Update in diagnosis and management of interstitial lung disease

Abstract

The field of interstitial lung disease (ILD) has undergone significant evolution in recent years, with an increasing incidence and more complex, ever expanding disease classification. In their most severe forms, these diseases lead to progressive loss of lung function, respiratory failure and eventually death. Despite notable advances, progress has been challenged by a poor understanding of pathological mechanisms and patient heterogeneity, including variable progression. The diagnostic pathway is thus being continually refined, with the introduction of tools such as transbronchial cryo lung biopsy and a move towards genetically aided, precision medicine. In this review, we focus on how to approach a patient with ILD and the diagnostic process.

Keywords: Cryoscopic lung biopsy; idiopathic pulmonary fibrosis; interstitial lung disease.

© Royal College of Physicians 2017. All rights reserved.

Figures

Fig 1.

Schematic classification of interstitial lung diseases according to aetiology. The finding of histological usual interstitial pneumonitis in a patient with an idiopathic interstitial pneumonia leads to the specific diagnosis of idiopathic pulmonary fibrosis. NSIP = non-specific interstitial pneumonitis.

Fig 2.

The pathogenesis of idiopathic pulmonary fibrosis. 1 – In an initiating phase, there is lung alveolar epithelial damage with loss of the normal lung architecture and disruption of the basement membrane across which gas exchange takes place. With further epithelial damage and apoptosis, comes upregulation of epithelial integrins, such as αvβ6, and a phase of fibroproliferative repair dominates – driven by high levels of TGF-β. Released in an inactive form, this cytokine requires an activation step facilitated by integrins that bind the Arg-Gly-Asp (arginine-glycine-aspartic acid; RGD) motif of pro-TGFβ and promote its cleavage and activation. 2 – Locally activated TGF-β drives the recruitment of fibroblasts and a feed-forward cycle of further TGF-β production. 3 – Under these conditions, fibroblasts differentiate into myofibroblasts that express high levels of integrin αvβ6, are resistant to apoptosis and lay down a collagen matrix. 4 – Once collagen has been laid down in a lung, the architecture of which is already distorted, gas exchange is no longer efficient. There is a change in the vasculature of the lung parenchyma with both fall-out of blood vessels and neo-angiogenesis driven by local production of vascular endothelial and platelet derived growth factors (VEGF and PDGF). At this final phase, the lung is irreversibly scarred. AEC = alveolar epithelial cell; PDGF = platelet-derived growth factor; TGF-β = transforming growth factor beta; TNF-α = tumour necrosis factor alpha; VEGF = vascular endothelial growth factor.

Fig 3.

Diagnostic criteria for a definite usual interstitial pneumonitis pattern on high resolution computerised tomography. 1 – subpleural, basal predominance (red arrows); 2 – reticular abnormality (blue arrow); 3 – honeycombing with or without traction bronchiectasis (yellow arrow); 4 – absence of features inconsistent with usual interstitial pneumonitis pattern.

Fig 4.

Comparison between transbronchial cryo lung biopsy (A) and traditional forceps transbronchial biopsy (B) performed on the same patient at two different sittings. Transbronchial cryo lung biopsy shows preserved architecture of parenchymal tissue with a total biopsy area of 46.81 mm2 and mean biopsy area of 11.7 mm2. Traditional forceps transbronchial biopsy is characterised by crush and haemorrhagic artefact with a total biopsy area of 14.11 mm2 and mean biopsy area of 2.8 mm2.

Fig 5.

Diagnostic algorithm for idiopathic pulmonary fibrosis, in part adapted from the ATS/ERS consensus statement. HRCT = high-resolution computerised tomography; ILD = interstitial lung disease; IPF = idiopathic pulmonary fibrosis; UIP = usual interstitial pneumonitis

Fig 6.

The role of specialist multidisciplinary teams and specialist referral centres in the diagnosis and management of interstitial lung disease. CTD = connective tissue disease; ILD = interstitial lung disease; IPF = idiopathic pulmonary fibrosis; LAM = lymphangioleiomyomatosis; LCH = Langerhans cell histiocytosis; MDT = multidisciplinary team; NSIP = non-specific interstitial pneumonitis

Fig 7.

Schematic interstitial lung disease treatment algorithm. *No robust evidence for managing exacerbations with variation between centres, should be discussed with specialist centre if possible. BAL = bronchoalveolar lavage; GOR = gastro-oesophageal reflux; HRCT = high-resolution computerised tomography; ILD = interstitial lung disease; IPF = idiopathic pulmonary fibrosis; MDT = multidisciplinary team; PFT = pulmonary function test; PHT = pulmonary hypertension

Fig 8.

Positron emission tomography signal superimposed on high-resolution computerised tomography scan of a patient with usual interstitial pneumonitis. A region of interest has been drawn around the area of highest standardised uptake value.