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Sleep Med Res > Volume 13(1); 2022 > Article
Sakuma, Shinomiya, Takahara, and Mizuno: Awake Hypercapnic Ventilatory Response in Obstructive Sleep Apnea Syndrome


Background and Objective

Decreased ventilatory response to carbon dioxide or hypercapnic ventilatory response (HCVR) is a feature of pediatric obstructive sleep apnea (OSA) and is also known to diminish during sleep in obese adolescents (age, 12–16 years) with OSA. It reduces minute ventilation, air flow, and tidal volume during inspiration, as well as upper airway obstruction. The purpose of this study was to investigate awake HCVR in adult patients with OSA and to elucidate its association with sleep apnea.


HCVR was measured before performing polysomnography (PSG). PSG is performed as the evaluation method during sleep, and the severity of apnea is evaluated by apnea hypopnea index. Patient background, PSG data and HCVR were examined.


Awake HCVR was greater in patients with severe OSA than in patients with mild and moderate OSA, and in severe OSA patients, the HCVR during awaking was higher in patients with larger changes in saturation of percutaneous oxygen during sleep. Awake HCVR did not differ by age, but it was greater in morbidly obese patients with OSA than in thin patients with OSA. The most frequent apnea pattern of OSA was obstructive, regardless of severity; although with an increasing severity of OSA, the central pattern decreased and the mixed pattern increased in frequency. The appearance of the mixed pattern increased in the augmented HCVR group.


This study suggested that awake HCVR could be used as an index of progression and a factor to determine the effects of treatment in patients with OSA.


There are three major types of sleep-related breathing disorders (SRBD): 1) obstructive sleep apnea (OSA), which is caused by airway obstruction; 2) central sleep apnea (CSA), which is caused by a decrease or cessation of stimulation from the respiratory center in the medulla oblongata; and 3) mixed sleep apnea (MSA), which involves the 2 types, with the central pattern preceding the obstructive pattern. OSA accounts for the majority of SRBDs and its onset had been proposed to be affected by the following four factors, according to White et al. [1]: 1) anatomical factor, which is caused by narrowing of the pharynx; 2) instability of the respiratory center; 3) decreased pharyngeal reflex in sleep or aging; and 4) low arousal threshold, which results in a greater likelihood of waking up [1-5]. The regulation of respiratory function comprises 3 components, including chemical, neural, and behavioral controls; the effects of the chemical control are known to relatively increase with the induction of sleep [6]. In chemical control, the central chemoreceptors in the medulla oblongata detect the partial pressure of carbon dioxide (PaCO2) in the arterial blood to control breathing. When the PaCO2 increases above the normal level of 40 mm Hg, the respiratory center sends signals to increase minute ventilation, in order to eliminate the carbon dioxide (CO2). Conversely, when the PaCO2 drops below 40 mm Hg, the stimulation from the respiratory center stops, and CSA is induced [7,8]. In MSA, respiration attempts to resume when the PaCO2 increases due to CSA, but the reflex activity of the upper airway dilator muscles is inhibited or decreases, resulting in obstruction and constriction of the upper airway, followed by the appearance of OSA [9].
Polysomnography (PSG) is a technique to diagnose and assess the severity of SRBD. However, it cannot assess the causative factors, such as the shape or collapsibility of the upper airway, or quantitatively evaluate the function of respiratory regulation. The maintenance of normal partial pressure of oxygen (PaO2) in arterial blood and PaCO2 is controlled by the respiratory regulation function, which can be assessed through ventilatory response examinations. Hypoxia and hypercapnia are the two types of ventilatory stimulation [10-12]. Kronenberg et al. [13] reported that the ventilatory response to hypoxia was weaker in older individuals than in younger individuals. They also investigated the ventilatory response to hypercapnia by maintaining PaO2 at ≥ 200 mm Hg through oxygen inhalation, in order to eliminate the effects of hypoxia. As a result, they found that the ventilatory response to hypercapnia, similar to hypoxia, as less in older individuals than in younger individuals.
Due to the fact that PaCO2 is responsible for the chemical control of respiration, evaluation of the ventilatory response to CO2 (hypercapnic ventilatory response [HCVR]) is important [14,15]. When the changes in HCVR during the transition from the awake to the sleep states are large, CSA occurs due to diminished PaCO2. Small changes in HCVR are accompanied by periodic breathing, in which there is repeated fluctuation in tidal volume [16,17]. In recent years, reduction in HCVR had been implicated in the pathophysiology of pediatric and obese adolescent (age, 12–16 years) OSA [18-20]. However, in adult patients with OSA, awake HCVR had been reported to be augmented, decreased, or similar, compared with that in healthy adults, indicating the absence of a consensus [19,21-24].
Based on the above reports, we hypothesized that HCVR could be an index of respiratory response and that worsening of the HCVR increases the appearance of CSA and MSA, resulting in the exacerbation of OSA. The purpose of this study was to investigate awake HCVR in order to elucidate the association of HCVR in SRBD with the severity and pattern of respiratory impairment in adult OSA.



This study investigated 652 patients (504 males and 148 females) who visited the Kanazawa Medical University Hospital Sleep Medicine Center between September 2007 and October 2017 with a chief complaint of snoring or apnea and who were diagnosed as OSA, based on PSG (Table 1). This study was approved by the ethics review board of Kanazawa Medical University (NO. G118), and written informed consent was obtained for patient data collection.

Measurement of awake CO2 ventilatory response

HCVR was measured before performing PSG. HCVR was measured in the awake state using a modification of the Read hyperoxic hypercapnic rebreathing technique [19]. End-tidal PCO2 (PetCO2) was measured by infrared capnometry (Minato Medical Science Co. Ltd., Osaka, Japan) and the flow rate was measured with a heated pneumotachograph (Minato Medical Science Co. Ltd.). In the present study, a closed system with a mixed air bag containing 7% CO2 + 40% to 93% O2 was used. The patients breathed in room air for several minutes through a mouthpiece to establish baseline values, and the inhalation valve was switched to inhalation of a high level of CO2 at the end of exhalation. Then, the patient was asked to take 2–3 deep breaths, and breathe normally. Within approximately 3 seconds, the mixed venous CO2 and PetCO2 in the system reached equilibrium and the patient was encouraged to continue breathing normally until PetCO2 increased by 1% from the original value. All tests were completed within 5 minutes to avoid respiratory acidosis. The elevation in PetCO2 and increase in ventilation volume were measured for the next 5 minutes [10].


During the PSG examination, we measured the nasal airflow with a nasal pressure sensor, the mouth airflow with a thermistor, and the abdominal and chest respiratory movements with inductance plethysmography. The sleep condition was determined by a 2-channel electroencephalogram, eye movement, and chin electromyogram. Saturation of percutaneous oxygen (SpO2) and heart rate were measured with a pulse oximeter. The oxygen desaturation index (ODI) was defined as the number of times in 1 hour that the SpO2 was 3% below baseline. OSA was defined as a ≥ 10-second decrease in tidal volume to ≤ 10% of the immediately-preceding stable respiration, even with respiratory effort. Obstructive hypopnea was defined as a reduction in tidal volume to ≤ 30% for ≥ 10 seconds and ≥ 3% decrease in SpO2 or the appearance of arousal response, even with respiratory effort. The number of apnea and hypopnea events in 1 hour was defined as the apnea-hypopnea index (AHI). This study classified the patients with AHI of < 5 as healthy; ≥ 5–< 15 as mild OSA, ≥ 15–< 30 as moderate OSA, ≥ 30–< 50 as severe OSA, and ≥ 50 as very severe OSA [25].
Sleep and arousals were scored according to standard criteria. Apnea was scored when nasal airflow reduced to < 10% of baseline for ≥ 10 sec. Obstructive apneas were scored when the thoracoabdominal effort signals showed continuing respiratory excursions, and central apnea was scored when respiratory efforts were absent [26,27]. Mixed apnea was scored when respiratory effort was absent during the first half of the apnea and three or more obstructed breaths occurred before resumption of airflow [28]. Central apnea was scored when respiratory effort was absent during the apnea [26]. The percentage of obstructive apneas, mixed apnea and central apnea was estimated as OSA%, MSA% and CSA% relative to all apneas.

Statistical Analysis

Comparisons of age, body mass index (BMI), longest duration of apnea, minimum SpO2, arousal index, ODI, HCVR, CSA%, MSA% and OSA% between the groups were performed using analysis of variance (ANOVA) with Bonferroni corrections for multiple comparisons. The significance of differences in the distributions of gender between the groups was determined by the chi-squared test. Binary logistic regression analysis of HCVR was performed to exclude the effects of age, BMI, AHI and ODI. All analyses were performed using the statistical software SPSS 26.0 (IBM Corp., Armonk, NY, USA). All data were expressed as mean ± standard deviation. A p value < 0.05 was considered statistically significant.


In order to compare the effect of patient characteristics on the CO2 ventilatory response, awake HCVR was assessed in terms of AHI, ODI, age, and BMI. Patients were stratified into four OSA groups in terms of AHI: mild (n = 100), moderate (n = 182), severe (n = 174), and very severe (n = 196) (Tables 1 and 2). Patients were stratified into four ODI groups as follows: mild (ODI < 15/hr), moderate (15/hr ≤ ODI < 30/hr), severe (30/hr ≤ ODI < 50/hr), and very severe (ODI ≥ 50/hr) (Table 2). The four age groups were 20–39 years (n = 81), 40–59 years (n = 273), 60–79 years (n = 272), and ≥ 80 years (n = 26). The four BMI groups were < 20 kg/m2, ≥ 20–< 25 kg/m2, ≥ 25–< 30 kg/m2, and ≥ 30 kg/m2. In order to compare the percentages of apnea events among the central, mixed and obstructive patterns, the patients were divided into three groups according to AHI (mild, n = 100; moderate, n = 182; and severe, n = 370) and into three groups based on HCVR, including the low (< 0.5 L/min/mm Hg, n = 24), normal (≥ 0.5–< 2.7 L/min/mm Hg, n = 498), and augmented groups (≥ 2.7 L/min/mm Hg, n = 130). The study population had a mean age of 58 ± 14 years (range, 20–86 years), and the mean values were 26.7 ± 5.1 kg/m2 (range, 18.07–62.94 kg/m2) for BMI; 38.7 ± 23.8 for AHI; and 1.9 ± 1.2 L/min/mm Hg for HCVR slope. The number of patients by OSA severity was 100 in the mild group, 182 in the moderate group, 174 in the severe group, and 196 in the very severe group. There was no significant difference in age among the groups. With increasing OSA severity, the BMI increased, the longest duration of apnea increased, and the minimum SpO2 decreased (Table 1). In the analysis by apnea severity, very severe OSA had augmented awake HCVR, compared with that in mild or severe OSA. Awake HCVR was augmented in the ODI > 50/hr group, compared with that in the ODI < 49/hr group (Table 2). Awake HCVR did not significantly differ by age, but it was significantly augmented in the morbidly obese OSA group than in the thin OSA group (Table 2). The frequency of CSA was significantly less in the severe and very severe OSA groups than in the moderate OSA groups (Table 3). The frequency of MSA was significantly higher in the very severe OSA group than in the mild, moderate, and severe OSA groups and was significantly higher in the severe OSA group than in the mild OSA group (Table 3). However, regardless of the severity, the frequency of OSA was not significantly different among the groups (Table 3). The percentages of CSA and OSA were not significantly different among the low, normal, and augmented awake HCVR groups, but the percentage of MSA was significantly higher in the augmented awake HCVR group than in the low awake HCVR group (Table 4). In order to evaluate the effect of age, BMI, AHI and ODI on HCVR, the patients were divided into two groups using cutoff values of 2.7 L/min/mm Hg for HCVR, 60 years old for age, 25 kg/m2 for BMI, 60/hr for AHI, and 30/hr for ODI, and univariable and multivariable analysis of HCVR were performed in terms of these risk factors. BMI had a significant effect on HCVR in both univariable and multivariable analysis. The ODI tended to affect HCVR only in univariable analysis (Table 5). Furthermore, when we divided the patients into three groups using HCVR cut-off values of 0.5 and 2.7 L/min/mm Hg (normal HCVR versus low HCVR group, normal HCVR versus augmented HCVR group), and performed univariable and multivariable analysis of HCVR in a similar way, BMI was seen to affect HCVR in both univariable and multivariable analysis in the comparison between the normal HCVR group and the low HCVR group, and the normal group and the augmented HCVR group (Table 5).


In this study, we found that awake HCVR was augmented in very severe OSA, compared with that in mild and severe OSA, and that it was augmented in those with ODI > 50/hr than in those with ODI < 49/hr. A higher AHI resulted in greater reduction in CSA and greater increase in MSA. The percentage of OSA appearance was not different, regardless of the AHI. On the other hand, the percentage of MSA appearance was increased in the augmented HCVR group; this was thought to be related with the changes in the clinical state of OSA. Multivariable analysis of HCVR showed that BMI was an independent risk factor affecting awake HCVR.
Patients with untreated very severe OSA have abnormal HCVR because of the recurring apnea events at night and the associated elevation in PaCO2, as well as the decrease in PaCO2 with the resumption of respiration after the apnea. Based on our results (Table 2), a greater severity of OSA could lead to repeated ventilation abnormalities in response to changes in PaCO2 during sleep, thereby, inducing unstable chemical control of respiration and, ultimately, the augmentation of awake HCVR [29].
Awake HCVR was significantly greater in OSA patients with BMI ≥ 30 kg/m2 than in those with BMI < 20 kg/m2 (Table 2), and the group with high BMI had high awake HCVR (Table 5); this implied augmentation in awake HCVR due to obesity. This finding was in line with the results of the study by Narkiewicz et al. [30], who showed that HCVR was enhanced in the obese group [30-32]. This augmentation in HCVR may be explained by the synergistic action between increased PaCO2 and decreased PaO2 in the carotid bodies during HCVR measurement, because PaO2 declines further in obese patients [33]. Moreover, the leptin called “obesity gene,” which is a powerful appetite suppressant, increases with an increasing degree of obesity [34]. Leptin regulates the central chemical reflex and its plasma concentration is known to be positively correlated with HCVR [22]. Because increased leptin is observed with sympathetic nerve activation in OSA [35], it is possible the leptin elevation that accompanies the increase in BMI may also be associated with the augmentation of HCVR.
Kronenberg et al. [13] reported that the ventilatory response to hypoxia and hypercapnia was decreased in older individuals. The present study did not show aging-related reduction in HCVR; older adults maintained a level of HCVR that was similar to that in young adults (Table 2). Binary logistic analysis of HCVR with age, BMI, AHI and ODI showed that only BMI affected HCVR (Table 5). Because HCVR was augmented in obese individuals, compared with that in non-obese individuals, the high BMI in our study patients was presumed to have suppressed the effects of aging on diminishing the HCVR [33]. We postulated that in older obese patients with OSA, the awake HCVR did not decline, the sleep HCVR was maintained or even augmented, the respiratory response was augmented by a slight change in CO2, the respiration became unstable, and the MSA appeared more frequently. On the other hand, age-associated decreases in the ventilatory response are brought about by a decline in respiratory muscle strength and hardening of the rib cage; consequently, these do not simply reflect respiratory center activity. To correct for the reduction in respiratory muscle strength in the elderly, Peterson et al. measured airway occlusion pressure, P0.1, which is determined as the change in mouth pressure within 0.1 second from the start of inspiration. As a result, they found that the ventilatory responses to hypoxia and hypercapnia were significantly reduced in older individuals, even after correcting for the decreased respiratory muscle strength [36,37]. Khoo [38] described the response to ventilatory changes as the “loop gain (LG) theory”; specifically, the respiratory response to changes in ventilation is large and unstable with a large LG, but is small and stable with a small LG. In OSA with a high LG, a hyper-responsive state arises when breathing resumes after apnea, and patients become prone to recurring cycles of hyperventilation and hypoventilation, such as in CSA or Cheyne-Stokes respiration. Dernaika et al. [39] reported that patients with untreated OSA have a low apnea threshold for PaCO2 and unstable respiration in response to changes in PaCO2, although the condition improved after about 1 to 3 months of continuous positive airway pressure (CPAP) [39-41].
In the present study, we did not observe a significant difference in the percentage of OSA, regardless of apnea severity. On the other hand, CSA appeared less frequently and MSA appeared more frequently in severe and very severe OSA than in mild and moderate OSA (Table 3). To our knowledge, there had been no previous reports that investigated the frequency of CSA or MSA in patients with OSA. HCVR is known to exacerbate with the worsening of OSA [39-41] and that HCVR exacerbation contributes to the onset of CSA [16,17]. These were contradictory to our findings. However, the BMI was high in the severe and very severe groups (Table 1). This difference in body frame may have affected the frequency of OSA in the severe and very severe groups [5], thereby, inducing the changes in the frequency of MSA.
Compared with the low HCVR group, the augmented HCVR group had a significantly greater frequency of MSA appearance. The augmented HCVR group also had more frequent CSA and fewer OSA compared with the low HCVR group, albeit without statistical significance (Table 4). According to a previous report, OSA can appear with the recovery of PaCO2, potentially resulting in MSA [42]. Moreover, in patients with OSA, the difference in PCO2 levels between resting respiration and apnea threshold had been reported to be chronically reduced and that there was augmented ventilatory response by the chemoreceptor to changes in PCO2 [43]. These above reports suggested that the transition to the CSA was associated with the elevation in HCVR. However, there had been no previous reports on HCVR elevation and the accompanying transition from OSA to MSA. Indeed, the results of the present study implicate the values of HCVR measurements.
There were several limitations to this study. First, a large proportion of the study patients were middle-aged or older (Table 1). Since aging is known to modulate sleep respiration, the HCVR in this study may have been affected by the age of the patients. Future studies that include HCVR measurements in young adults are necessary. Second, although the HCVR measurements in this study were performed after confirming that there was no decrease in SpO2 in room air, but unlike Kronenberg et al. [13], PaO2 was not maintained at 200 mm Hg or higher. The slight changes in PaO2 due to changes in ventilation volume during measurement may have affected the outcomes. Third, ventilatory impairment may have induced changes in the ventilatory response to hypercapnia. Finally, patients with cardiovascular or cerebrovascular disease, which may affect the ventilatory response, were not completely excluded. Therefore, investigations in OSA patients without underlying diseases are necessary.
In conclusion, this study suggested that measurements of awake HCVR could become a predictor of the transition to MSA and CSA in patients with OSA. Awake HCVR is a potential index of OSA progression and a convenient tool to assess the effects of treatment, such as outpatient CPAP.


Availability of Data and Material
All data generated or analyzed during the study are included in this published article (and its supplementary information files).
Authors’ Contributions
Conceptualization: Shiro Mizuno. Data curation: Takashi Sakuma, Shohei Shinomiya, Yutaka Takahara, Shiro Mizuno. Formal analysis: Takashi Sakuma, Shiro Mizuno. Investigation: Takashi Sakuma. Methodology: Shiro Mizuno. Project administration: Shiro Mizuno. Software: Shiro Mizuno. Supervision: Shiro Mizuno. Validation: Shiro Mizuno. Visualization: Shiro Mizuno. Writing—review & editing: Shiro Mizuno.
Conflicts of Interest
The authors have no potential conflicts of interest to disclose.
Funding Statement


We thank Mr. Masato Nakamura for his assistance in conducting the HCVR measurements for this study.


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Table 1.
Physical measurements and sleep respiratory disorder parameters in patients with OSA
Parameter Mild (AHI < 15/hr) Moderate (15 ≤ AHI < 30) Severe (30 ≤ AHI < 50) Very severe (AHI ≥ 50)
N (male/female) 100 (71/29) 182 (138/44) 174 (131/43) 196 (167/29)
Age (yr) 57 ± 14.5 57.4 ± 13.1 59.3 ± 12.9 56.5 ± 14.2
BMI (kg/m2) 24.3 ± 3.6 25.6 ± 4.5 26.6 ± 4.2* 29.1 ± 6.0*
LD of apnea (sec) 31.5 ± 17.3 42.0 ± 23.0* 48.0 ± 20.0* 64.0 ± 26.0*
Minimum SpO2 (%) 87.7 ± 4.6 84 ± 5.6* 82 ± 6.4* 72.0 ± 14.0*
Arousal index (/hr) 21.3 ± 6.7 28.8 ± 7.4* 39.2 ± 9.2* 63.65 ± 15.8*
ODI (/hr) 5.2 ± 4.0 14.9 ± 9.9* 29.8 ± 10.7* 60.8 ± 18.1*

Data are presented as the mean ± standard deviation.

* Significantly different compared with the mild group (p < 0.05);

Significantly different compared with the moderate group (p < 0.05);

Significantly different compared with the severe group (p < 0.05).

OSA, obstructive sleep apnea; AHI, apnea hypopnea index; BMI, body mass index; LD, longest duration; ODI, oxygen desaturation index; SpO2, saturation of percutaneous oxygen.

Table 2.
Awake HCVR in terms of apnea severity, ODI, age, BMI
Variable HCVR (L/min/mm Hg)
Apnea severity (/hr)
 Mild (AHI < 15) 1.7 ± 0.9
 Moderate (15 ≤ AHI < 30) 1.9 ± 1.3
 Severe (30 ≤ AHI < 50) 1.8 ± 1.1
 Very severe (AHI ≥ 50) 2.1 ± 1.2*
ODI (/hr)
 Mild (ODI < 15) 1.9 ± 1.1
 Moderate (15 ≤ ODI < 30) 1.8 ± 1.3
 Severe (30 ≤ ODI < 50) 1.7 ± 0.9
 Very severe (ODI ≥ 50) 2.2 ± 1.2
Age (yr)
 20–39 1.7 ± 0.9
 40–59 1.9 ± 1.3
 60–79 1.8 ± 1.1
 ≥ 80 2.1 ± 1.2
BMI (kg/m2)
 < 20 1.2 ± 0.6
 ≥ 20–< 25 1.8 ± 1.3
 ≥ 25–< 30 1.9 ± 0.9
 ≥ 30 2.1 ± 1.4§

Data are presented as the mean ± standard deviation.

* Significantly different compared with the mild and severe group (p < 0.05);

Significantly different compared with the mild, moderate, and severe group (p < 0.05);

Significantly different compared with the 20–39-year-old and 60–79-year-old group (p < 0.05);

§ Significantly different compared with the BMI < 20 group (p < 0.05).

HCVR, hypercapnic ventilatory response; AHI, apnea hypopnea index; ODI, oxygen desaturation index; BMI, body mass index.

Table 3.
Percentage of the different apnea patterns in terms of OSA severity
Mild (AHI < 15/hr) Moderate (15 ≤ AHI < 30) Severe (30 ≤ AHI < 50) Very severe (AHI ≥ 50)
CSA% 15.0 ± 24.0 15.0 ± 23.0 8.0 ± 15.0 9.0 ± 15.0
MSA% 4.0 ± 12.0 7.0 ± 11.0 12.0 ± 17.0* 9.0 ± 14.0*
OSA% 74.0 ± 34.0 78.0 ± 28.0 80.0 ± 25.0 82.0 ± 24.0

Data are presented as the mean ± standard deviation.

* Significantly different compared with the mild group (p < 0.05);

Significantly different compared with the moderate group (p < 0.05);

Significantly different compared with the severe group (p < 0.05).

CSA%, percentage of central sleep apnea; MSA%, percentage of mixed sleep apnea; OSA%, percentage of obstructive sleep apnea.

Table 4.
Percentage of the different apnea patterns in terms of awake HCVR
HCVR (L/min/mm Hg) < 0.5 ≥ 0.5–< 2.7 ≥ 2.7
CSA% 5.0 ± 12.0 11.0 ± 19.0 12.0 ± 21.0
MSA% 5.0 ± 11.0 9.0 ± 15.0 13.0 ± 18.0*
OSA% 86.0 ± 25.0 79.0 ± 27.0 73.0 ± 30.0

Data are presented as the mean ± standard deviation.

* Significantly different compared with the low group (p < 0.05).

HCVR, hypercapnic ventilatory response; CSA%, percentage of central sleep apnea; MSA%, percentage of mixed sleep apnea; OSA%, percentage of obstructive sleep apnea.

Table 5.
Univariable and multivariable analysis of risk factors for HCVR
Univariable analysis
Multivariable analysis
Odds ratio (95% CI) p-value Odds ratio (95% CI) p-value
Two groups: HCVR (< 2.7 L/min/mm Hg vs. ≥ 2.7 L/min/mm Hg)
 Age (yr) 0.385 (0.571–1.241) 0.646 0.936 (0.630–1.391) 0.742
 BMI (kg/m2) 2.057 (1.305–3.134) 0.001 1.941 (1.247–3.022) 0.003
 AHI (/hr) 1.331 (0.898–1.971) 0.154 1.046 (0.557–1.965) 0.888
 ODI (/hr) 1.405 (0.956–2.065) 0.084 1.130 (0.605–2.113) 0.701
Two groups: HCVR (≥ 0.5–< 2.7 L/min/mm Hg vs. < 0.5 L/min/mm Hg)
 Age (yr) 1.156 (0.509–2.623) 0.729 0.938 (0.418–2.237) 0.938
 BMI (kg/m2) 0.377 (0.158–0.897) 0.027 0.388 (0.155–0.970) 0.043
 AHI (/hr) 1.173 (0.511–2.691) 0.707 2.249 (0.786–6.437) 0.131
 ODI (/hr) 0.669 (0.281–1.592) 0.364 0.503 (0.163–1.553) 0.232
Two groups: HCVR (≥ 0.5–< 2.7 L/min/mm Hg vs. ≥ 2.7 L/min/mm Hg)
 Age (yr) 0.848 (0.574–1.252) 0.406 0.938 (0.630–1.397) 0.752
 BMI (kg/m2) 1.968 (1.289–3.004) 0.002 1.859 (1.191–2.902) 0.006
 AHI (/hr) 1.340 (0.903–1.989) 0.146 1.102 (0.584–2.080) 0.764
 ODI (/hr) 1.380 (0.937–2.032) 0.103 1.080 (0.575–2.026) 0.812

HCVR, hypercapnic ventilatory response; CI, confidence interval; BMI, body mass index; AHI, apnea hypopnea index; ODI, oxygen desaturation index.