Characteristics and Outcomes Among Patients With Early Venous Thromboembolic Events After Lung Transplant.

BACKGROUND: Despite several previous studies reporting a high frequency of venous thromboembolism (VTE) after lung transplant (LT), few actionable risk factors have been identified. There are limited data regarding the practice patterns of anticoagulation use among patients with LT. METHODS: All adult patients with single or bilateral LT between 2012 and 2016 were included (n = 324; mean age, 56.3 ± 13.3 years; male, 61.1%). Demographic, clinical, and laboratory variables before and after LT were recorded. Follow-up data included survival up to 3 years post-transplant. Development of VTE during the first 30 days after LT was the primary outcome variable. RESULTS: The overall incidence of VTE during the first 30 days after LT was 29.9% (n = 97), among which the majority were upper extremity thromboses. Female sex, personal history of VTE, hospitalization at the time of transplant, and use of 3 or more central venous catheters during index hospitalization were independently associated with VTE. The use of anticoagulants was independently associated with a reduced risk of VTE. Despite increased morbidity, the development of VTE was not associated with worse post-transplant survival. CONCLUSIONS: A significant proportion of patients develop early VTE after LT. Limiting the number of central catheters to < 3 during the post-transplant period, along with the early institution of thromboprophylaxis, may lower the risk of VTE.

Respiratory syncytial virus activates epidermal growth factor receptor to suppress interferon regulatory factor 1-dependent interferon-lambda and antiviral defense in airway epithelium.

Respiratory syncytial virus (RSV) persists as a significant human pathogen that continues to contribute to morbidity and mortality. In children, RSV is the leading cause of lower respiratory tract infections, and in adults RSV causes pneumonia and contributes to exacerbations of chronic lung diseases. RSV induces airway epithelial inflammation by activation of the epidermal growth factor receptor (EGFR), a tyrosine kinase receptor. Recently, EGFR inhibition was shown to decrease RSV infection, but the mechanism(s) for this effect are not known. Interferon (IFN) signaling is critical for innate antiviral responses, and recent experiments have implicated IFN-λ (lambda), a type III IFN, as the most significant IFN for mucosal antiviral immune responses to RSV infection. However, a role for RSV-induced EGFR activation to suppress airway epithelial antiviral immunity has not been explored. Here, we show that RSV-induced EGFR activation suppresses IFN regulatory factor (IRF) 1-induced IFN-λ production and increased viral infection, and we implicate RSV F protein to mediate this effect. EGFR inhibition, during viral infection, augmented IRF1, IFN-λ, and decreased RSV titers. These results suggest a mechanism for EGFR inhibition to suppress RSV by activation of endogenous epithelial antiviral defenses, which may be a potential target for novel therapeutics.