2. Cao TBT, Quoc QL, Yang EM, et al. Tissue inhibitor of metalloproteinase-1 enhances eosinophilic airway inflammation in severe asthma. Allergy Asthma Immunol Res 2023;15:451–472.

3. Quoc QL, Choi Y, Thi Bich TC, Yang EM, Shin YS, Park HS. S100A9 in adult asthmatic patients: a biomarker for neutrophilic asthma. Exp Mol Med 2021;53:1170–1179.

4. Bich TCT, Quoc QL, Choi Y, et al. Serum amyloid A1: a biomarker for neutrophilic airway inflammation in adult asthmatic patients. Allergy Asthma Immunol Res 2022;14:40–58.

5. Lee DH, Jang JH, Sim S, Choi Y, Park HS. Epithelial autoantigen-specific IgG antibody enhances eosinophil extracellular trap formation in severe asthma. Allergy Asthma Immunol Res 2022;14:479–493.

6. Ricciardolo FLM, Carriero V, Bertolini F. Which therapy for non-type(T)2/T2-low asthma. J Pers Med 2021;12:10.

7. Moore WC, Hastie AT, Li X, et al. Sputum neutrophil counts are associated with more severe asthma phenotypes using cluster analysis. J Allergy Clin Immunol 2014;133:1557–1563e5.

8. Shi B, Li W, Hao Y, et al. Characteristics of inflammatory phenotypes among patients with asthma: relationships of blood count parameters with sputum cellular phenotypes. Allergy Asthma Clin Immunol 2021;17:47.

9. Kyriakopoulos C, Gogali A, Bartziokas K, Kostikas K. Identification and treatment of T2-low asthma in the era of biologics. ERJ Open Res 2021;7:00309–2020.

10. Shah SP, Grunwell J, Shih J, Stephenson S, Fitzpatrick AM. Exploring the utility of noninvasive type 2 inflammatory markers for prediction of severe asthma exacerbations in children and adolescents. J Allergy Clin Immunol Pract 2019;7:2624–2633e2.

11. Heaney LG, Busby J, Hanratty CE, et al. Composite type-2 biomarker strategy versus a symptom-risk-based algorithm to adjust corticosteroid dose in patients with severe asthma: a multicentre, single-blind, parallel group, randomised controlled trial. Lancet Respir Med 2021;9:57–68.

12. Carr TF. Treatment approaches for the patient with T2 low asthma. Ann Allergy Asthma Immunol 2021;127:530–535.

13. Wen Y, Reid DW, Zhang D, Ward C, Wood-Baker R, Walters EH. Assessment of airway inflammation using sputum, BAL, and endobronchial biopsies in current and ex-smokers with established COPD. Int J Chron Obstruct Pulmon Dis 2010;5:327–334.

14. Agache I, Strasser DS, Pierlot GM, Farine H, Izuhara K, Akdis CA. Monitoring inflammatory heterogeneity with multiple biomarkers for multidimensional endotyping of asthma. J Allergy Clin Immunol 2018;141:442–445.

15. Schleich FN, Manise M, Sele J, Henket M, Seidel L, Louis R. Distribution of sputum cellular phenotype in a large asthma cohort: predicting factors for eosinophilic vs neutrophilic inflammation. BMC Pulm Med 2013;13:11.

16. Spanevello A, Confalonieri M, Sulotto F, et al. Induced sputum cellularity. Reference values and distribution in normal volunteers. Am J Respir Crit Care Med 2000;162(3 Pt 1):1172–1174.

17. Simpson JL, Scott R, Boyle MJ, Gibson PG. Inflammatory subtypes in asthma: assessment and identification using induced sputum. Respirology 2006;11:54–61.

18. Belda J, Leigh R, Parameswaran K, O’Byrne PM, Sears MR, Hargreave FE. Induced sputum cell counts in healthy adults. Am J Respir Crit Care Med 2000;161(2 Pt 1):475–478.

19. Hur GY, Ye YM, Yang E, Park HS. Serum potential biomarkers according to sputum inflammatory cell profiles in adult asthmatics. Korean J Intern Med 2020;35:988–997.

20. Ntontsi P, Loukides S, Bakakos P, et al. Clinical, functional and inflammatory characteristics in patients with paucigranulocytic stable asthma: comparison with different sputum phenotypes. Allergy 2017;72:1761–1767.

21. Bullone M, Carriero V, Bertolini F, et al. Elevated serum IgE, oral corticosteroid dependence and IL-17/22 expression in highly neutrophilic asthma. Eur Respir J 2019;54:1900068.

22. Chupp GL, Lee CG, Jarjour N, et al. A chitinase-like protein in the lung and circulation of patients with severe asthma. N Engl J Med 2007;357:2016–2027.

23. Hinks TSC, Brown T, Lau LCK, et al. Multidimensional endotyping in patients with severe asthma reveals inflammatory heterogeneity in matrix metalloproteinases and chitinase 3-like protein 1. J Allergy Clin Immunol 2016;138:61–75.

24. Gibson PG, Simpson JL, Saltos N. Heterogeneity of airway inflammation in persistent asthma : evidence of neutrophilic inflammation and increased sputum interleukin-8. Chest 2001;119:1329–1336.

25. Kuipers I, Louis R, Manise M, et al. Increased glutaredoxin-1 and decreased protein S-glutathionylation in sputum of asthmatics. Eur Respir J 2013;41:469–472.

26. Hastie AT, Moore WC, Meyers DA, et al. Analyses of asthma severity phenotypes and inflammatory proteins in subjects stratified by sputum granulocytes. J Allergy Clin Immunol 2010;125:1028–1036e13.

27. Tliba O, Panettieri RA Jr. Paucigranulocytic asthma: uncoupling of airway obstruction from inflammation. J Allergy Clin Immunol 2019;143:1287–1294.

28. Diver S, Khalfaoui L, Emson C, et al. Effect of tezepelumab on airway inflammatory cells, remodelling, and hyperresponsiveness in patients with moderate-to-severe uncontrolled asthma (CASCADE): a double-blind, randomised, placebo-controlled, phase 2 trial. Lancet Respir Med 2021;9:1299–1312.

29. Wechsler ME, Ruddy MK, Pavord ID, et al. Efficacy and safety of itepekimab in patients with moderate-to-severe asthma. N Engl J Med 2021;385:1656–1668.

30. Kelsen SG, Agache IO, Soong W, et al. Astegolimab (anti-ST2) efficacy and safety in adults with severe asthma: A randomized clinical trial. J Allergy Clin Immunol 2021;148:790–798.

31. Crim C, Stone S, Millar V, et al. IL-33 receptor inhibition in subjects with uncontrolled asthma: a randomized, placebo-controlled trial. J Allergy Clin Immunol Glob 2022;1:198–208.

32. Watz H, Uddin M, Pedersen F, et al. Effects of the CXCR2 antagonist AZD5069 on lung neutrophil recruitment in asthma. Pulm Pharmacol Ther 2017;45:121–123.

33. O’Byrne PM, Metev H, Puu M, et al. Efficacy and safety of a CXCR2 antagonist, AZD5069, in patients with uncontrolled persistent asthma: a randomised, double-blind, placebo-controlled trial. Lancet Respir Med 2016;4:797–806.

34. Djukanović R, Harrison T, Johnston SL, et al. The effect of inhaled IFN-β on worsening of asthma symptoms caused by viral infections. a randomized trial. Am J Respir Crit Care Med 2014;190:145–154.

35. McCrae C, Olsson M, Gustafson P, et al. INEXAS: a phase 2 randomized trial of on-demand inhaled interferon beta-1a in severe asthmatics. Clin Exp Allergy 2021;51:273–283.

36. Busse WW, Holgate S, Kerwin E, et al. 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;188:1294–1302.

37. Clinical Trials.gov. Study to assess the efficacy and safety of CJM112 in patients with inadequately controlled severe asthma [Internet] Bethesda (MD): National Library of Medicine, c2017. [cited 2023 May 13]. Available from: https://clinicaltrials.gov/ct2/show/NCT03299686. 38. Brightling CE, Nair P, Cousins DJ, Louis R, Singh D. Risankizumab in severe asthma - a phase 2a, placebo-controlled trial. N Engl J Med 2021;385:1669–1679.

39. Hernandez ML, Mills K, Almond M, et al. IL-1 receptor antagonist reduces endotoxin-induced airway inflammation in healthy volunteers. J Allergy Clin Immunol 2015;135:379–385.

40. Kardas G, Panek M, Kuna P, Damiański P, Kupczyk M. Monoclonal antibodies in the management of asthma: Dead ends, current status and future perspectives. Front Immunol 2022;13:983852.

41. Clinical Trials.gov. A phase 2a study to evaluate the effects of sirukumab in subjects with severe poorly controlled asthma [Internet] Bethesda (MD): National Library of Medicine, c2016. [cited 2023 May 13]. Available from: https://clinicaltrials.gov/ct2/show/NCT02794519. 42. Clinical Trials.gov. PrecISE (precision interventions for severe and/or exacerbation-prone asthma) network study [Internet] Bethesda (MD): National Library of Medicine, c2019. [cited 2023 May 13]. Available from: https://clinicaltrials.gov/study/NCT04129931. 43. Berry MA, Hargadon B, Shelley M, et al. Evidence of a role of tumor necrosis factor alpha in refractory asthma. N Engl J Med 2006;354:697–708.

44. Wenzel SE, Barnes PJ, Bleecker ER, et al. A randomized, double-blind, placebo-controlled study of tumor necrosis factor-alpha blockade in severe persistent asthma. Am J Respir Crit Care Med 2009;179:549–558.

45. Huang CY, Chung CL, Hu TH, Chen JJ, Liu PF, Chen CL. Recent progress in TGF-β inhibitors for cancer therapy. Biomed Pharmacother 2021;134:111046.

46. Sartiani L, Bartolucci G, Pallecchi M, Spinelli V, Cerbai E. Pharmacological basis of the antifibrotic effects of pirfenidone: Mechanistic insights from cardiac in-vitro and in-vivo models. Front Cardiovasc Med 2022;9:751499.

47. Jin R, Xu J, Gao Q, et al. IL-33-induced neutrophil extracellular traps degrade fibronectin in a murine model of bronchopulmonary dysplasia. Cell Death Discov 2020;6:33.

48. Pelaia C, Pelaia G, Crimi C, et al. Tezepelumab: a potential new biological therapy for severe refractory asthma. Int J Mol Sci 2021;22:4369.

49. Pham DL, Ban GY, Kim SH, et al. Neutrophil autophagy and extracellular DNA traps contribute to airway inflammation in severe asthma. Clin Exp Allergy 2017;47:57–70.

50. Quoc QL, Cao TBT, Moon JY, et al. Contribution of monocyte and macrophage extracellular traps to neutrophilic airway inflammation in severe asthma. Allergol Int 2024;73:81–93.

51. Badi YE, Salcman B, Taylor A, et al. IL1RAP expression and the enrichment of IL-33 activation signatures in severe neutrophilic asthma. Allergy 2023;78:156–167.

52. Chung KF. Asthma phenotyping: a necessity for improved therapeutic precision and new targeted therapies. J Intern Med 2016;279:192–204.

53. Rahmawati SF, Te Velde M, Kerstjens HAM, Dömling ASS, Groves MR, Gosens R. Pharmacological rationale for targeting IL-17 in asthma. Front Allergy 2021;2:694514.

54. Li SF, Gong MJ, Zhao FR, et al. Type I interferons: distinct biological activities and current applications for viral infection. Cell Physiol Biochem 2018;51:2377–2396.

55. Bhakta NR, Christenson SA, Nerella S, et al. IFN-stimulated gene expression, type 2 inflammation, and endoplasmic reticulum stress in asthma. Am J Respir Crit Care Med 2018;197:313–324.

56. Annunziato F, Romagnani C, Romagnani S. The 3 major types of innate and adaptive cell-mediated effector immunity. J Allergy Clin Immunol 2015;135:626–635.

57. Kim J, Chang Y, Bae B, et al. Innate immune crosstalk in asthmatic airways: Innate lymphoid cells coordinate polarization of lung macrophages. J Allergy Clin Immunol 2019;143:1769–1782e11.

58. Raundhal M, Morse C, Khare A, et al. High IFN-γ and low SLPI mark severe asthma in mice and humans. J Clin Invest 2015;125:3037–3050.

59. Gauthier M, Chakraborty K, Oriss TB, et al. Severe asthma in humans and mouse model suggests a CXCL10 signature underlies corticosteroid-resistant Th1 bias. JCI Insight 2017;2:e94580.

60. Singhania A, Wallington JC, Smith CG, et al. Multitissue transcriptomics delineates the diversity of airway T cell functions in asthma. Am J Respir Cell Mol Biol 2018;58:261–270.

61. Östling J, van Geest M, Schofield JPR, et al. IL-17-high asthma with features of a psoriasis immunophenotype. J Allergy Clin Immunol 2019;144:1198–1213.

62. Krishnamoorthy N, Douda DN, Brüggemann TR, et al. Neutrophil cytoplasts induce TH17 differentiation and skew inflammation toward neutrophilia in severe asthma. Sci Immunol 2018;3:eaao4747.

63. Pelletier M, Maggi L, Micheletti A, et al. Evidence for a crosstalk between human neutrophils and Th17 cells. Blood 2010;115:335–343.

64. Clinical Trials.gov. Efficacy and safety of BI 655066/ABBV-066 (Risankizumab) in patients with severe persistent asthma [Internet] Bethesda (MD): National Library of Medicine, c2015. [cited 2023 May 13]. Available from: https://clinicaltrials.gov/ct2/show/NCT02443298. 65. Hinks TSC, Levine SJ, Brusselle GG. Treatment options in type-2 low asthma. Eur Respir J 2021;57:2000528.

66. Fricker M, Qin L, Sánchez-Ovando S, et al. An altered sputum macrophage transcriptome contributes to the neutrophilic asthma endotype. Allergy 2022;77:1204–1215.

67. van der Veen TA, de Groot LES, Melgert BN. The different faces of the macrophage in asthma. Curr Opin Pulm Med 2020;26:62–68.

68. Kim RY, Pinkerton JW, Essilfie AT, et al. Role for NLRP3 inflammasome-mediated, IL-1β-dependent responses in severe, steroid- resistant asthma. Am J Respir Crit Care Med 2017;196:283–297.

69. Lachowicz-Scroggins ME, Dunican EM, Charbit AR, et al. Extracellular DNA, neutrophil extracellular traps, and inflammasome activation in severe asthma. Am J Respir Crit Care Med 2019;199:1076–1085.

70. Choi Y, Park H, Park HS, Kim YK. Extracellular vesicles, a key mediator to link environmental microbiota to airway immunity. Allergy Asthma Immunol Res 2017;9:101–106.

71. Choi Y, Lee Y, Park HS. Which factors associated with activated eosinophils contribute to the pathogenesis of aspirin-exacerbated respiratory disease? Allergy Asthma Immunol Res 2019;11:320–329.

72. Choi Y, Sim S, Park HS. Distinct functions of eosinophils in severe asthma with type 2 phenotype: clinical implications. Korean J Intern Med 2020;35:823–833.

73. Choi Y, Park HS, Jee YK. Urine microbial extracellular vesicles can be potential and novel biomarkers for allergic diseases. Allergy Asthma Immunol Res 2021;13:5–7.

74. Lee DH, Park HK, Lee HR, et al. Immunoregulatory effects of Lactococcus lactis-derived extracellular vesicles in allergic asthma. Clin Transl Allergy 2022;12:e12138.

75. Choi Y, Park HS, Kim YK. Bacterial extracellular vesicles: a candidate molecule for the diagnosis and treatment of allergic diseases. Allergy Asthma Immunol Res 2023;15:279–289.

76. Sim S, Lee DH, Kim KS, et al. Micrococcus luteus-derived extracellular vesicles attenuate neutrophilic asthma by regulating miRNAs in airway epithelial cells. Exp Mol Med 2023;55:196–204.

77. Yokoyama A, Kohno N, Fujino S, et al. Circulating interleukin-6 levels in patients with bronchial asthma. Am J Respir Crit Care Med 1995;151:1354–1358.

78. Chu DK, Al-Garawi A, Llop-Guevara A, et al. Therapeutic potential of anti-IL-6 therapies for granulocytic airway inflammation in asthma. Allergy Asthma Clin Immunol 2015;11:14.

79. Peters MC, McGrath KW, Hawkins GA, et al. Plasma interleukin-6 concentrations, metabolic dysfunction, and asthma severity: a cross-sectional analysis of two cohorts. Lancet Respir Med 2016;4:574–584.

80. Gubernatorova EO, Namakanova OA, Gorshkova EA, Medvedovskaya AD, Nedospasov SA, Drutskaya MS. Novel anti-cytokine strategies for prevention and treatment of respiratory allergic diseases. Front Immunol 2021;12:601842.

81. Peters MC, Ringel L, Dyjack N, et al. A transcriptomic method to determine airway immune dysfunction in T2-high and T2-low asthma. Am J Respir Crit Care Med 2019;199:465–477.

82. Avci AB, Feist E, Burmester GR. Targeting IL-6 or IL-6 receptor in rheumatoid arthritis: what’s the difference? BioDrugs 2018;32:531–546.

83. Thomas PS, Yates DH, Barnes PJ. Tumor necrosis factor-alpha increases airway responsiveness and sputum neutrophilia in normal human subjects. Am J Respir Crit Care Med 1995;152:76–80.

84. Kramer EL, Mushaben EM, Pastura PA, et al. Early growth response-1 suppresses epidermal growth factor receptor-mediated airway hyperresponsiveness and lung remodeling in mice. Am J Respir Cell Mol Biol 2009;41:415–425.

85. Halwani R, Al-Muhsen S, Al-Jahdali H, Hamid Q. Role of transforming growth factor-β in airway remodeling in asthma. Am J Respir Cell Mol Biol 2011;44:127–133.