Imaging Patterns Are Associated with Interstitial Lung Abnormality Progression and Mortality

Abstract

Rationale: Interstitial lung abnormalities (ILA) are radiologic abnormalities on chest computed tomography scans that have been associated with an early or mild form of pulmonary fibrosis. Although ILA have been associated with radiologic progression, it is not known if specific imaging patterns are associated with progression or risk of mortality.Objectives: To determine the role of imaging patterns on the risk of death and ILA progression.Methods: ILA (and imaging pattern) were assessed in 5,320 participants from the AGES-Reykjavik Study, and ILA progression was assessed in 3,167 participants. Multivariable logistic regression was used to assess factors associated with ILA progression, and Cox proportional hazards models were used to assess time to mortality.Measurements and Main Results: Over 5 years, 327 (10%) had ILA on at least one computed tomography, and 1,435 (45%) did not have ILA on either computed tomography. Of those with ILA, 238 (73%) had imaging progression, whereas 89 (27%) had stable to improved imaging; increasing age and copies of MUC5B genotype were associated with imaging progression. The definite fibrosis pattern was associated with the highest risk of progression (odds ratio, 8.4; 95% confidence interval, 2.7-25; P = 0.0003). Specific imaging patterns were also associated with an increased risk of death. After adjustment, both a probable usual interstitial pneumonia and usual interstitial pneumonia pattern were associated with an increased risk of death when compared with those indeterminate for usual interstitial pneumonia (hazard ratio, 1.7; 95% confidence interval, 1.2-2.4; P = 0.001; hazard ratio, 3.9; 95% confidence interval, 2.3-6.8; P , 0.0001), respectively.Conclusions: In those with ILA, imaging patterns can be used to help predict who is at the greatest risk of progression and early death.

Interstitial Lung Abnormalities: What Radiologists Should Know

“…Jin et al ( 14 ) defined fibrotic ILA as a reticular abnormality with or without honeycombing, and 39% of ILA cases in the lung cancer screening population were considered to be fibrotic. Meanwhile, in a study by Araki et al ( 15 ), more than 80% of ILA cases were reticular, but less than 10% were categorized as “definite fibrosis.” Similarly, Putman et al ( 16 ) did not include a reticular abnormality as “definite fibrosis.” Because a fibrotic ILA is more strongly associated with image progression and increased mortality ( 14 16 ), its definition, as well as classification, should be standardized.…”

“…However, centrilobular nodularity, which is common in smoking-related respiratory bronchiolitis, is usually not associated with pulmonary fibrosis ( 32 ). Jin et al ( 14 ) did not consider centrilobular nodularity alone to be sufficient evidence for ILAs, and Putman et al ( 16 ) reported that imaging patterns of centrilobular nodules decreased the likelihood of progression (odds ratio: 0.2; 95% CI: 0.1–0.5), and they were not associated with mortality. Based on these findings, it is likely that ILA should be defined in a format that excludes centrilobular nodularity from the existing description.…”

“…Classifying ILA is important because some specific imaging patterns are associated with progression or risk of mortality. Recently, Putman et al ( 16 ) created an additional subset of “definite fibrosis,” which is characterized by image findings of traction bronchiectasis and honeycombing and associated with the highest risk of progression (odds ratio: 8.4; 95% CI: 2.7–25). Thus, refining the ILA phenotype by stratifying those at a higher risk of adverse clinical outcomes is necessary.…”

“…Previous studies demonstrated that image patterns more closely associated with usual interstitial pneumonia (UIP) pattern were more likely to progress on follow-up imaging ( 11 15 16 ). Several studies have reported on the rates of imaging progression, from 20% in 2 years ( 14 ) to 73% in 5 years ( 16 ). Jin et al ( 14 ) reported that none of the fibrotic ILA cases improved, and 37% of them progressed at a 2-year follow-up.…”

“…Jin et al ( 14 ) reported that none of the fibrotic ILA cases improved, and 37% of them progressed at a 2-year follow-up. Putman et al ( 16 ) showed that all participants with UIP or probable UIP patterns progressed on subsequent imaging, and patients with definite fibrosis patterns had a 70% increase in the risk of death compared with those without definite fibrosis. Figure 8 includes serial CT images showing a progression from a fibrotic ILA to the UIP pattern.…”