Venkata Lakshmi Sthanam

Background: Chronic obstructive pulmonary disease (COPD) is characterized by airway remodeling, which may affect tracheal morphology. However, the relationship between tracheal morphometry and COPD severity, quality of life, functional capacity, and mortality remains poorly understood. Objective: To investigate the associations between CT-derived tracheal lumen eccentricity and clinical outcomes in COPD. Methods: We analyzed data from 8,383 participants in the multicenter COPDGene study. Tracheal lumen eccentricity (ε) was calculated at each cross-section using the major and minor axes lengths and deriving final value using the arithmetic mean across all tracheal slices, where ε = 0 represents a circle and ε > 0 indicates an ellipse. Baseline assessments included spirometry measurements, 6-minute walk distance (6MWD), St. George’s Respiratory Questionnaire (SGRQ), and the modified Medical Research Council (mMRC) dyspnea score. Longitudinal assessments included annualized lung function change and all-cause mortality. Multivariable models were used to evaluate associations between tracheal eccentricity and clinical outcomes. Results: Tracheal eccentricity increased with severity of airflow obstruction (0.60±0.07, 0.61±0.07, 0.62±0.07, 0.64±0.08, and 0.64±0.08 in GOLD stages 0 through 4, respectively). Higher tracheal eccentricity was independently associated with lower FEV ₁ (β = −0.30 L, 95% CI: −0.47 to −0.14, p1 /FVC (β = −0.06, 95% CI: −0.09 to −0.04, p<0.001), lower 6MWD (β = −15.7 m, 95% CI: −25.2 to −6.2, p=0.001), higher SGRQ score (β = 16.9, 95% CI: 11.2 to 22.5, p<0.001), higher mMRC dyspnea score (β = 0.4, 95% CI: 0.1 to 0.6, p=0.007), and accelerated lung function decline (β = −23.8 ml/year, 95% CI: −2.48 to −45.13, p=0.029). Increased tracheal eccentricity is associated with increased all-cause mortality (adjusted HR: 1.81 [95% CI, 1.01-3.26]; p = 0.047). Conclusions: These findings suggest that tracheal morphology may serve as an imaging biomarker for COPD outcomes, supported by significant associations with lower quality of life, lung function decline, and all-cause mortality.

Rationale: Conventional CT-derived pulmonary vascular metrics quantify vascular pruning but do not assess spatial heterogeneity of vascular architecture. In COPD, peripheral microvascular pruning coexists with compensatory central vessel dilation, paradoxically preserving total vessel volume while reducing effective vascular penetration into lung parenchyma. Objectives: To develop and validate Vascular Proximity Coverage (VPC), a novel distance-based CT biomarker quantifying spatial efficiency of pulmonary vascular distribution. Methods: This retrospective analysis included 7,881 COPDGene participants with complete vascular segmentations. VPC is estimated by integrating the area under the cumulative lung tissue coverage curve at distances 0–10 mm from segmented vessel voxels. Multivariable models were used to assess associations with lung function, six-minute walk distance (6MWD), St. George’s Respiratory Questionnaire (SGRQ), mMRC dyspnea score and all-cause mortality adjusting for demographics, smoking, emphysema, scanner type, and BV5. We stratified the cohort into four groups defined by the median values of BV5 and VPC, yielding discordant (high-BV5/low-VPC, low-BV5/high-VPC) and concordant (high/high, low/low) vascular phenotypes. Results: VPC declined across disease severity (5.82 ± 0.50 in non-smokers to 5.21 ± 0.64 in GOLD 4; p5 ) and total vessel volume, quantify the amount of visible vasculature but do not assess how effectively vessels reach the lung parenchyma for efficient gas exchange. In COPD, peripheral microvascular pruning commonly coexists with compensatory central vessel dilation, leading to preserved or increased total vascular volume despite compromised functional vascular distribution. What This Study Adds to the Field: Vascular Proximity Coverage (VPC) is a novel distance-based CT biomarker that quantifies the spatial efficiency of pulmonary vascular distribution by measuring cumulative lung tissue coverage across distances from vessel walls. In 7,881 COPDGene participants, including non-smokers and PRISm subjects, lower VPC was independently associated with decreased lung function, reduced exercise capacity, worsened quality of life, and increased all-cause mortality over a median 10.8-year follow-up after adjusting for BV ₅ and emphysema. VPC identified a high-risk phenotype with preserved vessel volume but impaired distribution (high-BV5/low-VPC) that carried 24% increased mortality risk and detected subclinical vascular dysfunction in smokers with normal spirometry.

The new CT metric PiSlope quantified the amount of remodeling along the entire visualized airway and was associated with dyspnea, quality of life, functional capacity, exacerbations, lung function decline, and mortality.