Proteasome Inhibitor Carfilzomib-Based Therapy for Antibody-Mediated Rejection of the Pulmonary Allograft: Use and Short-Term Findings.

We present this observational study of lung transplant recipients (LTR) treated with carfilzomib (CFZ)-based therapy for antibody-mediated rejection (AMR) of the lung. Patients were considered responders to CFZ if complement-1q (C1q)-fixing ability of their immunodominant (ID) donor-specific anti-human leukocyte antibody (DSA) was suppressed after treatment. Treatment consisted of CFZ plus plasma exchange and immunoglobulins. Fourteen LTRs underwent CFZ for 20 ID DSA AMR. Ten (71.4%) of LTRs responded to CFZ. DSA IgG mean fluorescence intensity (MFI) fell from 7664 (IQR 3230-11 874) to 1878 (653-7791) after therapy (p = 0.001) and to 1400 (850-8287) 2 weeks later (p = 0.001). DSA C1q MFI fell from 3596 (IQR 714-14 405) to <30 after therapy (p = 0.01) and <30 2 weeks later (p = 0.02). Forced expiratory volume in 1s ( FEV1 ) fell from mean 2.11 L pre-AMR to 1.92 L at AMR (p = 0.04). FEV1 was unchanged after CFZ (1.91 L) and subsequently rose to a maximum of 2.13 L (p = 0.01). Mean forced expiratory flow during mid forced vital capacity (25-75) (FEF25-75 ) fell from mean 2.5 L pre-AMR to 1.95 L at AMR (p = 0.01). FEF25-75 rose after CFZ to 2.54 L and reached a maximum of 2.91 L (p = 0.01). Responders had less chronic lung allograft dysfunction or progression versus nonresponders (25% vs. 83%, p = 0.04). No deaths occurred within 120 days and 7 patients died post CFZ therapy of allograft failure. Larger prospective interventional studies are needed to further describe the benefit of CFZ-based therapy for pulmonary AMR.

Long-Term Follow-up of a Randomized Controlled Trial Evaluating a Mobile Health Intervention for Self-Management in Lung Transplant Recipients.

Mobile health interventions may help transplant recipients follow their complex medical regimens. Pocket Personal Assistant for Tracking Health (Pocket PATH) is one such intervention tailored for lung transplant recipients. A randomized controlled trial showed Pocket PATH's superiority to usual care for promoting the self-management behaviors of adherence, self-monitoring and communication with clinicians during posttransplant year 1. Its long-term impact was unknown. In this study, we examined associations between Pocket PATH exposure during year 1 and longer term clinical outcomes-mortality and bronchiolitis obliterans syndrome (BOS)-among 182 recipients who survived the original trial. Cox regression assessed whether (a) original group assignment and (b) performance of self-management behaviors during year 1 predicted time to outcomes. Median follow-up was 5.7 years after transplant (range 4.2-7.2 years). Pocket PATH exposure had no direct effect on outcomes (p-values >0.05). Self-monitoring was associated with reduced mortality risk (hazard ratio [HR] 0.45; 95% confidence interval [CI] 0.22-0.91; p = 0.027), and reporting abnormal health indicators to clinicians was associated with reduced risks of mortality (HR 0.15; 95% CI 0.04-0.65; p = 0.011) and BOS (HR 0.27; 95% CI 0.08-0.86; p = 0.026), regardless of intervention group assignment. Although Pocket PATH did not have a direct impact on long-term outcomes, early improvements in self-management facilitated by Pocket PATH may be associated with long-term clinical benefit.

Pattern and Predictors of Hospital Readmission During the First Year After Lung Transplantation.

Hospital readmission after lung transplantation negatively affects quality of life and resource utilization. A secondary analysis of data collected prospectively was conducted to identify the pattern of (incidence, count, cumulative duration), reasons for and predictors of readmission for 201 lung transplant recipients (LTRs) assessed at 2, 6, and 12 mo after discharge. The majority of LTRs (83.6%) were readmitted, and 64.2% had multiple readmissions. The median cumulative readmission duration was 19 days. The main reasons for readmission were other than infection or rejection (55.5%), infection only (25.4%), rejection only (9.9%), and infection and rejection (0.7%). LTRs who required reintubation (odds ratio [OR] 1.92; p = 0.008) or were discharged to care facilities (OR 2.78; p = 0.008) were at higher risk for readmission, with a 95.7% cumulative incidence of readmission at 12 mo. Thirty-day readmission (40.8%) was not significantly predicted by baseline characteristics. Predictors of higher readmission count were lower capacity to engage in self-care (incidence rate ratio [IRR] 0.99; p = 0.03) and discharge to care facilities (IRR 1.45; p = 0.01). Predictors of longer cumulative readmission duration were older age (arithmetic mean ratio [AMR] 1.02; p = 0.009), return to the intensive care unit (AMR 2.00; p = 0.01) and lower capacity to engage in self-care (AMR 0.99; p = 0.03). Identifying LTRs at risk may assist in optimizing predischarge care, discharge planning and long-term follow-up.

A Randomized Controlled Trial of a Mobile Health Intervention to Promote Self-Management After Lung Transplantation.

Lung transplant recipients are encouraged to perform self-management behaviors, including (i) monitoring health indicators, (ii) adhering to their regimen, and (iii) reporting abnormal health indicators to the transplant coordinator, yet performance is suboptimal. When hospital discharge was imminent, this two-group trial randomized 201 recipients to use either the mobile health (mHealth) intervention (n = 99) or usual care (n = 102), to compare efficacy for promoting self-management behaviors (primary outcomes) and self-care agency, rehospitalization, and mortality (secondary outcomes) at home during the first year after transplantation. The mHealth intervention group performed self-monitoring (odds ratio [OR] 5.11, 95% confidence interval [CI] 2.95-8.87, p < 0.001), adhered to medical regimen (OR 1.64, 95% CI 1.01-2.66, p = 0.046), and reported abnormal health indicators (OR 8.9, 95% CI 3.60-21.99, p < 0.001) more frequently than the usual care group. However, the two groups did not differ in rehospitalization (OR 0.78, 95% CI 0.36-1.66, p = 0.51) or mortality (hazard ratio 1.71, 0.68-4.28, p = 0.25). The positive impact of the mHealth intervention on self-management behaviors suggests that the intervention holds promise and warrants further testing.