Fabiola G Rizzatti1, Diego R Mazzotti2, Jesse Mindel3, Greg Maislin2, Brendan T Keenan2, Lia Bittencourt4, Ning-Hung Chen5, Peter A Cistulli6, Nigel McArdle7, Frances M Pack2, Bhajan Singh7, Kate Sutherland6, Bryndis Benediktsdottir8, Ingo Fietze9, Thorarinn Gislason8, Diane C Lim2, Thomas Penzel10, Bernd Sanner11, Fang Han12, Qing Yun Li13, Richard Schwab2, Sergio Tufik4, Allan I Pack2, Ulysses J Magalang14. 1. Departamento de Psicobiologia, Universidade Federal de São Paulo, São Paulo, Brazil; Departamento de Medicina, Universidade Federal de São Carlos, São Paulo, Brazil. 2. Center for Sleep and Circadian Neurobiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA. 3. Division of Pulmonary, Critical Care, and Sleep Medicine, The Ohio State University Wexner Medical Center, Columbus, OH. 4. Departamento de Psicobiologia, Universidade Federal de São Paulo, São Paulo, Brazil. 5. Division of Pulmonary, Critical Care Medicine and Sleep Medicine, Chang Gung Memorial Hospital, Taoyuan City, Taiwan. 6. Charles Perkins Centre, Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia; Department of Respiratory and Sleep Medicine, Royal North Shore Hospital, Sydney, NSW, Australia. 7. West Australian Sleep Disorders Research Institute, Sir Charles Gairdner Hospital, Nedlands, WA, Australia. 8. Department of Sleep Medicine, Landspitali University Hospital, Reykjavík, Iceland; Medical Faculty, University of Iceland, Reykjavik, Iceland. 9. Interdisciplinary Center of Sleep Medicine, Charité University Hospital, Berlin, Germany. 10. Interdisciplinary Center of Sleep Medicine, Charité University Hospital, Berlin, Germany; Saratov State University, Saratov, Russia. 11. Department of Pulmonary Medicine, Agaplesion Bethesda Krankenhaus Wuppertal, Wuppertal, Germany. 12. Department of Respiratory Medicine, Peking University, Beijing, China. 13. Department of Respiratory and Critical Care Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. 14. Division of Pulmonary, Critical Care, and Sleep Medicine, The Ohio State University Wexner Medical Center, Columbus, OH; Neuroscience Research Institute, The Ohio State University Wexner Medical Center, Columbus, OH. Electronic address: ulysses.magalang@osumc.edu.
Abstract
BACKGROUND: Extreme phenotypes of OSA have not been systematically defined. RESEARCH QUESTION: This study developed objective definitions of extreme phenotypes of OSA by using a multivariate approach. The utility of these definitions for identifying characteristics that confer predisposition toward or protection against OSA is shown in a new prospective sample. STUDY DESIGN AND METHODS: In a large international sample, race-specific liability scores were calculated from a weighted logistic regression that included age, sex, and BMI. Extreme cases were defined as individuals with an apnea-hypopnea index (AHI) ≥ 30 events/hour but low likelihood of OSA based on age, sex, and BMI (liability scores > 90th percentile). Similarly, extreme controls were individuals with an AHI < 5 events/hour but high likelihood of OSA (liability scores < 10th percentile). Definitions were applied to a prospective sample from the Sleep Apnea Global Interdisciplinary Consortium, and differences in photography-based craniofacial and intraoral phenotypes were evaluated. RESULTS: This study included retrospective data from 81,338 individuals. A total of 4,168 extreme cases and 1,432 extreme controls were identified by using liability scores. Extreme cases were younger (43.1 ± 14.7 years), overweight (28.6 ± 6.8 kg/m2), and predominantly female (71.1%). Extreme controls were older (53.8 ± 14.1 years), obese (34.0 ± 8.1 kg/m2), and predominantly male (65.8%). These objective definitions identified 29 extreme cases and 87 extreme controls among 1,424 Sleep Apnea Global Interdisciplinary Consortium participants with photography-based phenotyping. Comparisons suggest that a greater cervicomental angle increases risk for OSA in the absence of clinical risk factors, and smaller facial widths are protective in the presence of clinical risk factors. INTERPRETATION: This objective definition can be applied in sleep centers throughout the world to consistently define OSA extreme phenotypes for future studies on genetic, anatomic, and physiologic pathways to OSA.
BACKGROUND: Extreme phenotypes of OSA have not been systematically defined. RESEARCH QUESTION: This study developed objective definitions of extreme phenotypes of OSA by using a multivariate approach. The utility of these definitions for identifying characteristics that confer predisposition toward or protection against OSA is shown in a new prospective sample. STUDY DESIGN AND METHODS: In a large international sample, race-specific liability scores were calculated from a weighted logistic regression that included age, sex, and BMI. Extreme cases were defined as individuals with an apnea-hypopnea index (AHI) ≥ 30 events/hour but low likelihood of OSA based on age, sex, and BMI (liability scores > 90th percentile). Similarly, extreme controls were individuals with an AHI < 5 events/hour but high likelihood of OSA (liability scores < 10th percentile). Definitions were applied to a prospective sample from the Sleep Apnea Global Interdisciplinary Consortium, and differences in photography-based craniofacial and intraoral phenotypes were evaluated. RESULTS: This study included retrospective data from 81,338 individuals. A total of 4,168 extreme cases and 1,432 extreme controls were identified by using liability scores. Extreme cases were younger (43.1 ± 14.7 years), overweight (28.6 ± 6.8 kg/m2), and predominantly female (71.1%). Extreme controls were older (53.8 ± 14.1 years), obese (34.0 ± 8.1 kg/m2), and predominantly male (65.8%). These objective definitions identified 29 extreme cases and 87 extreme controls among 1,424 Sleep Apnea Global Interdisciplinary Consortium participants with photography-based phenotyping. Comparisons suggest that a greater cervicomental angle increases risk for OSA in the absence of clinical risk factors, and smaller facial widths are protective in the presence of clinical risk factors. INTERPRETATION: This objective definition can be applied in sleep centers throughout the world to consistently define OSA extreme phenotypes for future studies on genetic, anatomic, and physiologic pathways to OSA.
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Authors: Steven J Holfinger; M Melanie Lyons; Brendan T Keenan; Diego R Mazzotti; Jesse Mindel; Greg Maislin; Peter A Cistulli; Kate Sutherland; Nigel McArdle; Bhajan Singh; Ning-Hung Chen; Thorarinn Gislason; Thomas Penzel; Fang Han; Qing Yun Li; Richard Schwab; Allan I Pack; Ulysses J Magalang Journal: Chest Date: 2021-10-27 Impact factor: 9.410
Authors: Naima Laharnar; Sebastian Herberger; Lisa-Kristin Prochnow; Ning-Hung Chen; Peter A Cistulli; Allan I Pack; Richard Schwab; Brendan T Keenan; Diego R Mazzotti; Ingo Fietze; Thomas Penzel Journal: Nat Sci Sleep Date: 2021-11-09