Increased Airway Wall Thickness in Interstitial Lung Abnormalities and Idiopathic Pulmonary Fibrosis

Abstract

Rationale: There is increasing evidence that aberrant processes occurring in the airways may precede the development of idiopathic pulmonary fibrosis (IPF); however, there has been no prior confirmatory data derived from imaging studies.

Objectives: To assess quantitative measures of airway wall thickness (AWT) in populations characterized for interstitial lung abnormalities (ILA) and for IPF.

Methods: Computed tomographic imaging of the chest and measures of AWT were available for 6,073, 615, 1,167, and 38 participants from COPDGene (Genetic Epidemiology of COPD study), ECLIPSE (Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints study), and the Framingham Heart Study (FHS) and in patients with IPF from the Brigham and Women's Hospital Herlihy Registry, respectively. To evaluate these associations, we used multivariable linear regression to compare a standardized measure of AWT (the square root of AWT for airways with an internal perimeter of 10 mm [Pi10]) and characterizations of ILA and IPF by computed tomographic imaging of the chest.

Results: In COPDGene, ECLIPSE, and FHS, research participants with ILA had increased measures of Pi10 compared with those without ILA. Patients with IPF had mean measures of Pi10 that were even greater than those noted in research participants with ILA. After adjustment for important covariates (e.g., age, sex, race, body mass index, smoking behavior, and chronic obstructive pulmonary disease severity when appropriate), research participants with ILA had increased measures of Pi10 compared with those without ILA (0.03 mm in COPDGene, 95% confidence interval [CI], 0.02-0.03; P < 0.001; 0.02 mm in ECLIPSE, 95% CI, 0.005-0.04; P = 0.01; 0.07 mm in FHS, 95% CI, 0.01-0.1; P = 0.01). Compared with COPDGene participants without ILA older than 60 years of age, patients with IPF were also noted to have increased measures of Pi10 (2.0 mm, 95% CI, 2.0-2.1; P < 0.001). Among research participants with ILA, increases in Pi10 were correlated with reductions in lung volumes in some but not all populations.

Conclusions: These results demonstrate that measurable increases in AWT are consistently noted in research participants with ILA and in patients with IPF. These findings suggest that abnormalities of the airways may play a role in, or be correlated with, early pathogenesis of pulmonary fibrosis.

Trial registration: ClinicalTrials.gov NCT00608764 NCT00292552.

Keywords: airways; idiopathic pulmonary fibrosis; interstitial lung abnormalities; lung capacity; square root of AWT for airways with an internal perimeter of 10 mm.

Figures

Figure 1.

The median, minimum, maximum, and first and third quartiles (bottom and top of boxes) of the square root of airway wall thickness (in mm) of hypothetical airways with internal perimeter of 10 mm (Pi10) are shown for each cohort, with individual data points superimposed. Blue boxes represent subjects without interstitial lung abnormalities (ILA), and yellow boxes represent subjects with ILA. COPDGene = Genetic Epidemiology of COPD; ECLIPSE = Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints; FHS = Framingham Heart Study.

Figure 2.

Axial and coronal slices from computed tomographic scans of participants in COPDGene and David E. Herlihy Data Registry and DNA repository of interstitial lung disease. Top: Patient without interstitial lung abnormalities (ILA) from COPDGene revealing an absence of reticular changes. Top inset: Narrow airway walls of an airway with approximate internal perimeter of 10 mm. Middle: Subject from COPDGene with ILA and definite fibrosis showing subpleural reticular changes and traction bronchiectasis. Middle inset: Thickened airway walls of an airway with approximate internal perimeter of 10 mm. Bottom: Patient with IPF from David E. Herlihy Data Registry and DNA repository of interstitial lung disease with fibrotic changes showing subpleural reticular changes, honeycombing, and traction bronchiectasis. Bottom inset: Thickened airway walls of proximal right upper lobe airways.