Citation for published version (APA): Ouwens, J. P. (2002). The Groningen lung transplant program: 10 years of experience Groningen: s.n.

Transcription

1 University of Groningen The Groningen lung transplant program Ouwens, Jan Paul IMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite from it. Please check the document version below. Document Version Publisher's PDF, also known as Version of record Publication date: 22 Link to publication in University of Groningen/UMCG research database Citation for published version (APA): Ouwens, J. P. (22). The Groningen lung transplant program: 1 years of experience Groningen: s.n. Copyright Other than for strictly personal use, it is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), unless the work is under an open content license (like Creative Commons). Take-down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim. Downloaded from the University of Groningen/UMCG research database (Pure): For technical reasons the number of authors shown on this cover page is limited to 1 maximum. Download date:

2 Long-term quality of life in patients surviving at least 55 after lung transplantation. K.M. Vermeulen, J.P. Ouwens, W. van der Bij, W.J. de Boer, G.H. Koëter and E.M.TenVergert. Submitted: General Hospital Psychiatry 9

3 Abstract: Aim of the present study was to examine the long-term effect of lung transplantation (LTx) on Health Related Quality of Life (HRQL). This study was conducted among 28 patients who survived at least 55 after LTx. Measures included the Nottingham Health Profile (NHP), questions concerning lung-specific problems, the State-Trait Anxiety Inventory (STAI), the Self-rating Depression Scale (ZUNG), the Index of Well-Being (IWB), the Karnofsky performance index, and questions concerning activities of daily life (ADL). Before transplantation patients reported restrictions on almost all HRQL measures. Until approximately 43 after transplantation there were significant improvements on most NHP dimensions, and more patients could walk without dyspnea. Significant improvements occurred with regard to the levels of anxiety, depression, and well being, and the scores on the Karnofsky performance index improved. Activities of daily life could be performed without help by most patients. After approximately 43 patients experienced more dyspnea, anxiety, depression, and a lower level of well being. It may be concluded that patients experience a stable and better overall HRQL after transplantation. Long-term after LTx patients experience a decline on several HRQLdimensions, which may be explained by an increase of comorbid conditions and Bronchiolitis Obliterans Syndrome (BOS). 91

4 Introduction: Lung transplantation (LTx) is a treatment option for patients with an end-stage lung disease. Between 1982 and 21, more than 12 single and double lung transplantations have been performed worldwide 1. The one-year survival after lung transplantation is reported to be approximately 7% for both single and double lung transplantation, whereas the 4-year survival is approximately 5% 1. Although survival has improved to a modest degree over time, there is not much known about the physical, psychological and social functioning longterm after LTx. Health Related Quality of Life (HRQL) is an accepted outcome measure to assess the effectiveness of lung transplantation. Previous studies that were focussed on changes in HRQL following LTx, generally report improvements in HRQL after transplantation Studies that assessed HRQL a relative long time after LTx suggest that these improvements appear to remain stable over time Stavem 7 conducted a cross-sectional survey with an average time since transplantation of 38 and, concluded that patients surviving LTX can expect considerable improvement on most dimensions of HRQL. Limbos 8 assessed HRQL in a pre and a post transplant group. The mean time since transplantation was 44 (range 6,-119,8). The author concludes that lung transplant recipients have better general, physical and psychological health than their pre-transplant counterparts, but results suggest that both groups experience impairment in several areas of psychological functioning. In a study that focussed on female lung transplant candidates and recipients 9, mean time since transplantation in the post group was 47 (range 7,5-119,8). From this study it can be concluded that overall quality of life improves following LTx. Cohen used a cross-sectional study design 1 in which the time since transplantation ranged from 1 to 12,4. Crosssectional analyses indicated significantly better adjustment and quality of life post-transplant. Gross 11 used a combination of a longitudinal and a cross-sectional design in which HRQL was assessed up to >36 after transplantation, and concluded that there were dramatic improvements in health status and HRQL after successful lung transplant, and that these improvements remained stable over time. However, note that most of these studies assessed HRQL by means of a cross-sectional study design, and assessed HRQL at only one time point post-ltx. Besides differences between groups pre- and post transplantation, these studies are limited by the fact that they analyzed a rather heterogeneous population of post transplantation patients especially with regard to time since transplantation. This wide range in time since transplantation makes it difficult to measure changes in HRQL over time, or to observe a certain trend in HRQL-status after LTx. The difficulty of tracking the same patients over a longer period of time may explain this lack of long-term results from longitudinal studies in LTx patients. However, from a methodological point of view, the best way to determine HRQL outcomes after LTx is to follow patients prospectively before and after they undergo transplantation 12. Since 1992, in the Groningen lung transplant program an ongoing HRQL assessment is being conducted among transplant candidates and recipients. This creates an excellent opportunity to perform longitudinally designed studies. The aim of the present study was to examine the long-term effect of LTx on HRQL using a prospective, longitudinal study design. We followed 28 patients though the transplant experience until 55 after LTx, and assessed the HRQL before LTx, and at several time points after LTx. 92

5 Methods: Patients Between December 1992 and October 2, 133 patients underwent lung transplantation. Treatment procedures and follow-up activities were performed according to the treatment protocol 16. Sixty-one patients were eligible for our study because they were transplanted at least 55 earlier. However, 24 of these 61 patients died before the end of the 55-month followup period and 8 were temporarily not able to fill in one or more questionnaires after transplantation because of serious health problems. One patient was excluded from the HRQL study because of a re-transplantation. This leaves the number of included patients in this study at 28. Questionnaires All patients have been asked to fill in HRQL questionnaires at several stages in the program from the moment they were placed on the waiting list. Self-administered questionnaires were by sent mail. The first questionnaire was sent directly after patients were placed on the waiting list. After LTx, questionnaires were sent at 4 and 7 and from that moment on every 6. To assess the physical, psychological and social functions of the patient, generic measures, disease-specific measures and domain-specific measures were used in all questionnaires. The generic measure used was the Nottingham Health Profile (NHP, part 1) 17. This questionnaire contains 38 items, covering six domains: mobility, pain, energy, sleep, social isolation and emotional reactions. The NHP was developed as a measure for perceived health and has been validated in several patient populations and healthy volunteers 17. For the disease-specific part of the HRQL measurement, a number of questions were composed concerning specific problems of LTx patients, such as dyspnea experienced during the following activities: making haste, walking at normal pace, walking at own pace, and standing still. In addition to this, the severity of dyspnea was assessed. Domain-specific measures consisted of the State-Trait Anxiety Inventory (STAI) 18 to assess general anxiety, the Self-rating Depression Scale (S)-ZUNG 19 to assess depressive symptoms, and the Index of Well-Being (IWB) 2 to measure patients satisfaction with their actual situation. On the Karnofsky performance index 21, patients were asked to report to what extent they were able to take care of themselves. Furthermore, a number of questions were composed to measure independence while performing activities of daily life (ADL), like washing or dressing oneself. Data analyses All data analyses were performed using the SPSS 1. program (SPSS 1.;SPSS, Inc; Chicago). Descriptive statistics were performed to assess the demographic characteristics of the patients, grades of dyspnea, ADL-functions, and comorbid conditions. The Kolmogorov- Smirnov test was used to compare the distribution of the patients responses to each HRQLmeasure with the standard normal distribution. Scores on the NHP, did not fit the normal distribution and consequently a non-parametric Friedman test was used to assess changes in HRQL before and directly (4 ) after LTx. Post-hoc comparisons between two points of follow-up were made using the Wilcoxon signed ranks test. Scores on the STAI, ZUNG, IWB and Karnofsky Performance Index did fit the normal distribution. Therefore, repeated measures ANOVA were used to assess changes in HRQL before and directly (4 ) after LTx. Post-hoc comparisons between two points of 93

6 follow-up were made using a student's t-test. P-values <.5 were considered statistically significant. Adjustments were made to p-values for the multiple comparisons 22. Table 1: Demographic characteristics of lung transplant patients Demographic characteristics of lung transplant patients (n=28) Age, mean (range) Gender: Male/Female (%) Diagnoses, n (%) Emphysema Cystic fibrosis Bronchiectasies Pulmonary fibrosis Pulmonary hypertension Bilateral lung transplantation, n (%) Single lung transplantation, n (%) Days on waiting list, mean (range) Work (before transplantation) Working for pay, n (%) Number of hours/wk, median (range) Work (55 after transplantation) Working for pay, n (%) Number of hours/wk, median (range) 4 (18-59) 6,7/39,3 15 (53,6) 6 (21,4) 2 ( 7,1) 2 ( 7,2) 3 (1,7) 25 (89,3) 3 (1,7) 372 (7-993) 7 (25,) 12 (1-28) 7 (25,) 17 (3-4) Results: Patients Demographic characteristics are given in table 1. The patients in this study group were between 18 and 59 years old (mean 4). Of the 28 patients, 17 were male. Fifteen patients were diagnosed with emphysema, which was the main diagnosis for transplantation. In 73% of these patients emphysema was due to alpha-1-antitrypsine deficiency. Of the 28 patients, 25 underwent bilateral lung transplantation. The average stay on the waiting list was 372 days (range days). HRQL pre-transplantation Scores on the six dimensions of the NHP show that patients experienced restrictions on the dimensions mobility, energy, and sleep (table 2). scores on these dimensions were 4, 55, and 26, respectively, whereas the reference value for the general population is below 15. Table 3 shows to what extend waiting list patients suffered from dyspnea during walking at different paces. During making haste, 71% of the patients reported to suffer very much from dyspnea, while this percentage was 57 during walking at normal pace. Dyspnea is reported as an important limitation before LTx. 94

7 Table 2: NHP-scores* before and after lung transplantation. NHP-1 Dimension Mobility Median Pain Median Energy Median Sleep Median Social (isolation) Median Emotional (reaction) Median Before After LTx (n=28) LTx (n=28) month month month s s s 39,91 34,29 19,21 2,35 4,62 54,95 6,8 33,16 26,21 16,1 28,19 17,75 24,17 16,44 13,95 16,66 6,21 11,6 5,1 14,57 4,43 19,27 13,3 2,85 5,6 14,6 5,4 14,26 5,52 1,35 5,86 18,82 4,86 17,17 8,16 13,49 4,78 16,94 3,26 1,5 6,39 12,38 7,23 21,47 9,19 24,2 7,46 14,52 5,4 11,6 3,71 1,75 31 month s 8,9 18,55 5,75 14,68 19,59 3,85 1,44 22,99 7,7 13,35 7,7 17,3 43 month s 7,94 14,74 6,86 17,63 15,42 28,95 8,5 17, 8,23 18,98 6,69 16,83 55 month s 15,1 2,4 4,15 1,92 22,2 36,33 16,62 23,26 1,53 19,68 9,57 19,44 P- value** <1,572 < * Range from possible scores from to 1;, best possible health status; 1, worst possible health status; reference value mean< 15. ** Significance for difference between medians (Friedman test) Significant difference with previous time-point (Wilcoxon test) scores on the STAI, ZUNG, IWB and Karnofsky-index are presented in table 4. Scores on the STAI showed no significant difference with the reference value. ZUNG-scores however, were significantly higher than the reference value (p<.1). Moreover, patients experienced a significantly lower level of well being (IWB) and a significantly lower score on the Karnofsky performance index. Most patients experienced difficulties in performing activities of daily life especially in going up and down stairs. Only 4% of the patients could perform this activity without effort (figures 1a-1d). Before transplantation 7 (25%) of the patients were working for pay (median, 12 h/wk). 95

8 Table 3: Grades of dyspnea Activity (%) Making haste Very much Little Not Not performed Before LTx (n=28) 71,4 14,4 14,4 After LTx (n=28) 4 month s 7,4 81,5 11,1 7 29,6 7,4 19 7,7 15,4 65,4 11, ,4 15,4 61,5 7, ,5 62,5 25, 55 12,5 2,8 54,2 12,5 Walking at normal pace Very much Little Not Not performed 57,1 17,9 25, 3,7 7,4 81,5 7,4 25,9 7,4 3,7 3,8 23,1 65,4 7,7 15,4 15,4 69,2 8, 4, 8, 8, 4,2 2,8 66,7 8,3 Walking at own pace Very much Little Not Not performed 28,6 57,1 7,1 7,1 11,1 88,9 14,8 85,2 7,7 15,4 76,9 14,8 14,8 7,4 8, 84, 8, 2,8 75, 4,2 Stand still * Very much Little Not Not performed 39,3 42,9 1,7 7,1 3,7 96,3 14,8 81,5 3,7 7,7 7,7 84,6 * Patient had to stop walking at own pace due to breathlessness 11,1 18,5 7,4 8, 84, 8, 2,8 75, 4,2 HRQL post transplantation Four after transplantation, scores on NHP dimensions mobility, energy, sleep, social isolation, and 'emotional reaction' improved statistically significant (table 2). From 4 until 43 after transplantation, scores on all NHP dimensions remained more or less stable. After 43 a decline in scores on all dimensions, except pain, was observed. However, on none of these dimensions, this decline was statistically significant. Patients reported less suffering from dyspnea (table 3) in the period after LTx. Four after LTx the percentage of patients without dyspnea during making haste increased from to 82%. Forty-three after LTx, 63% of the patients suffer from dyspnea during making haste. Scores on the STAI, ZUNG, IWB and Karnofsky improved statistically significant 4 after LTx (table 4). 96

9 Table 4: STAI, ZUNG, IWB, and Karnofsky scores* before and after lung transplantation. Test STAI ZUNG IWB Karnofs ky Ref. Value Before LTx (n=28) <=37 4,28 1,45 <=33 53,43 8,75 >12 9,6 2,35 >=9 59,29 11,84 After LTx (n=28) 4 31,3 1,34 4,22 9,66 12,71 2,7 87,86 11,1 7 29,48 7,13 38,89 8,57 12,45 2,16 87,86 11, ,47 8,3 38,99 1,31 11,93 2,58 89,26 9, ,56 11,13 34,2 11,54 11,56 2,94 86,3 13, ,29 11,16 43,92 11,72 12,37 2,5 88,8 1, ,34 4,8 55,85 5,82 9,68 2,22 82,4 14,22 p- value* * < 1 6,68 < 1 * Range from possible scores: STAI, 2 to 8; ZUNG, 25 to 1; IWB, 14,7 to 2,1; Karnofsky, 1 to ; best possible health status on the left, worst possible health status on the right. ** P-values for analysis of variance, repeated measures ANOVA Significant difference with previous time-point (t-test) STAI, IWB and Karnofsky scores remained stable until 43 after LTx. Between 31 and 43 and between 43 and 55 after LTx significant declines in ZUNG scores were observed. Between 43 and 55 significant declines of STAI-, and IWB-scores were observed. Activities of daily life could be performed without help by most patients 4 after LTx (figures 1a-1d). At 55 more patients performed all activities of daily life with effort or with help. Walking stairs could be performed without effort by 62 % of the patients and walking could be performed without effort by 71 % of the patients at 55. Fifty-five after lung transplantation, 7 patients (25%) were working for pay with a median of 17 hours a week. 97

10 Figure 1a: washing 1% 8% 6% 4% 2% not performed unable with help able with help with effort without effort % pre-tx Figure 1b: walking 1% 8% 6% 4% 2% not performed unable with help able with help with effort without effort % pre-tx Figure 1c:walking stairs 1% 8% 6% 4% 2% not performed unable with help able with help with effort without effort % pre-tx Figure 1d: dressing 1% 8% 6% 4% 2% not performed unable with help able with help with effort without effort % pre-tx after lung transplantation 98

11 Discussion: The present study shows improvements on several dimensions of HRQL four after LTx compared to the situation before LTx in patients that survived at least 55 after LTx. Significant improvements were shown with regard to NHP dimensions 'mobility', 'energy', and 'social isolation'. More patients were able to walk without dyspnea during walking at different paces. There were significant improvements with regard to the levels of anxiety and depression, and the level of well being, and the scores on the Karnofsky performance index improved statistically significant. Activities of daily life could be performed without help by most patients. This positive trend was sustained until 43 after LTx. Between 4 and 43 after LTx scores on most measures were within or close to the reference values. However, 31 after LTx, significant declines in ZUNG scores were observed. Between 43 and 55 after LTx patients experienced more suffering from dyspnea, significantly more anxiety, and a significantly lower level of well being. Our results are generally in line with other findings. With regard to anxiety, however, we found that, at the moment of placement on the waiting list, patients experienced no more anxiety than the general population did. This in contrast to other authors who found higher anxiety levels before lung transplantation. As discussed elsewhere 4, this relative low anxiety levels may indicate that patients are initially relived about being accepted to the waiting list. During the waiting time period anxiety levels among these patients may increase 14. Despite the positive changes in HRQL, only 7 patients (25%) are employed in paid work 55 after LTx. Firstly, this may be caused by the Dutch social security system, which has a low threshold for benefit payments to ill employees, and makes it particularly unfavorable for employers to hire people with a higher risk of absence due to illness. Secondly, it was suggested by others 15 that patients, given their uncertain future, prefer not to spend their remaining years working, particularly if their usual job was not very satisfying. Striking result of our study is that 43 after transplantation a decline in HRQL is observed with regard to dyspnea, anxiety, depression, and well-being. We suspected that comorbidity due to the usage of immunosuppressive medication and the development of Bronchiolitis Obliterans Syndrome (BOS) could be of influence on this decline in HRQL. Hosenpud 25 mentioned the importance of focussing on late morbidity following thoracic transplantation. Moreover, Surman 26 reported that symptomatology associated with immunosuppressant medication is more likely to occur with time and is a major source of distress for many patients after liver transplantation. Following these suggestions, we conducted a pilot study in which we focussed on comorbidity and BOS. Preliminary results of this pilot study showed an increase in the number of patients suffering from insulin dependent diabetes mellitus, drug-treated hyperlipidemia, a progressive degrease in kidney function, and BOS especially between 43 and 55. This increase of comorbid conditions long-term after LTx, and especially the development of BOS can probably explain the decline in HRQL with regard to dyspnea, anxiety, depression, and well-being. From literature 5, it has been known that patients with BOS experience a lower HRQL than recipients without this condition. An explanation for the fact that in our population these restrictions appear especially on the dimensions anxiety, depression and well-being may be that patients are aware of the fact that once they have developed BOS, best treatment results in stabilization. Awareness of their unfavorable prognosis may stimulate feelings of anxiety and depression, and result in a lower level of well-being. Obviously, this is just a first impression, and further research is necessary to draw firm conclusions. The fact that other authors did not report such findings is likely due to the lack of prospective longitudinal studies with such a long period of follow-up. 99

12 A remark has to be made with regard to our study population. In the present longitudinal study, patients who died before the end of the study period and patients who were not able to fill in all questionnaires because of serious health problems were excluded. This may cause a certain bias. Consequently the use of data from surviving patients who completed all questionnaires probably results in a better overall HRQL than the actual situation in the total group of all lung transplant recipients. It may be concluded that patients experience a stable and better overall HRQL after transplantation. Long-term after LTx patients experience more dyspnea, anxiety, depression, and a lower level of well-being. The increased comorbidity and BOS may explain these declines. Knowledge about these long-term effects of LTx can help LTx can help doctors and patients in making well informed treatment decisions and stimulate the development of appropriate treatment interventions with regard to the physical, psychological and social functioning of patients, which may improve the rate of successful outcome. References: 1. Hosenpud JD, Bennett LE, Keck BM, et al. The Registry of the International Society for Heart and Lung Transplantation Eighteenth Official Report-21. J Heart Lung Transplant 21; 2: TenVergert EM, red. Evaluatie-onderzoek longtransplantatie (Medical technology assessment of the lung transplant program). Groningen, the Netherlands: Office for MTA, University Hospital Groningen, 1996 (in Dutch) 3. Mannes GPM, Essink-Bot ML, Koëter GH, et al. Lung transplantation and quality of life. Preliminary results. Eur Respir Rev 1997; 7: TenVergert EM, Essink-Bot ML, Geertsma A, et al. The effect of lung transplantation on health related quality of life; a longitudinal study. Chest 1998; 113: van den Berg JW, Geertsma A, van der Bij W et al. Bronchiolitis obliterans syndrome after lung transplantation and health-related quality of life. Am J Respir Crit Care Med 2; 161: Ramsey, Patrick DL, Lewis S, et al. Improvement in quality of life after lung transplantation: A preliminary study. J Heart Lung Transplant 1995; 14: Stavem K, Bjørtuft Ø, Lund MB, Kongshaug K, Geiran O, Boe J. Health related quality of life in lung transplant candidates and recipients. Respiration 2; 67: Limbos MM, Joyce DP, Chan CKN, Kesten S. Psychological functioning and quality of life in lung transplant candidates and recipients. Chest 2;118: Limbos MM, Chan CK, Kesten S. Quality of life in female lung transplant candidates and recipients. Chest 1997: 112: Cohen L, Littlefield C, Kelly P, et al. Predictors of quality of life and adjustment after lung transplantation. Chest 1998: 113: Gross CR, Savik K, Bolman RM, et al. Long-term health status and quality of life outcomes of lung transplant recipients. Chest 1995:18; Lanuza DM, Lefaiver C, Cabe M, et al. Prospective study of functional status and quality of life before and after lung transplantation. Chest 2;118: MacNaughton KL, Rodrique JR, Cicale M, et al. Health related quality of life and symptom frequency before and after lung transplantation. Clin Transplant 1998; 12: Craven J: Psychiatric aspects of lung transplant. Can J Psych 199; 35:

13 15.Littlefield C, Abbey S, Fiducia D, et al. Quality of life following transplantation of the heart, liver and lungs. Gen Hosp Psych 1996; 18:36S-47S 16. de Boer WJ, Mannes G.P.M. Treatment protocol lung transplantation. Groningen: University Hospital Groningen, Hunt MS, McEwen J, McKenna SP. Measuring health status. London: Croom Helm, Spelberger CD, Gorsuch RL, Lushene RE, eds. STAI manual for the state-trait anxiety inventory. Palo Alto, California: Consulting Psychologists Press, Zung WWK, Durham NC. A self-rating depression scale. Arch Gen Psychiatry 198; 35: Campbell A. Subjective measures of well-being. Am Psychol 1976; 31: Karnofsky DA, Abelman WH, Craver LF, et. al. The use of the nitrogen mustards in the palliative treatment of carcinoma. Cancer 1948; 1: Hochberg Y, Benjamin Y. More powerful procedures for multiple significance testing. Sta Med 199, 9: Hayden AM, Robert RC, Kriett JM, et al. Primary diagnosis predicts prognosis of lung transplant candidates. Transplantation 1993; 55: Paradis I, Yousem S, Griffith B. Airway obstruction and bronchiolitis obliterans after lung transplantation. Clin Chest Med 1993: 14: Hosenpud JD, Bennett LE, Keck BM, et al. The Registry of the International Society for Heart and Lung Transplantation 2; 19: Surman OS. Psychiatric aspects of liver transplantation. Psychosomatics 1994; 35: