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Review

Investigational anti IL-13 asthma treatments: a 2023 update

, ORCID Icon, , ORCID Icon & ORCID Icon
Pages 373-386 | Received 19 Mar 2023, Accepted 15 May 2023, Published online: 18 May 2023

References

  • Marone G, Granata F, Pucino V, et al. The intriguing role of interleukin 13 in the pathophysiology of asthma. Front Pharmacol. 2019;10:1387.
  • Junttila IS. Tuning the cytokine responses: an update on interleukin (IL)-4 and IL-13 receptor complexes. Front Immunol. 2018;9:888.
  • Keegan AD, Zamorano J, Keselman A, et al. IL-4 and IL-13 receptor signaling from 4PS to insulin receptor substrate 2: there and back again, a historical view. Front Immunol. 2018;9:1037.
  • Goenka S, Kaplan MH. Transcriptional regulation by STAT6. Immunol Res. 2011;50(1):87–96.
  • LaPorte SL, Juo ZS, Vaclavikova J, et al. Molecular and structural basis of cytokine receptor pleiotropy in the interleukin-4/13 system. Cell. 2008;132(2):259–272. DOI:10.1016/j.cell.2007.12.030
  • Graber P, Gretener D, Herren S, et al. The distribution of IL-13 receptor alpha1 expression on B cells, T cells and monocytes and its regulation by IL-13 and IL-4. Eur J Immunol. 1998;28(12):4286–4298.
  • Andrews AL, Holloway JW, Puddicombe SM, et al. Kinetic analysis of the interleukin-13 receptor complex. J Biol Chem. 2002;277(48):46073–46078. DOI:10.1074/jbc.M209560200
  • Wilson MS, Elnekave E, Mentink-Kane MM, et al. IL-13Rα2 and IL-10 coordinately suppress airway inflammation, airway-hyperreactivity, and fibrosis in mice. J Clin Invest. 2007;117(10):2941–2951. DOI:10.1172/JCI31546
  • Tabata Y, Khurana Hershey GK. IL-13 receptor isoforms: breaking through the complexity. Curr Allergy Asthma Rep. 2007;7(5):338–345.
  • Yasunaga S, Yuyama N, Arima K, et al. The negative-feedback regulation of the IL-13 signal by the IL-13 receptor α2 chain in bronchial epithelial cells. Cytokine. 2003;24(6):293–303. DOI:10.1016/j.cyto.2003.08.006
  • Penke LR, Ouchi H, Speth JM, et al. Transcriptional regulation of the IL-13Rα2 gene in human lung fibroblasts. Sci Rep. 2020;10(1):1083. DOI:10.1038/s41598-020-57972-1
  • Chen W, Sivaprasad U, Gibson AM, et al. IL-13 receptor α2 contributes to development of experimental allergic asthma. J Allergy Clin Immunol. 2013;132(4):951–8.e86. DOI:10.1016/j.jaci.2013.04.016
  • Chibana K, Trudeau JB, Mustovich AT, et al. IL-13 induced increases in nitrite levels are primarily driven by increases in inducible nitric oxide synthase as compared with effects on arginases in human primary bronchial epithelial cells. Clin Exp Allergy. 2008;38(6):936–946. DOI:10.1111/j.1365-2222.2008.02969.x
  • Maeda D, Kubo T, Kiya K, et al. Periostin is induced by IL-4/IL-13 in dermal fibroblasts and promotes RhoA/ROCK pathway-mediated TGF-β1 secretion in abnormal scar formation. J Plast Surg Hand Surg. 2019;53(5):288–294. DOI:10.1080/2000656X.2019.1612752
  • Kuperman DA, Huang X, Koth LL, et al. Direct effects of interleukin-13 on epithelial cells cause airway hyperreactivity and mucus overproduction in asthma. Nat Med. 2002;8(8):885–889. DOI:10.1038/nm734
  • Bonser LR, Zlock L, Finkbeiner W, et al. Epithelial tethering of MUC5AC-rich mucus impairs mucociliary transport in asthma. J Clin Invest. 2016;126(6):2367–2371.
  • Saha SK, Berry MA, Parker D, et al. Increased sputum and bronchial biopsy IL-13 expression in severe asthma. J Allergy Clin Immunol. 2008;121(3):685–691. DOI:10.1016/j.jaci.2008.01.005
  • Corren J. Role of interleukin-13 in asthma. Curr Allergy Asthma Rep. 2013;13(5):415–420.
  • Grünig G, Warnock M, Wakil AE, et al. Requirement for IL-13 independently of IL-4 in experimental asthma. Science. 1998;282(5397):2261–2263. DOI:10.1126/science.282.5397.2261
  • Blanchard C, Durual S, Estienne M, et al. Eotaxin-3/CCL26 gene expression in intestinal epithelial cells is up-regulated by interleukin-4 and interleukin-13 via the signal transducer and activator of transcription 6. Int J Biochem Cell Biol. 2005;37(12):2559–2573. DOI:10.1016/j.biocel.2005.06.010
  • Bochner BS, Klunk DA, Sterbinsky SA, et al. IL-13 selectively induces vascular cell adhesion molecule-1 expression in human endothelial cells. J Immunol. 1995;154(2):799–803. DOI:10.4049/jimmunol.154.2.799
  • Pope SM, Brandt EB, Mishra A, et al. 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. DOI:10.1067/mai.2001.118600
  • Van der Pouw Kraan TC, Van der Zee JS, Boeije LC, et al. The role of IL-13 in IgE synthesis by allergic asthma patients. Clin Exp Immunol. 1998;111(1):129–135. DOI:10.1046/j.1365-2249.1998.00471.x
  • Cai F, Hornauer H, Peng K, et al. Bioanalytical challenges and improved detection of circulating levels of IL-13. Bioanalysis. 2016;8(4):323–332. DOI:10.4155/bio.15.254
  • Nair P, O’Byrne PM. The interleukin-13 paradox in asthma: effective biology, ineffective biologicals. Eur Respir J. 2019;53(2):1802250. DOI:10.1183/13993003.02250-2018.
  • Pham TH, Chen C, Colice G, et al. Tezepelumab normalizes serum interleukin-5 and -13 levels in patients with severe, uncontrolled asthma. Ann Allergy Asthma Immunol. 2021;127(6):689–691. DOI:10.1016/j.anai.2021.08.008
  • Matera MG, Rogliani P, Calzetta L, et al. TSLP inhibitors for asthma: current status and future prospects. Drugs. 2020;80(5):449–458. DOI:10.1007/s40265-020-01273-4
  • Gauvreau GM, Sehmi R, Ambrose CS, et al. Thymic stromal lymphopoietin: its role and potential as a therapeutic target in asthma. Expert Opin Ther Targets. 2020;24(8):777–792. DOI:10.1080/14728222.2020.1783242
  • Lipworth B, Jabbal S, Kuo CR. Anti-interleukin 13 for asthma: stick or twist? Lancet Respir Med. 2018;6(9):e46–47.
  • Floc’h A L, Allinne J, Nagashima K, et al. Dual blockade of IL-4 and IL-13 with dupilumab, an IL-4Rα antibody, is required to broadly inhibit type 2 inflammation. Allergy. 2020;75(5):1188–1204. DOI:10.1111/all.14151
  • Ricciardolo FLM, Bertolini F, Carriero V. The role of dupilumab in severe asthma. Biomedicines. 2021;9(9):1096.
  • Harb H, Chatila TA. Mechanisms of dupilumab. Clin Exp Allergy. 2020;50(1):5–14.
  • Bao K, Reinhardt RL. The differential expression of IL-4 and IL-13 and its impact on type-2 immunity. Cytokine. 2015;75(1):25–37.
  • May RD, Fung M. Strategies targeting the IL-4/IL-13 axes in disease. Cytokine. 2015;75(1):89–116.
  • May RD, Monk PD, Cohen ES, et al. 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. DOI:10.1111/j.1476-5381.2011.01659.x
  • Popovic B, Breed J, Rees DG, et al. Structural characterisation reveals mechanism of IL-13-neutralising monoclonal antibody tralokinumab as inhibition of binding to IL-13Rα1 and IL-13Rα2. J Mol Biol. 2017;429(2):208–219. DOI:10.1016/j.jmb.2016.12.005
  • Piper E, Brightling C, Niven R, et al. A phase II placebo-controlled study of tralokinumab in moderate-to-severe asthma. Eur Respir J. 2013;41(2):330–338. DOI:10.1183/09031936.00223411
  • Brightling CE, Chanez P, Leigh R, et al. 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. DOI:10.1016/S2213-2600(15)00197-6
  • Russell RJ, Chachi L, FitzGerald JM, et al. Effect of tralokinumab, an interleukin-13 neutralising monoclonal antibody, on eosinophilic airway inflammation in uncontrolled moderate-to-severe asthma (MESOS): a multicentre, double-blind, randomised, placebo-controlled phase 2 trial. Lancet Respir Med. 2018;6(7):499–510. DOI:10.1016/S2213-2600(18)30201-7
  • Panettieri RA Jr, Sjöbring U, Péterffy A, et al. Tralokinumab for severe, uncontrolled asthma (STRATOS 1 and STRATOS 2): two randomised, double-blind, placebo-controlled, phase 3 clinical trials. Lancet Respir Med. 2018;6(7):511–525. DOI:10.1016/S2213-2600(18)30184-X.
  • Busse WW, Brusselle GG, Korn S, et al. Tralokinumab did not demonstrate oral corticosteroid-sparing effects in severe asthma. Eur Respir J. 2019;53(2):1800948. DOI:10.1183/13993003.00948-2018.
  • Zhang Y, Cheng J, Li Y, et al. The safety and efficacy of anti-IL-13 treatment with tralokinumab (CAT-354) in moderate to severe asthma: a systematic review and meta-analysis. J Allergy Clin Immunol Pract. 2019;7(8):2661–2671. DOI:10.1016/j.jaip.2019.05.030
  • Duggan S. Tralokinumab: first approval. Drugs. 2021;81(14):1657–1663.
  • FDA approves Adbry for treatment of moderate-to-severe atopic dermatitis. [cited Mar 13, 2023]. Available from: https://www.pharmacytimes.com/view/fda-approves-adbry-for-treatment-of-moderate-to-severe-atopic-dermatitis.
  • Hodsman P, Ashman C, Cahn A, et al. A phase 1, randomized, placebo-controlled, dose-escalation study of an anti-IL-13 monoclonal antibody in healthy subjects and mild asthmatics. Br J Clin Pharmacol. 2013;75(1):118–128. DOI:10.1111/j.1365-2125.2012.04334.x
  • De Boever EH, Ashman C, Cahn AP, et al. 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. DOI:10.1016/j.jaci.2014.01.002
  • Tripp CS, Cuff C, Campbell AL, et al. RPC4046, a novel anti-interleukin-13 antibody, blocks IL-13 binding to IL-13 α1 and α2 receptors: a randomized, double-blind, placebo-controlled, dose-escalation first-in-human study. Adv Ther. 2017;34(6):1364–1381. DOI:10.1007/s12325-017-0525-8
  • Dellon ES, Collins MH, Rothenberg ME, et al. Long-term efficacy and tolerability of RPC4046 in an open-label extension trial of patients with eosinophilic esophagitis. Clin Gastroenterol Hepatol. 2021;19(3):473–483. DOI:10.1016/j.cgh.2020.03.036
  • Gauvreau GM, Boulet LP, Cockcroft DW, et al. Effects of interleukin-13 blockade on allergen-induced airway responses in mild atopic asthma. Am J Respir Crit Care Med. 2011;183(8):1007–1014. DOI:10.1164/rccm.201008-1210OC
  • Kasaian MT, Raible D, Marquette K, et al. IL-13 antibodies influence IL-13 clearance in humans by modulating scavenger activity of IL-13Rα2. J Immunol. 2011;187(1):561–569. DOI:10.4049/jimmunol.1100467
  • van Hartingsveldt B, Nnane IP, Bouman-Thio E, et al. Safety, tolerability and pharmacokinetics of a human anti-interleukin-13 monoclonal antibody (CNTO 5825) in an ascending single-dose first-in-human study. Br J Clin Pharmacol. 2013;75(5):1289–1298. DOI:10.1111/j.1365-2125.2012.04477.x
  • Gozzard N, Lightwood D, Tservistas M, et al. Novel inhaled delivery of anti-IL-13 MAb (FAb fragment): preclinical efficacy in allergic asthma. Eur Respir J. 2017;50:A4019.
  • Burgess G, Boyce M, Jones M, et al. Randomized study of the safety and pharmacodynamics of inhaled interleukin-13 monoclonal antibody fragment VR942. EBioMedicine. 2018;35:67–75.
  • Adis Insight. Eblasakimab - ASLAN Pharmaceuticals. [cited Mar 13, 2023]. Available from: https://adisinsight.springer.com/drugs/800013682.
  • Veverka KA, Kobayashi K, Menezes J, et al. Interim analysis results from a proof-of concept study for ASLAN004 in adult moderate to severe atopic dermatitis: a double blind, randomized, placebo-controlled study. J Clin Aesthet Dermatol. 2022;15(4 Suppl 1):S13.
  • Ultsch M, Bevers J, Nakamura G, et al. Structural basis of signaling blockade by anti-IL-13 antibody lebrikizumab. J Mol Biol. 2013;425(8):1330–1339. DOI:10.1016/j.jmb.2013.01.024
  • Corren J, Lemanske RF, Hanania NA, et al. Lebrikizumab treatment in adults with asthma. N Engl J Med. 2011;365(12):1088–1098. DOI:10.1056/NEJMoa1106469
  • McClintock D, Corren J, Hanania N, et al. Lebrikizumab, an anti IL-13 monoclonal antibody, reduces severe asthma exacerbations over 32 weeks in adults with inadequately controlled asthma. Am J Respir Crit Care Med. 2012;185:A3959.
  • Scheerens H, Arron J, Choy D, et al. Lebrikizumab treatment reduces serum periostin levels in asthma patients with elevated baseline levels of periostin. Am J Respir Crit Care Med. 2012;185:A3960.
  • Scheerens H, Arron JR, Zheng Y, et al. The effects of lebrikizumab in patients with mild asthma following whole lung allergen challenge. Clin Exp Allergy. 2014;44(1):38–46. DOI:10.1111/cea.12220
  • Hanania NA, Noonan M, Corren J, et al. Lebrikizumab in moderate-to-severe asthma: pooled data from two randomised placebo-controlled studies. Thorax. 2015;70(8):748–756. DOI:10.1136/thoraxjnl-2014-206719
  • Hanania NA, Korenblat P, Chapman KR, et al. Efficacy and safety of lebrikizumab in patients with uncontrolled asthma (LAVOLTA I and LAVOLTA II): replicate, phase 3, randomised, double-blind, placebo-controlled trials. Lancet Respir Med. 2016;4(10):781–796. DOI:10.1016/S2213-2600(16)30265-X.
  • Austin CD, Gonzalez Edick M, Ferrando RE, et al. A randomized, placebo-controlled trial evaluating effects of lebrikizumab on airway eosinophilic inflammation and remodelling in uncontrolled asthma (CLAVIER). Clin Exp Allergy. 2020;50(12):1342–1351. DOI:10.1111/cea.13731
  • Szefler SJ, Roberts G, Rubin AS, et al. Efficacy, safety, and tolerability of lebrikizumab in adolescent patients with uncontrolled asthma (ACOUSTICS). Clin Transl Allergy. 2022;12(7):e12176. DOI:10.1002/clt2.12176.
  • Adis insight lebrikizumab – dermira. [cited Mar 13, 2023]. Available from: https://adisinsight.springer.com/drugs/800024496
  • Kasaian MT, Tan XY, Jin M, et al. 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. DOI:10.1124/jpet.108.136515
  • Oh CK, Geba GP, Molfino N. Investigational therapeutics targeting the IL-4/IL-13/STAT-6 pathway for the treatment of asthma. Eur Respir Rev. 2010;19(115):46–54.
  • Bieber T. Interleukin-13: targeting an underestimated cytokine in atopic dermatitis. Allergy. 2020;75(1):54–62.
  • Majumdar S, Ghosh A, Saha S. Modulating interleukins and their receptors interactions with small chemicals using in silico approach for asthma. Curr Top Med Chem. 2018;18(13):1123–1134.
  • Georas SN, Donohue P, Connolly M, et al. JAK inhibitors for asthma. J Allergy Clin Immunol. 2021;148(4):953–963. DOI:10.1016/j.jaci.2021.08.013.
  • Barnes PJ, Page C. Kinases as novel therapeutic targets in asthma and chronic obstructive pulmonary disease. Pharmacol Rev. 2016;68(3):788–815.
  • Ashino S, Takeda K, Li H, et al. Janus kinase 1/3 signaling pathways are key initiators of TH differentiation and lung allergic responses. J Allergy Clin Immunol. 2014;133(4):1162–1174. DOI:10.1016/j.jaci.2013.10.036
  • Calbet M, Ramis I, Calama E, et al. Novel inhaled pan-JAK inhibitor, LAS194046, reduces allergen-induced airway inflammation, late asthmatic response, and pSTAT activation in brown Norway rats. J Pharmacol Exp Ther. 2019;370(2):137–147. DOI:10.1124/jpet.119.256263
  • Machado MAÁ, Moura CS, Guerra SF, et al. Effectiveness and safety of tofacitinib in rheumatoid arthritis: a cohort study. Arthritis Res Ther. 2018;20(1):60. DOI:10.1186/s13075-018-1539-6
  • Bissonnette R, Papp KA, Poulin Y, et al. Topical tofacitinib for atopic dermatitis: a phase IIa randomized trial. Br J Dermatol. 2016;175(5):902–911. DOI:10.1111/bjd.14871
  • Bieber T, Simpson EL, Silverberg JI, et al. Abrocitinib versus placebo or dupilumab for atopic dermatitis. N Engl J Med. 2021;384(12):1101–1112. DOI:10.1056/NEJMoa2019380
  • Betancor D, Valverde-Monge M, Sastre J. Upadacitinib-induced remission of allergic asthma: a case report. J Allergy Clin Immunol Pract. 2021;9(11):4162–4163.
  • Braithwaite IE, Cai F, Tom JA, et al. Inhaled JAK inhibitor GDC-0214 reduces exhaled nitric oxide in patients with mild asthma: a randomized, controlled, proof-of-activity trial. J Allergy Clin Immunol. 2021;148(3):783–789. DOI:10.1016/j.jaci.2021.02.042
  • Chen H, Kunder R, Zou Y, et al. Inhaled JAK inhibitor GDC-4379 reduces FeNO in patients with mild asthma. Eur Respir J. 2021;58: OA1196.
  • Pfeifer ND, Guerin T, Colley K, et al. Safety, pharmacokinetics, and pharmacodynamics of TD-8236, an inhaled pan-JAK inhibitor, following single- and multiple-ascending doses in healthy volunteers and mild asthmatics. Eur Respir J. 2021;58: OA1195.
  • Wiegman CH, Russell KE, Seiffert J, et al. The selective pan-Janus kinase (JAK) inhibitor Vr588 demonstrates potent anti-inflammatory activity in a murine chronic house dust mite (HDM) model of asthma. Am J Respir Crit Care Med. 2015;191:A6435.
  • Zak M, Hanan EJ, Lupardus P, et al. Discovery of a class of highly potent Janus Kinase 1/2 (JAK1/2) inhibitors demonstrating effective cell-based blockade of IL-13 signaling. Bioorg Med Chem Lett. 2019;29(12):1522–1531. DOI:10.1016/j.bmcl.2019.04.008
  • Ma Q, Tong H, Jing J. High throughput virtual screening strategy to develop a potential treatment for bronchial asthma by targeting interleukin 13 cytokine signaling. Allergol IMMUNOPATH (Madr). 2022;50(6):22–31.
  • Wang W, Li Y, Lv Z, et al. Bronchial allergen challenge of patients with atopic asthma triggers an alarmin (IL-33, TSLP, and IL-25) response in the airways epithelium and submucosa. J Immunol. 2018;201(8):2221–2231. DOI:10.4049/jimmunol.1800709
  • Venkataramani S, Low S, Weigle B, et al. Design and characterization of Zweimab and Doppelmab, high affinity dual antagonistic anti-TSLP/IL13 bispecific antibodies. Biochem Biophys Res Commun. 2018;504(1):19–24. DOI:10.1016/j.bbrc.2018.08.064
  • Staton TL, Peng K, Owen R, et al. A phase I, randomized, observer-blinded, single and multiple ascending-dose study to investigate the safety, pharmacokinetics, and immunogenicity of BITS7201A, a bispecific antibody targeting IL-13 and IL-17, in healthy volunteers. BMC Pulm Med. 2019;19(1):5. DOI:10.1186/s12890-018-0763-9
  • Wu F, Huang Y, Zhang P, et al. Interleukin-13 peptide vaccine induces protective humoral immunity in murine asthma models. Oncotarget. 2017;9(6):6678–6690. DOI:10.18632/oncotarget.19950
  • Mohsen MO, Bachmann MF. Virus-like particle vaccinology, from bench to bedside. Cell Mol Immunol. 2022;19(9):993–1011.
  • Conde E, Bertrand R, Balbino B, et al. Dual vaccination against IL-4 and IL-13 protects against chronic allergic asthma in mice. Nat Commun. 2021;12(1):2574. DOI:10.1038/s41467-021-22834-5
  • Foerster J, Molęda A. Feasibility analysis of interleukin-13 as a target for a therapeutic vaccine. Vaccines (Basel). 2019;7(1):20.
  • Dunican EM, Elicker BM, Gierada DS, et al. Mucus plugs in patients with asthma linked to eosinophilia and airflow obstruction. J Clin Invest. 2018;128(3):997–1009. DOI:10.1172/JCI95693
  • Jia G, Erickson RW, Choy DF, et al. Periostin is a systemic biomarker of eosinophilic airway inflammation in asthmatic patients. J Allergy Clin Immunol. 2012;130(3):647–654. DOI:10.1016/j.jaci.2012.06.025
  • Agrawal S, Townley RG. Role of periostin, FENO, IL-13, lebrikzumab, other IL-13 antagonist and dual IL-4/IL-13 antagonist in asthma. Expert Opin Biol Ther. 2014;14(2):165–181.
  • Emson C, Pham TH, Manetz S, et al. Periostin and dipeptidyl peptidase-4: potential biomarkers of interleukin 13 pathway activation in asthma and allergy. Immunol Allergy Clin North Am. 2018;38(4):611–628. DOI:10.1016/j.iac.2018.06.004
  • Gallagher A, Edwards M, Nair P, et al. Anti-interleukin-13 and anti-interleukin-4 agents versus placebo, anti-interleukin-5 or anti-immunoglobulin-E agents, for people with asthma. Cochrane Database Syst Rev. 2021;10(10):CD012929. DOI:10.1002/14651858.CD012929.pub2.
  • Chiba Y, Nakazawa S, Todoroki M, et al. Interleukin-13 augments bronchial smooth muscle contractility with an up-regulation of RhoA protein. Am J Respir Cell Mol Biol. 2009;40(2):159–167. DOI:10.1165/rcmb.2008-0162OC
  • Busse WW, Viswanathan R. What has been learned by cytokine targeting of asthma? J Allergy Clin Immunol. 2022;150(2):235–249. DOI:10.1016/j.jaci.2022.06.010
  • Steinke JW. Anti-interleukin-4 therapy. Immunol Allergy Clin North Am. 2004;24(4):599–614.
  • Shankar A, McAlees JW, Lewkowich IP. Modulation of IL-4/IL-13 cytokine signaling in the context of allergic disease. J Allergy Clin Immunol. 2022;150(2):266–276.
  • Scott G, Asrat S, Allinne J, et al. IL-4 and IL-13, not eosinophils, drive type 2 airway inflammation, remodeling and lung function decline. Cytokine. 2023;162:156091.
  • Haase P, Voehringer D. Regulation of the humoral type 2 immune response against allergens and helminths. Eur J Immunol. 2021;51(2):273–279.
  • Agusti A, Gibson PG, McDonald VM. Treatable traits in airway disease: from theory to practice. J Allergy Clin Immunol Pract. 2023;11(3):713–723. DOI:10.1016/j.jaip.2023.01.011
  • Suruki RY, Daugherty JB, Boudiaf N, et al. The frequency of asthma exacerbations and healthcare utilization in patients with asthma from the UK and USA. BMC Pulm Med. 2017;17(1):74.
  • Bjerke T, Gaustadnes M, Nielsen S, et al. Human blood eosinophils produce and secrete interleukin 4. Respir med. 1996;90(5):271–277. DOI:10.1016/S0954-6111(96)90098-0
  • Levy ML, Bacharier LB, Bateman E, et al. Key recommendations for primary care from the 2022 Global Initiative for Asthma (GINA) update. NPJ Prim Care Respir Med. 2023;33(1):7. DOI:10.1038/s41533-023-00330-1

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