Biomarcadores nas doenças respiratórias obstrutivas crônicas: a próxima página
Biomarkers for chronic obstructive respiratory diseases: the next page
Hisbello S. Campos
Resumo
Nas últimas décadas, consensos e diretrizes vêm orientando padronizações terapêuticas que, mesmo baseadas em evidências, partem do princípio de que o mesmo medicamento é bom para todos que têm a mesma doença. Essa conduta vai de encontro aos conhecimentos atuais sobre os mecanismos envolvidos na patogenia da maior parte das disfunções clínicas. Doenças são produto da conjunção de fatores genéticos, ambientais e comportamentais. Polimorfismos genéticos, microbioma, exposições ambientais e agentes etiológicos se conjugam, determinando processos etiopatogênicos complexos que fundamentam a expressão clínica. Propor padronizações terapêuticas que não levem em consideração as diferenças potenciais que tornam única cada pessoa doente, atenta contra o bom senso. Hoje se reconhece a necessidade de uma abordagem personalizada, que considere a premissa de que, em cada indivíduo, a doença pode ter diferentes alvos terapêuticos, e que cada pessoa pode responder diferentemente à mesma abordagem terapêutica. Nessa nova perspectiva, biomarcadores capazes de identificar o mecanismo patogênico responsável pela disfunção em cada indivíduo e o alvo terapêutico são instrumentos fundamentais. A identificação desses biomarcadores é uma etapa importante na transição do modelo atual da prática médica para a medicina de precisão, na qual a abordagem preventiva e terapêutica levará em consideração a variabilidade genética, o ambiente e o estilo de vida de cada pessoa. Possivelmente, essa nova prática médica permitirá aumentar as taxas de sucesso terapêutico na asma e na doença pulmonar obstrutiva crônica, problemas respiratórios crônicos de prevalência elevada com uma gama ampla e variada de apresentações clínicas e respostas às terapias atuais.
Palavras-chave
Abstract
In recent decades, consensuses and guidelines have guided therapeutic standards which, though based on evidence, assume that the same drug is good for everyone who has the same disease. This behavior is inconsistent with current knowledge on the mechanisms involved in the pathogenesis of most clinical disorders. Diseases are the product of the conjunction of genetic, environmental and behavioral factors. Genetic polymorphisms, microbiome, environmental exposures and etiological agents combine to determine complex etiopathogenic processes that support clinical expression. Proposing standardized therapies disregarding the potential differences that make each diseased person unique threatens common sense. Today, we recognize the need for a personalized approach considering the premise that in each individual the disease may have different therapeutic targets and that each person may respond differently to the same therapeutic approach. In this new perspective, biomarkers capable of identifying the pathogenic mechanism responsible for the dysfunction in each individual and the therapeutic target are fundamental instruments. Identification of these biomarkers is an important step for a transition from the current model of medical practice to precision medicine, in which preventive and therapeutic approach will take into account genetic variability, environment and the lifestyle of each person. This new medical approach may potentially increase therapeutic success rates in asthma and chronic obstructive pulmonary disease, both highly prevalent chronic respiratory problems with a wide range of clinical presentations and responses to current therapies.
Keywords
References
1. Guo F, Svenningsen S, Kirby M, Capaldi DP, Sheikh K, Fenster A, et al. Thoracic CT-MRI coregistration for regional pulmonary structure-function measurements of obstructive lung disease. Med Phys. 2017;44(5):1718‑33.
2. Steckling N, Gotti A, Bose-O'Reilly S, Chapizanis D, Costopoulou D, De Vocht F, et al. Biomarkers of exposure in environment-wide association studies - Opportunities to decode the exposome using human biomonitoring data. Environ Res. 2018;164:597-624.
3. Cocker J, Jones K, Bos PM. Biological monitoring guidance values for chemical incidents. Toxicol Lett. 2014;231(3):324-7.
4. Buclin T, Gotta V, Fuchs A, Widmer N, Aronson J. Monitoring drug therapy. Br J Clin Pharmacol. 2012;73(6):917-23.
5. Biomarkers Definitions Working Group. Biomarkers and surrogates endpoints: preferred definitions and conceptual framework. Clin Pharmacol Ther. 2001;69(3):89-95.
6. Matthews H, Hanison J, Nirmalan N. “Omics”-Informed Drug and Biomarker Discovery: Opportunities, Challenges and Future Perspectives. Proteomes. 2016;4(3). pii: E28. doi: 10.3390/ proteomes4030028.
7. Chambliss AB, Chan DW. Precision medicine: from pharmacogenomics to pharmacoproteomics. Clin Proteomics. 2016 Sep 26;13:25. eCollection 2016.
8. Strobel EJ, Watters KE, Loughrey D, Lucks JB. RNA systems biology: uniting functional discoveries and structural tools to understand global roles of RNAs. Curr Opin Biotechnol. 2016;39:182-91.
9. Duarte TT, Spencer CT. Personalized Proteomics: The Future of Precision Medicine. Proteomes 2016;4(4):29.
10. Gstaiger M, Aebersold R. Appying mass spectrometry-based proteomics to genetics, genomics and network biology. Nat Rev Genet. 2009;10(9):617-27.
11. Kell DB, Oliver SG. The metabolome 18 years on: a concept comes of age. Metabolomics. 2016;12(9):148.
12. Lin E, Lane HY. Machine learning and systems genomics approaches for multi-omics data. Biomark Res. 2017;5:2.
13. Soler-Cataluña JJ, Cosío B, Izquierdo JL, López-Campos JL, Marín JM, Agüero R, et al. Consensus document on the overlap phenotype COPD-asthma in COPD. Arch Broncopneumol. 2012;48:331-7.
14. World Health Organization. 2015 Asthma, COPD and Asthma-COPD Overlap Syndrome (ACOS). Disponível em: http://ginasthma.org/asthma-copd-and-asthma-copd-overlap-syndrome-acos/ .
15. Borril ZL, Roy K, Singh D. Exhaled breath analysis: biomarkers in COPD. Eur Respir J. 2008;32:472-68.
16. Alving K, Weitzberg E, Lundberg JM. Increased amount of nitric oxide in exhaled air of asthmatics. Eur Respir J. 1993;6:1368-70.
17. Blitzer ML, Loh E, Roddy MA, Stamler JS, Creager MA. Endotheliumderived nitric oxide regulates systemic and pulmonary vascular resistance during acute hypoxia in humans. J Am Coll Cardiol. 1996; 28:591.
18. Jain B, Rubinstein I, Robbins RA, Leise KL, Sisson JH. Modulation of airway epithelial cell ciliary beat frequency by nitric oxide. Biochem Biophys Res Commun. 1993;191(1):83-8.
19. Belvisi MG, Ward JK, Mitchell JA, Barnes PJ. Nitric oxide as a neurotransmitter in human airways. Arch Int Pharmacodyn Ther. 1995;329:97.
20. Paraskakis E, Brindicci C, Fleming L, Krol R, Kharitonov SA, Wilson NM, et al. Measurement of bronchial and alveolar nitric oxide production in normal children and children with asthma. Am J Respir Crit Care Med. 2006;174:260.
21. Dweik RA, Boggs PB, Erzurum SC, Irvin CG, Leigh MW, Lundberg JO, et al. An official ATS clinical practice guideline: interpretation of exhaled nitric oxide levels (FENO) for clinical applications. Am J Respir Crit Care Med. 2011;184:602‑15.
22. Oh MJ, Lee JY, Lee BJ, Choi DC. Exhaled nitric oxide measurement is useful for the exclusion of nonasthmatic eosinophilic bronchitis in patients with chronic cough. Chest. 2008;134:990. Referências 23. Konstantinidi EM, Lappas AS, Tzortzi AS, Beharakis PK. Exhaled breath condensate: Technical and diagnostic aspects. Scient World J. 2015. 2015:435160. doi: 10.1155/2015/435160.
24. Balazs Antus. Oxidative stress markers in sputum. Oxidative Medicine and Cellular Longevity. 2016. doi.org/10.1155/2016/2930434.
25. Brusselle GG, Joos GE, Bracke KR. New insights into the immunology of chronic obstructive pulmonary disease. The Lancet. 2011;9795:10115-26.
26. Makris D, Tzanakis N, Damianaki A, Ntaoukakis E, Neofytou E, Zervou M, et al. Microsatellite DNA instability and COPD exacerbations. Eur Respir J. 2008;3:612-8.
27. Cazzola M, MacNee W, Martinez FJ, Rabe KF, Franciosi LG, Barnes PJ, et al. Outcomes for COPD pharmacological trials: from lung function to biomarkers. Eur Respir J. 2008;31:416-68.
28. Simpson JL, Scott R, Boyle MJ, Gibson PG. Inflammatory subtypes in asthma: assessment and identification using induced sputum. Respirology. 2006;11:54-61.
29. Leung JM, Sin DD. Biomarkers in airway diseases. Can Respir J. 2013;20:180-2.
30. Paone G, Leone V, Conti V, De Marchis L, Ialleni E, Graziani C, et al. Blood and sputum biomarkers in COPD and asthma: a review. Eur Rev Med Pharmacol Sci. 2016;20:698-708.
31. Wagener AH, de Nijs SB, Lutter R, Sousa AR, Weersink EJ, Bel EH, et al. External validation of blood eosinophils, FE(NO) and serum periostina as surrogates for sputum eosinophils in asthma. Thorax. 2015;70:115-20.
32. Berezikov E. Evolution of microRNA diversity and regulation in animals. Nat Rev Genet. 2011;12:846-60.
33. Friedman RC, Farh KK, Burge CB, Bartel DP. Most mammalian miRNA are conserved targets of microRNAs. Genome. 2009;19:95‑105.
34. Markou A, Zavridou M, Lianidou ES. miRNA-21 as a novel therapeutic target in lung cancer. Lung Cancer (Auckl). 2016;7:19-27.
35. Lee JS, Ahn Y, Won HS, Sun DS, Kim YH, Ko YH. Prognostic role of the microRNA-200 family in various carcinomas: a systematic review and meta-analysis. Biomed Res Int. 2017;1928021. doi:
10.1155/2017/1928021
36. Maltby S, Plank M, Tay HL, Collison A, Foster PS. Targeting microRNA function in respiratory diseases: mini-review. Front Physiol. 2016;7:21-31.
37. Ding Y, Sun X, Shan PF. MicroRNAs and Cardiovascular Disease in Diabetes Mellitus. Biomed Res Int. 2017;4080364. doi: 10.1155/2017/4080364.
38. Correia CN, Nalpas NC, McLoughlin KE, Browne JA, Gordon SV, MacHugh DE, et al. Circulating microRNAs as potential biomarkers of infectious disease. Front Immunol. 2017;8:118.
39. Tay HL, Plank M, Collison A, Mattes J, Kumar RK, Foster PS. MicroRNA: potential biomarkers and therapeutic targets. Ann Med. 2014;46(8):633-9.
40. De Smet EG, Mestdagh P, Vandesompele J, Brusselle GG, Bracke KR. Non-coding RNAs in the pathogenesis of COPD. Thorax. 2015;70:782-91.
41. Banerjee A, Luettich K. MicroRNA as potential biomarkers of smoking-related diseases. Biomarkers Med. 2012;6(5);671-84.
42. Janssen HL, Reesink HW, Lawitz EJ, Zeuzem S, Rodriguez-Torres M, Patel K, et al. Treatment of HCV infection by targeting microRNA. N Engl J Med. 2013;368:1685-94.
Submitted date:
06/13/2018
Accepted date:
09/14/2018
Facebook
LinkedIn
Mendeley
StumbleUpon
Reddit
Email