Lung perfusion and emphysema distribution affect the outcome of endobronchial valve therapy

Figures & data

Figure 1 Quantification of baseline CT and perfusion scintigrams prior to ELVR with valves.

Notes: CT scans on inspiration were assessed by MeVisPULMO^3D for segmentation of emphysema clusters in the lung. The brown colored areas show pixels of <−950 Hounsfield units, suggestive of emphysema. The numbers in the CT indicate the percentage of emphysema in each lung lobe relative to the total number of voxels in the respective lobe. The HI is defined as the difference in emphysema score between TL and INL. A high HI indicates a more heterogeneous emphysema. The numbers in the perfusion scintigrams indicate the tracer activity in the respective region as percentage of both lungs, calculated for the geometric mean. The patients were grouped into high and low levels of the medians of HI (12.2%) and INL perfusion (14.7%) among all patients. The red circle marks the TL for ELVR. Views are from anterior to posterior. (A) Example of a patient with high HI (13%) and high INL perfusion (18%). (B) Example of a patient with high HI (30%) and low INL perfusion (10%). (C) Example of a patient with low HI (5%) and high INL perfusion (15%). (D) Example of a patient with low HI (8%) and low INL perfusion (3%).
Abbreviations: CT, computed tomograms; ELVR, endoscopic lung volume reduction; FEV₁, forced expiratory volume in 1 second; 6MWT, 6-minute walk test; HI, heterogeneity index; TL, target lobe; INL, ipsilateral nontarget lobe.

Table 1 Patient baseline characteristics and clinical outcome with respect to baseline INL perfusion

Parameters	Below median INL perfusion (<14.7%)	Above median INL perfusion (>14.7%)	P-value
n	27	27
Baseline INL perfusion	11.1±3.2	17.9±3.2	0.001
Sex, n, (male/female)	19/8	12/15	ns
Age (yr)	67.8±5.7	68.5±5.5	ns
BMI (kg/m^2)	26.9±4.4	23.7±4.9	0.023
Smoking history (pack-yr)	49.7±18.2	46.5±23.8	ns
HI <12.2%	12	13	ns
HI ≥12.2%	13	13
Treatment site			0.002
RUL	3	4
RLL	1	3
LUL	12	1
LLL	11	19
Baseline FEV1 (% pred)	27.4±7.4	25.9±6.4	ns
Baseline VC (% pred)	67.2±13.7	61.7±12.4	ns
Baseline RV (% pred)	212±44	222±31	ns
Baseline TLC (% pred)	121±16	123±11	ns
Baseline KCO (% pred)	32.3±18.1	39.0±21.3	ns
Baseline 6MWT (m)	240±81	212±96	ns
Baseline SGRQ (points)	64.0±11.7	65.8±14.1	ns
ΔFEV1 (%)	24.9±26.1	22.2±23.8	ns
ΔVC (%)	17.4±21.9	12.0±21.1	ns
ΔRV (%)	−6.7±16.9	−8.8±18.6	ns
ΔTLC (%)	−0.1±8.0	−3.1±11.7	ns
ΔKCO (%)	38.9±57.1	23.6±55.9	ns
Δ6MWT (m)	8.0±45.3	58.8±69.6	0.014
ΔSGRQ (points)	−7.2±13.9	−11.8±13.7	ns

Notes: Data are presented as mean ± standard deviation. P-values were calculated for categorical variables using the chi-square test and Fisher’s exact test and for continuous variables using the Mann–Whitney U-test.

Abbreviations: INL, ipsilateral nontarget lobe; ns, not significant; BMI, body mass index; HI, heterogeneity index; RUL, right upper lobe; RLL, right lower lobe; LUL, left upper lobe; LLL, left lower lobe; FEV₁, forced expiratory volume in 1 second; VC, vital capacity; RV, residual volume; TLC, total lung capacity; KCO, diffusing capacity of the lung for carbon monoxide (corrected for lung volume); 6MWT, 6-minute walk test; SGRQ, St George’s Respiratory Questionnaire; Δ, change from baseline to follow-up.

Table 2 Patient baseline characteristics and clinical outcome with respect to baseline HI

Parameters	Homogeneous emphysema (<12.2% HI)	Heterogeneous emphysema (≥12.2% HI)	P-value
n	27	27
Baseline HI	6.4±3.3	21.2±6.5	0.001
Sex, n, (male/female)	15/12	16/11	ns
Age (yr)	66.6±5.3	69.0±5.9	ns
BMI (kg/m^2)	25.5±4.5	24.3±5.4	ns
Smoking history (pack-yr)	48.7±25.9	47.2±15.3	ns
Treatment site			ns
RUL	6	1
RLL	3	1
LUL	5	7
LLL	13	18
Baseline FEV1 (% pred)	26.6±7.3	25.7±6.9	ns
Baseline VC (% pred)	64.4±13.7	64.0±13.8	ns
Baseline RV (% pred)	215±31	215±36	ns
Baseline TLC (% pred)	121±13	121±11	ns
Baseline KCO (% pred)	31.4±16.7	37.9±22.4	ns
Baseline 6MWT (m)	232±77	215±96	ns
Baseline SGRQ (points)	64.1±14.4	66.8±11.7	ns
ΔFEV1 (%)	14.9±19.9	32.7±27.3	0.012
ΔVC (%)	14.9±23.3	16.7±23.8	ns
ΔRV (%)	−7.8±14.9	−7.8±20.0	ns
ΔTLC (%)	−1.7±9.5	−1.7±10.7	ns
ΔKCO (%)	31.3±52.9	29.1±60.1	ns
Δ6MWT (m)	32.8±73.9	38.2±50.8	ns
ΔSGRQ (points)	−9.8±14.6	−10.1±14.3	ns

Notes: Data are presented as mean ± standard deviation. P-values were calculated for categorical variables using the chi-square test and Fisher’s exact test and for continuous variables using the Mann–Whitney U-test.

Abbreviations: HI, heterogeneity index; ns, not significant; BMI, body mass index; RUL, right upper lobe; RLL, right lower lobe; LUL, left upper lobe; LLL, left lower lobe; FEV₁, forced expiratory volume in 1 second; VC, vital capacity; RV, residual volume; TLC, total lung capacity; KCO, diffusing capacity of the lung for carbon monoxide (corrected for lung volume); 6MWT, 6-minute walk test; SGRQ, St George’s Respiratory Questionnaire; Δ, change from baseline to follow-up.

Figure 2 Clinical outcomes of patients after ELVR with valves.

Notes: The parameters were assessed prior to and 3 months after treatment. P-values were calculated using the Wilcoxon test. (A) TLV. TLV was quantified from computed tomograms before and after ELVR using the MeVisPULMO^3D software. (B) FEV₁. (C) RV. (D) VC. (E) SGRQ. (F) 6MWT. Data are presented as mean and standard deviation. Numbers indicate relative change.
Abbreviations: ELVR, endoscopic lung volume reduction; TLV, target lobe volume; FEV₁, forced expiratory volume in 1 second; RV, residual volume; VC, vital capacity; SGRQ, St George’s Respiratory Questionnaire; 6MWT, 6-minute walk test.

Figure 3 Correlation between lung perfusion and HI.

Notes: The HI is defined as the difference in emphysema score between TL and INL. P-values were calculated using the Student’s t-test. (A) Correlation between HI and perfusion of the TL. (B) Correlation between HI and perfusion of the INL.
Abbreviations: HI, heterogeneity index; TL, target lobe; INL, ipsilateral nontarget lobe; r, Pearson’s correlation coefficient; ns, not significant.

Figure 4 Correlations between perfusion of the INL, HI and outcome parameters.

Notes: P-values were calculated using the Student’s t-test. (A) Correlation between INL perfusion and change in Δ6MWT after ELVR. (B) Correlation between HI and ΔFEV₁ after ELVR.

Abbreviations: INL, ipsilateral nontarget lobe; HI, heterogeneity index; 6MWT, 6-minute walk test; ELVR, endoscopic lung volume reduction; FEV₁, forced expiratory volume in 1 second; r, Pearson’s correlation coefficient; Δ, change from baseline to follow-up.

Figure 5 Clinical outcome according to baseline percentage perfusion of the INL and the HI.

Notes: P-values were calculated using the Mann–Whitney U-test. (A and C) Change in 6MWT relative to INL perfusion. High INL perfusion includes all patients with INL perfusion >14.7%. Low INL perfusion includes all patients with INL perfusion >14.7%. (B and D) Change in FEV₁ relative to HI. High HI includes all patients with a difference in emphysema scores between TL and INL of >12.2%. Low HI includes all patients with a difference in emphysema scores between TL and INL of <12.2%.
Abbreviations: INL, ipsilateral nontarget lobe; HI, heterogeneity index; 6MWT, six-minute walk test; FEV₁, forced expiratory volume in 1 second; perf, perfusion; TL, target lobe; INL, ipsilateral nontarget lobe; Δ, change from baseline to follow-up.

Figure S1 Correlations with baseline percentage perfusion of the TL.

Notes: P-values were calculated using the Student’s t-test. (A) Correlation between TL perfusion and ΔTLV. (B) Correlation between TL perfusion and ΔFEV₁. (C) Correlation between TL perfusion and ΔRV. (D) Correlation between TL perfusion and ΔVC. (E) Correlation between TL perfusion and ΔSGRQ. (F) Correlation between TL perfusion and Δ6MWT.

Abbreviations: TL, target lobe; Δ, change from baseline to follow-up; TLV, target lobe volume; r, Pearson’s correlation coefficient; ns, not significant; FEV₁, forced expiratory volume in 1 second; RV, residual volume; SGRQ, St George’s Respiratory Questionnaire; 6MWT, 6-minute walk test distance; VC, vital capacity.

Figure S2 Correlations with baseline percentage perfusion of the INL.

Notes: P-values were calculated using the Student’s t-test. (A) Correlation between INL perfusion and ΔTLV. (B) Correlation between INL perfusion and ΔFEV₁. (C) Correlation between INL perfusion and ΔRV. (D) Correlation between INL perfusion and ΔVC. (E) Correlation between INL perfusion and ΔSGRQ. (F) Correlation between INL perfusion and Δ6MWT.

Abbreviations: INL, ipsilateral nontarget lobe; Δ, change from baseline to follow-up; TLV, target lobe volume; r, Pearson’s correlation coefficient; ns, not significant; FEV₁, forced expiratory volume in 1 second; RV, residual volume; SGRQ, St George’s Respiratory Questionnaire; 6MWT, 6-minute walk test distance; VC, vital capacity.

Figure S3 Correlations with baseline HI.

Notes: HI is the difference in emphysema scores between the potential TL and the ipsilateral lobe. P-values were calculated using the Student’s t-test. (A) Correlation between HI and ΔTLV. (B) Correlation between HI and ΔFEV₁. (C) Correlation between HI and ΔRV. (D) Correlation between HI and ΔVC. (E) Correlation between HI and ΔSGRQ. (F) Correlation between HI and Δ6MWT.

Abbreviations: HI, heterogeneity index; TL, target lobe; Δ, change from baseline to follow-up; TLV, target lobe volume; r, Pearson’s correlation coefficient; ns, not significant; FEV₁, forced expiratory volume in 1 second; RV, residual volume; SGRQ, St George’s Respiratory Questionnaire; 6MWT, 6-minute walk test distance; VC, vital capacity.

Figure S4 Correlations between baseline perfusion and ES for each lung lobe.

Notes: P-values were calculated using the Student’s t-test. (A) Correlation between baseline perfusion and ES for the RUL. (B) Correlation between baseline perfusion and ES for the LUL. (C) Correlation between baseline perfusion and ES for the RLL. (D) Correlation between baseline perfusion and ES for the LLL.

Abbreviations: ES, emphysema score; RUL, right upper lobe; LUL, left upper lobe; RLL, right lower lobe; LLL, left lower lobe; r, Pearson’s correlation coefficient.

Table S1 Patient baseline characteristics and clinical outcome with respect to baseline TL perfusion

Parameters	Below median TL perfusion (<8.11%)	Above median TL perfusion (≥8.11%)	P-value
N	27	27
Baseline TL perfusion	4.8±1.7	11.9±2.7	0.001
Sex, n, (male/female)	14/13	17/10	ns
Age (yr)	69.8±5.7	66.6±5.0	0.027
BMI (kg/m^2)	25.1±5.1	25.5±4.8	ns
Smoking history (pack-yr)	42.3±15.9	53.6±24.0	ns
HI <12.2%	11	14	ns
HI ≥12.2%	14	12
Treatment site			0.001
RUL	2	5
RLL	0	4
LUL	2	11
LLL	23	7
Baseline FEV1 (% pred)	27.4±6.5	25.8 ±7.3	ns
Baseline VC (% pred)	65.3±11.9	63.6±14.7	ns
Baseline RV (% pred)	217±40	217±36	ns
Baseline TLC (% pred)	123±17	120±11	ns
Baseline KCO (% pred)	43.4±23.0	28.9±13.9	0.042
Baseline 6MWT (m)	239±80	212±98	ns
Baseline SGRQ (points)	63.0±12.4	66.7±13.0	ns
ΔFEV1 (%)	19.8±22.4	27.3±26.8	ns
ΔVC (%)	14.1±23.2	15.2±20.0	ns
ΔRV (%)	−9.8±17.9	−5.6±17.4	ns
ΔTLC (%)	−3.2±11.2	−0.04±8.6	ns
ΔKCO (%)	17.4±52.6	42.1±57.8	ns
Δ6MWT (m)	26.4±47.2	38.8±76.0	ns
ΔSGRQ (points)	−7.1±13.8	−11.9±13.8	ns

Notes: Data are presented as mean ± standard deviation. P-values were calculated for categorical variables using the chi-square test and Fisher’s exact test, and for continuous variables using the Mann–Whitney U-test.

Abbreviations: TL perfusion, baseline percentage perfusion of TL; TL, target lobe; ns, not significant; BMI, body mass index; HI, heterogeneity index; RUL, right upper lobe; RLL, right lower lobe; LUL, left upper lobe; LLL, left lower lobe; FEV₁, forced expiratory volume in 1 second; VC, vital capacity; RV, residual volume; TLC, total lung capacity; KCO, diffusing capacity of the lung for carbon monoxide; SGRQ, St George’s Respiratory Questionnaire; 6MWT, 6-minute walk test distance; Δ, change from baseline to follow-up.

Table S2 Clinical outcome after ELVR

Parameters	Baseline	Follow-up	Absolute change	Relative change (%)	P-value
FEV1 (% pred)	26.2±6.9	32.0±9.3	5.8±6.5	23.8±24.9	0.001
VC (% pred)	64.0±13.4	72.8±15.3	8.8±12.1	15.9±23.2	0.001
RV (% pred)	219±38	200±46	−18.7±37.1	−8.0±17.3	0.001
TLC (% pred)	123±14	120±17	−2.4±12.2	−1.8±9.9	0.129
KCO (% pred)	34.6±19.8	35.2±14.8	4.9±13.4	31.1±55.0	0.013
6MWT (m)	222±89	257±103	34.6±62.3	28.0±84.4	0.001
SGRQ (points)	65.7±13.3	55.4±16.6	−10.1±14.0	−15.4±20.4	0.001

Notes: Data are presented as mean ± standard deviation. Numbers may not sum up to total due to rounding. P-values were calculated using the Wilcoxon test.

Abbreviations: ELVR, endoscopic lung volume reduction; FEV₁, forced expiratory volume in 1 second; RV, residual volume; VC, vital capacity; TLC, total lung capacity; KCO, diffusing capacity of the lung for carbon monoxide; SGRQ, St George’s Respiratory Questionnaire; 6MWT, 6-minute walk test distance.

Table S3 Patient groups with respect to perfusion and emphysema heterogeneity

	Low TL perfusion (<8.11%)	High TL perfusion (≥8.11%)	P-value
HI <12.2%	11	14	0.579
HI ≥12.2%	14	12
	Low INL perfusion (<14.7%)	High INL perfusion (≥14.7%)	P-value
HI <12.2%	12	13	1.0
HI ≥12.2%	13	13

Notes: Numbers indicate numbers of patients in each group. P-values were calculated using the chi-square test.

Abbreviations: TL, target lobe; HI, heterogeneity index; INL, ipsilateral nontarget lobe.