Standardized evaluation of lung congestion during COPD exacerbation better identifies patients at risk of dying

Figures & data

Table 1 Characteristics of patients with and without pulmonary congestion at baseline, assessed by standardized and routine procedure

	Pulmonary congestion by standardized assessment			Pulmonary congestion by routine assessment
	Present (n=16)	Not present (n=83)	P-value	Present (n=14)	Not present (n=85)	P-value
Age, years	73.3 (9.6)	71.1 (8.8)	0.419	76.0 (8.7)	70.7 (8.8)	0.049
Female	8 (50%)	39 (47%)	0.825	6 (43%)	41 (48%)	0.709
Medical history
History of HF	7 (44%)	7 (8.4%)	0.0002	4 (29%)	10 (12%)	0.108
History of HT	9 (56%)	22 (27%)	0.019	6 (43%)	25 (29%)	0.315
FEV1, litera	0.84 (0.35)	0.93 (0.47)	0.777	1.01 (0.50)	0.90 (0.44)	0.576
FEV1/FVC, %a	0.43 (0.09)	0.46 (0.15)	0.799	0.43 (0.11)	0.46 (0.15)	0.688
BMI, kg/m^2a	21.4 (5.8)	23.0 (5.1)	0.099	21.7 (3.6)	22.9 (5.4)	0.630
Findings on admission
Peripheral edema	7 (44%)	11 (13%)	0.004	3 (21%)	15 (18%)	0.715
Heart rate, min^−1	100.8 (16.9)	100.9 (23.5)	0.739	90.4 (18.4)	102.6 (22.7)	0.055
SaO2, %	83.2 (8.2)	91.0 (5.9)	0.0001	87.2 (7.7)	90.1 (6.7)	0.087
PaCO2, kPaa	6.9 (2.1)	5.9 (1.4)	0.097	6.4 (1.9)	6.0 (1.5)	0.333
PaO2, kPaa	6.8 (1.5)	8.6 (1.8)	0.0004	7.7 (2.4)	8.4 (1.7)	0.127
Biochemistry
CRP, mg/L	67 (22–88)	26 (9–66)	0.078	60 (40–74)	25 (9–72)	0.088
NT-proBNP, pg/mL	2,681 (585–3,571)	339 (150–973)	0.001	2,331 (351–3,483)	370 (145–1,019)	0.005
Chest radiograph
Patient supine	12 (75%)	26 (31%)	0.002	7 (50%)	31 (36%)	0.335
Infiltrate	4 (25%)	7 (8.4%)	0.075	2 (14%)	9 (11%)	0.653
ECG
Atrial fibrillation	2 (13%)	5 (6.0%)	0.315	4 (29%)	3 (3.5%)	0.007
Prior MI on ECG	9 (56%)	26 (31%)	0.056	4 (29%)	31 (36%)	0.765

Notes: The data are presented as numbers (percent of the column total), mean (standard deviation), or median (interquartile range). The table includes variables that differ (P<0.20) between the presence and absence of CHF in any of the two radiological assessments. Age, sex, and lung function were included by convention.

a Spirometry, BMI, and blood gas were available for 88, 94, and 97 patients, respectively.

Abbreviations: BMI, body mass index; CHF, congestive heart failure; CRP, C-reactive protein; ECG, electrocardiogram; FEV₁, forced expiratory volume in 1 second; FVC, forced vital capacity; HF, heart failure; HT, arterial hypertension; MI, myocardial infarction; NT-proBNP, N-terminal prohormone of brain natriuretic peptide; PaCO₂, arterial partial pressure of CO₂; PaO₂, arterial partial pressure of O₂; SaO₂, arterial oxygen saturation.

Figure 1 Randomly selected chest radiographs assessed negative in the routine assessment and positive in the standardized assessment.

Notes: (A) FEV₁ =2.3 L, FEV₁/FVC =0.6, NT-proBNP =109 pg/mL. (B) FEV₁ =1.0 L, FV₁/FVC =0.38, NT-proBNP =4,310 pg/mL.
Abbreviations: FEV₁, forced expiratory volume in 1 second; FVC, forced vital capacity; NT-proBNP, N-terminal prohormone of brain natriuretic peptide.

Figure 2 ROC curves for the routine (red dashed) and standardized (blue) assessments.

Notes: Age-adjusted logrank P<0.0001 between R−/S− and R−/S+; age-adjusted P=0.049 between R+/S− and R−/S+. The results were based on the 99 index admissions.

Abbreviations: COPD, chronic obstructive pulmonary disease; R−, radiological assessment negative; R+, radiological assessment positive; S−, standardized assessment negative; S+, standardized assessment positive; ROC, receiver-operating characteristics.

Figure 3 Survival after acute exacerbation of COPD, stratified by radiologic evaluation of pulmonary congestion on admission.

Notes: For the routine assessments, AUC =0.54; for the standardized assessments, AUC =0.62.
Abbreviations: AUC, area under the curve; ROC, receiver operating characteristics.

Table 2 Number of mortalities (with mortality rates per 100 patient-years) in patients with AECOPD, by selected dichotomous covariables

Covariable	No	Yes	P-valuea
Female sex	27 (25)	30 (34)	0.250
History of HF	46 (26)	11 (59)	0.019
History of HT	34 (23)	23 (44)	0.034
AF on admission	51 (27)	6 (64)	0.078
Peripheral edema	40 (23)	17 (81)	<0.0001
Supine posture	28 (21)	29 (46)	0.003
Radiological infiltrate	49 (27)	8 (47)	0.186

Note:

a Logrank P-value for equality of survival.

Abbreviations: AECOPD, acute exacerbation of COPD; COPD, chronic obstructive pulmonary disease; AF, atrial fibrillation; HF, heart failure; HT, hypertension.

Table 3 Number of mortalities (with mortality rates per 100 patient-years) in patients with AECOPD, by quartiles of selected continuous covariables

Covariable (with quartile limits)	Q1	Q2	Q3	Q4	P-valuea
Age, years (63.8; 71.4; 78.6)	8 (14)	14 (26)	15 (33)	20 (48)	0.030
BMI, kg/m^2 (19.5; 21.9; 25.4)†	15 (35)	17 (47)	10 (18)	11 (19)	0.043
SaO2, % (87; 92; 94)	21 (76)	13 (25)	7 (11)	16 (30)	<0.0001
PaO2, kPa (7.0; 8.2; 9.4)†	20 (69)	13 (25)	10 (17)	13 (23)	0.001

Notes:

a Logrank P-value for equality of survival.

† BMI and PaO₂ were available for 94 and 97 patients, respectively.

Abbreviations: AECOPD, acute exacerbation of COPD; COPD, chronic obstructive pulmonary disease; BMI, body mass index; PaO₂, arterial partial pressure of oxygen; SaO₂, arterial oxygen saturation.

Table 4 Hazard ratios (with 95% confidence intervals) for dying during a median of 1.9 years follow up after acute exacerbation of COPD

Covariable	Hazard ratio (95% CI)	P-value
Age (per 5 years)	1.2 (1.01–1.4)	0.036
Female sex	1.8 (1.006–3.2)	0.048
Peripheral edema	2.5 (1.4–4.8)	0.004
Supine posture	1.8 (1.008–3.2)	0.047
Pulmonary congestion by routine assessment	1.7 (0.85–3.5)	0.128
Pulmonary congestion by standardized assessment	2.4 (1.2–4.7)	0.016

Note: The hazard ratios were based on 215 observations in 99 patients in an extended Cox regression analysis.

Abbreviations: CI, confidence interval; COPD, chronic obstructive pulmonary disease.

Table 5 Geometric mean (with number of observations) of baseline NT-proBNP concentration (pg/mL), by selected dichotomous variables

Covariable	No	Yes	P-valuea
Female sex	600 (60)	573 (57)	0.880
History of HF	429 (85)	930 (14)	0.063
AF on admission	438 (92)	1,537 (7)	0.026
Peripheral edema	514 (81)	909 (18)	0.037
Supine posture	363 (61)	746 (38)	0.015

Notes:

a t-test P-value for the difference in the natural logarithm of NT-proBNP concentrations.

Abbreviations: AF, atrial fibrillation; HF, heart failure; NT-proBNP, N-terminal prohormone of brain natriuretic peptide.

Table 6 Geometric mean of baseline NT-proBNP concentrations (pg/mL), by quartiles of selected continuous variables

Covariable (with quartile limits)	Q1	Q2	Q3	Q4	P-valuea
Age, years (63.8; 71.4; 78.6)	207	380	492	1,311	<0.0001
BMI, kg/m^2 (19.5; 21.9; 25.4)	594	994	281	301	0.006
HR, min^−1 (84; 99; 116)	782	318	438	495	0.181
SaO2, % (87; 92; 94)	1,134	419	220	540	0.0005
PaO2, kPa (7.0; 8.2; 9.4)	891	362	326	499	0.070
PaCO2, kPa (5.0; 5.7; 6.6)	575	443	276	738	0.110
CRP, mg/L (9; 29; 73)	486	265	502	831	0.005

Note:

a ANOVA P-value for the difference in the natural logarithm of NT-proBNP concentrations.

Abbreviations: ANOVA, analysis of variance; BMI, body mass index, CRP, C-reactive protein; HR, heart rate; NT-proBNP, N-terminal prohormone of brain natriuretic peptide; PaO₂, arterial partial pressure of oxygen; PaCO₂, arterial partial pressure of carbon dioxide; SaO₂, arterial oxygen saturation.

Table 7 Relative concentration of NT-proBNP in patients with acute exacerbation of COPD

	Relative NT-proBNP	P-value
Age (per 5 years)	1.4 (1.2–1.6)	<0.0001
Female	1.4 (0.84–2.2)	0.221a
CRP quartile		0.059b (for trend)
1. (<9 mg/L)	1
2. (9–29 mg/L)	1.1 (0.75–1.6)	0.635
3. (29–73 mg/L)	1.3 (0.86–1.9)	0.224
4. (≥73 mg/L)	1.7 (1.1–2.7)	0.014
Pulmonary congestion by routine assessment	1.6 (0.96–2.6)	0.069
Pulmonary congestion by standardized assessment	1.8 (1.2–2.6)	0.003

Notes: The results were analyzed in a linear mixed model with 218 observations from 99 patients.

a Sex was kept in the model by convention

b CRP was kept in the model in spite of P>0.05 as its removal resulted in poorer model fit.

Abbreviations: COPD, chronic obstructive pulmonary disease; CRP, C-reactive protein; NT-proBNP, N-terminal prohormone of brain natriuretic peptide.