Asma tem cura?
Is asthma curable?
Hisbello da Silva Campos
Resumo
A asma é o produto de processos coordenados, interligados e complexos que têm origem nos genes/epigenética, microbioma e ambiente/estilo de vida. Os medicamentos atualmente disponíveis não são capazes de interferir com a inserção da asma no organismo. A abordagem terapêutica atual envolve fármacos que visam controlar os sintomas e antagonizar parte dos efeitos de algumas das citocinas envolvidas. Dessa forma, o tratamento atual visa o controle da asma e não a sua cura. Mecanismos epigenéticos traduzem os estímulos microbiômicos e ambientais em comportamento celular alterado. Por essa razão, a identificação de marcadores epigenéticos certamente apontará novos alvos terapêuticos e, idealmente, estratégias para reverter o comportamento celular alterado no trato respiratório. Aí, sim, poderíamos dizer que a asma tem cura.
Palavras-chave
Abstract
Asthma is the product of coordinated, interconnected and complex processes that originate in genes/epigenetics, microbiome, and environment/lifestyle. Currently available drugs are not able to interfere with the insertion of asthma into the body. The current therapeutic approach involves drugs that aim to control symptoms and antagonize part of the effects of some of the cytokines involved. Thus, the current treatment is aimed at controlling asthma and not curing it. Epigenetic mechanisms translate the microbiological and environmental stimuli into altered cellular behavior. For this reason, the identification of epigenetic markers will certainly point out to new therapeutic targets and, ideally, strategies to reverse the altered cellular behavior in the respiratory tract. Then, yes, we could say that asthma is curable.
Keywords
Referências
1. Lolas Stepke F. Proposiciones para una teoría de la Medicina. Santiago de Chile: Editorial Universitaria; 1992. p. 213.
2. Jackson DJ, Hartert TV, Martinez FD, Weiss ST, Fahy JV. Asthma: NHLBI Workshop on the Primary Prevention of Chronic Lung Diseases. Ann Am Thorac Soc. 2014;11 Suppl 3(Suppl 3):S139‑45.
3. Yunginger JW. A community-based study of the epidemiology of asthma. Incidence rates. Am Rev Respir Dis. 1992;146:888-94.
4. Arshad SH, Raza A, Lau L, Bawakid K, Karmaus W, Zhang H, et al. Pathophysiological characterization of asthma transitions across adolescence. Respir Res. 2014;15(1):153.
5. Szefler SJ. Advances in pediatric asthma in 2014: Moving toward a population health perspective. J Allergy Clin Immunol. 2015;135(3):644-52.
6. Dumas O, Laurent E, Bousquet J, Metspalu A, Milani L, Kauffmann F, et al. Occupational irritants and asthma: an Estonian cross-sectional study of 34,000 adults. Eur Respir J. 2014;44(3):647-56.
7. Wu W, Bleecker E, Moore W, Busse WW, Castro M, Chung KF, et al. Unsupervised phenotyping of Severe Asthma Research Program participants using expanded lung data. J Allergy Clin Immunol. 2014;133(5):1280-8.
8. Kuruvilla ME, Lee F E-H, Lee GB. Understanding Asthma phenotype, endotyes, and mechanisms of Disease. Clin Ver Allergy Immunol. 2019;56(2):219-33.
9. Al-Sajee D, Sehmi R, Hawke TJ, El-Gammal A, Howie KJ, Watson RM, et al. Expression of IL-33 and TSLP and Their Receptors in Asthmatic Airways after Inhaled Allergen Challenge. Am J Respir Crit Care Med. 2018;198(6):805-7.
10. Hirose K, Iwata A, Tamachi T, Nakajima H. Allergic airway inflammation: key players beyond the Th2 cell pathway. Immunol Rev. 2017;278(1):145-61.
11. Sze E, Bhalla A, Nair P. Mechanisms and therapeutic strategies for non-T2 asthma. Allergy. 2020;75:311-25.
12. Ntontsi P, Photiades A, Zervas E, Xanthou G, Samitas, K. Genetics and Epigenetics in Asthma. Int J Mol Sci. 2021;22(5):2412. doi:10.3390/ijms22052412.
13. Ferreira MAR, Mathur R, Vonk JM, Szwajda A, Brumpton B, Granell R, et al. Genetic Architectures of Childhood- and Adult-Onset Asthma Are Partly Distinct. Am J Hum Genet. 2019;104(4):665-84.
14. DeVries, A. Vercelli, D. Epigenetic Mechanisms in Asthma. Ann Am Thorac Soc. 2016;13(Suppl1):S48-S50.
15. Brook PO, Perry MM, Adcock IM, Durham AL. Epigenome-modifying tools in asthma. Epigenomics. 2015;7(6):1017-32.
16. Lovinsky-Desir S, Miller RL. Epigenetics, asthma, and allergic diseases: A review of the latest advancements. Curr Allergy Asthma Rep. 2012;12: 211-20.
17. Martin EM, Fry RC. Environmental influences on the epigenome: exposure-associated DNA methylation in human populations, Annual Review of Public Health. 2018;39:309-33.
18. Bae DJ, Jun JA, Chang HS, Park JS, Park CS. Epigenetic Changes in Asthma: Role of DNA CpG Methylation. Tuberc Respir Dis (Seoul). 2020;83(1):1‑13.
19. Strachan DP. Hay fever, hygiene and household size. BMJ. 1989;299:1259‑60
20. Martinez FD, Holt PG. Role of microbial burden in the aetiology of allergy and asthma. Lancet. 1999;354(Suppl II):12-5.
21. Strachan DP. Family size, infection and atopy: the first decade of the “hygiene hypothesis”. Thorax. 2000;55(Suppl1):S2-S10.
22. Qin J, Li R, Raes J, Arumugam M, Burgdorf KS, Manichanh C, et al. A human gut microbial gene catalogue established by metagenomic sequencing. Nature. 2010 Mar 4;464(7285):59-65.
23. Chotirmall SH, Gellatly SL, Budden KF, Mac Aogain M, Shukla SD, Wood DL, et al. Microbiomes in respiratory health and disease: An Asia-Pacific perspective. Respirology. 2017 Feb;22(2):240‑50.
24. Dang AT, Marsland BJ. Microbes, metabolites, and the gut-lung axis. Mucosal Immunol. 2019;12:843-50.
25. Budden KF, Shukla SD, Rehman SF, Bowerman KL, Keely S, Hugenholtz P, et al. Functional effects of the microbiota in chronic respiratory disease. Lancet Respir Med. 2019;7(10):907-20.
26. Murrison LB, Brandt EB, Myers JB, Hershey GKK. Environmental exposures and mechanisms in allergy and asthma development. J Clin Invest. 2019;129(4):1504-15.
27. van Woerden HC, Gregory C, Brown R, Marchesi JR, Hoogendoorn B, Matthews IP. Differences in fungi present in induced sputum samples from asthma patients and non-atopic controls: a community based case control study. BMC Infect Dis. 2013;13:69.
28. McGregor MC, Krings JG, Nair P, Castro M. Role of Biologics in Asthma. Am J Respir Crit Care Med. 2019;199(4):433-45.
29. Busse W, Chupp G, Nagase H, Albers FC, Doyle S, Shen Q, et al. Anti-IL-5 treatments in patients with severe asthma by blood eosinophil thresholds: Indirect treatment comparison. J Allergy Clin Immunol. 2019;143(1):190-200.e20.
30. Casale TB, Pacou M, Mesana L, Farge G, Sun SX, Castro M. Reslizumab Compared with Benralizumab in Patients with Eosinophilic Asthma: A Systematic Literature Review and Network Meta-Analysis. J Allergy Clin Immunol Pract. 2019;7(1):122-130. e1.
31. Bourdin A, Husereau D, Molinari N et cols. Matching-adjusted indirect comparison of benralizumab versus interleukin-5 inhibitors: systematic review. Eur Respir J. 2018;52:1801393.
32. Bourdin A, Husereau D, Molinari N, Golam S, Siddiqui MK, Lindner L, et al. Matching-adjusted indirect comparison of benralizumab versus interleukin-5 inhibitors for the treatment of severe asthma: a systematic review. Eur Respir J. 2018;52(5):1801393.
33. Rebollo RA. O legado hipocrático e sua fortuna no período grecoromano: de Cós a Galeno. SCIENTLÆ studia. 2006;4(1):45-82.
34. Brook PO, Perry MM, Adcock IM, Durham AL. Epigenome-modifying tools in asthma. Epigenomics. 2015;7(6):1017-32.
Submetido em:
18/10/2021
Aceito em:
11/12/2021
Facebook
Google+
Twitter
LinkedIn
Mendeley
StumbleUpon
CiteULike
Reddit
Email