Guiding therapeutic plasma exchange for antibody-mediated rejection treatment in lung transplant recipients - a retrospective study.

Antibody-Mediated Rejection (AMR) due to donor-specific antibodies (DSA) is associated with poor outcomes after lung transplantation. Currently, there are no guidelines regarding the selection of treatment protocols. We studied how DSA characteristics including titers, C1q, and mean fluorescence intensity (MFI) values in undiluted and diluted sera may predict a response to therapeutic plasma exchange (TPE) and inform patient prognosis after treatment. Among 357 patients consecutively transplanted without detectable pre-existing DSAs between 01/01/16 and 12/31/18, 10 patients were treated with a standardized protocol of five TPE sessions with IVIG. Based on DSA characteristics after treatment, all patients were divided into three groups as responders, partial responders, and nonresponders. Kaplan-Meier Survival analyses showed a statistically significant difference in patient survival between those groups (P = 0.0104). Statistical analyses showed that MFI in pre-TPE 1:16 diluted sera was predictive of a response to standardized protocol (R2  = 0.9182) and patient survival (P = 0.0098). Patients predicted to be nonresponders who underwent treatment with a more aggressive protocol of eight TPE sessions with IVIG and bortezomib showed improvements in treatment response (P = 0.0074) and patient survival (P = 0.0253). Dilutions may guide clinicians as to which patients would be expected to respond to a standards protocol or require more aggressive treatment.

COVID-19 in lung transplant recipients.

Solid organ transplant recipients are considered at high risk for COVID-19 infection due to chronic immune suppression; little data currently exists on the manifestations and outcomes of COVID-19 infection in lung transplant recipients. Here we report 8 cases of COVID-19 identified in patients with a history of lung transplant. We describe the clinical course of disease as well as preexisting characteristics of these patients.

Non-pharmacological treatments for COPD.

Chronic obstructive pulmonary disease (COPD) affects roughly 10% of the global population and is growing in prevalence annually. COPD is characterized by progressive non-reversible narrowing of airways mainly due to cigarette smoking. Therapeutic interventions aimed at altering this progressive disease course can largely be grouped into pharmacological or non-pharmacological therapies. The focus of this paper is on the non-pharmacological aspects of COPD management, reviewing the current literature to provide an evidence-based management approach. Non-pharmacological therapies reviewed in this article include the implementation of comprehensive care models utilizing a coordinated multidisciplinary team, tele-monitoring and patient-centred approach to optimize COPD care and improve compliance. Preventing progression of COPD via smoking cessation remains of paramount importance, and newer therapeutic options including electronic cigarettes show promise in small studies as cessation aids. COPD has systemic manifestations that can be ameliorated with the enrollment in pulmonary rehabilitation programmes, which focus on exercise endurance to improve dyspnoea and quality of life. Advanced therapeutics for COPD includes lung volume reduction surgery for a pre-specified cohort and minimally invasive bronchoscopic valves that in recent reviews show promise. Lastly, patients on maximal COPD therapy with progressive disease can be referred for lung transplantation; however, this often requires a highly selected and motivated patient and care team. Survival rates for lung transplantation are improving; thus, this procedure remains a viable option as more expertise and experience are gained.

Venous thromboembolism in lung transplant recipients real world experience from a high volume center.

BACKGROUND: Venous thromboembolism (VTE) post lung transplantation is common and has been associated with worse post transplant survival. We report a comprehensive single center review of VTE incidence in the first post transplant year, investigate modifiable risk factors and assess impact on short term outcomes. METHODS: Retrospective review of all lung transplant recipients between August 2016 to 2018 at Temple University Hospital. Patients were followed for 1 year post transplant. All patients were screened for deep venous thrombosis (DVT) within the first 2 weeks with a venous duplex study. Pre transplant, intra operative, post operative variables, and peri-operative practice patterns were compared between VTE positive and VTE negative groups. Logistic regression modeling was used to identify risk factors for early VTE (VTE within 30 days after transplant). RESULTS: A total of 235 patients were included in the study, 58 patients (24.7%) developed a VTE in the first post transplant year. Median time to diagnosis was 17 days. Of the patients with VTE, 76% had an isolated DVT, 13.5 % had an isolated pulmonary embolism (PE), and 10.3% had concomitant DVT and PE. In a multivariate logistic regression model, cardiopulmonary bypass (CPB) (OR 1.93 p = 0.015) and interruption of VTE prophylaxis (OR 4.42 p < 0.0001) were predictive of early VTE. CONCLUSION: VTE post lung transplant is common despite the use of prophylactic anticoagulation. CPB use and interruption of DVT prophylaxis are risk factors for early post transplant VTE. Measures to ensure consistent and uninterrupted prophylaxis may help decrease VTE incidence after lung transplantation.

Features of COPD as Predictors of Lung Cancer.

BACKGROUND: Lung cancer is a leading cause of death and hospitalization for patients with COPD. A detailed understanding of which clinical features of COPD increase risk is needed. METHODS: We performed a nested case-control study of Genetic Epidemiology of COPD (COPDGene) Study subjects with and without lung cancer, age 45 to 80 years, who smoked at least 10-pack years to identify clinical and imaging features of smokers, with and without COPD, that are associated with an increased risk of lung cancer. The baseline evaluation included spirometry, high-resolution chest CT scanning, and respiratory questionnaires. New lung cancer diagnoses were identified over 8 years of longitudinal follow-up. Cases of lung cancer were matched 1:4 with control subjects for age, race, sex, and smoking history. Multiple logistic regression analyses were used to determine features predictive of lung cancer. RESULTS: Features associated with a future risk of lung cancer included decreased FEV1/FVC (OR, 1.28 per 10% decrease [95% CI, 1.12-1.46]), visual severity of emphysema (OR, 2.31, none-trace vs mild-advanced [95% CI, 1.41-3.86]), and respiratory exacerbations prior to study entry (OR, 1.39 per increased events [0, 1, and ≥ 2] [95% CI, 1.04-1.85]). Respiratory exacerbations were also associated with small-cell lung cancer histology (OR, 3.57 [95% CI, 1.47-10]). CONCLUSIONS: The degree of COPD severity, including airflow obstruction, visual emphysema, and respiratory exacerbations, was independently predictive of lung cancer. These risk factors should be further studied as inclusion and exclusion criteria for the survival benefit of lung cancer screening. Studies are needed to determine if reduction in respiratory exacerbations among smokers can reduce the risk of lung cancer.