Pediatric Obesity-Hypoventilation Syndrome 

Obesity-hypoventilation syndrome (OHS) is a relatively uncommon finding in children who are obese, with an estimated frequency of 1-3%. Stated from a different point of view, 10% of patients with obstructive sleep apnea (OSA) are obese.

No firm diagnostic criteria to define OHS are recognized; this fact, along with limited pediatric studies and discrepant definitions of obesity and abnormal pediatric polysomnographic findings, make the diagnosis somewhat difficult. However, obesity, sleep-disordered breathing, and hypercarbia during wakefulness are features generally described with OHS. Other features include excessive daytime sleepiness, hyperactivity, poor school performance with difficulty attending to tasks and impaired memory, hypoxia, and signs of cor pulmonale.

In adults, male sex and obesity are common risk factors for OSA. Apnea, loud disruptive snoring, and daytime sleepiness are frequent presenting complaints. In children, however, neither these risk factors nor the symptom profile is as predictive for OSA, except in children who are obese.^{[1, 2, 3]}

In fact, 27% of children with OSA have failure to thrive. In one study, daytime sleepiness occurred with the same overall frequency as in control subjects; in another, daytime sleepiness was more frequent in obese children with OSA. Mental retardation has also been associated with OHS.

Education about pediatric sleep disorders is limited in US medical schools. Attempts are under way to improve awareness of sleep disorders and their impact on the health of children with obesity.

For patient education resources, see the Sleep Disorders Center, as well as Disorders That Disrupt Sleep (Parasomnias).

Go to Obesity and Obesity in Children for complete information on this topic.

The exact mechanism by which obesity-hypoventilation syndrome (OHS) develops is unknown; however, it is believed to be primarily related to abnormalities in ventilatory drive and response to hypoxia and hypercarbia, rather than to mechanical factors related to excessive body weight. Other authors feel that body weight and, more important, the distribution of body fat, hormones, and upper airway size and dynamics play important roles.

Additionally, animal studies are addressing circulating plasma leptin levels and their effect on expression of several hypothalamic neuropeptides. Leptin is also involved in respiratory control. Leptin-deficient mice (ob/ob) have been found to have hypoventilation, obesity, and an impairment in hypercapnic ventilatory response in both wakefulness and sleep, which suggests that leptin may play a central role in OHS.^[4]

Associated upper airway obstruction is important in the occurrence of obstructive sleep apnea (OSA) with hypoventilation or hypopnea (OSA/H) because OSA/H is observed more frequently when the 2 conditions occur together, in comparison with the simultaneous presentation of OSA/H and simple obesity.

Other factors that may play a role in the development of airway obstruction during sleep include rapid eye movement (REM) atonia, increased soft tissue and fatty infiltration around the neck, decreased chest wall compliance, and decreased lung volumes (especially in the supine position) secondary to the upward displacement of the diaphragm caused by increased abdominal fat. In children, tonsillar hypertrophy added to obesity appears to be more predictive of abnormal polysomnographic findings.

Causes of OHS include the following:

• Drugs
• Environment
• Heredity
• Lifestyle
• Eating habits
• Genetic syndromes

Patient history

Although pediatricians have long valued a good history and physical examination, studies have indicated that the predictive value of the recorded history and physical examination, compared with that of overnight polysomnography, is only 30-50% in patients with obesity-hypoventilation syndrome (OHS).

Symptoms during sleep may include the following^{[5, 6]} :

• Enuresis - This symptom alone has a predictive value of 46% for obstructive sleep apnea (OSA).
• Snoring intensity higher than 30 dB - This symptom has a predictive value of 60% for OSA. Characteristically, snoring tends to be worse during flareups of nasal allergies and during upper respiratory infections (URIs). Approximately 10% of children who snore have significant sleeping and breathing problems.
• Restless sleep
• Parasomnias, especially nightmares and sleep walking
• Witnessed apneas
• Irregular breathing patterns in sleep
• Sweating at night
• Sleep with head extended

During wakefulness, symptoms may include the following:

• Chronic mouth breathing
• Daytime sleepiness - This occurs much less frequently in children with OSA than in their adult counterparts, except in children who are obese.
• Hyperactivity - Younger children are more likely to show symptoms of sleep deprivation than excessive daytime sleepiness (EDS).
• Morning headaches
• Cyanosis
• Cardiac rhythm disturbances
• Systemic hypertension, pulmonary hypertension
• Poor school performance, poor memory, or poor concentration

In particular, a careful drug and alcohol history should be obtained. Sleep apnea and daytime sleepiness can be aggravated by the use of alcohol, sedating antihistamines, central nervous system (CNS) depressants, and some over-the-counter (OTC) cold preparations.

An increased incidence of hyperreactive airways (ie, asthma) is observed in children with who are obese (30%). Decreased exercise tolerance is also observed in children who are obese.

Physical examination

The physical examination begins in the waiting room. Evaluate sleepy children who cannot stay awake during the course of a physical examination or who consistently are found sleeping in the waiting room. Fewer than 10% of children who are obese have endogenous obesity. Therefore each child should be assessed for dysmorphic features, short stature, developmental delay, and abnormal genitalia.

With obesity, tidal volume can be decreased with a resultant increase in respiratory rate to maintain minute ventilation. Every child who is obese should be screened for hypertension. Hypertension in children is defined as systolic blood pressure, diastolic blood pressure, or both in the 95th percentile or higher on 3 or more separate visits.

Cyanosis in this scenario is suggestive of cor pulmonale.

The degree of obesity and fat distribution has an impact on the degree of respiratory symptoms during wakefulness and sleep. Adjusted body mass index (BMI) in the 95th percentile or higher is the most frequently used measure. BMI is not static during childhood and is age-specific and gender-specific. Skinfold thickness and bioelectric impedance are additional measures for obesity.

During a head, ears, eyes, nose, and throat (HEENT) examination, pay specific attention to features of various cardiofacial dysmorphologies, especially those associated with macroglossia, retrognathia, micrognathia, or high-arched palate. Note large tonsils and adenoids, dental malocclusion, and oropharyngeal crowding secondary to a large uvula or low-hanging soft palate. Evidence of nasal obstruction can be sought by simple rhinoscopy. Large adenoids, nasal polyps, cysts, deviation of the nasal septum, and swollen nasal turbinates can limit nasal airflow.

In the neck area, search for evidence of compression secondary to chin folds, excessive fatty deposition, tumors, lymph nodes, or thyroid.

Thoracic kyphosis has been associated with obesity. An acquired pectus excavatum resulting from increased muscle use in overcoming the extrathoracic obstruction with sleep has been described in children with OSA. Some of the syndromes (eg, Prader-Willi syndrome) associated with OHS also have an increased incidence of scoliosis. Pay attention to the possibility of additional risk factors for restrictive ventilatory defects. Cor pulmonale may be suggested by a displaced cardiac impulse and a loud pulmonic second (heart) sound (P2). Measured tidal volume may be decreased.

Abdominal obesity is associated with an upward displacement of the diaphragm, which is more pronounced in the supine position.

Ankle edema, in this context, is suggestive of congestive heart failure. Digital clubbing is associated with pulmonary osteoarthropathy

Rhodes data show decreased academic performance. Consider this diagnosis when evaluating a child who has obesity and a learning disability.^[7] Comorbid conditions (eg, thyroid disease, diabetes) should be considered. Consider evaluation of potential complications (eg, cor pulmonale, systemic hypertension).^[8]

The differential diagnosis includes the following:

Beckwith-Wiedemann Syndrome

Prader-Willi Syndrome

Obstructive sleep apnea

Sleep Apnea

Other problems to be considered include the following:

• Narcolepsy
• Use (abuse) of sedatives and antihistamines
• Sleep deprivation
• Sleep-related breathing disorders

Obesity-hypoventilation syndrome (OHS) may be associated with daytime hypoxemia and hypercarbia. Response to carbon dioxide is decreased in obstructive sleep apnea (OSA). Hematocrit levels may be elevated in children with chronic hypoxemia.

On chest radiography, specifically note evidence of chest wall deformities, heart size, and evidence of congestive heart failure.

On echocardiography, right ventricular hypertrophy can be observed with OSA plus hypoventilation or hypopnea (OSA/H) in association with chronic hypoxemia.

On electrocardiography (ECG), cardiac dysrhythmias and right bundle branch block (RBBB) have been reported.

Flow-volume loop

The sawtooth pattern associated with upper airway obstruction may be observed.

Spirometry

In a study by Mallory et al, most children (58%) had abnormal pulmonary function findings, which were primarily obstructive in nature.^[9]

A study by Fung et al showed significant changes in forced vital capacity (FVC) in boys who were overweight but not in girls who were overweight.^[10] This is consistent with the finding that fat distribution in adolescents who are overweight and obese differs from that seen in adults and is gender specific. Boys tend to accumulate fat in the abdominal area, whereas girls tend to accumulate fat in the subscapular area.

Maximum voluntary ventilation may be decreased.

Lung volumes

Patterns of fat distribution differ in adolescents who are overweight and obese. Because of the impact of the abdominal fat on the diaphragm, the expiratory reserve volume (ERV) is decreased, and, as a result, the FVC is also decreased. Adult studies show the ERV to be severely decreased in patients with extreme and morbid obesity.

Biring et al along found ERV to be the most sensitive indicator of obesity.^[11] Many reasons have been offered in addition to the mass effect on the position of the diaphragm. These include decreased diaphragmatic mobility, decreased respiratory compliance, decreased respiratory muscle strength, and fatty infiltration of the respiratory muscles.

Diffusion

Studies of diffusion have yielded varying results. Inselma et al reported children with decreased diffusing capacity of lung for carbon monoxide (DLCO).^[12] By contrast, Biring et al studied a group of patients aged 13-78 years and reported that the DLCO and alveolar volume were normal, except in those who were extremely obese.^[11]

Airway resistance may be increased. Inspiratory and expiratory pressures were normal in the study by Inselma et al.^[12]

Overnight polysomnography

In children and adolescents, morbid obesity can be associated with hypoventilation, hypoxia, and hypercarbia during sleep.^{[13, 14]} Others may present with evidence of obstructive sleep apnea (see the image below).

Multiple sleep latency test

The multiple sleep latency test (MSLT) can be useful in the evaluation of patients complaining of excessive daytime sleepiness. The MSLT is performed on the day following the overnight polysomnogram. Its findings can be used to assess pathologic sleepiness and contribute to a diagnosis of narcolepsy.

Supportive and adjunctive therapy

Currently, noninvasive ventilatory support (eg, nasal continuous positive airway pressure ventilation [NCPAP]) with supplemental oxygen, when necessary, is the treatment of choice, along with weight loss.

Weight loss is recommended in individuals with obesity but is often difficult to achieve and sustain. In addition, although weight loss remains a cornerstone to the treatment of obesity, it may not always improve the symptoms of obstructive sleep apnea (OSA) and hypoventilation or hypopnea (OSA/H).

The introduction of continuous positive airway pressure (CPAP) or noninvasive positive pressure ventilation for children with OSA may benefit from the gradual introduction of ventilatory support, beginning with lower than effective pressures initially and working up to effective pressure. Behavioral modification techniques have been helpful, particularly in young children and in children with developmental delay.

Pharmacologic therapy

The use of central respiratory stimulants in the treatment of obesity-hypoventilation syndrome (OHS) appears intermittently in the literature.^[15] However, reports are primarily anecdotal or of very limited scope. Progesterone, theophylline, protriptyline, and buspirone have been used in some studies.

Medications may be required for the treatment of comorbidities of obesity, which include hypertension, dyslipidemia, and metabolic syndrome.

An increased incidence of asthma has been seen in children who are obese.^[16] Management guidelines for asthma are outlined in the United States Department of Health and Human Services National Asthma Education and Prevention Program Expert Panel Report and 2007 Update.^[17]

Surgical therapy

Surgical options include the following:

• Tonsillectomy
• Adenoidectomy
• Adenotonsillectomy (may be successful even when weight loss alone does not produce satisfactory resolution of symptoms)
• Tracheostomy
• Uvulopalatopharyngoplasty (UPPP)
• Mandibular advancement surgery

In children with apnea, an increased risk of postoperative complications after relief of upper airway obstruction is observed when the patient history includes young age (< 2-3 y), morbid obesity, hypotonia, cor pulmonale, or severe OSA. In such patients, strongly consider cardiorespiratory monitoring in a pediatric recovery or special care unit. Postoperative pulmonary edema may be observed.

Consultations

In pediatric patients, sleep medicine may be practiced within various subspecialties, including pediatric pulmonology, pediatric otolaryngology, pediatric neurology, and child psychiatry. Also, a small number of board-certified sleep specialists are pediatricians.

• Pediatric pulmonologist
• Pediatric cardiologist
• Pediatric anesthesiologist
• Pediatric otolaryngologist
• Pediatric endocrinologist
• Nutritionist

Long-term management

Patients receiving noninvasive nocturnal ventilatory support should be monitored for the following:

• Compliance
• Need for changes in pressure support
• Need for changes in mask size
• Complications and adverse effects of treatment
• Recurrence or progression of symptoms

Further inpatient care

Obesity has been linked to metabolic syndrome, with a prevalence that increases with advancing degrees of obesity. This high prevalence warrants consideration in children who are obese, both inpatient and follow-up care.

Cardiovascular risk factors, including evaluation of blood pressure, should be assessed.

Prevention

Childhood and adolescent obesity are both associated with an increased incidence of adult obesity. Good nutrition is a deterrent. Tailor specific diets to meet the nutritional and growth requirements of the child and to facilitate weight loss.

Physical activity is also a deterrent. A graded exercise plan is suggested. Consideration of the exercise tolerance of each individual child is important. Awareness of the increased incidence of asthma and lack of physical conditioning in these children is important when designing and implementing a graded exercise program.

Sustained weight loss is difficult. The cardiovascular consequences of obesity include dysrhythmias, right ventricular hypertrophy, and congestive heart failure. Children with obesity have an increased incidence of asthma, and exercise tolerance may be limited. Results of pulmonary function testing in children with obesity vary.

Pulmonary consequences observed in children and adolescents include an increased frequency of reactive airways, poor exercise tolerance, increased work of breathing, and increased oxygen consumption. The few people who develop obesity-hypoventilation syndrome (OHS) experience right-side heart failure with right ventricular hypertrophy.