Table 2.

Associations of the TRS with Moderate to Severe COPD and Outcomes Related to COPD Heterogeneity

Outcome	COPDGene Testing Sample		ECLIPSE
	TRS	P Value	TRS	P Value
Moderate to severe COPD, OR (95% CI)	3.35 (2.48–4.53)	<0.0001	N/A	N/A
SGRQ total score	0.4 (0.053)	<0.0001	3.2 (0.85)	0.00021
6-min-walk distance	−140 (19)	<0.0001	−61 (19)	0.0015
% LAA <−950 HU	0.53 (0.078)	<0.0001	0.12 (0.04)	0.0033
Perc15	−7.7 (1.2)	<0.0001	−5.4 (2.5)	0.033
Pi10	0.19 (0.026)	<0.0001	0.0023 (0.0092)	0.8
WA%	2.1 (0.37)	<0.0001	0.58 (0.18)	0.0018

Definition of abbreviations: % LAA = % low-attenuation area; CI = confidence interval; COPD = chronic obstructive pulmonary disease; COPDGene = Genetic Epidemiology of COPD; CT = computed tomography; ECLIPSE = Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-points; HU = Hounsfield units; N/A = not applicable; OR = odds ratio; Perc15 = 15th percentile of the lung density histogram on inspiratory scans; Pi10 = square root of wall area of a hypothetical airway with internal perimeter of 10 mm; TRS = transcriptional risk score; SGRQ = St. George’s Respiratory Questionnaire; WA% = wall area percent.

Data are shown as β (SE) unless otherwise indicated. Multivariable models were constructed in the testing sample of COPDGene and ECLIPSE. Covariates included age, sex, race, pack-years of smoking, and current smoking status. The model for 6-minute-walk distance was additionally adjusted for height and weight. Models for CT imaging variables (% LAA <−950 HU, Perc15, Pi10, and WA%) were additionally adjusted for CT scanner and body mass index. Bonferroni-adjusted significance level is P < 0.05/7 outcomes = 0.007. ECLIPSE included 468 individuals with microarray and follow-up FEV₁ data; all of these participants had moderate to severe COPD, so replication of this outcome could not be performed.