Emerging therapies and respiratory infections: Focus on the impact of immunosuppressants and immunotherapies.

Host defences to infection are based upon an integrated system of physical and biochemical barriers, innate and adaptive immunity. Weakness in any of these defensive elements leads to increased susceptibility to specific pathogens. Understanding how medical therapies disrupt host defences is key to the successful prevention, diagnosis and management of respiratory infection in the immunocompromised host.

Variable Sequestration of Antifungals in an Extracorporeal Membrane Oxygenation Circuit.

Fungal infections are common and frequently associated with clinical failure in patients receiving extracorporeal membrane oxygenation (ECMO). Antifungal drugs have physicochemical characteristics associated with a higher likelihood of sequestration onto ECMO circuitry potentially leading to a subtherapeutic drug concentration. The percentage of sequestration of the antifungal drugs-caspofungin, posaconazole, and voriconazole-was determined using an ex vivo ECMO model. The circuits were primed with whole human blood, sodium chloride 0.9%, and human albumin solution. Serial 2 ml samples were taken at baseline, 0.5, 1, 2, 6, 12, and 24 hours after drug addition, paired with non-ECMO controls stored in a water bath at 37°C. Mean loss from the blood-primed ECMO circuits and controls at 24 hours relative to baseline were 80% and 61% for caspofungin ( p = ns), 64% and 11% for posaconazole ( p < 0.005), and 27% and 19% for voriconazole ( p < 0.05). Calculated AUC 0-24 showed a 44% for caspofungin ( p = ns), 30.6% posaconazole ( p < 0.005), and 9% loss for voriconazole ( p = 0.003) compared with the controls, suggesting therapeutic concentrations of these antifungal agents cannot be guaranteed with standard dosing in patients on ECMO. Posaconazole exhibited the greatest loss to the ECMO circuit correlating with both high lipophilicity and protein binding of the drug.

Reproductive health after thoracic transplantation: An ISHLT expert consensus statement.

Pregnancy after thoracic organ transplantation is feasible for select individuals but requires multidisciplinary subspecialty care. Key components for a successful pregnancy after lung or heart transplantation include preconception and contraceptive planning, thorough risk stratification, optimization of maternal comorbidities and fetal health through careful monitoring, and open communication with shared decision-making. The goal of this consensus statement is to summarize the current evidence and provide guidance surrounding preconception counseling, patient risk assessment, medical management, maternal and fetal outcomes, obstetric management, and pharmacologic considerations.