Minimal Important and Detectable Differences of Respiratory Measures in Outpatients with AECOPD^†

Figures & data

Table 1. Anchor and distribution-based methods to estimate the minimal important and detectable differences.

Method	Approach	Statistics
Anchor-based method	ROC curve	–
	Linear regression analysis	–
Distribution-based method	ES	$({\text{mean}}_{\mathrm{T}4}-{\text{mean}}_{\mathrm{T}1})/\sqrt{{(\mathrm{S}\mathrm{D}}_{\mathrm{T}1}^2+{\text{SD}}_{\mathrm{T}4}^2)/2}$
	0.5 times SD	$0.5\times {\text{SD}}_{\mathrm{T}1}$
	SEM	${\text{SD}}_{\mathrm{T}1}\mathrm{ }\sqrt{(1-{\text{ICC}}_{\mathrm{1,2}}\mathrm{ })}$
	MDC95	${\text{MDC}}_{95}=\text{SEM}\times 1.96\times \sqrt{2}$

ES, effect size; MDC₉₅, minimal detectable change at the 95% level of confidence; ROC, receiver operator characteristics; SD, standard deviation; SEM, standard error of measurement.

Table 2. Sample characterisation.

Characteristics	Patients with AECOPD (n = 44)	Patients included for RS analysis (n = 25)
Age, years,	68.2 ± 9.1	70.0 ± 9.8
Sex (male), n(%)	31 (70.5)	16 (47.1)
BMI, kg/m^2	25.9 ± 4.8	26.7 ± 4.9
Smoking status, n(%) Current Former Never	8 (18.2) 22 (50.0) 14 (31.8)	4 (16.0) 11 (44.0) 10 (40.0)
Packs/year	45.0 [22.0–67.3]	30.0 [15.0–70.0]
Exacerbations/year, n(%) 0 1 ≥ 2	8 (18.2) 11 (25.0) 25 (56.8)	5 (20.0) 5 (20.0) 15 (60.0)
FEV1, L	1.22 ± 0.51	1.25 ± 0.54
FEV1,%predicted	51.1 ± 20.3	54.2 ± 20.6
FEV1/FVC, %	50.5 ± 13.6	51.7 ± 13.8
GOLD stages, n(%)
A	6 (13.6)	4 (6.8)
B	5 (11.4)	3 (5.1)
C	5 (11.4)	5 (8.5)
D	26 (59.1)	13 (22.0)
Medication, n(%)
Antibiotics	28 (65.1)	17 (70.8)
Bronchodilators
SABA	9 (20.9)	3 (12.5)
SAMA	6 (14.0)	3 (12.5)
SABA/SAMA combination	6 (14.0)	6 (25.0)
LABA	5 (11.6)	3 (12.5)
LAMA	22 (51.2)	13 (54.2)
LABA/LAMA combination	5 (11.6)	2 (8.3)
ICS	7 (16.3)	5 (20.8)
ICS/LABA combination	27 (62.8)	16 (66.7)
Xanthines	16 (37.2)	8 (33.3)
LTRA	4 (9.3)	3 (12.5)
Expectorants	20 (46.5)	12 (50)
Oral corticosteroids	9 (20.9)	5 (20.8)
mMRC	1.0 [0.5–2.0]	1.0 [0.5–2.0]

Values are presented as mean ± standard deviation or median [interquartile range], unless otherwise stated.

BMI, body mass index; FEV1, forced expiratory volume in one second (at stability); FVC, forced vital capacity (at stability); GOLD, global initiative for chronic obstructive lung disease; ICS, inhaled corticosteroids; LABA, long-acting beta-agonists; LAMA, long-acting muscarinic antagonists; LTRA, leukotriene receptor antagonist; mMRC, modified British Medical Research Council questionnaire; SD, standard deviation; SABA, short-acting beta agonists; SAMA, short-acting muscarinic-antagonist.

Table 3. Mean scores at the onset of AECOPD (T1), after 45 days of AECOPD (T4) and mean change for the respiratory measurement by the COPD Assessment Score.

	Exacerbation onset	Stability post exacerbation	Mean difference	p Value
ΔSpO2	92.6 ± 2.6	94.0 ± 2.7	1.3 ± 2.5	0.004
≥2 CAT	92.7 ± 2.6	94.0 ± 2.8	1.5 ± 2.7
<2 CAT	92.2 ± 2.6	94.0 ± 2.4	2.0 ± 2.1
ΔMBS	2.3 ± 2.2	1.0 ± 1.9	−1.3 ± 2.1	0.001
≥2 CAT	2.2 ± 2.2	0.7 ± 1.2	−1.5 ± 2.1
<2 CAT	2.8 ± 2.6	2.4 ± 3.9	−0.4 ± 1.8
ΔmMRC	2.6 ± 1.0	1.4 ± 1.0	−0.9 ± 1.1	<0.001
≥2 CAT	2.3 ± 1.1	1.3 ± 0.9	−1.1 ± 0.9
<2 CAT	1.8 ± 0.8	2.4 ± 2.0	0.4 ± 0.6
ΔInspiratory CR	1.4 ± 1.6	0.7 ± 1.0	−0.7 ± 1.1	0.013
≥2 CAT	1.4 ± 1.7	0.6 ± 0.8	−0.6 ± 1.1
<2 CAT	1.4 ± 1.7	1.5 ± 1.8	−1.0 ± 1.1
ΔExpiratory CR	1.3 ± 2.0	0.3 ± 6.5	−0.1 ± 2.2	0.026
≥2 CAT	1.1 ± 1.7	0.3 ± 0.7	−0.8 ± 1.8
<2 CAT	3.5 ± 4.9	0.4 ± 0.7	−3.5 ± 4.9
ΔInspiratory %Wh	8.1 ± 13.7	2.0 ± 5.8	−6.3 ± 16.3	0.096
≥2 CAT	7.6 ± 14.3	2.3 ± 6.2	−5.6 ± 16.9
<2 CAT	13.7 ± 1.9	0.0 ± 0.0	−13.7 ± 1.9
ΔExpiratory %Wh	16.2 ± 8.4	8.4 ± 17.0	−5.6 ± 30.7	0.307
≥2 CAT	17.6 ± 23.6	6.9 ± 15.9	−9.8 ± 29.9
<2 CAT	2.1 ± 3.0	18.7 ± 24.1	25.5 ± 23.1
FEV1	1.09 ± 0.51	1.23 ± 0.50	0.12 ± 0.33	0.037
≥2 CAT	1.11 ± 0.53	1.30 ± 0.50	0.16 ± 0.34
<2 CAT	0.98 ± 0.43	0.86 ± 0.28	−0.07 ± 0.26
FEV1%predicted	46.2 ± 18.2	52.8 ± 20.0	5.6 ± 14.3	0.049
≥2 CAT	48.2 ± 18.8	56.5 ± 19.2	6.9 ± 14.9
<2 CAT	36.3 ± 10.7	32.4 ± 10.2	−1.2 ± 8.0

Values are presented as mean ± standard deviation.

%Wh, wheeze occupation rate; CAT, COPD assessment test; CR, crackle; FEV₁ (L), forced expiratory volume in one second; MBS, modified Borg scale; mMRC, Modified British Medical Research Council questionnaire; SpO₂ (%), peripheral oxygen saturation.

Figure 1. Correlations between changes in the CAT and changes in the (A) modified Borg scale, (b) modified British Medical Research Council questionnaire (mMRC) and (C) forced expiratory volume in one second (FEV₁).

Figure 2. ROCs to discriminate between patients improving above and below the MID in CAT (i.e. two points) for the modified British Medical Research Council questionnaire (mMRC).

Figure 3. Linear regression between the CAT and the (A) modified Borg scale, (b) modified British Medical Research Council questionnaire (mMRC) and (C) FEV₁.

Table 4. Anchor-based and distribution-based estimates of the minimal important and detectable differences of the respiratory measures.

	Anchor-based methods		Distribution-based method
Measures	ROC curve	Linear regression analysis	ES	0.5*SD	SEM	MDC95	Pooled value
MBS	–	0.8	0.37	1.1	0.5	1.4	0.9
mMRC	0.5	0.6	0.80	0.5	0.4	1.2	0.6
FEV1		0.03	0.28	0.3	0.1	0.3	0.15
FEV1%predicted	–	–	0.34	9.1	3.6	10.1	7.6
SpO2	–	–	0.52	1.3	0.9	2.4	1.5
Insp. CR	–	–	0.48	0.8	0.7	1.9	1.1
Exp CR	–	–	0.65	1.1	1.6	4.5	2.4
Insp. %Wh	–	–	0.58	7.1	9.3	25.8	14.1
Exp. %Wh	–	–	0.39	11.8	22.7	63.0	32.5

%Wh, wheeze occupation rate; CR, crackle; ES, effect size; FEV₁, forced expiratory volume in one second; MBS, modified Borg scale; MDC95, minimal detectable change at the 95% level of confidence; mMRC, Modified British Medical Research Council questionnaire; ROC, receiver operating characteristic; SD, standard deviation; SEM, standard error of measurement; SpO₂, peripheral oxygen saturation.Results are presented as absolute values.

Figure 4. Summary plots of the pooled values of the MID and MDD for the (A) modified Borg scale; (B) modified British Medical Research Council (mMRC) questionnaire and (C) forced expiratory volume in one second (FEV1), percentage predicted. The horizontal plots represent the minimal clinically important difference estimates derived in this study, classified per method. Where appropriate the estimates include the 95% confidence interval. The bold dotted vertical line resembles the MID estimate as obtained from the literature for stable patients with COPD.