Palabras clave
Alergia e inmunología
Fármacos biológicos
Resumen
El asma grave es una enfermedad compleja, que requiere un enfoque y diagnóstico diferencial ordenado e identificación de endotipos para el correcto abordaje y tratamiento. El tratamiento farmacológico cuenta cada vez con más moléculas a disposición del personal médico para el control efectivo de los síntomas. Esta revisión muestra una síntesis de la bibliografía actual acerca del diagnóstico, fisiopatología y tratamiento del asma grave, mediante la lectura crítica previa de la evidencia científica en buscadores como Medline, Scopus y Embase.
Palabras clave: Asma bronquial; Alergia e inmunología; Fármacos biológicos.
Referencias
Global Initiative for Ashtma. Global Strategy for Ashtma Management and Prevention. www.ginasthma.org
GEMA 5.2. Guía Española para el Manejo del Asma. Sociedad Española de Neumología y Cirugía Torácica. 2022;
Menzies-Gow A, Moore WC, Wechsler ME. Difficult-to-Control Asthma Management in Adults. J Allergy Clin Immunol Pract. Feb 2022;10(2):378-384. doi:10.1016/j.jaip.2021.12.007
Pizzichini MMM, Cancado JED. Severe asthma phenotyping: does the definition of different phenotypes matter? J Bras Pneumol. Jul 8 2022;48(3):e20220176. doi:10.36416/1806-3756/e20220176
Fahy JV. Type 2 inflammation in asthma--present in most, absent in many. Nat Rev Immunol. Jan 2015;15(1):57-65. doi:10.1038/nri3786
Escamilla-Gil JM, Fernandez-Nieto M, Acevedo N. Understanding the Cellular Sources of the Fractional Exhaled Nitric Oxide (FeNO) and Its Role as a Biomarker of Type 2 Inflammation in Asthma. Biomed Res Int. 2022;2022:5753524. doi:10.1155/2022/5753524
Maspero J, Adir Y, Al-Ahmad M, et al. Type 2 inflammation in asthma and other airway diseases. ERJ Open Res. Jul 2022;8(3)doi:10.1183/23120541.00576-2021
Hong H, Liao S, Chen F, Yang Q, Wang DY. Role of IL-25, IL-33, and TSLP in triggering united airway diseases toward type 2 inflammation. Allergy. Nov 2020;75(11):2794-2804. doi:10.1111/all.14526
Werder RB, Zhang V, Lynch JP, et al. Chronic IL-33 expression predisposes to virus-induced asthma exacerbations by increasing type 2 inflammation and dampening antiviral immunity. J Allergy Clin Immunol. May 2018;141(5):1607-1619 e9. doi:10.1016/j.jaci.2017.07.051
Kimura H, Francisco D, Conway M, et al. Type 2 inflammation modulates ACE2 and TMPRSS2 in airway epithelial cells. J Allergy Clin Immunol. Jul 2020;146(1):80-88 e8. doi:10.1016/j.jaci.2020.05.004
Peters MC, Wenzel SE. Intersection of biology and therapeutics: type 2 targeted therapeutics for adult asthma. Lancet. Feb 1 2020;395(10221):371-383. doi:10.1016/S0140-6736(19)33005-3
Hassoun D, Moui A, Colas L, Blanc FX, Magnan A. [Update in severe asthma physiopathology and treatments]. Rev Med Interne. Aug 2019;40(8):508-516. Actualites physiopathologiques et therapeutiques dans l'asthme severe. doi:10.1016/j.revmed.2019.04.007
Klein M, Gagnon PA, Salem M, Chakir J. IL-13 modulates exosome production and miRNAs cargo in bronchial epithelial cells in severe asthma. ERJ Open Research. 2022;8(suppl 8):39. doi:10.1183/23120541.LSC-2022.39
Klein M, Dijoux E, Dilasser F, et al. [New protagonists in asthma pathophysiology]. Presse Med. Mar 2019;48(3 Pt 1):255-261. Nouveaux acteurs dans la physiopathologie de l'asthme. doi:10.1016/j.lpm.2019.01.004
Colombo R, da Silva Rosario S, Nesello PFT, et al. Effect of airway narrowing in asthma: active learning through a simple and didactic model. Adv Physiol Educ. Sep 1 2018;42(3):473-476. doi:10.1152/advan.00053.2018
Lourenco LO, Ribeiro AM, Lopes F, Tiberio I, Tavares-de-Lima W, Prado CM. Different Phenotypes in Asthma: Clinical Findings and Experimental Animal Models. Clin Rev Allergy Immunol. Feb 2022;62(1):240-263. doi:10.1007/s12016-021-08894-x
Lambrecht BN, Hammad H, Fahy JV. The Cytokines of Asthma. Immunity. Apr 16 2019;50(4):975-991. doi:10.1016/j.immuni.2019.03.018
Barnes PJ. Targeting cytokines to treat asthma and chronic obstructive pulmonary disease. Nat Rev Immunol. Jul 2018;18(7):454-466. doi:10.1038/s41577-018-0006-6
Ayakannu R, Abdullah NA, Radhakrishnan AK, Lechimi Raj V, Liam CK. Relationship between various cytokines implicated in asthma. Hum Immunol. Sep 2019;80(9):755-763. doi:10.1016/j.humimm.2019.04.018
Pizaña-Montero JA, Huerta-López JG, Pedroza-Melendez A. Biomarcadores para el diagnóstico endotípico del asma y su tratamiento. Alerg Asma Inmunol Pediatr. 2020;29(3):99-107.
Popovic-Grle S, Stajduhar A, Lampalo M, Rnjak D. Biomarkers in Different Asthma Phenotypes. Genes (Basel). May 25 2021;12(6)doi:10.3390/genes12060801
Kaur R, Chupp G. Phenotypes and endotypes of adult asthma: Moving toward precision medicine. J Allergy Clin Immunol. Jul 2019;144(1):1-12. doi:10.1016/j.jaci.2019.05.031
Wenzel SE. Severe Adult Asthmas: Integrating Clinical Features, Biology, and Therapeutics to Improve Outcomes. Am J Respir Crit Care Med. Apr 1 2021;203(7):809-821. doi:10.1164/rccm.202009-3631CI
Couillard S, Jackson DJ, Wechsler ME, Pavord ID. Workup of Severe Asthma. Chest. Dec 2021;160(6):2019-2029. doi:10.1016/j.chest.2021.07.008
Extremera Ortega AM, Moreno Lozano L, Gonzalez Jimenez OM, et al. Findings in Chest High-Resolution Computed Tomography in Severe Asthma. J Investig Allergol Clin Immunol. Apr 19 2022;32(2):146-147. doi:10.18176/jiaci.0725
Silva T, Zanon M, Altmayer S, et al. High-resolution CT pulmonary findings in children with severe asthma. J Pediatr (Rio J). Jan-Feb 2021;97(1):37-43. doi:10.1016/j.jped.2019.10.011
Roach DJ, Ruangnapa K, Fleck RJ, et al. Structural lung abnormalities on computed tomography correlate with asthma inflammation in bronchoscopic alveolar lavage fluid. J Asthma. Sep 2020;57(9):968-979. doi:10.1080/02770903.2019.1622714
King GG, Farrow CE, Chapman DG. Dismantling the pathophysiology of asthma using imaging. Eur Respir Rev. Jun 30 2019;28(152)doi:10.1183/16000617.0111-2018
Agache I, Eguiluz-Gracia I, Cojanu C, et al. Advances and highlights in asthma in 2021. Allergy. Nov 2021;76(11):3390-3407. doi:10.1111/all.15054
Kunc P, Fabry J, Lucanska M, Pecova R. Biomarkers of Bronchial Asthma. Physiol Res. Mar 27 2020;69(Suppl 1):S29-S34. doi:10.33549/physiolres.934398
Arismendi E, Picado Valles C. Current Role of Biomarkers in Severe Uncontrolled Asthma. Arch Bronconeumol (Engl Ed). Jun 2020;56(6):347-348. Papel de los biomarcadores en el asma grave no controlada en la actualidad. doi:10.1016/j.arbres.2019.08.001
Svenningsen S, Fowler SJ, Nair P. Clinical biomarkers and noninvasive assessment of severe asthma. In: Chung KFIEGPG, ed. Severe Asthma. European Respiratory Society; 2019:359.
Matsumoto-Sasaki M, Suzuki M, Kimura H, et al. Association of longitudinal changes in quality of life with comorbidities and exacerbations in patients with severe asthma. Allergol Int. Oct 2022;71(4):481-489. doi:10.1016/j.alit.2022.05.009
Rogliani P, Sforza M, Calzetta L. The impact of comorbidities on severe asthma. Curr Opin Pulm Med. Jan 2020;26(1):47-55. doi:10.1097/MCP.0000000000000640
Wang W, Lin J, Zhou X, et al. Associations between comorbidities and annual incidence plus frequency of asthma exacerbation hospitalisation during the past year: data from CARN study. BMC Pulm Med. Jul 1 2022;22(1):261. doi:10.1186/s12890-022-02038-3
Gaffin JM, Castro M, Bacharier LB, Fuhlbrigge AL. The Role of Comorbidities in Difficult-to-Control Asthma in Adults and Children. J Allergy Clin Immunol Pract. Feb 2022;10(2):397-408. doi:10.1016/j.jaip.2021.11.016
Chen M, Choo E, Yoo B, et al. No difference in omalizumab efficacy in patients with asthma by number of asthma-related and allergic comorbidities. Ann Allergy Asthma Immunol. Jun 2021;126(6):666-673. doi:10.1016/j.anai.2021.01.015
Kack U, van Hage M, Gronlund H, Lilja G, Asarnoj A, Konradsen JR. Allergic sensitization to lipocalins reflects asthma morbidity in dog dander sensitized children. Clin Transl Allergy. May 2022;12(5):e12149. doi:10.1002/clt2.12149
Lopez Couso VP, Tortajada-Girbes M, Rodriguez Gil D, Martinez Quesada J, Palacios Pelaez R. Fungi Sensitization in Spain: Importance of the Alternaria alternata Species and Its Major Allergen Alt a 1 in the Allergenicity. J Fungi (Basel). Aug 3 2021;7(8)doi:10.3390/jof7080631
Miller JD. The Role of Dust Mites in Allergy. Clin Rev Allergy Immunol. Dec 2019;57(3):312-329. doi:10.1007/s12016-018-8693-0
Monteverde-Fernandez N, Diaz-Rubio F, Vasquez-Hoyos P, Rotta AT, Gonzalez-Dambrauskas S, Network LA. Variability in care for children with severe acute asthma in Latin America. Pediatr Pulmonol. Feb 2021;56(2):384-391. doi:10.1002/ppul.25212
Griffiths D, Giancola LM, Welsh K, et al. Asthma control and psychological health in pediatric severe asthma. Pediatr Pulmonol. Jan 2021;56(1):42-48. doi:10.1002/ppul.25120
Pamuk G, Le Bourgeois M, Abou Taam R, et al. The economic burden of allergic comorbidities in pediatric severe asthma. Pediatr Allergy Immunol. Oct 2021;32(7):1559-1565. doi:10.1111/pai.13532
Licari A, Manti S, Chiappini E, Ciprandi G, Marseglia GL. Severe asthma in children: Current goals and unmet needs. Pediatr Allergy Immunol. Feb 2020;31 Suppl 24:40-42. doi:10.1111/pai.13168
Pijnenburg MW, Fleming L. Advances in understanding and reducing the burden of severe asthma in children. Lancet Respir Med. Oct 2020;8(10):1032-1044. doi:10.1016/S2213-2600(20)30399-4
Fainardi V, Saglani S. An approach to the management of children with problematic severe asthma. Acta Biomed. Sep 7 2020;91(3):e2020055. doi:10.23750/abm.v91i3.9603
Perez AV, Pol AB, Hernandez ER, Lorenzo MG, Serra AG, Bosque-Garcia M. Characterization of severe asthma in the pediatric population. Allergol Immunopathol (Madr). 2021;49(2):60-65. doi:10.15586/aei.v49i2.65
Ioachimescu OC, Desai NS. Nonallergic Triggers and Comorbidities in Asthma Exacerbations and Disease Severity. Clin Chest Med. Mar 2019;40(1):71-85. doi:10.1016/j.ccm.2018.10.005
Lezmi G, Lejeune S, Pin I, et al. Factors Associated with Asthma Severity in Children: Data from the French COBRAPed Cohort. J Allergy Clin Immunol Pract. May 2021;9(5):1969-1979. doi:10.1016/j.jaip.2020.12.027
Ren J, Xu J, Zhang P, Bao Y. Prevalence and Risk Factors of Asthma in Preschool Children in Shanghai, China: A Cross-Sectional Study. Front Pediatr. 2021;9:793452. doi:10.3389/fped.2021.793452
McLoughlin RF, Berthon BS, Wood LG. Weight loss in obese children with asthma - is it important? Paediatr Respir Rev. Mar 2021;37:10-14. doi:10.1016/j.prrv.2020.02.007
Chowdhury NU, Guntur VP, Newcomb DC, Wechsler ME. Sex and gender in asthma. Eur Respir Rev. Dec 31 2021;30(162)doi:10.1183/16000617.0067-2021
Miyasaka T, Dobashi-Okuyama K, Kawakami K, Masuda-Suzuki C, Takayanagi M, Ohno I. Sex Plays a Multifaceted Role in Asthma Pathogenesis. Biomolecules. Apr 29 2022;12(5)doi:10.3390/biom12050650
Munoz FA, Benton LD, Kops SA, Kowalek KA, Seckeler MD. Greater length of stay and hospital charges for severe asthma in children with depression or anxiety. Pediatr Pulmonol. Nov 2020;55(11):2908-2912. doi:10.1002/ppul.25061
Hoch H, Kattan M, Szefler SJ. Challenges in managing difficult-to-treat asthma in children: Stop, look, and listen. Pediatr Pulmonol. Mar 2020;55(3):791-794. doi:10.1002/ppul.24554
Plaza-Gonzalez S, Zabala-Banos MDC, Astasio-Picado A, Jurado-Palomo J. Psychological and Sociocultural Determinants in Childhood Asthma Disease: Impact on Quality of Life. Int J Environ Res Public Health. Feb 24 2022;19(5)doi:10.3390/ijerph19052652
Alharbi AS, Yousef AA, Alharbi SA, et al. Severe asthma in children: An official statement from Saudi Pediatric Pulmonology Association. Saudi Med J. Apr 2022;43(4):329-340. doi:10.15537/smj.2022.4.43.20210756
Agache I, Lau S, Akdis CA, et al. EAACI Guidelines on Allergen Immunotherapy: House dust mite-driven allergic asthma. Allergy. May 2019;74(5):855-873. doi:10.1111/all.13749
Busse WW, Haselkorn T, Rosén K, Trzaskoma BL, Ortiz B, Szefler SJ. Greater Treatment Benefit with Omalizumab in Children with Increased Asthma Severity: Exploratory Analyses from the
Inner-City Anti-IgE Therapy for Asthma (ICATA) Study. Journal of Allergy and Clinical Immunology. 2018;141(2):AB14. doi:10.1016/j.jaci.2017.12.045
Busse WW, Bleecker ER, FitzGerald JM, et al. Long-term safety and efficacy of benralizumab in patients with severe, uncontrolled asthma: 1-year results from the BORA phase 3 extension trial. Lancet Respir Med. Jan 2019;7(1):46-59. doi:10.1016/S2213-2600(18)30406-5
Korn S, Bourdin A, Chupp G, et al. Integrated Safety and Efficacy Among Patients Receiving Benralizumab for Up to 5 Years. J Allergy Clin Immunol Pract. Dec 2021;9(12):4381-4392 e4. doi:10.1016/j.jaip.2021.07.058
Chung Y, Katial R, Mu F, et al. Real-world effectiveness of benralizumab: Results from the ZEPHYR 1 Study. Ann Allergy Asthma Immunol. Jun 2022;128(6):669-676 e6. doi:10.1016/j.anai.2022.02.017
Pelaia C, Crimi C, Benfante A, et al. Therapeutic Effects of Benralizumab Assessed in Patients with Severe Eosinophilic Asthma: Real-Life Evaluation Correlated with Allergic and Non-Allergic Phenotype Expression. J Asthma Allergy. 2021;14:163-173. doi:10.2147/JAA.S297273
Pelaia C, Busceti MT, Vatrella A, et al. Real-life rapidity of benralizumab effects in patients with severe allergic eosinophilic asthma: Assessment of blood eosinophils, symptom control, lung function and oral corticosteroid intake after the first drug dose. Pulm Pharmacol Ther. Oct 2019;58:101830. doi:10.1016/j.pupt.2019.101830
Pelaia C, Crimi C, Nolasco S, et al. Switch from Omalizumab to Benralizumab in Allergic Patients with Severe Eosinophilic Asthma: A Real-Life Experience from Southern Italy. Biomedicines. Dec 3 2021;9(12)doi:10.3390/biomedicines9121822
Menzella F, Bargagli E, Aliani M, et al. ChAracterization of ItaliaN severe uncontrolled Asthmatic patieNts Key features when receiving Benralizumab in a real-life setting: the observational rEtrospective ANANKE study. Respir Res. Feb 19 2022;23(1):36. doi:10.1186/s12931-022-01952-8
Jackson D, Dube S, Morris T, Hassan B, Pfeffer PE. Improvement of Clinical Outcomes in Severe Eosinophilic Asthma Patients Treated with Benralizumab in Real-World Clinical Practice in England: XALOC Study Programme. B32 ASTHMA OUTCOMES. American Thoracic Society; 2020:A3028-A3028. American Thoracic Society International Conference Abstracts.
FitzGerald JM, Bleecker ER, Menzies-Gow A, et al. Predictors of enhanced response with benralizumab for patients with severe asthma: pooled analysis of the SIROCCO and CALIMA studies. Lancet Respir Med. Jan 2018;6(1):51-64. doi:10.1016/S2213-2600(17)30344-2
Trudo F, Hirsch I, Gopalan G, Martin U. Impact of Body Mass Index on Efficacy of Benralizumab in Patients with Severe, Uncontrolled Eosinophilic Asthma: Pooled Analysis of the SIROCCO and CALIMA Trials. A101 MECHANISMS AND CLINICAL FEATURES OF SEVERE ASTHMA. 2018;(308):A2490-A2490. American Thoracic Society International Conference Abstracts. doi:doi:10.1164/ajrccm-conference.2018.197.1_MeetingAbstracts.A2490
1164/ajrccm-conference.2018.197.1_MeetingAbstracts.A2490
Ibrahim H, O'Sullivan R, Casey D, et al. The effectiveness of Reslizumab in severe asthma treatment: a real-world experience. Respir Res. Dec 20 2019;20(1):289. doi:10.1186/s12931-019-1251-3
Pavord ID, Bel EH, Bourdin A, et al. From DREAM to REALITI-A and beyond: Mepolizumab for the treatment of eosinophil-driven diseases. Allergy. Mar 2022;77(3):778-797. doi:10.1111/all.15056
Albers FC, Papi A, Taille C, et al. Mepolizumab reduces exacerbations in patients with severe eosinophilic asthma, irrespective of body weight/body mass index: meta-analysis of MENSA and MUSCA. Respir Res. Jul 30 2019;20(1):169. doi:10.1186/s12931-019-1134-7
Casale TB, Burnette A, Bourdin A, et al. Oral corticosteroid-sparing effects of mepolizumab in severe eosinophilic asthma: evidence from randomized controlled trials and real-world studies. Ther Adv Respir Dis. Jan-Dec 2022;16:17534666221107313. doi:10.1177/17534666221107313
Charles D, Shanley J, Temple SN, Rattu A, Khaleva E, Roberts G. Real-world efficacy of treatment with benralizumab, dupilumab, mepolizumab and reslizumab for severe asthma: A
systematic review and meta-analysis. Clin Exp Allergy. May 2022;52(5):616-627. doi:10.1111/cea.14112
Domingo Ribas C, Maspero J, Castro M, et al. Dupilumab Reduced Oral Corticosteroid Use And Improved Clinical Outcomes Regardless Of Baseline Ocs Dose In Patients With Uncontrolled, Severe Asthma In The Liberty Asthma Venture Study. CHEST. 2021;160(4):A1893-A1897. doi:10.1016/j.chest.2021.07.1680
Maspero JF, FitzGerald JM, Pavord ID, et al. Dupilumab efficacy in adolescents with uncontrolled, moderate-to-severe asthma: LIBERTY ASTHMA QUEST. Allergy. Aug 2021;76(8):2621-2624. doi:10.1111/all.14872
Szefler SJ, Roberts G, Rubin AS, et al. Efficacy, safety, and tolerability of lebrikizumab in adolescent patients with uncontrolled asthma (ACOUSTICS). Clin Transl Allergy. Jul 2022;12(7):e12176. doi:10.1002/clt2.12176
Papaioannou AI, Fouka E, Papakosta D, Papiris S, Loukides S. Switching between biologics in severe asthma patients. When the first choice is not proven to be the best. Clin Exp Allergy. Feb 2021;51(2):221-227. doi:10.1111/cea.13809
Esta obra está bajo una licencia internacional Creative Commons Atribución-NoComercial 4.0.
Derechos de autor 2023 Revista Alergia México