Rationale and Objectives
Computed tomography (CT) airways measurements can be used as surrogates to spirometric measurements for assessing bronchodilation in a particular patient with chronic obstructive pulmonary disease. Although spirometric measurements show variations within the opening hours of a hospital department, we aimed to compare the variability of CT airways measurements between morning and afternoon in patients with chronic obstructive pulmonary disease to that of spirometric measurements.
Materials and Methods
Twenty patients had pulmonary function tests and CT around 8 am and 4 pm . Luminal area (LA) and wall thickness (WT) of third and fourth generation airways were measured twice by three readers. The percentage of airway area occupied by the wall (WA%) and the square root of wall area at an internal perimeter of 10 mm (√WAPi10) were calculated. The effects of examination time, reader, and measurement session on CT airways measurements were assessed, and the variability of these measurements was compared to that of spirometric measurements.
Results
Variability of LA 3rd and LA 4th was greater than that of spirometric measurements ( P values ranging from <.001 to .033). There was no examination time effect on √WAPi10, WT 3rd , LA 4th , or WA% 4th ( P values ranging from .102 to .712). There was a reader effect on all CT airways measurements ( P values ranging from <.001 to .028), except in WT 3rd ( P > .999). There was no effect of measurement session on any CT airway measurement ( P values ranging from .535 to >.999).
Conclusion
As the variability of LA 3rd and LA 4th is greater than that of spirometric measurements, clinical studies should include cohorts with larger numbers of patients when considering LA than when considering spirometric measurements as end points.
Introduction
Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease characterized by a persistent airflow limitation measured by spirometry . The major determinants of this limitation are pulmonary emphysema and airways disease, each of which coexists at various degrees in any given patient. The differences in degrees and varying relationships between determinants have suggested the need for phenotyping COPD . Computed tomography (CT)—through objective quantification of pulmonary emphysema and airways disease—could help in achieving clinically meaningful phenotyping . Although CT quantification of pulmonary emphysema has been extensively addressed , some studies have reported that airways disease could also be quantified at CT through several measurements obtained in proximal airways that are correlated to histologic measurements of distal airways : the wall thickness (WT); the luminal area (LA); the percentage of airway area occupied by the wall (WA%); and the square root of wall area at an internal perimeter of 10 mm (√WAPi10). Moreover, recent studies suggested that some of these CT airways measurements could be used as surrogate to spirometric measurements for assessing bronchodilation in a particular patient with COPD . Nevertheless, although spirometric measurements may show variations within the opening hours of a hospital department, the variability of the CT airways measurements as compared to that of spirometric measurements remains unknown . This knowledge could be of importance in the perspective of using CT airways measurements as end points instead of spirometric measurements . The purpose of our study was therefore to compare the variability of CT airways measurements between morning and afternoon in patients with COPD with that of spirometric measurements.
Materials and Methods
Subjects
Twenty consecutive ambulatory patients were recruited from the COPD clinic of our institution. This group comprised 14 men and 4 women who fulfilled the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria , including ≥40 years of age, smoking history of 10 pack-years or more, and a post-bronchodilator forced expiratory volume in one second to forced vital capacity ratio (FEV 1 /FVC) less than 0.7. These patients also fulfilled the following criteria: no COPD exacerbation or respiratory infection in the 4 weeks before the study; no concomitant pulmonary disease (eg, tuberculosis, bronchiectasis); no pulmonary resection; and no active malignancy or malignancy of any organ within the past 5 years. Age was 64 ± 11 years (mean ± standard deviation). COPD was graded as GOLD I in two patients, as GOLD II in 13 patients, as GOLD III in four patients, and as GOLD IV in one patient . Mean smoking history was 36 pack-years ± 13. On the same day, the patients performed twice pulmonary function tests (PFT) and chest CT scans: the first ones in the morning (around 8 am ) and the second ones in the afternoon (around 4 pm ). This schedule was arbitrarily chosen to cover the opening hours of an imaging department. Treatments in our 20 patients were short-acting β2-agonists (two patients), long-acting anticholinergics (six patients), combination of short-acting β2-agonists plus anticholinergics (eight patients), and combination of long-acting β2-agonists plus corticosteroids (four patients).
Pulmonary Function Tests
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CT Scans
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CT Airways Measurements
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Statistical Analyses
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Results
PFT Results
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TABLE 1
Comparisons of Pulmonary Function Tests Between Morning and Afternoon
Morning Afternoon_P_ Values FEV 1 (L) 1.68 ± 0.68 1.68 ± 0.66 .827 FEV 1 (% predicted) 56.8 ± 19.0 56.9 ± 18.1 .879 FVC (L) 3.01 ± 0.95 3.02 ± 0.94 .913 FVC (% predicted) 81.5 ± 18.2 81.0 ± 15.0 .741 FEV 1 /FVC (%) 53.93 ± 11.11 53.66 ± 10.67 .973 FEV 1 /FVC (% predicted) 70.2 ± 14.6 69.7 ± 13.4 .913 FRC (L) 5.24 ± 1.11 5.09 ± 1.00 .341 FRC (% predicted) 162.8 ± 39.9 156.9 ± 31.2 .225 TLC (L) 7.57 ± 1.20 7.37 ± 1.30 .106 TLC (% predicted) 120.5 ± 11.4 117 ± 12.5 .080 RV (L) 4.54 ± 0.95 4.11 ± 0.88 .082 RV (% predicted) 203.4 ± 43.8 182.9 ± 36 .061 RV/TLC (%) 60.21 ± 8.61 56.74 ± 8.30 .120 DLCO (mL/min/mm Hg) 14.12 ± 6.19 14.49 ± 6.32 .666 DLCO (% predicted) 52.7 ± 19.8 54.1 ± 19.9 .737 DLCO/VA (mL/min/mm Hg/L) 2.44 ± 0.83 2.71 ± 0.84 .185 DLCO/VA (% predicted) 61.6 ± 21.1 65.0 ± 21.6 .517
DLCO, diffusing capacity of carbon monoxide; FEV 1, forced expiratory volume in one second; FRC, functional residual capacity; RV, residual volume; TLC, total lung capacity; VC, vital capacity.
Pulmonary function data are expressed as percentages of predicted normal values established by the European Respiratory Society . Data are mean ± standard deviation of the mean.
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Variability of CT Airways Measurements and Spirometric Measurements
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TABLE 2
Comparison of Variability of CT Airways Measurements and Spirometric Measurements
P Values WAPi10 (mm) vs. FEV 1 (L) .091 WAPi10 (mm) vs. FEV 1 /FVC (%) .809 WT 3rd (mm) vs. FEV 1 (L) .748 WT 3rd (mm) vs. FEV 1 /FVC (%) .126 LA 3rd (mm 2 ) vs. FEV 1 (L).008 \* LA 3rd (mm 2 ) vs. FEV 1 /FVC (%)<.001 \* WA% 3rd (%) vs. FEV 1 (L) .573 WA% 3rd (%) vs. FEV 1 /FVC (%) .212 WT 4th (mm) vs. FEV 1 (L) .099 WT 4th (mm) vs. FEV 1 /FVC (%) .717 LA 4th (mm 2 ) vs. FEV 1 (L).033 \* LA 4th (mm 2 ) vs. FEV 1 /FVC (%)<.001 \* WA% 4th (%) vs. FEV 1 (L) .077 WA% 4th (%) vs. FEV 1 /FVC (%) .935
√WAPi10, square root of wall area at an internal perimeter of 10 mm; FEV1, forced expiratory volume in one second; FVC, forced vital capacity; LA, luminal area; WA%, percentage of total airway area occupied by the wall; WT, wall thickness.
P values in bold demonstrate significance.
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CT Airways Measurements
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TABLE 3
CT Airways Measurements—Effects of Measurement Session, Reader, and Time of CT Examination
CT Examination in the Morning CT Examination in the Afternoon Effect of Effect of Effect of Time of Reader 1 Reader 2 Reader 3 Reader 1 Reader 2 Reader 3 Session Reader Examination Session 1 Session 2 Session 1 Session 2 Session 1 Session 2 Session 1 Session 2 Session 1 Session 2 Session 1 Session 2P Values_P_ Values_P_ Values All measured airways Number 16 ± 7 16 ± 6 14 ± 5 15 ± 5 11 ± 5 11 ± 5 16 ± 6 17 ± 8 15 ± 5 16 ± 6 11 ± 5 12 ± 5 >.999<.001 .303 √WAPi10 (mm) 4.58 ± 0.29 4.68 ± 0.34 4.52 ± 0.29 4.58 ± 0.53 4.66 ± 0.33 4.66 ± 0.29 4.60 ± 0.27 4.62 ± 0.32 4.51 ± 0.23 4.56 ± 0.43 4.60 ± 0.22 4.60 ± 0.23 .428<.001 .712 Third generation airways Number 4 ± 2 4 ± 2 3 ± 2 3 ± 2 3 ± 2 3 ± 2 4 ± 2 4 ± 3 4 ± 2 4 ± 2 3 ± 1 3 ± 1 >.999<.001 .784 LA 3rd (mm 2 ) 13.7 ± 3 13.7 ± 3.2 16.2 ± 4.3 15.1 ± 4.0 16.4 ± 7.5 16.6 ± 7.3 12.7 ± 3.1 13.5 ± 2.6 14.3 ± 3.8 16.5 ± 4.8 14.5 ± 4.4 14.5 ± 3.8 >.999<.001.018 WT 3rd (mm) 1.49 ± 0.16 1,47 ± 0.15 1.45 ± 0.15 1.48 ± 0.17 1.48 ± 0.13 1.49 ± 0.13 1.47 ± 0.15 1.46 ± 0.16 1.46 ± 0.17 1.46 ± 0.17 1.47 ± 0.13 1.46 ± 0.13 >.999 >.999 .439 WA% 3rd (%) 66.4 ± 2.6 65.9 ± 2.8 63.2 ± 3.4 64.0 ± 4.6 64.5 ± 5.5 64.3 ± 5.4 67.1 ± 2.9 66.2 ± 2.3 65.2 ± 4.0 63.5 ± 3.6 65.2 ± 3.2 65.2 ± 3.3 >.999<.001.005 Fourth generation airways Number 12 ± 6 12 ± 5 11 ± 5 12 ± 5 8 ± 4 8 ± 4 12 ± 6 13 ± 7 11 ± 4 12 ± 5 8 ± 5 9 ± 5 .432<.001 .108 LA 4th (mm 2 ) 10.9 ± 2.7 10.5 ± 2.7 11.0 ± 2.8 10.6 ± 2.9 11.5 ± 2.7 11.4 ± 2.6 10.6 ± 2.4 10.6 ± 2.8 10.6 ± 2.8 10.4 ± 2.4 10.9 ± 2.7 11.1 ± 2.6 .952.005 .102 WT 4th (mm) 1.46 ± 0.13 1.49 ± 0.16 1.44 ± 0.14 1.44 ± 0.16 1.47 ± 0.12 1.47 ± 0.12 1.45 ± 0.11 1.45 ± 0.12 1.42 ± 0.10 1.42 ± 0.14 1.46 ± 0.11 1.45 ± 0.11 >.999<.001.010 WA% 4th (%) 69.1 ± 2.0 70.1 ± 1.4 68.7 ± 1.7 69.1 ± 2.4 68.6 ± 2.5 68.7 ± 2.5 69.3 ± 2.2 69.5 ± 2.1 68.8 ± 2.4 69.1 ± 2.0 69.2 ± 2.6 69.0 ± 2.5 .535.028 .484
√WAPi10, square root of wall area at an internal perimeter of 10 mm; LA, luminal area; WA%, percentage of total airway area occupied by the wall; WT, wall thickness.
Data are mean ± standard deviation of the mean. P values in bold demonstrate significance.
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Discussion
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