Between June 1993 and June 2004, 90 LTxs, including 5 retransplantations, were performed at our institution. Adult patients who were able to self-complete the HRQL instruments and who had undergone > 2 years of follow-up after LTx were considered to be eligible for the analysis. Forty-four consecutive adult lung transplant recipients (mean [± SD] age, 44.8 ± 11.6 years) with > 2 years of follow-up after LTx (median follow-up time, 63 months; range, 24 to 84 months) qualified for the study. The following patients were excluded from the study: 18 patients who died during the first 2 years following LTx; 3 children; 1 patient who underwent LTx at our institution, but was followed up elsewhere after the procedure; 1 Vietnamese patient who required the presence of a translator and was, therefore, unable to self-complete the quality-of-life instruments; and 18 patients who had not completed 2 years of follow-up after LTx by the time the analyses began. Nineteen of the 44 patients (43%) were women. Of 44 lung transplant recipients, 14 (32%) had received a single lung transplant and 30 (68%) had received a bilateral sequential transplant. Indications for single LTx were pulmonary emphysema (10 patients), idiopathic pulmonary fibrosis (3 patients), and pulmonary fibrosis following paraquat intoxication (1 patient). Indications for bilateral LTx were pulmonary emphysema (14 patients), cystic fibrosis (9 patients), idiopathic pulmonary fibrosis (2 patients), primary pulmonary hypertension (2 patients), thromboembolic disease (1 patient), bronchiolitis obliterans (1 patient), and lymphangiomyomatosis (1 patient). Patients with pulmonary emphysema included the diagnoses of emphysema and a1-antitrypsin deficiency. The indication for single or bilateral LTx was based on the underlying disease, organ availability, and length of time spent on the waiting list. The protocol for the study was approved by the ethical committee of the institution. Informed consent was obtained before LTx from all patients.
Immunosuppression Protocol and Clinical Follow-up After LTx
Standard immunosuppression therapy including steroids, cy-closporine A, and azathioprine was used between 1993 and 1999. Details on the initial immunosuppression regimen were presented in another report. Over time, the immunosuppression protocol has been changed at our institution to include new drugs that became available. Consequently, cyclosporine A and azathio-prine have been gradually replaced by tacrolimus and mycophe-nolate mofetil in the majority of our patients since 1998. Doses of tacrolimus were adjusted to maintain serum levels between 7 and 10 |J.g/L as determined by immunoassay (Abbot Laboratories; Abbot Park, IL). Doses of mycophenolate mofetil (25 to 35 mg/kg/d, with a maximum of 2 g/d) were adjusted to maintain trough levels of mycophenolic acid of > 1.0 mg/L, and were monitored by assay (Emit Syva Dade Assay; Behring Diagnostics, Inc; San Jose, CA).
Before LTx, patients were regularly seen at the outpatient clinic, with the exception of one patient who had undergone LTx as a salvage therapy after massive paraquat poisoning. Following hospital discharge after LTx, patients were scheduled for outpatient visits twice a month for clinical follow-up and therapeutic adjustments. Comprehensive clinical evaluations were performed at 3, 6, 9, and 12 months during the first year after LTx, and every 6 months thereafter, or whenever needed for the investigation of potential clinical complications, such as respiratory tract infections or acute rejection. These clinical evaluations included, among others, spirometry, 6MWT, and fiberoptic bronchoscopy with transbronchial biopsies. The diagnosis of BOS followed the criteria recommended by the International Society for Heart and Lung Transplantation.
HRQL and Pulmonary Function Assessments
HRQL was evaluated before and longitudinally after LTx using two different assays, the French-validated version of the St. George respiratory questionnaire (SGRQ) and a visual analog scale (VAS). These two assays were simultaneously performed throughout the follow-up period. The SGRQ contains questions addressing the following three main domains: respiratory symptoms; daily activities limitation; and disease impact on social and psychological functioning. Partial scores corresponding to each domain of the questionnaire were calculated. A derived global score of well-being (ie, SGRQ global score), ranging from 0 to 100%, is calculated from the difference between the highest possible score and the sum of the scores obtained in the three domains contained in the instrument. For intraindividual comparisons, a 4-point (4%) change between scores obtained during follow-up is indicative of clinical relevance. For the purpose of the present study, a global score of 100% was defined as an optimal state of well-being. The scores were prospectively compiled for each patient each time the questionnaire was completed.
In addition to the SGRQ, patients were invited to self-assess their global state of well-being using a VAS. For this purpose, the EuroQoL VAS was calibrated from 0 to 100 mm, and was labeled respectively as the worst and best possible state of health sustained by Canadian Health&Care Mall canadianhealthncaremallcom. The results obtained by the SGRQ scores were compared to the rates of the VAS.
The spirometry (FEV1) and 6MWT findings were used as clinical indicators of outcome. The FEV1, 6MWT, SGRQ, and VAS were performed simultaneously within the year preceding LTx, then at 6 and at 12 months post-LTx, and then once a year thereafter for the analyses.
The data obtained in this study presented a normal distribution. The results are shown as absolute values, percent predicted values (FEV1), the mean ± SEM, and median (range). Unpaired t tests were used to compare demographic data between single and bilateral lung transplant recipients. Repeated-measures analysis of variance was used to compare the FEV1 values, the 6MWT results, and the SGRQ global and domain-specific scores between patients following a single or a bilateral LTx. Post hoc Bonferroni analyses were applied to compare outcomes between the groups studied at each time point. Stratified analyses of variance with repeated measures were performed to compare (1) outcomes at 3 years after LTx in the overall group of patients between those who had undergone LTx before 1998 and patients transplanted after 1998, when changes in the immunosuppression protocol had been made and (2) between single and bilateral lung transplant recipients in the same time periods. The Pearson correlation test was used to compare the scores obtained from the simultaneous completion of the SGRQ with the measurement of FEV1, 6MWT results, and VAS score throughout the follow-up period. The data are presented as the overall correlation coefficients, irrespective of time after LTx. The relative risk and the 95% confidence interval were calculated to estimate the impact of BOS between single and double lung transplant recipients. The Fisher Exact Test was employed to compare the occurrence of infections and acute rejections following a single or a bilateral LTx. Adjustments were made to p values for the multiple comparisons. Data analyses were performed using a statistical software package (GraphPad PRISM, version 3.00 for Windows; GraphPad Software; San Diego, CA). A p value of < 0.05 was considered to be statistically significant.