Subclinical interstitial lung disease: why you should care

Abstract

The widespread use of high-resolution computed tomography in clinical and research settings has increased the detection of interstitial lung abnormalities (ILA) in asymptomatic and undiagnosed individuals. We reported that in smokers, ILA were present in about 1 of every 12 high-resolution computed tomographic scans; however, the long-term significance of these subclinical changes remains unclear. Studies in families affected with pulmonary fibrosis, smokers with chronic obstructive pulmonary disease, and patients with inflammatory lung disease have shown that asymptomatic and undiagnosed individuals with ILA have reductions in lung volume, functional limitations, increased pulmonary symptoms, histopathologic changes, and molecular profiles similar to those observed in patients with clinically significant interstitial lung disease (ILD). These findings suggest that, in select at-risk populations, ILA may represent early stages of pulmonary fibrosis or subclinical ILD. The growing interest surrounding this topic is motivated by our poor understanding of the inciting events and natural history of ILD, coupled with a lack of effective therapies. In this perspective, we outline past and current research focused on validating radiologic, physiological, and molecular methods to detect subclinical ILD. We discuss the limitations of the available cross-sectional studies and the need for future longitudinal studies to determine the prognostic and therapeutic implications of subclinical ILD in populations at risk of developing clinically significant ILD.

Figure 1.

Diagnostic algorithm and recommended follow-up of individuals with subclinical interstitial lung disease (ILD). CT = computed tomography; Dl_CO = carbon monoxide diffusing capacity; HRCT = high-resolution computed tomography; ILA = interstitial lung abnormalities; PCP = primary care physician; PFTs = pulmonary function tests.

Figure 2.

Subclinical interstitial lung disease in familial pulmonary fibrosis (FPF). High-resolution computed tomography (HRCT) prone images (A and B) and lung histology (C and D; video-assisted thoracic surgery lung biopsies) were obtained in two asymptomatic brothers with first-degree relatives affected with FPF. The younger brother was asymptomatic; his HRCT shows mild subpleural fibrosis (A), whereas his biopsy demonstrated patchy, temporally uniform interstitial fibrosis with focal organizing pneumonia (C). The older brother did not have a diagnosis of FPF but did have a history of mild exertional dyspnea and abnormal pulmonary function tests; he had an HRCT that showed moderate subpleural fibrosis with minimal honeycombing (B) and a lung biopsy that demonstrated the geographic heterogeneity of usual interstitial pneumonia (D, arrowhead indicates fibroblast foci).