Structural Predictors of Lung Function Decline in Young Smokers with Normal Spirometry

Abstract

Rationale: Chronic obstructive pulmonary disease (COPD) due to tobacco smoking commonly presents when extensive lung damage has occurred. Objectives: We hypothesized that structural change would be detected early in the natural history of COPD and would relate to loss of lung function with time. Methods: We recruited 431 current smokers (median age, 39 yr; 16 pack-years smoked) and recorded symptoms using the COPD Assessment Test (CAT), spirometry, and quantitative thoracic computed tomography (QCT) scans at study entry. These scan results were compared with those from 67 never-smoking control subjects. Three hundred sixty-eight participants were followed every six months with measurement of postbronchodilator spirometry for a median of 32 months. The rate of FEV₁ decline, adjusted for current smoking status, age, and sex, was related to the initial QCT appearances and symptoms, measured using the CAT. Measurements and Main Results: There were no material differences in demography or subjective CT appearances between the young smokers and control subjects, but 55.7% of the former had CAT scores greater than 10, and 24.2% reported chronic bronchitis. QCT assessments of disease probability-defined functional small airway disease, ground-glass opacification, bronchovascular prominence, and ratio of small blood vessel volume to total pulmonary vessel volume were increased compared with control subjects and were all associated with a faster FEV₁ decline, as was a higher CAT score. Conclusions: Radiological abnormalities on CT are already established in young smokers with normal lung function and are associated with FEV₁ loss independently of the impact of symptoms. Structural abnormalities are present early in the natural history of COPD and are markers of disease progression. Clinical trial registered with www.clinicaltrials.gov (NCT03480347).

Keywords: FEV1; chronic obstructive pulmonary disease; early COPD; lung function; quantitative computed tomography.

Figure 1.

Flow diagram outlining selection of the study cohort and healthy control subjects. COPD = chronic obstructive pulmonary disease; CT = computed tomography; qCT = quantitative computed tomography.

Figure 2.

Comparison of quantitative computed tomography parameters by disease probability measure and three-dimensional texture analysis methods between the BEACON cohort and healthy control subjects. (A–D) Differences in DPM_AirTrap (A), DPM_Emph (B), DPM_Healthy (C), and Pi10 (D). (E–G) Difference in prominent bronchovascular bundles (expressed as a percentage of lung field) (E), ground-glass opacity (F), and honeycombing (G), using the three-dimensional texture analysis method. (H) Difference in the ratio of SVV_0.75 to TPVV. Comparisons were made using the Mann-Whitney test. BEACON = British Early COPD Network; DPM_AirTrap = disease probability measure–defined air trapping; DPM_Emph = disease probability measure–defined emphysema; DPM_Healthy = disease probability measure–defined healthy lung; Pi10 = square root of the wall area of a hypothetical airway with a 10-mm inner perimeter (larger values indicate thicker airway walls); SVV_0.75 = small vessel volume (vessels with radii ⩽0.75 mm); TPVV = total pulmonary vessel volume.

Figure 2.

Comparison of quantitative computed tomography parameters by disease probability measure and three-dimensional texture analysis methods between the BEACON cohort and healthy control subjects. (A–D) Differences in DPM_AirTrap (A), DPM_Emph (B), DPM_Healthy (C), and Pi10 (D). (E–G) Difference in prominent bronchovascular bundles (expressed as a percentage of lung field) (E), ground-glass opacity (F), and honeycombing (G), using the three-dimensional texture analysis method. (H) Difference in the ratio of SVV_0.75 to TPVV. Comparisons were made using the Mann-Whitney test. BEACON = British Early COPD Network; DPM_AirTrap = disease probability measure–defined air trapping; DPM_Emph = disease probability measure–defined emphysema; DPM_Healthy = disease probability measure–defined healthy lung; Pi10 = square root of the wall area of a hypothetical airway with a 10-mm inner perimeter (larger values indicate thicker airway walls); SVV_0.75 = small vessel volume (vessels with radii ⩽0.75 mm); TPVV = total pulmonary vessel volume.

Figure 3.

Visual examples of the image-based metrics. Top panels demonstrate midcoronal sections from a nonsmoking subject (right) with 9% AMFM-defined bronchovascular bundles (pink) and 0.6% ground-glass opacities (green) and a participant in the smoking cohort with 15% bronchovascular bundles and 18% ground-glass opacities. Middle panels demonstrate two members of the baseline smoking cohort. On the left is a participant with disease probability measure (DPM)–defined 25% air trapping (yellow) but no emphysema, and on the right is a participant with DPM-defined 29% air trapping (yellow) and 5.7% emphysema (red). The DPM results are shown within a midcoronal section of a topographic multiplanar reformatted (VIDA Diagnostics) (37) view in which the airways are flattened into a single plane with the parenchyma similarly warped. In the bottom panels, smoking participants at the extremes of the SVV_.75/TVV distribution are displayed, with ratios of 0.085% (left) and 0.404% (right). Vessels with diameters of 0.75 mm or less are displayed in red, and larger vessels are displayed in dark purple. AMFM = adaptive multiple-feature method; SVV_.75 = small vessel volume (vessels with radii ⩽0.75 mm); TVV = total vessel volume.