz, Y. Pharmacodynamics of omalizumab: implications for optimised dosing strategies and clinical efficacy in the treatment of allergic asthma. Curr. Med. Res. Opin., 2003, 19(6), 491-498. [http://dx.doi.org/10.1185/030079903125002171]. [PMID: 14594521].
[59]
Hanania, N.A.; Wenzel, S.; Rosén, K.; Hsieh, H.J.; Mosesova, 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].
[60]
Hanania, N.A.; Alpan, O.; Hamilos, D.L.; Condemi, J.J.; Reyes-Rivera, I.; Zhu, J.; Rosen, K.E.; Eisner, M.D.; Wong, D.A.; Busse, W. Omalizumab in severe allergic asthma inadequately controlled with standard therapy: a randomized trial. Ann. Intern. Med., 2011, 154(9), 573-582. [http://dx.doi.org/10.7326/0003-4819-154-9-201105030-00002]. [PMID: 21536936].
[61]
Bousquet, J.; Cabrera, P.; Berkman, N.; Buhl, R.; Holgate, S.; Wenzel, S.; Fox, H.; Hedgecock, S.; Blogg, M.; Cioppa, G.D. The effect of treatment with omalizumab, an anti-IgE antibody, on asthma exacerbations and emergency medical visits in patients with severe persistent asthma. Allergy, 2005, 60(3), 302-308. [http://dx.doi.org/10.1111/j.1398-9995.2004.00770.x]. [PMID: 15679714].
[62]
Garcia, G.; Magnan, A.; Chiron, R.; Contin-Bordes, C.; Berger, P.; Taillé, C.; Devouassoux, G.; de Blay, F.; Couderc, L.J.; Didier, A.; O’Callaghan, D.S.; Girodet, P.O.; Bourdeix, I.; Le Gros, V.; Humbert, M. A proof-of-concept, randomized, controlled trial of omalizumab in patients with severe, difficult-to-control, nonatopic asthma. Chest, 2013, 144(2), 411-419. [http://dx.doi.org/10.1378/chest.12-1961]. [PMID: 23579324].
[63]
Shimizu, Y.; Dobashi, K.; Fueki, N.; Fueki, M.; Okada, T.; Tomioka, S.; Makino, S.; Mori, M. Changes of immunomodulatory cytokines associated with omalizumab therapy for severe persistent asthma. J. Biol. Regul. Homeost. Agents, 2011, 25(2), 177-186. [PMID: 21880206].
[64]
Tajiri, T.; Matsumoto, H.; Gon, Y.; Ito, R.; Hashimoto, S.; Izuhara, K.; Suzukawa, M.; Ohta, K.; Ono, J.; Ohta, S.; Ito, I.; Oguma, T.; Inoue, H.; Iwata, T.; Kanemitsu, Y.; Nagasaki, T.; Niimi, A.; Mishima, M. Utility of serum periostin and free IgE levels in evaluating responsiveness to omalizumab in patients with severe asthma. Allergy, 2016, 71(10), 1472-1479. [http://dx.doi.org/10.1111/all.12922]. [PMID: 27113353].
[65]
Jensen-Jarolim, E.; Bax, H.J.; Bianchini, R.; Capron, M.; Corrigan, C.; Castells, M.; Dombrowicz, D.; Daniels-Wells, T.R.; Fazekas, J.; Fiebiger, E.; Gatault, S.; Gould, H.J.; Janda, J.; Josephs, D.H.; Karagiannis, P.; Levi-Schaffer, F.; Meshcheryakova, A.; Mechtcheriakova, D.; Mekori, Y.; Mungenast, F.; Nigro, E.A.; Penichet, M.L.; Redegeld, F.; Saul, L.; Singer, J.; Spicer, J.F.; Siccardi, A.G.; Spillner, E.; Turner, M.C.; Untersmayr, E.; Vangelista, L.; Karagiannis, S.N. AllergoOncology - the impact of allergy in oncology: EAACI position paper. Allergy, 2017, 72(6), 866-887. [http://dx.doi.org/10.1111/all.13119]. [PMID: 28032353].
[66]
Busse, W.; Buhl, R.; Fernandez Vidaurre, C.; Blogg, M.; Zhu, J.; Eisner, M. D.; Canvin, J. Omalizumab and the risk of malignancy: Results from a pooled analysis J Allergy Clin Immunol, 2012, 129, 983-989- e6. http://dx.doi.org/10.1016/j.jaci.2012.01.033] [PMID: 22365654]
[67]
Long, A.; Rahmaoui, A.; Rothman, K. J.; Guinan, E.; Eisner, M.; Bradley, M. S.; Iribarren, C.; Chen, H.; Carrigan, G.; Rosen, K.; Szefler, S. J. Incidence of malignancy in patients with moderate-to-severe asthma treated with or without omalizumab. J Allergy Clin Immunol,, 2014, 134, 560- 567- e4. [http://dx.doi.org/10.1016/j.jaci.2014.02.007] [PMID: 7 24679845]
[68]
Namazy, J.; Cabana, M.D.; Scheuerle, A.E.; Thorp, J.M., Jr; Chen, H.; Carrigan, G.; Wang, Y.; Veith, J.; Andrews, E.B. The Xolair Pregnancy Registry (EXPECT): the safety of omalizumab use during pregnancy. J. Allergy Clin. Immunol., 2015, 135(2), 407-412. [http://dx.doi.org/10.1016/j.jaci.2014.08.025]. [PMID: 25441639].
[69]
Iribarren, C.; Rahmaoui, A.; Long, A. A.; Szefler, S. J.; Bradley, M. S.; Carrigan, G.; Eisner, M. D.; Chen, H.; Omachi, T. A.; Farkouh, M. E.; Rothman, K. J. Cardiovascular and cerebrovascular events among patients receiving omalizumab: Results from EXCELS, a prospective cohort study in moderate to severe asthma. J. Allergy Clin. Immunol, 2017, 139, 1489-1495- e5. [http://dx.doi.org/10.1016/j.jaci.2016.07.038] [PMID: 27639934]
[70]
Hamid, Q.; Azzawi, M.; Ying, S.; Moqbel, R.; Wardlaw, A.J.; Corrigan, C.J.; Bradley, B.; Durham, S.R.; Collins, J.V.; Jeffery, P.K. Expression of mRNA for interleukin-5 in mucosal bronchial biopsies from asthma. J. Clin. Invest., 1991, 87(5), 1541-1546. [http://dx.doi.org/10.1172/JCI115166]. [PMID: 2022726].
[71]
Robinson, D.; Hamid, Q.; Bentley, A.; Ying, S.; Kay, A.B.; Durham, S.R. Activation of CD4+ T cells, increased TH2-type cytokine mRNA expression, and eosinophil recruitment in bronchoalveolar lavage after allergen inhalation challenge in patients with atopic asthma. J. Allergy Clin. Immunol., 1993, 92(2), 313-324. [http://dx.doi.org/10.1016/0091-6749(93)90175-F]. [PMID: 8349942].
[72]
Broughton, S.E.; Nero, T.L.; Dhagat, U.; Kan, W.L.; Hercus, T.R.; Tvorogov, D.; Lopez, A.F.; Parker, M.W. The βc receptor family - Structural insights and their functional implications. Cytokine, 2015, 74(2), 247-258. [http://dx.doi.org/10.1016/j.cyto.2015.02.005]. [PMID: 25982846].
[73]
Humbert, M.; Corrigan, C.J.; Kimmitt, P.; Till, S.J.; Kay, A.B.; Durham, S.R. Relationship between IL-4 and IL-5 mRNA expression and disease severity in atopic asthma. Am. J. Respir. Crit. Care Med., 1997, 156(3 Pt 1), 704-708. [http://dx.doi.org/10.1164/ajrccm.156.3.9610033]. [PMID: 9309982].
[74]
Rosas, M.; Dijkers, P.F.; Lindemans, C.L.; Lammers, J.W.; Koenderman, L.; Coffer, P.J. IL-5-mediated eosinophil survival requires inhibition of GSK-3 and correlates with beta-catenin relocalization. J. Leukoc. Biol., 2006, 80, 186-195. [http://dx.doi.org/10.1189/jlb.1105636]. [PMID: 16684889].
[75]
Kolbeck, R.; Kozhich, A.; Koike, M.; Peng, L.; Andersson, C.K.; Damschroder, M.M.; Reed, J.L.; Woods, R.; Dall'acqua, W.W.; Stephens, G.L.; Erjefalt, J.S.; Bjermer, L.; Humbles, A. A.; Gossage, D.; Wu, H.; Kiener, P.A.; Spitalny, G.L.; Mackay, C.R.; Molfino, N.A.; Coyle, A.J. MEDI-563, a humanized anti-IL-5 receptor alpha mAb with enhanced antibody-dependent cell-mediated cytotoxicity function J Allergy Clin Immunol, 2010, 125, 1344-1353- e2. [http://dx.doi.org/10.1016/j.jaci.2010.04.004] [PMID: 20513525]
[76]
Phillips, C.; Coward, W.R.; Pritchard, D.I.; Hewitt, C.R. Basophils express a type 2 cytokine profile on exposure to proteases from helminths and house dust mites. J. Leukoc. Biol., 2003, 73(1), 165-171. [http://dx.doi.org/10.1189/jlb.0702356]. [PMID: 12525574].
[77]
Fallon, P.G.; Ballantyne, S.J.; Mangan, N.E.; Barlow, J.L.; Dasvarma, A.; Hewett, D.R.; McIlgorm, A.; Jolin, H.E.; McKenzie, A.N. Identification of an interleukin (IL)-25-dependent cell population that provides IL-4, IL-5, and IL-13 at the onset of helminth expulsion. J. Exp. Med., 2006, 203(4), 1105-1116. [http://dx.doi.org/10.1084/jem.20051615]. [PMID: 16606668].
[78]
Nussbaum, J.C.; Van Dyken, S.J.; von Moltke, J.; Cheng, L.E.; Mohapatra, A.; Molofsky, A.B.; Thornton, E.E.; Krummel, M.F.; Chawla, A.; Liang, H.E.; Locksley, R.M. Type 2 innate lymphoid cells control eosinophil homeostasis. Nature, 2013, 502(7470), 245-248. [http://dx.doi.org/10.1038/nature12526]. [PMID: 24037376].
[79]
Shahabuddin, S.; Ponath, P.; Schleimer, R.P. Migration of eosinophils across endothelial cell monolayers: interactions among IL-5, endothelial-activating cytokines, and C-C chemokines. J. Immunol., 2000, 164(7), 3847-3854. [http://dx.doi.org/10.4049/jimmunol.164.7.3847]. [PMID: 10725746].
[80]
Ochiai, K.; Kagami, M.; Matsumura, R.; Tomioka, H. IL-5 but not interferon-gamma (IFN-gamma) inhibits eosinophil apoptosis by up-regulation of bcl-2 expression. Clin. Exp. Immunol., 1997, 107(1), 198-204. [http://dx.doi.org/10.1046/j.1365-2249.1997.d01-884.x]. [PMID: 9010276].
[81]
Kita, H. Eosinophils: multifaceted biological properties and roles in health and disease. Immunol. Rev., 2011, 242(1), 161-177. [http://dx.doi.org/10.1111/j.1600-065X.2011.01026.x]. [PMID: 21682744].
[82]
Rosenberg, H.F.; Dyer, K.D.; Foster, P.S. Eosinophils: changing perspectives in health and disease. Nat. Rev. Immunol., 2013, 13(1), 9-22. [http://dx.doi.org/10.1038/nri3341]. [PMID: 23154224].
[83]
Nissim Ben Efraim, A.H.; Levi-Schaffer, F. Roles of eosinophils in the modulation of angiogenesis. Chem. Immunol. Allergy, 2014, 99, 138-154. [http://dx.doi.org/10.1159/000353251]. [PMID: 24217607].
[84]
Galdiero, M.R.; Varricchi, G.; Seaf, M.; Marone, G.; Levi-Schaffer, F.; Marone, G. Bidirectional mast cell - eosinophil Interactions in inflammatory disorders and cancer. Front. Med. (Lausanne), 2017, 4, 103. [http://dx.doi.org/10.3389/fmed.2017.00103]. [PMID: 28791287].
[85]
Klion, A.D.; Nutman, T.B. The role of eosinophils in host defense against helminth parasites. J. Allergy Clin. Immunol., 2004, 113(1), 30-37. [http://dx.doi.org/10.1016/j.jaci.2003.10.050]. [PMID: 14713904].
[86]
Wu, D.; Molofsky, A.B.; Liang, H.E.; Ricardo-Gonzalez, R.R.; Jouihan, H.A.; Bando, J.K.; Chawla, A.; Locksley, R.M. Eosinophils sustain adipose alternatively activated macrophages associated with glucose homeostasis. Science, 2011, 332(6026), 243-247. [http://dx.doi.org/10.1126/science.1201475]. [PMID: 21436399].
[87]
Bochner, B.S. Novel Therapies for Eosinophilic Disorders. Immunol. Allergy Clin. North Am., 2015, 35(3), 577-598. [http://dx.doi.org/10.1016/j.iac.2015.05.007]. [PMID: 26209901].
[88]
Chu, V.T.; Fröhlich, A.; Steinhauser, G.; Scheel, T.; Roch, T.; Fillatreau, S.; Lee, J.J.; Löhning, M.; Berek, C. Eosinophils are required for the maintenance of plasma cells in the bone marrow. Nat. Immunol., 2011, 12(2), 151-159. [http://dx.doi.org/10.1038/ni.1981]. [PMID: 21217761].
[89]
Patella, V.; de Crescenzo, G.; Marinò, I.; Genovese, A.; Adt, M.; Gleich, G.J.; Marone, G. Eosinophil granule proteins activate human heart mast cells. J. Immunol., 1996, 157(3), 1219-1225. [PMID: 8757629].
[90]
Varricchi, G.; Harker, J.; Borriello, F.; Marone, G.; Durham, S.R.; Shamji, M.H. T follicular helper (Tfh) cells in normal immune responses and in allergic disorders. Allergy, 2016, 71(8), 1086-1094. [http://dx.doi.org/10.1111/all.12878]. [PMID: 26970097].
[91]
Bel, E.H.; Wenzel, S.E.; Thompson, P.J.; Prazma, C.M.; Keene, O.N.; Yancey, S.W.; Ortega, H.G.; Pavord, I.D. Oral glucocorticoid-sparing effect of mepolizumab in eosinophilic asthma. N. Engl. J. Med., 2014, 371(13), 1189-1197. [http://dx.doi.org/10.1056/NEJMoa1403291]. [PMID: 25199060].
[92]
Castro, M.; Mathur, S.; Hargreave, F.; Boulet, L.P.; Xie, F.; Young, J.; Wilkins, H.J.; Henkel, T.; Nair, P. Reslizumab for poorly controlled, eosinophilic asthma: a randomized, placebo-controlled study. Am. J. Respir. Crit. Care Med., 2011, 184(10), 1125-1132. [http://dx.doi.org/10.1164/rccm.201103-0396OC]. [PMID: 21852542].
[93]
Haldar, P.; Brightling, C.E.; Hargadon, B.; Gupta, S.; Monteiro, W.; Sousa, A.; Marshall, R.P.; Bradding, P.; Green, R.H.; Wardlaw, A.J.; Pavord, I.D. Mepolizumab and exacerbations of refractory eosinophilic asthma. N. Engl. J. Med., 2009, 360(10), 973-984. [http://dx.doi.org/10.1056/NEJMoa0808991]. [PMID: 19264686].
[94]
Kips, J.C.; O’Connor, B.J.; Langley, S.J.; Woodcock, A.; Kerstjens, H.A.; Postma, D.S.; Danzig, M.; Cuss, F.; Pauwels, R.A. Effect of SCH55700, a humanized anti-human interleukin-5 antibody, in severe persistent asthma: a pilot study. Am. J. Respir. Crit. Care Med., 2003, 167(12), 1655-1659. [http://dx.doi.org/10.1164/rccm.200206-525OC]. [PMID: 12649124].
[95]
Nair, P.; Pizzichini, M.M.; Kjarsgaard, M.; Inman, M.D.; Efthimiadis, A.; Pizzichini, E.; Hargreave, F.E.; O’Byrne, P.M. Mepolizumab for prednisone-dependent asthma with sputum eosinophilia. N. Engl. J. Med., 2009, 360(10), 985-993. [http://dx.doi.org/10.1056/NEJMoa0805435]. [PMID: 19264687].
[96]
Ortega, H.G.; Liu, M.C.; Pavord, I.D.; Brusselle, G.G.; FitzGerald, J.M.; Chetta, A.; Humbert, M.; Katz, L.E.; Keene, O.N.; Yancey, S.W.; Chanez, P. Mepolizumab treatment in patients with severe eosinophilic asthma. N. Engl. J. Med., 2014, 371(13), 1198-1207. [http://dx.doi.org/10.1056/NEJMoa1403290]. [PMID: 25199059].
[97]
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].
[98]
Varricchi, G.; Bagnasco, D.; Ferrando, M.; Puggioni, F.; Passalacqua, G.; Canonica, G.W. Mepolizumab in the management of severe eosinophilic asthma in adults: current evidence and practical experience. Ther. Adv. Respir. Dis., 2017, 11(1), 40-45. [http://dx.doi.org/10.1177/1753465816673303]. [PMID: 27856823].
[99]
Flood-Page, P.T.; Menzies-Gow, A.N.; Kay, A.B.; Robinson, D.S. Eosinophil’s role remains uncertain as anti-interleukin-5 only partially depletes numbers in asthmatic airway. Am. J. Respir. Crit. Care Med., 2003, 167(2), 199-204. [http://dx.doi.org/10.1164/rccm.200208-789OC]. [PMID: 12406833].
[100]
Basu, A.; Dalal, A.A.; Canonica, G.W. The use of mepolizumab: healthcare resources and costs versus placebo in a clinical trial setting. Value Health, 2015.
[101]
Haldar, P.; Brightling, C.E.; Singapuri, A.; Hargadon, B.; Gupta, S.; Monteiro, W.; Bradding, P.; Green, R.H.; Wardlaw, A.J.; Ortega, H.; Pavord, I.D. Outcomes after cessation of mepolizumab therapy in severe eosinophilic asthma: a 12-month follow-up analysis. J. Allergy Clin. Immunol., 2014, 133(3), 921-923. [http://dx.doi.org/10.1016/j.jaci.2013.11.026]. [PMID: 24418480].
[102]
Corren, J.; Shapiro, G.; Reimann, J.; Deniz, Y.; Wong, D.; Adelman, D.; Togias, A. Allergen skin tests and free IgE levels during reduction and cessation of omalizumab therapy. J. Allergy Clin. Immunol., 2008, 121(2), 506-511. [http://dx.doi.org/10.1016/j.jaci.2007.11.026]. [PMID: 18269927].
[103]
Kupryś-Lipińska, I.; Kuna, P. Loss of asthma control after cessation of omalizumab treatment: real life data. Postepy Dermatol. Alergol., 2014, 31(1), 1-5. [http://dx.doi.org/10.5114/pdia.2014.40553]. [PMID: 24683390].
[104]
Gevaert, P.; Lang-Loidolt, D.; Lackner, A.; Stammberger, H.; Staudinger, H.; Van Zele, T.; Holtappels, G.; Tavernier, J.; van Cauwenberge, P.; Bachert, C. Nasal IL-5 levels determine the response to anti-IL-5 treatment in patients with nasal polyps. J. Allergy Clin. Immunol., 2006, 118(5), 1133-1141. [http://dx.doi.org/10.1016/j.jaci.2006.05.031]. [PMID: 17088140].
[105]
Wang, Y.H.; Liu, Y.J. Thymic stromal lymphopoietin, OX40-ligand, and interleukin-25 in allergic responses. Clin. Exp. Allergy, 2009, 39(6), 798-806. [http://dx.doi.org/10.1111/j.1365-2222.2009.03241.x]. [PMID: 19400908].
[106]
Bjermer, L.; Lemiere, C.; Maspero, J.; Weiss, S.; Zangrilli, J.; Germinaro, M. Reslizumab for inadequately controlled asthma with elevated blood eosinophil levels: a randomized phase 3 study. Chest, 2016, 150(4), 789-798. [http://dx.doi.org/10.1016/j.chest.2016.03.032]. [PMID: 27056586].
[107]
Castro, M.; Zangrilli, J.; Wechsler, M.E.; Bateman, E.D.; Brusselle, G.G.; Bardin, P.; Murphy, K.; Maspero, J.F.; O’Brien, C.; Korn, S. Reslizumab for inadequately controlled asthma with elevated blood eosinophil counts: results from two multicentre, parallel, double-blind, randomised, placebo-controlled, phase 3 trials. Lancet Respir. Med., 2015, 3(5), 355-366. [http://dx.doi.org/10.1016/S2213-2600(15)00042-9]. [PMID: 25736990].
[108]
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].
[109]
Busse, W.W.; Katial, R.; Gossage, D.; Sari, S.; Wang, B.; Kolbeck, R.; Coyle, A.J.; Koike, M.; Spitalny, G.L.; Kiener, P.A.; Geba, G.P.; Molfino, N.A. Safety profile, pharmacokinetics, and biologic activity of MEDI-563, an anti-IL-5 receptor alpha antibody, in a phase I study of subjects with mild asthma. J Allergy Clin Immunol,, 2010, 125, 1237- 1244- e2. [http://dx.doi.org/10.1016/j.jaci.2010.04.005] [PMID: 20513521]
[110]
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 benralizumab on airway eosinophils in asthmatic patients with sputum eosinophilia. J Allergy Clin Immunol,, 2013, 132, 1086-1096- e5. [http://dx.doi.org/10.1016/j.jaci.2013.05.020] [PMID: 23866823]
[111]
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].
[112]
Bleecker, E.R.; FitzGerald, J.M.; Chanez, P.; Papi, A.; Weinstein, S.F.; Barker, P.; Sproule, S.; Gilmartin, G.; Aurivillius, M.; Werkström, V.; Goldman, M. Efficacy and safety of benralizumab for patients with severe asthma uncontrolled with high-dosage inhaled corticosteroids and long-acting β2-agonists (SIROCCO): a randomised, multicentre, placebo-controlled phase 3 trial. Lancet, 2016, 388(10056), 2115-2127. [http://dx.doi.org/10.1016/S0140-6736(16)31324-1]. [PMID: 27609408].
[113]
Nair, P.; Wenzel, S.; Rabe, K.F.; Bourdin, A.; Lugogo, N.L.; Kuna, P.; Barker, P.; Sproule, S.; Ponnarambil, S.; Goldman, M. Oral glucocorticoid-sparing effect of benralizumab in severe asthma. N. Engl. J. Med., 2017, 376(25), 2448-2458. [http://dx.doi.org/10.1056/NEJMoa1703501]. [PMID: 28530840].
[114]
Nowak, R.M.; Parker, J.M.; Silverman, R.A.; Rowe, B.H.; Smithline, H.; Khan, F.; Fiening, J.P.; Kim, K.; Molfino, N.A. A randomized trial of benralizumab, an antiinterleukin 5 receptor α monoclonal antibody, after acute asthma. Am. J. Emerg. Med., 2015, 33(1), 14-20. [http://dx.doi.org/10.1016/j.ajem.2014.09.036]. [PMID: 25445859].
[115]
Brooks, C.R.; van Dalen, C.J.; Hermans, I.F.; Gibson, P.G.; Simpson, J.L.; Douwes, J. Sputum basophils are increased in eosinophilic asthma compared with non-eosinophilic asthma phenotypes. Allergy, 2017, 72(10), 1583-1586. [http://dx.doi.org/10.1111/all.13185]. [PMID: 28426171].
[116]
Suzuki, Y.; Wakahara, K.; Nishio, T.; Ito, S.; Hasegawa, Y. Airway basophils are increased and activated in eosinophilic asthma. Allergy, 2017, 72(10), 1532-1539. [http://dx.doi.org/10.1111/all.13197]. [PMID: 28474352].
[117]
Anderson, W.C., III; Szefler, S.J. New and future strategies to improve asthma control in children. J. Allergy Clin. Immunol., 2015, 136(4), 848-859. [http://dx.doi.org/10.1016/j.jaci.2015.07.007]. [PMID: 26318072].
[118]
Marone, G.; Galli, S.J.; Kitamura, Y. Probing the roles of mast cells and basophils in natural and acquired immunity, physiology and disease. Trends Immunol., 2002, 23(9), 425-427. [http://dx.doi.org/10.1016/S1471-4906(02)02274-3]. [PMID: 12200056].
[119]
Varricchi, G.; Granata, F.; Loffredo, S.; Genovese, A.; Marone, G. Angiogenesis and lymphangiogenesis in inflammatory skin disorders. J. Am. Acad. Dermatol., 2015, 73(1), 144-153. [http://dx.doi.org/10.1016/j.jaad.2015.03.041]. [PMID: 25922287].
[120]
Palm, N.W.; Rosenstein, R.K.; Medzhitov, R. Allergic host defences. Nature, 2012, 484(7395), 465-472. [http://dx.doi.org/10.1038/nature11047]. [PMID: 22538607].
[121]
Marone, G.; Varricchi, G.; Loffredo, S.; Galdiero, M.R.; Rivellese, F.; de Paulis, A. Are Basophils and Mast Cells Masters in HIV Infection? Int. Arch. Allergy Immunol., 2016, 171(3-4), 158-165. [http://dx.doi.org/10.1159/000452889]. [PMID: 27960171].
[122]
de Vries, J.E. The role of IL-13 and its receptor in allergy and inflammatory responses. J. Allergy Clin. Immunol., 1998, 102(2), 165-169. [http://dx.doi.org/10.1016/S0091-6749(98)70080-6]. [PMID: 9723655].
[123]
Hajoui, O.; Janani, R.; Tulic, M.; Joubert, P.; Ronis, T.; Hamid, Q.; Zheng, H.; Mazer, B.D. Synthesis of IL-13 by human B lymphocytes: regulation and role in IgE production. J. Allergy Clin. Immunol., 2004, 114(3), 657-663. [http://dx.doi.org/10.1016/j.jaci.2004.05.034]. [PMID: 15356573].
[124]
Dakhama, A.; Collins, M.L.; Ohnishi, H.; Goleva, E.; Leung, D.Y.; Alam, R.; Sutherland, E.R.; Martin, R.J.; Gelfand, E.W. IL-13-producing BLT1-positive CD8 cells are increased in asthma and are associated with airway obstruction. Allergy, 2013, 68(5), 666-673. [http://dx.doi.org/10.1111/all.12135]. [PMID: 23573812].
[125]
Jia, Y.; Fang, X.; Zhu, X.; Bai, C.; Zhu, L.; Jin, M.; Wang, X.; Hu, M.; Tang, R.; Chen, Z. IL-13+ Type 2 Innate Lymphoid Cells Correlate with Asthma Control Status and Treatment Response. Am. J. Respir. Cell Mol. Biol., 2016, 55(5), 675-683. [http://dx.doi.org/10.1165/rcmb.2016-0099OC]. [PMID: 27314535].
[126]
Hancock, A.; Armstrong, L.; Gama, R.; Millar, A. Production of interleukin 13 by alveolar macrophages from normal and fibrotic lung. Am. J. Respir. Cell Mol. Biol., 1998, 18(1), 60-65. [http://dx.doi.org/10.1165/ajrcmb.18.1.2627]. [PMID: 9448046].
[127]
Fushimi, T.; Okayama, H.; Shimura, S.; Saitoh, H.; Shirato, K. Dexamethasone suppresses gene expression and production of IL-13 by human mast cell line and lung mast cells. J. Allergy Clin. Immunol., 1998, 102(1), 134-142. [http://dx.doi.org/10.1016/S0091-6749(98)70064-8]. [PMID: 9679857].
[128]
Ochensberger, B.; Daepp, G.C.; Rihs, S.; Dahinden, C.A. Human blood basophils produce interleukin-13 in response to IgE-receptor-dependent and -independent activation. Blood, 1996, 88(8), 3028-3037. [PMID: 8874201].
[129]
Redrup, A.C.; Howard, B.P.; MacGlashan, D.W., Jr; Kagey-Sobotka, A.; Lichtenstein, L.M.; Schroeder, J.T. Differential regulation of IL-4 and IL-13 secretion by human basophils: their relationship to histamine release in mixed leukocyte cultures. J. Immunol., 1998, 160(4), 1957-1964. [PMID: 9469459].
[130]
Borriello, F.; Longo, M.; Spinelli, R.; Pecoraro, A.; Granata, F.; Staiano, R.I.; Loffredo, S.; Spadaro, G.; Beguinot, F.; Schroeder, J.; Marone, G. IL-3 synergises with basophil-derived IL-4 and IL-13 to promote the alternative activation of human monocytes. Eur. J. Immunol., 2015, 45(7), 2042-2051. [http://dx.doi.org/10.1002/eji.201445303]. [PMID: 25824485].
[131]
Akaiwa, M.; Yu, B.; Umeshita-Suyama, R.; Terada, N.; Suto, H.; Koga, T.; Arima, K.; Matsushita, S.; Saito, H.; Ogawa, H.; Furue, M.; Hamasaki, N.; Ohshima, K.; Izuhara, K. Localization of human interleukin 13 receptor in non-haematopoietic cells. Cytokine, 2001, 13(2), 75-84. [http://dx.doi.org/10.1006/cyto.2000.0814]. [PMID: 11145846].
[132]
McKenzie, G.J.; Fallon, P.G.; Emson, C.L.; Grencis, R.K.; McKenzie, A.N. Simultaneous disruption of interleukin (IL)-4 and IL-13 defines individual roles in T helper cell type 2-mediated responses. J. Exp. Med., 1999, 189(10), 1565-1572. [http://dx.doi.org/10.1084/jem.189.10.1565]. [PMID: 10330435].
[133]
LaPorte, S.L.; Juo, Z.S.; Vaclavikova, J.; Colf, L.A.; Qi, X.; Heller, N.M.; Keegan, A.D.; Garcia, K.C. Molecular and structural basis of cytokine receptor pleiotropy in the interleukin-4/13 system. Cell, 2008, 132(2), 259-272. [http://dx.doi.org/10.1016/j.cell.2007.12.030]. [PMID: 18243101].
[134]
Wynn, T.A. Type 2 cytokines: mechanisms and therapeutic strategies. Nat. Rev. Immunol., 2015, 15(5), 271-282. [http://dx.doi.org/10.1038/nri3831]. [PMID: 25882242].
[135]
Chatila, T.A. Interleukin-4 receptor signaling pathways in asthma pathogenesis. Trends Mol. Med., 2004, 10(10), 493-499. [http://dx.doi.org/10.1016/j.molmed.2004.08.004]. [PMID: 15464449].
[136]
Gour, N.; Wills-Karp, M. IL-4 and IL-13 signaling in allergic airway disease. Cytokine, 2015, 75(1), 68-78. [http://dx.doi.org/10.1016/j.cyto.2015.05.014]. [PMID: 26070934].
[137]
Chen, W.; Sivaprasad, U.; Tabata, Y.; Gibson, A.M.; Stier, M.T.; Finkelman, F.D.; Hershey, G.K. IL-13R alpha 2 membrane and soluble isoforms differ in humans and mice. J. Immunol., 2009, 183(12), 7870-7876. [http://dx.doi.org/10.4049/jimmunol.0901028]. [PMID: 20007572].
[138]
Ingram, J.L.; Kraft, M. IL-13 in asthma and allergic disease: asthma phenotypes and targeted therapies. J. Allergy Clin. Immunol., 2012, 130(4), 829-842. [http://dx.doi.org/10.1016/j.jaci.2012.06.034]. [PMID: 22951057].
[139]
Kasaian, M.T.; Raible, D.; Marquette, K.; Cook, T.A.; Zhou, S.; Tan, X.Y.; Tchistiakova, L. IL-13 antibodies influence IL-13 clearance in humans by modulating scavenger activity of IL-13Rα2. J. Immunol., 2011, 187(1), 561-569. [http://dx.doi.org/10.4049/jimmunol.1100467]. [PMID: 21622864].
[140]
Fichtner-Feigl, S.; Strober, W.; Kawakami, K.; Puri, R.K.; Kitani, A. IL-13 signaling through the IL-13alpha2 receptor is involved in induction of TGF-beta1 production and fibrosis. Nat. Med., 2006, 12(1), 99-106. [http://dx.doi.org/10.1038/nm1332]. [PMID: 16327802].
[141]
Fujisawa, T.; Joshi, B.; Nakajima, A.; Puri, R.K. A novel role of interleukin-13 receptor alpha2 in pancreatic cancer invasion and metastasis. Cancer Res., 2009, 69(22), 8678-8685. [http://dx.doi.org/10.1158/0008-5472.CAN-09-2100]. [PMID: 19887609].
[142]
He, C.H.; Lee, C.G.; Dela Cruz, C.S.; Lee, C.M.; Zhou, Y.; Ahangari, F.; Ma, B.; Herzog, E.L.; Rosenberg, S.A.; Li, Y.; Nour, A.M.; Parikh, C.R.; Schmidt, I.; Modis, Y.; Cantley, L.; Elias, J.A. Chitinase 3-like 1 regulates cellular and tissue responses via IL-13 receptor α2. Cell Rep., 2013, 4(4), 830-841. [http://dx.doi.org/10.1016/j.celrep.2013.07.032]. [PMID: 23972995].
[143]
Oettgen, H.C.; Geha, R.S. IgE regulation and roles in asthma pathogenesis. J. Allergy Clin. Immunol., 2001, 107(3), 429-440. [http://dx.doi.org/10.1067/mai.2001.113759]. [PMID: 11240941].
[144]
Punnonen, J.; Aversa, G.; Cocks, B.G.; McKenzie, A.N.; Menon, S.; Zurawski, G.; de Waal Malefyt, R.; de Vries, J.E. Interleukin 13 induces interleukin 4-independent IgG4 and IgE synthesis and CD23 expression by human B cells. Proc. Natl. Acad. Sci. USA, 1993, 90(8), 3730-3734. [http://dx.doi.org/10.1073/pnas.90.8.3730]. [PMID: 8097323].
[145]
Gould, H.J.; Sutton, B.J. IgE in allergy and asthma today. Nat. Rev. Immunol., 2008, 8(3), 205-217. [http://dx.doi.org/10.1038/nri2273]. [PMID: 18301424].
[146]
Horie, S.; Okubo, Y.; Hossain, M.; Sato, E.; Nomura, H.; Koyama, S.; Suzuki, J.; Isobe, M.; Sekiguchi, M. Interleukin-13 but not interleukin-4 prolongs eosinophil survival and induces eosinophil chemotaxis. Intern. Med., 1997, 36(3), 179-185. [http://dx.doi.org/10.2169/internalmedicine.36.179]. [PMID: 9144009].
[147]
Luttmann, W.; Knoechel, B.; Foerster, M.; Matthys, H.; Virchow, J.C., Jr; Kroegel, C. Activation of human eosinophils by IL-13. Induction of CD69 surface antigen, its relationship to messenger RNA expression, and promotion of cellular viability. J. Immunol., 1996, 157(4), 1678-1683. [PMID: 8759755].
[148]
Pope, S.M.; Brandt, E.B.; Mishra, A.; Hogan, S.P.; Zimmermann, N.; Matthaei, K.I.; Foster, P.S.; Rothenberg, M.E. IL-13 induces eosinophil recruitment into the lung by an IL-5- and eotaxin-dependent mechanism. J. Allergy Clin. Immunol., 2001, 108(4), 594-601. [http://dx.doi.org/10.1067/mai.2001.118600]. [PMID: 11590387].
[149]
Bochner, B.S.; Klunk, D.A.; Sterbinsky, S.A.; Coffman, R.L.; Schleimer, R.P. IL-13 selectively induces vascular cell adhesion molecule-1 expression in human endothelial cells. J. Immunol., 1995, 154(2), 799-803. [PMID: 7529288].
[150]
Rosenberg, H.F.; Phipps, S.; Foster, P.S. Eosinophil trafficking in allergy and asthma. J. Allergy Clin. Immunol., 2007, 119(6), 1303-1310. [http://dx.doi.org/10.1016/j.jaci.2007.03.048]. [PMID: 17481712].
[151]
Webb, D.C.; McKenzie, A.N.; Koskinen, A.M.; Yang, M.; Mattes, J.; Foster, P.S. Integrated signals between IL-13, IL-4, and IL-5 regulate airways hyperreactivity. J. Immunol., 2000, 165(1), 108-113. [http://dx.doi.org/10.4049/jimmunol.165.1.108]. [PMID: 10861042].
[152]
Nilsson, G.; Nilsson, K. Effects of interleukin (IL)-13 on immediate-early response gene expression, phenotype and differentiation of human mast cells. Comparison with IL-4. Eur. J. Immunol., 1995, 25(3), 870-873. [http://dx.doi.org/10.1002/eji.1830250337]. [PMID: 7705421].
[153]
Kaur, D.; Hollins, F.; Woodman, L.; Yang, W.; Monk, P.; May, R.; Bradding, P.; Brightling, C.E. Mast cells express IL-13R alpha 1: IL-13 promotes human lung mast cell proliferation and Fc epsilon RI expression. Allergy, 2006, 61(9), 1047-1053. [http://dx.doi.org/10.1111/j.1398-9995.2006.01139.x]. [PMID: 16918506].
[154]
Wills-Karp, M. IL-12/IL-13 axis in allergic asthma. J. Allergy Clin. Immunol., 2001, 107(1), 9-18. [http://dx.doi.org/10.1067/mai.2001.112265]. [PMID: 11149983].
[155]
Doucet, C.; Brouty-Boyé, D.; Pottin-Clémenceau, C.; Canonica, G.W.; Jasmin, C.; Azzarone, B. Interleukin (IL) 4 and IL-13 act on human lung fibroblasts. Implication in asthma. J. Clin. Invest., 1998, 101(10), 2129-2139. [http://dx.doi.org/10.1172/JCI741]. [PMID: 9593769].
[156]
Kuperman, D.A.; Huang, X.; Koth, L.L.; Chang, G.H.; Dolganov, G.M.; Zhu, Z.; Elias, J.A.; Sheppard, D.; Erle, D.J. Direct effects of interleukin-13 on epithelial cells cause airway hyperreactivity and mucus overproduction in asthma. Nat. Med., 2002, 8(8), 885-889. [http://dx.doi.org/10.1038/nm734]. [PMID: 12091879].
[157]
Kondo, M.; Tamaoki, J.; Takeyama, K.; Isono, K.; Kawatani, K.; Izumo, T.; Nagai, A. Elimination of IL-13 reverses established goblet cell metaplasia into ciliated epithelia in airway epithelial cell culture. Allergol. Int., 2006, 55(3), 329-336. [http://dx.doi.org/10.2332/allergolint.55.329]. [PMID: 17075276].
[158]
Corne, J.; Chupp, G.; Lee, C.G.; Homer, R.J.; Zhu, Z.; Chen, Q.; Ma, B.; Du, Y.; Roux, F.; McArdle, J.; Waxman, A.B.; Elias, J.A. IL-13 stimulates vascular endothelial cell growth factor and protects against hyperoxic acute lung injury. J. Clin. Invest., 2000, 106(6), 783-791. [http://dx.doi.org/10.1172/JCI9674]. [PMID: 10995789].
[159]
Detoraki, A.; Staiano, R.I.; Granata, F.; Giannattasio, G.; Prevete, N.; de Paulis, A.; Ribatti, D.; Genovese, A.; Triggiani, M.; Marone, G. Vascular endothelial growth factors synthesized by human lung mast cells exert angiogenic effects. J. Allergy Clin. Immunol, 2009, 123 1142-9-1149. , e1-5.
[http://dx.doi.org/10.1016/j.jaci.2009.01.044]
[160]
Detoraki, A.; Granata, F.; Staibano, S.; Rossi, F.W.; Marone, G.; Genovese, A. Angiogenesis and lymphangiogenesis in bronchial asthma. Allergy, 2010, 65(8), 946-958. [http://dx.doi.org/10.1111/j.1398-9995.2010.02372.x]. [PMID: 20415716].
[161]
Wong, C.K.; Ho, C.Y.; Ko, F.W.; Chan, C.H.; Ho, A.S.; Hui, D.S.; Lam, C.W. Proinflammatory cytokines (IL-17, IL-6, IL-18 and IL-12) and Th cytokines (IFN-gamma, IL-4, IL-10 and IL-13) in patients with allergic asthma. Clin. Exp. Immunol., 2001, 125(2), 177-183. [http://dx.doi.org/10.1046/j.1365-2249.2001.01602.x]. [PMID: 11529906].
[162]
Alasandagutti, M.L.; Ansari, M.S.; Sagurthi, S.R.; Valluri, V.; Gaddam, S. Role of IL-13 Genetic Variants in Signalling of Asthma. Inflammation, 2017, 40(2), 566-577. [http://dx.doi.org/10.1007/s10753-016-0503-3]. [PMID: 28083766].
[163]
Lee, Y.C.; Lee, K.H.; Lee, H.B.; Rhee, Y.K. Serum levels of interleukins (IL)-4, IL-5, IL-13, and interferon-gamma in acute asthma. J. Asthma, 2001, 38(8), 665-671. [http://dx.doi.org/10.1081/JAS-100107544]. [PMID: 11758895].
[164]
Park, S.W.; Jangm, H.K.; An, M.H.; Min, J.W.; Jang, A.S.; Lee, J.H.; Park, C.S. Interleukin-13 and interleukin-5 in induced sputum of eosinophilic bronchitis: comparison with asthma. Chest, 2005, 128(4), 1921-1927. [http://dx.doi.org/10.1016/S0012-3692(15)52584-1]. [PMID: 16236836].
[165]
Siddiqui, S.; Cruse, G.; McKenna, S.; Monteiro, W.; Mistry, V.; Wardlaw, A.; Brightling, C. IL-13 expression by blood T cells and not eosinophils is increased in asthma compared to non-asthmatic eosinophilic bronchitis. BMC Pulm. Med., 2009, 9, 34. [http://dx.doi.org/10.1186/1471-2466-9-34]. [PMID: 19602238].
[166]
Berry, M.A.; Parker, D.; Neale, N.; Woodman, L.; Morgan, A.; Monk, P.; Bradding, P.; Wardlaw, A.J.; Pavord, I.D.; Brightling, C.E. Sputum and bronchial submucosal IL-13 expression in asthma and eosinophilic bronchitis. J. Allergy Clin. Immunol., 2004, 114(5), 1106-1109. [http://dx.doi.org/10.1016/j.jaci.2004.08.032]. [PMID: 15536417].
[167]
Saha, S.K.; Berry, M.A.; Parker, D.; Siddiqui, S.; Morgan, A.; May, R.; Monk, P.; Bradding, P.; Wardlaw, A.J.; Pavord, I.D.; Brightling, C.E. Increased sputum and bronchial biopsy IL-13 expression in severe asthma. J. Allergy Clin. Immunol., 2008, 121(3), 685-691. [http://dx.doi.org/10.1016/j.jaci.2008.01.005]. [PMID: 18328894].
[168]
Tsilogianni, Z.; Hillas, G.; Bakakos, P.; Aggelakis, L.; Konstantellou, E.; Papaioannou, A.I.; Papaporfyriou, A.; Papiris, S.; Koulouris, N.; Loukides, S.; Kostikas, K. Sputum interleukin-13 as a biomarker for the evaluation of asthma control. Clin. Exp. Allergy, 2016, 46(11), 1498. [http://dx.doi.org/10.1111/cea.12825]. [PMID: 27790845].
[169]
Tsilogianni, Z.; Hillas, G.; Bakakos, P.; Aggelakis, L.; Konstantellou, E.; Papaioannou, A.I.; Papaporfyriou, A.; Papiris, S.; Koulouris, N.; Loukides, S.; Kostikas, K. Sputum interleukin-13 as a biomarker for the evaluation of asthma control. Clin. Exp. Allergy, 2016, 46(7), 923-931. [http://dx.doi.org/10.1111/cea.12729]. [PMID: 26990030].
[170]
Huang, S.K.; Xiao, H.Q.; Kleine-Tebbe, J.; Paciotti, G.; Marsh, D.G.; Lichtenstein, L.M.; Liu, M.C. IL-13 expression at the sites of allergen challenge in patients with asthma. J. Immunol., 1995, 155(5), 2688-2694. [PMID: 7650396].
[171]
Kroegel, C.; Julius, P.; Matthys, H.; Virchow, J.C., Jr; Luttmann, W. Endobronchial secretion of interleukin-13 following local allergen challenge in atopic asthma: relationship to interleukin-4 and eosinophil counts. Eur. Respir. J., 1996, 9(5), 899-904. [http://dx.doi.org/10.1183/09031936.96.09050899]. [PMID: 8793449].
[172]
Bodey, K.J.; Semper, A.E.; Redington, A.E.; Madden, J.; Teran, L.M.; Holgate, S.T.; Frew, A.J. Cytokine profiles of BAL T cells and T-cell clones obtained from human asthmatic airways after local allergen challenge. Allergy, 1999, 54(10), 1083-1093. [http://dx.doi.org/10.1034/j.1398-9995.1999.00889.x]. [PMID: 10536887].
[173]
Barceló, B.; Pons, J.; Fuster, A.; Sauleda, J.; Noguera, A.; Ferrer, J.M.; Agustí, A.G. Intracellular cytokine profile of T lymphocytes in patients with chronic obstructive pulmonary disease. Clin. Exp. Immunol., 2006, 145(3), 474-479. [http://dx.doi.org/10.1111/j.1365-2249.2006.03167.x]. [PMID: 16907916].
[174]
Prieto, J.; Lensmar, C.; Roquet, A.; van der Ploeg, I.; Gigliotti, D.; Eklund, A.; Grunewald, J. Increased interleukin-13 mRNA expression in bronchoalveolar lavage cells of atopic patients with mild asthma after repeated low-dose allergen provocations. Respir. Med., 2000, 94(8), 806-814. [http://dx.doi.org/10.1053/rmed.2000.0826]. [PMID: 10955758].
[175]
Naseer, T.; Minshall, E.M.; Leung, D.Y.; Laberge, S.; Ernst, P.; Martin, R.J.; Hamid, Q. Expression of IL-12 and IL-13 mRNA in asthma and their modulation in response to steroid therapy. Am. J. Respir. Crit. Care Med., 1997, 155(3), 845-851. [http://dx.doi.org/10.1164/ajrccm.155.3.9117015]. [PMID: 9117015].
[176]
Bagnasco, D.; Ferrando, M.; Varricchi, G.; Passalacqua, G.; Canonica, G.W. A Critical Evaluation of Anti-IL-13 and Anti-IL-4 Strategies in Severe Asthma. Int. Arch. Allergy Immunol., 2016, 170(2), 122-131. [http://dx.doi.org/10.1159/000447692]. [PMID: 27637004].
[177]
May, R.D.; Monk, P.D.; Cohen, E.S.; Manuel, D.; Dempsey, F.; Davis, N.H.; Dodd, A.J.; Corkill, D.J.; Woods, J.; Joberty-Candotti, C.; Conroy, L.A.; Koentgen, F.; Martin, E.C.; Wilson, R.; Brennan, N.; Powell, J.; Anderson, I.K. Preclinical 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].
[178]
Piper, E.; Brightling, C.; Niven, R.; Oh, C.; Faggioni, R.; Poon, K.; She, D.; Kell, C.; May, R.D.; Geba, G.P.; Molfino, N.A. A phase II placebo-controlled study of tralokinumab in moderate-to-severe asthma. Eur. Respir. J., 2013, 41(2), 330-338. [http://dx.doi.org/10.1183/09031936.00223411]. [PMID: 22743678].
[179]
Brightling, C.E.; Chanez, P.; Leigh, R.; O’Byrne, P.M.; Korn, S.; She, D.; May, R.D.; Streicher, K.; Ranade, K.; Piper, E. Efficacy and safety of tralokinumab in patients with severe uncontrolled asthma: a randomised, double-blind, placebo-controlled, phase 2b trial. Lancet Respir. Med., 2015, 3(9), 692-701. [http://dx.doi.org/10.1016/S2213-2600(15)00197-6]. [PMID: 26231288].
[180]
Ultsch, M.; Bevers, J.; Nakamura, G.; Vandlen, R.; Kelley, R.F.; Wu, L.C.; Eigenbrot, C. Structural basis of signaling blockade by anti-IL-13 antibody Lebrikizumab. J. Mol. Biol., 2013, 425(8), 1330-1339. [http://dx.doi.org/10.1016/j.jmb.2013.01.024]. [PMID: 23357170].
[181]
Corren, J.L.R.F.; Hanania, N.A.; Korenblat, P.E.; Parsey, M.V.; Arron, J.R. Lebrikuzumab treatment in adults with asthma. N. Engl. J. Med., 2011, 365, 1088-1098. [http://dx.doi.org/10.1056/NEJMoa1106469]. [PMID: 21812663].
[182]
Noonan, M.; Korenblat, P.; Mosesova, S.; Scheerens, H.; Arron, J. R.; Zheng, Y.; Putnam, W. S.; Parsey, M. V.; Bohen, S. P.; Matthews, J. G. Dose-ranging study of lebrikizumab in asthmatic patients not receiving inhaled steroids. J Allergy Clin Immunol, 2013, 132 567-574. , e12.
[http://dx.doi.org/10.1016/j.jaci.2013.03.051]
[183]
Scheerens, H.; Arron, J.R.; Zheng, Y.; Putnam, W.S.; Erickson, R.W.; Choy, D.F.; Harris, J.M.; Lee, J.; Jarjour, N.N.; Matthews, J.G. The effects of lebrikizumab in patients with mild asthma following whole lung allergen challenge. Clin. Exp. Allergy, 2014, 44(1), 38-46. [http://dx.doi.org/10.1111/cea.12220]. [PMID: 24131304].
[184]
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.; 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].
[185]
Kasaian, M.T.; Tan, X.Y.; Jin, M.; Fitz, L.; Marquette, K.; Wood, N.; Cook, T.A.; Lee, J.; Widom, A.; Agostinelli, R.; Bree, A.; Schlerman, F.J.; Olland, S.; Wadanoli, M.; Sypek, J.; Gill, D.; Goldman, S.J.; Tchistiakova, L. Interleukin-13 neutralization by two distinct receptor blocking mechanisms reduces immunoglobulin E responses and lung inflammation in cynomolgus monkeys. J. Pharmacol. Exp. Ther., 2008, 325(3), 882-892. [http://dx.doi.org/10.1124/jpet.108.136515]. [PMID: 18337474].
[186]
Hua, F.; Ribbing, J.; Reinisch, W.; Cataldi, F.; Martin, S. A pharmacokinetic comparison of anrukinzumab, an anti- IL-13 monoclonal antibody, among healthy volunteers, asthma and ulcerative colitis patients. Br. J. Clin. Pharmacol., 2015, 80(1), 101-109. [http://dx.doi.org/10.1111/bcp.12589]. [PMID: 25614144].
[187]
Reinisch, W.; Panés, J.; Khurana, S.; Toth, G.; Hua, F.; Comer, G.M.; Hinz, M.; Page, K.; O’Toole, M.; Moorehead, T.M.; Zhu, H.; Sun, Y.; Cataldi, F. Anrukinzumab, an anti-interleukin 13 monoclonal antibody, in active UC: efficacy and safety from a phase IIa randomised multicentre study. Gut, 2015, 64(6), 894-900. [http://dx.doi.org/10.1136/gutjnl-2014-308337]. [PMID: 25567115].
[188]
De Boever, E.H.; Ashman, C.; Cahn, A.P.; Locantore, N.W.; Overend, P.; Pouliquen, I.J.; Serone, A.P.; Wright, T.J.; Jenkins, M.M.; Panesar, I.S.; Thiagarajah, S.S.; Wenzel, S.E. Efficacy and safety of an anti-IL-13 mAb in patients with severe asthma: a randomized trial. J. Allergy Clin. Immunol., 2014, 133(4), 989-996. [http://dx.doi.org/10.1016/j.jaci.2014.01.002]. [PMID: 24582316].
[189]
Steinke, J.W. Anti-interleukin-4 therapy. Immunol. Allergy Clin. North Am., 2004, 24(4), 599-614. vi. [vi ]. [http://dx.doi.org/10.1016/j.iac.2004.06.008] [PMID: 15474861]
[190]
Hart, T.K.; Blackburn, M.N.; Brigham-Burke, M.; Dede, K.; Al-Mahdi, N.; Zia-Amirhosseini, P.; Cook, R.M. Preclinical efficacy and safety of pascolizumab (SB 240683): a humanized anti-interleukin-4 antibody with therapeutic potential in asthma. Clin. Exp. Immunol., 2002, 130(1), 93-100. [http://dx.doi.org/10.1046/j.1365-2249.2002.01973.x]. [PMID: 12296858].
[191]
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].
[192]
Beck, L.A.; Thaçi, D.; Hamilton, J.D.; Graham, N.M.; Bieber, T.; Rocklin, R.; Ming, J.E.; Ren, H.; Kao, R.; Simpson, E.; Ardeleanu, M.; Weinstein, S.P.; Pirozzi, G.; Guttman-Yassky, E.; Suárez-Fariñas, M.; Hager, M.D.; Stahl, N.; Yancopoulos, G.D.; Radin, A.R. Dupilumab treatment in adults with moderate-to-severe atopic dermatitis. N. Engl. J. Med., 2014, 371(2), 130-139. [http://dx.doi.org/10.1056/NEJMoa1314768]. [PMID: 25006719].
[193]
Wenzel, S.; Wilbraham, D.; Fuller, R.; Getz, E.B.; Longphre, M. Effect of an interleukin-4 variant on late phase asthmatic response to allergen challenge in asthmatic patients: results of two phase 2a studies. Lancet, 2007, 370(9596), 1422-1431. [http://dx.doi.org/10.1016/S0140-6736(07)61600-6]. [PMID: 17950857].
[194]
Slager, R. E.; Otulana, B. A.; Hawkins, G. A.; Yen, Y. P.; Peters, S. P.; Wenzel, S. E.; Meyers, D. A.; Bleecker, E. R. IL-4 receptor polymorphisms predict reduction in asthma exacerbations during response to an anti-IL-4 receptor alpha antagonist. J Allergy Clin Immunol, 2012, 130, 516- 522>.e4.
[195]
Liu, S.; Verma, M.; Michalec, L.; Liu, W.; Sripada, A.; Rollins, D.; Good, J.; Ito, Y.; Chu, H.; Gorska, M.M.; Martin, R.J.; Alam, R. Steroid resistance of airway type 2 innate lymphoid cells from patients with severe asthma: The role of thymic stromal lymphopoietin. J. Allergy Clin. Immunol., 2018, 141(1), 257-268.e6. [DOI: 10.1016/j.jaci.2017.03.032]. [PMID: 28433687].
[196]
Soumelis, V.; Reche, P.A.; Kanzler, H.; Yuan, W.; Edward, G.; Homey, B.; Gilliet, M.; Ho, S.; Antonenko, S.; Lauerma, A.; Smith, K.; Gorman, D.; Zurawski, S.; Abrams, J.; Menon, S.; McClanahan, T.; de Waal-Malefyt Rd, R.; Bazan, F.; Kastelein, R.A.; Liu, Y.J. Human epithelial cells trigger dendritic cell mediated allergic inflammation by producing TSLP. Nat. Immunol., 2002, 3(7), 673-680. [http://dx.doi.org/10.1038/ni805]. [PMID: 12055625].
[197]
Pandey, A.; Ozaki, K.; Baumann, H.; Levin, S.D.; Puel, A.; Farr, A.G.; Ziegler, S.F.; Leonard, W.J.; Lodish, H.F. Cloning of a receptor subunit required for signaling by thymic stromal lymphopoietin. Nat. Immunol., 2000, 1(1), 59-64. [http://dx.doi.org/10.1038/76923]. [PMID: 10881176].
[198]
Park, L.S.; Martin, U.; Garka, K.; Gliniak, B.; Di Santo, J.P.; Muller, W.; Largaespada, D.A.; Copeland, N.G.; Jenkins, N.A.; Farr, A.G.; Ziegler, S.F.; Morrissey, P.J.; Paxton, R.; Sims, J.E. Cloning of the murine thymic stromal lymphopoietin (TSLP) receptor: Formation of a functional heteromeric complex requires interleukin 7 receptor. J. Exp. Med., 2000, 192(5), 659-670. [http://dx.doi.org/10.1084/jem.192.5.659]. [PMID: 10974032].
[199]
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].
[200]
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].
[201]
Elyaman, W.; Bradshaw, E.M.; Uyttenhove, C.; Dardalhon, V.; Awasthi, A.; Imitola, J.; Bettelli, E.; Oukka, M.; van Snick, J.; Renauld, J.C.; Kuchroo, V.K.; Khoury, S.J. IL-9 induces differentiation of TH17 cells and enhances function of FoxP3+ natural regulatory T cells. Proc. Natl. Acad. Sci. USA, 2009, 106(31), 12885-12890. [http://dx.doi.org/10.1073/pnas.0812530106]. [PMID: 19433802].
[202]
Chang, H.C.; Sehra, S.; Goswami, R.; Yao, W.; Yu, Q.; Stritesky, G.L.; Jabeen, R.; McKinley, C.; Ahyi, A.N.; Han, L.; Nguyen, E.T.; Robertson, M.J.; Perumal, N.B.; Tepper, R.S.; Nutt, S.L.; Kaplan, M.H. The transcription factor PU.1 is required for the development of IL-9-producing T cells and allergic inflammation. Nat. Immunol., 2010, 11(6), 527-534. [http://dx.doi.org/10.1038/ni.1867]. [PMID: 20431622].
[203]
Nowak, E.C.; Weaver, C.T.; Turner, H.; Begum-Haque, S.; Becher, B.; Schreiner, B.; Coyle, A.J.; Kasper, L.H.; Noelle, R.J. IL-9 as a mediator of Th17-driven inflammatory disease. J. Exp. Med., 2009, 206(8), 1653-1660. [http://dx.doi.org/10.1084/jem.20090246]. [PMID: 19596803].
[204]
Rauber, S.; Luber, M.; Weber, S.; Maul, L.; Soare, A.; Wohlfahrt, T.; Lin, N.Y.; Dietel, K.; Bozec, A.; Herrmann, M.; Kaplan, M.H.; Weigmann, B.; Zaiss, M.M.; Fearon, U.; Veale, D.J.; Cañete, J.D.; Distler, O.; Rivellese, F.; Pitzalis, C.; Neurath, M.F.; McKenzie, A.N.J.; Wirtz, S.; Schett, G.; Distler, J.H.W.; Ramming, A. Resolution of inflammation by interleukin-9-producing type 2 innate lymphoid cells. Nat. Med., 2017, 23(8), 938-944. [http://dx.doi.org/10.1038/nm.4373]. [PMID: 28714991].
[205]
Parker, J.M.; Oh, C.K.; LaForce, C.; Miller, S.D.; Pearlman, D.S.; Le, C.; Robbie, G.J.; White, W.I.; White, B.; Molfino, N.A. Safety profile and clinical activity of multiple subcutaneous doses of MEDI-528, a humanized anti-interleukin-9 monoclonal antibody, in two randomized phase 2a studies in subjects with asthma. BMC Pulm. Med., 2011, 11, 14. [http://dx.doi.org/10.1186/1471-2466-11-14]. [PMID: 21356110].
[206]
Gauvreau, G.; Parker, J.M.; Sari, S.; White, B.; Molfino, N.A.A. Randomized, Duble-Blind, Placebo Controlled Multicenter Study To Evaluate the Efficacy of a Humanized Interleukin-9 Monoclonal Antibody (MEDI-528) on the Late Asthmatic Response in Adults with Atopic Asthma. Am. J. Respir. Crit. Care Med., 2009, 179, A3639. [DOI: 10.1164/ajrccm-conference.2009.179.1_Meeting Abstracts.A3639].
[207]
Oh, C.K.; Leigh, R.; McLaurin, K.K.; Kim, K.; Hultquist, M.; Molfino, N.A. A randomized, controlled trial to evaluate the effect of an anti-interleukin-9 monoclonal antibody in adults with uncontrolled asthma. Respir. Res., 2013, 14, 93. [http://dx.doi.org/10.1186/1465-9921-14-93]. [PMID: 24050312].
[208]
Keatings, V.M.; O’Connor, B.J.; Wright, L.G.; Huston, D.P.; Corrigan, C.J.; Barnes, P.J. Late response to allergen is associated with increased concentrations of tumor necrosis factor-alpha and IL-5 in induced sputum. J. Allergy Clin. Immunol., 1997, 99(5), 693-698. [http://dx.doi.org/10.1016/S0091-6749(97)70032-0]. [PMID: 9155837].
[209]
Kavanaugh, A.; McInnes, I.; Mease, P.; Krueger, G.G.; Gladman, D.; Gomez-Reino, J.; Papp, K.; Zrubek, J.; Mudivarthy, S.; Mack, M.; Visvanathan, S.; Beutler, A. Golimumab, a new human tumor necrosis factor alpha antibody, administered every four weeks as a subcutaneous injection in psoriatic arthritis: Twenty-four-week efficacy and safety results of a randomized, placebo-controlled study. Arthritis Rheum., 2009, 60(4), 976-986. [http://dx.doi.org/10.1002/art.24403]. [PMID: 19333944].
[210]
Wenzel, S.E.; Barnes, P.J.; Bleecker, E.R.; Bousquet, J.; Busse, W.; Dahlén, S.E.; Holgate, S.T.; Meyers, D.A.; Rabe, K.F.; Antczak, A.; Baker, J.; Horvath, I.; Mark, Z.; Bernstein, D.; Kerwin, E.; Schlenker-Herceg, R.; Lo, K.H.; Watt, R.; Barnathan, E.S.; Chanez, P. A randomized, double-blind, placebo-controlled study of tumor necrosis factor-alpha blockade in severe persistent asthma. Am. J. Respir. Crit. Care Med., 2009, 179(7), 549-558. [http://dx.doi.org/10.1164/rccm.200809-1512OC]. [PMID: 19136369].
[211]
Borriello, F.; Iannone, R.; Di Somma, S.; Vastolo, V.; Petrosino, G.; Visconte, F.; Raia, M.; Scalia, G.; Loffredo, S.; Varricchi, G.; Galdiero, M.R.; Granata, F.; Del Vecchio, L.; Portella, G.; Marone, G. Lipopolysaccharide-elicited TSLPR expression enriches a functionally discrete subset of human CD14+ CD1c+ monocytes. J. Immunol., 2017, 198(9), 3426-3435. [http://dx.doi.org/10.4049/jimmunol.1601497]. [PMID: 28341671].
[212]
Borriello, F. Iannone, R.; Di Somma, S.; Loffredo, S.; Scamardella, E.; Galdiero, M.R.; Varricchi, G.; Granata, F.; Portella, G.; Marone, G. GM-CSF and IL-3 modulate human monocyte TNF-α production and renewal in in vitro models of trained immunity. Front. Immunol., 2017, 7, 680. [http://dx.doi.org/10.3389/fimmu.2016.00680]. [PMID: 28138327].
[213]
Staiano, R.I.; Loffredo, S.; Borriello, F.; Iannotti, F.A.; Piscitelli, F.; Orlando, P.; Secondo, A.; Granata, F.; Lepore, M.T.; Fiorelli, A.; Varricchi, G.; Santini, M.; Triggiani, M.; Di Marzo, V.; Marone, G. Human lung-resident macrophages express CB1 and CB2 receptors whose activation inhibits the release of angiogenic and lymphangiogenic factors. J. Leukoc. Biol., 2016, 99(4), 531-540. [http://dx.doi.org/10.1189/jlb.3HI1214-584R]. [PMID: 26467187].
[214]
Brusselle, G.G.; Vanderstichele, C.; Jordens, P.; Deman, R.; Slabbynck, H.; Ringoet, V.; Verleden, G.; Demedts, I.K.; Verhamme, K.; Delporte, A.; Demeyere, B.; Claeys, G.; Boelens, J.; Padalko, E.; Verschakelen, J.; Van Maele, G.; Deschepper, E.; Joos, G.F. Azithromycin for prevention of exacerbations in severe asthma (AZISAST): a multicentre randomised double-blind placebo-controlled trial. Thorax, 2013, 68(4), 322-329. [http://dx.doi.org/10.1136/thoraxjnl-2012-202698]. [PMID: 23291349].
[215]
Gibson, P.G.; Yang, I.A.; Upham, J.W.; Reynolds, P.N.; Hodge, S.; James, A.L.; Jenkins, C.; Peters, M.J.; Marks, G.B.; Baraket, M.; Powell, H.; Taylor, S.L.; Leong, L.E.X.; Rogers, G.B.; Simpson, J.L. Effect of azithromycin on asthma exacerbations and quality of life in adults with persistent uncontrolled asthma (AMAZES): a randomised, double-blind, placebo-controlled trial. Lancet, 2017, 390(10095), 659-668. [http://dx.doi.org/10.1016/S0140-6736(17)31281-3]. [PMID: 28687413].
[216]
Sorbello, V.; Ciprandi, G.; Di Stefano, A.; Massaglia, G.M.; Favatà, G.; Conticello, S.; Malerba, M.; Folkerts, G.; Profita, M.; Rolla, G.; Ricciardolo, F.L. Nasal IL-17F is related to bronchial IL-17F/neutrophilia and exacerbations in stable atopic severe asthma. Allergy, 2015, 70(2), 236-240. [http://dx.doi.org/10.1111/all.12547]. [PMID: 25394579].
[217]
Ricciardolo, F.L.M.; Sorbello, V.; Folino, A.; Gallo, F.; Massaglia, G.M.; Favatà, G.; Conticello, S.; Vallese, D.; Gani, F.; Malerba, M.; Folkerts, G.; Rolla, G.; Profita, M.; Mauad, T.; Di Stefano, A.; Ciprandi, G. Identification of IL-17F/frequent exacerbator endotype in asthma. J. Allergy Clin. Immunol., 2017, 140(2), 395-406. [http://dx.doi.org/10.1016/j.jaci.2016.10.034]. [PMID: 27931975].
[218]
Busse, W.W.; Holgate, S.; Kerwin, E.; Chon, Y.; Feng, J.; Lin, J.; Lin, S.L. Randomized, double-blind, placebo-controlled study of brodalumab, a human anti-IL-17 receptor monoclonal antibody, in moderate to severe asthma. Am. J. Respir. Crit. Care Med., 2013, 188(11), 1294-1302. [http://dx.doi.org/10.1164/rccm.201212-2318OC]. [PMID: 24200404].
[219]
Ferrando, M.; Bagnasco, D.; Varricchi, G.; Bernardi, S.; Bragantini, A.; Passalacqua, G.; Canonica, G.W. Personalized medicine in allergy. Allergy Asthma Immunol. Res., 2017, 9(1), 15-24. [http://dx.doi.org/10.4168/aair.2017.9.1.15]. [PMID: 27826958].
[220]
Cooper, P.J.; Ayre, G.; Martin, C.; Rizzo, J.A.; Ponte, E.V.; Cruz, A.A. Geohelminth infections: a review of the role of IgE and assessment of potential risks of anti-IgE treatment. Allergy, 2008, 63(4), 409-417. [http://dx.doi.org/10.1111/j.1398-9995.2007.01601.x]. [PMID: 18315729].
[221]
Carretero, R.; Sektioglu, I.M.; Garbi, N.; Salgado, O.C.; Beckhove, P.; Hämmerling, G.J. Eosinophils orchestrate cancer rejection by normalizing tumor vessels and enhancing infiltration of CD8(+) T cells. Nat. Immunol., 2015, 16(6), 609-617. [http://dx.doi.org/10.1038/ni.3159]. [PMID: 25915731].
[222]
Lucarini, V.; Ziccheddu, G.; Macchia, I.; La Sorsa, V.; Peschiaroli, F.; Buccione, C.; Sistigu, A.; Sanchez, M.; Andreone, S.; D’Urso, M.T.; Spada, M.; Macchia, D.; Afferni, C.; Mattei, F.; Schiavoni, G. IL-33 restricts tumor growth and inhibits pulmonary metastasis in melanoma-bearing mice through eosinophils. Oncoimmunolog, 2017, 6(6)e1317420 [http://dx.doi.org/10.1080/2162402X.2017.1317420]. [PMID: 28680750].
[223]
Varricchi, G.; Galdiero, M.R.S. L., Lucarini, V., G, M., Mattei, F., G, M. and Schiavoni, G.; Eosinophils: the Unsung Heroes in Cancer? (in press). OncoImmunology, 2017.
[224]
Roufosse, F.; de Lavareille, A.; Schandene, L.; Cogan, E.; Georgelas, A.; Wagner, L.; Xi, L.; Raffeld, M.; Goldman, M.; Gleich, G. J.; Klion, A. Mepolizumab as a corticosteroid-sparing agent in lymphocytic variant hypereosinophilic syndrome. J. Allergy Clin. Immunol., 2010, 126, 828-835. e3.
[http://dx.doi.org/10.1016/j.jaci.2010.06.049]
[225]
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. 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].
[226]
Ferrando, M.; Bagnasco, D.; Braido, F.; Varricchi, G.; Canonica, G.W. Biosimilars in allergic diseases. Curr. Opin. Allergy Clin. Immunol., 2016, 16(1), 68-73. [http://dx.doi.org/10.1097/ACI.0000000000000226]. [PMID: 26595424].
[227]
Faria, R.; McKenna, C.; Palmer, S. Optimizing the position and use of omalizumab for severe persistent allergic asthma using cost-effectiveness analysis. Value Health, 2014, 17(8), 772-782. [http://dx.doi.org/10.1016/j.jval.2014.07.009]. [PMID: 25498772].
[228]
Yoshikawa, H.; Iwata, M.; Matsuzaki, H.; Ono, R.; Murakami, Y.; Taba, N.; Honjo, S.; Motomura, C.; Odajima, H. Impact of omalizumab on medical cost of childhood asthma in Japan. Pediatr. Int. (Roma), 2016, 58(5), 425-428. [http://dx.doi.org/10.1111/ped.12936]. [PMID: 27173421].
[229]
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].


Rights & PermissionsPrintExport Cite as

Article Details

VOLUME: 26
ISSUE: 16
Year: 2019
Page: [2801 - 2822]
Pages: 22
DOI: 10.2174/0929867325666180110094542
Price: $58

Article Metrics

PDF: 38
HTML: 4
EPUB: 2
PRC: 2