Outcome following single vs bilateral lung transplantation in recipients 60 years of age and older

AIMS: The significant shortage of donor organs in lung transplantation necessitates a careful selection of lung transplant recipients. The outcome of lung transplant recipients aged 60 years and older has not been analyzed systematically. METHODS: We retrospectively reviewed our experience with older recipients. Between January 1999 and July 2003, 248 patients underwent lung transplantation at our institution, of which 18 were aged 60 years and older (7.3%, range 60-66, mean 62 +/- 1.1). RESULTS: Eleven (61%) of the recipients 60 years and older received a single (SLTx) and seven (39%), a bilateral lung transplant. Donor age in the single transplant cohort was 30 +/- 4 years. It was 33 +/- 3 years in bilateral patients. Posttransplant ventilation time was significantly different among groups, with 282 +/- 32 hours after bilateral and 56 +/- 13 hours after transplant (P < .05). Also significantly longer was the length of the ICU stay in the bilateral group. First PaO2 in the ICU was not different among the two groups. The 1-year survival in the single transplant group was significantly better compared to the bilateral group with 73% versus 43%, respectively. CONCLUSIONS: The 1-year survival following lung transplantation in patients older than 60 years is markedly reduced compared to recipients under 60 years of age. If a lung transplant is considered in a recipient above the age of 60 years, a single transplant should be favoured. If that is not indicated, patients over 60 should be very carefully selected for bilateral transplant.     

Analysis of lung transplant recipients surviving beyond 5 years

INTRODUCTION: We started lung transplantation (LT) in October 1993 and review the status of recipients who have survived beyond 5 years. METHODS: A retrospective review of patients undergoing LT from October 1993 to October 1998 included pulmonary function data, incidence of bronchiolitis obliterans syndrome (BOS), functional status, and survival. RESULTS: Of 73 transplantations 41 (56%) patients have survived beyond 5 years (study group), including 23 men and 18 women of age 33.2 +/- 15.6 years. Indications for LT were as follows: cystic fibrosis (n = 16), emphysema (n = 13), pulmonary fibrosis (n = 8), and other (n = 4). Actuarial survival at 5, 7, and 9 years was 56%, 53%, and 43%, respectively. Freedom from BOS was 63%, 56%, and 50% at 5, 7, and 9 years, respectively. The median percent predicted FEV1 was 67%, 56%, and 56%, respectively. Also, 79% of recipients had no limitations in their daily activities; 65% were active and working. Only 5% of patients showed some degree of limitation at 5 years posttransplantation. When survivors beyond 5 years were compared with nonsurvivors beyond 5 years, differences were observed: nonsurvivors more frequently required bypass (P = .01), experienced longer postoperative intubation times (P = .01), and exhibited lower PaO2 at 12 months posttransplantation (P < .01). CONCLUSION: Our data show good survival rates among patients surviving beyond 5 years after LT, with a moderate incidence of BOS at 9 years posttransplantation. Despite the incidence of BOS, these patients have good pulmonary function and activity status.     

Successful transplant outcomes using pediatric en bloc kidneys into adult recipients

En bloc pediatric kidneys have been used in adult renal transplantation for over 30 years. Despite the duration of this experience, issues such as increased technical difficulties and associated complications, hyperfiltration injury, and ultimately a limited allograft half-life have limited the use of these organs at many centers. To date, however, the collected experience suggests that these organs may in fact be an excellent source of allografts for adult transplantation. The present paper was a retrospective review of the experience using en bloc kidneys for adult transplantation from two institutions. These results support the use of these kidneys. Actual patient and graft survival at 2 years was 97% and 94% respectively.     

Influence of panel-reactive antibodies on posttransplant outcomes in lung transplant recipients

BACKGROUND: Panel-reactive antibody (PRA) is used to estimate the degree of humoral sensitization in the recipient before transplantation. Although pretransplant sensitization is associated with increased complications in other solid organ transplant recipients, less is known about the outcome of sensitized lung transplant recipients. Therefore, we sought to determine the impact of elevated pretransplant PRA on clinical outcomes after lung transplantation. METHODS: The records of the first 200 lung transplant operations performed at Duke University Medical Center were reviewed. The outcomes of sensitized patients, PRA greater than 10% before transplantation (n = 18), were compared with the outcomes of nonsensitized patients. RESULTS: Sensitized patients experienced a significantly greater number of median ventilator days posttransplant (9 +/- 8) as compared with nonsensitized recipients (1 +/- 11; p = 0.0008). There were no significant differences between the number of episodes of acute rejection; however, there was a significantly increased incidence of bronchiolitis obliterans syndrome occurring in untreated sensitized recipients (56%) versus nonsensitized (23%; p = 0.044). In addition, there was a trend towards decreased survival in the sensitized recipients, with a 2-year survival of 58% in sensitized recipients as compared with 73% in the nonsensitized patients (p = 0.31). CONCLUSIONS: Sensitized lung transplant recipients experience more acute and chronic complications after transplantation. These patients probably warrant alternative management strategies.     

Long-term outcomes of sensitized lung transplant recipients after peri-operative desensitization

The Toronto Lung Transplant Program has been using a peri-operative desensitization regimen of plasma exchange, intravenous immune globulin, and antithymocyte globulin in order to accept donor-specific antibody (DSA)-positive lung transplants safely since 2008. There are no long-term data on the impact of this practice on allograft survival or the development of chronic lung allograft dysfunction (CLAD). We extended our prior study to include long-term follow-up of 340 patients who received lung transplants between January 1, 2008 and December 31, 2011. We compared allograft survival and CLAD-free survival among patients in three cohorts: DSA-positive, panel reactive antibody (PRA)-positive/DSA-negative, and unsensitized at the time of transplant. The median follow-up time in this extension study was 6.7 years. Among DSA-positive, PRA-positive/DSA-negative, and unsensitized patients, the median allograft survival was 8.4, 7.9, and 5.8 years, respectively (p = .5908), and the median CLAD-free survival was 6.8, 7.3, and 5.7 years, respectively (p = .5448). This follow-up study confirms that long-term allograft survival and CLAD-free survival of patients who undergo DSA-positive lung transplants with the use of our protocol do not differ from other lung transplant recipients. Use of protocols such as ours, therefore, may improve access to transplant for sensitized candidates.     

Postoperative outcomes of lung transplant recipients with preformed donor-specific antibodies

OBJECTIVESFew studies have evaluated the outcomes of lung transplantation (LTx) in recipients with preformed donor-specific antibodies (DSAs). This study investigated the postoperative changes in preformed DSAs based on prospectively collected data of DSAs, and the influences of preformed DSAs on postoperative outcomes among LTx recipients. Open in a separate windowMETHODSBetween July 2010 and December 2019, 216 recipients underwent LTx (81 living-donor lobar lung transplants and 135 deceased-donor lung transplants). We reviewed 8 cases with preformed DSAs to determine postoperative changes in DSAs and compared postoperative outcomes between recipients with and without DSAs.RESULTSThe preoperative mean fluorescence intensity of preformed DSAs ranged from 1141 to 14 695. Two recipients experienced antibody-mediated rejection within 2 weeks after LTx. DSAs disappeared in 7 recipients; however, 1 recipient experienced the relapse of DSAs and died from chronic lung allograft syndrome (CLAD), whereas 1 recipient had persisting DSAs within the study period and died from CLAD. Neither overall survival (OS) nor CLAD-free survival was significantly different between recipients with and without DSAs (P = 0.26 and P = 0.17, respectively). However, both OS and CLAD-free survival were significantly lower in recipients with DSAs against HLA class II than in those without these antibodies {5-year OS: 25.0% [95% confidence interval (CI): 0.9–66.5%] vs 72.1% (95% CI: 63.8–78.9%), P = 0.030 and 5-year CLAD-free survival: 26.7% (95% CI: 1.0–68.6%) vs 73.7% (95% CI: 66.5–79.5%), P = 0.002}.CONCLUSIONSPrognosis in recipients experiencing the relapse of preformed DSAs and those with persisting DSAs may be poor. The recipients with anti-HLA class II preformed DSAs had a significantly worse prognosis.     

Early outcomes of antireflux surgery for United States lung transplant recipients

Background

This study aimed to evaluate early outcomes after antireflux surgery for lung transplant (LTx) recipients in the United States.

Methods

Adult patients undergoing elective antireflux surgery between 2003 and 2008 were identified in the Nationwide Inpatient Sample. A propensity-matched analysis compared early outcomes between prior LTx recipients and well-matched control subjects consisting of non-LTx patients undergoing elective antireflux surgery during the same era. The primary outcome was inpatient mortality, and the secondary outcomes were hospital length of stay (LOS), perioperative complications, and hospital costs.

Results

During the study period, 401 LTx recipients underwent elective antireflux surgery. These patients were well matched with 401 control patients in terms of age, sex, individual and overall comorbidity burden, hospital teaching status, hospital location, hospital antireflux volume, and open versus laparoscopic approach. The overall operative mortality rate was 1.4 %, with no difference between the groups. The overall and individual morbidity rates also were similar. The LOS and hospital costs were significantly greater in the LTx group. Multivariable logistic regression analysis confirmed that prior LTx did not confer an increased risk of inpatient mortality after antireflux surgery.

Conclusions

To date, this is the largest study to examine outcomes of antireflux surgery for LTx recipients. Operative mortality and morbidity appear to be comparable with those of the general population, although resource utilization is greater. Based on these data, trials to evaluate the role of antireflux surgery in preserving allograft function after LTx should not be hindered by a perceived notion of prohibitive operative risk in this patient population.     

Pregnancy in lung transplant recipients

Eight female lung transplant recipients, all of whom became pregnant after transplant, were reported to the National Transplantation Pregnancy Registry from US transplant centers. Outcomes of the 8 pregnancies were 4 live births, 3 therapeutic abortions, and 1 spontaneous abortion. Three of the 4 newborns were premature, with low birth weight (< 2500 grams). Rejection during pregnancy occurred in 3 pregnancies (38%). All 8 transplant recipients reported at least 1 complication during pregnancy, including shortness of breath, rejection, and infection. Two of the 4 deliveries were by cesarean section. At follow-up, all children were developing well with no residual problems. Female lung transplant recipients may face higher risks during pregnancy than other solid organ transplant recipients.     

Tuberculosis in lung transplant recipients

BACKGROUND: Post-lung transplant infection is one of the leading causes of morbidity and mortality. The cause and incidence are similar in many series; however, infections such as Mycobacterium tuberculosis are influenced by the epidemiologic situation. The authors present a prospective and observational study to define the incidence, clinical presentation, and course of tuberculosis in a cohort of lung transplant patients at a single center in Spain. METHODS: Between 1990 and 2002, cutaneous delayed-type hypersensitivity testing and pathologic and microbiologic study of explanted lungs were conducted in 187 lung transplant patients. Serial bronchoscopies with transbronchial biopsy and bronchioalveolar lavage were performed during follow-up. The diagnosis of tuberculosis was established only when M. tuberculosis was identified in any sample or when histopathologic study was conclusive. RESULTS: Forty-eight patients were classified as anergic (25.6%) and 61 (32.6%) were classified as having a positive tuberculin skin test. Of the 109 patients, 95 received latent tuberculosis infection prophylaxis. Tuberculosis was diagnosed in 12 patients (6.41%); in six of them, diagnosis was determined from the explanted lungs. The remainder were diagnosed during follow-up. Fever and dyspnea were the most common symptoms. Chest radiographic findings presented an alveolar pattern. All patients responded well to antituberculous therapy; no deaths were attributable to tuberculosis. CONCLUSIONS: In the authors' experience, tuberculosis is not rare in lung transplant patients and can be managed successfully with antituberculous therapy without rifampin. A systematic protocol for diagnosing tuberculosis of the explanted lung is useful for reducing tuberculous complications of the implanted lung.     

Hypogammaglobulinemia in lung transplant recipients

BACKGROUND: Infectious complications continue to represent a significant source of morbidity and mortality in lung transplant recipients. Identifying specific, remediable immune defects is of potential value. After one lung transplant patient with recurrent infections was noted to be severely hypogammaglobulinemic, a screening program for humoral immune defects was instituted. The objectives were to define the prevalence of hypogammaglobulinemia in lung transplant recipients, assess levels of antibody to specific pathogens, and correlate infectious disease outcomes and survival with immunoglobulin levels. METHODS: All lung transplant recipients followed at a single center between October 1996 and June 1999 underwent a posttransplant humoral immune status survey as part of routine posttransplant follow-up. This survey consists of total immunoglobulin levels (IgG, IgM, IgA), IgG subclasses (IgG1-4), and antibody titers to Pneumococcus, diphtheria, and tetanus. Since February 1997, this survey has been incorporated into the pretransplant evaluation as well. Humoral survey results for October 1996 through July 1999 were recorded, and clinical information on major infectious disease outcomes was obtained from chart reviews, discharge summaries, the Cleveland Clinic Unified Transplant Database, and review of all microbiological studies and pathology results for each patient. RESULTS: Of 67 patients with humoral immune surveys drawn posttransplant, 47 (70%) had IgG levels less than 600 mg/dl (normal 717-1410 mg/dl), of which 25 (37%) had IgG levels less than 400 mg/dl ("lowest IgG group") and 22 (33%) had IgG levels between 400 and 600 mg/dl ("moderately low IgG group"). A total of 20 patients (30%) had IgG levels of more than 600 mg/dl ("normal IgG group"). Infections that were significantly more common in the lowest IgG group, and more common in the moderately low IgG group than the normal IgG group, included: number of pneumonias (P=0.0006), bacteremias (P=0.02), total bacterial infections (P=0.002), tissue-invasive cytomegalovirus (P=0.01), invasive aspergillosis (P=0.001), total fungal infections (P=0.001), and total infections (P=0.006). Median hospital days per posttransplant year was significantly different in the three groups (11.0 vs. 7.4 vs. 2.8 days, P=0.0003.) Invasive aspergillosis occurred in 44% of the lowest IgG group, 9% of the moderately low IgG group, and 0% of the normal IgG group (P<0.001). Survival was poorest in the lowest IgG group and intermediate in the moderately low IgG group. IgG subclass deficiencies occurred in a variety of patterns. Hypogammaglobulinemic patients lacked protective responses to Pneumococcus in 14/47 (30%), diphtheria in 15%, and tetanus in 19%. In a group of 48 patients screened pretransplant, 90% had normal immunoglobulin levels. CONCLUSIONS: Hypogammaglobulinemia in lung transplant recipients is more common than has been previously recognized. An IgG level of less than 400 mg/dl identifies a group at extremely high risk of bacterial and fungal infections, tissue-invasive cytomegalovirus, and poorer survival. Immunoglobulin monitoring may offer an opportunity for intensive surveillance, tapering of immunosuppression, and preemptive therapy for infection.     

Genotypes associated with tacrolimus pharmacokinetics impact clinical outcomes in lung transplant recipients

Most lung transplantation immunosuppression regimens include tacrolimus. Single nucleotide polymorphisms (SNPs) in genes important to tacrolimus bioavailability and clearance (ABCB1, CYP3A4, and CYP3A5) are associated with differences in tacrolimus pharmacokinetics. We hypothesized that polymorphisms in these genes would impact immunosuppression‐related outcomes. We categorized ABCB1, CYP3A4, and CYP3A5 SNPs for 321 lung allograft recipients. Genotype effects on time to therapeutic tacrolimus level, interactions with antifungal medications, concentration to dose (C₀/D), acute kidney injury, and rejection were assessed using linear models adjusted for subject characteristics and repeat measures. Compared with CYP3A poor metabolizers (PM), time to therapeutic tacrolimus trough was increased by 5.1 ± 1.6 days for CYP3A extensive metabolizers (EM, P < 0.001). In the post‐operative period, CYP3A intermediate metabolizers spent 1.2 ± 0.5 days less (P = 0.01) and EM spent 2.1 ± 0.5 days less (P < 0.001) in goal tacrolimus range than CYP3A PM. Azole antifungals interacted with CYP3A genotype in predicting C₀/D (P < 0.001). Increased acute kidney injury rates were observed in subjects with high ABCB1 function (OR 3.0, 95% CI 1.1‐8.6, P = 0.01). Lower rates of acute cellular rejection were observed in subjects with low ABCB1 function (OR 0.36, 95% CI 0.07‐0.94, P = 0.02). Recipient genotyping may help inform tacrolimus dosing decisions and risk of adverse clinical outcomes.     

Effect of early tracheostomy on clinical outcomes in critically ill lung transplant recipients

Objectives

The purpose of this study was to evaluate the effect of early tracheostomy in patients following lung transplantation and to determine its optimal timing and influence on clinical outcomes.

Methods

We retrospectively reviewed records of 96 adult patients who underwent lung transplantation at our institution between August 2008 and January 2016. Time-to-tracheostomy was defined based on timing of the procedure: “early” if less than 3 days or “late” if 3 or more days after lung transplantation.

Results

Forty-nine patients (51%) underwent tracheostomy 3.2?±?1.8 days after lung transplantation. Among these patients, 21 patients (42.9%) underwent early tracheostomy and 28 patients (57.1%) underwent late tracheostomy. Multivariable logistic regression analysis indicated that preoperative performance status was a significant predictor for tracheostomy (p?=?0.006, odds ratio 2.72). Patients in the early tracheostomy group began walking (p?=?0.003) and oral feeding (p?=?0.0006) earlier and had a shorter duration of mechanical ventilation (p?=?0.04) and shorter length of intensive care unit (p?=?0.01) and hospital stay (p?=?0.04) than patients in the late tracheostomy group. No significant differences in postoperative walking (p?=?0.06), oral feeding (p?=?0.17), or length of hospital stay (p?=?0.37) were observed between patients who underwent early tracheostomy and those who did not undergo tracheostomy.

Conclusions

Early tracheostomy following lung transplantation decreased both intensive care and hospital stay, due to improved postoperative recovery, even in patients with poor preoperative conditions. Furthermore, length of hospital stay in patients with early tracheostomy was similar to that of patients without tracheostomy after lung transplantation.

     

Anaesthetic management of bone marrow transplant recipients less than two years of age

The charts and anaesthetic records of 97 infants less than two years of age who underwent bone marrow transplantation at the University of Minnesota from 1978–1992 were retrospectively reviewed. These infants underwent 564 general anaesthetics. There were 48 perioperative complications, most (39) involving the airway. There were 20 difficult intubations occurring in 13 patients. The causes of the difficult intubations were anatomical abnormalities (12), mucositis (4), pharyngeal oedema (3) and emesis upon induction of anaesthesia (1). Four intraoperative deaths occurred. The deaths were caused by haemorrhage (2), pulmonary embolism (1) and myocardial ischaemia (1). Four patients died within 72 h of surgery; one from cerebral oedema following an intraoperative cardiac arrest, one from fungal septicaemia, one from haemorrhage and one from multiple organ failure following an intracerebral haematoma. Infants undergoing bone marrow transplantation are at high risk for perioperative morbidity and mortality, particularly from complications involving the airway, bleeding or sepsis.