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Volume: 12 Issue: 4 August 2014

FULL TEXT

ARTICLE
Risk Factors Associated With Survival After Lung Transplant in Iran

Objectives: Limited information is available about risk factors associated with survival after lung transplant in Iranian recipients. This study evaluated the effect of recipient and donor characteristics on survival after lung transplant.

Materials and Methods: This retrospective study included 69 lung transplants (single, 31 patients [45%]; bilateral, 38 patients [55%]), from 2000 to 2013, at the National Research Institute of Tuberculosis and Lung Diseases, Masih Daneshvari Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran. The Kaplan-Meier method was used to calculate survival, and variables were evaluated with multivariate analysis.

Results: There were 54 male recipients (78%), and the most frequent indications for transplant included pulmonary fibrosis in 31 patients (45%) and bronchiectasis in 23 patients (33%). Recipient mean age was 36 ± 13 years and body mass index was 20 ± 4 kg/m2. Mean half-life (all recipients) was 2 ± 1 years and survival was 73% at 1 month, 67% at 1 year, and 40% at 5 years after transplant. For recipients who survived > 2 weeks after transplant half-life and survival were similar to previously international reported results. Recipient age, sex, type of transplant, body mass index, and pulmonary artery pressure were not associated with survival. Survival was significantly higher with recipient bronchiectasis, younger donors, and female donors.

Conclusions: Survival after lung transplant was better with recipients who had bronchiectasis and donors that were younger or female. Patient selection, invasive monitoring, and supportive techniques such as extracorporeal membrane oxygenation for unstable patients during surgery may be helpful.


Key words : Body mass index, Bronchiectasis, End-stage lung disease, Pulmonary fibrosis

Introduction

Although lung transplant is the only option to improve survival for patients who have many end-stage lung diseases, it is a complex intervention.1 In 2009, there were 3272 lung transplants reported to the International Society for Heart and Lung Transplantation registry, the highest of any year to date. There are > 2500 lung transplants performed annually at > 150 lung transplant centers world-wide.1,2 The annual growth in reported procedures has been steady since the year 2000. The half-life of adult lung recipients was 5.5 years between January 1994 and June 2010, which is longer than the half-life reported in the 2009 report. The unadjusted survival was 88% at 3 months, 79% at 1 year, 64% at 3 years, 53% at 5 years, and 30% at 10 years, similar to a previous report.3 According to United States Department of Health and Human Services, lung survival of patients in 2009 was 92.3% at 3 months, 83.3% at 1 year, 66.2% at 3 years, 54.4% at 5 years, and 28.6% at 10 years.4 However, the 5-year survival (55%-60%) is worse after lung transplant than other organ transplants.5 Survival was 51% at 1 year and 36% at 5 years in Iranian lung recipients who had transplant at Masih Daneshvari Hospital from 2000 to 2009.6

Solid-organ transplant involves the allocation of life-saving but inherently limited resources. Therefore, it is important to identify potentially modifiable perioperative recipient variables that may affect survival after transplant. Some studies have evaluated recipient and donor characteristics and have shown that survival is associated with some recipient factors after lung transplant such as age and sex at transplant, body mass index (BMI), nutritional status, type of transplant, and underlying lung disease.7-12 However, some studies investigated sex and age donors, they did not find a significant association with survival.10,13 However, a literature search showed no previous studies about the effect of different factors on lung transplant mortality in Iran. The purpose of this study was to evaluate the effect of recipient and donor characteristics on survival after lung transplant in Iran.

Materials and Methods

Data source
This retrospective study evaluated primary lung transplant recipients from 2000 to 2013. There were 72 transplants, and 3 patients were excluded from the analysis because of revision transplant (2 patients) and heart-lung transplant (1 patient), leaving 69 transplants included in the analysis. All data were supplied by the Masih Daneshvari Hospital (National Research Institute of Tuberculosis and Lung Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran), which is a university-based hospital and referral center for lung transplant. Indications and contraindications for lung transplant were consistent with widely accepted criteria. The analyses were limited to patients undergoing lung transplant at this center, which was 1 of the 2 active lung transplant centers in Iran in 2013. The registry contained data about all patients who had lung transplant since the first transplant in 2000. The date of lung transplant and the last follow-up were known for every recipient. Patients were followed and examined weekly up to 3 months after transplant and monthly from 3 months to 1 year; subsequent follow-up was performed whenever recipients had any complications.

Examined variables
The primary outcome was time from lung transplant until death or August 2013. Mortality from all causes was included. Recipient variables were evaluated including age at lung transplant, sex, BMI, type of transplant (single or bilateral), underlying lung disease, and pulmonary artery pressure before transplant. Donor variables included age, sex, and cause of brain death.

Statistical analyses
Data analyses were performed with statistical software (R 3.0, Institute for Statistics and Mathematics, Wirtschaftsuniversität Wien, Vienna, Austria). A time-to-event analysis was performed using Kaplan-Meier method to calculate survival at different times. For multivariate analysis, exponential survival accelerated failure time model was used to assess the effect of the variables on survival after lung transplant. Accelerated failure time models described the increase or decrease of survival as a function of predictor variables. The acceleration factor was a key measure of association obtained in an accelerated failure time model showing a ratio of survival times corresponding to any fixed value of survival.14 Data were presented as mean ± standard deviation, and acceleration factors were reported with 95% confidence intervals. Patients were censored when they were alive at the latest follow-up. All tests were 2-tailed, and statistical significance was defined by P ≤ .05.

Results

In the 69 lung transplants, most donors and recipients were male, and there was a similar number of single and bilateral lung transplants (Table 1). The most common underlying diseases in recipients were pulmonary fibrosis and bronchiectasis (Table 1). In the 42 recipients (61%) who died after lung transplant, the most common causes of death included hemodynamic instability and infection (Table 1). The cause of donor brain death was trauma in 31 donors (43%). Survival (all patients) at 5 years after transplant was 40% (Table 2). There were 16 patients (23%) who died within 2 weeks after transplant; after excluding these patients, survival at 5 years after transplant was 50% (Table 2).

The multivariate analysis showed that recipient age, sex, type of transplant, and BMI were not significant predictors of survival (Table 3). The half-life for recipients who had bronchiectasis increased by an acceleration factor of 6.83 compared with recipients who had pulmonary fibrosis; survival was similar between patients who had chronic obstructive pulmonary disease and emphysema and patients who had pulmonary fibrosis (Table 3). The half-life for recipients was significantly lower when the donor was 1 year younger older than when the donor was 1 year older younger (Table 3). Recipient survival was significantly greater when the donor was female (Table 3).

Discussion

This study focused on the risk factors associated with survival after lung transplant in Iranian recipients. The data showed that recipient age at transplant and sex were not associated with recipient survival. In contrast, previous studies reported that age and female sex had a significant effect on better long-term survival.8,11 Another previous study showed that outcomes in patients who had interstitial lung disease were comparable or better with single than bilateral lung transplant, and short- and long-term survival were not significantly different for the 2 types of procedures.15 The findings based on United Network for Organ Sharing data showed that bilateral lung transplant had significantly better survival than single lung transplant.3 The present study did not confirm a significant effect of type of transplant on survival that was previously reported.8 In 38 patients who had bilateral lung transplant, 19 patients (50%) died soon after surgery because of technical issues, possibly because of more frequent technical complications after bilateral than single lung transplant.

Malnourished and obese surgical patients have higher postoperative morbidity and mortality. In a previous study, the risk of dying within 90 days after transplant was 4-fold greater in patients who had a pretransplant BMI < 17 or > 25 than patients who had normal BMI. Patients who have end-stage lung disease also have malnutrition, known as lung cachexia (BMI < 19 kg/m2).10 In United Network for Organ Sharing data about 11 411 adult primary lung transplants, mortality was higher in underweight, overweight, and obese patients than patients with normal weight (18.5 kg/m2 < BMI < 24.5 kg/m2).9 The present study did not show a significant association between BMI and survival (Table 3). Recipients frequently had been referred late to the waiting list and physiotherapy was received late or not received. The mean BMI was very low (Table 1) and 61% patients were cachectic, which may explain the absence of an observed effect of BMI on survival (Table 3).

The present results showed significantly better survival in patients who had bronchiectasis than pulmonary fibrosis (Table 3), but previous studies showed that cystic fibrosis patients had higher frequency of death after lung transplant than patients who had chronic obstructive pulmonary disease.9 Although there was a significant effect of high systolic pulmonary artery pressure on risk of death among pulmonary fibrosis patients in United Network for Organ Sharing data,16 there was no significant relation observed between pulmonary artery pressure and mortality in the present study (Table 3). A previous study also showed that recipient sex, donor-recipient sex mismatch, and each sex combination had no effect on survival at 5, 10, and 20 years.13 Although a previous study showed no significant association between donor age and early death after lung transplant, in the present study, younger donors were associated with better survival (Table 3).10

In a previous study with 2204 recipients who died, 10% to 20% recipients died because of infection and technical reasons within 30 days after transplant.3 In the present study, early deaths were caused by hemodynamic instability and infection (Table 2). Insufficient oxygen consumption and poor pulmonary rehabilitation may cause high pulmonary artery pressure and severe deconditioning in lung transplant patients. In addition, patients may be referred to the lung transplant clinic late with an unstable clinical condition. Recurrent infection without effective treatment may cause severe pleural adhesions. These issues complicated the surgical procedures and may have contributed to low short-term survival. In contrast, recipients who survived > 2 weeks after lung transplant had improved half-life and survival similar to the International Society for Heart and Lung Transplantation report in 2011 (Table 2).3 Poor compliance and discontinuation of medication may have caused infection and low long-term survival.

In summary, the present study showed that recipient survival may be improved by selecting recipients who have bronchiectasis and using lungs from younger donors (Table 3). Further study may include evaluation of more factors that may affect survival such as time on the waiting list and time-dependent covariates such as infection and rejection status of recipients after lung transplant. Although there was low survival observed after lung transplant, survival may be improved by studying factors such as patient selection, invasive monitoring, and supportive techniques such as extracorporeal membrane oxygenation for unstable patients during surgery.


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Volume : 12
Issue : 4
Pages : 290 - 294
DOI : 10.6002/ect.2014.0029


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From the 1Department of Biostatistics, Faculty of Medical Sciences, Tarbiat Modares University; the 2Lung Transplant Research Center, Masih Daneshvari Hospital, National Research Institute of Tuberculosis and Lung Diseases, and the 3Department of Biostatistics, Faculty of Paramedical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
Acknowledgements: None of the authors has a financial relationship with a commercial entity or other conflicts of interest. There was no funding for this study.
Corresponding author: Ebrahim Hajizadeh, PhD, Associate Professor, Department of Biostatistics, Faculty of Medical Sciences, Tarbiat Modares University, P.O. Box 14115-333, Tehran, Iran
Phone: +98 21 8288 3810
Fax: +98 21 8288 3810
E-mail: hajizadeh@modares.ac.ir