Development and Progression of Interstitial Lung Abnormalities in the Framingham Heart Study

Abstract

Rationale: The relationship between the development and/or progression of interstitial lung abnormalities (ILA) and clinical outcomes has not been previously investigated.Objectives: To determine the risk factors for, and the clinical consequences of, having ILA progression in participants from the Framingham Heart Study.Methods: ILA were assessed in 1,867 participants who had serial chest computed tomography (CT) scans approximately 6 years apart. Mixed effect regression (and Cox) models were used to assess the association between ILA progression and pulmonary function decline (and mortality).Measurements and Main Results: During the follow-up period 660 (35%) participants did not have ILA on either CT scan, 37 (2%) had stable to improving ILA, and 118 (6%) had ILA with progression (the remaining participants without ILA were noted to be indeterminate on at least one CT scan). Increasing age and increasing copies of the MUC5B promoter polymorphism were associated with ILA progression. After adjustment for covariates, ILA progression was associated with a greater FVC decline when compared with participants without ILA (20 ml; SE, 66 ml; P = 0.0005) and with those with ILA without progression (25 ml; SE, 611 ml; P = 0.03). Over a median follow-up time of approximately 4 years, after adjustment, ILA progression was associated with an increase in the risk of death (hazard ratio, 3.9; 95% confidence interval, 1.3-10.9; P = 0.01) when compared with those without ILA.Conclusions: These findings demonstrate that ILA progression in the Framingham Heart Study is associated with an increased rate of pulmonary function decline and increased risk of death.

Diffuse parenchymal lung disease

“…In three previous studies the prevalence of ILAs ranged from 3% to 10%, with estimates of progression ranging from 20% at 2 years to 46% at 4 years [6,12,13]. In a recently published study by ARAKI et al [14], the results were comparable: ILAs were prevalent in 6% of total cases, and in 3% (n=53) of the initial scans, of which 43% (n=23) demonstrated progressive imaging abnormalities over ∼6 years of follow-up time. Consistent with previous reports, the progression of ILAs to imaging findings consistent with usual interstitial pneumonia (UIP) was seen in 4% of cases.…”

“…Consistent with previous reports, the progression of ILAs to imaging findings consistent with usual interstitial pneumonia (UIP) was seen in 4% of cases. ILAs have been defined in the majority of those studies as bi-basal reticular changes (around 80% of ILA cases showed this pattern in the study by ARAKI et al [14]), with a large minority that progressed and, for those who progress, a significant increase in the risk of death (HR 3.9, 95% CI 1. [15].…”

The role of high-resolution computed tomography in the follow-up of diffuse lung disease

“…In general, progression of HRCT abnormalities is associated with increased mortality. In an analysis of nearly 2000 patients in the Framingham heart study [43], 6% were found to have worsening interstitial lung abnormalities on serial computed tomographies, which was associated with increased mortality (hazard ratio of 3.9). Serial HRCTs may be able to identify a subset of patients with more rapid progression of disease.…”

Subclinical Interstitial Lung Abnormalities: Toward the Early Detection of Idiopathic Pulmonary Fibrosis?

“…In four recent cohorts, the presence of ILAs was associated with a significant increase in mortality (15), and in the study of Araki and colleagues, ILA progression was predictive of a fourfold increase in the risk of death (3). It is these findings that indicate that the goal of achieving earlier IPF diagnosis is plausible and should be pursued, but it is essential that the correct ILA subgroup be selected for further study.…”

“…Given that ILAs can, in fact, be characterized morphologically, exactly as is routine practice in established interstitial lung disease, it is increasingly important that abnormalities compatible with early IPF (i.e., subpleural reticular ILA) be evaluated more selectively than has been the case in many reports. The separation between fibrotic and nonfibrotic ILAs, made in a number of studies (3,(8)(9)(10)(11)(12)(13)(14), is not sufficient in itself, as limited fibrosis is variably present in smoking-related respiratory bronchiolitis and in many other non-IPF contexts. Even in studies in which ILA subgroups have been clearly described, important clinical associations have mostly been defined for ILAs as a single amalgamated entity.…”