MELANIA DIRCE OLIVEIRA MARQUES
Projetos de Pesquisa
Unidades Organizacionais
Instituto do Coração, Hospital das Clínicas, Faculdade de Medicina - Médico
13 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 13
- Phenotyping Pharyngeal Pathophysiology using Polysomnography in Patients with Obstructive Sleep Apnea(2018) SANDS, Scott A.; EDWARDS, Bradley A.; TERRILL, Philip I.; TARANTO-MONTEMURRO, Luigi; AZARBARZIN, Ali; MARQUES, Melania; HESS, Lauren B.; WHITE, David P.; WELLMAN, AndrewRationale: Therapies for obstructive sleep apnea (OSA) could be administered on the basis of a patient's own phenotypic causes (""traits"") if a clinically applicable approach were available. Objectives: Here we aimed to provide a means to quantify two key contributors to OSA-pharyngeal collapsibility and compensatory muscle responsiveness-that is applicable to diagnostic polysomnography. Methods: Based on physiological definitions, pharyngeal collapsibility determines the ventilation at normal (eupneic) ventilatory drive during sleep, and pharyngeal compensation determines the rise in ventilation accompanying a rising ventilatory drive. Thus, measuring ventilation and ventilatory drive (e.g., during spontaneous cyclic events) should reveal a patient's phenotypic traits without specialized intervention. We demonstrate this concept in patients with OSA (N = 29), using a novel automated noninvasive method to estimate ventilatory drive (polysomnographic method) and using ""gold standard"" ventilatory drive (intraesophageal diaphragm EMG) for comparison. Specialized physiological measurements using continuous positive airway pressure manipulation were employed for further comparison. The validity of nasal pressure as a ventilation surrogate was also tested (N = 11). Measurements and Main Results: Polysomnography-derived collapsibility and compensation estimates correlated favorably with those quantified using gold standard ventilatory drive (R = 0.83, P < 0.0001; and R = 0.76, P < 0.0001; respectively) and using continuous positive airway pressuremanipulation (R = 0.67, P < 0.0001; and R = 0.64, P < 0.001; respectively). Polysomnographic estimates effectively stratified patients into high versus low subgroups (accuracy, 69-86% vs. ventilatory drive measures; P < 0.05). Traits were near-identical using nasal pressure versus pneumotach (N = 11, R >= 0.98, both traits; P < 0.001). Conclusions: Phenotypes of pharyngeal dysfunction in OSA are evident from spontaneous changes in ventilation and ventilatory drive during sleep, enabling noninvasive phenotyping in the clinic. Our approach may facilitate precision therapeutic interventions for OSA.
- Predicting sleep apnea responses to oral appliance therapy using polysomnographic airflow(2020) VENA, Daniel; AZARBARZIN, Ali; MARQUES, Melania; BEECK, Sara Op de; VANDERVEKEN, Olivier M.; EDWARDS, Bradley A.; CALIANESE, Nicole; HESS, Lauren B.; RADMAND, Reza; HAMILTON, Garun S.; JOOSTEN, Simon A.; TARANTO-MONTEMURRO, Luigi; KIM, Sang-Wook; VERBRAECKEN, Johan; BRAEM, Marc; WHITE, David P.; SANDS, Scott A.; WELLMAN, AndrewStudy Objectives: Oral appliance therapy is an increasingly common option for treating obstructive sleep apnea (OSA) in patients who are intolerant to continuous positive airway pressure (CPAP). Clinically applicable tools to identify patients who could respond to oral appliance therapy are limited. Methods: Data from three studies (N = 81) were compiled, which included two sleep study nights, on and off oral appliance treatment. Along with clinical variables, airflow features were computed that included the average drop in airflow during respiratory events (event depth) and flow shape features, which, from previous work, indicates the mechanism of pharyngeal collapse. A model was developed to predict oral appliance treatment response (>50% reduction in apnea-hypopnea index [AHI] from baseline plus a treatment AHI <10 events/h). Model performance was quantified using (1) accuracy and (2) the difference in oral appliance treatment efficacy (percent reduction in AHI) and treatment AHI between predicted responders and nonresponders. Results: In addition to age and body mass index (BMI), event depth and expiratory ""pinching"" (validated to reflect palatal prolapse) were the airflow features selected by the model. Nonresponders had deeper events, ""pinched"" expiratory flow shape (i.e. associated with palatal collapse), were older, and had a higher BMI. Prediction accuracy was 74% and treatment AHI was lower in predicted responders compared to nonresponders by a clinically meaningful margin (8.0 [5.1 to 11.6] vs. 20.0 [12.2 to 29.5] events/h, p < 0.001). Conclusions: A model developed with airflow features calculated from routine polysomnography, combined with age and BMI, identified oral appliance treatment responders from nonresponders. This research represents an important application of phenotyping to identify alternative treatments for personalized OSA management. Statement of Significance Treatment response to oral appliance in patients with obstructive sleep apnea can be predicted at baseline from metrics derived from routine polysomnography.
- 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.
- Retropalatal and retroglossal airway compliance in patients with obstructive sleep apnea(2018) MARQUES, Melania; GENTA, Pedro R.; AZARBARZIN, Ali; SANDS, Scott A.; TARANTO-MONTEMURRO, Luigi; MESSINEO, Ludovico; WHITE, David P.; WELLMAN, AndrewObjectives: We hypothesized that preferential retropalatal as compared to retroglossal collapse in patients with obstructive sleep apnea was due to a narrower retropalatal area and a higher retropalatal compliance. Patients with a greater retropalatal compliance would exhibit a recognizable increase in negative effort dependence (NED). Methods: Fourteen patients underwent upper airway endoscopy with simultaneous recordings of airflow and pharyngeal pressure during natural sleep. Airway areas were obtained by manually outlining the lumen. Compliance was calculated by the change of airway area from end-expiration to a pressure swing of -5 cm H2O. NED was quantified for each breath as [peak inspiratory flow minus flow at -5 cm H2O]/[peak flow] x 100. Results: Compared to the retroglossal airway, the retropalatal airway was smaller at end-expiration (p < 0.001), and had greater absolute and relative compliances (p < 0.001). NED was positively associated with retropalatal relative area change (r = 0.47; p < 0.001). Conclusions: Retropalatal airway is narrower and more collapsible than retroglossal airway. Retropalatal compliance is reflected in the clinically-available NED value.
- Predicting epiglottic collapse in patients with obstructive sleep apnoea(2017) AZARBARZIN, Ali; MARQUES, Melania; SANDS, Scott A.; BEECK, Sara Op de; GENTA, Pedro R.; TARANTO-MONTEMURRO, Luigi; MELO, Camila M. de; MESSINEO, Ludovico; VANDERVEKEN, Olivier M.; WHITE, David P.; WELLMAN, AndrewObstructive sleep apnoea (OSA) is characterised by pharyngeal obstruction occurring at different sites. Endoscopic studies reveal that epiglottic collapse renders patients at higher risk of failed oral appliance therapy or accentuated collapse on continuous positive airway pressure. Diagnosing epiglottic collapse currently requires invasive studies (imaging and endoscopy). As an alternative, we propose that epiglottic collapse can be detected from the distinct airflow patterns it produces during sleep. 23 OSA patients underwent natural sleep endoscopy. 1232 breaths were scored as epiglottic/nonepiglottic collapse. Several flow characteristics were determined from the flow signal (recorded simultaneously with endoscopy) and used to build a predictive model to distinguish epiglottic from nonepiglottic collapse. Additionally, 10 OSA patients were studied to validate the pneumotachograph flow features using nasal pressure signals. Epiglottic collapse was characterised by a rapid fall(s) in the inspiratory flow, more variable inspiratory and expiratory flow and reduced tidal volume. The cross-validated accuracy was 84%. Predictive features obtained from pneumotachograph flow and nasal pressure were strongly correlated. This study demonstrates that epiglottic collapse can be identified from the airflow signal measured during a sleep study. This method may enable clinicians to use clinically collected data to characterise underlying physiology and improve treatment decisions.
- 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.
- Quantifying the Arousal Threshold Using Polysomnography in Obstructive Sleep Apnea(2018) SANDS, Scott A.; TERRILL, Philip I.; EDWARDS, Bradley A.; MONTEMURRO, Luigi Taranto; AZARBARZIN, Ali; MARQUES, Melania; MELO, Camila M. de; LORING, Stephen H.; BUTLER, James P.; WHITE, David P.; WELLMAN, AndrewStudy Objectives: Precision medicine for obstructive sleep apnea (OSA) requires noninvasive estimates of each patient's pathophysiological ""traits."" Here, we provide the first automated technique to quantify the respiratory arousal threshold-defined as the level of ventilatory drive triggering arousal from sleep-using diagnostic polysomnographic signals in patients with OSA. Methods: Ventilatory drive preceding clinically scored arousals was estimated from polysomnographic studies by fitting a respiratory control model (Terrill et al.) to the pattern of ventilation during spontaneous respiratory events. Conceptually, the magnitude of the airflow signal immediately after arousal onset reveals information on the underlying ventilatory drive that triggered the arousal. Polysomnographic arousal threshold measures were compared with gold standard values taken from esophageal pressure and intraoesophageal diaphragm electromyography recorded simultaneously (N = 29). Comparisons were also made to arousal threshold measures using continuous positive airway pressure (CPAP) dial-downs (N = 28). The validity of using (linearized) nasal pressure rather than pneumotachograph ventilation was also assessed (N = 11). Results: Polysomnographic arousal threshold values were correlated with those measured using esophageal pressure and diaphragm EMG (R = 0.79, p < .0001; R = 0.73, p = .0001), as well as CPAP manipulation (R = 0.73, p < .0001). Arousal threshold estimates were similar using nasal pressure and pneumotachograph ventilation (R = 0.96, p < .0001). Conclusions: The arousal threshold in patients with OSA can be estimated using polysomnographic signals and may enable more personalized therapeutic interventions for patients with a low arousal threshold.
- 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.