Functional respiratory imaging: heterogeneity of acute exacerbations of COPD

Figures & data

Figure 1 Overview of the FRI concept. Patients are first scanned. Then, the CT images are segmented, and the rendering of the airways is calculated. Then, a 3-dimensional model of the lung is developed. Finally, flow is simulated in this model using CFD techniques.¹⁸

Abbreviations: CFD, computational fluid dynamics; CT, computed tomography; FRI, functional respiratory imaging.

Table 1 Patient characteristics (n=47)

Patient characteristics	Value
Sex (male/female)	27/20
Age (years)	68.0±9.9
GOLD stage 2/3/4	19/22/6
Current smokers/ex-smokers/never smokers	13/33/1
Pack-years	46.5±22.2
Treatment in outpatient setting/hospital setting	9/38
Days between exacerbation and stable state measurements	55.1±22.7

Notes: Results are shown as mean ± standard deviation or n. Demographics presented were measured during screening, and the lung function data presented in this table were measured at stable state.

Abbreviation: GOLD, Global initiative for chronic Obstructive Lung Disease.

Table 2 Change from exacerbation to stable state in lung function and FRI parameters

Parameters	At exacerbation	At stable state	Mean change	Significance
FEV1 (L)	1.15±0.43	1.31±0.50	0.16±0.25	<0.01*
FEV1 (% predicted)	45.92±15.05	51.89±16.83	5.97±9.15	<0.01*
iVawFRC (mL)	34.78±14.20	36.28±12.87	1.50±7.65	0.19
iVawTLC (mL)	54.79±16.05	56.49±16.32	1.70±4.65	0.02*
FRC (L)	4.83±1.31	4.62±1.17	−0.22±0.58	0.01*
iVlobeFRC (L)	5.01±1.18	4.75±1.10	−0.25±0.61	<0.01*
TLC (L)	6.72±1.42	6.74±1.30	0.02±0.60	0.81
iVlobeTLC (L)	6.47±1.18	6.49±1.14	0.02±0.41	0.76
Raw (kPa·s/L)	0.71±0.24	0.63±0.34	−0.10±0.29	0.04*
iRawFRC (kPa·s/L)	0.11±0.13	0.06±0.08	−0.04±0.12	0.03*
iRawTLC (kPa·s/L)	0.04±0.03	0.04±0.02	−0.01±0.02	0.03*
IC (L)	1.96±0.59	2.20±0.73	0.14±0.27	<0.01*
RV (L)	3.87±1.23	3.66±1.02	−0.21±0.76	0.07
TCO (mmol/min/kPa)	3.52±1.50	3.53±1.63	0.06±0.67	0.54
Patient-reported outcomes
SGRQ	62.18±15.31	48.60±20.51	−14.62±18.88	<0.01*
CCQ	3.40±1.20	2.41±1.30	−1.00±1.45	<0.01*
CAT	24.06±7.81	18.23±8.13	−5.83±11.28	<0.01*
mMRC	3.11±1.15	2.43±1.17	−0.67±1.23	<0.01*

Notes: Values are shown as mean ± SD. Correlations are reported as p-value and r.

* p-value <0.05.

Abbreviations: CAT, COPD Assessment Test; CCQ, Clinical COPD Questionnaire; FEV₁, forced expiratory volume in 1 second; FRC, functional residual capacity; FRI, functional respiratory imaging; IC, inspiratory capacity; iRaw, airway resistance measured by FRI; iVaw, airway volume measured by FRI; iVlobe, lobar volume measured by FRI; mMRC, modified Medical Research Council dyspnea scale; Raw, airway resistance measured by plethysmography; RV, residual volume; SD, standard deviation; SGRQ, the Saint George’s Respiratory Questionnaire; TCO, transfer factor for carbon monoxide; TLC, total lung capacity.

Figure 2 Variability in changes from exacerbation to stable state in iVlobe at TLC in individual patients (8 patients randomly selected). The scale represents the percent change in the volume of the different lung lobes at TLC; red represents an increase in volume, while blue represents a decrease.

Abbreviations: iVlobe, lobar volume measured by FRI; TLC, total lung capacity.

Figure 3 Variability in changes from exacerbation to stable state in siRaw at TLC in individual patients (8 patients randomly selected). The scale represents the percent change in the resistance of the different airway branches at TLC; red represents an increase in resistance, while blue represents a decrease.

Abbreviations: siRaw, specific airway resistance measured by FRI; TLC, total lung capacity.

Table 3 Correlation between change in FRI parameters and changes in classical pulmonary function tests and in the quality of life, from exacerbation to stable state

Change in pulmonary function parameter or patient-reported outcome	Change in FRI parameter (level of measurement)	r	p-value
Primary end points
FEV1 (L)	iVlobe (FRC)	0.26	0.08
FEV1 (L)	iVaw (TLC)	0.21	0.16
FEV1 (L)	siVaw (FRC)	0.34	0.02*
IC (L)	iVlobe (FRC)	0.35	0.06
IC (L)	iVaw (TLC)	0.09	0.62
IC (L)	siVaw (FRC)	0.05	0.78
Raw	iRaw (FRC)	0.33	0.04*
sRaw	siRaw (TLC)	0.13	0.42
Secondary end points
SGRQ	FEV1 (L)	0.24	0.11
SGRQ	iVlobe (FRC)	0.14	0.38
SGRQ	iVaw (TLC)	0.12	0.45
SGRQ	siVaw (FRC)	0.17	0.26
SGRQ	siRaw (TLC)	0.28	0.07
CCQ	FEV1 (L)	0.20	0.17
CCQ	iVlobe (FRC)	0.24	0.11
CCQ	iVaw (TLC)	0.12	0.41
CCQ	siVaw (FRC)	0.14	0.34
CCQ	siRaw (TLC)	0.36	0.01*
CAT	FEV1 (L)	0.38	0.01*
CAT	iVlobe (FRC)	0.26	0.08
CAT	iVaw (TLC)	0.26	0.08
CAT	siVaw (FRC)	0.17	0.24
CAT	siRaw (TLC)	0.42	<0.01*
mMRC	FEV1 (L)	0.31	0.04*
mMRC	iVlobe (FRC)	0.12	0.45
mMRC	iVaw (TLC)	0.17	0.25
mMRC	siVaw (FRC)	0.36	0.01*
mMRC	siRaw (TLC)	0.30	0.045*

Notes: Correlations are reported as p-value and r.

* p-value <0.05.

Abbreviations: CAT, COPD Assessment Test; CCQ, Clinical COPD Questionnaire; FEV₁, forced expiratory volume in 1 second; FRC, functional residual capacity; FRI, functional respiratory imaging; IC, inspiratory capacity; iRaw, airway resistance measured by FRI; iVaw, airway volume measured by FRI; iVlobe, lobar volume measured by FRI; mMRC, modified Medical Research Council dyspnea scale; Raw, airway resistance measured by plethysmography; RV, residual volume; SGRQ, the Saint George’s Respiratory Questionnaire; sRaw, specific airway resistance measured by pulmonary function test; siRaw, specific airway resistance measured by FRI; siVaw, specific airway volumes measured by FRI; TCO, transfer factor for carbon monoxide; TLC, total lung capacity.

Table 4 Changes in functional respiratory imaging parameters from exacerbation to stable state in 2 individual patients with similar changes in classical pulmonary function tests

Parameters	Patient 1		Patient 2
	Baseline	Change (%)	Baseline	Change (%)
FEV1	0.82 L	+7.32	0.77 L	+9.09
iVawFRC	32.41 mL	−6.29	7.37 mL	+95.72
iVawTLC	42.20 mL	+14.79	29.13 mL	+3.06
FRC	4.86 L	−9.88	2.92 L	+12.67
iVlobeFRC	201.13% predicted	−28.33	118.52% predicted	+4.87
TLC	6.22 L	−0.96	4.59 L	+3.92
iVlobeTLC	140.62% predicted	−6.14	95.35% predicted	+1.43
Raw	0.441 kPa·s/L	+20.18	1.060 kPa·s/L	−18.96
iRawFRC	0.05 kPa·s/L	+5.51	0.17 kPa·s/L	−89.90
iRawTLC	0.09 kPa·s/L	−51.35	0.05 kPa·s/L	−0.82

Abbreviations: FEV₁, forced expiratory volume in 1 second; FRC, functional residual capacity; iRaw, airway resistance measured by FRI; iVaw, airway volume measured by FRI; iVlobe, lobar volume measured by FRI; Raw, airway resistance measured by plethysmography; TLC, total lung capacity.

Figure 4 FRI images of 2 patients displaying the changes in airway volume. The scale represents the percent change in the volume of the different airway branches at the different lung levels. Green represents an improvement, while red represents a worsening. The airway volume is the volume of the lumen of the airways and does thus represent the volume of air inside the airways. The airways are measured starting from the trachea at the top of the sternum up to the point where no distinction can be made between the intraluminal and alveolar air. This is where the airway diameter is around 1–2 mm. One can infer that an increase in airway volume means bronchodilation has occurred.¹⁸

Abbreviations: FRC, functional residual capacity; FRI, functional respiratory imaging; TLC, total lung capacity.

Figure 5 FRI images of 2 patients displaying the changes in lobar volume. The scale represents the percent change in the volume of the different airway branches at the different lung levels; green represents an improvement, while red represents a worsening.

Abbreviations: FRC, functional residual capacity; FRI, functional respiratory imaging; TLC, total lung capacity.

De BackerJWVosWGGorleCDFlow analyses in the lower airways: patient-specific model and boundary conditionsMed Eng Phys200830787287918096425

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