Adherence is associated with a favorable outcome after lung transplantation

Autoři: Anna Bertram aff001;  Jan Fuge aff002;  Hendrik Suhling aff002;  Igor Tudorache aff004;  Axel Haverich aff003;  Tobias Welte aff002;  Jens Gottlieb aff002
Působiště autorů: Department of Nephrology and Hypertension, Hannover Medical School, Hannover, Germany aff001;  Department of Respiratory Medicine, Hannover Medical School, Hannover, Germany aff002;  Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), Member of the German Center for Lung Research (DZL), Gießen, Germany aff003;  Department of Cardiothoracic, Transplantation and Vascular Surgery, Hannover Medical School, Hannover, Germany aff004
Vyšlo v časopise: PLoS ONE 14(12)
Kategorie: Research Article
doi: 10.1371/journal.pone.0226167


Non-adherence to therapy is associated with impaired outcome in solid organ allograft recipients. Outcome data are limited after lung transplantation. In a single-center cohort study, adherence was assessed in 427 patients undergoing lung transplantation from 2010 to 2013. Objective criteria of adherence were judged by health care workers on every visit on a five item Likert scale including trough level monitoring, home spirometry and contact with an overall rating of adherence between 0 and 100%. Cut-off values for good vs. suboptimal adherence were defined retrospectively. Primary outcome was allograft survival, secondary outcomes were patient survival, prevalence of chronic lung allograft dysfunction, hospitalizations, renal function and quality of life. Follow-up ended on 31st December 2018. Median adherence was 86% on 6,623 visits, this cut-off was used as a discriminator between good and suboptimal adherers. Patients with good adherence within the first three years showed better 5-year allograft (74% vs. 60%, p = 0.003) and patient survival (79% vs. 64%, p<0.001) and lower prevalence of chronic allograft dysfunction (33% vs. 45%, p = 0.011) after 5 years compared to patients with suboptimal adherence. A multidimensional adherence score proved to be a simple tool to assess adherence in clinical practice. Suboptimal adherence was associated with impaired outcome in lung transplant patients.

Klíčová slova:

Exercise – Lung transplantation – Patients – Quality of life – Renal transplantation – Spirometry – Sports and exercise medicine – Outpatient clinics


1. Vandervest KM, Zamora MR. Recipient risk factors and lung transplant outcomes. Curr Opin Organ Transplant. 2013 Oct;18(5):531–6. doi: 10.1097/MOT.0b013e32836519ec 23995373

2. Martin-Gandul C, Mueller NJ, Pascual M, Manuel O. The Impact of Infection on Chronic Allograft Dysfunction and Allograft Survival After Solid Organ Transplantation. Am J Transplant. 2015 Dec;15(12):3024–40. doi: 10.1111/ajt.13486 26474168

3. Oliva M, Singh TP, Gauvreau K, Vanderpluym CJ, Bastardi HJ, Almond CS. Impact of medication non-adherence on survival after pediatric heart transplantation in the U.S.A. J Heart Lung Transplant. 2013 Sep;32(9):881–8.

4. Almeshari K, Pall A, Chaballout A, Elgamal H, Almana H, Alzayer F, et al. Targeted monitoring of donor-specific HLA antibodies following renal transplantation. Clin Transpl. 2011;395–400. 22755437

5. Sellarés J, de Freitas DG, Mengel M, Reeve J, Einecke G, Sis B, et al. Understanding the causes of kidney transplant failure: the dominant role of antibody-mediated rejection and nonadherence. Am J Transplant. 2012 Feb;12(2):388–99. doi: 10.1111/j.1600-6143.2011.03840.x 22081892

6. Clifford S, Perez-Nieves M, Skalicky AM, Reaney M, Coyne KS. A systematic literature review of methodologies used to assess medication adherence in patients with diabetes. Curr Med Res Opin. 2014 Jun;30(6):1071–85. doi: 10.1185/03007995.2014.884491 24432796

7. Møldrup C, Stein J, Søndergaard B. “Patients don’t lie”; a view on adherence in asthma. Pharm World Sci PWS. 2010 Dec;32(6):795–8. doi: 10.1007/s11096-010-9439-0 20924676

8. Pabst S, Bertram A, Zimmermann T, Schiffer M, de Zwaan M. Physician reported adherence to immunosuppressants in renal transplant patients: Prevalence, agreement, and correlates. J Psychosom Res. 2015 Nov;79(5):364–71. doi: 10.1016/j.jpsychores.2015.09.001 26526310

9. Robiner WN, Flaherty N, Fossum TA, Nevins TE. Desirability and feasibility of wireless electronic monitoring of medications in clinical trials. Transl Behav Med. 2015 Sep;5(3):285–93. doi: 10.1007/s13142-015-0316-1 26327934

10. Hsiau M, Fernandez HE, Gjertson D, Ettenger RB, Tsai EW. Monitoring nonadherence and acute rejection with variation in blood immunosuppressant levels in pediatric renal transplantation. Transplantation. 2011 Oct 27;92(8):918–22. doi: 10.1097/TP.0b013e31822dc34f 21857278

11. Castleberry AW, Bishawi M, Worni M, Erhunmwunsee L, Speicher PJ, Osho AA, et al. Medication Nonadherence After Lung Transplantation in Adult Recipients. Ann Thorac Surg. 2017 Jan;103(1):274–80. doi: 10.1016/j.athoracsur.2016.06.067 27624294

12. Kugler C, Fuehner T, Dierich M, DeWall C, Haverich A, Simon A, et al. Effect of adherence to home spirometry on bronchiolitis obliterans and graft survival after lung transplantation. Transplantation. 2009 Jul 15;88(1):129–34. doi: 10.1097/TP.0b013e3181aad129 19584692

13. Verleden GM, Vos R, Vanaudenaerde B, Dupont L, Yserbyt J, Van Raemdonck D, et al. Current views on chronic rejection after lung transplantation. Transpl Int. 2015 Oct;28(10):1131–9. doi: 10.1111/tri.12579 25857869

14. Suhling H, Dettmer S, Greer M, Fuehner T, Avsar M, Haverich A, et al. Phenotyping Chronic Lung Allograft Dysfunction Using Body Plethysmography and Computed Tomography. Am J Transplant. 2016 May 20;

15. Hurst NP, Kind P, Ruta D, Hunter M, Stubbings A. Measuring health-related quality of life in rheumatoid arthritis: validity, responsiveness and reliability of EuroQol (EQ-5D). Br J Rheumatol. 1997 May;36(5):551–9. doi: 10.1093/rheumatology/36.5.551 9189057

16. Bjørtuft O, Johansen B, Boe J, Foerster A, Holter E, Geiran O. Daily home spirometry facilitates early detection of rejection in single lung transplant recipients with emphysema. Eur Respir J. 1993 May;6(5):705–8. 8390943

17. Suhling H, Rademacher J, Zinowsky I, Fuge J, Greer M, Warnecke G, et al. Conventional vs. tablet computer-based patient education following lung transplantation—a randomized controlled trial. PloS One. 2014;9(6):e90828. doi: 10.1371/journal.pone.0090828 24608864

18. Bosma OH, Vermeulen KM, Verschuuren EA, Erasmus ME, van der Bij W. Adherence to immunosuppression in adult lung transplant recipients: prevalence and risk factors. J Heart Lung Transplant. 2011 Nov;30(11):1275–80. doi: 10.1016/j.healun.2011.05.007 21724418

19. Denhaerynck K, Steiger J, Bock A, Schäfer-Keller P, Köfer S, Thannberger N, et al. Prevalence and risk factors of non-adherence with immunosuppressive medication in kidney transplant patients. Am J Transplant. 2007 Jan;7(1):108–16. doi: 10.1111/j.1600-6143.2006.01611.x 17109727

20. Shellmer DA, Zelikovsky N. The challenges of using medication event monitoring technology with pediatric transplant patients. Pediatr Transplant. 2007 Jun;11(4):422–8. doi: 10.1111/j.1399-3046.2007.00681.x 17493224

21. Dobbels F, De Geest S, van Cleemput J, Droogne W, Vanhaecke J. Effect of late medication non-compliance on outcome after heart transplantation: a 5-year follow-up. J Heart Lung Transplant. 2004 Nov;23(11):1245–51. doi: 10.1016/j.healun.2003.09.016 15539122

22. Artinian NT, Harden JK, Kronenberg MW, Vander Wal JS, Daher E, Stephens Q, et al. Pilot study of a Web-based compliance monitoring device for patients with congestive heart failure. Heart Lung J Crit Care. 2003 Aug;32(4):226–33.

23. Profit D, Rohatagi S, Zhao C, Hatch A, Docherty JP, Peters-Strickland TS. Developing a Digital Medicine System in Psychiatry: Ingestion Detection Rate and Latency Period. J Clin Psychiatry. 2016 Jul 5;

24. Belknap R, Weis S, Brookens A, Au-Yeung KY, Moon G, DiCarlo L, et al. Feasibility of an ingestible sensor-based system for monitoring adherence to tuberculosis therapy. PloS One. 2013;8(1):e53373. doi: 10.1371/journal.pone.0053373 23308203

25. Kalantarian H, Motamed B, Alshurafa N, Sarrafzadeh M. A wearable sensor system for medication adherence prediction. Artif Intell Med. 2016 May;69:43–52. doi: 10.1016/j.artmed.2016.03.004 27068873

26. Dobbels F, Berben L, De Geest S, Drent G, Lennerling A, Whittaker C, et al. The psychometric properties and practicability of self-report instruments to identify medication nonadherence in adult transplant patients: a systematic review. Transplantation. 2010 Jul 27;90(2):205–19. doi: 10.1097/TP.0b013e3181e346cd 20531073

27. Drick N, Seeliger B, Fuge J, Tudorache I, Greer M, Welte T, et al. Self-reported non-adherence to immunosuppressive medication in adult lung transplant recipients-A single-center cross-sectional study. Clin Transplant. 2018 Apr;32(4):e13214. doi: 10.1111/ctr.13214 29380445

28. Shi L, Liu J, Fonseca V, Walker P, Kalsekar A, Pawaskar M. Correlation between adherence rates measured by MEMS and self-reported questionnaires: a meta-analysis. Health Qual Life Outcomes. 2010;8:99. doi: 10.1186/1477-7525-8-99 20836888

29. Schäfer-Keller P, Steiger J, Bock A, Denhaerynck K, De Geest S. Diagnostic accuracy of measurement methods to assess non-adherence to immunosuppressive drugs in kidney transplant recipients. Am J Transplant. 2008 Mar;8(3):616–26. doi: 10.1111/j.1600-6143.2007.02127.x 18294158

30. Gallagher BD, Muntner P, Moise N, Lin JJ, Kronish IM. Are two commonly used self-report questionnaires useful for identifying antihypertensive medication nonadherence? J Hypertens. 2015 May;33(5):1108–13. doi: 10.1097/HJH.0000000000000503 25909704

31. Burnier M, Wuerzner G, Struijker-Boudier H, Urquhart J. Measuring, analyzing, and managing drug adherence in resistant hypertension. Hypertens Dallas Tex 1979. 2013 Aug;62(2):218–25.

32. Dobbels F, Vanhaecke J, Dupont L, Nevens F, Verleden G, Pirenne J, et al. Pretransplant predictors of posttransplant adherence and clinical outcome: an evidence base for pretransplant psychosocial screening. Transplantation. 2009 May 27;87(10):1497–504. doi: 10.1097/TP.0b013e3181a440ae 19461486

33. De Geest S, Burkhalter H, Bogert L, Berben L, Glass TR, Denhaerynck K, et al. Describing the evolution of medication nonadherence from pretransplant until 3 years post-transplant and determining pretransplant medication nonadherence as risk factor for post-transplant nonadherence to immunosuppressives: the Swiss Transplant Cohort Study. Transpl Int. 2014 Jul;27(7):657–66. doi: 10.1111/tri.12312 24628915

34. Levy L, Huszti E, Tikkanen J, Ghany R, Klement W, Ahmed M, et al. The impact of first untreated subclinical minimal acute rejection on risk for chronic lung allograft dysfunction or death after lung transplantation. Am J Transplant. 2019 Aug 9;

35. Su GC-W, Greanya ED, Partovi N, Yoshida EM, Shapiro RJ, Levy RD. Assessing medication adherence in solid-organ transplant recipients. Exp Clin Transplant. 2013 Dec;11(6):475–81. doi: 10.6002/ect.2013.0060 24344939

36. Takemoto SK, Pinsky BW, Schnitzler MA, Lentine KL, Willoughby LM, Burroughs TE, et al. A retrospective analysis of immunosuppression compliance, dose reduction and discontinuation in kidney transplant recipients. Am J Transplant. 2007 Dec;7(12):2704–11. doi: 10.1111/j.1600-6143.2007.01966.x 17868065

37. Flippin MS, Canter CE, Balzer DT. Increased morbidity and high variability of cyclosporine levels in pediatric heart transplant recipients. J Heart Lung Transplant. 2000 Apr;19(4):343–9. doi: 10.1016/s1053-2498(00)00061-9 10775814

38. Kreuzer M, Prüfe J, Oldhafer M, Bethe D, Dierks M-L, Müther S, et al. Transitional Care and Adherence of Adolescents and Young Adults After Kidney Transplantation in Germany and Austria: A Binational Observatory Census Within the TRANSNephro Trial. Medicine (Baltimore). 2015 Dec;94(48):e2196.

39. Gallagher HM, Sarwar G, Tse T, Sladden TM, Hii E, Yerkovich ST, et al. Erratic tacrolimus exposure, assessed using the standard deviation of trough blood levels, predicts chronic lung allograft dysfunction and survival. J Heart Lung Transplant. 2015 Nov;34(11):1442–8. doi: 10.1016/j.healun.2015.05.028 26186804

40. De Bleser L, Dobbels F, Berben L, Vanhaecke J, Verleden G, Nevens F, et al. The spectrum of nonadherence with medication in heart, liver, and lung transplant patients assessed in various ways. Transpl Int. 2011 Sep;24(9):882–91. doi: 10.1111/j.1432-2277.2011.01296.x 21740471

41. Dew MA, Dabbs AD, Myaskovsky L, Shyu S, Shellmer DA, DiMartini AF, et al. Meta-analysis of medical regimen adherence outcomes in pediatric solid organ transplantation. Transplantation. 2009 Sep 15;88(5):736–46. doi: 10.1097/TP.0b013e3181b2a0e0 19741474

42. Dew MA, DiMartini AF, De Vito Dabbs A, Zomak R, De Geest S, Dobbels F, et al. Adherence to the Medical Regimen During the First Two Years After Lung Transplantation. Transplantation. 2008 Jan 27;85(2):193–202. doi: 10.1097/TP.0b013e318160135f 18212623

43. Germani G, Lazzaro S, Gnoato F, Senzolo M, Borella V, Rupolo G, et al. Nonadherent behaviors after solid organ transplantation. Transplant Proc. 2011 Feb;43(1):318–23. doi: 10.1016/j.transproceed.2010.09.103 21335213

44. Defrancq C, De Wilde N, Raes A, Van Biervliet S, Vande Velde S, Van Winckel M, et al. Intra-patient variability in tacrolimus exposure in pediatric liver transplant recipients: Evolution, risk factors, and impact on patient outcomes. Pediatr Transplant. 2019 Mar 27;e13388. doi: 10.1111/petr.13388 30916883

45. Singer JP, Peterson ER, Snyder ME, Katz PP, Golden JA, D’Ovidio F, et al. Body composition and mortality after adult lung transplantation in the United States. Am J Respir Crit Care Med. 2014 Nov 1;190(9):1012–21. doi: 10.1164/rccm.201405-0973OC 25233138

46. Ihle F, Neurohr C, Huppmann P, Zimmermann G, Leuchte H, Baumgartner R, et al. Effect of inpatient rehabilitation on quality of life and exercise capacity in long-term lung transplant survivors: a prospective, randomized study. J Heart Lung Transplant. 2011 Aug;30(8):912–9. doi: 10.1016/j.healun.2011.02.006 21489819

47. Langer D, Burtin C, Schepers L, Ivanova A, Verleden G, Decramer M, et al. Exercise training after lung transplantation improves participation in daily activity: a randomized controlled trial. Am J Transplant. 2012 Jun;12(6):1584–92. doi: 10.1111/j.1600-6143.2012.04000.x 22390625

48. Duerinckx N, Burkhalter H, Engberg SJ, Kirsch M, Klem M-L, Sereika SM, et al. Correlates and Outcomes of Posttransplant Smoking in Solid Organ Transplant Recipients: A Systematic Literature Review and Meta-analysis. Transplantation. 2016 Jul 29;

49. Teichman BJ, Burker EJ, Weiner M, Egan TM. Factors associated with adherence to treatment regimens after lung transplantation. Prog Transplant Aliso Viejo Calif. 2000 Jun;10(2):113–21.

50. Vanhoof JMM, Vandenberghe B, Geerts D, Philippaerts P, De Mazière P, DeVito Dabbs A, et al. Shedding light on an unknown reality in solid organ transplant patients’ self-management: A contextual inquiry study. Clin Transplant. 2018 Aug;32(8):e13314. doi: 10.1111/ctr.13314 29897621

51. Becker S, Kribben A, Meister S, Diamantidis CJ, Unger N, Mitchell A. User profiles of a smartphone application to support drug adherence—experiences from the iNephro project. PloS One. 2013;8(10):e78547. doi: 10.1371/journal.pone.0078547 24194946

52. Shellmer DA, Dew MA, Mazariegos G, DeVito Dabbs A. Development and field testing of Teen Pocket PATH(®), a mobile health application to improve medication adherence in adolescent solid organ recipients. Pediatr Transplant. 2016 Feb;20(1):130–40. doi: 10.1111/petr.12639 26916967

53. Sabaté E. Adherence to Long-Term Therapies: Evidence for Action. Geneva: World Health Organization; 2003.

Článek vyšel v časopise


2019 Číslo 12