Predictors of persistent disease in biologic treated type 2 diffuse/eosinophilic chronic rhinosinusitis undergoing surgery.

biologics biomarkers nasal polyps resident eosinophils sinusitis therapeutic response type 2 inflammation

Journal

International forum of allergy & rhinology
ISSN: 2042-6984
Titre abrégé: Int Forum Allergy Rhinol
Pays: United States
ID NLM: 101550261

Informations de publication

Date de publication:
08 Oct 2023
Historique:
revised: 09 09 2023
received: 08 06 2023
accepted: 23 09 2023
pubmed: 8 10 2023
medline: 8 10 2023
entrez: 8 10 2023
Statut: aheadofprint

Résumé

Biologic therapy targeting type 2 chronic rhinosinusitis with nasal polyps (CRSwNP) has greatly improved disease control but nonresponders exist in a proportion of patients in phase 3 trials and clinical practice. This study explores the serum and histologic changes in biologic treated CRSwNP that predict disease control. A cross-sectional study was performed of patients with CRSwNP on biologics for their asthma, who underwent endoscopic sinus surgery while on biologic therapy. At the 6-month postoperative assessment, patients with poorly controlled CRSwNP while on biologic therapy were compared to patients who were controlled. Blood and mucosal samples taken at the time of surgery 6 months prior were assessed to predict disease control. A total of 37 patients were included (age 47.8 ± 12.4 years, 43.2% female). Those with poorly controlled disease had reduced tissue eosinophils (% >100 cells/high-powered field: 8.3% vs. 50.0%, p < 0.001) and increased serum neutrophils (5.2 ± 2.7 vs. 3.7 ± 1.1 × 10 Low tissue eosinophils and increased serum neutrophils while on biologics predict for poor response in the biological treatment of with CRSwNP. A serum neutrophil level of ≥5.75 × 10

Sections du résumé

BACKGROUND BACKGROUND
Biologic therapy targeting type 2 chronic rhinosinusitis with nasal polyps (CRSwNP) has greatly improved disease control but nonresponders exist in a proportion of patients in phase 3 trials and clinical practice. This study explores the serum and histologic changes in biologic treated CRSwNP that predict disease control.
METHODS METHODS
A cross-sectional study was performed of patients with CRSwNP on biologics for their asthma, who underwent endoscopic sinus surgery while on biologic therapy. At the 6-month postoperative assessment, patients with poorly controlled CRSwNP while on biologic therapy were compared to patients who were controlled. Blood and mucosal samples taken at the time of surgery 6 months prior were assessed to predict disease control.
RESULTS RESULTS
A total of 37 patients were included (age 47.8 ± 12.4 years, 43.2% female). Those with poorly controlled disease had reduced tissue eosinophils (% >100 cells/high-powered field: 8.3% vs. 50.0%, p < 0.001) and increased serum neutrophils (5.2 ± 2.7 vs. 3.7 ± 1.1 × 10
CONCLUSION CONCLUSIONS
Low tissue eosinophils and increased serum neutrophils while on biologics predict for poor response in the biological treatment of with CRSwNP. A serum neutrophil level of ≥5.75 × 10

Identifiants

pubmed: 37805956
doi: 10.1002/alr.23282
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

© 2023 The Authors. International Forum of Allergy & Rhinology published by Wiley Periodicals LLC on behalf of American Academy of Otolaryngic Allergy and American Rhinologic Society.

Références

Mullol J, Azar A, Buchheit KM, Hopkins C, Bernstein JA. Chronic rhinosinusitis with nasal polyps: quality of life in the biologics era. J Allergy Clin Immunol Pract. 2022;10(6):1434-1453. doi:10.1016/j.jaip.2022.03.002. e9.
Iqbal IZ, Kao SS, Ooi EH. The role of biologics in chronic rhinosinusitis: a systematic review. Int Forum Allergy Rhinol. 2020;10(2):165-174. doi:10.1002/alr.22473
Laidlaw TM, Buchheit KM. Biologics in chronic rhinosinusitis with nasal polyposis. Ann Allergy Asthma Immunol. 2020;124(4):326-332. doi:10.1016/j.anai.2019.12.001
Kim C, Han J, Wu T, et al. Role of biologics in chronic rhinosinusitis with nasal polyposis: state of the art review. Otolaryngol Head Neck Surg. 2021;164(1):57-66. doi:10.1177/0194599820939964
Patel GB, Peters AT. The role of biologics in chronic rhinosinusitis with nasal polyps. Ear Nose Throat J. 2021;100(1):44-47. doi:10.1177/0145561320964653
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, placebo-controlled, parallel-group phase 3 trials. Lancet. 2019;394(10209):1638-1650. doi:10.1016/S0140-6736(19)31881-1
Han JK, Bachert C, Fokkens W, et al. Mepolizumab for chronic rhinosinusitis with nasal polyps (SYNAPSE): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Respir Med. 2021;9(10):1141-1153. doi:10.1016/S2213-2600(21)00097-7
Bachert C, Han JK, Desrosiers MY, et al. Efficacy and safety of benralizumab in chronic rhinosinusitis with nasal polyps: a randomized, placebo-controlled trial. J Allergy Clin Immunol. 2022;149(4):1309-1317. doi:10.1016/j.jaci.2021.08.030. e12.
Wang X, Zhang N, Bo M, et al. Diversity of T(H) cytokine profiles in patients with chronic rhinosinusitis: a multicenter study in Europe, Asia, and Oceania. J Allergy Clin Immunol. 2016;138(5):1344-1353. doi:10.1016/j.jaci.2016.05.041
Kips JC, O'Connor BJ, Langley SJ, et al. 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. doi:10.1164/rccm.200206-525OC
Flood-Page P, Swenson C, Faiferman I, et al. A study to evaluate safety and efficacy of mepolizumab in patients with moderate persistent asthma. Am J Respir Crit Care Med. 2007;176(11):1062-1071. doi:10.1164/rccm.200701-085OC
Ortega HG, Yancey SW, Mayer B, et al. Severe eosinophilic asthma treated with mepolizumab stratified by baseline eosinophil thresholds: a secondary analysis of the DREAM and MENSA studies. The Lancet Respiratory Medicine. 2016;4(7):549-556. doi:10.1016/S2213-2600(16)30031-5
Menzies-Gow A, Corren J, Bourdin A, et al. Tezepelumab in adults and adolescents with severe, uncontrolled asthma. N Engl J Med. 2021;384(19):1800-1809. doi:10.1056/NEJMoa2034975
Fokkens WJ, Viskens AS, Backer V, et al. EPOS/EUFOREA update on indication and evaluation of Biologics in Chronic Rhinosinusitis with Nasal Polyps 2023. Rhinology. 2023;61(3):194-202. doi:10.4193/Rhin22.489
Li W, Ho J, Grayson JW, et al. Evaluation of diffuse type 2 dominant or eosinophilic chronic rhinosinusitis with corticosteroid irrigation after surgical neosinus cavity formation. JAMA Otolaryngol Head Neck Surg. 2021;147(4):360-367. doi:10.1001/jamaoto.2020.5286
Snidvongs K, Lam M, Sacks R, et al. Structured histopathology profiling of chronic rhinosinusitis in routine practice. Int Forum Allergy Rhinol. 2012;2(5):376-385. doi:10.1002/alr.21032
Toma S, Hopkins C. Stratification of SNOT-22 scores into mild, moderate or severe and relationship with other subjective instruments. Rhinology. 2016;54(2):129-133. doi:10.4193/Rhino15.072
Psaltis AJ, Li G, Vaezeafshar R, Cho KS, Hwang PH. Modification of the Lund-Kennedy endoscopic scoring system improves its reliability and correlation with patient-reported outcome measures. Laryngoscope. 2014;124(10):2216-2223. doi:10.1002/lary.24654
Brown WC, Senior B. A critical look at the efficacy and costs of biologic therapy for chronic rhinosinusitis with nasal polyposis. Curr Allergy Asthma Rep. 2020;20(6):16. doi:10.1007/s11882-020-00910-y
Whittington MD, McQueen RB, Ollendorf DA, et al. Assessing the value of mepolizumab for severe eosinophilic asthma: a cost-effectiveness analysis. Ann Allergy Asthma Immunol. 2017;118(2):220-225. doi:10.1016/j.anai.2016.10.028
Grosse SD. Assessing cost-effectiveness in healthcare: history of the $50,000 per QALY threshold. Expert Rev Pharmacoecon Outcomes Res. 2008;8(2):165-178. doi:10.1586/14737167.8.2.165
Fokkens WJ, Mullol J, Kennedy D, et al. Mepolizumab for chronic rhinosinusitis with nasal polyps (SYNAPSE): in-depth sinus surgery analysis. Allergy. 2023;78(3):812-821. doi:10.1111/all.15434
Oykhman P, Paramo FA, Bousquet J, Kennedy DW, Brignardello-Petersen R, Chu DK. Comparative efficacy and safety of monoclonal antibodies and aspirin desensitization for chronic rhinosinusitis with nasal polyposis: a systematic review and network meta-analysis. J Allergy Clin Immunol. 2022;149(4):1286-1295. doi:10.1016/j.jaci.2021.09.009
Nakayama T, Yoshikawa M, Asaka D, et al. Mucosal eosinophilia and recurrence of nasal polyps-new classification of chronic rhinosinusitis. Rhinology. 2011;49(4):392-396. doi:10.4193/Rhino10.261
Laidlaw TM, Prussin C, Panettieri RA, et al. Dexpramipexole depletes blood and tissue eosinophils in nasal polyps with no change in polyp size. Laryngoscope. 2019;129(2):E61-e66. doi:10.1002/lary.27564
Tomassen P, Vandeplas G, Van Zele T, et al. Inflammatory endotypes of chronic rhinosinusitis based on cluster analysis of biomarkers. J Allergy Clin Immunol. 2016;137(5):1449-1456. doi:10.1016/j.jaci.2015.12.1324. e4.
Feldman S, Kasjanski R, Poposki J, et al. Chronic airway inflammation provides a unique environment for B cell activation and antibody production. Clin Exp Allergy. 2017;47(4):457-466. doi:10.1111/cea.12878
Kariyawasam HH, James LK. Do B cells rather than eosinophils drive chronic rhinosinusitis with nasal polyps? Lancet Respir Med. 2021;9(10):e97. doi:10.1016/s2213-2600(21)00223-x
Weller PF, Spencer LA. Functions of tissue-resident eosinophils. Nat Rev Immunol. 2017;17(12):746-760. doi:10.1038/nri.2017.95
Kanda A, Yun Y, Bui DV, et al. The multiple functions and subpopulations of eosinophils in tissues under steady-state and pathological conditions. Allergol Int. 2021;70(1):9-18. doi:10.1016/j.alit.2020.11.001
Abdala-Valencia H, Coden ME, Chiarella SE, et al. Shaping eosinophil identity in the tissue contexts of development, homeostasis, and disease. J Leukoc Biol. 2018;104(1):95-108. doi:10.1002/JLB.1MR1117-442RR
Lombardi C, Berti A, Cottini M. The emerging roles of eosinophils: implications for the targeted treatment of eosinophilic-associated inflammatory conditions. Curr Res Immunol. 2022;3:42-53. doi:10.1016/j.crimmu.2022.03.002
Esnault S, Johansson MW, Mathur SK. Eosinophils, beyond IL-5. Cells. 2021;10(10):2615. doi:10.3390/cells10102615
Chu VT, Beller A, Rausch S, et al. Eosinophils promote generation and maintenance of immunoglobulin-A-expressing plasma cells and contribute to gut immune homeostasis. Immunity. 2014;40(4):582-593. doi:10.1016/j.immuni.2014.02.014
Jung Y, Wen T, Mingler MK, et al. IL-1β in eosinophil-mediated small intestinal homeostasis and IgA production. Mucosal Immunol. 2015;8(4):930-942. doi:10.1038/mi.2014.123
Mesnil C, Raulier S, Paulissen G, et al. Lung-resident eosinophils represent a distinct regulatory eosinophil subset. J Clin Invest. 2016;126(9):3279-3295. doi:10.1172/jci85664
Ho J, Hamizan AW, Alvarado R, Rimmer J, Sewell WA, Harvey RJ. Systemic predictors of eosinophilic chronic rhinosinusitis. Am J Rhinol Allergy. 2018;32(4):252-257. doi:10.1177/1945892418779451
Wright HL, Moots RJ, Bucknall RC, Edwards SW. Neutrophil function in inflammation and inflammatory diseases. Rheumatology (Oxford). 2010;49(9):1618-1631. doi:10.1093/rheumatology/keq045
Herrero-Cervera A, Soehnlein O, Kenne E. Neutrophils in chronic inflammatory diseases. Cell Mol Immunol. 2022;19(2):177-191. doi:10.1038/s41423-021-00832-3
Nakagome K, Matsushita S, Nagata M. Neutrophilic Inflammation in severe asthma. Int Arch Allergy Immunol. 2012;158(Suppl 1):96-102. doi:10.1159/000337801
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(1):57-70. doi:10.1111/cea.12859
Bachert C, Sousa AR, Han JK, et al. Mepolizumab for chronic rhinosinusitis with nasal polyps: treatment efficacy by comorbidity and blood eosinophil count. J Allergy Clin Immunol. 2022;149(5):1711-1721.e6. doi:10.1016/j.jaci.2021.10.040
Delemarre T, Holtappels G, De Ruyck N, et al. A substantial neutrophilic inflammation as regular part of severe type 2 chronic rhinosinusitis with nasal polyps. J Allergy Clin Immunol. 2021;147(1):179-188.e2. doi:10.1016/j.jaci.2020.08.036
Nadif R, Siroux V, Oryszczyn MP, et al. Heterogeneity of asthma according to blood inflammatory patterns. Thorax. 2009;64(5):374-380. doi:10.1136/thx.2008.103069

Auteurs

Lu Hui Png (LH)

Rhinology and Skull Base Research Group, St Vincent's Centre for Applied Medical Research, University of New South Wales, Sydney, Australia.
Department of Otorhinolaryngology - Head and Neck Surgery, Singapore General Hospital, Singapore, Singapore.
Faculty of Medicine and Health Sciences, Macquarie University, Sydney, Australia.

Larry Kalish (L)

Rhinology and Skull Base Research Group, St Vincent's Centre for Applied Medical Research, University of New South Wales, Sydney, Australia.
Department of Otolaryngology, Head and Neck Surgery, Concord General Hospital, University of Sydney, Sydney, Australia.
Faculty of Medicine, University of Sydney, Sydney, Australia.

Raewyn G Campbell (RG)

Rhinology and Skull Base Research Group, St Vincent's Centre for Applied Medical Research, University of New South Wales, Sydney, Australia.
Faculty of Medicine and Health Sciences, Macquarie University, Sydney, Australia.
Department of Otolaryngology, Head and Neck Surgery, Royal Prince Alfred Hospital, Sydney, Australia.

Kachorn Seresirikachorn (K)

Rhinology and Skull Base Research Group, St Vincent's Centre for Applied Medical Research, University of New South Wales, Sydney, Australia.
Faculty of Medicine and Health Sciences, Macquarie University, Sydney, Australia.
Department of Otolaryngology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
Endoscopic Nasal and Sinus Surgery Excellence Center, King Chulalongkorn Memorial Hospital, Bangkok, Thailand.
Doctor of Philosophy Program in Medical Sciences (International Program), Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.

Tobias Albrecht (T)

Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital Tübingen, Tübingen, Germany.

Nelufer Raji (N)

Rhinology and Skull Base Research Group, St Vincent's Centre for Applied Medical Research, University of New South Wales, Sydney, Australia.

Christine Choy (C)

Rhinology and Skull Base Research Group, St Vincent's Centre for Applied Medical Research, University of New South Wales, Sydney, Australia.

Janet Rimmer (J)

Rhinology and Skull Base Research Group, St Vincent's Centre for Applied Medical Research, University of New South Wales, Sydney, Australia.
Woolcock Institute, University of Sydney, Sydney, Australia.
Faculty of Medicine, Notre Dame University, Sydney, Australia.

Peter Earls (P)

Rhinology and Skull Base Research Group, St Vincent's Centre for Applied Medical Research, University of New South Wales, Sydney, Australia.
Department of Anatomical Pathology, St Vincent's Hospital, Darlinghurst, Australia.

Raymond Sacks (R)

Rhinology and Skull Base Research Group, St Vincent's Centre for Applied Medical Research, University of New South Wales, Sydney, Australia.
Faculty of Medicine and Health Sciences, Macquarie University, Sydney, Australia.
Department of Otolaryngology, Head and Neck Surgery, Concord General Hospital, University of Sydney, Sydney, Australia.

Richard J Harvey (RJ)

Rhinology and Skull Base Research Group, St Vincent's Centre for Applied Medical Research, University of New South Wales, Sydney, Australia.
Faculty of Medicine and Health Sciences, Macquarie University, Sydney, Australia.

Classifications MeSH