Sleep-Disordered Breathing, Orofacial Growth, and Prevention of Obstructive Sleep Apnea.
Sleep medicine clinics
2019; 14 (1): 13–20
Pediatric sleep medicine: a key sub-specialty for the pediatrician.
Re: Withdrawal of Advanced Notice of Proposed Rulemaking (ANPRM) on Obstructive Sleep Apnea (OSA) Does Not Mean Examiners and Employers Should Ignore Safety Risks.
Journal of occupational and environmental medicine
Mouth breathing, "nasal disuse," and pediatric sleep-disordered breathing
SLEEP AND BREATHING
2015; 19 (4): 1257-1264
Abnormal breathing during sleep is related to intrinsic and extrinsic factors that are present early in life. Investigation of fetal development and early-in-life orofacial growth allows recognition of risk factors that lead to change in upper airway patency, which leads to abnormal upper airway resistance, abnormal inspiratory efforts, and further increase in resistance and progressive narrowing of the collapsible upper airway. Such evolution can be recognized by appropriate clinical evaluation, specific polysomnographic patterns, and orofacial imaging. Recognition of the problems should lead to appropriate treatments and prevention of obstructive sleep apnea and its comorbidities.
View details for PubMedID 30709527
Emerging drugs for common conditions of sleepiness: obstructive sleep apnea and narcolepsy
EXPERT OPINION ON EMERGING DRUGS
2015; 20 (4): 571-582
Adenotonsillectomy (T&A) may not completely eliminate sleep-disordered breathing (SDB), and residual SDB can result in progressive worsening of abnormal breathing during sleep. Persistence of mouth breathing post-T&As plays a role in progressive worsening through an increase of upper airway resistance during sleep with secondary impact on orofacial growth.Retrospective study on non-overweight and non-syndromic prepubertal children with SDB treated by T&A with pre- and post-surgery clinical and polysomnographic (PSG) evaluations including systematic monitoring of mouth breathing (initial cohort). All children with mouth breathing were then referred for myofunctional treatment (MFT), with clinical follow-up 6 months later and PSG 1 year post-surgery. Only a limited subgroup followed the recommendations to undergo MFT with subsequent PSG (follow-up subgroup).Sixty-four prepubertal children meeting inclusion criteria for the initial cohort were investigated. There was significant symptomatic improvement in all children post-T&A, but 26 children had residual SDB with an AHI > 1.5 events/hour and 35 children (including the previous 26) had evidence of "mouth breathing" during sleep as defined [minimum of 44 % and a maximum of 100 % of total sleep time, mean 69 ± 11 % "mouth breather" subgroup and mean 4 ± 3.9 %, range 0 and 10.3 % "non-mouth breathers"]. Eighteen children (follow-up cohort), all in the "mouth breathing" group, were investigated at 1 year follow-up with only nine having undergone 6 months of MFT. The non- MFT subjects were significantly worse than the MFT-treated cohort. MFT led to normalization of clinical and PSG findings.Assessment of mouth breathing during sleep should be systematically performed post-T&A and the persistence of mouth breathing should be treated with MFT.
View details for DOI 10.1007/s11325-015-1154-6
View details for PubMedID 25877805
Current Treatment of Selected Pediatric Sleep Disorders
2012; 9 (4): 791-800
Obstructive sleep apnea (OSA) and narcolepsy are sleep disorders associated with high prevalence and high symptomatic burden including prominent sleepiness, daytime dysfunction and poor nocturnal sleep. Both have elevated risk of poor health outcomes. Current therapies are often underutilized, cumbersome, costly or associated with residual symptoms.This review covers current available therapies for OSA and narcolepsy as well as discusses areas for potential drug development, and agents in the therapeutic pipeline, including the cannabinoid dronabinol (OSA), the histamine inverse agonist/ antagonist pitolisant (narcolepsy), and stimulants with uncertain and/or multiple activities such as JZP-110 and JZP-386 (narcolepsy, possibly OSA). Finally it addresses new approaches and uses for therapies currently on the market such as the carbonic anhydrase inhibitor acetazolamide (OSA).Both OSA and narcolepsy are conditions of sleepiness for which lifelong treatments are likely to be required. In OSA, while continuous positive airway pressure will likely remain the gold standard therapy for the foreseeable future, there is plenty of room for integrating phenotypes and variants of OSA into therapeutic strategies to lead to better, more personalized disease modification. In narcolepsy, unlike OSA, drug therapy is the current mainstay of treatment. Advances using novel mechanisms to treat targeted symptoms such as sleepiness and/or novel agents that can treat more than one symptom of narcolepsy, hold promise. However, cost, convenience and side effects remain challenges.
View details for DOI 10.1517/14728214.2015.1115480
View details for PubMedID 26558298
Update on emerging drugs for insomnia
EXPERT OPINION ON EMERGING DRUGS
2012; 17 (3): 295-298
While pediatric sleep disorders are relatively common, treatments are often not straightforward. There is often a paucity of gold standard studies and data available to guide clinicians, treatments may yield arguably incomplete results, interventions may require chronic use, and/ or involve multiple modalities including behavioral interventions that require high parental and family commitment. This review points out diagnostic differences compared to adults and focuses on current therapy for selected common pediatric sleep disorders including sleep disordered breathing/ obstructive sleep apnea, narcolepsy, and restless legs syndrome. Other common pediatric sleep disorders, such as insomnia and parasomnias, are not covered.
View details for DOI 10.1007/s13311-012-0149-2
View details for Web of Science ID 000310325000010
View details for PubMedID 23055049
View details for PubMedCentralID PMC3480565
Hiding in plain sight Risk factors for REM sleep behavior disorder
2012; 79 (5): 402-403
Narcolepsy in adolescents.
Adolescent medicine: state of the art reviews
2010; 21 (3): 542-?
In recent years, there has been no evidence that the problem of chronic insomnia has faded in the least in US adults; on the contrary, a recent estimate of annual lost productivity due to insomnia was $63.2 billion dollars. However, the proportion of insomniacs who are treated continues to be low, indicating the need for continued development and dissemination of effective therapies. Hypnotic drug development has arguably become more focused in recent years, particularly upon the highly anticipated novel target, the orexin (hypocretin) system. Merck's suvorexant (MK-4305) is the first compound of the so-called dual orexin receptor antagonist (DORA) class expected to be submitted for FDA approval, with a new drug application anticipated in 2012. While there has also been some new activity in the modulation of well-characterized targets with well-characterized agents, such as CNS histamine receptors with low-dose doxepin, a decades-old antidepressant and GABA(A) with sublingual zolpidem, experience with melatonin and serotonin modulators suggests that other targets also exist. Diversifying insomnia drug targets may expand possibilities for customizing hypnotic administration to individualized patient presentation and mechanistic underpinnings. In addition, it may offer improved avenues for combining medications with non-drug treatments such as cognitive behavioral therapy for insomnia (CBT-I).
View details for DOI 10.1517/14728214.2012.693158
View details for Web of Science ID 000307998500003
View details for PubMedID 22920041
MEDICAL CLINICS OF NORTH AMERICA
2010; 94 (3): 563-?
Narcolepsy is a disorder of children and adolescence, but until recently it was often not identified until adulthood, with a reported time from onset to diagnosis of about a decade. This disorder affects approximately 0.05% of the population and starts in childhood and adolescence about half of the time. With narcolepsy, the boundaries between wake, sleep, and dreams are blurred. The cardinal features of narcolepsy-cataplexy are daytime somnolence, cataplexy (sometimes occurring long after onset of sleepiness), sleep paralysis, and hypnagogic hallucinations. Weight gain, disturbed nocturnal sleep, and social/school functional changes are common; reactive substance use to maintain wakefulness during the day may also be seen. Males and females are equally affected. It is classically associated with HLA DQB1*0602, the most specific genetic marker for narcolepsy across all ethnic groups. CSF hypocretin has recently been found to be depleted in this disorder, and late-breaking data support that the disease is caused by autoimmune destruction of hypocretin-producing neurons in the hypothalamus. There is no known cure for narcolepsy. Therapies include behavioral/ scheduling modification, medications to combat daytime sleepiness and cataplexy, and treatment of concomitant disorders leading to daytime sleepiness. The differential diagnosis for this disorder should include other disorders of excessive daytime sleepiness with a proclivity toward onset in adolescence, such as delayed sleep phase syndrome, obstructive sleep apnea, and insufficient sleep time; substance use; and less commonly neurologic disorders such as Klein Levin syndrome, Prader-Willi syndrome, and others. Immunomodulator therapy and hypocretin replacement are proposed therapies that hold promise for the future.
View details for PubMedID 21302860
Emerging drugs for insomnia: new frontiers for old and novel targets
EXPERT OPINION ON EMERGING DRUGS
2009; 14 (3): 411-422
Insomnia is not only the most common sleep disorder in the population, it is a frequent complaint heard overall by primary care physicians and specialists alike. Given the high prevalence of this disorder, its tendency to persist, and the frequency with which patients complain of symptoms in practice, it is imperative to have an understanding of basic sleep-wake mechanisms and the evolving field of pharmacologic approaches to enhance sleep. Currently, pharmacologic approaches are among the most widely used therapies for insomnia. This article reviews sleep-wake mechanisms, the neuroanatomic targets for sleep and wake-promoting agents, and discusses currently used agents to promote sleep and investigational hypnotics.
View details for DOI 10.1016/j.mcna.2010.02.012
View details for Web of Science ID 000278853600010
View details for PubMedID 20451033
Multiple Sleep Latency Test and Maintenance of Wakefulness Test
2008; 134 (4): 854-861
Insomnia is the most prevalent sleep disorder, with up to 50% of the US adult population reporting symptoms of insomnia on a weekly basis and approximately 12% with insomnia disorder. Comorbid conditions such as depression and anxiety are frequent. Insomnia is more common with older age, female gender and socioeconomic status. Traditionally, therapy has focused on GABA(A) receptor agonists, and off-label antidepressant and antihistamine use.With increased understanding of complex neural networks involved in sleep and wake, hypnotics are being developed to target a broader variety of receptors with increasing selectivity. This review summarizes promising compounds in Phase II and III trials with evidence supporting efficacy for treatment of insomnia.5-HT(2A) and 5-HT(2C) antagonists, melatonergic (MT1/MT2) agonists, orexin receptor (OX1/OX2) antagonists, as well as GABA(A) receptor agonists are reviewed and summarized. Data are collected from PubMed and Pharmaprojects database searches, company websites, recent scientific meeting presentations and abstracts.A variety of drugs targeting several pathways, including GABA(A) agonism, MT1/MT2 agonism, 5-HT(2A) antagonism, OX1/OX2 antagonism and others, are in Phase II and III trials. More work should be done to understand the impact of these drugs in certain populations and in the context of comorbid conditions.
View details for DOI 10.1517/14728210903171948
View details for PubMedID 19708818
Nasal obstruction in children with sleep-disordered breathing
ANNALS ACADEMY OF MEDICINE SINGAPORE
2008; 37 (8): 645-648
Excessive daytime sleepiness and fatigue are common complaints in the sleep clinic. The objective evaluation and quantification of these symptoms is important for both the diagnosis of underlying health problems and for gauging treatment response. The multiple sleep latency test measures physiologic sleepiness, whereas the maintenance of wakefulness test (MWT) aims to measure manifest sleepiness. Neither test correlates well with subjective measures of sleep such as the Epworth sleepiness scale and the Stanford sleepiness scale. Although in the past methodological testing differences existed, in 2005 updated practice parameters were published, promoting the standardization of testing procedures. In recent years, there has been an effort to document daytime sleepiness when associated with occupational risk. However, these laboratory-based tests may not reflect or predict real-life experience. Normative data for both tests, particularly the MWT, are limited, and are inadequate for the evaluation of pediatric patients, shift workers, and others.
View details for DOI 10.1378/chest.08-0822
View details for Web of Science ID 000260097600032
View details for PubMedID 18842919
Nasal obstruction secondary to pathological enlargement of inferior nasal turbinates contributes to sleep-disordered breathing (SBD) in prepubertal children, but treatments designed to address turbinate enlargement are often not performed. The aims of these studies are: (1) to appreciate the contribution to SDB of untreated enlarged nasal turbinates in prepubertal children; and (2) to report our experience with treatment of enlarged nasal turbinates in young children with SDB.Children with enlarged nasal turbinates who underwent adenotonsillectomy (T&A) had significantly less improvement in postoperative apnoea-hypopnoea index (AHI) compared to those treated with concomitant turbinate reduction. Children in the untreated turbinate hypertrophy group subsequently underwent radiofrequency ablation of the inferior nasal turbinates; following this procedure, AHI was no different than AHI of those without hypertrophy.In an analysis of safety and effectiveness of radiofrequency treatment of the nasal turbinates, we found the procedure to be a well-tolerated component of SDB treatment.We conclude that radiofrequency (RF) treatment of inferior nasal turbinates is a safe and effective treatment in young prepubertal children with SDB. When indicated, it should be included in the treatment plan for prepubertal children with SDB. However, the duration of effectiveness is variable and therapy may need to be repeated if turbinate hypertrophy recurs.
View details for PubMedID 18797556