El efecto de las terapias biológicas sobre el remodelado de la vía aérea en el asma grave: Una revisión integrativa de la evidencia disponible
DOI:
https://doi.org/10.66201/ss.v1.14Palabras clave:
asma grave, remodelado, terapias biológicas, fibrosis subepitelial, inflamación T2, dupilumab, mepolizumab, TCAR, biopsia, componentes lábilesResumen
Antecedentes: El asma grave se caracteriza por el remodelado de la vía aérea, que incluye alteraciones estructurales persistentes como fibrosis subepitelial (MBR) e hiperplasia del músculo liso bronquial (MLB). Estos cambios provocan obstrucción fija y resistencia a corticosteroides. Las terapias biológicas (anti-IgE, anti-IL-5, anti-IL-4Rα, anti-TSLP) controlan la inflamación, pero su capacidad para revertir el remodelado establecido es la principal pregunta clínica sin resolver. El objetivo fue sintetizar la evidencia sobre este efecto y evaluar las discrepancias entre hallazgos histológicos e imagenológicos.
Métodos: Se ejecutó una revisión integrativa de la literatura con búsqueda sistemática en cuatro bases de datos primarias (PubMed, Scopus, Embase, CENTRAL), hasta marzo de 2026. Se incluyeron estudios en adultos con asma grave que reportaron desenlaces cuantificados de remodelado estructural medido por biopsia endobronquial o técnicas de imagen (TCAR, EBUS). Se seleccionaron 23 estudios, incluyendo cinco ensayos clínicos aleatorizados (ECA), para el análisis cualitativo.
Resultados: Se identificó una disociación consistente entre la supresión de la inflamación T2 y los efectos histológicos. Los ECA de alto rigor metodológico (mepolizumab-BOBCAT, tezepelumab-CASCADE) no mostraron cambios en el grosor de la MBR ni en la masa del MLB tras 12 meses de supresión eosinofílica profunda. Sin embargo, estudios imagenológicos (dupilumab, tezepelumab) reportaron reducciones significativas en el grosor de la pared y el taponamiento mucoso. Esto se explica porque la TCAR detecta la resolución de componentes lábiles (moco, edema), no la fibrosis fija medida por biopsia.
Conclusiones: La evidencia sugiere que la supresión de la inflamación T2 es insuficiente para revertir la fibrosis establecida en el corto plazo, debido a la autonomía del remodelado y el lento recambio de colágeno. El beneficio estructural de los biológicos se asocia principalmente a la modulación de componentes lábiles.
Referencias
Hsieh A, Assadinia N, Hackett TL. Airway remodeling heterogeneity in asthma and its relationship to disease outcomes. Front Physiol [Internet]. 2023 Jan 19;14:1113100. Available from: https://doi.org/10.3389/fphys.2023.1113100
Hough KP, Curtiss ML, Blain TJ, Liu RM, Trevor J, Deshane JS, et al. Airway remodeling in asthma. Front Med (Lausanne) [Internet]. 2020 May 21;7:191. Available from: https://doi.org/10.3389/fmed.2020.00191
Savin IA, Zenkova MA, Sen’kova AV. Bronchial asthma, airway remodeling and lung fibrosis as successive steps of one process. Int J Mol Sci [Internet]. 2023 Nov 7;24(22):16042. Available from: https://doi.org/10.3390/ijms242216042
Bajbouj K, Hachim MY, Ramakrishnan RK, Fazel H, Mustafa J, Alzaghari S, et al. IL-13 augments histone demethylase JMJD2B/KDM4B expression levels, activity, and nuclear translocation in airway fibroblasts in asthma. J Immunol Res [Internet]. 2021 Feb 22;2021:6629844. Available from: https://doi.org/10.1155/2021/6629844
Varricchi G, Ferri S, Pepys J, Poto R, Spadaro G, Nappi E, et al. Biologics and airway remodeling in severe asthma. Allergy [Internet]. 2022 Dec;77(12):3538–52. Available from: https://doi.org/10.1111/all.15473
Busse WW, Melén E, Menzies-Gow AN. Holy Grail: the journey towards disease modification in asthma. Eur Respir Rev [Internet]. 2022 Mar 31;31(163):210183. Available from: https://doi.org/10.1183/16000617.0183-2021
Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ [Internet]. 2021 Mar 29;372:n71. Available from: https://doi.org/10.1136/bmj.n71
Whittemore R, Knafl K. The integrative review: updated methodology. J Adv Nurs [Internet]. 2005 Dec [cited 2025 Nov 27];52(5):546–53. Available from: http://dx.doi.org/10.1111/j.1365-2648.2005.03621.x
Sterne JAC, Savović J, Page MJ, Elbers RG, Blencowe NS, Boutron I, et al. RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ [Internet]. 2019 Aug 28;366:l4898. Available from: https://doi.org/10.1136/bmj.l4898
Abujabal R, Alanta TM, Alhamidi RS, Altaie AM, Sahnoon L, Mdkhana B, et al. IL-5 signaling in asthmatic derived fibroblasts exacerbates airway remodeling through ECM dysregulation and apoptosis resistance. Respir Res [Internet]. 2025 Nov 4;26(1):307. Available from: https://doi.org/10.1186/s12931-025-03371-x
Domvri K, Porpodis K. Targeting inflammation or remodeling in asthma? Is there a right way? Front Med (Lausanne) [Internet]. 2023 Nov 23;10:1241920. Available from: https://doi.org/10.3389/fmed.2023.1241920
Górka K, Gross-Sondej I, Górka J, Stachura T, Polok K, Celejewska-Wójcik N, et al. Assessment of airway remodeling using endobronchial ultrasound in asthma-COPD overlap. J Asthma Allergy [Internet]. 2021 Jun 14;14:663–74. Available from: https://doi.org/10.2147/jaa.s306421
Djukanović R, Wilson SJ, Kraft M, Jarvis D, Holgate ST, Howarth PH. Effects of anti-IgE (omalizumab) in persistent severe asthma. Am J Respir Crit Care Med [Internet]. 2007;175(1):17–24. Available from: https://doi.org/10.1164/rccm.200602-287OC
Domingo C, Mirapeix RM, González-Barcala FJ, Forné C, García F. Omalizumab in severe asthma: Effect on oral corticosteroid exposure and remodeling. A randomized open-label parallel study. Drugs [Internet]. 2023 Aug [cited 2026 Mar 25];83(12):1111–23. Available from: http://dx.doi.org/10.1007/s40265-023-01905-5
Ma J, Ma Q, Yang J, Liang P, Zhou J, Ma J, et al. The clinical and pathological histology efficacy of biological therapy for severe asthma with a phenotype of type 2 inflammation - systematic review. Front Immunol [Internet]. 2025 Apr 15;16:1531986. Available from: https://doi.org/10.3389/fimmu.2025.1531986
Shi H, Chen Z, Lei Q, Sun F, Ma D, Niu T, et al. Utilizing chest CT to assess the impact of omalizumab treatment on airway remodeling in refractory asthma [Internet]. Research Square. 2023. Available from: https://doi.org/10.21203/rs.3.rs-3339444/v1
Bakakos A, Ampazis D, Papaioannou AI, Loukides S, Bakakos P. The role of endobronchial biopsies in evaluating biologic therapy response in severe asthma. Int J Mol Sci [Internet]. 2025 Aug 8;26(16):7692. Available from: https://doi.org/10.3390/ijms26167692
Poto R, Criscuolo G, Marone G, Brightling CE, Varricchi G. Human lung mast cells: Therapeutic implications in asthma. Int J Mol Sci [Internet]. 2022 Nov 21;23(22):14466. Available from: https://doi.org/10.3390/ijms232214466
Haldar P, Brightling CE, Hargadon B, Gupta S, Monteiro W, Sousa A, et al. Mepolizumab and exacerbations of refractory eosinophilic asthma. Lancet [Internet]. 2015;386(9997):977–84. Available from: https://doi.org/10.1016/S0140-6736(15)00524-2
Visca D, Ardesi F, Zappa M, Grossi S, Pignatti P, Vanetti M, et al. The effect of benralizumab on inflammation in severe asthma: a real-life analysis. Ther Adv Respir Dis [Internet]. 2024 Jan;18:17534666241304685. Available from: https://doi.org/10.1177/17534666241304685
Jakiela B, Górka K, Gross-Sondej I, Mikrut S, Okoń K, Sadowski P, et al. Type 2 gene expression signature in severe asthma associates with more advanced airway remodeling. Clin Transl Allergy [Internet]. 2025 Jun;15(6):e70060. Available from: https://doi.org/10.1002/clt2.70060
AbuJabal R, Ramakrishnan RK, Bajbouj K, Hamid Q. Role of IL-5 in asthma and airway remodelling. Clin Exp Allergy [Internet]. 2024 Aug;54(8):538–49. Available from: https://doi.org/10.1111/cea.14489
Castro M, Papi A, Porsbjerg C, Lugogo NL, Brightling CE, González-Barcala FJ, et al. Effect of dupilumab on exhaled nitric oxide, mucus plugs, and functional respiratory imaging in patients with type 2 asthma (VESTIGE): a randomised, double-blind, placebo-controlled, phase 4 trial. Lancet Respir Med [Internet]. 2025 Mar [cited 2026 Mar 26];13(3):208–20. Available from: http://dx.doi.org/10.1016/S2213-2600(24)00362-X
Tajiri T, Suzuki M, Nishiyama H, Ozawa Y, Kurokawa R, Takeda N, et al. Efficacy of dupilumab for airway hypersecretion and airway wall thickening in patients with moderate-to-severe asthma: A prospective, observational study. Allergol Int [Internet]. 2024 Jul [cited 2026 Mar 26];73(3):406–15. Available from: http://dx.doi.org/10.1016/j.alit.2024.02.002
Varricchi G, Brightling CE, Grainge C, Lambrecht BN, Chanez P. Airway remodelling in asthma and the epithelium: on the edge of a new era. Eur Respir J [Internet]. 2024 Apr;63(4):2301619. Available from: https://doi.org/10.1183/13993003.01619-2023
Varricchi G, Poto R, Lommatzsch M, Brusselle G, Braido F, Virchow JC, et al. Biologics and airway remodeling in asthma: early, late, and potential preventive effects. Allergy [Internet]. 2025 Feb;80(2):408–22. Available from: https://doi.org/10.1111/all.16382
Diver S, Khalfaoui L, Emson C, Wenzel SE, Menzies-Gow A, Wechsler ME, 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 [Internet]. 2021 Nov;9(11):1299–312. Available from: https://doi.org/10.1016/s2213-2600(21)00226-5
Sverrild A, Hansen S, Hvidtfeldt M, Clausson CM, Cozzolino O, Cerps S, et al. The effect of tezepelumab on airway hyperresponsiveness to mannitol in asthma (UPSTREAM). The European respiratory journal [Internet]. 2021 Dec 31 [cited 2026 Mar 26];59(1). Available from: http://dx.doi.org/10.1183/13993003.01296-2021
Nordenmark LH, Hellqvist Å, Emson C, Diver S, Porsbjerg C, Griffiths JM, et al. Tezepelumab and mucus plugs in patients with moderate-to-severe asthma. NEJM Evid [Internet]. 2023 Oct 20 [cited 2026 Mar 26];2(10):EVIDoa2300135. Available from: http://dx.doi.org/10.1056/EVIDoa2300135
Tsuge M, Ikeda M, Tsukahara H. Novel lung growth strategy with biological therapy targeting airway remodeling in childhood bronchial asthma. Children (Basel) [Internet]. 2022 Aug 19;9(8):1253. Available from: https://doi.org/10.3390/children9081253
Bush A. Update in paediatric asthma. Curr Opin Pulm Med [Internet]. 2025 May 1;31(3):279–86. Available from: https://doi.org/10.1097/mcp.0000000000001160
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Derechos de autor 2026 Francine Aquino De Carvalho Almeida, Breno Alexandre Rocha Oliveira, Felipe Bonfim, Noemi Siqueira Simão, Otávio Gabriel De Souza Tôrres, Pedro Arthur Costa Gois, Andrea Paola Britos Gómez (Autor/a)
Esta obra está bajo una licencia internacional Creative Commons Atribución 4.0.
