Epithelial Mechanism of Disease | Epicascade

1. Langdon C, Mullol J. Nasal polyps in patients with asthma: prevalence, impact, and management challenges. J Asthma Allergy. 2016;9:45-53. 2. Ha J-G, Cho H-J. Unraveling the role of epithelial cells in the development of chronic rhinosinusitis. Int J Mol Sci. 2023;24(18):14229. 3. Kato A, Schleimer RP, Bleier BS. Mechanisms and pathogenesis of chronic rhinosinusitis. J Allergy Clin Immunol. 2022;149(5):1491-1503. 4. Calvén J, Ax E, Rådinger M. The airway epithelium—a central player in asthma pathogenesis. Int J Mol Sci. 2020;21(23):8907. 5. Peters A, Zhao X, Near AM, et al. Real-world outcomes following biologic initiation in US patients with chronic rhinosinusitis with nasal polyps. Adv Ther. 2025;42(4):1783-1799. 6. Bachert C, Zhang N, Cavaliere C, Weiping W, Gevaert E, Krysko O. Biologics for chronic rhinosinusitis with nasal polyps. J Allergy Clin Immunol. 2020;145(3):725-739.

CRSwNP=chronic rhinosinusitis with nasal polyps.

REFERENCES

*Data refers to patients starting a biologic targeting downstream mediators.

CRSwNP=chronic rhinosinusitis with nasal polyps; INCs=intranasal corticosteroids; OCS=oral corticosteroid.

REFERENCES

1. Kato A, Schleimer RP, Bleier BS. Mechanisms and pathogenesis of chronic rhinosinusitis. J Allergy Clin Immunol. 2022;149(5):1491-1503. 2. Peters A, Han J, Spahn J, et al. Real-world outcomes following biologic initiation in US patients with chronic rhinosinusitis with nasal polyps. Presented at: ACAAI Annual Scientific Meeting; October 24-28, 2024; Boston, MA. 3. Bachert C, Zhang N, Cavaliere C, Weiping W, Gevaert E, Krysko O. Biologics for chronic rhinosinusitis with nasal polyps. J Allergy Clin Immunol. 2020;145(3):725-739. 4. 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.e9. 5. van der Veen J, Seys SF, Timmermans M, et al. Real-life study showing uncontrolled rhinosinusitis after sinus surgery in a tertiary referral
centre. Allergy. 2017;72(2):282-290. 6. DeConde AS, Mace JC, Levy JM, Rudmik L, Alt JA, Smith TL. Prevalence of polyp recurrence after endoscopic sinus surgery for chronic rhinosinusitis with nasal polyposis. Laryngoscope. 2017;127(3):550-555. 7. Claeys N, Teeling MT, Legrand P, et al. Patients unmet needs in chronic rhinosinusitis with nasal polyps care: a patient advisory board statement of EUFOREA. Front Allergy. 2021;2:761388. 8. Starry A, Hardtstock F, Wilke T, et al. Epidemiology and treatment of patients with chronic rhinosinusitis with nasal polyps in Germany—a claims data study. Allergy. 2022;77(9):2725-2736.

1. Kato A, Schleimer RP, Bleier BS. Mechanisms and pathogenesis of chronic rhinosinusitis. J Allergy Clin Immunol. 2022;149(5):1491-1503. 2. Peters A, Han J, Spahn J, et al. Real-world outcomes following biologic initiation in US patients with chronic rhinosinusitis with nasal polyps. Presented at: ACAAI Annual Scientific Meeting; October 24-28, 2024; Boston, MA. 3. Bachert C, Zhang N, Cavaliere C, Weiping W, Gevaert E, Krysko O. Biologics for chronic rhinosinusitis with nasal polyps. J Allergy Clin Immunol. 2020;145(3):725-739.
4. 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.e9. 5. van der
Veen J, Seys SF, Timmermans M, et al. Real-life study showing uncontrolled rhinosinusitis after sinus surgery in a tertiary referral centre. Allergy. 2017;72(2):282-290. 6. DeConde AS, Mace JC, Levy JM, Rudmik L, Alt JA, Smith TL. Prevalence of polyp recurrence after endoscopic sinus surgery for chronic rhinosinusitis with nasal polyposis. Laryngoscope. 2017;127(3):550-555. 7. Claeys N, Teeling MT, Legrand P, et al. Patients unmet needs in chronic rhinosinusitis with nasal polyps care: a patient advisory board statement of EUFOREA. Front Allergy. 2021;2:761388. 8. Starry A, Hardtstock F, Wilke T, et al. Epidemiology and treatment of patients with chronic rhinosinusitis with nasal polyps in Germany—a claims data study. Allergy. 2022;77(9):2725-2736.

Image adapted from Kato A, et al. 2022² and Bachert C, et al. 2020.⁷
CRSwNP=chronic rhinosinusitis with nasal polyps; IL=interleukin; ILC2=type 2 innate lymphoid cell; Th=T helper; TSLP=thymic stromal lymphopoietin.

REFERENCES

1. Ha J-G, Cho H-J. Unraveling the role of epithelial cells in the development of chronic rhinosinusitis. Int J Mol Sci. 2023;24(18):14229. 2. Kato A, Schleimer RP, Bleier BS. Mechanisms and pathogenesis of chronic rhinosinusitis. J Allergy Clin Immunol. 2022;149(5):1491-1503. 3. Calvén J, Ax E, Rådinger M. The airway epithelium—a central player in asthma pathogenesis. Int J Mol Sci. 2020;21(23):8907. 4. Laulajainen-Hongisto A, Toppila-Salmi SK, Luukkainen A, Kern R. Airway epithelial dynamics in allergy and related chronic inflammatory airway diseases. Front Cell Dev Biol. 2020;8:204. 5. Stevens WW, Peters AT, Tan BK, et al. Associations between inflammatory endotypes and clinical presentations in chronic rhinosinusitis. J Allergy Clin Immunol Pract. 2019;7(8):2812-2820.e3. 6. Staudacher AG, Peters AT, Kato A, Stevens WW. Use of endotypes, phenotypes, and inflammatory markers to guide treatment decisions in chronic rhinosinusitis. Ann Allergy Asthma Immunol. 2020;124(4):318-325. 7. Bachert C, Zhang N, Cavaliere C, Weiping W, Gevaert E, Krysko O. Biologics for chronic rhinosinusitis with nasal polyps. J Allergy Clin Immunol. 2020;145(3):725-739.

CRSwNP=chronic rhinosinusitis with nasal polyps; EoE=eosinophilic esophagitis.

REFERENCES

1. Langdon C, Mullol J. Nasal polyps in patients with asthma: prevalence, impact, and management challenges. J Asthma Allergy. 2016;9:45-53. 2. Ha J-G, Cho H-J. Unraveling the role of epithelial cells in the development of chronic rhinosinusitis. Int J Mol Sci. 2023;24(18):14229. 3. Kato A, Schleimer RP, Bleier BS. Mechanisms and pathogenesis of chronic rhinosinusitis. J Allergy Clin Immunol. 2022;149(5):1491-1503. 4. Calvén J, Ax E, Rådinger M. The airway epithelium—a central player in asthma pathogenesis. Int J Mol Sci. 2020;21(23):8907. 5. Berni Canani R, Caminati M, Carucci L, Eguiluz-Gracia I. Skin, gut, and lung barrier: physiological interface and target of intervention for preventing and treating allergic diseases. Allergy. 2024;79(6):1485-1500.

EoE=eosinophilic esophagitis.

REFERENCES

1. Berni Canani R, Caminati M, Carucci L, Eguiluz-Gracia I. Skin, gut, and lung barrier: physiological interface and target of intervention for preventing and treating allergic diseases. Allergy. 2024;79(6):1485-1500. 2. Hill DA, Muir AB. The immune-epithelial interface in eosinophilic esophagitis: a conversation. Front Allergy. 2023;4:1270581. 3. Salvador Nunes VS, Straumann A, Salvador Nunes L, Schoepfer AM, Greuter T. Eosinophilic esophagitis beyond eosinophils – an emerging phenomenon overlapping with eosinophilic esophagitis: Collegium Internationale Allergologicum (CIA) update 2023. Int Arch Allergy Immunol. 2023;184(5):411-420. 4. Bredenoord AJ, Patel K, Schoepfer AM, et al. Disease burden and unmet need in eosinophilic esophagitis. Am J Gastroenterol. 2022;117(8):1231-1241. 5. Dellon ES, Rothenberg ME, Collins MH, et al. N Engl J Med. 2022;387(25):2317-2330. 6. Dellon ES. Management of refractory eosinophilic oesophagitis. Nat Rev Gastroenterol Hepatol. 2017;14(8):479-490. 7. Simon D, Radonjic-Hösli S, Straumann A, Yousefi S, Simon HU. Active eosinophilic esophagitis is characterized by epithelial barrier defects and eosinophil extracellular trap formation. Allergy. 2015;70(4):443-452.

CRSwNP=chronic rhinosinusitis with nasal polyps; EoE=eosinophilic esophagitis.

REFERENCES

1. Hill DA, Muir AB. The immune-epithelial interface in eosinophilic esophagitis: a conversation. Front Allergy. 2023;4:1270581. 2. Salvador Nunes VS, Straumann A, Salvador Nunes L, Schoepfer AM, Greuter T. Eosinophilic esophagitis beyond eosinophils – an emerging phenomenon overlapping with eosinophilic esophagitis: Collegium Internationale Allergologicum (CIA) update 2023. Int Arch Allergy Immunol. 2023;184(5):411-420. 3. Dellon ES, Muir AB, Katzka DA, et al. ACG clinical guideline: diagnosis and management of eosinophilic esophagitis. Am J Gastroenterol. 2025;120(1):31-59. 4. Kato A, Schleimer RP, Bleier BS. Mechanisms and pathogenesis of chronic rhinosinusitis. J Allergy Clin Immunol. 2022;149(5):1491-1503. 5. Berni Canani R, Caminati M, Carucci L, Eguiluz-Gracia I. Skin, gut, and lung barrier: physiological interface and target of intervention for preventing and treating allergic diseases. Allergy. 2024;79(6):1485-1500. 6. Calvén J, Ax E, Rådinger M. The airway epithelium—a central player in asthma pathogenesis. Int J Mol Sci. 2020;21(23):8907. 7. Ha J-G, Cho H-J. Unraveling the role of epithelial cells in the development of chronic rhinosinusitis. Int J Mol Sci. 2023;24(18):14229. 8. Dellon ES, Kim HP, Sperry SLW, Rybnicek DA, Woosley JT, Shaheen NJ. A phenotypic analysis shows that eosinophilic esophagitis is a progressive fibrostenotic disease. Gastrointest Endosc. 2014;79(4):577-585.e4.

*Data from an observational cross-sectional study of 147 US adults with EoE. Adaptive eating behaviors were defined as taking smaller bites, chewing more, eating slowly, or drinking more water during meals.²
^†Data from a web-based survey of 184 US adults with EoE. Data showed the impact of perceived stigma over the past 12 months in adults.³
^‡Data from the US Nationwide Emergency Department Sample were used to estimate weighted annual EoE-associated ED visits from 2009 to 2019.⁴
^‖Retrospective study of 721 patients across 15 Dutch hospitals (1996-2015). Percentage of patients who presented with features of endoscopic fibrostenosis increased with longer diagnostic delay, from 56% (delay ≤2 years) to 92% (delay ≥21 years). Percentage of patients who presented with esophageal stricture also increased with diagnostic delay, from 19% (≤2 years) to 52% (≥20 years).⁸
^¶TSLP expression was calculated using an ordinal scoring system (0=none, 1=mild, 2=medium, 3=strong, 4=very strong) to represent how widely the cytokine marker was expressed in tissue sections, while nuclear expression of IL-33 and IL-25 was calculated by counting the number of infiltrating cytokine-positive cells in the area.¹¹

ED=emergency department; EoE=eosinophilic esophagitis; IL=interleukin; PPI=proton pump inhibitor; TSLP=thymic stromal lymphopoietin.

REFERENCES

1. Young E, Philpott H. Pathophysiology of dysphagia in eosinophilic esophagitis: causes, consequences, and management. Dig Dis Sci. 2022;67(4):1101-1115. 2. de Rooij WE, Evertsz FB, Lei A, Bredenoord AJ. General well-being and coping strategies in adult eosinophilic esophagitis patients. J Neurogastroenterol Motil. 2022;28(3):390-400. 3. Gold BD, Goodwin B, Davis K, et al. Health-related quality of life and perceived stigma in eosinophilic esophagitis: a real-world, US, web-based survey. Gastro Hep Adv. 2024;3(8):1087-1097. 4. Lam AY, Lee JK, Coward S, et al. Epidemiologic burden and projections for eosinophilic esophagitis-associated emergency department visits in the United States: 2009-2030. Clin Gastroenterol Hepatol. 2023;21(12):3041-3050.e3. 5. Dellon ES. Management of refractory eosinophilic oesophagitis. Nat Rev Gastroenterol Hepatol. 2017;14(8):479-490. 6. Dellon ES, Rothenberg ME, Collins MH, et al. N Engl J Med. 2022;387(25):2317-2330. 7. Bredenoord AJ, Patel K, Schoepfer AM, et al. Disease burden and unmet need in eosinophilic esophagitis. Am J Gastroenterol. 2022;117(8):1231-1241. 8. Warners MJ, Oude Nijhuis RAB, de Wijkerslooth LRH, Smout AJPM, Bredenoord AJ. The natural course of eosinophilic esophagitis and long-term consequences of undiagnosed disease in a large cohort. Am J Gastroenterol. 2018;113(6):836-844. 9. Syverson EP, Hait E. Update on emerging pharmacologic therapies for patients with eosinophilic esophagitis. Gastroenterol Hepatol (N Y). 2022;18(4):207-212. 10. Berni Canani R, Caminati M, Carucci L, Eguiluz-Gracia I. Skin, gut, and lung barrier: physiological interface and target of intervention for preventing and treating allergic diseases. Allergy. 2024;79(6):1485-1500. 11. Simon D, Radonjic-Hösli S, Straumann A, Yousefi S, Simon HU. Active eosinophilic esophagitis is characterized by epithelial barrier defects and eosinophil extracellular trap formation. Allergy. 2015;70(4):443-452.

EoE=eosinophilic esophagitis; IgE=immunoglobulin E; IL=interleukin; T2=type 2 disease; TSLP=thymic stromal lymphopoietin.

REFERENCES

1. Berni Canani R, Caminati M, Carucci L, Eguiluz-Gracia I. Skin, gut, and lung barrier: physiological interface and target of intervention for preventing and treating allergic diseases. Allergy. 2024;79(6):1485-1500. 2. Bredenoord AJ, Patel K, Schoepfer AM, et al. Disease burden and unmet need in eosinophilic esophagitis. Am J Gastroenterol. 2022;117(8):1231-1241. 3. Salvador Nunes VS, Straumann A, Salvador Nunes L, Schoepfer AM, Greuter T. Eosinophilic esophagitis beyond eosinophils – an emerging phenomenon overlapping with eosinophilic esophagitis: Collegium Internationale Allergologicum (CIA) update 2023. Int Arch Allergy Immunol. 2023;184(5):411-420.

TAKE IT FROM THE TOP IN CRSwNP^1-3

The epithelium is the first point of contact for INSULTS^1-3

In response to insults, the epithelium releases EPITHELIAL CYTOKINES (such as TSLP, IL-33, and IL-25),^1-4

which can drive multiple DOWNSTREAM INFLAMMATORY PATHWAYS^1-4

AND CAN LEAD TO MULTIPLE CLINICAL MANIFESTATIONS^1-3,5,6

GUIDE TO EPITHELIAL-DRIVEN INFLAMMATION

TAKE IT FROM THE TOP IN CRSwNP1-3

The epithelium is the first point of contact for INSULTS1-3

In response to insults, the epithelium releases EPITHELIAL CYTOKINES (such as TSLP, IL-33, and IL-25),1-4

which can drive multiple DOWNSTREAM INFLAMMATORY PATHWAYS1-4

AND CAN LEAD TO MULTIPLE CLINICAL MANIFESTATIONS1-3,5,6

GUIDE TO EPITHELIAL-DRIVEN INFLAMMATION

TAKE IT FROM THE TOP IN CRSwNP^1-3

The epithelium is the first point of contact for INSULTS^1-3

In response to insults, the epithelium releases EPITHELIAL CYTOKINES (such as TSLP, IL-33, and IL-25),^1-4

which can drive multiple DOWNSTREAM INFLAMMATORY PATHWAYS^1-4

AND CAN LEAD TO MULTIPLE CLINICAL MANIFESTATIONS^1-3,5,6