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* From the Department of Pulmonology (Drs. van den Berg, Postma, van der Bij, and Koëter) and Office for Medical Technology Assessment (Drs. van Enckevort and TenVergert), University Hospital, Groningen, the Netherlands.
Correspondence to: Jan W. K. van den Berg, MD, PhD, Department of Pulmonology, Isala Clinics, PO Box 10.500, 8000 GM Zwolle, the Netherlands; e-mail: j.w.k.van.den.berg{at}isala.nl
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Abstract |
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Design: Follow-up costs were prospectively investigated in a medical technology assessment of the Dutch Lung Transplant Program, in relation to the development of the BOS. First, average follow-up costs per week per patient were compared between patients who did or did not develop BOS. Second, in the BOS group, these costs were compared before and after the onset of BOS.
Setting: Dutch Lung Transplant Program, University Hospital of Groningen.
Results: Data on 53 patients (37 patients without BOS and 16 with BOS) who underwent transplantation between November 1990 and April 1995 were available. The average follow-up time of these 53 patients was 1.5 years. The follow-up costs amounted to an average (in Dutch guilders [Dfl]) of 1,774/wk for non-BOS patients, compared to 3,072/wk for BOS patients (+ 73%; p = 0.002; one Dfl = 50 cents US currency). This difference in costs was largely accounted for by an increase in used health-care resources, in particular hospitalization and medication. For the BOS patients, the average costs per week before and after the onset of BOS were 1,941 Dfl and 2,422 Dfl, respectively.
Conclusion: BOS is associated with substantial extra costs. These findings reemphasize the need to focus efforts on prevention of BOS to enhance the cost-effectiveness of lung transplantation.
Key Words: bronchiolitis obliterans • cost analysis • lung transplantation
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Introduction |
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TOPAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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In addition to a lower survival advantage, the costs of follow-up after transplantation are higher for lung transplantation compared to heart or liver transplantation.1 It is not fully disclosed which factors contribute to the higher costs of follow-up after lung transplantation. The aim of the present study was to assess the contribution of chronic transplant dysfunction to the higher costs of follow-up of lung transplantation. Those costs were calculated in patients who underwent transplantation between 1990 and 1995, ie, before the introduction of the newer immunosuppressive drugs, thus allowing for a fair comparison under standard triple immunosuppression.
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Materials and Methods |
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TOPAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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Patients
All patients who survived > 60 days after transplantation were
considered at risk for developing BOS and were included in the study.
The costs of their outpatient follow-up phase were studied.
BOS
BOS was diagnosed according to the criteria of the International
Society for Heart and Lung Transplantation.7
A diagnosis
of BOS was based on a decline of the FEV1 to
< 80% of a baseline value, or on the histologic evidence of
obliterative bronchiolitis in biopsies. All patients were seen
frequently at the outpatient clinic. On all visits to the outpatient
clinic and twice a week when patients were admitted to the hospital,
spirometry was recorded, allowing for an accurate diagnosis of BOS.
Immunosuppression
All patients received standard triple immunosuppression,
consisting of cyclosporin A (aiming at initial postoperative plasma
trough levels of 400 µg/L, tapering to a maintenance level of 150
µg/L [high-performance liquid chromatography] from 3 weeks
postoperatively onwards), and azathioprine, 1- to 3-mg/kg maintenance
dose. Intraoperatively, methylprednisolone, 1,000 mg, was administered,
followed by three doses of 125 mg on the first postoperative day.
Subsequently, oral prednisolone, 1 mg/kg/d, was initiated and
subsequently reduced to an initial maintenance dose of 15 mg/d. Rabbit
antithymocyte globulin was administered during the first postoperative
week as immunosuppression induction. Acute rejection was treated with a
3-day course of methylprednisolone, 500 to 1,000 mg/d, followed by oral
prednisolone, tapering the dose over several days. In cases of
persistent rejection or when BOS was diagnosed, cytolytic therapy with
rabbit antithymocyte globulin was commenced.
Costs
All costs related to the lung transplant procedure were
calculated per patient per week of follow-up, from the moment of
discharge after the transplant procedure until death or the end of the
study period. The costs consisted of health-care costs
(hospitalization, outpatient visits, medication, professional home
help); patient and family costs (traveling expenses, medical tools,
special diets, nonprofessional home help); and production losses (paid
or unpaid work). If possible, full resource costs were estimated (base
year 1992) for BOS and non-BOS patients.8
Volume data
(ie, quantities of resources used) within the UHG were
largely obtained from the detailed hospital accounting system and from
case report forms. Volume data outside the UHG were gathered by
questionnaires completed by the recipients at 1 month, 4 months, and 7
months posttransplantation and every 6 months thereafter. Information
was requested about the following items: work (paid and unpaid);
hospitalizations and outpatient visits in hospitals other than the UHG,
hospitalizations in nursing homes; location of the hospitals and
nursing homes (to assess traveling costs); home help; use of
medication, medical tools (eg, wheelchair), clothes, and
special food. Unit prices within the UHG were largely based on
information from the financial administration of the hospital. For
instance, the costs of one day of hospitalization in the intensive care
and normal care departments were based on detailed information on costs
of staff, materials, accommodation, cleaning, food, laundry, and
overhead for those departments. Unit prices outside the hospital were
based on external information sources.9
Production losses
were estimated on the basis of the friction costs method of
Koopmanschap et al,10
using a friction period of 3 months.
To assess the influence of BOS on costs of follow-up, the total costs of follow-up divided by the number of weeks in follow-up were compared for both groups. Additionally, in patients developing BOS, the costs per week of follow-up were compared prior to and after the onset of BOS.
Statistical Analysis
The costs did not display a normal distribution. Hence,
differences in costs between patients with and without BOS were tested
by the Mann-Whitney U test. Differences in costs before and
after development of BOS were analyzed with the Wilcoxon signed
rank test. A p < 0.05 was considered statistically significant.
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Results |
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Discussion |
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The bulk of the extra costs was caused by an increase in days spent in the hospital; obviously, patients were admitted to the hospital more often for obtaining a diagnosis or undergoing treatment, either directed at the allograft dysfunction or at associated infections. The latter is reflected in the increased costs of medication. As only cyclosporine, azathioprine, and prednisolone were available for standard immunosuppressive therapy at the time of the study, the results are not biased by conversions to a different scheme of maintenance immunosuppressive drugs. The average number of days per week spent in the hospital may be high when compared to the results of a study by Ramsey et al.12 This may be explained by the fact that the follow-up protocol (with the exception of visits to the outpatient clinic) was performed on an inpatient basis in our hospital at the time of the study.
A possible confounding factor is the comparison of two potentially different groups of patients, or a different length of follow-up of two groups. As can be seen in Table 1 , the patients developing BOS differ slightly from those who do not with respect to underlying diagnosis. To the best of our knowledge, however, patient characteristics have not been reported as risk factors for development of BOS. The average length of follow-up per patient was comparable in the two groups (492 days in the patients without BOS, and 559 days in those developing BOS).
Although the costs per week of follow-up were higher after onset of BOS, the difference did not achieve statistical significance, which may be due to the fact that the number of patients developing BOS was small. Furthermore, we found that the costs started to increase gradually, even before a diagnosis of BOS was made. This probably reflects the impact of reported risk factors for BOS, ie, an increased number and severity of rejection episodes 13 14 and possibly cytomegalovirus disease.14
BOS is rarely responsive to medical treatment.15 Stabilization of the decline in pulmonary function can be achieved sometimes through augmented immunosuppression.16 Recently, several new immunosuppressive drugs have been introduced for use in lung transplantation.17 Results from studies with tacrolimus suggest that the prevalence of BOS is significantly lower in patients treated with tacrolimus, compared to patients treated with cyclosporine.18 Tacrolimus has also been used with some success as rescue therapy for BOS in two small, uncontrolled studies.19 20 Preliminary experience with the use of mycophenolate mofetil in lung transplantation suggests that mycophenolate mofetil is superior to azathioprine in reducing the incidence of BOS.21 In many countries, however, these drugs have not been licensed yet for use in lung transplantation. In general, these newer immunosuppresive drugs are more expensive than the old ones. Concerns for additional costs to lung transplantation, already one of the most expensive medical interventions available, may have prevented the drug regulatory agencies from licensing these drugs. If these newer drugs, however, are effective in lowering the incidence of BOS, or postponing its onset, such a restrictive, "penny-wise" approach may be eventually disadvantageous, both to lung transplant recipients and to the overall costs of a lung transplant program.
In conclusion, our results show that the development of BOS adds considerably to the costs of lung transplantation. This, in conjunction with a reduced life expectancy associated with BOS, markedly reduces the cost-effectiveness of lung transplantation. Our data stress the need to focus efforts on prevention of BOS to enhance cost-effectiveness of lung transplantation or, at the least, to improve the quality of life of these patients.
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Footnotes |
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Received for publication December 15, 1999. Accepted for publication July 10, 2000.
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This article has been cited by other articles:
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  A. Boehler and M. Estenne Post-transplant bronchiolitis obliterans Eur. Respir. J., December 1, 2003; 22(6): 1007 - 1018. [Abstract] [Full Text] [PDF]
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 A. DeVito Dabbs, L. A. Hoffman, A. T. Iacono, C. L. Wells, W. Grgurich, T. G. Zullo, K. R. McCurry, and J. H. Dauber Pattern and Predictors of Early Rejection After Lung Transplantation Am. J. Crit. Care., November 1, 2003; 12(6): 497 - 507. [Abstract] [Full Text] [PDF]
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