Brian M. McGinley

Contribution of male sex, age, and obesity to mechanical instability of the upper airway during sleep

Male sex, obesity, and age are risk factors for obstructive sleep apnea, although the mechanisms by which these factors increase sleep apnea susceptibility are not entirely understood. This study examined the interrelationships between sleep apnea risk factors, upper airway mechanics, and sleep apnea susceptibility. In 164 (86 men, 78 women) participants with and without sleep apnea, upper airway pressure-flow relationships were characterized to determine their mechanical properties [pharyngeal critical pressure under hypotonic conditions (passive Pcrit)] during non-rapid eye movement sleep. In multiple linear regression analyses, the effects of body mass index and age on passive Pcrit were determined in each sex. A subset of men and women matched by body mass index, age, and disease severity was used to determine the sex effect on passive Pcrit. The passive Pcrit was 1.9 cmH(2)O [95% confidence interval (CI): 0.1-3.6 cmH(2)O] lower in women than men after matching for body mass index, age, and disease severity. The relationship between passive Pcrit and sleep apnea status and severity was examined. Sleep apnea was largely absent in those individuals with a passive Pcrit less than -5 cmH(2)O and increased markedly in severity when passive Pcrit rose above -5 cmH(2)O. Passive Pcrit had a predictive power of 0.73 (95% CI: 0.65-0.82) in predicting sleep apnea status. Upper airway mechanics are differentially controlled by sex, obesity, and age, and partly mediate the relationship between these sleep apnea risk factors and obstructive sleep apnea.

Upper airway neuromuscular compensation during sleep is defective in obstructive sleep apnea

Obstructive sleep apnea is the result of repeated episodes of upper airway obstruction during sleep. Recent evidence indicates that alterations in upper airway anatomy and disturbances in neuromuscular control both play a role in the pathogenesis of obstructive sleep apnea. We hypothesized that subjects without sleep apnea are more capable of mounting vigorous neuromuscular responses to upper airway obstruction than subjects with sleep apnea. To address this hypothesis we lowered nasal pressure to induce upper airway obstruction to the verge of periodic obstructive hypopneas (cycling threshold). Ten patients with obstructive sleep apnea and nine weight-, age-, and sex-matched controls were studied during sleep. Responses in genioglossal electromyography (EMG(GG)) activity (tonic, peak phasic, and phasic EMG(GG)), maximal inspiratory airflow (V(I)max), and pharyngeal transmural pressure (P(TM)) were assessed during similar degrees of sustained conditions of upper airway obstruction and compared with those obtained at a similar nasal pressure under transient conditions. Control compared with sleep apnea subjects demonstrated greater EMG(GG), V(I)max, and P(TM) responses at comparable levels of mechanical and ventilatory stimuli at the cycling threshold, during sustained compared with transient periods of upper airway obstruction. Furthermore, the increases in EMG(GG) activity in control compared with sleep apnea subjects were observed in the tonic but not the phasic component of the EMG response. We conclude that sustained periods of upper airway obstruction induce greater increases in tonic EMG(GG), V(I)max, and P(TM) in control subjects. Our findings suggest that neuromuscular responses protect individuals without sleep apnea from developing upper airway obstruction during sleep.

Effect of a High-Flow Open Nasal Cannula System on Obstructive Sleep Apnea in Children

OBJECTIVE: Obstructive sleep apnea syndrome in children is associated with significant morbidity. Continuous positive airway pressure (CPAP) treats obstructive apnea in children, but is impeded by low adherence. We, therefore, sought to assess the effect of warm humidified air delivered through an open nasal cannula (treatment with nasal insufflation [TNI]) on obstructive sleep apnea in children with and without adenotonsillectomy. METHODS: Twelve participants (age: 10 ± 1 years; BMI: 35 ± 14 kg/m2), with obstructive apnea-hypopnea syndrome ranging from mild to severe (2–36 events per hour) were administered 20 L/min of air through a nasal cannula. Standard sleep architecture, sleep-disordered breathing, and arousal indexes were assessed at baseline, on TNI, and on CPAP. Additional measures of the percentage of time with inspiratory flow limitation, respiratory rate, and inspiratory duty cycle were assessed at baseline and on TNI. RESULTS: TNI reduced the amount of inspiratory flow limitation, which led to a decrease in respiratory rate and inspiratory duty cycle. TNI improved oxygen stores and decreased arousals, which decreased the occurrence of obstructive apnea from 11 ± 3 to 5 ± 2 events per hour (P < .01). In the majority of children, the reduction in the apnea-hypopnea index on TNI was comparable to that on CPAP. CONCLUSIONS: TNI offers an alternative to therapy to CPAP in children with mild-to-severe sleep apnea. Additional studies will be needed to determine the efficacy of this novel form of therapy.

Prevalence and severity of obstructive sleep apnea and snoring in infants with Pierre Robin sequence.

Objective To evaluate the prevalence and severity of obstructive sleep apnea in infants with Pierre Robin sequence prior to airway intervention and determine whether snoring correlates with the presence of obstructive sleep apnea in this population. Design Retrospective case series. Setting Urban tertiary care teaching hospital. Participants/Methods Review of infants with Pierre Robin sequence who underwent polysomnography in the first year of life from 2002 to 2007. Only results from the initial polysomnography were analyzed. A subgroup of consecutive prospectively tested patients was also evaluated. Results A total of 33 infants with Pierre Robin sequence were identified. Of these, 13 (39%), 11 girls and two boys, underwent polysomnography in the first year of life. The mean age at evaluation was 48 days (range, 7 to 214 days). Seven nonconsecutive and six consecutive patients were included, and no significant differences were seen between groups. Obstructive sleep apnea was identified in 11 of 13 (85%) infants. The mean obstructive apnea-hypopnea index was 33.5 (range, 0 to 85.7). Obstructive sleep apnea severity was mild in 2 of 11 (18%), moderate in 3 of 11 (27%), and severe in 6 of 11 (55%). Mean end-tidal Pco2 measurements were elevated at 59 mm Hg (range, 47 to 76 mm Hg). Mean oxygen saturation nadir was decreased at 80% (range, 68% to 93%). Snoring occurred in only 7 of 13 (54%). Of the subjects with obstructive sleep apnea, snoring occurred in 6 of 11 (55%). Conclusion The high incidence of obstructive sleep apnea in this group suggests that polysomnography should be promptly performed in children with Pierre Robin sequence. Although snoring was seen in the majority, the absence of snoring did not exclude the presence of obstructive sleep apnea.

Characterization of Obstructive Sleep Apnea Before and After Tongue-Lip Adhesion in Children With Micrognathia

Objectives To characterize airway obstruction before and after tongue-lip adhesion in children with micrognathia using polysomnography. Design Retrospective pilot case series. Participants and Methods Evaluation of all children with micrognathia who underwent tongue-lip adhesion and polysomnography before and after surgery from 2002 to 2007 (N = 8). Results Eight children met inclusion criteria; six were girls. The mean interval between polysomnography and tongue-lip adhesion was 6 days (range, 2 to 13 days) preoperatively and 17 days (range, 5 to 32 days) postoperatively. Severe obstructive sleep apnea was identified in seven of eight (88%) children, with a mean preoperative obstructive apnea hypopnea index of 52.6 events per hour (range, 7.1 to 85.7 events per hour). None had significant central sleep apneas (>5 per hour). Tongue-lip adhesion resulted in a mean decrease of 34.5 events per hour (range, −65.8 to 71.6 events per hour). After tongue-lip adhesion, seven of eight (87.5%) patients had an improved obstructive apnea hypopnea index, with resolution of obstructive sleep apnea in one child and improvement to mild (two) and moderate (two) obstructive sleep apnea in four others. Only one child had an obstructive apnea hypopnea index that increased after tongue-lip adhesion. Peak end-tidal pCO2 measurements were elevated in all eight children before surgery at a mean of 60 mm Hg (range, 52 to 76 mm Hg) that improved to 51 mm Hg (range, 45 to 59 mm Hg), with normal peak levels in four children. Oxygen saturation nadir improved from 73% (range, 58% to 81%) to 82% (range, 65% to 94%). Conclusions Tongue-lip adhesion may be performed in micrognathic infants to alleviate airway obstruction. Polysomnographic evaluation in this pilot study before and after surgery suggests that tongue-lip adhesion usually improves obstructive sleep apnea, but only 38% had complete resolution. Future studies of tongue-lip adhesion efficacy should include Polysomnographic evaluation.

Leptin and the control of pharyngeal patency during sleep in severe obesity

RATIONALE Obesity imposes mechanical loads on the upper airway, resulting in flow limitation and obstructive sleep apnea (OSA). In previous animal models, leptin has been considered to serve as a stimulant of ventilation and may prevent respiratory depression during sleep. We hypothesized that variations in leptin concentration among similarly obese individuals will predict differences in compensatory responses to upper airway obstruction during sleep. METHODS An observational study was conducted in 23 obese women [body mass index (BMI): 46 ± 3 kg/m(2), age: 41 ± 12 yr] and 3 obese men (BMI: 46 ± 3 kg/m(2), age: 43 ± 4 yr). Subjects who were candidates for bariatric surgery were recruited to determine upper airway collapsibility under hypotonic conditions [pharyngeal critical pressure (passive PCRIT)], active neuromuscular responses to upper airway obstruction during sleep, and overnight fasting serum leptin levels. Compensatory responses were defined as the differences in peak inspiratory airflow (ΔVImax), inspired minute ventilation (ΔVI), and pharyngeal critical pressure (ΔPCRIT) between the active and passive conditions. RESULTS Leptin concentration was not associated with sleep disordered breathing severity, passive PCRIT, or baseline ventilation. In the women, increases in serum leptin concentrations were significantly associated with increases in ΔVImax (r(2) = 0.44, P < 0.001), ΔVI (r(2) = 0.40, P < 0.001), and ΔPCRIT (r(2) = 0.19, P < 0.04). These responses were independent of BMI, waist-to-hip ratio, neck circumference, or sagittal girth. CONCLUSION Leptin may augment neural compensatory mechanisms in response to upper airway obstruction, minimizing upper airway collapse, and/or mitigating potential OSA severity. Variability in leptin concentration among similarly obese individuals may contribute to differences in OSA susceptibility.

Compensatory responses to upper airway obstruction in obese apneic men and women

Defective structural and neural upper airway properties both play a pivotal role in the pathogenesis of obstructive sleep apnea. A more favorable structural upper airway property [pharyngeal critical pressure under hypotonic conditions (passive Pcrit)] has been documented for women. However, the role of sex-related modulation in compensatory responses to upper airway obstruction (UAO), independent of the passive Pcrit, remains unclear. Obese apneic men and women underwent a standard polysomnography and physiological sleep studies to determine sleep apnea severity, passive Pcrit, and compensatory airflow and respiratory timing responses to prolonged periods of UAO. Sixty-two apneic men and women, pairwise matched by passive Pcrit, exhibited similar sleep apnea disease severity during rapid eye movement (REM) sleep, but women had markedly less severe disease during non-REM (NREM) sleep. By further matching men and women by body mass index and age (n = 24), we found that the lower NREM disease susceptibility in women was associated with an approximately twofold increase in peak inspiratory airflow (P = 0.003) and inspiratory duty cycle (P = 0.017) in response to prolonged periods of UAO and an ∼20% lower minute ventilation during baseline unobstructed breathing (ventilatory demand) (P = 0.027). Thus, during UAO, women compared with men had greater upper airway and respiratory timing responses and a lower ventilatory demand that may account for sex differences in sleep-disordered breathing severity during NREM sleep, independent of upper airway structural properties and sleep apnea severity during REM sleep.

Treatment alternatives for sleep-disordered breathing in the pediatric population

Purpose for review Childhood sleep-disordered breathing (SDB) is associated with a myriad of health problems that underscore the need for early diagnosis and treatment. Children with SDB present with behavior problems, deficits of general intelligence, learning and memory deficits, evidence of brain neuronal injury, increased cardiovascular risk, and poor quality of life. Children are in a rapid state of cognitive development; therefore, alterations of health and brain function associated with SDB could permanently alter a childs social and economic potential, especially if the disorder is not recognized early in life or is treated inadequately. Recent findings There is evidence that the majority of the problems associated with SDB improve with treatment. Treatment strategies are now being aimed at mechanisms underlying the disorder. There are multiple treatment options available to children; some are novel, with pending treatments on the horizon that may replace age-old therapies such as adenotonsillectomy or nasal positive pressure. Summary It is imperative that healthcare workers actively seek out signs and symptoms of SDB in patients to improve early detection and treatment for prevention of long-term morbidity.

Day Care Increases the Risk of Respiratory Morbidity in Chronic Lung Disease of Prematurity

OBJECTIVES: Infants and children with chronic lung disease of prematurity (CLDP) are at increased risk for morbidity and mortality from respiratory viral infections. Exposure to respiratory viruses may be increased in the day care environment. The risk of respiratory morbidity from day care attendance in the CLDP population is unknown. We therefore sought to determine if day care attendance is a significant risk factor for increased respiratory morbidity and symptoms in infants and children with CLDP. METHODS: Between January 2008 and October 2009, parents of infants and children with CLDP were surveyed. Information on perinatal history, sociodemographic information, day care attendance, and indicators of respiratory morbidity, including emergency department (ED) visits, hospitalizations, systemic corticosteroid use, antibiotic use, and respiratory symptoms, was collected on children <3 years of age. Logistic regression models were constructed to examine associations between exposure to day care and respiratory morbidities. RESULTS: Data were collected from 111 patients with CLDP. The average gestational age was 26.2 ± 2.0 weeks. Day care attendance was associated with significantly higher adjusted odds for ED visits (odds ratio [OR]: 3.74 [95% confidence interval (CI): 1.41–9.91]; P < .008), systemic corticosteroid use (OR: 2.22 [CI: 1.10–4.49]; P < .026), antibiotic use (OR: 2.40 [CI: 1.08–5.30]; P < .031), and days with trouble breathing (OR: 2.72 [CI: 1.30–5.69]; P < .008). Although there was an increased OR for hospitalization (OR: 3.22 [CI: 0.97–10.72]; P < .057), this did not reach statistical significance. CONCLUSIONS: We found that day care attendance is associated with increased respiratory morbidities in young children with CLDP. Physicians should consider screening for and educating caregivers about the risks of day care attendance by young children with CLDP.

Polysomnographic Values in Adolescents With Ataxia Telangiectasia

Most adolescents with ataxia telangiectasia (A‐T) develop progressive bulbar muscle weakness and decreased pulmonary reserve. The purpose of this study was to define the patterns of sleep and respiration during sleep, and to identify sleep‐related breathing problems in subjects with A‐T. To address these issues, overnight polysomnography was performed on 12 adolescents with A‐T. Eleven of the 12 subjects completed overnight polysomnography. The median age was 16 years (range, 13–20 years). All subjects in the study were wheelchair‐bound and the median forced vital capacity (% predicted of normal) was 44% (range, 16–82%). The mean sleep efficiency was 72.6% with a mean apnea hypopnea index (AHI) of 0.7 events/hr (range, 0–2.2). The majority of apnea/hypopneas were REM related. The mean central apnea index was 0.1 events/hr (range, 0–0.2). The mean oxygen saturation nadir was 92.7% (range, 87–96) and the mean peak end‐tidal carbon dioxide ET  CO 2 value was 53.8 mm Hg (range, 49–60). Two of 11 subjects had ET  CO 2 values ≥50 mm Hg for more than 50% of total sleep time. In this study, the majority of A‐T adolescents had infrequent partial or complete upper airway obstructions during sleep and minimal nighttime hypoxemia. They did, however, have decreased sleep efficiency most likely, due in part, to their underlying neurological condition. This decrease in total sleep time may underestimate hypoventilation. Based on these findings, overnight polysomnography should be considered in adolescents with A‐T, particularly in those in which there is a clinical suspicion of sleep related breathing abnormalities. Pediatr Pulmonol. 2008; 43:674–679.