Incidental discovery of interstitial lung disease: diagnostic approach, surveillance and perspectives

Abstract

The incidental discovery of pre-clinical interstitial lung disease (ILD) has led to the designation of interstitial lung abnormalities (ILA), a radiological entity defined as the incidental finding of computed tomography (CT) abnormalities affecting more than 5% of any lung zone. Two recent documents have redefined the borders of this entity and made the recommendation to monitor patients with ILA at risk of progression. In this narrative review, we will focus on some of the limits of the current approach, underlying the potential for progression to full-blown ILD of some patients with ILA and the numerous links between subpleural fibrotic ILA and idiopathic pulmonary fibrosis (IPF). Considering the large prevalence of ILA in the general population (7%), restricting monitoring only to cases considered at risk of progression appears a reasonable approach. However, this suggestion should not prevent pulmonary physicians from pursuing an early diagnosis of ILD and timely treatment where appropriate. In cases of suspected ILD, whether found incidentally or not, the pulmonary physician is still required to make a correct ILD diagnosis according to current guidelines, and eventually treat the patient accordingly.

FIGURE 1

Case of clinical evolution from interstitial lung abnormalities (ILA), early idiopathic pulmonary fibrosis (IPF) (subclinical), mild IPF and to advanced IPF. A 70-year-old man without risk factors for interstitial lung disease (ILD). He presented to the Forlì ILD Clinic, V. Poletti, for the incidental finding of ILA, was reclassified to early IPF after multidisciplinary revision of radiological and pathological findings on lung biopsy and during the follow-up evolved to mild IPF, advanced IPF and ultimately died of the disease. a) ILA. Incidental finding of reticular subpleural abnormalities with traction bronchiectasis. Pulmonary function tests: forced vital capacity (FVC) 129%, diffusing capacity of the lung for carbon monoxide (D_LCO) 82%. No symptoms. b) Early IPF. The lung biopsy showed a definite usual interstitial pneumonia pattern and the case was reclassified as early IPF. c) Mild IPF. After 2 years of follow-up the D_LCO dropped to 73%. The patient remained asymptomatic, with FVC around 120%. d) Advanced IPF. After 7 years of follow-up the FVC dropped to 60%, D_LCO to 40% and the patient became symptomatic. The patient died after 10 years of follow-up.

FIGURE 2

Forced vital capacity (FVC) annual trends of early idiopathic pulmonary fibrosis (IPF) and interstitial lung abnormalities (ILA). Participants without ILA had a mean decrease in FVC of 35 mL (sd 44 mL) per year, those with ILA without progression 40 mL (sd 44 mL) decrease per year, and ILA with progression had a mean decline of 64 mL (sd 51 mL) per year. Participants with ILA compared with non-ILA had a −20 mL greater loss in FVC per year and progressive ILA compared with nonprogressive ILA had a −25 mL greater loss in FVC per year [15]. Pre-clinical IPF shows a yearly FVC decline of 83 mL, compared with the 200 mL of the IPF population enrolled in clinical trials [12, 13, 33]. D_LCO: diffusing capacity of the lung for carbon monoxide.

FIGURE 3

Summary of shared features between interstitial lung abnormalities (ILA) and idiopathic pulmonary fibrosis (IPF). CRP: C-reactive protein; CT: computed tomography; GF-15: growth differentiation factor 15; IL: interleukin; MMP: matrix metalloproteinase; Nox: nitric oxide; OR: odds ratio; TNFR: tumour necrosis factor α receptor II; UIP: usual interstitial pneumonia.

FIGURE 4

Proposed algorithm for diagnosis and management of interstitial lung abnormalities (ILA), early interstitial lung disease (ILD) (both subclinical and pre-clinical) and mild ILD. BAL: bronchoalveolar lavage; CT: computed tomography; HRCT: high-resolution computed tomography; IPF: idiopathic pulmonary fibrosis; PFT: pulmonary function test; UIP: usual interstitial pneumonia.