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Endotyping Sleep Apnea One Breath at a Time: An Automated Approach for Separating Obstructive from Central Sleep-disordered Breathing

Parekh, Ankit; Tolbert, Thomas M; Mooney, Anne M; Ramos-Cejudo, Jaime; Osorio, Ricardo S; Treml, Marcel; Herkenrath, Simon-Dominik; Randerath, Winfried J; Ayappa, Indu; Rapoport, David M
PMID: 34449303
ISSN: 1535-4970
CID: 5147022

The interaction between sleep-disordered breathing and apolipoprotein E genotype on cerebrospinal fluid biomarkers for Alzheimer's disease in cognitively normal elderly individuals

Osorio, Ricardo S; Ayappa, Indu; Mantua, Janna; Gumb, Tyler; Varga, Andrew; Mooney, Anne M; Burschtin, Omar E; Taxin, Zachary; During, Emmanuel; Spector, Nicole; Biagioni, Milton; Pirraglia, Elizabeth; Lau, Hiuyan; Zetterberg, Henrik; Blennow, Kaj; Lu, Shou-En; Mosconi, Lisa; Glodzik, Lidia; Rapoport, David M; de Leon, Mony J
Previous studies have suggested a link between sleep disordered breathing (SDB) and dementia risk. In the present study, we analyzed the relationship between SDB severity, cerebrospinal fluid (CSF) Alzheimer's disease-biomarkers, and the ApoE alleles. A total of 95 cognitively normal elderly participants were analyzed for SDB severity, CSF measures of phosphorylated-tau (p-tau), total-tau (t-tau), and amyloid beta 42 (Abeta-42), as well as ApoE allele status. In ApoE3+ subjects, significant differences were found between sleep groups for p-tau (F[df2] = 4.3, p = 0.017), and t-tau (F[df2] = 3.3, p = 0.043). Additionally, among ApoE3+ subjects, the apnea and/or hypopnea with 4% O2-desaturation index was positively correlated with p-tau (r = 0.30, p = 0.023), t-tau (r = 0.31, p = 0.021), and Abeta-42 (r = 0.31, p = 0.021). In ApoE2+ subjects, the apnea and/or hypopnea with 4% O2-desaturation index was correlated with lower levels of CSF Abeta-42 (r = -0.71, p = 0.004), similarly to ApoE4+ subjects where there was also a trend toward lower CSF Abeta-42 levels. Our observations suggest that there is an association between SDB and CSF Alzheimer's disease-biomarkers in cognitively normal elderly individuals. Existing therapies for SDB such as continuous positive airway pressure could delay the onset to mild cognitive impairment or dementia in normal elderly individuals.
PMID: 24439479
ISSN: 0197-4580
CID: 851792

Multinight recording and analysis of continuous positive airway pressure airflow in the home for titration and management of sleep disordered breathing

Callahan, Cynthia Y; Norman, Robert G; Taxin, Zachary; Mooney, Anne M; Rapoport, David M; Ayappa, Indu
OBJECTIVES: The authors examined magnitude/variability of residual sleep disordered breathing (SDB) at pressures around the therapeutic continuous positive airway pressure (CPAP), and described a multinight approach to CPAP titration/retitration consisting of recording airflow and summarizing SDB over multiple nights at multiple pressures and choosing an optimal pressure from these summarized data. DESIGN: Prospective, single-center nonblinded study. PATIENTS: Ten female/18 male patients with obstructive sleep apnea-hypopnea syndrome (OSAHS) (respiratory disturbance index [RDI] 67/h), 17 newly-initiated, 11 chronic CPAP users. INTERVENTIONS: A custom CPAP device (Fisher & Paykel Healthcare) recording airflow and pre-programmed to vary CPAP between 2-3 cm H2O below and 1-2 cm H2O above prescription pressure as determined by a full laboratory titration. RESULTS: Airflow and pressure continuously recorded for multiple nights (15.9 +/- 5.1 nights) at four to seven different pressures in each patient. SDB events manually scored from the airflow as apnea (airflow reduction > 90%), hypopnea (airflow reduction > 30% lasting 10 to 120 sec with inspira-tory flow limitation [IFL]) and runs of sustained IFL > 2 min identified. RDI = (apnea + hypopnea)/total sleep time calculated for each night and an obstruction index, including sustained IFL, also was calculated. PressureMultinight was obtained for each patient from multiple nights of data using two mathematical techniques. Night-to-night variability of SDB indices was low in some patients and significant in others. PressureMultinight could be determined in 17 of 28 patients and was similar to the in-laboratory pressure. CONCLUSIONS: This study showed that recording multiple nights of CPAP airflow in the home and analyzing these data for residual SDB provided useful information, including the possibility of determining a therapeutic prescription for fixed CPAP in most patients and identification of others with significant physiologic variability of SDB. CITATION: Callahan CY; Norman RG; Taxin Z; Mooney AM; Rapoport DM; Ayappa I. Multinight recording and analysis of continuous positive airway pressure airflow in the home for titration and management of sleep disordered breathing. SLEEP 2013;36(4):535-545.
PMID: 23543909
ISSN: 0161-8105
CID: 271422

Sleep-disordered breathing, aging and risk for alzheimer's disease in cognitively normal subjects [Meeting Abstract]

Osorio, R S; Mantua, J; Ayappa, I; Mooney, A M; Taxin, Z; Murray, J; Biagioni, M; Randall, C; Li, Y; Cummings, M; Spector, N; Rejon, A; Lau, H; Glodzik, L; Rapoport, D M; De, Leon M J
RATIONALE: Previous studies have shown that sleep-disordered breathing (S
ISSN: 1073-449x
CID: 1769262

Snoring Without Apnea, Evaluation

Chapter by: Mooney, Anne M; Taxin, Zachary H
in: Encyclopedia of Otolaryngology, Head and Neck Surgery by Kountakis, Stilianos E [Eds]
Berlin, Heidelberg : Springer Berlin Heidelberg, 2013
pp. 2518-2523
ISBN: 3642234992
CID: 1808312

OSAHS, Diagnosis

Chapter by: Mooney, Anne M; Taxin, Zachary H
in: Encyclopedia of Otolaryngology, Head and Neck Surgery by Kountakis, Stilianos E [Eds]
Berlin, Heidelberg : Springer Berlin Heidelberg, 2013
pp. 1939-1947
ISBN: 3642234992
CID: 1808322

Sleep Quality, Short-Term and Long-Term CPAP Adherence

Somiah, Manya; Taxin, Zachary; Keating, Joseph; Mooney, Anne M; Norman, Robert G; Rapoport, David M; Ayappa, Indu
STUDY OBJECTIVES: Adherence to CPAP therapy is low in patients with obstructive sleep apnea/hypopnea syndrome (OSAHS). The purpose of the present study was to evaluate the utility of measures of sleep architecture and sleep continuity on the CPAP titration study as predictors of both short- and long-term CPAP adherence. METHODS: 93 patients with OSAHS (RDI 42.8 +/- 34.3/h) underwent in-laboratory diagnostic polysomnography, CPAP titration, and follow-up polysomnography (NPSG) on CPAP. Adherence to CPAP was objectively monitored. Short-term (ST) CPAP adherence was averaged over 14 days immediately following the titration study. Long-term (LT) CPAP adherence was obtained in 56/93 patients after approximately 2 months of CPAP use. Patients were grouped into CPAP adherence groups for ST (< 2 h, 2-4 h, and > 4 h) and LT adherence (< 4 h, > 4 h). Sleep architecture, sleep disordered breathing (SDB) indices, and daytime outcome variables from the diagnostic and titration NPSGs were compared between CPAP adherence groups. RESULTS: There was a significant relationship between ST and LT CPAP adherence (r = 0.81, p < 0.001). Neither ST nor LT adherence were related to demographic variables, baseline severity of untreated SDB, sleep architecture, or measures of daytime impairment. Good CPAP adherence groups had significantly lower %N2 and greater %REM on the titration NPSG. A model combining change in sleep efficiency and change in sleep continuity between the diagnostic and titration NPSGs predicted 17% of the variance in LT adherence (p = 0.006). CONCLUSIONS: These findings demonstrate that characteristics of sleep architecture, even on the titration NPSG, may predict some of the variance in CPAP adherence. Better sleep quality on the titration night was related to better CPAP adherence, suggesting that interventions to improve sleep on/prior to the CPAP titration study might be used as a therapeutic intervention to improve CPAP adherence. CITATION: Somiah M; Taxin Z; Keating J; Mooney AM; Norman RG; Rapoport DM; Ayappa I. Sleep quality, short-term and long-term CPAP adherence. J Clin Sleep Med 2012;8(5):489-500.
PMID: 23066359
ISSN: 1550-9389
CID: 180096

Relative Prolongation of Inspiratory Time Predicts High versus Low Resistance Categorization of Hypopneas

Mooney, Anne M; Abounasr, Khader K; Rapoport, David M; Ayappa, Indu
STUDY OBJECTIVES: Sleep disordered breathing events conceptually separate into "obstructive" and "central" events. Esophageal manometry is the definitive but invasive means of classifying hypopneas. The purpose of this project was to identify noninvasive markers for discriminating high vs. low resistance hypopneas. METHODS: Forty subjects with obstructive or central sleep apnea underwent diagnostic polysomnography with nasal cannula airflow and esophageal manometry; 200% resistance relative to reference breaths was used to define "high" resistance. Noninvasive parameters from 292 randomly selected hypopneas in 20 subjects were analyzed and correlated to resistance. The best parameter and cutoff for predicting high relative resistance was determined and tested prospectively in 2 test sets in the 20 remaining subjects. Test Set A: 15 randomly selected hypopneas in each subject; Test Set B: all hypopneas in 7 subjects. RESULTS: In the development set, prolongation of inspiratory time during the 2 smallest breaths of a hypopnea (T(i)) relative to baseline had the best correlation to high relative resistance. In the Test Set A, relative T(i) > 110% classified obstructive events with sensitivity = 72%, specificity = 77%, PPV = 64%, NPV = 83%. Similar numbers were obtained for classification of hypopneas based on presence of flow limitation (FL) alone. When either relative T(i) or presence of FL were used to define high resistance, sensitivity = 84%, specificity = 74%, PPV = 65%, NPV = 89%. Similar results were obtained for Test Set B. CONCLUSIONS: Relative prolongation of T(i) is a good noninvasive predictor of high/low resistance in a dataset with both FL and NFL hypopneas. Combination of FL and relative T(i) improves this classification. The use of T(i) to separate obstructive and central hypopneas needs to be further tested for clinical utility (outcomes and treatment effects). CITATION: Mooney AM; Abounasr KK; Rapoport DM; Ayappa I. Relative prolongation of inspiratory time predicts high versus low resistance categorization of hypopneas. J Clin Sleep Med 2012;8(2):177-185.
PMID: 22505863
ISSN: 1550-9389
CID: 164368

Reproducibility and pattern of experimental human sleep disordered breathing (S [Meeting Abstract]

Callahan, C Y; Taxin, Z; Mooney, A M; Rapoport, D M; Ayappa, I A
RATIONALE: Sub-therapeutic pressure has long been used as a sham-control for CPAP studies. We have previously suggested creating an experimental human model of obstructive sleep apnea (Am J Respir Crit Care Med 183;2011:A6073) using suboptimal pressure to induce a controlled amount of S
ISSN: 1073-449x
CID: 1768812

An experimental human model of sleep disordered breathing [Meeting Abstract]

Ayappa, I A; Keating, J; Norman, R G; Mooney, A M; Walsleben, J A; Rapoport, D M
Experimental models of human sleep disordered breathing (S
ISSN: 1073-449x
CID: 177187