The diagnosis of idiopathic pulmonary fibrosis: current and future approaches

Abstract

With the recent development of two effective treatments for patients with idiopathic pulmonary fibrosis, an accurate diagnosis is crucial. The traditional approach to diagnosis emphasises the importance of thorough clinical and laboratory evaluations to exclude secondary causes of disease. High-resolution CT is a critical initial diagnostic test and acts as a tool to identify patients who should undergo surgical lung biopsy to secure a definitive histological diagnosis of usual interstitial pneumonia pattern. This diagnostic approach faces several challenges. Many patients with suspected idiopathic pulmonary fibrosis present with atypical high-resolution CT characteristics but are unfit for surgical lung biopsy, therefore preventing a confident diagnosis. The state of the art suggests an iterative, multidisciplinary process that incorporates available clinical, laboratory, imaging, and histological features. Recent research has explored genomic techniques to molecularly phenotype patients with interstitial lung disease. In the future, clinicians will probably use blood-specific or lung-specific molecular markers in combination with other clinical, physiological, and imaging features to enhance diagnostic efforts, refine prognostic recommendations, and influence the initial or subsequent treatment options. There is an urgent and increasing need for well designed, large, prospective studies measuring the effect of different diagnostic approaches. Ultimately, this will help to inform the development of guidelines and tailor clinical practice for the benefit of patients.

Figure 1. High-resolution CT imaging of interstitial pneumonia patterns: different diagnostic categories

(A) Usual interstitial pneumonia pattern: axial chest high-resolution CT image taken at the level of the lower lobes, depicting multilayered subpleural honeycombing without evidence of features inconsistent with a usual interstitial pneumonia pattern. (B) Possible usual interstitial pneumonia: axial chest high-resolution CT image taken at the level of the lower lobes, depicting bilateral symmetrical reticular abnormalities containing areas of traction bronchiectasis, but no clear evidence of subpleural honeycombing. Although there are admixed areas of ground glass opacification, the predominant abnormality is of reticulation. (C) Inconsistent with usual interstitial pneumonia: axial chest high-resolution CT image taken below the level of the carina, depicting diffuse ground glass abnormalities in a predominantly peripheral distribution. Mild traction bronchiectasis is shown in the left upper lobe and right upper lobe, indicating that a proportion of the ground glass abnormality represents fibrosis.

Figure 2. Effect of multidisciplinary diagnostic approach on diagnosis in interstitial pneumonias

(A) Interobserver agreement among clinicians and radiologists in the evaluation of patients with idiopathic interstitial pneumonias. Step 1: individual assessment of high-resolution CT data alone. Step 2: individual assessment of high-resolution CT plus clinical data. Step 3: group discussion of high-resolution CT plus clinical data. Step 4: group discussion of high-resolution CT, clinical, and surgical lung biopsy data. Step 5: consensus diagnosis among all participants. Adapted from Flaherty and colleagues. (B)The effect of bronchial cryobiopsy and surgical lung biopsy on diagnostic confidence in patients with idiopathic pulmonary fibrosis during multidisciplinary team evaluation. Step 2: addition of clinical and radiological data. Step 4: addition of bronchoalveolar lavage data. Step 6: addition of biopsy data. Step 8: addition of follow-up data. Reproduced with permission from Tomassetti and colleagues. BLC=bronchial cryobiopsy. IPF-H=idiopathic pulmonary fibrosis diagnosis made with high confidence. SLB=surgical lung biopsy.

Figure 3. Traditional and future algorithms for the diagnosis of interstitial lung disease

(A) Traditional approach to diagnosis of interstitial lung disease that includes high-resolution CT to identify the pattern of usual interstitial pneumonia. Surgical lung biopsy is recommended in patients with a high-resolution CT pattern of possible usual interstitial pneumoniaor inconsistent with usual interstitial pneumonia in an appropriate clinical setting. Multidisciplinary diagnosis is recommended as a key feature of the diagnostic pathway. Adapted from Raghu and colleagues. (B) Modified recommendation in which high-resolution CT retains a crucial initial diagnostic role. In cases in which high-resolution CT is diagnostic of an alternative process, a diagnosis is assured. As systemic or lung-specific biological markers evolve, these could become key diagnostic or prognostic markers that will supplement clinical and imaging evaluation, and potentially obviate the need for surgical lung biopsy. HRCT=high-resolution CT. ILD=interstitial lung disease. IPF=idiopathic pulmonary fibrosis. MDD=multidisciplinary diagnosis. UIP=usual interstitial pneumonia.