Vessel and Airway Characteristics in One-Year Computed Tomography-defined Rapid Emphysema Progression: SPIROMICS

Abstract

Rationale: Rates of emphysema progression vary in chronic obstructive pulmonary disease (COPD), and the relationships with vascular and airway pathophysiology remain unclear. Objectives: We sought to determine if indices of peripheral (segmental and beyond) pulmonary arterial dilation measured on computed tomography (CT) are associated with a 1-year index of emphysema (EI; percentage of voxels <-950 Hounsfield units) progression. Methods: Five hundred ninety-nine former and never-smokers (Global Initiative for Chronic Obstructive Lung Disease stages 0-3) were evaluated from the SPIROMICS (Subpopulations and Intermediate Outcome Measures in COPD Study) cohort: rapid emphysema progressors (RPs; n = 188, 1-year ΔEI > 1%), nonprogressors (n = 301, 1-year ΔEI ± 0.5%), and never-smokers (n = 110). Segmental pulmonary arterial cross-sectional areas were standardized to associated airway luminal areas (segmental pulmonary artery-to-airway ratio [PAAR_seg]). Full-inspiratory CT scan-derived total (arteries and veins) pulmonary vascular volume (TPVV) was compared with small vessel volume (radius smaller than 0.75 mm). Ratios of airway to lung volume (an index of dysanapsis and COPD risk) were compared with ratios of TPVV to lung volume. Results: Compared with nonprogressors, RPs exhibited significantly larger PAAR_seg (0.73 ± 0.29 vs. 0.67 ± 0.23; P = 0.001), lower ratios of TPVV to lung volume (3.21 ± 0.42% vs. 3.48 ± 0.38%; P = 5.0 × 10^-12), lower ratios of airway to lung volume (0.031 ± 0.003 vs. 0.034 ± 0.004; P = 6.1 × 10^-13), and larger ratios of small vessel volume to TPVV (37.91 ± 4.26% vs. 35.53 ± 4.89%; P = 1.9 × 10^-7). In adjusted analyses, an increment of 1 standard deviation in PAAR_seg was associated with a 98.4% higher rate of severe exacerbations (95% confidence interval, 29-206%; P = 0.002) and 79.3% higher odds of being in the RP group (95% confidence interval, 24-157%; P = 0.001). At 2-year follow-up, the CT-defined RP group demonstrated a significant decline in postbronchodilator percentage predicted forced expiratory volume in 1 second. Conclusions: Rapid one-year progression of emphysema was associated with indices indicative of higher peripheral pulmonary vascular resistance and a possible role played by pulmonary vascular-airway dysanapsis.

Keywords: chronic obstructive pulmonary disease; lung imaging; multicenter trials; pulmonary parenchyma; quantitative CT.

Figure 1.

Flowchart of methods for defining the three groups of participants used in this analysis: former smoker RPs, former smoker NPs, and NSs with computed tomography imaging at TLC at V1 and V2. EI = emphysema index; GOLD = Global Initiative for Chronic Obstructive Lung Disease; NP = nonprogressor; NS = never-smoker; RP = rapid emphysema progressor; TLC = total lung capacity; V1 = baseline visit; V2 = 1-year visit.

Figure 2.

Computed tomography–derived image of the human airway tree labeled with the target airway segments serving to direct the identification of the target arterial segments used for our standardized arterial cross-sectional area metric (segmental pulmonary artery–to–airway ratio): RB4 (blue), LB4 (cyan), RB10 (red), and LB10 (green). LB = left bronchus; RB = right bronchus.

Figure 3.

Box-plot distribution of airway cross-sectional area (CSA), arterial CSA, and segmental pulmonary artery–to–airway ratio (PAAR_seg) for each segment and for each participant group: rapid emphysema progressors (RP), non–emphysema progressors (NPs), and never-smokers (NSs). The boxes extend from the 25th to 75th percentiles, the horizontal line indicates the median, and the triangles indicate the means. The whiskers extend to the minimum and maximum values. The mean ± standard deviation values averaged across segments are given in the table in the top right panel. A two-way mixed-model analysis of variance revealed that both the group and airway branch factors were significant, but their interaction was not significant. A pairwise post hoc test was performed between groups using measurements from all airway branches. Results that significantly differ (P < 0.05) from one another are marked as follows: *RPs versus NPs and ^†NSs versus RPs. Note that arterial area dominates the values for PAAR_seg, and the conclusion that PAAR_seg is larger in RPs compared with NPs and NSs holds for each individual airway–arterial segment pair. lb = left bronchus; rb = right bronchus.

Figure 4.

(Left) The mean total pulmonary vascular volume (TPVV) relative to the associated lung volume (TPVV–to–lung volume ratio) is shown for the rapid emphysema progressor (RP), non–emphysema progressor (NP), and never-smoker (NS) groups. The boxes extend from the 25th to 75th percentiles, the horizontal line indicates the median, and the triangles indicate the means. The ratio of TPVV to lung volume is significantly lower in the RP group compared with NPs and NSs. (Middle) Volumetric displays of TPVV coded for vessels with radius greater than 0.75 mm (blue) and vessels with radius less than 0.75 mm (SVV_0.75; pink). (Right) SVV_0.75/TPVV ratios for the NS, RP, and RP cohorts. The ratio is significantly higher in the RP group than either the NP or NS group.

Figure 5.

Box-plot distribution of airway–to–lung volume ratios for the rapid emphysema progressor (RP), non–emphysema progressor (NP), and never-smoker (NS) groups. The boxes extend from the 25th to 75th percentiles, the horizontal line indicates the median, and the triangles indicate the means. The ratio of airway to lung volume was significantly smaller in the RP group compared with the NP and NS groups. The ratio of airway to lung volume among NPs was marginally but significantly smaller than that among NSs.

Figure 6.

The baseline emphysema index significantly correlated with the individual average PAAR_seg for the whole lung (top left) and for each of the individual lobes. ○ Represents whole lung measurements and × represents lobar measurements. PAAR_seg = segmental pulmonary artery–to–airway ratio.

Figure 7.

A scatterplot showing that baseline postbronchodilator FEV₁% predicted significantly correlated with the average PAAR_seg assessed for each member of the rapid emphysema progressor group. FEV₁ = forced expiratory volume in 1 second; PAAR_seg = segmental pulmonary artery–to–airway ratio.

Figure 8.

A statistically significant (P = 0.028) relationship was observed between baseline emphysema index (EI) and one-year change in EI for the whole lung (top left), which suggests that past rate of emphysema progression is a predictor of future rate of progression. This same relationship was highly significant when evaluated for the left and right lower lobes (bottom left and bottom right, respectively) but not for the other lobes. o represents whole lung measurements and x represents lobar measurements.