In-home evaluation of efficacy and titration of a mandibular advancement device for obstructive sleep apnea

There is increasing evidence that mandibular advancement devices (MADs) can be an effective treatment for some patients with obstructive sleep apnea, a highly prevalent chronic disease. In this study, the objectives were to objectively assess the effectiveness of MAD therapy using a limited channel recorder, and to develop a model for identifying patients who may be appropriate for MAD therapy as the initial treatment option. Thirty patients were prospectively recruited and studied at two independent dentist offices and the participants’ homes. Subjects wore the ARES Unicorder for two nights before insertion of the MAD, and again when the dentist determined that the patient had reached the titration endpoint. Self-reported measures of depression, sleepiness, and quality of life were obtained pre- and posttreatment. The reviewer was blinded to the study status while the physiological signals were being visually inspected. Significant reductions in the apnea/hypopnea index (AHI), hypoxemia measures, and snoring level were observed posttreatment. Twenty-seven of the 30 (90%) patients had a posttreatment AHI (using a 4% desaturation for hypopneas) below a clinical cut-off of 10. All but one patient (97%) exhibited at least a 50% decrease in AHI or had a posttreatment AHI ≤ 10. Significant differences in body mass index, weight, and neck circumference in patients with posttreatment AHIs above and below a clinical cut-off of five were identified. The linear regression used to predict the posttreatment AHI using pretreatment data resulted in an R2 of 0.68. The model correctly predicted two patients who were unable to obtain a posttreatment AHI of 10 or less. This study was designed to demonstrate two models of collaboration between a dental sleep medicine specialist and a sleep medicine physician in the monitoring of a patient treated with a MAD. The outcome data suggest that the limited channel recording system can be used as an alternative to laboratory polysomnography to reduce the cost of MAD treatment, and to improve the quality and consistency of posttreatment patient care

Induction of Eosinophil Apoptosis by the Cyclin-Dependent Kinase Inhibitor AT7519 Promotes the Resolution of Eosinophil-Dominant Allergic Inflammation

Eosinophils not only defend the body against parasitic infection but are also involved in pathological inflammatory allergic diseases such as asthma, allergic rhinitis and contact dermatitis. Clearance of apoptotic eosinophils by macrophages is a key process responsible for driving the resolution of eosinophilic inflammation and can be defective in allergic diseases. However, enhanced resolution of eosinophilic inflammation by deliberate induction of eosinophil apoptosis using pharmacological agents has not been previously demonstrated. Here we investigated the effect of a novel cyclin-dependent kinase inhibitor drug, AT7519, on human and mouse eosinophil apoptosis and examined whether it could enhance the resolution of a murine model of eosinophil-dominant inflammation in vivo.Eosinophils from blood of healthy donors were treated with AT7519 and apoptosis assessed morphologically and by flow-cytometric detection of annexin-V/propidium iodide staining. AT7519 induced eosinophil apoptosis in a concentration dependent manner. Therapeutic administration of AT7519 in eosinophil-dominant allergic inflammation was investigated using an established ovalbumin-sensitised mouse model of allergic pleurisy. Following ovalbumin challenge AT7519 was administered systemically at the peak of pleural inflammation and inflammatory cell infiltrate, apoptosis and evidence of macrophage phagocytosis of apoptotic eosinophils assessed at appropriate time points. Administration of AT7519 dramatically enhanced the resolution of allergic pleurisy via direct induction of eosinophil apoptosis without detriment to macrophage clearance of these cells. This enhanced resolution of inflammation was shown to be caspase-dependent as the effects of AT7519 were reduced by treatment with a broad spectrum caspase inhibitor (z-vad-fmk).Our data show that AT7519 induces human eosinophil apoptosis and enhances the resolution of a murine model of allergic pleurisy by inducing caspase-dependent eosinophil apoptosis and enhancing macrophage ingestion of apoptotic eosinophils. These findings demonstrate the utility of cyclin-dependent kinase inhibitors such as AT7519 as potential therapeutic agents for the treatment of eosinophil dominant allergic disorders