Targeting cytokines to treat asthma and chronic obstructive pulmonary disease

1.Barnes, P. J. et al. Power obstructive pulmonary illness. Nat. Rev. Primers 1, 15076 (2015).2.Postma, D. S. & Rabe, Ok. F. The asthma-COPD overlap syndrome. N. Engl. J. Med. 373, 1241–1249 (2015).Three.Barnes, P. J. Bronchial asthma-COPD overlap. Chest 149, 7–eight (2016).Four.Worth, D., Fletcher, M. & van der Molen, T. Bronchial asthma management and administration in eight,000 European sufferers: the REcognise Bronchial asthma and LInk to Signs and Expertise (REALISE) survey. NPJ Prim. Care Respir. Med. 24, 14009 (2014).5.Gross, N. J. & Barnes, P. J. New therapies for bronchial asthma and continual obstructive pulmonary illness. Am. J. Respir. Crit. Care Med. 195, 159–166 (2017).6.Chung, Ok. F. Concentrating on the interleukin pathway within the therapy of bronchial asthma. Lancet 386, 1086–1096 (2015).7.Lefaudeux, D. et al. U-BIOPRED medical grownup bronchial asthma clusters linked to a subset of sputum omics. J. Allergy Clin. Immunol. 139, 1797–1807 (2017).eight.Barnes, P. J. Mobile and molecular mechanisms of bronchial asthma and COPD. Clin. Sci. 131, 1541–1558 (2017).9.Ebbo, M., Crinier, A., Vely, F. & Vivier, E. Innate lymphoid cells: main gamers in inflammatory ailments. Nat. Rev. Immunol. 17, 665–678 (2017).10.Barnes, P. J. Pathophysiology of allergic irritation. Immunol. Rev. 242, 31–50 (2011).11.Hogg, J. C. et al. The character of small-airway obstruction in continual obstructive pulmonary illness. N. Engl. J. Med. 350, 2645–2653 (2004).12.Brusselle, G. G., Joos, G. F. & Bracke, Ok. R. New insights into the immunology of continual obstructive pulmonary illness. Lancet 378, 1015–1026 (2011).13.McDonough, J. E. et al. Small-airway obstruction and emphysema in continual obstructive pulmonary illness. N. Engl. J. Med. 365, 1567–1575 (2011).14.Galban, C. J. et al. Computed tomography-based biomarker offers distinctive signature for prognosis of COPD phenotypes and illness development. Nat. Med. 18, 1711–1715 (2012).15.Lange, P. et al. Lung-function trajectories resulting in continual obstructive pulmonary illness. N. Engl. J. Med. 373, 111–122 (2015).16.Barnes, P. J. Mechanisms of improvement of multimorbidity within the aged. Eur. Respir. J. 45, 790–806 (2015).17.Barnes, P. J. Glucocorticosteroids. Handb. Exp. Pharmacol. 237, 93–115 (2017).18.Barnes, P. J. Corticosteroid resistance in sufferers with bronchial asthma and continual obstructive pulmonary illness. J. Allergy Clin. Immunol. 131, 636–645 (2013).19.Ito, Ok. et al. Decreased histone deacetylase exercise in continual obstructive pulmonary illness. N. Engl. J. Med. 352, 1967–1976 (2005).20.Hew, M. et al. Relative corticosteroid insensitivity of peripheral blood mononuclear cells in extreme bronchial asthma. Am. J. Respir. Crit. Care Med. 174, 134–141 (2006).21.Molfino, N. A., Gossage, D., Kolbeck, R., Parker, J. M. & Geba, G. P. Molecular and medical rationale for therapeutic focusing on of interleukin-5 and its receptor. Clin. Exp. Allergy 42, 712–737 (2012).22.Leckie, M. J. et al. Results of an interleukin-5 blocking monoclonal antibody on eosinophils, airway hyperresponsiveness and the late asthmatic response. Lancet 356, 2144–2148 (2000). That is the primary research of an anti-IL-5 antibody in sufferers with bronchial asthma and exhibits a marked discount in blood and sputum eosinophils.
23.Flood-Web page, P. et al. A research to judge security and efficacy of mepolizumab in sufferers with average persistent bronchial asthma. Am. J. Respir. Crit. Care Med. 176, 1062–1071 (2007).24.Haldar, P. et al. Mepolizumab and exacerbations of refractory eosinophilic bronchial asthma. N. Engl. J. Med. 360, 973–984 (2009).25.Nair, P. et al. Mepolizumab for prednisone-dependent bronchial asthma with sputum eosinophilia. N. Engl. J. Med. 360, 985–993 (2009).26.Pavord, I. D. et al. Mepolizumab for extreme eosinophilic bronchial asthma (DREAM): a multicentre, double-blind, placebo-controlled trial. Lancet 380, 651–659 (2012). This can be a giant research of an anti-IL-5 antibody in sufferers with extreme eosinophilic bronchial asthma that exhibits an ~50% discount in acute exacerbations.
27.Bel, E. H. et al. Oral glucocorticoid-sparing impact of mepolizumab in eosinophilic bronchial asthma. N. Engl. J. Med. 371, 1189–1197 (2014).28.Ortega, H. G. et al. Mepolizumab therapy in sufferers with extreme eosinophilic bronchial asthma. N. Engl. J. Med. 371, 1198–1207 (2014).29.Powell, C., Milan, S. J., Dwan, Ok., Bax, L. & Walters, N. Mepolizumab versus placebo for bronchial asthma. Cochrane Database Syst. Rev. 7, CD010834 (2015).30.Chupp, G. L. et al. Efficacy of mepolizumab add-on remedy on health-related high quality of life and markers of bronchial asthma management in extreme eosinophilic bronchial asthma (MUSCA): a randomised, double-blind, placebo-controlled, parallel-group, multicentre, section 3b trial. Lancet Respir. Med. 5, 390–400 (2017).31.Wechsler, M. E. et al. Mepolizumab or placebo for eosinophilic granulomatosis with polyangiitis. N. Engl. J. Med. 376, 1921–1932 (2017).32.Kim, S., Marigowda, G., Oren, E., Israel, E. & Wechsler, M. E. Mepolizumab as a steroid-sparing therapy choice in sufferers with Churg-Strauss syndrome. J. Allergy Clin. Immunol. 125, 1336–1343 (2010).33.Castro, M. et al. Reslizumab for poorly managed, eosinophilic bronchial asthma: a randomized, placebo-controlled research. Am. J. Respir. Crit. Care Med. 184, 1125–1132 (2011).34.Castro, M. et al. Reslizumab for inadequately managed bronchial asthma with elevated blood eosinophil counts: outcomes from two multicentre, parallel, double-blind, randomised, placebo-controlled, section Three trials. Lancet Respir. Med. Three, 355–366 (2015).35.Bjermer, L. et al. Reslizumab for inadequately managed bronchial asthma with elevated blood eosinophil ranges: a randomized section Three research. Chest 150, 789–798 (2016).36.Brusselle, G., Germinaro, M., Weiss, S. & Zangrilli, J. Reslizumab in sufferers with inadequately managed late-onset bronchial asthma and elevated blood eosinophils. Pulm. Pharmacol. Ther. 43, 39–45 (2017).37.Corren, J., Weinstein, S., Janka, L., Zangrilli, J. & Garin, M. Part Three research of reslizumab in sufferers with poorly managed bronchial asthma: results throughout a broad vary of eosinophil counts. Chest 150, 799–810 (2016).38.Ghazi, A., Trikha, A. & Calhoun, W. J. Benralizumab—a humanized mAb to IL-5Ralpha with enhanced antibody-dependent cell-mediated cytotoxicity — a novel method for the therapy of bronchial asthma. Knowledgeable Opin. Biol. Ther. 12, 113–118 (2012).39.Kolbeck, R. et al. MEDI-563, a humanized anti-IL-5 receptor alpha mAb with enhanced antibody-dependent cell-mediated cytotoxicity operate. J. Allergy Clin. Immunol. 125, 1344–1353 (2010). This paper explains the mechanism of motion of benralizumab, an IL-5Rα-specific antibody that induces cytotoxicity.
40.Castro, M. et al. Benralizumab, an anti-interleukin 5 receptor alpha monoclonal antibody, versus placebo for uncontrolled eosinophilic bronchial asthma: a section 2b randomised dose-ranging research. Lancet Respir. Med. 2, 879–890 (2014).41.Khorasanizadeh, M., Eskian, M., Assa’advert, A. H., Camargo, C. A. Jr & Rezaei, N. Efficacy and security of benralizumab, a monoclonal antibody in opposition to IL-5Rα, in uncontrolled eosinophilic bronchial asthma. Int. Rev. Immunol. 35, 294–311 (2016).42.Bleecker, E. R. et al. Efficacy and security of benralizumab for sufferers with extreme bronchial asthma uncontrolled with high-dosage inhaled corticosteroids and long-acting beta2-agonists (SIROCCO): a randomised, multicentre, placebo-controlled section Three trial. Lancet 388, 2115–2127 (2016).43.FitzGerald, J. M. et al. Benralizumab, an anti-interleukin-5 receptor alpha monoclonal antibody, as add-on therapy for sufferers with extreme, uncontrolled, eosinophilic bronchial asthma (CALIMA): a randomised, double-blind, placebo-controlled section Three trial. Lancet 388, 2128–2141 (2016).44.Nair, P. et al. Oral glucocorticoid-sparing impact of benralizumab in extreme bronchial asthma. N. Engl. J. Med. 376, 2448–2458 (2017).45.Ferguson, G. T. et al. Benralizumab for sufferers with gentle to average, persistent bronchial asthma (BISE): a randomised, double-blind, placebo-controlled, section Three trial. Lancet Respir. Med. 5, 568–576 (2017).46.Nowak, R. M. et al. A randomized trial of benralizumab, an antiinterleukin 5 receptor alpha monoclonal antibody, after acute bronchial asthma. Am. J. Emerg. Med. 33, 14–20 (2015).47.Brightling, C. E. et al. Benralizumab for continual obstructive pulmonary illness and sputum eosinophilia: a randomised, double-blind, placebo-controlled, section 2a research. Lancet Respir. Med. 2, 891–901 (2014).48.Dasgupta, A. et al. A pilot randomised medical trial of mepolizumab in COPD with eosinophilic bronchitis. Eur. Respir. J. 49, 1602486 (2017).49.Pavord, I. D. et al. Mepolizumab for eosinophilic continual obstructive pulmonary illness. N. Engl. J. Med. 377, 1613–1629 (2017). Reference 48 and 49 are two giant research of an anti-IL-5 remedy in sufferers with COPD that present a small discount in exacerbations in sufferers with elevated blood eosinophils.
50.Leung, E., Al Efraij, Ok. & FitzGerald, J. M. The protection of mepolizumab for the therapy of bronchial asthma. Knowledgeable Opin. Drug Security 16, 397–404 (2017).51.Lugogo, N. et al. Lengthy-term efficacy and security of mepolizumab in sufferers with extreme eosinophilic bronchial asthma: a multi-center, open-label, section IIIb research. Clin. Ther. 38, 2058–2070.e1 (2016).52.Cabon, Y. et al. Comparability of anti-interleukin-5 therapies in sufferers with extreme bronchial asthma: world and oblique meta-analyses of randomized placebo-controlled trials. Clin. Exp. Allergy 47, 129–138 (2017). This can be a meta-analysis of revealed research of anti-IL-5 antibody therapy of extreme bronchial asthma.
53.Larose, M. C. et al. Correlation between CCL26 manufacturing by human bronchial epithelial cells and airway eosinophils: Involvement in sufferers with extreme eosinophilic bronchial asthma. J. Allergy Clin. Immunol. 136, 904–913 (2015).54.Kasaian, M. T. & Miller, D. Ok. IL-13 as a therapeutic goal for respiratory illness. Biochem. Pharmacol. 76, 147–155 (2008).55.Antoniu, S. A. Pitrakinra, a twin IL-Four/IL-13 antagonist for the potential therapy of bronchial asthma and eczema. Curr. Opin. Make investments. Medication 11, 1286–1294 (2010).56.Chiba, Y., Todoroki, M., Nishida, Y., Tanabe, M. & Misawa, M. A novel STAT6 inhibitor AS1517499 ameliorates antigen-induced bronchial hypercontractility in mice. Am. J. Respir. Cell Mol. Biol. 41, 516–524 (2009).57.Izuhara, Ok. et al. Roles of periostin in respiratory issues. Am. J. Respir. Crit. Care Med. 19, 949–956 (2016).58.Corren, J. et al. Lebrikizumab therapy in adults with bronchial asthma. N. Engl. J. Med. 365, 1088–1098 (2011).59.Hanania, N. A. et al. Lebrikizumab in moderate-to-severe bronchial asthma: pooled information from two randomised placebo-controlled research. Thorax 70, 748–756 (2015). References 58 and 59 are two giant research of an anti-IL-13 antibody that reveal little medical profit in sufferers with extreme kind 2 bronchial asthma.
60.Piper, E. et al. A section II placebo-controlled research of tralokinumab in moderate-to-severe bronchial asthma. Eur. Respir. J. 41, 330–338 (2013).61.Brightling, C. E. et al. Efficacy and security of tralokinumab in sufferers with extreme uncontrolled bronchial asthma: a randomised, double-blind, placebo-controlled, section 2b trial. Lancet. Resp. Med. Three, 692–701 (2015).62.Wenzel, S. et al. Dupilumab in persistent bronchial asthma with elevated eosinophil ranges. N. Engl. J. Med. 368, 2455–2466 (2013).63.Wenzel, S. et al. Dupilumab efficacy and security in adults with uncontrolled persistent bronchial asthma regardless of use of medium-to-high-dose inhaled corticosteroids plus a long-acting beta2 agonist: a randomised double-blind placebo-controlled pivotal section 2b dose-ranging trial. Lancet 388, 31–44 (2016). This can be a giant medical trial of an anti-IL-4Rα antibody in sufferers with average to extreme bronchial asthma, which exhibits marked enchancment of signs and lung operate and decreased exacerbations, even in sufferers with out elevated blood eosinophils.
64.Blauvelt, A. et al. Lengthy-term administration of moderate-to-severe atopic dermatitis with dupilumab and concomitant topical corticosteroids (LIBERTY AD CHRONOS): a 1-year, randomised, double-blinded, placebo-controlled, section Three trial. Lancet 389, 2287–2303 (2017).65.Kraft, M. & Worm, M. Dupilumab within the therapy of moderate-to-severe atopic dermatitis. Knowledgeable Rev. Clin. Immunol. 13, 301–310 (2017).66.Bachert, C. et al. Impact of subcutaneous dupilumab on nasal polyp burden in sufferers with continual sinusitis and nasal polyposis: a randomized medical trial. JAMA 315, 469–479 (2016).67.Mitchell, P. D. & O’Byrne, P. M. Epithelial-derived cytokines in bronchial asthma. Chest 151, 1338–1344 (2017).68.Ying, S. et al. Expression and mobile provenance of thymic stromal lymphopoietin and chemokines in sufferers with extreme bronchial asthma and continual obstructive pulmonary illness. J. Immunol. 181, 2790–2798 (2008).69.Gauvreau, G. M. et al. Results of an anti-TSLP antibody on allergen-induced asthmatic responses. N. Engl. J. Med. 370, 2102–2110 (2014).70.Corren, J. et al. Tezepelumab in adults with uncontrolled bronchial asthma. N. Engl. J. Med. 377, 936–946 (2017). This huge research exhibits good efficacy of an anti-TSLP antibody in sufferers with extreme bronchial asthma, with enchancment in signs and lung operate and decreased exacerbations, blood eosinophils and FeNO.
71.Nagarkar, D. R. et al. Thymic stromal lymphopoietin exercise is elevated in nasal polyps of sufferers with continual rhinosinusitis. J. Allergy Clin. Immunol. 132, 593–600 (2013).72.Verstraete, Ok. et al. Construction and antagonism of the receptor advanced mediated by human TSLP in allergy and bronchial asthma. Nat. Commun. eight, 14937 (2017).73.Xu, M. & Dong, C. IL-25 in allergic irritation. Immunol. Rev. 278, 185–191 (2017).74.Mitchell, P. D. & O’Byrne, P. M. Biologics and the lung: TSLP and different epithelial cell-derived cytokines in bronchial asthma. Pharmacol. Ther. 169, 104–112 (2017).75.Cheng, D. et al. Epithelial interleukin-25 is a key mediator in Th2-high, corticosteroid-responsive bronchial asthma. Am. J. Respir. Crit. Care Med. 190, 639–648 (2014).76.Christianson, C. A. et al. Persistence of bronchial asthma requires a number of suggestions circuits involving kind 2 innate lymphoid cells and IL-33. J. Allergy Clin. Immunol. 136, 59–68 (2015).77.Kubo, M. Innate and adaptive kind 2 immunity in lung allergic irritation. Immunol. Rev. 278, 162–172 (2017).78.Prefontaine, D. et al. Elevated IL-33 expression by epithelial cells in bronchial bronchial asthma. J. Allergy Clin. Immunol. 125, 752–754 (2010).79.Qiu, C. et al. Anti-interleukin-33 inhibits cigarette smoke-induced lung irritation in mice. Immunology 138, 76–82 (2013).80.Xia, J. et al. Elevated IL-33 expression in continual obstructive pulmonary illness. Am. J. Physiol. Lung Cell Mol. Physiol. 308, L619–L627 (2015).81.Vlahos, R., Bozinovski, S., Hamilton, J. A. & Anderson, G. P. Therapeutic potential of treating continual obstructive pulmonary illness (COPD) by neutralising granulocyte macrophage-colony stimulating issue (GM-CSF). Pharmacol. Ther. 112, 106–115 (2006).82.Molfino, N. A. et al. Part 2, randomised placebo-controlled trial to judge the efficacy and security of an anti-GM-CSF antibody (KB003) in sufferers with inadequately managed bronchial asthma. BMJ Open 6, e007709 (2016).83.Barnes, P. J. Position of GATA-Three in allergic ailments. Curr. Mol. Med. eight, 330–334 (2008).84.Finotto, S. et al. Remedy of allergic airway irritation and hyperresponsiveness by antisense-induced native blockade of GATA-Three expression. J. Exp. Med. 193, 1247–1260 (2001).85.Maneechotesuwan, Ok. et al. Suppression of GATA-Three nuclear import and phosphorylation: a novel mechanism of corticosteroid motion in allergic illness. PLoS Med. 6, e1000076 (2009).86.Krug, N. et al. Allergen-induced asthmatic responses modified by a GATA3-specific DNAzyme. N. Engl. J. Med. 372, 1987–1995 (2015). This research exhibits that an inhaled GATA3-blocking DNAzyme modestly reduces the response to inhaled allergen in sufferers with gentle bronchial asthma.
87.Berry, M. A. et al. Proof of a job of tumor necrosis issue alpha in refractory bronchial asthma. N. Engl. J. Med. 354, 697–708 (2006).88.Howarth, P. H. et al. Tumour necrosis issue (TNFalpha) as a novel therapeutic goal in symptomatic corticosteroid dependent bronchial asthma. Thorax 60, 1012–1018 (2005).89.Erin, E. M. et al. The results of a monoclonal antibody directed in opposition to tumour necrosis factor-alpha in bronchial asthma. Am. J. Respir. Crit. Care Med. 174, 753–762 (2006).90.Wenzel, S. E. et al. A randomized, double-blind, placebo-controlled research of TNF-α blockade in extreme persistent bronchial asthma. Am. J. Respir. Crit. Care Med. 179, 549–558 (2009). This huge research demonstrates a scarcity of impact and unwanted effects of anti-TNF remedy in sufferers with extreme bronchial asthma.
91.Rennard, S. I. et al. The protection and efficacy of infliximab in average to extreme continual obstructive pulmonary illness. Am. J. Respir. Crit. Care Med. 175, 926–934 (2007). This research exhibits a scarcity of medical impact and critical unwanted effects with an anti-TNF remedy in sufferers with extreme COPD.
92.Suissa, S., Ernst, P. & Hudson, M. TNF-alpha antagonists and the prevention of hospitalisation for continual obstructive pulmonary illness. Pulm. Pharmacol. Ther. 21, 234–238 (2008).93.Dentener, M. A. et al. Impact of infliximab on native and systemic irritation in continual obstructive pulmonary illness: a pilot research. Respiration 76, 275–282 (2008).94.Al-Ramli, W. et al. T(H)17-associated cytokines (IL-17A and IL-17F) in extreme bronchial asthma. J. Allergy Clin. Immunol. 123, 1185–1187 (2009).95.Ricciardolo, F. L. M. et al. Identification of IL-17F/frequent exacerbator endotype in bronchial asthma. J. Allergy Clin. Immunol. 140, 395–406 (2017).96.Alcorn, J. F., Crowe, C. R. & Kolls, J. Ok. TH17 cells in bronchial asthma and COPD. Annu. Rev. Physiol. 72, 495–516 (2010).97.Di Stefano, A. et al. Th17-related cytokine expression is elevated within the bronchial mucosa of steady COPD sufferers. Clin. Exp. Immunol 157, 316–324 (2009).98.Maneechotesuwan, Ok., Kasetsinsombat, Ok., Wongkajornsilp, A. & Barnes, P. J. Decreased indoleamine 2,Three-dioxygenase exercise and IL-10/IL-17 A ratio in sufferers with COPD. Thorax 68, 330–337 (2013).99.Shen, N., Wang, J., Zhao, M., Pei, F. & He, B. Anti-interleukin-17 antibodies attenuate airway irritation in tobacco-smoke-exposed mice. Inhal. Toxicol. 23, 212–218 (2011).100.McKinley, L. et al. TH17 cells mediate steroid-resistant airway irritation and airway hyperresponsiveness in mice. J. Immunol. 181, 4089–4097 (2008).101.Busse, W. W. et al. Randomized, double-blind, placebo-controlled research of brodalumab, a human anti-IL-17 receptor monoclonal antibody, in average to extreme bronchial asthma. Am. J. Respir. Crit. Care Med. 188, 1294–1302 (2013). This research exhibits a scarcity of medical impact of an anti-IL-17R antibody in sufferers with extreme bronchial asthma.
102.Eich, A. et al. A randomized, placebo-controlled section 2 trial of CNTO 6785 in continual obstructive pulmonary illness. COPD 14, 476–483 (2017).103.Duvallet, E., Semerano, L., Assier, E., Falgarone, G. & Boissier, M. C. Interleukin-23: a key cytokine in inflammatory ailments. Ann. Med. 43, 503–511 (2011).104.Fujii, U. et al. IL-23 is important for the event of elastase-induced pulmonary irritation and emphysema. Am. J. Respir. Cell. Mol. Biol. 55, 697–707 (2016).105.Benson, J. M. et al. Therapeutic focusing on of the IL-12/23 pathways: era and characterization of ustekinumab. Nat. Biotechnol. 29, 615–624 (2011).106.Papp, Ok. A. et al. Risankizumab versus ustekinumab for moderate-to-severe plaque psoriasis. N. Engl. J. Med. 376, 1551–1560 (2017).107.US Nationwide Library of Medication. ClincalTrials.gov https://clinicaltrials.gov/ct2/present/NCT02443298 (2018).108.Sousa, A. R., Lane, S. J., Nakhosteen, J. A., Lee, T. H. & Poston, R. N. 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