Diagnosing ILD. What is important in 2016? Chris Grainge

Diagnosing ILD What is important in 2016? Chris Grainge Senior Staff Specialist Respiratory Medicine John Hunter Hospital Conjoint A/Prof University of Newcastle

Conflict of interest I have acted as a paid consultant to Roche and Boehringer Ingelheim regarding treatment of IPF Boehringer Ingelheim have provided an unrestricted grant to support the regional interstitial lung disease service based at the John Hunter Hospital

Interstitial lung disease Over 100 forms of ILD have been described Diffuse infiltrative disorders of the lung characterised by Altered lung interstitium Possible fibrosis Possible inflammatory infiltrate Meyer, K. Trans Resp Med. 2014

Interstitial lung disease major groups Idiopathic interstitial pneumonias - IPF, COP, NSIP, RBILD, DIP, AIP, LIP Connective tissue disease associated ILD (CTD-ILD) / IPAF Sarcoid Iatrogenic disease (drugs, radiation etc) Eosinophilic ILD eosinophilic pneumonia Occupational lung disease Hypersensitivity pneumonitis Inherited eg familial pulmonary fibrosis Primary disease eg Langerhans histiocytosis Meyer, K. Trans Resp Med. 2014

Correct ILD diagnosis is vital in 2016 Distinguishing between the ILDs can be difficult Correct diagnosis allows Correct management Prognostication Study / trials

Correct ILD diagnosis is vital in 2016 survival in IPF, non-ipf and unclassifiable ILD Ryerson et al. ERJ. 2013

Correct ILD diagnosis is vital in 2016 Previously treatment was either non existent or semiuniform There is now a major division between therapy in the treatment of IPF versus non IPF IIP including IPF IPAF idiopathic pneumonia with autoimmune features CTD-ILD Rheumatoid Scleroderma Dermatomyostits

Asymptomatic period Presentation to primary care Referral to secondary care History, examination, investigations Diagnosis by individual clinician Treatment observation Antifibrotic therapy Pirfenidone Nintedanib Immunosuppression Trials Transplant Palliative care

Best diagnosis is multidisciplinary Synthesis of clinical, radiological and pathological data Helps define a diagnosis on the basis of often ill defined clinical / radiological or pathological data Best for patients Best for clinicians Chartrand, S. J Rheumatology, 2016

The MDT- why bother? Groups of people are smarter than individuals Even if those individuals are experts Applicable in almost every field..

The MDT- why bother? Ask the audience. Right 92% of the time Except in Russia

The MDT- why bother - improves outcomes ILD MDT is a dynamic, interactive process The dynamic exchange of information, rather than reading a report, improves interobserver variability and diagnostic confidence Improves recognition of rare diseases Is currently gold standard for diagnosis of ILD Flaherty, K. Am J Respir Crit Care Med. 2004

The MDT why bother we will have to Pirfenidone has been approved by the TGA Results of the recent PBS committee are awaited but.. Expected that MDT diagnosis will be a requirement for prescribing

The MDT - unclassifiable disease About 10% following MDT Easier to make that call at MDT Acceptance of uncertainty easier with more people Despite unclassifiable still able to give prognostic information Ryerson et al. ERJ. 2013. Jo, H. BMC Pulmonary Medicine, 2016

The MDT- composition Made up of; Respiratory physicians Radiologists (with a respiratory interest) Pathologists (with a respiratory interest) ILD Specialist nurse(s) Rheumatologists / immunologists Palliative care Jo, H. BMC Pulmonary Medicine, 2016

The MDT- large centres do better Academic centres vs community physicians? Examined same data going to academic centres and community physicians Academic centres had better agreement between physicians, radiologists and pathologists Community physicians more likely to diagnose IPF Academic centres considered more possible diagnoses Flaherty, K. Am J Respir Crit Care Med. 2006

Specialist centres for ILD improve survival In IPF delayed access to a tertiary care centre associated with Higher risk of death Independent of disease severity Early referral to an ILD centre should be considered in ILD Lamas, D. Am J Respir Crit Care Med. 2011

What is a specialist centre for ILD Defined in the UK as Seeing more than 500 ILD patients per year Having an ILD MDT meeting Having ILD specialist nurses Having experience in specialist (antifibrotic) medication Idiopathic pulmonary fibrosis (2013) NICE guideline CG163

Specialist centres for ILD in Australia? Case load Specialist ILD clinic with rheumatology / immunology input ILD MDT with rheumatology / immunology ILD specialist nurses Experience with specialist medication Access to specialist diagnostic techniques A hub and spoke arrangement

Larger samples from cryobiopsy Image courtesy of Jonothan Wiliamson, Liverpool Hospital

Secondary pulmonary lobule The centrilobular artery (in blue) and the terminal bronchiole run in the center. Lymphatics and veins (in red) run within the interlobular septa

Larger samples from cryobiopsy Yarmus et al, Chest. 2013

Normal alveolar structure from cryobiopsy

Asymptomatic period Presentation to primary care Referral to secondary care Biopsy; Surgical Cryobiopsy both (COLDICE trial) Combined Clinic; Rheumatology Immunology Respiratory clinic IPF registry MDT Investigation Examination History discussion Respiratory Respiratory Structured Radiology PFTs Pathology Proforma Immunology / Rheumatology Radiological Checklist Palliative care Haematological Rheumatology Dermatology Exposures Protocols Rashes Nail Standardised bed FHx changes Subtle Subtle Extended? symptoms signs Diagnosis by ATS/ERS guidelines +/- disease behaviour Counseling / review by specialist nurse History exposures, connective tissue dx symptoms, drugs etc Examination meticulous examination for CTD features Investigations HRCT (protocol) bloods, PFT, 6MW Clinical review? Combined clinic Treatment observation Immunosuppression Antifibrotic therapy Pirfenidone Nintedanib Trials Transplant Palliative care

Disease behaviour assessment Reversible and self limiting Reversible but with risk of progression Stable, but residual disease present Progressive irreversible disease, but possibility of stabilisation Progressive irreversible disease despite therapy Jo, H. BMC Pulmonary Medicine, 2016

Summary diagnosis of ILD in 2016 Differentiation vital Diagnosis is difficult spread the pain Best done at MDT Survival better in specialist centres Need hub and spoke models