Obstructive Sleep Apnea in Craniofacial Anomalies: Severity of the Respiratory Disorder and Its Relationship with Airway and Maxillomandibular Complex Dimensions, Airflow Behavior, and Cardiovascular, Hormonal, and Genetic Profiles.

• Grant number: 24/19841-0
• Support Opportunities: Research Projects - Thematic Grants
• Start date: November 01, 2025
• End date: October 31, 2030
• Field of knowledge: Health Sciences - Dentistry
• Principal Investigator: Ivy Kiemle Trindade Suedam
• Grantee: Ivy Kiemle Trindade Suedam
• Host Institution: Faculdade de Odontologia de Bauru (FOB). Universidade de São Paulo (USP). Bauru , SP, Brazil
• Pesquisadores principais: Carlos Ferreira dos Santos ; Daniela Gamba Garib Carreira
• Associated researchers: Amelia Fischer Drake ; Ana Paula Fukushiro ; Geraldo Lorenzi Filho ; Marília Afonso Rabelo Buzalaf ; Ronald P Strauss ; Sergio Henrique Kiemle Trindade

Abstract

Problem Statement: Obstructive sleep apnea (OSA), highly prevalent in the global population, is characterized by recurrent obstructions of the upper airway (UA), resulting in oxygen desaturation, sleep fragmentation, and consequent sympathetic activation, with alterations in cardiovascular parameters. Craniofacial discrepancies, such as those observed in individuals with cleft lip and palate (CLP), contribute to UA narrowing and may lead to OSA. Possible circadian endocrine and inflammatory dysfunctions are additional contributing factors. Expected Results: It is expected to identify a significant correlation between UA narrowing, increased resistance to airflow, and OSA severity. Severe OSA is also expected to be associated with elevated blood pressure, greater hypoxic load, and hormonal alterations related to cortisol and melatonin, particularly in the CLP population. A genetic panel identifying polymorphisms associated with OSA is also anticipated. Finally, the development of a risk algorithm for OSA is proposed, aimed at providing the scientific and clinical community with an accurate model capable of identifying and predicting the risk of OSA. Materials and Methods: Four groups will be prospectively evaluated: 1) Control individuals without OSA, 2) Control individuals with OSA, 3) Individuals with surgically treated CLP without OSA, 4) Individuals with surgically treated CLP with OSA. These groups will be subdivided into children and adults, resulting in eight subgroups, to be evaluated through the following assessments: 1) Type III polygraphy (Neurovirtual®) and high-resolution type IV polygraphy (Biologix®), which provide the apnea-hypopnea index, oxyhemoglobin saturation, and hypoxic load; 2) Clinical evaluation: measurement of blood pressure and sleep quality using validated questionnaires (PSQ for children and BERLIN for adults); 3) Anthropometric analysis: measurement of neck and abdominal circumference; 4) Bioimpedance: assessment of BMI and body composition (lean mass, fat, and water); 5) Rhinopharyngometry (Eccovision®): clinical measurement of UA dimensions; 6) Computed tomography: 3D cephalometric analysis (IKT-SNAP and 3D SLICER®), 3D UA measurements (Mimics® and Dolphin®), and computational fluid dynamics analysis (ANSYS®) to simulate and quantify inspiratory airflow resistance; 7) Hormonal profile (ELISA - Salimetrics®): salivary measurements of cortisol and melatonin, hormones associated with wakefulness and sleep; 8) Whole-exome sequencing (Next-Generation Sequencing - NGS - Illumina platform): development of a genetic panel to identify polymorphisms associated with OSA and CLP; 9) Artificial intelligence: creation of a machine learning algorithm to assess the risk of OSA in individuals with CLP. It is believed that UA narrowing due to craniofacial dysmorphism, particularly in individuals with CLP, negatively impacts airflow, predisposing them to OSA. Cardiovascular parameters and hormonal profiles may be affected by OSA and contribute to disorder severity. Finally, the study aims to identify potential genetic markers for OSA and understand how these markers are regulated in OSA cases. Understanding these relationships is essential to identify risk factors and develop effective treatments for OSA. (AU)