A associação da taxa de adesão ao tratamento fisioterapêutico em diferentes características genotípicas na fibrose cística
The association of adherence rate to physiotherapeutic treatment in different genotypic characteristics in cystic fibrosis
Marilia Simone de Oliveira, Carolina Haddad Martins, Diego Campos de Moura, Luanna Rodrigues Leite, Evanirso da Silva Aquino
Resumo
Introdução: A Fibrose Cística (FC) é uma doença genética causada por mutações no gene regulador da transmembrana da fibrose cística -CFTR, sendo a mutação Delta F508 a mais prevalente e associada a formas mais graves. O tratamento fisioterapêutico é essencial no manejo da FC, mas a adesão costuma ser baixa, especialmente em pacientes com mutações severas. Objetivo: Verificar se há diferença na taxa de adesão ao tratamento fisioterapêutico entre diferentes categorias genotípicas e sua associação com exacerbações e função pulmonar. Métodos: Estudo descritivo, transversal e analítico com pacientes com FC de até 18 anos. Foram avaliadas a adesão relatada e aferida, o escore de Fuchs, a função pulmonar e o genótipo. As mutações foram classificadas em homozigose para Delta F508, heterozigose para Delta F508 e outras. A análise estatística utilizou Kolmogorov-Smirnov, correlação de Spearman e ANOVA com Bonferroni (α < 0,05). Resultados: Foram incluídos 108 pacientes, predominando homozigotos para Delta F508 (46,3%). As medianas de adesão relatada e aferida foram 8,0 e 8,5, respectivamente, e o escore de Fuchs foi 1,0. Não houve diferenças significativas entre as categorias genotípicas e a adesão (p > 0,05) nem com os Sinais Clínicos de Exacerbação (SCE). Observou-se, contudo, correlação negativa significativa entre adesão e SCE (r = -0,3; p < 0,01) e correlação positiva entre adesão e VEF1/CVF (r = 0,2 e 0,3; p < 0,05). Conclusão: A maior adesão ao tratamento fisioterapêutico associa-se à redução de exacerbações e à melhor preservação da função pulmonar, independentemente do genótipo.
Palavras-chave
Abstract
Background: Cystic fibrosis (CF) is a genetic disease caused by mutations in the Cystic Fibrosis Transmembrane Conductance Regulator -CFTR gene, with the Delta F508 mutation being the most prevalent and associated with more severe clinical manifestations. Physiotherapeutic treatment is essential for CF management; however, adherence is often low, especially among patients with severe mutations. Aim: To verify whether there are differences in physiotherapy treatment adherence rates among different genotypic categories and to assess their association with pulmonary exacerbations and lung function. Methods: A descriptive, cross-sectional, and analytical study was conducted with CF patients aged up to 18 years. Reported and measured adherence, Fuchs score, pulmonary function, and genotype were evaluated. Mutations were classified as homozygous Delta F508, heterozygous Delta F508, or other mutations. Statistical analysis used the Kolmogorov–Smirnov test, Spearman correlation, and ANOVA with Bonferroni correction (α < 0.05). Results: A total of 108 patients were included, with Delta F508 homozygotes being predominant (46.3%). Median reported and measured adherence scores were 8.0 and 8.5, respectively, and the median Fuchs score was 1.0. No significant differences were observed between genotypic categories and adherence (p > 0.05) or clinical signs of exacerbation (SCE). However, a significant negative correlation was found between adherence and SCE (r = –0.3; p < 0.01) and a positive correlation between adherence and the FEV1/FVC ratio (r = 0.2 and 0.3; p < 0.05). Conclusion: Higher adherence to physiotherapeutic treatment is associated with fewer pulmonary exacerbations and better preservation of lung function, regardless of genotype.
Keywords
References
1. Camargos ACR, Ferreira GM, Santos JF, Lanza FC, Rocha NA. Fisioterapia em pediatria: da evidência à prática clínica. Rio de Janeiro: Medbook; 2019.
2. Gramegna A, Contarini M, Aliberti S, Casciaro R, Blasi F, Castellani C. From Ivacaftor to triple combination: a systematic review of efficacy and safety of CFTR modulators in people with cystic fibrosis. Int J Mol Sci. 2020;21(16):5882. https://doi.org/10.3390/ijms21165882. PMid:32824306.
3. Chen Q, Shen Y, Zheng J. A review of cystic fibrosis: basic and clinical aspects. Animal Model Exp Med. 2021;4(3):220-32. https://doi.org/10.1002/ame2.12180. PMid:34557648.
4. De Boeck K, Zolin A. Year to year change in FEV1 in patients with cystic fibrosis and different mutation classes. J Cyst Fibros. 2016;16(2):239-45. https://doi.org/10.1016/j. jcf.2016.09.009. PMid:27745801.
5. Button BM, Wilson C, Dentice R, Cox NS, Middleton A, Tannenbaum E, et al. Physiotherapy for cystic fibrosis in Australia and New Zealand: a clinical practice guideline. Respirology. 2016;21(4):656-67. https://doi.org/10.1111/ resp.12764. PMid:27086904.
6. Williams CA, Stevens D. Physical activity and exercise training in young people with cystic fibrosis: current recommendations and evidence. J Sport Health Sci. 2012;2(1):39-46. https://doi.org/10.1016/j.jshs.2012.11.002.
7. Spinou A. Physiotherapy in cystic fibrosis: a comprehensive clinical overview. Pneumon (Athens). 2018;31(1):35-43.
8. Llorente RPA, García CB, Martín JJG. The importance of adherence and compliance with treatment in cystic fibrosis. In: Sriramulu D, editor. Cystic fibrosis – renewed hopes through research. Rijeka: InTech; 2012. https://doi. org/10.5772/25884.
9. O’Donohoe R, Fullen BM. Adherence of subjects with cystic fibrosis to their home program: a systematic review. Respir Care. 2014;59(11):1731-46. https://doi.org/10.4187/ respcare.02990. PMid:25233386.
10. Eaton CK, Beachy S, McLean CA, Nicolais CJ, Bernstein R, Sáez-Clarke E, et al. Misunderstandings, misperceptions, and missed opportunities: perspectives on adherence barriers from people with cystic fibrosis, caregivers, and CF team members. Patient Educ Couns. 2020;103(8):1587-94. https:// doi.org/10.1016/j.pec.2020.02.025. PMid:32098744.
11. Santuzzi CH, Liberato FMG, Morau SAC, Oliveira DNFF, Nascimento LR. Adherence and barriers to general and respiratory exercises in cystic fibrosis. Pediatr Pulmonol. 2020;55(10):2646-52. https://doi.org/10.1002/ppul.24912. PMid:32558990.
12. Modi AC, Lim CS, Yu N, Geller D, Wagner MH, Quittner AL. A multi-method assessment of treatment adherence for children with cystic fibrosis. J Cyst Fibros. 2006;5(3):177-85. https://doi.org/10.1016/j.jcf.2006.03.002. PMid:16679071.
13. CF Care. Visual analogue scale for adherence and non-adherence [Internet]. CF Care; 2022 [citado em 23 Jun 2024]. Disponível em: https://www.cfcare.net/vasana-itp-tools
14. Fuchs HJ, Borowitz DS, Christiansen DH, Morris EM, Nash ML, Ramsey BW, et al. Effect of aerosolized recombinant human DNase on exacerbations of respiratory symptoms and on pulmonary function in patients with cystic fibrosis. N Engl J Med. 1994;331(10):637-42. https://doi.org/10.1056/ NEJM199409083311003. PMid:7503821.
15. Miller MR, Hankinson J, Brusasco V, Burgos F, Casaburi R, Coates A, et al. Standardisation of spirometry. Eur Respir J. 2005;26(2):319-38. https://doi.org/10.1183/09031936.05.0 0034805. PMid:16055882.
16. Quanjer PH, Stanojevic S, Cole TJ, Baur X, Hall GL, Culver BH, et al. Multi-ethnic reference values for spirometry for the 3–95 year age range: the global lung function 2012 equations. Eur Respir J. 2012;40(6):1324-43. https://doi. org/10.1183/09031936.00080312. PMid:22743675.
17. Eakin MN, Bilderback A, Boyle MP, Mogayzel PJ, Riekert KA. Longitudinal association between medication adherence and lung health in people with cystic fibrosis. J Cyst Fibros. 2011;10(4):258-64. https://doi.org/10.1016/j.jcf.2011.03.005. PMid:21458391.
18. Quittner AL, Zhang J, Marynchenko M, Chopra PA, Signorovitch J, Yushkina Y, et al. Pulmonary medication adherence and health-care use in cystic fibrosis. Chest. 2014;146(1):142-51. https://doi.org/10.1378/chest.13-1926. PMid:24480974.
19. Narayanan S, Mainz JG, Gala S, Tabori H, Grossoehme D. Adherence to therapies in cystic fibrosis: a targeted literature review. Expert Rev Respir Med. 2017;11(2):129-45. https://doi.org/10.1080/17476348.20 17.1280399. PMid:28107795.
20. Vermeire E, Hearnshaw H, Van Royen P, Denekens J. Patient adherence to treatment: three decades of research. A comprehensive review. J Clin Pharm Ther. 2001;26(5):331- 42. https://doi.org/10.1046/j.1365-2710.2001.00363.x. PMid:11679023.
21. Oliboni LS, Castro MS. Métodos para aferir a adesão à farmacoterapia em doenças crônicas: uma revisão narrativa. J Assist Farm Farm. 2022;2(4). https://doi.org/10.22563/2525- 7323.2017.v2.n4.p.16-28.
22. Cella D, Riley W, Stone A, Rothrock N, Reeve B, Yount S, et al. Initial adult health item banks and first wave testing of the Patient-Reported Outcomes Measurement Information System (PROMIS™) network: 2005–2008. J Clin Epidemiol. 2010;63(11):1179-94. https://doi.org/10.1016/j. jclinepi.2010.04.011. PMid:20685078.
23. Liu Y, Yuan C, Wang J, Shen N, Shen M, Hinds PS. Chinese version of Pediatric Patient-Reported Outcomes Measurement Information System short form measures: reliability, validity, and factorial structure assessment in children with cancer in China. Cancer Nurs. 2019;42(6):430- 8. https://doi.org/10.1097/NCC.0000000000000633. PMid:30124482.
24. Plevinsky JM, Gutierrez-Colina AM, Carmody JK, Hommel KA, Crosby LE, McGrady ME, et al. Patient-reported outcomes of pediatric adherence and self-management: a systematic review. J Pediatr Psychol. 2020;45(3):340-57. https://doi. org/10.1093/jpepsy/jsz096. PMid:31845997.
25. Eddy L, Khastou L, Cook KF, Amtmann D. Item selection in self-report measures for children and adolescents with disabilities: lessons from cognitive interviews. J Pediatr Nurs. 2011;26(6):559-65. https://doi.org/10.1016/j. pedn.2010.07.004. PMid:22055376.
26. Kalichman SC, Amaral CM, Swetzes C, Jones M, Macy R, Kalichman MO, et al. A simple single-item rating scale to measure medication adherence: further evidence for convergent validity. J Int Assoc Physicians AIDS Care. 2009;8(6):367-74. https://doi. org/10.1177/1545109709352884. PMid:19952289.
27. Garfield S, Eliasson L, Clifford S, Willson A, Barber N. Developing the Diagnostic Adherence to Medication Scale (the DAMS) for use in clinical practice. BMC Health Serv Res. 2012;12(1):350. https://doi.org/10.1186/1472-6963-12-350. PMid:23039138.
28. Oates GR, Stepanikova I, Gamble S, Gutierrez HH, Harris WT. Adherence to airway clearance therapy in pediatric cystic fibrosis: socioeconomic factors and respiratory outcomes. Pediatr Pulmonol. 2015;50(12):1244-52. https:// doi.org/10.1002/ppul.23317. PMid:26436321.
29. Wildman MJ, O’Cathain A, Maguire C, Arden MA, Hutchings M, Bradley J, et al. Self-management intervention to reduce pulmonary exacerbations by supporting treatment adherence in adults with cystic fibrosis: a randomised controlled trial. Thorax. 2022;77(5):461-9. https://doi. org/10.1136/thoraxjnl-2021-217594. PMid:34556552.
30. Akoglu H. User’s guide to correlation coefficients. Turk J Emerg Med. 2018;18(3):91-3. https://doi.org/10.1016/j. tjem.2018.08.001. PMid:30191186.
31. Lechtzin N, West N, Allgood S, Wilhelm E, Khan U, Mayer- Hamblett N, et al. Rationale and design of a randomized trial of home electronic symptom and lung function monitoring to detect cystic fibrosis pulmonary exacerbations: the Early Intervention in Cystic Fibrosis Exacerbation (eICE) trial. Contemp Clin Trials. 2013;36(2):460-9. https://doi. org/10.1016/j.cct.2013.09.004. PMid:24055998.
32. Andrade EF, Fonseca DLO, Silva FAA, Menna BSS. A avaliação evolutiva da espirometria na fibrose cística. J Pneumol. 2001;27(3):130-6. https://doi.org/10.1590/S0102- 35862001000300002.
33. Dalcin PTR, Rampon G, Pasin LR, Ramon GM, Abrahão CLO, Oliveira VZ. Adesão ao tratamento em pacientes com fibrose cística. J Bras Pneumol. 2007;33(6):663-70. https://doi. org/10.1590/S1806-37132007000600009. PMid:18200366.
34. White H, Shaw N, Denman S, Pollard K, Wynne S, Peckham DG. Variation in lung function as a marker of adherence to oral and inhaled medication in cystic fibrosis. Eur Respir J. 2017;49(3):1600987. https://doi. org/10.1183/13993003.00987-2016. PMid:28275171.
35. Carneiro GV, Oliveira FSD, Pereira LA, Rezende ÉRMDA, Gonçalves LCP, Azevedo VMGDO. Association between phenotypic and genotypic characteristics and disease severity in individuals with cystic fibrosis. Rev Paul Pediatr. 2022;41:e2021286. https://doi.org/10.1590/1984- 0462/2023/41/2021286. PMid:36102402.
36. Hansen CME, Breukelman AJ, van den Bemt PMLA, Zwitserloot AM, van Dijk L, van Boven JFM. Medication adherence to CFTR modulators in patients with cystic fibrosis: a systematic review. Eur Respir Rev. 2024;33(173):240060. https://doi. org/10.1183/16000617.0060-2024. PMid:39142708.
Submitted date:
02/13/2025
Accepted date:
07/13/2026
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