A negative expiratory pressure test during wakefulness for evaluating the risk of obstructive sleep apnea in patients referred for sleep studies

OBJECTIVE: Obstructive sleep apnea is characterized by increased upper airway collapsibility during sleep. The present study investigated the use of the negative expiratory pressure test as a method to rule out obstructive sleep apnea. METHODS: Flow limitation was evaluated in 155 subjects. All subjects underwent a diurnal negative expiratory pressure test and a nocturnal sleep study. The severity of sleep apnea was determined based on the apneahypopnea index. Flow limitation was assessed by computing the exhaled volume at 0.2, 0.5, and 1.0 s (V0.2, V0.5, and V1.0, respectively) during the application of a negative expiratory pressure and expressed as a percentage of the previous exhaled volume. Receiver-operating characteristic curves were constructed to identify the optimal threshold volume at 0.2, 0.5, and 1.0 s for obstructive sleep apnea detection. RESULTS: Mean expiratory volumes at 0.2 and 0.5 s were statistically higher (p <0.01) in healthy subjects than in all obstructive sleep apneic groups. Increasing disease severity was associated with lower expiratory volumes. The V0.2 (%) predictive parameters for the detection of sleep apnea were sensitivity (81.1%), specificity (93.1%), PPV (98.1%), and NPV (52.9%). Sensitivity and NPV were 96.9% and 93.2%, respectively, for moderate-to-severe obstructive sleep apnea, and both were 100% for severe obstructive sleep apnea. CONCLUSION: Flow limitation measurement by V 0.2 (%) during wakefulness may be a very reliable method to identify obstructive sleep apnea when the test is positive and could reliably exclude moderate and severe obstructive sleep apnea when the test is negative. The negative expiratory pressure test appears to be a useful screening test for suspected obstructive sleep apnea

Rewiring innate and adaptive immunity with TLR9 agonist to treat osteosarcoma

Background Osteosarcoma (OS) is the most common primary bone tumor in children and adolescent. Surgery and multidrug chemotherapy are the standard of treatment achieving 60-70% of event-free survival for localized disease at diagnosis. However, for metastatic disease, the prognosis is dismal. Exploiting immune system activation in the setting of such unfavorable mesenchymal tumors represents a new therapeutic challenge. Methods In immune competent OS mouse models bearing two contralateral lesions, we tested the efficacy of intralesional administration of a TLR9 agonist against the treated and not treated contralateral lesion evaluating abscopal effect. Multiparametric flow cytometry was used to evaluate changes of the tumor immune microenviroment. Experiments in immune- deficient mice allowed the investigation of the role of adaptive T cells in TLR9 agonist effects, while T cell receptor sequencing was used to assess the expansion of specific T cell clones. Results TLR9 agonist strongly impaired the growth of locally-treated tumors and its therapeutic effect also extended to the contralateral, untreated lesion. Multiparametric flow cytometry showed conspicuous changes in the immune landscape of the OS immune microenvironment upon TLR9 engagement, involving a reduction in M2-like macrophages, paralleled by increased infiltration of dendritic cells and activated CD8 T cells in both lesions. Remarkably, CD8 T cells were needed for the induction of the abscopal effect, whereas they were not strictly necessary for halting the growth of the treated lesion. T cell receptor (TCR) sequencing of tumor infiltrating CD8 T cells showed the expansion of specific TCR clones in the treated tumors and, remarkably, their selected representation in the contralateral untreated lesions, providing the first evidence of the rewiring of tumor-associated T cell clonal architectures. Conclusions Overall these data indicate that the TLR9 agonist acts as an in situ anti-tumor vaccine, activating an innate immune response sufficient to suppress local tumor growth while inducing a systemic adaptive immunity with selective expansion of CD8 T cell clones, which are needed for the abscopal effect

Obstructive Sleep Apnea Is Associated with Liver Damage and Atherosclerosis in Patients with Non-Alcoholic Fatty Liver Disease

We assessed whether obstructive sleep apnea (OSA) and nocturnal hypoxemia are associated with severity of liver fibrosis and carotid atherosclerosis in patients with biopsy-proven NAFLD and low prevalence of morbid obesity. Secondary aim was to explore the association of OSA and hypoxemia with NASH and severity of liver pathological changes

Observational study on efficacy of negative expiratory pressure test proposed as screening for obstructive sleep apnea syndrome among commercial interstate bus drivers - protocol study

<p>Abstract</p> <p>Background</p> <p>Obstructive sleep apnea (OSA) is a respiratory disease characterized by the collapse of the extrathoracic airway and has important social implications related to accidents and cardiovascular risk. The main objective of the present study was to investigate whether the drop in expiratory flow and the volume expired in 0.2 s during the application of negative expiratory pressure (NEP) are associated with the presence and severity of OSA in a population of professional interstate bus drivers who travel medium and long distances.</p> <p>Methods/Design</p> <p>An observational, analytic study will be carried out involving adult male subjects of an interstate bus company. Those who agree to participate will undergo a detailed patient history, physical examination involving determination of blood pressure, anthropometric data, circumference measurements (hips, waist and neck), tonsils and Mallampati index. Moreover, specific questionnaires addressing sleep apnea and excessive daytime sleepiness will be administered. Data acquisition will be completely anonymous. Following the medical examination, the participants will perform a spirometry, NEP test and standard overnight polysomnography. The NEP test is performed through the administration of negative pressure at the mouth during expiration. This is a practical test performed while awake and requires little cooperation from the subject. In the absence of expiratory flow limitation, the increase in the pressure gradient between the alveoli and open upper airway caused by NEP results in an increase in expiratory flow.</p> <p>Discussion</p> <p>Despite the abundance of scientific evidence, OSA is still underdiagnosed in the general population. In addition, diagnostic procedures are expensive, and predictive criteria are still unsatisfactory. Because increased upper airway collapsibility is one of the main determinants of OSA, the response to the application of NEP could be a predictor of this disorder. With the enrollment of this study protocol, the expectation is to encounter predictive NEP values for different degrees of OSA in order to contribute toward an early diagnosis of this condition and reduce its impact and complications among commercial interstate bus drivers.</p> <p>Trial registration</p> <p><it>Registro Brasileiro de Ensaios Clinicos </it>(local acronym RBEC) [Internet]: Rio de Janeiro (RJ): <it>Instituto de Informaçao Cientifica e Tecnologica em Saude </it>(Brazil); 2010 - Identifier RBR-7dq5xx. Cross-sectional study on efficacy of negative expiratory pressure test proposed as screening for obstructive sleep apnea syndrome among commercial interstate bus drivers; 2011 May 31 [7 pages]. Available from <url>http://www.ensaiosclinicos.gov.br/rg/RBR-7dq5xx/</url>.</p

Role of different nocturnal monitorings in the evaluation of CPAP titration by autoCPAP devices

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