Sleep hypoventilation and daytime hypercapnia in stable chronic obstructive pulmonary disease

Figures & data

Figure 1 Study population.

Abbreviation: PSG, polysomnography.

Table 1 Differences between subjects with and without CHRF and subjects with and without SH; values as median (interquartile range), N=100

	Normocapnic N=76a	CHRF N=24	P	No SH N=85	SH N=15	P
Demographic data
Sex, female	41 (54)*	20 (83)*	0.010	49 (58)*	12 (80)*	0.102
Age, years	64 (11)	68 (15)	0.032	65 (11)	64 (15)	0.854
BMI, kg/m^2	25.5 (6.99)	22.9 (9.06)	0.199	24.8 (6.67)	27.1 (11.3)	0.916
Smoking habit
Pack years	34 (23)	25 (18)	0.068	32 (22)	31 (26)	0.783
Current smoker	14 (18)*	2 (8)*	0.345	14 (17)*	2 (13)*	0.679
Spirometry
FVC, % of predb	79.5 (24.3)	57.0 (21.0)	0.000	73.5 (25)	67.0 (31.0)	0.841
FEV1, % pred	43.0 (24.8)	25.0 (11.0)	0.000	40.0 (24.0)	34.0 (27.0)	0.296
FEV1/FVC, ratio	0.46 (0.12)	0.37 (0.09)	0.000	0.44 (0.14)	0.40 (0.18)	0.185
DLCO, mmol/min/kPac	3.59 (2.45)	2.44 (1.39)	0.000	3.34 (2.20)	2.89 (1.64)	0.385
RV/TLC, ratiod	0.57 (0.11)	0.72 (0.12)	0.000	0.60 (0.16)	0.65 (0.22)	0.297
Medication
LTOT	3 (4)*	12 (50)*	0.000	8 (9)*	7 (47)*	0.001
SABA/LABA	71 (93)*	24 (100)*	0.333	80 (94)*	15 (100)*	1.00
Theophylline	3 (4)*	1 (4)*	1.00	4 (5)*	0 (0)*	1.00
Steroid po	2 (3)*	3 (13)*	0.088	5 (6)*	0 (0)*	1.00
Clinical data
CAT, score	17.0 (6.0)	21.0 (6.0)	0.004	18.0 (7.0)	18.5 (7.0)	0.593
MMRC, score	2.0 (1.0)	3.0 (2.0)	0.000	2.0 (1.0)	2.0 (2.0)	0.561
6MWD, metere	468 (173)	293 (110)	0.000	438 (186)	370 (203)	0.419
BODE indexf	3.0 (3.0)	6.0 (2.0)	0.000	3.0 (3.0)	6.0 (5.0)	0.122
Laboratory data
PaO2, kPag	9.33 (1.47)	8.23 (1.84)	0.010	9.13 (1.64)	9.88 (2.28)	0.166
PaCO2, kPa	5.14 (0.76)	6.83 (0.68)	–	5.33 (0.945)	6.67 (2.09)	0.010
BEh	0.85 (1.91)	6.44 (3.79)	0.000	1.56 (2.86)	4.36 (5.94)	0.019
CHRF	–	–	–	15 (18)*	9 (60)*	0.001
Sleep time and awakenings
TST, min	352 (76)	337 (112)	0.218	348 (77)	354 (92)	0.369
REM% TST	21.9 (7.2)	20.5 (10.7)	0.366	21.5 (7.8)	22.1 (10.4)	0.916
WASO, min	46 (43)	53 (109)	0.468	50 (70)	39 (32)	0.265
Awake	24 (16)	24 (25)	0.904	24 (17)	21 (19)	0.245
Sleep arousals
TAI	16.7 (9.4)	20.2 (15.7)	0.116	17.3 (11.0)	14.4 (13.5)	0.466
AAI	1.3 (2.7)	1.6 (4.0)	0.862	1.30 (3.00)	1.80 (3.60)	0.888
HAI	2.8 (3.5)	2.0 (3.2)	0.183	2.60 (3.90)	2.60 (3.30)	0.714
Sleep apneas/hypopneas
AHI	9.2 (10.5)	9.6 (13.5)	0.589	9.0 (10.4)	9.9 (14.0)	0.996
AHI ≥15	20 (26)*	7 (29)*	0.784	23 (27)*	4 (27)*	1.00
CAHI ≥1	3 (4)*	1 (4)*	1.00	4 (5)*	0 (0)*	1.00
MAHI ≥1	3 (4)*	2 (8)*	0.591	4 (5)*	1 (7)*	0.564
HI	5.3 (4.9)	4.6 (7.6)	0.274	5.2 (6.3)	5.3 (4.9)	0.798
Sleep hypoventilation
Mean ΔPtcCO2, kPa	0.44 (0.34)	0.54 (0.50)	0.081	0.40 (0.33)	0.88 (0.74)	0.000
Max ΔPtcCO2, kPa	0.83 (0.41)	1.21 (0.81)	0.003	0.80 (0.37)	1.63 (0.91)	0.000
REM max ΔPtcCO2, kPa	1.02 (0.51)	1.40 (1.16)	0.009	0.95 (0.51)	1.79 (0.67)	0.000
NR max ΔPtcCO2, kPa	0.75 (0.40)	1.19 (0.78)	0.002	0.75 (0.35)	1.58 (0.91)	0.000
REM min SpO2, %	82.4 (11.2)	81.1 (25.7)	0.111	82.2 (10.7)	79.0 (31.7)	0.308
NR min SpO2, %	87.2 (6.7)	84.7 (19.3)	0.034	86.4 (7.0)	87.9 (10.7)	0.828
SH	6 (8)*	9 (38)*	0.001	–	–	–

Notes: Normocapnic, P_aCO₂ <6.3 kPa.

* N (% of N) instead of median (interquartile range).

a One missing P_aCO₂ replaced with value at arrival in the hospital =5.40 kPa.

b N=99; one missing from routine spirometry, reason unknown.

c N=84; 16 missing from DLCO because of insufficient vital capacity or because they could not hold their breath for 10 seconds.

d N=91; nine missing from body pletysmography because of claustrophobia.

e N=96; four missing from 6MWD, reason unknown.

f N=93; seven missing from BODE index.

g N=99; one missing from P_aO₂ and P_aCO₂, unable to hit artery.

h N=98; two missing from S_pO₂ and BE, technical problem with analysis.

Abbreviations: 6MWD, 6 minutes walking distance; AAI, apnea arousal index; AHI, apnea/hypopnea index; Awake, number of awakenings after sleep onset; BE, base excess in arterial blood; BMI, body mass index; BODE, BMI/obstruction/dyspnea/exercise capacity; CAHI, central AHI; CAT, COPD assessment test; CHRF, chronic hypercapnic respiratory failure (P_aCO₂ ≥6.3 kPa); DLCO, diffusing capacity of the lung for carbon monoxide; FEV_1, forced expiratory volume first second; FEV₁ % of pred, FEV₁ percentage of predicted; FVC, forced vital capacity; FVC % of pred, FVC percentage of predicted; HAI, hypopnea arousal index; HI, hypopnea index; LTOT, long-term oxygen therapy; MAHI, mixed AHI; Max ΔP_tcCO_2, maximum sleep increase in transcutaneous carbon dioxide from awake, supine rest; Mean ΔP_tcCO₂, mean sleep increase in transcutaneous carbon dioxide from awake, supine rest; MMRC, modified medical research council questionnaire; NR max ΔP_tcCO₂, as above in non-REM sleep; NR min S_pO, non-REM sleep minimum oxygen saturation measured by pulse oximetry; P_aCO_2, arterial pressure of carbon dioxide; P_aO_2, arterial pressure of oxygen; REM% TST, rapid eye movement – sleep percentage of total sleep time; REM max ΔP_tcCO_2, as above in REM sleep; REM min S_pO₂, REM sleep minimum oxygen saturation measured by pulse oximetry; RV, residual volume; SABA/LABA, short/long acting beta-two receptor agonist; SH, sleep hypoventilation according to American Academy of Sleep Medicine definition; steroid po, oral prednisolone; TAI, total arousal index; TLC, total lung capacity; TST, total sleep time; WASO, minutes awake after sleep onset.

Figure 2 ΔP_tcCO₂ according to sleep stages.

Notes: Each bar represents the sleep stage median value of the mean, and alternatively the maximum ΔP_tcCO₂ in kPa. The first and third cluster represent the group with no SH; the second and fourth cluster represent the group with SH.
Abbreviations: ΔP_tcCO_2, increase in carbon dioxide from supine, awake rest before sleep; N0, stage N0 sleep; N1, stage N1 sleep; N2, stage N2 sleep; N3, stage N3 sleep; REM, rapid eye movement sleep; SH, sleep hypoventilation according to American Academy of Sleep Medicine definition.

Table 2 Blood gases in COPD and overlap subjects, as median (interquartile range), N=52

	COPD AHI <5 N=25	Overlap AHI ≥15 N=27	P-value
Sleep
Mean ΔPtcCO2, kPa	0.34 (0.43)	0.54 (0.29)	0.117
Max ΔPtcCO2, kPa	0.76 (0.56)	0.94 (0.50)	0.101
REM max ΔPtcCO2, kPa	0.86 (0.51)	1.18 (0.69)	0.210
NREM max ΔPtcCO2, kPa	0.71 (0.59)	0.89 (0.49)	0.117
REM min SpO2, %	87.0 (7.7)	78.0 (10.0)	0.000
NREM min SpO2, %	88.5 (5.6)	83.0 (11.2)	0.001
Awake
PaO2, kPaa	9.51 (1.92)	9.11 (1.92)	0.059
PaCO2, kPaa	5.36 (2.12)	5.38 (1.43)	0.880
SaO2 %b	96.2 (3.2)	95.3 (3.4)	0.251

Notes: Prevalence of overlap could not be calculated as data on daytime sleepiness was not available.

a N=24 in COPD group; one missing from P_aO₂ and P_aCO₂, unable to hit artery.

b N=23 in COPD group; two missing from S_pO₂ due to technical problem with analysis.

Abbreviations: AHI, apnea/hypopnea Index; Max ΔP_tcCO₂, maximum increase in transcutaneous carbon dioxide pressure from supine, awake rest; Mean ΔP_tcCO₂, mean increase in transcutaneous carbon dioxide pressure from supine, awake rest; min S_pO_2, minimum oxygen saturation measured by pulse oximetry; NREM, nonrapid eye movement sleep; REM, rapid eye movement sleep; P_aCO₂, arterial pressure of carbon dioxide; P_aO₂, arterial pressure of oxygen at 2:00 pm prior to sleep; S_aO₂, arterial oxygen saturation; COPD, chronic obstructive pulmonary disease.

Table S1 Sleep parameters according to age, compared to reference populations with normal lung function, N=100

Age groups	46–59 years Results (Reference values*) N=29		60–69 years Results (Reference values*) N=47		70–82 years Results (Reference values^) N=24
	Mean	SD	Mean	SD	Mean	SD
Sleep summary
TST, min	347 (367)	56.7 (58.0)	360 (349)	54.0 (51.5)	296 (335)	56.3 (na)
Awake	21 (9.7)	9.1 (5.2)	27 (14.6)	12 (6.7)	36 (na)	30.1 (na)
WASO, min	40 (na)	40 (na)	60 (na)	39 (na)	105 (75)	61 (na)
SES,%	90 (90)	11 (7.1)	86 (9.1)	86 (7.9)	74 (82)	15 (na
Sleep stage percentage of total sleep time
N1	13 (5.2)	6.6 (4.2)	17 (4.8)	7.1 (3.3)	21 (12)	11.7 (na)
N2	39 (63)	8.4 (17)	41 (68)	7.3 (13)	37 (56)	10 (na)
N3	26 (8.8)	9.4 (7.3)	21 (8.7)	11 (7.9)	22 (13)	12 (na)
REM	22 (23)	7.2 (7.5)	21 (19)	6.2 (8.5)	20 (19)	8.5 (na)

Notes:

* Reference values according to M. Hirschkowitz et al⁹

^ Reference values according to M. Ohayon et al (adapted from graph)¹⁰

Abbreviations: TST, total sleep time; Awake, number of awakenings; WASO, minutes wake after sleep onset; SES, sleep efficiency from sleep start; N1, stage N1 sleep; N2, stage N2 sleep; N3, stage N3 sleep; REM, rapid eye movement sleep; na, not available.

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