Diffuse Interstitial Lung Diseases: Is There Really Anything New?

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1 : Is There Really Anything New? Sujal R. Desai, MBBS, MD ESTI SPEAKER SUNDAY Society of Thoracic Radiology San Antonio, Texas March 2014 Diffuse Interstitial Lung Disease The State of Play DILDs Is There Really Anything New? Sujal R Desai Kings College Hospital, London DILD of known cause Drugs, collagen vascular disease / UIP / COP LIP NSIP Granulomatous DILD Sarcoidosis Others Langerhans cell histiocytosis, LAM ATS/ERS International Multidisciplinary Consensus Classification of the Am J Respir Crit Care Med 2002;165:277 Background Re-classification of idiopathic interstitial pneumonias (2002); change in concept of a single diagnostic gold-standard Classification update (2013) - likely to fine-tune So What Is New? Advances in understanding of ILDs in many (apparently disparate) fields Diffuse Interstitial Lung Disease So Whats New? Classification update Changes in diagnostic criteria/certainty New guidelines for diagnosis of UIP / Atypical features & clinical predictors of UIP NSIP UIP vs NSIP vs HP Natural history / acute exacerbation in Genetic linkages, short telomeres & ageing g lung New entities Classification Update (2013) 77

2 SUNDAY Classification Update (2013) Cryptogenic fibrosing alveolitis = (no longer provisional) Distinction between Major, Rare and Unclassifiable IIPs Chronic vs SR-ILDs vs acute/subacute t Clinical (biological) behaviour patterns Multidisciplinary evaluation Chronic Smoking-related Acute/subacute Chronic Smoking-related Acute/subacute Chronic Smoking-related Acute/subacute Chronic Smoking-related Acute/subacute 78

3 SUNDAY RARE IIPs Idiopathic LIP Idiopathic Pleuroparenchymal Fibroelastosis UNCLASSIFIABLE Inadequate C-R-P data OR Major C-R-P discordance OR Inadequate ATS / ERS recognition, characterisation OR Complex HRCT/pathology patterns Usual Interstitial Pneumonia/ Typical HRCT Features Usual Interstitial Pneumonia/ Typical HRCT Features Usual Interstitial Pneumonia/ Typical HRCT Features UIP Pattern Subpleural, basal Reticular pattern Honeycombing ± traction bx Absence of features inconsistent with UIP pattern Inconsistent with UIP Upper/mid-zone Peribronchovascular GGO > reticular Micronodules ++ Multiple cysts Diffuse mosaicism/airtrapping (>3 lobes) Consolidation Possible UIP Pattern Subpleural, basal Reticular pattern Absence of features inconsistent with UIP pattern Inconsistent with UIP Upper/mid-zone Peribronchovascular GGO > reticular Micronodules ++ Multiple cysts Diffuse mosaicism/airtrapping (>3 lobes) Consolidation Raghu G et al. ATS/ERS/JRS/ALAT statement: idiopathic pulmonary fibrosis: evidence-based guidelines for diagnosis and management Am J Respir Crit Care Med 2011;183: Raghu G et al. ATS/ERS/JRS/ALAT statement: idiopathic pulmonary fibrosis: evidence-based guidelines for diagnosis and management Am J Respir Crit Care Med 2011;183:

4 SUNDAY Usual Interstitial Pneumonia Atypical HRCT Features Non-diagnostic HRCT Findings 98 patients with biopsy-proven UIP (n=73) and NSIP (n=23) HRCT evaluation: Definite/Probable UIP; Definite/Probable NSIP; Indeterminate HISTOLOGICAL DIAGNOSIS UIP NSIP Total Definite UIP Probable UIP Indeterminate Probable NSIP Definite NSIP Total Flaherty et al. Radiological versus histological diagnosis in UIP and NSIP: survival implications. Thorax 2003;58: biopsy-proven (Core Group) Two other cohorts Clinical/HRCT (n=20) Mixed (n=48: NSIP, sarcoid, chronic HP,, Hx, OP) 3 thoracic radiologists List of differential diagnoses (no limits) Likelihood : 0=condition not included in DDx; 1=5-25% (unlikely); 2= 30-65% (intermediate); 3= 70-95% (high) and 4=100% (definite) Sverzellati N et al. Biopsy-proved idiopathic pulmonary fibrosis: spectrum of nondiagnostic thin-section CT diagnoses Radiology 2010;254: Non-diagnostic HRCT Findings Non-diagnostic HRCT Findings Obs 1: NSIP [ 70%] Obs 2: NSIP [ 70%] Obs 3: NSIP [ 70%] Obs 1: Sarcoidosis [100%] Obs 2: Sarcoidosis [100%] Obs 3: chp [55%]; NSIP [45%] Sverzellati N et al. Biopsy-proved idiopathic pulmonary fibrosis: spectrum of nondiagnostic thin-section CT diagnoses Radiology 2010;254: Sverzellati N et al. Biopsy-proved idiopathic pulmonary fibrosis: spectrum of nondiagnostic thin-section CT diagnoses Radiology 2010;254: Usual Interstitial Pneumonia/ Clinical Radiological (HRCT) Predictors Usual Interstitial Pneumonia/ Clinical Radiological Predictors Retrospective study 135 patients (UIP / =97; other IIPs=38) HRCT, PFTs, 6MWT (within 6/12 of biopsy)? Clinical-radiological predictors of or Non- IIP? CLINICAL - FUNCTIONAL Age Gender Ever Smoker FVC% Dlco% 6MWT variables Score Alveolar (lobar) Interstitial (lobar) 0 None None 1 GGO <5% Septal thick, no HC 2 GGO <25% HC <25% 3 GGO 25-49% HC 25-49% 4 GGO 50-75% HC 50-75% 5 GGO >75% HC >75% 80

5 Usual Interstitial Pneumonia/ Clinical Radiological Predictors Usual Interstitial Pneumonia/ Clinical Radiological Predictors SUNDAY Score Alveolar (lobar) Interstitial (lobar) 0 None None 1 GGO <5% Septal thick, no HC 2 GGO <25% HC <25% 3 GGO 25-49% HC 25-49% 4 GGO 50-75% HC 50-75% 5 GGO >75% HC >75% Usual Interstitial Pneumonia/ Clinical Radiological Predictors even modest amounts of fibrosis [on HRCT] without honeycombing, can be highly predictive of the presence of when combined with the patients age. NSIP Linkages UIP & NSIP Linkages UIP & NSIP Linkages NSIP UIP NSIP UIP Silva CIS et al. Nonspecific interstitial pneumonia and idiopathic pulmonary fibrosis: changes in pattern and distribution of disease over time. Radiology 2008;247: Silva CIS et al. Nonspecific interstitial pneumonia and idiopathic pulmonary fibrosis: changes in pattern and distribution of disease over time. Radiology 2008;247:

6 SUNDAY UIP & NSIP Linkages NSIP UIP HRCT Diagnostic Confidence Silva CIS et al. Nonspecific interstitial pneumonia and idiopathic pulmonary fibrosis: changes in pattern and distribution of disease over time. Radiology 2008;247: consecutive patients with biopsy-proven DILD Three thoracic radiologists Up to 3 diagnoses (in order of likelihood); level of confidence for 1 st choice HIGH CONFIDENCE (%) CORRECT (%) CHEST RADIOGRAPHY COMPUTED TOMOGRAPHY CORRECT FIRST CHOICE DIAGNOSIS % CHEST RADIOGRAPHY 57 CT 76 Usual interstitial pneumonia 89% Silicosis 93% Lymphangitis carcinomatosis 85% Sarcoidosis 77% Mathieson JR. Chronic diffuse infiltrative lung diseases: comparison of diagnostic accuracy of CT and chest radiolgraphy Radiology 1989;171: Mathieson JR. Chronic diffuse interstitial lung disease: comparison of diagnostic accuracy of CT and chest radiography Radiology 1989;171: Lynch DA. Can CT distinguish hypersensitivity pneumonitis from idiopathic pulmonary fibrosis AJR 1995;165:

7 SUNDAY Silva CIS et al. Chronic hypersensitivity pneumonitis: differentiation from idiopathic pulmonary fibrosis and non-specific interstitial pneumonia. Radiology 2008;246: Raghu G et al. ATS/ERS/JRS/ALAT statement: idiopathic pulmonary fibrosis: evidence-based guidelines for diagnosis and management Am J Respir Crit Care Med 2011;183: August December PROPOSED DIAGNOSTIC CRITERIA Established/concurrent diagnosis of Worsening breathlessness ( 30 days) HRCT New GGO and/or consolidation No infection (endotracheal aspirate/bal) Exclusion of alternative causes Collard H et al. Acute exacerbations of idiopathic pulmonary fibrosis Am J Respir Crit Care Med 2007;176:

8 SUNDAY Pulmonary Fibrosis Genetics and the Ageing Lung Pulmonary Fibrosis Genetics and the Ageing Lung Genetic predisposition to lung fibrosis? Family history in upto 20% of patients Mutations in genes coding for telomerase (htert and htr) of increasing interest Armanios MY et al. Telomerase mutations in families with idiopathic pulmonary fibrosis N Engl J Med 2007;356: Pulmonary Fibrosis Genetics and the Ageing Lung The New Kid on the Block 92-yr-old 78-yr-old (Idiopathic) Pleuroparenchymal Fibroelastosis Copley SJ et al. Lung morphology in the elderly: comparative CT study of subjects over 75 years old versus those under 55 years old Radiology 2009;251: Reddy TL et al. Pleuroparenchymal fibroelastosis: a spectrum of histopathological and imaging phenotypes Eur Respir J 2012;40: Whats Happened in the Last 5 Years? Diagnosis / Follow-up More precise definitions - /UIP Greater experience - UIP vs NSIP vs chronic HP Recognition of overlapping and evolving forms - NSIP UIP Variable prognosis of - rapid vs slow progress vs acute dt deterioration ti Importance of age and ageing Predictive value of age in UIP Normal ageing Links with genetics short telomeres New entities IPPFE 84

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