New models for donor-recipient matching in lung transplantations.

OBJECTIVE: One of the main problems of lung transplantation is the shortage of organs as well as reduced survival rates. In the absence of an international standardized model for lung donor-recipient allocation, we set out to develop such a model based on the characteristics of past experiences with lung donors and recipients with the aim of improving the outcomes of the entire transplantation process. METHODS: This was a retrospective analysis of 404 lung transplants carried out at the Reina Sofía University Hospital (Córdoba, Spain) over 23 years. We analyzed various clinical variables obtained via our experience of clinical practice in the donation and transplantation process. These were used to create various classification models, including classical statistical methods and also incorporating newer machine-learning approaches. RESULTS: The proposed model represents a powerful tool for donor-recipient matching, which in this current work, exceeded the capacity of classical statistical methods. The variables that predicted an increase in the probability of survival were: higher pre-transplant and post-transplant functional vital capacity (FVC), lower pre-transplant carbon dioxide (PCO2) pressure, lower donor mechanical ventilation, and shorter ischemia time. The variables that negatively influenced transplant survival were low forced expiratory volume in the first second (FEV1) pre-transplant, lower arterial oxygen pressure (PaO2)/fraction of inspired oxygen (FiO2) ratio, bilobar transplant, elderly recipient and donor, donor-recipient graft disproportion requiring a surgical reduction (Tailor), type of combined transplant, need for cardiopulmonary bypass during the surgery, death of the donor due to head trauma, hospitalization status before surgery, and female and male recipient donor sex. CONCLUSIONS: These results show the difficulty of the problem which required the introduction of other variables into the analysis. The combination of classical statistical methods and machine learning can support decision-making about the compatibility between donors and recipients. This helps to facilitate reliable prediction and to optimize the grafts for transplantation, thereby improving the transplanted patient survival rate.

Long-term Prognosis After Lung Transplantation: A Monocentric Study in 510 Patients.

INTRODUCTION: Lung transplantation is the final treatment option in patients with respiratory failure. Morbidity and mortality rates associated with the management of complications is high despite advances. Postoperative complications include acute transplant rejection, bronchiolitis obliterans, and infections. Because of that, the success of this treatment option depends on the correct choice of donor and candidates to receive a transplant. OBJECTIVE: This study aims to perform a survival analysis of transplanted patients in our center and determine predictive variables of mortality. PATIENTS AND METHODS: This study is a retrospective assessment of data collected from 510 patients at the Hospital University Reina Sofía from October 1993 to December 31, 2016. Patients who were retransplanted were excluded. We collected data regarding basal characteristics of the donors and candidates to receive a transplant. We analyzed the impact in terms of future survival of basal variables from donor and donor recipients. RESULTS: Five hundred ten patients were included (average age 44 ± 17 years, 69% male), with a maximum follow-up period of 21.6 years (average follow-up 4.52 years, interquartile ratio: 0.13 to 6.97 years). Two hundred twenty-seven patients died (54.3% of the total amount). The influence of donor's basal characteristics on mortality was analyzed; moreover, the relationship between basal variables and survival were analyzed using univariate analysis. Available variables were analyzed through multivariate analysis. CONCLUSION: Lung transplantation is a treatment option with an acceptable risk of morbidity and mortality. Increased awareness of features of evolution could help to reduce postoperative complications.

Analysis of the Incidence of Noncutaneous Neoplasia After Lung Transplantation and Its Impact on Prognosis.

INTRODUCTION: Increased survival in lung transplant recipients, the need for immunosuppressive therapy, and many risk factors before and after transplantation enhance the development of malignancies. This study sought to analyze the incidence of noncutaneous tumors after lung transplantation in our hospital, the risk factors for malignancy, and its impact on prognosis. PATIENTS AND METHODS: A retrospective analysis of clinical records of patients after lung transplantation in our hospital from October 1993 to December 2014. RESULTS: The study population included 443 patients. In total, 35 neoplasia developed in 33 patients (9.6%). Twelve cases were posttransplant lymphoproliferative disorders (PTLDs), 7 localized in the native lung, 7 gynecologic neoplasia (2 in the breast, 4 in the vulva, and 1 in the cervix), 3 in the colon, 2 in the nervous system (one was an astrocytoma), 2 in the prostate, 1 in the kidney, and 1 in the esophagus. The average time between transplantation and malignancy detection was 52.7 ± 45.4 months, being earlier in patients with PTLDs than in non-PTLD. Eleven patients who developed malignancy (all patients with neoplasia in native lung and in cervix, 1 in the colon, 1 PTLD, and 1 in the nervous system) died as a result of it. The only factor associated with an increased risk of malignancy in our population was smoking history. CONCLUSIONS: Almost 10% of lung transplant recipients developed some type of noncutaneous neoplasia and the most frequently diagnosed were PTLDs. Lung neoplasia compromised most survival in these patients.

Bone mineral density in patients with chronic obstructive pulmonary disease who are candidates for lung transplant.

UNLABELLED: INTRODUCTIóN: After cystic fibrosis, lung transplantation (LT) patients with prior chronic obstructive pulmonary disease (COPD) are most susceptible to loss of bone mineral density (BMD). OBJECTIVES: To determine the prevalence of BMD loss among COPD patients being evaluated as LT candidates, seeking to identify, their risk profile. PATIENTS AND METHODS: This cross-sectional study included COPD patients who were LT candidates evaluated from January 2007 to December 2009. To identify patients at risk of fracture, BMD at the femoral neck and lumbar spine was assessed by bone densitometry. For categorization, we followed the World Health Organization criteria. To evaluate the risk profile, we recorded data on age, sex, smoking, lung function forced expiratory volume in 1 second, distance covered in the 6-minute walk test, body mass index, and degree of dyspnea. We recorded individual data as well as grouped them the multidimensional BODE (Body mass index Obstruction Dyspnea Exercise capacity) index. RESULTS: The study cohort consisted of 64 patients (51 men and 13 women). The overall prevalence of low BMD in any of the explored territories was 84.4%, affecting 88.2% of men and 69.2% of women. Osteoporosis was identified in 56.2% of patients, reaching a serious degree in 11/64 (17.2%). No significant differences were observed in any evaluated parameter when patients were separated into those with normal versus pathological BMD. When patients with osteopenia and osteoporosis were compared, we observed that the former showed a lower exercise capacity (P=.023) and a higher BODE index (P=.002). CONCLUSIONS: The prevalence of a low BMD level was increased among male patients with a worse BODE index, especially due to a reduced exercise capacity.

Lung transplantation for bronchiolitis obliterans after allogenic bone marrow transplantation.

INTRODUCTION: Bronchiolitis obliterans (BO) occurring after allogeneic bone marrow transplant (ABMT) may be an expression of lung damage of multifactorial origins. At present, it is not a usual condition for lung transplant (LT), accounting for <1% of all indications in the international registry. We sought, to describe the clinical features and outcomes of patients undergoing LT for BO after ABMT in our group. PATIENTS AND METHODS: We undertook a cross-sectional study of patients with an indication for LT due to BO after ABMT from the beginning of our program. We recorded the type of transplant, patient age, clinical course, functional outcome, and survival. RESULTS: Among 313 LT, 13 cases (4.2%) were due to BO, including 3 after ABMT (0.96%). ABMT was indicated after bone marrow aplasia in 2 cases and acute myeloid leukemia in the other patient. The patients were 2 men (both 35 years old) and 1 woman, aged 25 years. All subjects received double elective LT at 24, 20, and 9 years post ABMT. At the time of LT, all displayed severe obstructive ventilatory defects with a forced expiratory volume in 1 second (FEV1)<30% and partial respiratory insufficiency. The initial immunosuppression was cyclosporine, mycophenolate mofetil, and steroids in all cases. Two of the subjects required changes in the immunosuppressive regimen: 1 due to chronic graft rejection with subsequent functional recovery and the other due to hematologic and neurologic toxicity. After 96, 37, and 9 months, all the patients were alive with baseline dyspnea of functional class 0 and a FEV1 of about 68%. CONCLUSION: LT is an effective therapy in terms of lung function and survival for patients with respiratory failure secondary to the development of BO after ABMT.

Bone mineral density in lung transplant candidates.

INTRODUCTION: The loss of bone mineral density (BMD) affects more than half of the patients on the waiting list for lung transplantation (LT), increasing their disease burden. OBJECTIVE: To describe the prevalence of BMD loss among patients evaluated as candidates for LT. PATIENTS AND METHODS: We included all hospitalized patients evaluated as LT candidates over the last 3 years, excluding pediatric subjects under 17 years of age. We estimated BMD in the femoral neck and lumbar spine. Categorization used the World Health Organization criteria. RESULTS: Among 156 patients, 64 (41%) had chronic obstructive pulmonary disease (COPD) with only 2 (3.1%) having densitometry before referral; 55 (35.3%), interstitial lung disease (ILD) with 9 (16.4%) BMD values; and 21 (13.5%) cystic fibrosis (CF) with only 3 (14.3%) with BMD screening. The 116 patients (74.4%) who had BMD below normal values included 84.4% of COPD, 67.3% of the ILD, and 81% of the CF patients. The detection of these patients allowed us to initiate preventive treatment depending on the degree of risk of bone fracture. Half of the patients evaluated were eventually included on the LT waiting list, with 70% of them finally receiving a transplant. CONCLUSIONS: Bone mineral loss was highly prevalent among this population but its investigation before referral for LT was scarce. Its identification allows primary or secondary prophylaxis to be started, seeking to reduce the risk of bone fracture after transplantation.

[Invasive mechanical ventilation in cystic fibrosis: Influence in lung transplant]. / Ventilación mecánica invasiva en fibrosis quística: influencia en el trasplante pulmonar.

INTRODUCTION: Invasive mechanical ventilation (IMV) in patients with advanced cystic fibrosis (CF) is a relative contraindication for lung transplant (LT) in adults, although there is currently no data on children. PATIENTS AND METHODS: An 8-year retrospective study on 21 children with CF who underwent LT was performed, analysing their results as they were receiving (n = 8) or not (n = 13) IMV pretransplant. Demographic and surgical data, postoperative course, lung function and survival (immediate and 1-year) were compared between both groups. The role of the IMV pretransplant as a postoperative risk factor was estimated (odds ratio) and Kaplan Meier survival study was performed in both groups. RESULTS: No differences in patient age, sex and nutritional parameters were observed between both groups. Those on IMV who received LT required more frequent and longer bypass, more need for tracheotomy, a higher number of rejection episodes per patient and multiorgan failure, longer PICU stay and longer time on IMV than those who were not on IMV when LT was received. Nevertheless, no differences could be found regarding graft function and immediate and 1-year survivals (62.5% vs. 92.3% with and without IMV respectively). On the other hand, long-term survival was significantly lower than in patients on IMV. CONCLUSIONS: In our experience, children with CF on IMV who receive LT have more complicated surgery and immediate postoperative course. Though immediate and 1-year results and survivals may be encouraging, medium and long-term ones are significantly lower.

[A lung transplant in a woman with bronchiolitis obliterans following an allogenic bone marrow transplant]. / Trasplante pulmonar por bronquiolitis obliterante tras trasplante alogénico de médula ósea.

Graft-versus-host disease is a major complication for bone marrow transplant recipients and is often a cause of late mortality. It can affect any tissue, and involvement of the lungs--target organs of particular importance--can lead to chronic respiratory failure due to bronchiolitis obliterans. We report the case of a lung transplant in a woman who developed bronchiolitis obliterans after receiving a marrow transplant to treat bone marrow aplasia. Three years later, clinical course was satisfactory, with full functional recovery.

[Prevalence of malnutrition among candidates for lung transplantation]. / Prevalencia de desnutrición en enfermos candidatos a trasplante pulmonar.

OBJECTIVES: To analyse the prevalence of malnutrition in candidates for lung transplantation and to establish if there are any differences in the prevalence of malnutrition among the different groups of patients regarding their illness. METHODS: We reviewed the nutritional evaluation of 163 consecutive transplant candidates referred to our hospital (1996-2001). The nutritional assessment included: clinical history, anthropometric measurements, bioelectrical impedance analysis, and biochemical measurements. The nutritional status diagnosis was determined following RWS Chang protocol. RESULTS: 163 patients (108 male/55 female; 42.9 +/- 14.7 yr.) agrupped into four main lung diseases groups: obstructive (chronic obstructive pulmonary disease): 60 (36.8%); interstitial (idiopathic pulmonary fibrosis): 45 (27.6%); septic (cystic fibrosis and bronchiectasis): 47 (28.8%); and vascular (primary pulmonary hypertension and miscellaneous etiology): 11 (6.7%). The prevalence of malnutrition is 60.9% (IC 95%; 53.4-68.4) and the most prevalent type is moderate caloric malnutrition (23.3%). Percentage of triceps skinfold thickness was lower in the septic group (65.1 +/- 43.0) than in the obstructive (94.8 +/- 53.9; p < 0.05) or in the interstitial one (130.3 +/- 61.5; p < 0.0001). Interstitial group had also the higher weight, BMI and percentage of ideal weight. Percentage of arm muscle circumference was only different between interstitial and septic groups (105.5 +/- 18.3 vs 95.9 +/- 11.1; p < 0.01). Resting energy expenditure was lower in septic patients. This group had lower levels of prealbumin than obstructive (17.6 +/- 4.7 vs 24.4 +/- 4.8 mg/dl; p < 0.0001) or interstitial groups (17.6 +/- 4.7 vs 27.3 +/- 7.7 mg/dl; p < 0.0001). CONCLUSIONS: Malnutrition in patients awaiting lung transplantation is highly prevalent, specially in septic and vascular lung diseases. Anthropometric measurements are a good and easy option to explore this problem. Nutritional rehabilitation of these patients could improve their postoperative course.

[Sequential double lung transplant in Kartagener's syndrome]. / Trasplante bipulmonar secuencial en el síndrome de Kartagener.

Very few cases of lung transplantation have been described for patients with Kartagener's syndrome. We report the first case to be published in Spain. A 15-year-old girl with complete Kartagener's syndrome underwent sequential transplantation of both lungs. Due to the unusual distribution of the organs in this syndrome, the bronchial stumps of donor and recipient had to be distributed differently. With the initial technical difficulties overcome, the patient now leads a normal life two years after transplantation.

[The first national program of pediatric lung transplantation: the experience in pediatric intensive care]. / Primer programa nacional de trasplante pulmonar infantil: experiencia en cuidados intensivos pediátricos.

OBJECTIVE: The aim of this study was to analyze the postoperative progress and medical management in the Pediatric Intensive Care Unit (PICU) of patients that underwent bilateral lung transplant. PATIENTS AND METHODS: From April 1997 to June 1998, 10 pediatric lung transplants were performed at the Hospital Reina Sofía (Córdoba, Spain). There were 4 males and 6 females (mean age 11.5 years, range 5 to 15 years). Indications for transplantation were cystic fibrosis (n = 9) and one pulmonary fibrosis secondary to viral infection. Before the transplant, two patients required mechanical ventilation for acute respiratory decompensation and one patient was ventilator-dependent. Immunosuppression consisted of corticosteroids, azathioprine and cyclosporine or tacrolimus. Post-transplantation management included early extubation, when possible, optimal fluid balance to prevent lung edema, low aggressive mechanical ventilation and adequate treatment of complications, such as rejection and infection. RESULTS: There were no peri-operative mortalities. The mean stay in the PICU was 28 days (median: 17 days) and the mean time on mechanical ventilation was 19 days (median: 5.5 days). The most frequent complications were rejection (n = 8), hyperglycemia (n = 6), renal failure (n = 4), arterial hypertension (n = 4) and respiratory infections (n = 3). There were no airway complications. CONCLUSIONS: Even if the post-operative period in pediatric lung transplant patients is difficult, the results have been good with an important improvement in the quality of life of these patients has been achieved.