Bronchiolitis Obliterans Syndrome and Additional Costs of Lung Transplantation

doi:10.1378/chest.118.6.1648

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Volume 118, Issue 6, December 2000, Pages 1648-1652

https://doi.org/10.1378/chest.118.6.1648 Get rights and content

Study objectives:

The influence of bronchiolitisobliterans syndrome (BOS) on costs after lung transplantation wasinvestigated by comparing the costs of patients with and without thiscondition.

Design:

Follow-up costs were prospectivelyinvestigated 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 betweenpatients 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 transplantationbetween November 1990 and April 1995 were available. The averagefollow-up time of these 53 patients was 1.5 years. The follow-up costsamounted to an average (in Dutch guilders [Dfl]) of 1,774/wk fornon-BOS patients, compared to 3,072/wk for BOS patients (+ 73%;p = 0.002; one Dfl = 50 cents US currency). This difference incosts was largely accounted for by an increase in used health-careresources, in particular hospitalization and medication. For the BOSpatients, the average costs per week before and after the onset of BOSwere 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 lungtransplantation.

Section snippets

Materials and Methods

In 1991, a technology assessment study of the Dutch Lung Transplant Program at the University Hospital of Groningen (UHG) wasinitiated by the Dutch National Health Insurance Board. From November1990 until April 1995, data were gathered on all patients entering the, Dutch Lung Transplant Program. The aim of the technology assessment wasto provide information on costs, clinical effectiveness, quality oflife, demand for lung transplantation, and supply ofdonors.⁶ In the present study, data

Results

Of the 57 patients who underwent transplantation between November1990 and April 1995, 53 patients survived > 60 days aftertransplantation and entered the outpatient follow-up phase. Sixteenpatients developed BOS during the study period. Patient characteristicsare specified in Table 1.

Table 2 presents the average costs of the outpatient follow-up phase expressedin Dutch guilders (Dfl) per patient per week for each category. Thetotal costs per week of follow-up were statistically

Discussion

More than 15 years ago, Burke et al¹¹ reported asyndrome of irreversible severe air flow obstruction and typicalhistologic features of obliterative bronchiolitis in several heart-lungrecipients. Today, BOS remains a major impediment to long-term successafter heart or lung transplantation. In the present study, for thefirst time, it was demonstrated that BOS is associated withconsiderable extra costs. This may not be surprising, as BOS isassociated with increased morbidity, mainly by

References (21)

MJ Al et al.
Cost-effectiveness of lung transplantation in The Netherlands: a scenario analysis
Chest
(1998)
JD Hosenpud et al.
The Registry of the International Society for Heart and Lung Transplantation: sixteenth official report–1999
J Heart Lung Transplant
(1999)
MA Koopmanschap et al.
The friction cost method for measuring indirect costs of disease
J Health Econ
(1995)
CM Burke et al.
Post-transplant obliterative bronchiolitis and other late lung sequelae in human heart-lung transplantation
Chest
(1984)
SD Ramsey et al.
The cost-effectiveness of lung transplantation: a pilot study, University of Washington Medical Center Lung Transplant Study Group
Chest
(1995)
I Paradis et al.
Airway obstruction and bronchiolitis obliterans after lung transplantation
Clin Chest Med
(1993)
GI Snell et al.
Cytolytic therapy for the bronchiolitis obliterans syndrome complicating lung trans- plantation
Chest
(1996)
DJ Ross et al.
FK506 “rescue” immunosuppression for obliterative bronchiolitis after lung transplantation
Chest
(1997)
S Sundaresan et al.
Prevalence and outcome of bronchiolitis obliterans syndrome after lung transplantation. Washington University Lung Transplant Group
Ann Thorac Surg
(1995)
H Reichenspurner et al.
Stanford experience with obliterative bronchiolitis after lung and heart-lung transplantation
Ann Thorac Surg
(1996)

There are more references available in the full text version of this article.

Cited by (25)

Self-reactive antibodies associated with bronchiolitis obliterans syndrome subtype of chronic lung allograft dysfunction
2021, Human Immunology
Citation Excerpt :
Bronchiolitis Obliterans Syndrome (BOS) continues to be the most prevalent presentation of CLAD accounting for 60–75% of cases [2]. In addition to being the leading cause of death after lung transplantation, BOS impairs quality of life, causes significant morbidity and increased costs [3]. Only few therapeutic options are now in place for management of BOS and is generally not reversible.
Chronic Lung Allograft Dysfunction (CLAD) remains the major limitation in long term survival after lung transplantation. Our objective is to evaluate for the presence of autoantibodies to self-antigens, which is a pathway along with complex interplay with immune as well as non-immune mechanisms that leads to a fibroproliferative process resulting in CLAD.
Serum profiles of IgG autoantibodies were evaluated using customized proteomic microarray with 124 antigens. Output from microarray analyzed as antibody scores is correlated with bronchiolitis obliterans (BOS) subtype of CLAD using Mann-Whitney U test or Fisher exact test. Autoantibodies were evaluated for their predictive value for progressive BOS using a Cox proportional hazard model. BOS free survival and overall survival was analyzed using Kaplan-Meier survival analysis.
Forty- two patients included in the study are grouped into “stable BOS” and “progressive BOS” for comparisons. Pulmonary fibrosis is the major indication for lung transplantation in our cohort. Progressive BOS group had significantly worse survival (p < 0.005). Sixteen IgG autoantibodies are significantly elevated at baseline in progressive BOS group. Six among them correlated with worse BOS free survival (p < 0.05). In addition, these six IgG autoantibodies remain elevated at three months and one year after lung transplantation.
Pre-existing IgG autoantibodies correlate with progressive BOS and survival in a single center, small cohort of lung transplant recipients. Further validation with larger sample size, external cohort and confirmation with additional tissue, bronchoalveolar lavage samples are necessary to confirm the preliminary findings in our study.
Exploring the meaning of chronic rejection after lung transplantation and its impact on clinical management and caregiving
2010, Journal of Pain and Symptom Management
Citation Excerpt :
This decline in survival is more rapid compared with other solid organ transplant recipients; three- and five-year survival rates are 80% and 74% for heart and 94% and 90% for kidney transplant recipients, respectively.2 The primary threat to survival and quality of life after lung transplantation is the development of chronic rejection, which manifests as bronchiolitis obliterans syndrome (BOS), and affects more than 34%–64% of recipients by Year 5.3–5 BOS is determined based on established criteria:6 evidence of ≥20% decline forced expiratory volume in one second (FEV1) from baseline (personal best) within a three-week interval in the absence of any confounding conditions (i.e., infection, acute cellular rejection, or airway stenosis) to explain the airflow obstruction.
Although the literature continues to portray chronic rejection after lung transplantation as ominous with no known treatment, no studies have examined family and clinician caregivers' perceptions of the diagnosis of chronic rejection and its impact on the course of clinical care. We explored the meaning and impact of chronic rejection from the perspective of family (n = 10) and clinician (n = 3) caregivers. We found that family caregivers considered the onset of chronic rejection to be inevitable, irreversible, unpredictable, and going back to pretransplant. Clinicians considered chronic rejection as a harbinger of deterioration and peril and expressed trepidation about informing recipients and their family caregivers about the diagnosis. Despite the heightened caregiving duties and challenges of treating chronic rejection, its unpredictable course and the prospect of retransplant instilled hope for stabilization or cure among most clinicians and caregivers, leading them to support recipients' wishes to pursue potentially futile treatments. Until recipients were no longer competent, caregivers believed all treatment options (including retransplant) had been exhausted, or suffering was prolonged, caregivers were reluctant to halt extraordinary treatment measures. Caregivers perceived that certainty regarding poor prognosis was required for palliative care and that palliative care was end-of-life care. Consequently, trials of aggressive treatment typically precluded palliative care.
Update in Surgical Therapy for Chronic Obstructive Pulmonary Disease
2007, Clinics in Chest Medicine
Citation Excerpt :
Furthermore, ISHLT Registry data reveal that most patients live without any activity limitations, and approximately 40% go back to part-time or full-time work, which is remarkable considering the universal presence of severe pretransplant disability [58]. It is important to note, however, that most of these outcome variables, along with health status, decline over time with the development of BOS [74,76]. Lung transplantation is associated with high short- and long-term mortality related to numerous potential complications.
Bullectomy for giant bullae, lung volume reduction surgery, and lung transplantation are three surgical therapies that may benefit highly selected patients with advanced chronic obstructive pulmonary disease. In this article, each procedure is reviewed, with an emphasis on guidelines for patient selection and clinical outcomes for the practicing pulmonologist. Recent results from the National Emphysema Treatment Trial, updated International Society for Heart and Lung Transplantation Registry data, and revised guidelines for patient selection for lung transplantation are discussed.
Economics of transplantation: a review of the literature
2006, Transplantation Reviews
Economic issues are important in transplantation. We reviewed the literature about health economics as well as transplantation and highlighted areas for further development.
We searched the MEDLINE database for the economic literature on kidney, kidney-pancreas, liver, heart, lung, and heart-lung economic studies.
The evidence that kidney transplantation provides better quality of life over dialysis and decreases costs are consistent. The economic evidence regarding kidney organ-shortage policies (donor action, expanded-criteria donor use) show that these are very cost-effective. Liver, heart, and lung transplantations provide quality-of-life benefits, increase health-care costs, and seem to be generally cost-effective. The cost-effectiveness of different indications, patient groups, and organ-shortage actions needs to be studied in non–kidney transplantation. Across all organs, there is a need to explore the quality-of-life impact of comorbidities and immunosuppressive medications. Surrogate outcomes may become an important tool in pharmacoeconomic research, whereas the use of Markov models and large registries such as the United States Renal Data System will continue to be widely used.
The contributions of health economics to transplantation are numerous. Future research are to be expected in the fields of quality of life, cost-effectiveness, insurance coverage, and organ allocation.
Bronchiolitis obliterans syndrome: Pathogenesis and management
2004, Seminars in Thoracic and Cardiovascular Surgery
Over the past 15 years, lung transplantation has become an established treatment for a variety of end-stage lung diseases, but medium- and long-term success has been limited by a high incidence of bronchiolitis obliterans syndrome (BOS). Immune mediated injury has been recognized as the leading cause of BOS, and the term is synonymous with chronic rejection. But recently, nonimmune mechanisms, such as gastroesophageal reflux, have been recognized as potential culprits. The results of various treatment options have generally been disappointing, and BOS has emerged as the leading cause of late morbidity and mortality after lung transplantation.
The impact of traffic air pollution on bronchiolitis obliterans syndrome and mortality after lung transplantation
2011, Thorax
Citation Excerpt :
These population-attributable fractions are significant not only in terms of patient suffering but also in terms of healthcare costs. The yearly mean cost after lung transplantation is €46100 for a stable patient and €79100 for a patient with BOS.37 38 In conclusion, the study found that exposure to traffic-related air pollution independently increased the risk of BOS and mortality in lung transplant patients and was associated with lung and systemic inflammation.
Approximately half of all patients who underwent a lung transplantation suffer from bronchiolitis obliterans syndrome (BOS), the clinical correlate of chronic rejection, within 5 years after transplantation. This prevalence is much higher than for other solid organ transplantations, possibly due to the lung's direct contact with the environment. The authors assessed the association between proximity of the home to major roads and BOS and mortality in a cohort of patients after lung transplantation.
The authors calculated hazard ratios for BOS and mortality in relation to proximity of the home to major roads, adjusting for relevant covariables, in 288 patients after lung transplantation at the Leuven University Hospital between 1997 and 2009 and with follow-up until August 2009. Inflammatory parameters in plasma and bronchoalveolar lavage were assessed in 207 patients.
During follow-up, 117 (41%) patients developed BOS and 61 (21%) died. Patients who lived within 171 m of a major road (lowest tertile) were 2.06 (95% CI 1.39 to 3.05) times more likely to develop BOS and 2.20 (1.25 to 3.86) times more likely to die than patients living farther away. The adjusted hazard ratios of BOS and mortality were 0.57 and 0.72 for each 10-fold increase in distance from major roads. Proximity to a major road was inversely associated with plasma C-reactive protein levels, neutrophil percentage and interleukin-6 concentration in bronchoalveolar lavage.
Traffic-related air pollution appears to constitute a serious risk of BOS and mortality after lung transplantation.

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Clinical InvestigationsTRANSPLANTATIONBronchiolitis Obliterans Syndrome and Additional Costs of Lung Transplantation

Study objectives:

Design:

Setting:

Results:

Conclusion:

Section snippets

Materials and Methods

Results

Discussion

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J Heart Lung Transplant

J Health Econ

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Clin Chest Med

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Prevalence and outcome of bronchiolitis obliterans syndrome after lung transplantation. Washington University Lung Transplant Group

Ann Thorac Surg

Stanford experience with obliterative bronchiolitis after lung and heart-lung transplantation

Ann Thorac Surg

Clinical Investigations
TRANSPLANTATION
Bronchiolitis Obliterans Syndrome and Additional Costs of Lung Transplantation