Diaphragmatic Movement at Rest and After Exertion: A Non-Invasive and Easy to Obtain Prognostic Marker in COPD

Figures & data

Table 1 Patient and Disease Characteristics

Characteristics	All Patients (n=96)	Patients with Primary Outcome (n=64)	Patients without Primary Outcome (n=32)	P-value
Age, years; mean (±SD)	65.1 ± 8.1	66.4 ± 7.8	62.5 ± 8.2	0.028
Male, n (%)	60 (62.5)	38 (59.4)	22 (68.8)	0.37
Active smokers, n (%)	33 (34.4)	21 (32.8)	12 (37.5)	0.66
Smoking pack-years, mean (±SD)	28.5 ± 14.9	30.7 ± 15.8	24.1 ± 11.7	0.016
FEV1 (%), mean (±SD)	55.8 ± 18.3	49.2 ± 17.3	69 ± 12	<0.001
FVC (%), mean (±SD)	77.9 ± 22.5	69.2 ± 18.8	95 ± 19	<0.001
Distance at 6MWT, mean (±SD)	372 ± 110	343 ± 100	431 ± 107	0.0002
CAT score, mean (±SD)	15.6 ± 9.2	19.2 ± 8.5	8.4 ± 5.8	<0.001
mMRC score:
0	11 (11.5%)	3 (4.7%)	8 (25%)	NA
1	15 (15.6%)	6 (9.4%)	9 (28.1%)
2	28 (29.2%)	15 (23.4%)	13 (40.1%)
3	41 (42.7%)	39 (60.9%)	2 (6.3%)
4	1 (1%)	1 (1.6%)	0
Moderate exacerbations in the previous year - mean (±SD)	0.73 ± 0.84	0.91 ± 0.85	0.38 ± 0.71	<0.001
Severe exacerbations in the previous year- mean (±SD)	0.97 ± 0.87	1.18 ± 0.95	0.56 ± 0.62	<0.001
Moderate exacerbations during follow-up, mean - mean (±SD)	0.86 ± 0.90	1.31 ± 0.8	0	NA
Severe exacerbations during follow-up, mean - mean (±SD)	0.45 ± 0.87	0.69 ± 0.99	0	NA
Right diaphragm amplitude at rest, mm	48.1 ± 11.4	44.8 ± 10.5	54.7 ± 10.3	<0.001
Right diaphragm amplitude after exertion, mm	41.9 ± 14.8	38 ± 13.7	49.8 ± 13.9	<0.001
Left diaphragm amplitude at rest, mm	47.6 ± 11.9	45.5 ± 11.4	51.8 ± 12.1	0.017
Left diaphragm amplitude after exertion, mm	41.1 ± 15.7	38.1 ± 15.2	47 ± 15.2	0.0049

Abbreviations: CAT, COPD assessment test; FEV1, Forced expiratory volume in 1 second; FVC, Forced vital capacity; NA, Not assessed; 6MWT, Six-minute walking test; SD, Standard deviation.

Figure 1 Maximal excursion of the right diaphragm at rest and after 6MWT. p<0.001 for both (A) vs (C) and (B) vs (D). The box represents the interquartile range (IQR). The horizontal black line in the box shows the median. The red dot shows the mean value. The vertical black line shows minimum (Q1 - 1.5*IQR) and maximum (Q3 + 1.5*IQR) values (whiskers). (A) Maximal right diaphragm movement at rest in patients without the primary outcome. (B) Maximal right diaphragm movement after 6MWT in patients without the primary outcome. (C) Maximal right diaphragm movement at rest in patients with the primary outcome. (D) Maximal right diaphragm movement after 6MWT in patients with the primary outcome.

Figure 2 Diaphragmatic movement at rest and after 6MWT according to the GOLD stage. The box represents the interquartile range (IQR). The horizontal black line in the box shows the median. The vertical black line shows minimum (Q1 - 1.5*IQR) and maximum (Q3 + 1.5*IQR) values (whiskers).

Figure 3 ROC curves for diaphragmatic movement at rest (left) and after 6MWT (right).

Figure 4 Survival curve for reaching the primary endpoint (time to exacerbation or death) stratified by diaphragmatic movement at rest (≥55 vs <55 mm).

Abbreviation: DM, diaphragmatic movement.

Figure 5 Survival curve for reaching the primary endpoint (time to exacerbation or death) stratified by diaphragmatic movement after 6MWT (≥53 vs <53 mm).

Abbreviation: DM, diaphragmatic movement.

Figure 6 Diaphragmatic movement at rest (left) and after 6MWT (right) according to the exacerbations. The box represents the interquartile range (IQR). The horizontal black line in the box shows the median. The vertical black line shows minimum (Q1 - 1.5*IQR) and maximum (Q3 + 1.5*IQR) values (whiskers).

Figure 7 Diaphragmatic movement at rest (left) and after 6MWT (right) according to mMRC group.

Table 2 Cox Multivariate Analysis to Determine Factors Associated with the Primary Outcome (Exacerbation or Death)

Variable	Univariate*			Multivariate
	HR	95% CI	P-value	HR	95% CI	P-value
Age, years	1.036	1.002–1.07	0.04
Gender, male	0.80	0.49–1.33	0.4
Active smoker	0.85	0.50–1.43	0.5
Smoking pack-years	1.023	1.006–1.04	0.01
FEV1, % predicted	0.96	0.94–0.97	<0.0001
FVC, % predicted	0.96	0.95–0.98	<0.0001	0.944	0.904–0.984	0.005
Distance at 6MWT	0.996	0.993–0.998	0.0006
CAT score	1.075	1.045–1.106	<0.0001	1.133	1.037–1.23	0.011
Moderate exacerbations in the previous year	1.76	1.33–2.34	<0.0001
Severe exacerbations in the previous year	2.16	1.61–2.93	<0.0001	5.446	4.33–6.59	0.004
Right diaphragm amplitude at rest	0.96	0.94–0.98	0.0004	0.932	0.867–0.997	0.033
Right diaphragm amplitude after exertion	0.97	0.95–0.99	0.0007

Notes: P values are based on the null hypothesis that all HRs relating to an explanatory variable equal unity (no effect). *Factors showing an association in the univariate analyses (P <0.2) were incorporated in the multivariable model. Final variable selection was performed using the backward stepwise selection method (likelihood ratio).

Abbreviations: CAT, COPD assessment test; FEV1, Forced expiratory volume in 1 second; FVC, Forced vital capacity; 6MWT, Six-minute walking test; SD, Standard deviation.