MELANIA DIRCE OLIVEIRA MARQUES
Projetos de Pesquisa
Unidades Organizacionais
Instituto do Coração, Hospital das Clínicas, Faculdade de Medicina - Médico
6 resultados
Resultados de Busca
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conferenceObject Simplified OSA Phenotyping of Respiratory Events for Predicting Oral Appliance Efficacy(2019) VENA, D.; AZARBARZIN, A.; EDWARDS, B. A.; RADMAND, R.; MARQUES, M.; TARANTO-MONTEMURRO, L. T.; CALIANESE, N.; WHITE, D.; LANDRY, S.; JOOSTEN, S. A.; HAMILTON, G.; THOMSON, L.; SANDS, S. A.; WELLMAN, D.- Loop gain in REM versus non-REM sleep using CPAP manipulation: A pilot study(2019) MESSINEO, Ludovico; TARANTO-MONTEMURRO, Luigi; AZARBARZIN, Ali; MARQUES, Melania; CALIANESE, Nicole; WHITE, David P.; WELLMAN, Andrew; SANDS, Scott A.
- Quantifying the magnitude of pharyngeal obstruction during sleep using airflow shape(2019) MANN, Dwayne L.; TERRILL, Philip I.; AZARBARZIN, Ali; MARIANI, Sara; FRANCIOSINI, Angelo; CAMASSA, Alessandra; GEORGESON, Thomas; MARQUES, Melania; TARANTO-MONTEMURRO, Luigi; MESSINEO, Ludovico; REDLINE, Susan; WELLMAN, Andrew; SANDS, Scott A.Rationale and objectives: Non-invasive quantification of the severity of pharyngeal airflow obstruction would enable recognition of obstructive versus central manifestation of sleep apnoea, and identification of symptomatic individuals with severe airflow obstruction despite a low apnoea-hypopnoea index (AHI). Here we provide a novel method that uses simple airflow-versus-time (""shape"") features from individual breaths on an overnight sleep study to automatically and non-invasively quantify the severity of airflow obstruction without oesophageal catheterisation. Methods: 41 individuals with suspected/diagnosed obstructive sleep apnoea (AHI range 0-91 events.h(-1)) underwent overnight polysomnography with gold-standard measures of airflow (oronasal pneumotach: ""flow"") and ventilatory drive (calibrated intraoesophageal diaphragm electromyogram: ""drive""). Obstruction severity was defined as a continuous variable (flow: drive ratio). Multivariable regression used airflow shape features (inspiratory/expiratory timing, flatness, scooping, fluttering) to estimate flow: drive ratio in 136264 breaths (performance based on leave-one-patient-out cross-validation). Analysis was repeated using simultaneous nasal pressure recordings in a subset (n=17). Results: Gold-standard obstruction severity (flow: drive ratio) varied widely across individuals independently of AHI. A multivariable model (25 features) estimated obstruction severity breath-by-breath (R-2=0.58 versus gold-standard, p<0.00001; mean absolute error 22%) and the median obstruction severity across individual patients (R-2=0.69, p<0.00001; error 10%). Similar performance was achieved using nasal pressure. Conclusions: The severity of pharyngeal obstruction can be quantified non-invasively using readily available airflow shape information. Our work overcomes a major hurdle necessary for the recognition and phenotyping of patients with obstructive sleep disordered breathing.
- The Combination of Atomoxetine and Oxybutynin Greatly Reduces Obstructive Sleep Apnea Severity A Randomized, Placebo-controlled, Double-Blind Crossover Trial(2019) TARANTO-MONTEMURRO, Luigi; MESSINEO, Ludovico; SANDS, Scott A.; AZARBARZIN, Ali; MARQUES, Melania; EDWARDS, Bradley A.; ECKERT, Danny J.; WHITE, David P.; WELLMAN, AndrewRationale: There is currently no effective pharmacological treatment for obstructive sleep apnea (OSA). Recent investigations indicate that drugs with noradrenergic and antimuscarinic effects improve genioglossus muscle activity and upper airway patency during sleep. Objectives: We aimed to determine the effects of the combination of a norepinephrine reuptake inhibitor (atomoxetine) and an antimuscarinic (oxybutynin) on OSA severity (apnea-hypopnea index [AHI]; primary outcome) and genioglossus responsiveness (secondary outcome) in people with OSA. Methods: A total of 20 people completed a randomized, placebo-controlled, double-blind, crossover trial comparing 1 night of 80 mg atomoxetine plus 5 mg oxybutynin (ato-oxy) to placebo administered before sleep. The AHI and genioglossus muscle responsiveness to negative esophageal pressure swings were measured via in-laboratory polysomnography. In a subgroup of nine patients, the AHI was also measured when the drugs were administered separately. Measurements and Main Results: The participants' median (interquartile range) age was 53 (46-58) years and body mass index was 34.8 (30.0-40.2) kg/m(2). ato-oxy lowered AHI by 63% (34-86%), from 28.5 (10.9-51.6) events/h to 7.5 (2.4-18.6) events/h (P < 0.001). Of the 15/20 patients with OSA on placebo (AHI > 10 events/hr), AHI was lowered by 74% (62-88%) (P < 0.001) and all 15 patients exhibited a >= 50% reduction. Genioglossus responsiveness increased approximately threefold, from 2.2 (1.1-4.7)%/cm H2O on placebo to 6.3 (3.0 to 18.3)%/cm H2O on ato-oxy (P < 0.001). Neither atomoxetine nor oxybutynin reduced the AHI when administered separately. Conclusions: A combination of noradrenergic and antimuscarinic agents administered orally before bedtime on 1 night greatly reduced OSA severity. These findings open new possibilities for the pharmacologic treatment of OSA.
- Structure and severity of pharyngeal obstruction determine oral appliance efficacy in sleep apnoea(2019) MARQUES, Melania; GENTA, Pedro R.; AZARBARZIN, Ali; TARANTO-MONTEMURRO, Luigi; MESSINEO, Ludovico; HESS, Lauren B.; DEMKO, Gail; WHITE, David P.; SANDS, Scott A.; WELLMAN, AndrewKey points Some patients with obstructive sleep apnoea (OSA) respond well to oral appliance therapy, whereas others do not for reasons that are unclear. In the present study, we used gold-standard measurements to demonstrate that patients with a posteriorly-located tongue (natural sleep endoscopy) exhibit a preferential improvement in collapsibility (lowered critical closing pressure) with oral appliances. We also show that patients with both posteriorly-located tongue and less severe collapsibility (predicted responder phenotype) exhibit greater improvements in severity of obstructive sleep apnoea (i.e. reduction in event frequency by 83%, in contrast to 48% in predicted non-responders). The present study suggests that the structure and severity of pharyngeal obstruction determine the phenotype of sleep apnoea patients who benefit maximally from oral appliance efficacy. center dot center dot center dot center dot A major limitation to the administration of oral appliance therapy for obstructive sleep apnoea (OSA) is that therapeutic responses remain unpredictable. In the present study, we tested the hypotheses that oral appliance therapy (i) reduces pharyngeal collapsibility preferentially in patients with posteriorly-located tongue and (ii) is most efficacious (reduction in apnoea-hypopnea index; AHI) in patients with a posteriorly-located tongue and less-severe baseline pharyngeal collapsibility. Twenty-five OSA patients underwent upper airway endoscopy during natural sleep to assess tongue position (type I: vallecula entirely visible; type II: vallecula obscured; type III: vallecula and glottis obscured), as well as obstruction as a result of other pharyngeal structures (e.g. epiglottis). Additional sleep studies with and without oral appliance were performed to measure collapsibility (critical closing pressure; Pcrit) and assess treatment efficacy. Overall, oral appliance therapy reduced Pcrit by 3.9 +/- 2.4 cmH(2)O (mean +/- SD) and AHI by 69 +/- 19%. Therapy lowered Pcrit by an additional 2.7 +/- 0.9 cmH(2)O in patients with posteriorly-located tongue (types II and III) compared to those without (type I) (P < 0.008). Posteriorly-located tongue (p = 0.03) and lower collapsibility (p = 0.04) at baseline were significant determinants of (greater-than-average) treatment efficacy. Predicted responders (type II and III and Pcrit < 1 cmH(2)O) exhibited a greater reduction in the AHI (83 +/- 9 vs. 48 +/- 8% baseline, P < 0.001) and a lower treatment AHI (9 +/- 6 vs. 32 +/- 15 events h(-1), P < 0.001) than predicted non-responders. The site and severity of pharyngeal collapse combine to determine oral appliance efficacy. Specifically, patients with a posteriorly-located tongue plus less-severe collapsibility are the strongest candidates for oral appliance therapy.
conferenceObject Loop Gain in REM Versus Non-REM Sleep Using CPAP Manipulation(2019) MESSINEO, L.; MONTEMURRO, L. Taranto; AZARBARZIN, A.; MARQUES, M.; CALIANESE, N.; WHITE, D. P.; WELLMAN, D.; SANDS, S. A.