Effects of bilateral lung transplantation on cardiac autonomic modulation and cardiorespiratory coupling: a prospective study.

BACKGROUND: Although cardiac autonomic modulation has been studied in several respiratory diseases, the evidence is limited on lung transplantation, particularly on its acute and chronic effects. Thus, we aimed to evaluate cardiac autonomic modulation before and after bilateral lung transplantation (BLT) through a prospective study on patients enrolled while awaiting transplant. METHODS: Twenty-two patients on the waiting list for lung transplantation (11 women, age 33 [24-51] years) were enrolled in a prospective study at Ospedale Maggiore Policlinico Hospital in Milan, Italy. To evaluate cardiac autonomic modulation, ten minutes ECG and respiration were recorded at different time points before (T0) and 15 days (T1) and 6 months (T2) after bilateral lung transplantation. As to the analysis of cardiac autonomic modulation, heart rate variability (HRV) was assessed using spectral and symbolic analysis. Entropy-derived measures were used to evaluate complexity of cardiac autonomic modulation. Comparisons of autonomic indices at different time points were performed. RESULTS: BLT reduced HRV total power, HRV complexity and vagal modulation, while it increased sympathetic modulation in the acute phase (T1) compared to baseline (T0). The HRV alterations remained stable after 6 months (T2). CONCLUSION: BLT reduced global variability and complexity of cardiac autonomic modulation in acute phases, and these alterations remain stable after 6 months from surgery. After BLT, a sympathetic predominance and a vagal withdrawal could be a characteristic autonomic pattern in this population.

Bone involvement in young adults with cystic fibrosis awaiting lung transplantation for end-stage respiratory failure.

Patients with cystic fibrosis awaiting lung transplantation for end-stage respiratory failure have high prevalence of reduced bone mineral density and fragility fracture. Suboptimal 25-hydroxyvitamin D levels could significantly contribute to the development of cystic fibrosis-related bone disease. INTRODUCTION: The assessment of the prevalence of cystic fibrosis-related bone disease (CFBD) and its associated risk factors in young adults with cystic fibrosis (CF) awaiting lung transplantation for end-stage respiratory failure. METHODS: Clinical characteristics, bone mineral density (BMD), the parameters of calcium metabolism, including vitamin D (25OHVitD) levels, and the presence of fragility fractures were evaluated in 42 CF patients (24 females, age 34.0 ± 8.4 years) consecutively referred as lung transplant candidates. RESULTS: Mean 25OHVitD levels (54.9 ± 26.2 nmol/L) were below the reference range and hypovitaminosis D (25OHVitD < 75 nmol/L) was found in 34 patients (81%) and daily calcium intakes (median 550 mg/day) were lower than recommended. A BMD below the expected range for age (Z-score of - 2.0 or lower) and at least one prevalent fragility fracture were found in 22 patients (52.4%) and 18 patients (45.2%), respectively. The coexistence of low BMD and the presence of fracture was observed in 13 patients (31.0%). In these patients, the prevalence of nephrolithiasis was higher than in the remaining ones (p = 0.046). The presence of kidney stones was associated with a worse bone status and with severe vitamin D deficiency. In the whole sample, femoral BMD Z-scores were directly correlated with albumin-adjusted calcium (p < 0.05) and 25OHVitD levels (p < 0.01). CONCLUSIONS: Despite the improvement of CF care, CFBD is still highly prevalent in young adults awaiting lung transplantation for end-stage CF. Suboptimal 25OHVitD levels could significantly contribute to the development of CFBD. The presence of nephrolithiasis could be an additional warning about the need for a careful evaluation of bone health in CF patients.

Effects of insulin therapy optimization with sensor augmented pumps on glycemic control and body composition in people with cystic fibrosis-related diabetes.

Objective: Cystic fibrosis (CF)-related diabetes (CFRD) resulting from partial-to-complete insulin deficiency occurs in 40-50% of adults with CF. In people with CFRD, poor glycemic control leads to a catabolic state that may aggravate CF-induced nutritional impairment and loss of muscle mass. Sensor augmented pump (SAP) therapy may improve glycemic control as compared to multiple daily injection (MDI) therapy. Research design and methods: This non-randomized clinical trial was aimed at evaluating the effects of insulin therapy optimization with SAP therapy, combined with a structured educational program, on glycemic control and body composition in individuals with insulin-requiring CFRD. Of 46 participants who were offered to switch from MDI to SAP therapy, 20 accepted and 26 continued the MDI therapy. Baseline demographic and clinical characteristics were balanced between groups using a propensity score-based overlap weighting procedure and weighted mixed-effects regression models were used to estimate changes in study outcomes. Results: After 24 months changes in HbA1c were: -1.1% (-12.1 mmol/mol) (95% CI: -1.5; -0.8) and -0.1% (-1 mmol/mol) (95% CI: -0.5; 0.3) in the SAP and MDI therapy group, respectively, with a between-group difference of -1.0 (-10 mmol/mol) (-1.5; -0.5). SAP therapy was also associated with a decrease in mean glucose (between group difference: -32 mg/dL; 95% CI: -44; -20) and an increase in TIR (between group difference: 19.3%; 95% CI 13.9; 24.7) and in fat-free mass (between group difference: +5.5 Kg, 95% CI: 3.2; 7.8). Conclusion: Therapy optimization with SAP led to a significant improvement in glycemic control, which was associated with an increase in fat-free mass.

Epstein-Barr Virus-Related Post-Transplant Lymphoproliferative Disorders in Cystic Fibrosis Lung Transplant Recipients: A Case Series.

BACKGROUND: Solid organ transplantation is associated with a higher risk of Epstein-Barr virus (EBV)-related lymphoproliferative disease due to immunosuppressive regimen. Little evidence is currently available on post-transplant lymphoproliferative disorders (PTLDs) in the lung transplant (LuTx) setting, particularly in cystic fibrosis (CF) recipients. METHODS: We retrospectively analyzed all the cases of PTLDs that occurred in our LuTx center between January 2015 and December 2017. We reviewed clinical and radiologic data, donor and recipient EBV serostatus, immunosuppressive therapy, histologic data, and follow-up of these patients. RESULTS: A total of 77 LuTxs were performed at our center in the study period; 39 (50.6%) patients had CF; 4 developed EBV-related PTLDs. They were all young (17-26 years) CF patients with high serum EBV DNA load. Disease onset was within the first 3 months after LuTx. In 3 cases presentation was associated with fever and infection-like symptoms, whereas in 1 case radiologic suspicion arose unexpectedly from a CT scan performed for different clinical reasons. Diagnosis was reached through lung biopsy in all cases. All patients received rituximab, cyclophosphamide, doxorubicin hydrochloride (hydroxydaunomycin), vincristine sulfate (Oncovin), and prednisone with variable response and complications. CONCLUSION: In our experience, the early development of EBV-related PTLD was a highly aggressive, life-threatening condition, which exclusively affected young CF patients in the early post-transplant period. The rate of this complication was relatively high in our population. Diagnosis with lung biopsy is crucial in all suspected cases and regular monitoring of EBV DNA levels is of utmost importance given the high correlation with PTLDs in patients at increased risk.

Surveillance Transbronchial Biopsy Program to Evaluate Acute Rejection After Lung Transplantation: A Single Institution Experience.

BACKGROUND: There is no unanimity in the literature regarding the value of transbronchial biopsies (TBBs) performed at a scheduled time after lung transplantation (surveillance TBBs [SBs]), compared to biopsies performed for suspected clinical acute rejection (clinically indicated TBBs [CIBs]). This study exposes an assessment of our experience over the last 4 years through a retrospective analysis of the data collected. METHODS: In our center, SBs are performed at 3, 6, and 12 months after a transplant. Data from 110 patients who underwent a TBB were collected from January 2013 to November 2017. Clinical and functional data along with the histologic results and complications were collected. RESULTS: Overall 251 procedures were performed: 223 for surveillance purposes and 28 for clinical indications. The SBs diagnostic rate was 84%. A grade 2 acute rejection (AR) was detected in 9 asymptomatic patients, all of whom were medically treated, with downgrading of AR documented in all cases. The rate of medical intervention in the SB group was 8%. The CIBs diagnostic rate was 96%. The rate of AR detected by CIBs was significantly higher than by SBs (36% versus 4%; P < .0001). Overall the major complication rate was 4%; no patients required transfusions and no mortality occurred in the patient cohort. CONCLUSIONS: The surveillance protocol did not eliminate the necessity of CIBs, but in 8% of patients early rejection was histologically assessed. The correlation between histologic and clinical data allows a more careful approach to transplanted patients.

Lobar Lung Transplantation From Deceased Donor: Monocentric Experience.

INTRODUCTION: Lung transplantation is considered a therapeutic option in selected patients affected by end-stage pulmonary disease. The mortality on the waiting list is mainly attributed to the shortage of the donor pool available for transplantation. There are various strategies to overcome this shortage; one of them is lobar transplantation. METHODS: The aim of the current study was to analyze the outcome of lobar lung transplantation from deceased donors in our Lung Transplant Center. Overall survival, perioperative mortality and morbidity, problem on bronchial anastomosis, and chronic rejection were prospectively recorded in a 5-year time-frame. RESULTS: From November 2010 to October 2015, we performed 100 lung transplantations; 6 of which (6%) were lobar transplantations from deceased donors. Three recipients were on an emergency list due to preoperative extracorporeal support. The causes of lobectomy leading to lobar transplantation were: size mismatch (3), iatrogenic vascular damage (2), and chronic atelectasis (1). One patient died 5 months after surgery for sepsis; and 5 patients were alive at the study end (median follow-up: 17.5 months). Prevalence of grade 3 primary graft dysfunction at 72 hours was 50%. One patient developed bronchial stenosis. No cases of chronic rejection were recorded. CONCLUSIONS: Lobar transplantation can be considered a valid tool to overcome the donor pool shortage in selected cases; such a technique has proved particularly useful in critically ill patients who were scheduled in an emergency transplant program.

Lung Allocation Score: A Single-Center Simulation.

BACKGROUND: The lung allocation score (LAS) was introduced in the United States in May 2005 with the main goal of reducing the waiting list mortality of patients with end-stage lung diseases, but also to enhance the lung transplant benefit and improve the management of urgent candidates. Several papers have reported that LAS resulted in a reduction of the waiting list mortality but no significant survival benefit was noted. METHODS: We evaluate the usefulness of LAS as a predictor for lung transplantation outcome in 123 patients listed for lung transplantation in an Italian center. Primary endpoints were waiting list mortality and posttransplant mortality at 1 year; secondary endpoints included perioperative circulatory support, cardiopulmonary bypass, primary graft dysfunction, and long-term survival after transplantation. RESULTS: We observed the absence of correlation between LAS and waiting list mortality. The LAS did not affect the long-term survival in our population. CONCLUSIONS: High LAS was predictive of primary graft dysfunction of grade 3 in the first 72 hours after transplantation.