Obstructive Apnea and Hypopnea Length

Version	Summary	Created by	Modification	Content Size	Created at	Operation
1		Lourdes M. DelRosso	+ 1495 word(s)	1495	2021-10-14 10:26:05	\|
2	format corrected.	Beatrix Zheng	+ 65 word(s)	1560	2021-10-22 07:50:00	\|

This entry is adapted from the peer-reviewed paper 10.3390/brainsci11101343

Breathing is an essential function that requires both metabolic and behavioral control during wakefulness but depends on metabolic control during sleep. Breathing also depends on the maturity of the neural centers and the strength of the respiratory muscles. In patients with sleep disordered breathing, breathing after an apneic event results from the interaction between chemoreceptors relaying information to brainstem neurons responsible for generating breathing patterns and influencing respiratory motor neurons controlling the airway muscles; both of these mechanisms are also affected by sleep stage physiology.

pediatric obstructive sleep apnea hypopnea length

1. Introduction

With sleep onset, muscle tone and minute ventilation are reduced with a subsequent increase in upper airway resistance ^[1]. REM sleep further decreases tidal volume and protective airway reflexes ^[2]. In obstructive sleep apnea, the obstructive event termination usually occurs simultaneously with an arousal, triggered by hypoxia, hypercapnia, and the presence of an occluded airway ^[3]. Obstructive sleep apnea syndrome (OSAS) is a sleep breathing disorder characterized by repeated episodes of partial or complete upper airway obstruction during the night ^[4]. This obstruction usually manifests itself with a reduction (hypopnea) or complete cessation (apnea) of the air flow in the upper airways with intermittent hypoxia and an oxidative imbalance, with increased production of reactive oxygen species, tumor necrosis factors, cytokines inflammatory diseases (IL2, IL4, IL6), lipid peroxidation, and cell-free DNA ^[5]. An obstructive apnea or hypopnea typically ends when an upper airway obstruction triggers a reflex stimulation of respiratory effort by the diaphragm, intercostal, and abdominal muscles, which generates enough pressure to produce an arousal or a gasp, resulting in airway opening and post apnea hyperpnea ^[6]. Normal children with normal muscle strength should be able to generate this increased intrathoracic pressure in a somewhat predictable manner. The literature, however, lacks information regarding the amount of time that children require to terminate an obstructive event. There is also a lack of understanding about the relation of apnea length to various comorbidities, such as neuromuscular conditions. We also do not know if the response to apnea varies with age. The American Academy of Sleep Medicine (AASM) scoring manual ^[7] recommends scoring pediatric obstructive events based on a two-breath rule. To score a pediatric obstructive apnea, there must be a drop in respiratory signal excursion of at least 90% for at least the duration of two breaths during baseline breathing. To score a pediatric hypopnea, the drop in signal excursion needs to be at least 30% for the duration of two breaths. As respiratory rate decreases from birth to puberty, the duration of each breath becomes longer. In obstructive sleep apnea, there must be evidence of respiratory effort. The AASM scoring manual states that after 13 years of age, it is up to the discretion of the sleep physician to score the studies using the adult criteria, which differs from pediatric criteria. For adults, obstructive apneas or hypopneas must be scored if they last for a minimum of 10 s. The duration of obstructive sleep apneas and hypopneas as a continuum over the different ages of children and adolescents, however, has not been previously reported.

2. Analysis on Results

In total, 268 pediatric polysomnograms were included in this study. The children’s mean age was 8.7 years (4.68 SD), the range was 1−18 years, 160 were male, and 108 were female.

Table 1 shows the results of the regression analysis taking into consideration the simultaneous effects of age, sex, and obstructive apnea/hypopnea index (the predictors) on both apnea and hypopnea during NREM and REM sleep (the dependent variables). Only age resulted to be significantly correlated with all four respiratory event durations, while both sex and severity of apnea did not seem to influence them. For this reason, our subsequent analyses focused on this correlation.

Table 1. Analysis of the simultaneous effects of age, sex, and obstructive apnea/hypopnea index on the duration of apnea and hypopnea during NREM and REM sleep, separately. The partial correlation coefficients are reported for each predictor, as well as their statistical significance.

		Age	oAHI	Sex
Apnea, NREM	Correlation	0.287	−0.015	0.067
	F	13.410	0.036	0.664
	p<	0.00035	NS	NS
Apnea, REM	Correlation	0.304	−0.032	−0.035
	F	15.168	0.155	0.187
	p<	0.00015	NS	NS
Hypopnea, NREM	Correlation	0.442	0.007	0.003
	F	36.165	0.007	0.001
	p<	0.000001	NS	NS
Hypopnea, REM	Correlation	0.390	−0.035	−0.119
	F	26.710	0.188	2.122
	p<	0.000001	NS	NS
oAHI = obstructive apnea/hypopnea index; NS = not significant.

Figure 1 shows, in detail, the correlation between age and each of the four respiratory event duration values. Again, all correlations were statistically significant, with duration showing a clear increase with age. All correlations were within the moderate-to-large size range (>0.30 to <0.50).

Figure 1. Correlation between age of participants and the respiratory event duration values considered in this study. The continuous line is the regression line, while the two dashed lines represent the limits of the area within which 95% of the points are expected.

Mean duration values of apnea and hypopnea events during NREM and REM sleep, separately, for each age group are reported in Table 2, as well as the number of subjects from which each value was calculated.

Table 2. Mean duration of apnea and hypopnea events, during NREM and REM sleep, separately, for each age group.

	Apnea, NREM		Apnea, REM		Hypopnea, NREM		Hypopnea, REM
Age, Years	N	Mean ± SD	N	Mean ± SD	N	Mean ± SD	N	Mean ± SD
1	5	9.4 ± 1.9	6	7.1 ± 0.7	6	10.7 ± 2.8	6	9.2 ± 1.8
2	19	9.8 ± 1.8	19	9.2 ± 1.7	18	11.3 ± 2.3	19	12.5 ± 3.8
3	20	11.3 ± 1.6	19	9.3 ± 1.7	20	12.8 ± 2.7	19	13.6 ± 3.2
4	17	11.4 ± 1.7	17	10.0 ± 2.8	18	13.1 ± 3.2	18	12.7 ± 3.2
5	19	11.4 ± 1.4	17	10.8 ± 2.8	18	14.1 ± 2.6	17	15.5 ± 4.5
6	18	11.1 ± 3.1	13	11.1 ± 2.7	18	15.0 ± 4.3	16	15.4 ± 6.7
7	18	11.3 ± 1.6	17	10.9 ± 2.4	20	14.9 ± 3.7	17	16.4 ± 4.9
8	12	10.7 ± 1.2	10	11.3 ± 1.6	12	14.5 ± 4.3	8	16.0 ± 3.7
9	15	12.2 ± 2.5	14	10.7 ± 2.2	18	16.3 ± 2.9	18	17.8 ± 5.1
10	7	12.5 ± 2.3	6	12.6 ± 1.6	9	18.8 ± 4.8	8	19.0 ± 7.4
11	16	11.7 ± 2.8	12	11.2 ± 2.3	19	15.4 ± 3.5	17	17.1 ± 4.8
12	10	10.5 ± 1.7	9	9.1 ± 1.2	12	13.5 ± 2.6	9	15.7 ± 3.1
13	11	13.0 ± 2.8	7	10.1 ± 2.1	13	16.1 ± 3.6	11	18.0 ± 9.6
14	13	12.4 ± 2.2	10	12.4 ± 2.4	16	16.2 ± 3.6	12	16.1 ± 4.4
15	11	13.3 ± 2.2	7	10.5 ± 2.8	17	19.4 ± 4.8	15	22.6 ± 11.9
16	9	13.2 ± 1.9	1	18.0	9	20.2 ± 5.4	6	21.2 ± 7.5
17	5	11.6 ± 0.7	4	12.8 ± 1.6	8	16.8 ± 4.0	7	18.4 ± 3.4
18	1	14.1	1	9.9	4	18.9 ± 10.5	4	13.3 ± 4.4

Finally, Figure 2 shows the median and the interval between the 5th and 95th centiles of apnea duration during NREM and REM sleep and hypopnea duration during NREM and REM sleep in different age groups (subjects were grouped into 3-year age subgroups: 1–3, 4–6, 7–9, 10–12, 13–15, and 16–18 years). This figure shows that the intersubject variability of apnea events is smaller than that of hypopnea events during both NREM and REM sleep; moreover, it tends to be constant at all ages, in contrast to that of hypopnea, which tends to be wider with advancing age, again, during both NREM and REM sleep. The graphs in Figure 2 also provide information on the minimum duration expected for the respiratory events, taking into consideration the 5th centile (bottom dotted line in each graph). The 5th centile of apnea duration during NREM sleep appears to be slightly above 8 s at all ages, with a slight tendency to increase in the oldest groups up to 10 s. During REM sleep, the 5th centile of apnea duration shows a gradual increase from approximately 6 s in the youngest children to 10 s in the oldest. The 5th centile of hypopnea duration during NREM sleep also shows a value just above 8 s in the youngest group and is longer than 10 s after the age of 6 years. Similarly, the 5th centile of hypopnea duration during REM sleep starts from values close to 8 s in the youngest group and is longer than 10 s after the age of 6 years.

Figure 2. Median (continuous line) and the interval between the 5th and 95th centiles (grey-shaded area) of apnea duration during NREM (a) and REM sleep (b) and hypopnea duration during NREM (c) and REM sleep (d) in different age groups.

3. Current Insights

Our current study reports reference values for apnea and hypopnea length in children with sleep disordered breathing without any other comorbidities and demonstrates our original hypothesis that their duration is not correlated with severity of sleep disordered breathing but with age. We have also demonstrated that the mean apnea/hypopnea length of 10 s is usually achieved at an earlier age than adolescence, but its minimum duration can be less than 10 s. If we consider that, at ages below 15 years, the respiratory rate is >20 breaths/min, the duration of two respiratory cycles is <6 s. Our data-driven analysis shows that an appropriate lower limit for apnea/hypopnea events might be 7−8 s in the youngest children and 10 s above the age of 6 years (as in adults).

There are currently no studies reporting apnea/hypopnea length in school age children and adolescents or across the continuum of the lifespan. Brockmann et al. ^[8] reported the median duration of obstructive apneas in infants at 1 month of age to be 5.1 s and the duration of hypopneas to be 6.6 s. In our study, mean apnea/hypopnea length at 1 year of age ranged from 7.1−10.7 s, demonstrating a longer duration of events than in infants. Also, in their study, Brockmann et al. ^[8] demonstrated that obstructive apnea was not as predominant in infants, with a mean obstructive AHI of 0.8/hour, while central apneas were more prominent in this age group, with a central apnea index of 4.1/hour. Of note, the duration of central events matched that of obstructive apneas, lasting 5.1 s ^[8]. Some studies in adults have measured apnea lengths at various ages. For example, McBrayer et al. ^[9] also found that apneas increased in length with age in adults but were longer in men than in women. For instance, in men, the duration of events during NREM sleep increased from 20.1 s in men aged 18−39 years to 23.8 s in the older age group (60-88 years), while in women in the younger age group (18−39 years), the apnea duration was 16.7 s compared to 20.6 s in the older age group ^[9]. During REM sleep, the events were longer than during NREM and also increased in duration with age. The authors also postulated that upper airway muscle tone can be responsible for the changes in apnea duration seen with aging ^[9]. These results match our findings, but we did not find a sex difference in children.

The prolongation of the duration of obstructive apneic events associated with age can be postulated to occur secondary to various mechanisms: upper airway muscle tone changes ^[10], reflex changes in chemoreceptor sensitivity ^[11], and shifts in sleep stages that occur naturally with age ^[12].

References

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Maniaci, A.; Iannella, G.; Cocuzza, S.; Vicini, C.; Magliulo, G.; Ferlito, S.; Cammaroto, G.; Meccariello, G.; De Vito, A.; Nicolai, A.; et al. Oxidative stress and inflammation biomarker expression in obstructive sleep apnea patients. J. Clin. Med. 2021, 10, 277.
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Lourdes DelRosso

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1. Introduction

2. Analysis on Results

3. Current Insights

References