1. Global Initiative for Asthma. Global Strategy for Asthma Management and Prevention, 2021. Available at: https://ginasthma.org/wp-content/uploads/2021/04/GINA-2021-Main-Report_FINAL_21_04_28-WMS.pdf. Accessed: 16.06.2021.
2. GINA. Pocket Guide for asthma management and prevention for adults and children older than 5 years. Updated 2021. Available at: https://ginasthma.org/wp-content/uploads/2021/04/Main-Pocket-Guide-2021-FINAL-WM.pdf. Accessed: 16.06.2021.
3. Gandhi NA, Bennett BL, Graham NMH, et al. Targeting key proximal drivers of type 2 inflammation in disease. Nat Rev Drug Discov. 2016;15(1):35-50. DOI:10.1038/nrd4624
4. Carr S, Watson W. Eosinophilic esophagitis. Allergy Asthma Clin Immunol. 2011;7(Suppl. 1):S8.
5. Steinke JW, Wilson JM. Aspirin-exacerbated respiratory disease: pathophysiological insights and clinical advances. J Asthma Allergy. 2016;9:37-43. DOI:10.2147/JAA.S88739
6. Robinson D, Humbert M, Buhl R, et al. Revisiting Type 2-high and Type 2-low airway inflammation in asthma: current knowledge and therapeutic implications. Clin Exp Allergy. 2017;47(2):161-75. DOI:10.1111/cea.12880
7. Carr TF, Berdnikovs S, Simon HU, et al. Eosinophilic bioactivities in severe asthma. World Allergy Organ J. 2016;9:21. DOI:10.1186/s40413-016-0112-5
8. Narendra D, Blixt J, Hanania NA. Immunological biomarkers in severe asthma. Semin Immunol. 2019;46:101332. DOI:10.1016/j.smim.2019.101332
9. Heffler E, Carpagnano GE, Favero E, et al. Fractional Exhaled Nitric Oxide (FENO) in the management of asthma: a position paper of the Italian Respiratory Society (SIP/IRS) and Italian Society of Allergy, Asthma and Clinical Immunology (SIAAIC). Multidiscip Resp Med. 2020;15:36. DOI:10.4081/mrm.2020.36
10. Katial RK, Bensch GW, Busse WW, et al. Changing Paradigms in the Treatment of Severe Asthma: The Role of Biologic Therapies. J Allergy Clin Immunol Pract. 2017;5(2S):S1-S14. DOI:10.1016/j.jaip.2016.11.029
11. Schleimer RP. Immunopathogenesis of Chronic Rhinosinusitis and Nasal Polyposis. Annu Rev Pathol. 2017;12:331-57. DOI:10.1146/annurev-pathol-052016-100401
12. Global Initiative for Asthma. GINA Report, Global Strategy for Asthma Management and Prevention, 2018.
13. Israel E, Reddel HK. Severe and Difficult-to-Treat Asthma in Adults. 
N Engl J Med. 2017;377:965-76. DOI:10.1056/NEJMra1608969
14. McLeod JJA, Baker B, Ryan JJ. Mast cell production and response to IL-4 and IL-13. Cytokine. 2015;75:57-61. DOI:10.1016/j.cyto.2015.05.019
15. Kaur D, Hollins F, Woodman L, et al. Mast cells express IL-13R alpha 1: IL-13 promotes human lung mast cell proliferation and Fc epsilon RI expression. Allergy. 2006;61:1047-53. DOI:10.1111/j.1398-9995.2006.01139.x
16. Agache I, Akdis CA, Akdis M, et al. EAACI Biologicals Guidelines – Recommendations for severe asthma. Allergy. 2021;76(1):14-44. DOI:10.1111/all.14425
17. Long-Term Safety Evaluation of Dupilumab in Patients With Asthma (LIBERTY ASTHMA TRAVERSE). Available at: https://clinicaltrials.gov/ct2/show/NCT02134028. Accessed: 19.04.2021.
18. Wechsler ME, Ford LB, Maspero JF, et al. Late Breaking Abstract – Dupilumab long-term safety and efficacy in patients with asthma: LIBERTY ASTHMA TRAVERSE. Eur Respir J. 2020;56(Suppl. 64):4613. DOI:10.1183/13993003.congress-2020.4613
19. Platts-Mills TA. The role of immunoglobulin E in allergy and asthma. Am J Respir Crit Care Med. 2001;164(8):S1-S5. DOI:10.1164/ajrccm.164.supplement_1.2103024
20. Alobid I, Benítez P, Bernal-Sprekelsen M, et al. Nasal polyposis and its impact on quality of life: comparison between the effects of medical and surgical treatments. Allergy. 2005;60:452-8. DOI:10.1111/j.1398-9995.2005.00725.x
21. Canonica GW, Malvezzi L, Blasi F, et al. Chronic rhinosinusitis with nasal polyps impact in severe asthma patients: Evidences from the Severe Asthma Network Italy (SANI) registry. Respir Med. 2020;166:105947. DOI:10.1016/j.rmed.2020.105947
22. Heffler E, Bagnasco D, Canonica GW, et al. Strategies to reduce corticosteroid-related adverse events in asthma. Curr Opin Allergy Clin Immunol. 2019;19:61-7. DOI:10.1097/ACI.0000000000000493
23. Bassiouni A, Wormald PJ. Role of frontal sinus surgery in nasal polyp recurrence. Laryngoscope. 2013;123:36-41. DOI:10.1002/lary.23610
24. Loftus C, Soler ZM, Koochakzadeh S, et al. Revision surgery rates in chronic rhinosinusitis with nasal polyps: meta-analysis of risk factors. Int Forum Allergy Rhinol. 2020;10:199-207. DOI:10.1002/alr.22487
25. Sella GCP, Tamashiro E, Sella JA, et al. Asthma Is the Dominant Factor for Recurrence in Chronic Rhinosinusitis. J Allergy Clin Immunol Pract. 2020;8(1):302‐9. DOI:10.1016/j.jaip.2019.08.007
26. Bilodeau L, Boulay ME, Prince P, et al. Comparative clinical and airway inflammatory features of asthmatics with or without polyps. Rhinology. 2010;48:420-5. DOI:10.4193/Rhino09.095
27. Fokkens WJ, Lund VJ, Hopkins C, et al. European Position Paper on Rhinosinusitis and Nasal Polyps 2020. Rhinology. 2020;58(Suppl. S29):1-464. DOI:10.4193/Rhin20.600
28. Schleimer RP, Berdnikovs S. Etiology of epithelial barrier dysfunction in patients with type 2 inflammatory diseases. J Allergy Clin Immunol. 2017;139(6):1752-61. DOI:10.1016/j.jaci.2017.04.010
29. Hulse KE, Stevens WW, Tan BK, Schleimer RP. Pathogenesis of nasal polyposis. Clin Exp Allergy. 2015;45(2):328-46. DOI:10.1111/cea.12472
30. Saatian B, Rezaee F, Desando S, et al. Interleukin-4 and interleukin-13 cause barrier dysfunction in human airway epithelial cells. Tissue Barriers. 2013;1(2):e24333. DOI:10.4161/tisb.24333
31. Sugita K, Steer CA, Martinez-Gonzalez I, et al. Type 2 innate lymphoid cells disrupt bronchial epithelial barrier integrity by targeting tight junctions through IL-13 in asthmatic patients. J Allergy Clin Immunol. 2018;141(1):300-10. DOI:10.1016/j.jaci.2017.02.038
32. Shinkai A, Yoshisue H, Koike M, et al. A novel human CC chemokine, eotaxin-3, which is expressed in IL-4-stimulated vascular endothelial cells, exhibits potent activity toward eosinophils. J Immunol. 1999;163(3):1602-10.
33. Yamada T, Miyabe Y, Ueki S, et al. Eotaxin-3 as a plasma biomarker for mucosal eosinophil infiltration in chronic rhinosinusitis. Front Immunol. 2019;10:74.
34. Kong DH, Kim YK, Kim MR, et al. Emerging Roles of Vascular Cell Adhesion Molecule-1 (VCAM-1) in Immunological Disorders and Cancer. Int J Mol Sci. 2018;19(4):1057. DOI:10.3390/ijms19041057
35. Doran E, Cai F, Holweg CTJ, et al. Interleukin-13 in Asthma and Other Eosinophilic Disorders. Front Med (Lausanne). 2017;4:139. DOI:10.3389/fmed.2017.00139
36. Yoshifuku K, Matsune S, Ohori J, et al. IL-4 and TNF-alpha increased the secretion of eotaxin from cultured fibroblasts of nasal polyps with eosinophil infiltration. Rhinology. 2007;45(3):235-41.
37. Kato A. Immunopathology of chronic rhinosinusitis. Allergol Int. 2015;64(2):121-30. DOI:10.1016/j.alit.2014.12.006
38. de Vries IJ, Langeveld-Wildschut EG, van Reijsen FC, et al. Adhesion molecule expression on skin endothelia in atopic dermatitis: effects of TNF-alpha and IL-4. J Allergy Clin Immunol. 1998;102(3):461-8.
39. Boyce JA, Mellor EA, Perkins B, et al. Human mast cell progenitors use alpha4-integrin, VCAM-1, and PSGL-1 E-selectin for adhesive interactions with human vascular endothelium under flow conditions. Blood. 2002;99(8):2890-6. DOI:10.1182/blood.v99.8.2890
40. Rosenberg HR, Phipps S, Foster PS, et al. Eosinophil trafficking in allergy and asthma. J Allergy Clin Immunol. 2007;119(6):1303-10. DOI:10.1016/j.jaci.2007.03.048
41. Borchers MT, Ansay T, DeSalle R, et al. In vitro assessment of chemokine receptor-ligand interactions mediating mouse eosinophil migration. J Leukoc Biol. 2002;71(6):1033-41. DOI:10.1189/jlb.71.6.1033
42. Nonaka M, Ogihara N, Fukumoto A, et al. Combined stimulation with Poly(I:C), TNF-alpha and Th2 cytokines induces TARC production by human fibroblasts from the nose, bronchioles and lungs. Int Arch Allergy Immunol. 2010;152(4):327-41. DOI:10.1159/000288286
43. Van Dyken SJ, Locksley RM. Interleukin-4- and interleukin-13-mediated alternatively activated macrophages: roles in homeostasis and disease. Annu Rev Immunol. 2013;31:317-43. DOI:10.1146/annurev-immunol-032712-095906
44. Takabayashi T, Kato A, Peters AT, et al. Excessive fibrin deposition in nasal polyps caused by fibrinolytic impairment through reduction of tissue plasminogen activator expression. Am J Respir Crit Care Med. 2013;187:49-57. DOI:10.1164/rccm.201207-1292OC
45. Takabayashi T, Kato A, Peters AT, et al. Increased expression of factor XIII-A in patients with chronic rhinosinusitis with nasal polyps. J Allergy Clin Immunol. 2013;132:584-92. DOI:10.1016/j.jaci.2013.02.003
46. Bachert C, et al. World Allergy Organ J. 2014;7:2.
47. Bachert C, Han JK, Desrosiers M, et al. Efficacy and safety of dupilumab in patients with severe chronic rhinosinusitis with nasal polyps (LIBERTY NP SINUS-24 and LIBERTY NP SINUS-52): results from two multicentre, randomised, double-blind, placebocontrolled, parallel-group phase 3 trials. Lancet. 2019;394(10209):1638-50. 
DOI:10.1016/S0140-6736(19)31881-1
48. Maspero JF, Katelaris CH, Busse WW, et al. Dupilumab Efficacy in Uncontrolled, Moderate-to-Severe Asthma with Self-Reported Chronic Rhinosinusitis. J Allergy Clin Immunol Pract. 2020;8(2):527-39. DOI:10.1016/j.jaip.2019.07.016
49. Tepper RS, Wise RS, Covar R, et al. Asthma outcomes: pulmonary physiology. J Allergy Clin Immunol. 2012;129(Suppl. 3):S65-S87. DOI:10.1016/j.jaci.2011.12.986

________________________________________________

1. Global Initiative for Asthma. Global Strategy for Asthma Management and Prevention, 2021. Available at: https://ginasthma.org/wp-content/uploads/2021/04/GINA-2021-Main-Report_FINAL_21_04_28-WMS.pdf. Accessed: 16.06.2021.
2. GINA. Pocket Guide for asthma management and prevention for adults and children older than 5 years. Updated 2021. Available at: https://ginasthma.org/wp-content/uploads/2021/04/Main-Pocket-Guide-2021-FINAL-WM.pdf. Accessed: 16.06.2021.
3. Gandhi NA, Bennett BL, Graham NMH, et al. Targeting key proximal drivers of type 2 inflammation in disease. Nat Rev Drug Discov. 2016;15(1):35-50. DOI:10.1038/nrd4624
4. Carr S, Watson W. Eosinophilic esophagitis. Allergy Asthma Clin Immunol. 2011;7(Suppl. 1):S8.
5. Steinke JW, Wilson JM. Aspirin-exacerbated respiratory disease: pathophysiological insights and clinical advances. J Asthma Allergy. 2016;9:37-43. DOI:10.2147/JAA.S88739
6. Robinson D, Humbert M, Buhl R, et al. Revisiting Type 2-high and Type 2-low airway inflammation in asthma: current knowledge and therapeutic implications. Clin Exp Allergy. 2017;47(2):161-75. DOI:10.1111/cea.12880
7. Carr TF, Berdnikovs S, Simon HU, et al. Eosinophilic bioactivities in severe asthma. World Allergy Organ J. 2016;9:21. DOI:10.1186/s40413-016-0112-5
8. Narendra D, Blixt J, Hanania NA. Immunological biomarkers in severe asthma. Semin Immunol. 2019;46:101332. DOI:10.1016/j.smim.2019.101332
9. Heffler E, Carpagnano GE, Favero E, et al. Fractional Exhaled Nitric Oxide (FENO) in the management of asthma: a position paper of the Italian Respiratory Society (SIP/IRS) and Italian Society of Allergy, Asthma and Clinical Immunology (SIAAIC). Multidiscip Resp Med. 2020;15:36. DOI:10.4081/mrm.2020.36
10. Katial RK, Bensch GW, Busse WW, et al. Changing Paradigms in the Treatment of Severe Asthma: The Role of Biologic Therapies. J Allergy Clin Immunol Pract. 2017;5(2S):S1-S14. DOI:10.1016/j.jaip.2016.11.029
11. Schleimer RP. Immunopathogenesis of Chronic Rhinosinusitis and Nasal Polyposis. Annu Rev Pathol. 2017;12:331-57. DOI:10.1146/annurev-pathol-052016-100401
12. Global Initiative for Asthma. GINA Report, Global Strategy for Asthma Management and Prevention, 2018.
13. Israel E, Reddel HK. Severe and Difficult-to-Treat Asthma in Adults. 
N Engl J Med. 2017;377:965-76. DOI:10.1056/NEJMra1608969
14. McLeod JJA, Baker B, Ryan JJ. Mast cell production and response to IL-4 and IL-13. Cytokine. 2015;75:57-61. DOI:10.1016/j.cyto.2015.05.019
15. Kaur D, Hollins F, Woodman L, et al. Mast cells express IL-13R alpha 1: IL-13 promotes human lung mast cell proliferation and Fc epsilon RI expression. Allergy. 2006;61:1047-53. DOI:10.1111/j.1398-9995.2006.01139.x
16. Agache I, Akdis CA, Akdis M, et al. EAACI Biologicals Guidelines – Recommendations for severe asthma. Allergy. 2021;76(1):14-44. DOI:10.1111/all.14425
17. Long-Term Safety Evaluation of Dupilumab in Patients With Asthma (LIBERTY ASTHMA TRAVERSE). Available at: https://clinicaltrials.gov/ct2/show/NCT02134028. Accessed: 19.04.2021.
18. Wechsler ME, Ford LB, Maspero JF, et al. Late Breaking Abstract – Dupilumab long-term safety and efficacy in patients with asthma: LIBERTY ASTHMA TRAVERSE. Eur Respir J. 2020;56(Suppl. 64):4613. DOI:10.1183/13993003.congress-2020.4613
19. Platts-Mills TA. The role of immunoglobulin E in allergy and asthma. Am J Respir Crit Care Med. 2001;164(8):S1-S5. DOI:10.1164/ajrccm.164.supplement_1.2103024
20. Alobid I, Benítez P, Bernal-Sprekelsen M, et al. Nasal polyposis and its impact on quality of life: comparison between the effects of medical and surgical treatments. Allergy. 2005;60:452-8. DOI:10.1111/j.1398-9995.2005.00725.x
21. Canonica GW, Malvezzi L, Blasi F, et al. Chronic rhinosinusitis with nasal polyps impact in severe asthma patients: Evidences from the Severe Asthma Network Italy (SANI) registry. Respir Med. 2020;166:105947. DOI:10.1016/j.rmed.2020.105947
22. Heffler E, Bagnasco D, Canonica GW, et al. Strategies to reduce corticosteroid-related adverse events in asthma. Curr Opin Allergy Clin Immunol. 2019;19:61-7. DOI:10.1097/ACI.0000000000000493
23. Bassiouni A, Wormald PJ. Role of frontal sinus surgery in nasal polyp recurrence. Laryngoscope. 2013;123:36-41. DOI:10.1002/lary.23610
24. Loftus C, Soler ZM, Koochakzadeh S, et al. Revision surgery rates in chronic rhinosinusitis with nasal polyps: meta-analysis of risk factors. Int Forum Allergy Rhinol. 2020;10:199-207. DOI:10.1002/alr.22487
25. Sella GCP, Tamashiro E, Sella JA, et al. Asthma Is the Dominant Factor for Recurrence in Chronic Rhinosinusitis. J Allergy Clin Immunol Pract. 2020;8(1):302‐9. DOI:10.1016/j.jaip.2019.08.007
26. Bilodeau L, Boulay ME, Prince P, et al. Comparative clinical and airway inflammatory features of asthmatics with or without polyps. Rhinology. 2010;48:420-5. DOI:10.4193/Rhino09.095
27. Fokkens WJ, Lund VJ, Hopkins C, et al. European Position Paper on Rhinosinusitis and Nasal Polyps 2020. Rhinology. 2020;58(Suppl. S29):1-464. DOI:10.4193/Rhin20.600
28. Schleimer RP, Berdnikovs S. Etiology of epithelial barrier dysfunction in patients with type 2 inflammatory diseases. J Allergy Clin Immunol. 2017;139(6):1752-61. DOI:10.1016/j.jaci.2017.04.010
29. Hulse KE, Stevens WW, Tan BK, Schleimer RP. Pathogenesis of nasal polyposis. Clin Exp Allergy. 2015;45(2):328-46. DOI:10.1111/cea.12472
30. Saatian B, Rezaee F, Desando S, et al. Interleukin-4 and interleukin-13 cause barrier dysfunction in human airway epithelial cells. Tissue Barriers. 2013;1(2):e24333. DOI:10.4161/tisb.24333
31. Sugita K, Steer CA, Martinez-Gonzalez I, et al. Type 2 innate lymphoid cells disrupt bronchial epithelial barrier integrity by targeting tight junctions through IL-13 in asthmatic patients. J Allergy Clin Immunol. 2018;141(1):300-10. DOI:10.1016/j.jaci.2017.02.038
32. Shinkai A, Yoshisue H, Koike M, et al. A novel human CC chemokine, eotaxin-3, which is expressed in IL-4-stimulated vascular endothelial cells, exhibits potent activity toward eosinophils. J Immunol. 1999;163(3):1602-10.
33. Yamada T, Miyabe Y, Ueki S, et al. Eotaxin-3 as a plasma biomarker for mucosal eosinophil infiltration in chronic rhinosinusitis. Front Immunol. 2019;10:74.
34. Kong DH, Kim YK, Kim MR, et al. Emerging Roles of Vascular Cell Adhesion Molecule-1 (VCAM-1) in Immunological Disorders and Cancer. Int J Mol Sci. 2018;19(4):1057. DOI:10.3390/ijms19041057
35. Doran E, Cai F, Holweg CTJ, et al. Interleukin-13 in Asthma and Other Eosinophilic Disorders. Front Med (Lausanne). 2017;4:139. DOI:10.3389/fmed.2017.00139
36. Yoshifuku K, Matsune S, Ohori J, et al. IL-4 and TNF-alpha increased the secretion of eotaxin from cultured fibroblasts of nasal polyps with eosinophil infiltration. Rhinology. 2007;45(3):235-41.
37. Kato A. Immunopathology of chronic rhinosinusitis. Allergol Int. 2015;64(2):121-30. DOI:10.1016/j.alit.2014.12.006
38. de Vries IJ, Langeveld-Wildschut EG, van Reijsen FC, et al. Adhesion molecule expression on skin endothelia in atopic dermatitis: effects of TNF-alpha and IL-4. J Allergy Clin Immunol. 1998;102(3):461-8.
39. Boyce JA, Mellor EA, Perkins B, et al. Human mast cell progenitors use alpha4-integrin, VCAM-1, and PSGL-1 E-selectin for adhesive interactions with human vascular endothelium under flow conditions. Blood. 2002;99(8):2890-6. DOI:10.1182/blood.v99.8.2890
40. Rosenberg HR, Phipps S, Foster PS, et al. Eosinophil trafficking in allergy and asthma. J Allergy Clin Immunol. 2007;119(6):1303-10. DOI:10.1016/j.jaci.2007.03.048
41. Borchers MT, Ansay T, DeSalle R, et al. In vitro assessment of chemokine receptor-ligand interactions mediating mouse eosinophil migration. J Leukoc Biol. 2002;71(6):1033-41. DOI:10.1189/jlb.71.6.1033
42. Nonaka M, Ogihara N, Fukumoto A, et al. Combined stimulation with Poly(I:C), TNF-alpha and Th2 cytokines induces TARC production by human fibroblasts from the nose, bronchioles and lungs. Int Arch Allergy Immunol. 2010;152(4):327-41. DOI:10.1159/000288286
43. Van Dyken SJ, Locksley RM. Interleukin-4- and interleukin-13-mediated alternatively activated macrophages: roles in homeostasis and disease. Annu Rev Immunol. 2013;31:317-43. DOI:10.1146/annurev-immunol-032712-095906
44. Takabayashi T, Kato A, Peters AT, et al. Excessive fibrin deposition in nasal polyps caused by fibrinolytic impairment through reduction of tissue plasminogen activator expression. Am J Respir Crit Care Med. 2013;187:49-57. DOI:10.1164/rccm.201207-1292OC
45. Takabayashi T, Kato A, Peters AT, et al. Increased expression of factor XIII-A in patients with chronic rhinosinusitis with nasal polyps. J Allergy Clin Immunol. 2013;132:584-92. DOI:10.1016/j.jaci.2013.02.003
46. Bachert C, et al. World Allergy Organ J. 2014;7:2.
47. Bachert C, Han JK, Desrosiers M, et al. Efficacy and safety of dupilumab in patients with severe chronic rhinosinusitis with nasal polyps (LIBERTY NP SINUS-24 and LIBERTY NP SINUS-52): results from two multicentre, randomised, double-blind, placebocontrolled, parallel-group phase 3 trials. Lancet. 2019;394(10209):1638-50. 
DOI:10.1016/S0140-6736(19)31881-1
48. Maspero JF, Katelaris CH, Busse WW, et al. Dupilumab Efficacy in Uncontrolled, Moderate-to-Severe Asthma with Self-Reported Chronic Rhinosinusitis. J Allergy Clin Immunol Pract. 2020;8(2):527-39. DOI:10.1016/j.jaip.2019.07.016
49. Tepper RS, Wise RS, Covar R, et al. Asthma outcomes: pulmonary physiology. J Allergy Clin Immunol. 2012;129(Suppl. 3):S65-S87. DOI:10.1016/j.jaci.2011.12.986