BSTP Review of 12 Case Studies Discussing the Challenges, Pathology, Immunogenicity, and Mechanisms of Inhaled Biologics.

The inhalation route is a relatively novel drug delivery route for biotherapeutics and, as a result, there is a paucity of published data and experience within the toxicology/pathology community. In recent years, findings arising in toxicology studies with inhaled biologics have provoked concern and regulatory challenges due, in part, to the lack of understanding of the expected pathology, mechanisms, and adversity induced by this mode of delivery. In this manuscript, the authors describe 12 case studies, comprising 18 toxicology studies, using a range of inhaled biotherapeutics (monoclonal antibodies, fragment antigen-binding antibodies, domain antibodies, therapeutic proteins/peptides, and an oligonucleotide) in rodents, nonhuman primates (NHPs), and the rabbit in subacute (1 week) to chronic (26 weeks) toxicology studies.

Inhaled Molgramostim Therapy in Autoimmune Pulmonary Alveolar Proteinosis.

Background: Autoimmune pulmonary alveolar proteinosis (aPAP) is a rare disease characterized by progressive surfactant accumulation and hypoxemia. It is caused by disruption of granulocyte-macrophage colony-stimulating factor (GM-CSF) signaling, which pulmonary alveolar macrophages require to clear surfactant. Recently, inhaled GM-CSF was shown to improve the partial pressure of arterial oxygen in patients with aPAP.

Analytical validation of a flow cytometric protocol for quantification of platelet microparticles in dogs.

Background: Platelet microparticles (PMPs) are subcellular procoagulant vesicles released upon platelet activation. In people with clinical diseases, alterations in PMP concentrations have been extensively investigated, but few canine studies exist.

Objectives: This study aims to validate a canine flow cytometric protocol for PMP quantification and to assess the influence of calcium on PMP concentrations.

The influence of inflammation and hematocrit on clot strength in canine thromboelastographic hypercoagulability.

Objective: To investigate parameters causing canine thromboelastographic hypercoagulability and to investigate whether thromboelastography (TEG) with Cytochalasin D (Cyt D) added is related to parameters of platelet activity.

Design: Prospective observational study on hemostatic and inflammatory parameters. Data were collected between November 2012 and July 2013.

Effect of probiotics on vaginal health in pregnancy. EFFPRO, a randomized controlled trial.

Background: Preterm delivery is a leading cause of neonatal morbidity and death. It often results from chorioamnionitis, which is a complication of bacterial vaginosis. Probiotics are effective in the treatment of bacterial vaginosis in women who were not pregnant; studies in pregnant woman are missing.