Rationale and Objectives
To analyze airway dimensions throughout the bronchial tree in severe asthmatic patients using multidetector row computed tomography (MDCT) focusing on airway narrowing.
Materials and Methods
Thirty-two patients with severe asthma underwent automated (BronCare software) analysis of their right lung bronchi, with counts of airways >3 mm long arising from the main bronchi (airway count) and bronchial dimension quantification at segmental and subsegmental levels (lumen area [LA], wall area [WA], and WA%). Focal bronchial stenosis was defined as >50% narrowing of maximal LA on contiguous cross-sectional slices. Severe asthmatics were compared to 13 nonsevere asthmatic patients and nonasthmatic (pooled) subjects (Wilcoxon rank tests, then stepwise logistic regression). Finally, cluster analysis of severe asthmatic patients and stepwise logistic regression identified specific imaging subgroups.
Results
The most significant differences between severe asthmatic patients and the pooled subjects were bronchial stenosis (subsegmental and all bronchi: P < .002) and WA% ( P < .0003). Stepwise logistic regression retained WA% as the only explanatory covariable ( P = .002). Two identified clusters of severe asthmatic patients differed for parameters characterizing airway narrowing (airway count: P = .0002; focal bronchial stenosis: P = .009). Airway count was as discriminant as forced expiratory volume in 1 second/forced vital capacity ( P = .01) to identify patients in each cluster, with both variables being correlated ( r = 0.59, P = .005).
Conclusions
Severe asthma–associated morphologic changes were characterized by focal bronchial stenoses and diffuse airway narrowing; the latter was associated with airflow obstruction. WA%, dependent on airway caliber, is the best parameter to identify severe asthmatic patients from pooled subjects.
Asthma is a heterogeneous condition, which may be characterized in terms of clinical, functional, and biological phenotypes . Approximately, 5%–10% of asthmatic patients have severe disease , associated with airway inflammation that induces structural changes over time. These changes are known as airway wall remodeling and include subepithelial fibrosis, enlarged mucous glands, smooth muscle hypertrophy and hyperplasia . Remodeling in severe asthma has functional consequences, with decreased forced expiratory volume in 1 second (FEV 1 ) and persistently increased bronchial hyper-responsiveness . However, whether functional alterations are associated with three-dimensional (3D) in vivo bronchial geometry modifications due to airway narrowing remains to be demonstrated.
Bronchial remodeling can be assessed quantitatively on bronchial biopsy specimens but histologic examination does not provide information on its variability throughout the bronchial tree . Moreover, data on bronchial tree geometry are sparse, mainly based on examination of rubber casts of airways . Nowadays, the morphologic consequences of remodeling in severe asthma need to be better understood as it would contribute to choosing the best adapted among new emerging treatments .
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Materials and methods
Patients
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Table 1
Comparisons of Clinical and Functional Parameters Between Severe Asthmatic Patients and the Pooled Group
Clinical Parameter Severe Asthma ( n = 32) Pooled Group ( n = 13)P Nonsevere Asthma ( n = 7) Nonasthmatic Subjects ( n = 6) Age (years) 48.6 (41–58) 42.7 (32–54) .24 46.8 (32–58) 38 (26–52) Weight (kg) 76.6 (66.5–87) 70.7 (64–77) .27 72.5 (57–93) 68.5 (65–77) Size (m) 1.67 (1.62–1.71) 1.67 (1.69–1.72) .3 1.66 (1.63–1.71) 1.72 (1.68–1.75) Sex (female/male) 21/11 8/5 1 5/2 3/3 Smoker (yes/no) 7/25 2/5 .6 2/5 — Asthma history ∗ Duration (years) 21.9 (9–33.5) 33.8 (18–50) .08 33.8 (18–50) — Atopy (yes/no) 16/15 6/1 .2 6/1 — Oral maintenance steroid therapy (yes/no) 10/21 0/7 .15 0/7 — PFT ∗ FEV 1 (% predicted) 71.8 (58–86) 80.5 (65–97) .36 80.5 (65–97) — FEV 1 /FVC (%) 62.2 (50–73) 71.2 (60–81) .1 71.2 (60–81) — Reversibility (yes/no) 10/21 4/3 .38 4/3 —
FEV 1 , forced expiratory volume in 1 second; FVC, forced vital capacity; PFT, pulmonary function tests.
Data are expressed as means (upper to lower quartile).
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MDCT Acquisitions
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Airway Computations
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Bronchus Analysis
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Statistical Analysis
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Table 2
Comparisons of MDCT Parameters Between Patients with Severe Asthma and Pooled Subjects
MDCT Parameter Severe Asthma ( n = 32) Pooled Group ( n = 13)P Nonsevere Asthma ( n = 7) Nonasthmatic Subjects ( n = 6) Airway count, n 99 (62–118) 153 (100–196) .01 137.1 (86–193) 181.2 (140–222) Stenosis, n Subsegmental bronchi 3.1 (1–5) 0.9 (0–1) .002 1.4 (0–3) 0.3 (0–1) Segmental bronchi 0.8 (0–1) 0.1 (0–0) .6 0.3 (0–1) 0 (0–0) All bronchi 3.9 (2–6) 1 (0–2) .002 1.7 (0–3) 0.3 (0–1) LA (mm²) Subsegmental bronchi 7.7 (4.8–9.1) 10.8 (8.3–11.1) .01 10.3 (9–11.1) 11.2 (8.1–14.9) Segmental bronchi 14.4 (10.4–19.1) 18.9 (15.1–22.2) .02 18.7 (15.3–22.9) 19.1 (14.6–22.4) All bronchi 9.8 (6.8–11.7) 13.3 (10.5–14.7) .01 13 (12.2–14.7) 13.6 (10.4–17.2) WA (mm²) Subsegmental bronchi 14.7 (12.8–16.8) 13 (11.6–13.7) .049 12.9 (12.5–13.7) 13.1 (11.1–15.4) Segmental bronchi 25 (21.3–27.9) 21.7 (19–24) .6 22.2 (19–24) 21.1 (14.8–24.1) All bronchi 17.6 (15.3–19.6) 15 .5 (10.5–14.7) .04 15.6 (14.9–16.1) 15.4 (13.4–18.5) WA% Subsegmental bronchi 68.2 (61.8–74.2) 56.5 (52.3–59.8) .0004 57 (51.9–61.4) 56 (52.3–59.2) Segmental bronchi 65.4 (59.3–70.5) 54.7 (49.5–59) .0008 55.5 (48.8–60) 53.7 (49.3–57.3) All bronchi 67.4 (61.4–73) 56 (52.6–59.6) .0003 56.5 (50.9–60.7) 55.4 (52.6–59.6)
LA, lumen area; WA, wall area; WA%, WA expressed as a percentage of total bronchial areas (LA + WA).
Data are expressed as means (upper to lower quartile).
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Results
Identification of Severe Asthmatic Patients
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Table 3
Stenoses of the Segmental and Subsegmental Bronchi Included in the Right Upper Lobe (B1, B2, and B3) and Anterior, Lateral, and Posterior Segments of the Right Lower Lobe (B8, B9, and B10) .
Bronchus Segmental Level Subsegmental Level Severe Asthma ( n = 32) Nonsevere Asthma ( n = 7) Nonasthmatic Subjects ( n = 6) Severe Asthma ( n = 32) Nonsevere Asthma ( n = 7) Nonasthmatic Subjects ( n = 6) B1 5 1 a: 4; b: 7 a: 1; b: 2 B2 2 1 a: 10; b: 4 a: 2 B3 5 a: 7; b: 10 a: 1; b: 1 B8 3 a: 8; b: 6 B9 9 1 a: 7; b: 6 a: 1 a: 1 B10 3 a: 11, b, c: 3; b: 8, c: 8 b: 1 a: 1 Total 27 3 0 99 9 2
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Cluster Analysis of Severe Asthmatic Patients
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Table 4
Comparisons of Clinical and Functional Parameters of the Two Severe Asthma Patient Clusters
Clinical Parameter Severe Asthma Patients ( n = 32)P Cluster 1 ( n = 13) Cluster 2 ( n = 19) Age (years) 48.6 (41–58) 45.2 (32–56) 50.9 (45–60) .26 Weight (kg) 76.6 (66.5–87) 73.5 (63–82) 78.8 (70–87) .18 Size (m) 1.67 (1.62–1.71) 1.69 (1.64–1.70) 1.66 (1.61–1.72) .34 Sex (female/male) 21/11 8/5 13/6 .7 Smoker (yes/no) 7/25 3/10 4/15 1 Asthma history Duration (years) 21.9 (9–33.5) 17.8 (7–33) 24.8 (13–36) .13 Atopy (yes/no) 16/15 7/6 9/9 1 Oral maintenance steroid therapy (yes/no) 10/21 3/10 7/11 .45 PFT FEV 1 (% predicted) 71.8 (58–86) 88 (80–93) 60.1 (52–72) .0002 FEV 1 /FVC (%) 62.2 (50–73) 74.5 (72–80) 53.4 (47–60) .0002 Reversibility (yes/no) 10/21 4/9 6/12 1
PFT, pulmonary function tests; FEV 1 , forced expiratory volume in 1 second; FVC, forced vital capacity.
Data are expressed as means (upper to lower quartile).
Table 5
Comparisons of MDCT Parameter Differences Between the Two Clusters of Severe Asthma Patients
Parameter Severe Asthma Patients ( n = 32)P Cluster 1 ( n = 13) Cluster 2 ( n = 19) Airway count, n 99 (62–118) 135.3 (111–158) 74.2 (57–91) .0002 Stenosis, n Subsegmental bronchi 3.1 (1–5) 1.9 (1–2) 3.9 (2–5) .02 Segmental bronchi 0.8 (0–1) 0.3 (0–1) 1.2 (0–2) .09 All bronchi 3.9 (2–6) 2.2 (1–2) 5.1 (3–6) .009 LA (mm²) Subsegmental bronchi 7.7 (4.8–9.1) 9.2 (7.3–10.4) 6.7 (4.3–8.5) .02 Segmental bronchi 14.4 (10.4–19.1) 16.3 (13–19.6) 13.1 (9.4–15.7) .06 All bronchi 9.8 (6.8–11.7) 11.3 (10.1–12.9) 8.8 (6.2–10.8) .03 WA (mm²) Subsegmental bronchi 14.7 (12.8–16.8) 15.1 (12.8–16.6) 14.6 (12.9–16.9) .96 Segmental bronchi 25 (21.3–27.9) 25.1 (21.4–25.5) 25.1 (21.2–28.3) .6 All bronchi 17.6 (15.3–19.6) 17.6 (10.1–12.9) 17.6 (15.6–20.8) .6 WA% Subsegmental bronchi 68.2 (61.8–74.2) 64 (57.7–70) 71.2 (65.8–77.6) .03 Segmental bronchi 65.4 (59.3–70.5) 61.2 (56.5–65.3) 68.2 (62.6–75.4) .04 All bronchi 67.4 (61.4–73) 63.3 (57.4–68.4) 70.3 (66.2–76.9) .04
LA, lumen area; WA, wall area; WA%, WA expressed as a percentage of total bronchial areas (LA + WA).
Data are expressed as means (upper to lower quartile).
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Discussion
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