The Interplay Between Obstructive Sleep Apnea Cognitive Dysfunction in Pediatric Patients

The Interplay Between Obstructive Sleep Apnea and Inflammatory Cytokines Induces Cognitive Dysfunction in Pediatric Patients

Objectives: Determination of the impact of obstructive sleep apnea (OSA) on the cognitive function (CF) and serum tumor necrosis factor-α (TNF-α), interleukin (IL)-6 and 1β levels in children aged 5-12 years and the effect of OSA management on these variables.

Patients & Methods: 224 patients were evaluated using the Pediatric Sleep Questionnaire, the NEPSY score for CF and Polysomnography (PSG) to grade OSA severity according to the Apnea/hypopnea index (AHI). Patients with adenotonsillar hypertrophy grade >2 will undergo the appropriate surgical intervention. Overweight or obese patients with mild or moderate OSAS will undergo 6-m trial of lifestyle intervention (LSI). Blood samples were obtained for ELISA estimation of cytokines' levels. At end of 6-m follow-up, all variables were re-evaluated

Study Overview

• Status: Completed
• Conditions: Obstructive Sleep Apnea
• Intervention / Treatment: Procedure: adenotonsillectomy; Behavioral: Lifestyle intervention

Detailed Description

All children aged 5-12 years who attended the outpatient clinics of Otorhinolaryngology and/or Pediatrics with complaints suggestive of OSAS were eligible for evaluation for exclusion and inclusion criteria according to the conditions of the Local Ethical Committee which approved the study protocol by number.

Evaluation Tools

1. Evaluation of body mass index (BMI): BMI was calculated according to Bray as weight (kg) divided by the square height (m2) and was interpreted according to the International Obesity Task Force (IOTF) BMI cut-offs according to the percentile of BMI adjusted for age and gender.
2. Pediatric Sleep Questionnaire (PSQ) using the sleep-related breathing disorders scale which consists of 3 domains including 22 items with three responses to each item Yes (=1), No (=0), and don't know = missed answer.
3. Neurocognitive Assessments using the NEPSY II score which is designed to assess six domains (Appendix 2), each domain was expressed as scaled scores with lower scores indicating cognitive dysfunction.

4. Otorhinolaryngologic assessment variables:

   • Assessment of the volume of the palatine tonsils using Brodsky grading scale Adenoid size was assessed by X-Ray soft tissue nasopharynx lateral view and graded according to. Assessment of the tongue position within the oral cavity to evaluate the extent of obstruction of the oral cavity by the tongue using the modified Mallampati method.
   • Polysomnography (PSG) was performed according to guidelines of the American Academy of Sleep Medicine (AASM) for the scoring of sleep and associated events. The hypopnea index (HI) indicated the number of hypopneas per hour of sleep and the Apnea/hypopnea index (AHI) is the summation of apnea and hypopnea indices.
5. Laboratory investigation: Venous blood samples (5 ml) were collected for ELISA estimation of serum levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-6, and 1β.

Diagnosis and grading of OSAS

1. Diagnosis of OSAS:

   Pediatric OSAS was diagnosed according to guidelines of the American Academy of Sleep Medicine (21) depending on both the clinical findings and the polysomnographic criteria for diagnosis.

2. OSAS severity grading OSAS severity was graded according to the apnea-hypopnea index (AHI) into mild if AHI was 1-4.9, moderate if AHI 5-9.9, or severe if AHI > 10 and if AHI was >30 OSAS is very severe.

• Study Type: Interventional
• Enrollment (Actual): 224
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Egypt
  • Assiut, Egypt
    • Al-Azhar University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 years to 12 years (CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Children in age range of 5-12 years with mild-to-severe OSAS, free of exclusion criteria were enrolled in the study.

Exclusion Criteria:

• The presence of craniofacial anomalies
• neurological disorders
• very severe OSAS
• OSAS complicated by complex comorbidities
• residual OSAS following adenotonsillectomy (AT), hypothyroidism, or refusal of the suggested therapeutic plans.
• children who failed or were unable to undergo the cognitive function evaluation and those whose parents refused to undergo polysomnography were also excluded from the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Surgical	Procedure: adenotonsillectomy; all patients with adenoid or tonsillar or adenotonsillar hypertrophy of grade >2 will undergo adenoidectomy, tonsillectomy or adenotonsillectomy (AT) according to the indication. Overweight or obese patients with mild or moderate OSAS will undergo 6-m trial of lifestyle intervention (LSI) and CPAP if indicated, responders will undergo more follow-up otherwise surgical interference was indicated
PLACEBO_COMPARATOR: non-Surgical	Behavioral: Lifestyle intervention; After baseline testing, all subjects began a structured 6-month LSI consisting of dietary modification and exercise. Intensive dietary counseling was provided weekly for the first 4 weeks of the intervention, monthly subsequently until 6 months. A target caloric deficit of ~250.500 cal/d was recommended throughout dietary counseling. Dietary regimen consisted of diets composed of nutrients contributing to total energy as 55% carbohydrate, 15% protein, and 30% fat. Other lifestyle changes included calorie restriction depending on reduction of the frequency of snack consumption, ingestion of low-calorie and low-fat snacks, limiting sugar-based carbonated drinks and the duration of television watching or mobile games. Exercise sessions consisted of both aerobic and strength training three times weekly.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Relive of OSAS	The effect of relieve of obstruction on sleep-related breathing disorders and cognitive function as judged by the Pediatric Sleep Questionnaire at end of follow up	6 months
Effect of weight reduction on sleep-related breathing disorders	The effect of relieve of obstruction and weight reduction on sleep-related breathing disorders as judged by the NESPY score at end of follow up	6 months

Collaborators and Investigators

• Sponsor: Al-Azhar University

Study record dates

Study Major Dates

• Study Start (ACTUAL): November 7, 2020
• Primary Completion (ACTUAL): March 1, 2021
• Study Completion (ACTUAL): June 15, 2021

Study Registration Dates

• First Submitted: June 1, 2022
• First Submitted That Met QC Criteria: June 13, 2022
• First Posted (ACTUAL): June 16, 2022

Study Record Updates

• Last Update Posted (ACTUAL): June 16, 2022
• Last Update Submitted That Met QC Criteria: June 13, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Nervous System Diseases; Respiratory Tract Diseases; Respiration Disorders; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Neurocognitive Disorders; Signs and Symptoms, Respiratory; Cognition Disorders; Sleep Apnea Syndromes; Sleep Apnea, Obstructive; Apnea; Cognitive Dysfunction
• Other Study ID Numbers: AUAREC20190509-12

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No