MELANIA DIRCE OLIVEIRA MARQUES
Projetos de Pesquisa
Unidades Organizacionais
Instituto do Coração, Hospital das Clínicas, Faculdade de Medicina - Médico
5 resultados
Resultados de Busca
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- 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.
- Breath-holding as a means to estimate the loop gain contribution to obstructive sleep apnoea(2018) MESSINEO, Ludovico; TARANTO-MONTEMURRO, Luigi; AZARBARZIN, Ali; MARQUES, Melania D. Oliveira; CALIANESE, Nicole; WHITE, David P.; WELLMAN, Andrew; SANDS, Scott A.Increased ""loop gain"" of the ventilatory control system promotes obstructive sleep apnoea (OSA) in some patients and offers an avenue for more personalized treatment, yet diagnostic tools for directly measuring loop gain in the clinical setting are lacking. Here we test the hypothesis that elevated loop gain during sleep can be recognized using voluntary breath-hold manoeuvres during wakefulness. Twenty individuals (10 OSA, 10 controls) participated in a single overnight study with voluntary breath-holding manoeuvres performed during wakefulness. We assessed (1) maximal breath-hold duration, and (2) the ventilatory response to 20 s breath-holds. For comparison, gold standard loop gain values were obtained during non-rapid eye movement (non-REM) sleep using the ventilatory response to 20 s pulses of hypoxic-hypercapnic gas (6% CO2-14% O-2, mimicking apnoea). Continuous positive airway pressure (CPAP) was used to maintain airway patency during sleep. Additional measurements included gold standard loop gain measurement during wakefulness and steady-state loop gain measurement during sleep using CPAP dial-ups. Higher loop gain during sleep was associated with (1) a shorter maximal breath-hold duration (r(2) = 0.49, P < 0.001), and (2) a larger ventilatory response to 20 s breath-holds during wakefulness (second breath; r(2) = 0.50, P < 0.001); together these factors combine to predict high loop gain (receiver operating characteristic area-under-curve: 92%). Gold standard loop gain values were remarkably similar during wake and non-REM sleep. The results show that elevated loop gain during sleep can be identified using simple breath-holding manoeuvres performed during wakefulness. This may have implications for personalizing OSA treatment.
- Stable Breathing in Patients With Obstructive Sleep Apnea Is Associated With Increased Effort but Not Lowered Metabolic Rate(2017) MELO, Camila M. de; TARANTO-MONTEMURRO, Luigi; BUTLER, James P.; WHITE, David P.; LORING, Stephen H.; AZARBARZIN, Ali; MARQUES, Melania; BERGER, Philip J.; WELLMAN, Andrew; SANDS, Scott A.Study objectives: In principle, if metabolic rate were to fall during sleep in a patient with obstructive sleep apnea (OSA), ventilatory requirements could be met without increased respiratory effort thereby favoring stable breathing. Indeed, most patients achieve periods of stable flow-limited breathing without respiratory events for periods during the night for reasons that are unclear. Thus, we tested the hypothesis that in patients with OSA, periods of stable breathing occur when metabolic rate (VO2) declines. Methods: Twelve OSA patients (apnea-hypopnea index > 15 events/h) completed overnight polysomnography including measurements of VO2 (using ventilation and intranasal PO2) and respiratory effort (esophageal pressure). Results: Contrary to our hypothesis, VO2 did not differ between stable and unstable breathing periods in non-REM stage 2 (208 +/- 20 vs. 213 +/- 18 mL/min), despite elevated respiratory effort during stable breathing (26 +/- 2 versus 23 +/- 2 cmH(2)O, p =.03). However, VO2 was lowered during deeper sleep (244 to 179 mL/min from non-REM stages 1 to 3, p =.04) in conjunction with more stable breathing. Further analysis revealed that airflow obstruction curtailed metabolism in both stable and unstable periods, since CPAP increased VO 2 by 14% in both cases (p =.02,.03, respectively). Patients whose VO2 fell most during sleep avoided an increase in PCO2 and respiratory effort. Conclusions: OSA patients typically convert from unstable to stable breathing without lowering metabolic rate. During sleep, OSA patients labor with increased respiratory effort but fail to satisfy metabolic demand even in the absence of overt respiratory events.
- Palatal prolapse as a signature of expiratory flow limitation and inspiratory palatal collapse in patients with obstructive sleep apnoea(2018) AZARBARZIN, Ali; SANDS, Scott A.; MARQUES, Melania; GENTA, Pedro R.; TARANTO-MONTEMURRO, Luigi; MESSINEO, Ludovico; WHITE, David P.; WELLMAN, AndrewIn some individuals with obstructive sleep apnoea (OSA), the palate prolapses into the velopharynx during expiration, limiting airflow through the nose or shunting it out of the mouth. We hypothesised that this phenomenon causes expiratory flow limitation (EFL) and is associated with inspiratory '' isolated '' palatal collapse. We also wanted to provide a robust noninvasive means to identify this mechanism of obstruction. Using natural sleep endoscopy, 1211 breaths from 22 OSA patients were scored as having or not having palatal prolapse. The patient-level site of collapse (tongue-related, isolated palate, pharyngeal lateral walls and epiglottis) was also characterised. EFL was quantified using expiratory resistance at maximal epiglottic pressure. A noninvasive EFL index (EFLI) was developed to detect the presence of palatal prolapse and EFL using the flow signal alone. In addition, the validity of using nasal pressure was assessed. A cut-off value of EFLI >0.8 detected the presence of palatal prolapse and EFL with an accuracy of >95% and 82%, respectively. The proportion of breaths with palatal prolapse predicted isolated inspiratory palatal collapse with 90% accuracy. This study demonstrates that expiratory palatal prolapse can be quantified noninvasively, is associated with EFL and predicts the presence of inspiratory isolated palatal collapse.
- 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.