Familial Aggregates in Obstructive Sleep Apnea Syndrome

doi:10.1378/chest.107.6.1545

Chest

Volume 107, Issue 6, June 1995, Pages 1545-1551

https://doi.org/10.1378/chest.107.6.1545 Get rights and content

Obstructive sleep apnea syndrome (OSAS) was diagnosed in 157 subjects based on clinical symptoms, physical evaluation, cephalometric x-ray films, and polysomnography. These index cases identified 844 living first-degree relatives. Mailings were sent to 792 (94%). The mailing consisted of two identical questionnaires, one for the family member of the index case and one to be given to a friend (not a relative) of approximately the same age. In response, we received 531 (63%) questionnaires from relatives and 198 (25%) questionnaires from age-matched nonrelated friends, which were used as a control group. A more extensive investigation was performed on first-degree relatives of the index group living in the San Francisco Bay Area or vicinity. Two hundred seventy-nine relatives (100%) were identified. One hundred sixty-six subjects (59%) as well as 69 age-matched friends (ie, 41% of the 166 relatives and 25% of the potential total group) agreed to participate in further studies. These subjects had interviews, clinical investigations, and nonattended ambulatory monitoring. Cephalometric x-ray films could be obtained on only 22 of 166 participating relatives and 6 of 69 friends. Body mass index was not a differentiating measure between relatives and friends. Odds ratios (ORs) were calculated from the questionnaire data. The report of tiredness, fatigue, and sleepiness did not distinguish family members from friends. The OR, however, progressively increases when there is a positive history of near nightly loud snoring (OR=1.78; 95% confidence interval [CI] 1.25-2.54) or a positive history of daytime sleepiness in conjunction with near nightly loud snoring (OR=3.11; 95% CI=1.94-4.99). The investigation in the Bay Area indicated that, when first-degree relatives were compared with friends, the complaint of daytime tiredness, sleepiness, or both with the presence of a high and narrow (ogival) hard palate sharply differentiated between friends and relatives (OR=10.9, 95%, CI=5.31-22.5). An Epworth Sleepiness Scale score of 9 or greater with the presence of another symptom associated with OSAS, and a respiratory disturbance index greater than 5 (number of apneas and hypopneas per hour of sleep >5) gave an OR of 45.6 (95% CI=18.8-11.0). Disproportionate craniofacial anatomy was common in familial groups with OSAS. Craniofacial familial features can be a strong indicator of risk for the development of OSAS.

Section snippets

Population

Index Case Identification: We identified obstructive sleep apneic patients (index cases) from subjects seen consecutively at the Stanford Sleep Disorders Clinic. All index cases had a complaint of daytime sleepiness, tiredness, or fatigue. All were reported to be loud, chronic snorers during sleep and presented, to varying degrees, with clinical symptoms associated with OSAS. All subjects underwent nocturnal polysomnography, which was conducted according to American Sleep Disorders Association

Results

Two different studies were performed. One was a questionnaire survey on a large population; the second one was a more extensive investigation with specific testing on a geographically defined population which was also part of the initial large population. The latter study shall be discussed first here.

Comment

The study reported here considered only first-degree relatives. Considering the number of potential subjects, a 63% response rate, particularly in the US environment, is large enough to bring valuable information. The risk of self-selection of affected individuals is always present and cannot be avoided completely in studies with this type of design, but the large database reduces the probability of selection bias. The study would have benefited if we had succeeded in obtaining a similar

ACKNOWLEDGMENT

The authors thank Michael Gulevich for editing the manuscript.

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Polysomnography is considered the gold standard tool to establish the diagnosis and severity of obstructive sleep apnea (OSA) syndrome in children; however, it cannot provide information regarding the mechanism or location of upper airway obstruction during sleep. The present chapter will focus on the role of imaging modalities in evaluating childhood OSA and how they may advance our understanding of the anatomical and functional aspects of the disorder. Although routine imaging for children with OSA is not required, advanced imaging techniques are an important component of the evaluation for some children, including those with complex medical comorbidities, craniofacial anomalies, and persistent disease following first-line therapy. In this chapter, we emphasize studies using magnetic resonance imaging, since this technique is noninvasive and provides the most quantitative and reliable data without ionizing radiation. Lateral neck radiography, sleep fluoroscopy, computed tomography, and optical coherence tomography are also discussed.
Upper airway imaging and endoscopy
2023, Encyclopedia of Sleep and Circadian Rhythms: Volume 1-6, Second Edition
Advances in upper airway imaging and endoscopy have provided insight into the pathogenesis of OSA and treatment selection and outcomes. These evaluations have demonstrated the following: upper airway obstruction most commonly occurs in the retropalatal region but often occurs in multiple regions; enlargement of the upper airway soft tissues and/or craniofacial bony abnormalities are important anatomical risk factors; and imaging and endoscopy can play a key role in selection and outcomes for treatments other than positive airway pressure. The growing availability of three-dimensional imaging methods and drug-induced sleep endoscopy increase the opportunity for patients to undergo detailed evaluation for personalized treatment rather than a one-size-fits-all approach.
Analysis of nasal airway symmetry and upper airway changes after rapid maxillary expansion
2021, American Journal of Orthodontics and Dentofacial Orthopedics
The objectives of this study were to assess the changes in right vs left nasal cavity volumes and minimum cross-sectional width, nasopharyngeal, and oropharyngeal volumes of the upper airway in response to rapid maxillary expansion (RME).
Pretreatment and posttreatment cone-beam computed tomography scans of 28 patients with a mean age of 9.86 ± 2.43 years and 20 age- and sex-matched controls were digitized and linear, angular, and volumetric measurements were obtained.
Nasopharyngeal volume, right, and left nasal cavity volumes, and minimum cross-sectional widths increased significantly 2 years post RME (P <0.05). These measurements did not show any significant increase in the control group (P >0.05), whereas the oropharyngeal volume increase for both groups was comparable (P = 0.92). In the experimental group, the right and left nasal cavity volumes were not significantly different at baseline or posttreatment. However, the change that occurred was significantly larger for the left nasal cavity. This change for the control group was more significant for the right nasal cavity. Maxillary right and left molar inclinations were positively correlated to the nasal cavity volume, showing that the more buccally inclined the maxillary molars were, the smaller the nasal cavity volume.
Nasopharyngeal and right and left nasal cavity volumes and minimum cross-sectional widths increase significantly after RME in young children. Expansion decreases the degree of difference in volume between the right and left nasal cavities. The buccal inclination of maxillary molars is correlated with nasal cavity volume.
Obstructive sleep apnea risk factors and symptoms in children with a known parental obstructive sleep apnea diagnosis
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To document symptoms and risk factors of obstructive sleep apnea (OSA) in children who have a parent diagnosed with OSA and compare them to an age and sex matched sample where parents are low risk for OSA.
We recruited 25 children with a parent diagnosed with OSA (P-OSA) and 29 age and gender matched children from the community whose parents scored low risk for OSA (P-NOSA). Comparisons were made using the OSA-18 questionnaire, anthropometric measurements, and mallampati score. Statistical analysis included t-tests for OSA-18 score and BMI measures and non parametric analysis for mallampati score. OSA-18 domain scores were analysed using T-test and Bonferroni correction for multiple comparisons.
Fifty-six percent of the P-OSA group had a mallampati score of III/IV compared to 11% in the P-NOSA sample (p = 0.005). There was a significant difference in BMI between the P-OSA sample (mean ± SD 19.5 ± 5.7 kg/m²) and the P-NOSA sample (16.95 ± 2.08 kg/m², p = 0.002). Forty-four percent of P-OSA children were found to be either overweight or obese (BMI z-score). None of the P-NOSA children fell into this category. No significant difference was found between the P-OSA and P-NOSA samples on the OSA-18 score (P-OSA 36.5 ± 8.1, P-NOSA 29.2 ± 9.1, p = 0.07). Five children in the P-OSA sample scored >60 but no P-NOSA children scored >60.
This study suggests that children with a parent diagnosed with OSA are more likely to have risk factors of pediatric OSA compared to age and sex matched children of parents without OSA but do not have more symptoms.
Defining Extreme Phenotypes of OSA Across International Sleep Centers
2020, Chest
Extreme phenotypes of OSA have not been systematically defined.
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.
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.
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.
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.
Sleep time and sleep-related symptoms across two generations – results of the community-based RHINE and RHINESSA studies
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To analyze the association between sleep-related symptoms and sleep length in parents and their children in relation to other risk factors in both generations.
The participants were parents (n = 5,855, age 54.3 ± 6.5 years, 45.2% men) who participated in the community-based Respiratory Health in Northern Europe (RHINE) study and one random member of their adult offspring (n = 5,855, age 30.2 ± 7.7 years, 41.5% men) who participated in the Respiratory Health in Northern Europe, Spain and Australia (RHINESSA) study. Both generations responded to identical questionnaires on sleep symptoms, including difficulty initiating sleep (DIS), difficulty maintaining sleep (DMS), early morning awakening (EMA), snoring, nocturnal sweating, nocturnal gastroesophageal reflux (nGER), sleep time and excessive daytime sleepiness (EDS). Insomnia was defined as either, or both, DIS and DMS in combination with EDS.
All sleep variables except nocturnal sweating were more common in offspring whose parents had reported the same symptom. After adjusting for age, gender, BMI, smoking, physical activity, education, center and parents' total number of children, there were independent associations between sleep symptoms in parents and offspring for DIS (adj. OR, 95% CI: 1.52, 1.20–1.93), DMS (1.34, 1.15–1.56), snoring (1.45, 1.15,1.83), nGER (1.65, 1.15–2.37), insomnia (1.39, 1.13–1.73), short sleep time (<6 h/night) (2.51, 1.72–3.68) and EDS (1.48, 1.26,1.72). There were no independent relationships between symptoms in parents and offspring for EMA, nocturnal sweating or long sleep time (>9 h/night).
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: Part of the work presented here in was supported by grant AG 07772 from the National Institute of Aging and by GCRC grant MO1 RR 00070 from the National Institutes of Health.

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Chest

Clinical Investigations: SleepFamilial Aggregates in Obstructive Sleep Apnea Syndrome

Section snippets

Population

Results

Comment

ACKNOWLEDGMENT

Lancet

Chest

Am J Orthod

Am J Orthod Dentofacial Orthop

Chest

Obstructive sleep apnea in family members

N Engl J Med

Familial “sleep apnea plus” syndrome: report of a family

Neurology

Familial childhood sleep apnea

Henry Ford Hosp J

A family study of sleep apnea: anatomic and physiologic interactions

Chest

Studies in the genetics of obstructive sleep apnea: familial aggregation of symptoms of sleep related breathing disorders

Am Rev Respir Dis

Familial influences on sleep apnea

eds

A manual of standardized terminology, techniques and a scoring system for sleep stages of human subjects

EEG arousals: scoring rules and examples

Sleep

Sleep and breathing

A new method for measuring daytime sleepiness: the Epworth Sleepiness Scale

Sleep

Clinical Investigations: Sleep
Familial Aggregates in Obstructive Sleep Apnea Syndrome