Characterizing functional lung heterogeneity in COPD using reference equations for CT scan-measured lobar volumes

Abstract

Background: CT scanning is increasingly used to characterize COPD. Although it is possible to obtain CT scan-measured lung lobe volumes, normal ranges remain unknown. Using COPDGene data, we developed reference equations for lobar volumes at maximal inflation (total lung capacity [TLC]) and relaxed exhalation (approximating functional residual capacity [FRC]).

Methods: Linear regression was used to develop race-specific (non-Hispanic white [NHW], African American) reference equations for lobar volumes. Covariates included height and sex. Models were developed in a derivation cohort of 469 subjects with normal pulmonary function and validated in 546 similar subjects. These cohorts were combined to produce final prediction equations, which were applied to 2,191 subjects with old GOLD (Global Initiative for Chronic Obstructive Lung Disease) stage II to IV COPD.

Results: In the derivation cohort, women had smaller lobar volumes than men. Height positively correlated with lobar volumes. Adjusting for height, NHWs had larger total lung and lobar volumes at TLC than African Americans; at FRC, NHWs only had larger lower lobes. Age and weight had no effect on lobar volumes at TLC but had small effects at FRC. In subjects with COPD at TLC, upper lobes exceeded 100% of predicted values in GOLD II disease; lower lobes were only inflated to this degree in subjects with GOLD IV disease. At FRC, gas trapping was severe irrespective of disease severity and appeared uniform across the lobes.

Conclusions: Reference equations for lobar volumes may be useful in assessing regional lung dysfunction and how it changes in response to pharmacologic therapies and surgical or endoscopic lung volume reduction.

Figure 1.

Consort diagram detailing selection of the model derivation cohort. AA = African American; GOLD = Global Initiative for Chronic Obstructive Lung Disease; GOLD U = FEV₁ < 80% predicted with a preserved FEV₁/FVC ratio (FEV₁/FVC ≥ 0.7); ILA = interstitial lung abnormality; NHW = non-Hispanic white; TLC = total lung capacity (measured on CT scan).

Figure 2.

A, Relationship between age and RUL volume at TLC (■, β=1.01, P = .43) and FRC (gray squares, β=1.42, P = .09). B, Relationship between age and RLL volume at TLC (■, β=0.11, P = .95) and FRC (gray squares, β=2.35, P = .002). FRC = functional residual capacity; RLL = right lower lobe; RUL = right upper lobe. See Figure 1 legend for expansion of other abbreviation.

Figure 3.

A, Relationship between height and RUL volume at TLC (■, β=19.2, P < .0001) and FRC (gray squares, β=9.6, P < .0001). B, Relationship between height and RLL volume at TLC (■, β=24.2, P < .0001) and FRC (gray squares, β=8.8, P < .0001). See Figure 1 and 2 legends for expansion of abbreviations.

Figure 4.

Consort diagram detailing selection of the model validation cohort. See Figure 1 legend for expansion of abbreviations.

Figure 5.

A, Percent predicted lobar volume at TLC ([CT scan-measured lobar volume/predicted lobar volume at TLC] × 100) by GOLD stage for NHW subjects. B, Percent predicted lobar volume at TLC by GOLD stage for AA subjects. The pattern of hyperinflation appears to be relatively consistent between the races: the upper lobes exceed 100% of the predicted volume even in moderate airflow obstruction (GOLD II), whereas the lower lobes only exceed 100% of the predicted volume in very severe disease (GOLD IV). Data are presented as means and SDs. LLL = left lower lobe; LUL = left upper lobe; RML = right middle lobe. See Figure 1 legend for expansion of other abbreviations.

Figure 6.

A, Lobar gas trapping ([CT scan-measured lobar volume/predicted lobar volume at FRC] × 100) by GOLD stage for NHW subjects. B, Lobar gas trapping by GOLD stage for AA subjects. For both races, there is progressive gas trapping with increasing airflow obstruction, and even GOLD II subjects have significant gas trapping. Data are presented as means and SDs. See Figure 1 legend for expansion of abbreviations.