Relationship Between Episodic Nocturnal Hypercapnia and History of Exacerbations in Patients with Advanced Chronic Obstructive Pulmonary Disease

Figures & data

Figure 1 Episodic nocturnal transcutaneous carbon dioxide pressure increase observed during overnight transcutaneous carbon dioxide pressure monitoring.

Notes: (A) Episodic nocturnal hypercapnia, (B) peak PtcCO₂ increase value, and PtcCO₂ increase range.

Abbreviation: PtcCO₂, transcutaneous carbon dioxide pressure.

Table 1 Patient Characteristics

Variable	All (n = 24)
Age (years) [IQR]	73.5 (64.5–78.8)
Male sex (%)	79.1
Body mass index (kg/m^2)	19.5 ± 3.7
Smoking history
Current smoker (%)	0
Long-term oxygen therapy (%)	16.7
FEV1 (% of predicted value)	30.2 ± 9.0
FVC (% of predicted value)	77.8 ± 24.8
FEV1/FVC ratio	29.2 ± 9.1
Nocturnal maximum PtcCO2 (mmHg)	48.6 ± 9.5
Nocturnal mean PtcCO2 (mmHg)	42.9 ± 9.2
PtcCO2 increases range (mmHg)	5.1 ± 3.3
pH	7.42 ± 0.03
PaCO2 (mmHg)	42.6 ± 7.1
PaO2 (mmHg)	75.4 ± 9.2
Bicarbonate (mmol/L)	28.0 ± 4.4
Hematocrit (%)	39.2 ± 5.7
Serum albumin (g/dL)	4.2 ± 0.4
Brain natriuretic peptide (ng/mL) [IQR]	21.5 (13.3–38.0)
mMRC	2.7 ± 0.8
COPD assessment test	23.4 ± 8.7
Treatment after overnight PtcCO2 monitoring
Home oxygen therapy only (%)	16.7
Home NPPV therapy only (%)	12.5
Home NPPV therapy plus oxygen therapy (%)	33.3

Notes: Parametric data are presented as mean ± standard deviation and nonparametric data as median (IQR). Other data are presented as proportions (%).

Abbreviations: PtcCO₂, transcutaneous carbon dioxide pressure; FEV₁, forced expiratory volume in 1 s; FVC, forced vital capacity; PaCO₂, arterial carbon dioxide pressure; PaO₂, arterial oxygen pressure; mMRC, Modified Medical Research Council dyspnea scale; COPD, chronic obstructive pulmonary disease; NPPV, non-invasive positive pressure ventilation; IQR, interquartile range.

Figure 2 Flow diagram representing the patient selection process.

Abbreviations: COPD, chronic obstructive pulmonary disease; PtcCO₂, transcutaneous carbon dioxide pressure; NPPV, non-invasive positive-pressure ventilation; CPAP, continuous positive airway pressure; PaCO₂, arterial carbon dioxide pressure.

Figure 3 Frequency distribution chart of exacerbations in the analyzed population.

Abbreviation: COPD, chronic obstructive pulmonary disease.

Table 2 Characteristics of Patients with and without Sleep-Associated Hypoventilation

Variable	Patients Without SH (n = 18)	Patients with SH (n = 6)	p value
Age (years) [IQR]	73.5 (65.5–76.5)	73.0 (60.0–81.5)	0.673
Body mass index (kg/m^2)	19.8 ± 2.7	19.8 ± 4.6	0.996
FEV1 (% of predicted value)	29.1 ± 8.2	25.6 ± 11.6	0.426
FVC (% of predicted value)	78.4 ± 24.0	67.1 ± 12.4	0.285
FEV1/FVC ratio	28.1 ± 6.2	30.8 ± 13.1	0.649
Nocturnal maximum PtcCO2 (mmHg)	45.3 ± 5.5	58.6 ± 12.5	0.047
Nocturnal mean PtcCO2 (mmHg)	40.2 ± 5.8	50.9 ± 13.0	0.010
PtcCO2 increases range (mmHg)	4.1 ± 2.4	8.3 ± 3.8	0.004
pH	7.43 ± 0.03	7.39 ± 0.03	0.012
PaCO2 (mmHg)	41.6 ± 6.9	48.3 ± 2.7	0.003
PaO2 (mmHg)	74.9 ± 9.8	71.0 ± 9.3	0.406
Bicarbonate (mmol/L)	27.4 ± 4.2	29.7 ± 0.9	0.039
Hematocrit (%)	41.2 ± 5.2	40.9 ± 8.7	0.927
Serum albumin (g/dL)	4.2 ± 0.4	4.2 ± 0.5	0.895
Brain natriuretic peptide (ng/mL) [IQR]	21.5 (13.5–35.2)	39.0 (9.8–103.5)	0.602
mMRC	2.7 ± 0.7	3.0 ± 0.6	0.382
COPD assessment test	23.0 ± 8.4	25.3 ± 10.0	0.649

Note: Parametric data are presented as mean ± standard deviation and nonparametric data as median (IQR).

Abbreviations: FEV₁, forced expiratory volume in 1 s; FVC, forced vital capacity; PtcCO₂, transcutaneous carbon dioxide pressure; PaCO₂, arterial carbon dioxide pressure; PaO₂, arterial oxygen pressure; mMRC, Modified Medical Research Council dyspnea scale; COPD, chronic obstructive pulmonary disease; IQR, interquartile range.

Table 3 Characteristics of Patients with and without Episodic Nocturnal Hypercapnia

Variable	Patients Without eNH (n = 13)	Patients with eNH (n = 11)	p value
Age (years) [IQR]	73.0 (64.0–76.0)	78 (60.5–81.0)	0.569
Body mass index (kg/m^2)	20.8 ± 2.2	18.7 ± 4.0	0.151
FEV1 (% of predicted value)	28.0 ± 8.4	28.5 ± 10.2	0.904
FVC (% of predicted value)	75.2 ± 28.2	75.9 ± 12.6	0.943
FEV1/FVC ratio	27.6 ± 5.6	30.1 ± 10.6	0.485
Nocturnal maximum PtcCO2 (mmHg)	46.8 ± 8.3	50.7 ± 10.7	0.320
Nocturnal mean PtcCO2 (mmHg)	41.6 ± 7.5	44.4 ± 11.0	0.487
PtcCO2 increases range (mmHg)	2.9 ± 1.5	7.8 ± 2.9	< 0.001
pH	7.44 ± 0.03	7.40 ± 0.04	0.016
PaCO2 (mmHg)	40.0 ± 6.8	47.1 ± 4.6	0.008
PaO2 (mmHg)	73.3 ± 9.8	74.6 ± 10.0	0.740
Bicarbonate (mmol/L)	26.4 ± 3.3	29.8 ± 3.5	0.024
Hematocrit (%)	41.8 ± 6.6	40.4 ± 5.7	0.600
Serum albumin (g/dL)	4.3 ± 0.4	4.0 ± 0.3	0.118
Brain natriuretic peptide (ng/mL) [IQR]	19.2 (9.2–34.6)	31.9 (14.7–140.8)	0.175
mMRC	2.7 ± 0.6	2.9 ± 0.7	0.434
COPD assessment test	24.3 ± 5.9	22.6 ± 10.7	0.667

Note: Parametric data are presented as mean ± standard deviation and nonparametric data as median (IQR).

Abbreviations: FEV₁, forced expiratory volume in 1 s; FVC, forced vital capacity; PtcCO₂, transcutaneous carbon dioxide pressure; PaCO₂, arterial carbon dioxide pressure; PaO₂, arterial oxygen pressure; mMRC, Modified Medical Research Council dyspnea scale; COPD, chronic obstructive pulmonary disease; IQR, interquartile range.

Table 4 Sensitivity, Specificity, and Odds Ratio Values of Sleep-Associated Hypoventilation and Episodic Nocturnal Hypercapnia for the Prediction of Chronic Obstructive Pulmonary Disease Exacerbations

	Sensitivity [95% Confidence Interval]	Specificity [95% Confidence Interval]	Odds Ratio [95% Confidence Interval]
Sleep-associated hypoventilation
Exacerbation events ≥ 1 times/year	25.0 [13.1–33.6]	75.0 [51.1–92.2]	1.0 [0.16–6.00]
Exacerbation events ≥ 2 times/year	12.5 [0.23–33.7]	68.8 [63.7–81.4]	0.3 [0.04–2.64]
Episodic nocturnal hypercapnia
Exacerbation events ≥ 1 times/year	62.5 [48.5–67.6]	87.5 [59.6–97.7]	11.1 [1.39–87.7]
Exacerbation events ≥ 2 times/year	75.0 [46.8–92.1]	68.8 [54.6–77.3]	6.6 [1.06–39.4]

Table 5 Sensitivity, Specificity, and Odds Ratio Values of Sleep-Associated Hypoventilation Criterion (1) and (2) for the Prediction of Chronic Obstructive Pulmonary Disease Exacerbations

	Sensitivity [95% Confidence Interval]	Specificity [95% Confidence Interval]	Odds Ratio [95% Confidence Interval]
SH Criterion 1
Exacerbation events ≥ 1 times/year	18.8 [8.20–27.3]	75.0 [53.8–92.1]	1.0 [0.10–4.41]
Exacerbation events ≥ 2 times/year	12.5 [2.30–36.0]	75.0 [69.9–86.8]	0.4 [0.06–3.69]
SH Criterion 2
Exacerbation events ≥ 1 times/year	12.5 [4.30–15.3]	94.1 [78.7–99.4]	2.3 [0.17–28.5]
Exacerbation events ≥ 2 times/year	5.90 [0.01–21.3]	87.5 [84.7–96.7]	0.4 [0.04–3.97]

Abbreviation: SH, sleep hypoventilation.