The new classification of the idiopathic interstitial pneumonias

1. The new classification of the idiopathic interstitial pneumonias Trieste symposium April 2013 Athol Wells Royal Brompton Hospital

2. AUW has no relevant conflicts of interest

3. Plan • Outline of revised classification • Key related issues • Rare disorders and entities in waiting • Diseases that do not read classification documents

4. Histologic and clinical classification of idiopathic interstitial pneumonias (ICCILD) 2002

5. The idiopathic interstitial pneumonias Major Idiopathic Interstitial Pneumonias Idiopathic pulmonary fibrosis Idiopathic nonspecific interstitial pneumonia Respiratory bronchiolitis interstitial lung disease Desquamative interstitial pneumonia Cryptogenic organizing pneumonia Acute interstitial pneumonia Rare Idiopathic Interstitial Pneumonias Idiopathic lymphoid interstitial pneumonia Idiopathic pleuropulmonary fibroelastosis Unclassifiable idiopathic interstitial pneumonias

6. CATEGORIZATION OF MAJOR IDIOPATHIC INTERSTITIAL PNEUMONIAS †DIP can occasionally occur in nonsmokers;

7. Histology no longer “pre-eminent”

8. Idiopathic NSIP: a true clinical entity? • Idiopathic NSIP designated a “provisional” entity in ATS/ERS 2002 • Important divergences between series in HRCT features, BAL findings and outcome data • Overlap in clinical and HRCT features increasingly observed with HP, IPF and COP

9. Idiopathic nonspecific interstitial pneumonia: report of an American Thoracic Society project Travis WD, Hunninghake G, King TE et al Am J Respir Crit Care Med 2008; 177:1338-1347

10. Conclusions • Idiopathic NSIP exists and has typical clinical and HRCT features • The diagnosis requires a dynamic integrated multi-disciplinary approach because of overlap with other disorders

11. Occurs most often in middle-aged women who are never-smokers

12. Angels on the head of a pin… • Should DIP and RBILD be in an IIP classification? • Serious disagreement on that point. • They should be because they are! Overlap with the other “IIPs” • DIP occurs also in non-smokers and both disorders are idiopathic within smokers

13. Creatures “rich and strange”

14. LIP LIP! LIP!!

17. The elephant in the room: patients who do not fit into a classification

18. “Unclassifiable disease” • Fleischner 2011 – “at least half of idiopathic cases” do not fit the current classification • Kevin Brown – In Denver, 30% of cases “cannot be classified” • Similarities at RBH – but what do we mean by “unclassifiable disease”?

19. “Unclassifiable disease” • Tentative first choice diagnosis, no convincing differential diagnosis • Overlapping disorders: IPF/HP, IPF/NSIP, HP/NSIP • No plausible first choice diagnosis

20. These cases account for <25% of all ILD cases …… but cause >95% of the angst To what extent does evidence-based treatment meet their needs?

21. Management in unclassifiable disease • Evidence-based management can be applied to overlapping disorders • But by definition, no evidence base exists for completely unclassifiable disease • An alternative classification approach is required

22. More nuanced terminology is not the answer • Constrictive bronchiolitis … follicular bronchiolitis … proliferative bronchiolitis … obliterative bronchiolitis … bronchiolitis obliterans organizing pneumonia … constrictive obliterative bronchiolitis … diffuse pan-bronchiolitis … cryptogenic organizing pneumonia … follicular obliterative bronchiolitis ….exudative bronchiolitis

23. Why do we need diagnoses/ classifications at all? • Pathogenetic insights: resulting in treatment advances • Clinical utility:A classification of disease is justified if it identifies important differences in natural history or treated course and is, thus, clinically useful in prognostic evaluation or management

24. We need a different question Historically, the primary question has been “what is the diagnosis”? Pragmatically, the primary question is “what are you going to do about it”?

25. There are over 1000 ILDs but only five management and monitoring strategies We therefore need a pragmatic classification of ILD into five entities, using simple terminology

26. Management/monitoring • Withold treatment altogether in self-limited reversible disease/stable irreversible disease – with separate monitoring strategies • Treat high for a response followed by maintenance therapy to preserve gains in major reversible disease with progression to irreversible disease • Treat to prevent all progression when this is realistic in progressive irreversible disease • Treat to slow progression in inexorably progressive irreversible disease

27. Chronic renal disease circa 2000 • Complex histological terms • Overlap between disorders • Entities not understood except by super-specialists • Prognosis not well tied to individual entities • Major disenchantment led to a radically simplified classification

28. Chronic kidney disease (KDOQI) classification 2002 • Essentially a prognostic classification • Simple categories based on three variables: degree of structural damage, degree of functional impairment (GFR), change in the next six months • Fine histological distinctions discarded

29. A classification based on pragmatic management ... • Specific diagnosis • Cause • Predominant morphologic abnormality • Severity • Longitudinal behaviour • Integrate these as follows

31. In idiopathic disease, with current therapies …….. • Self-limited inflammation • Stable fibrosis • Major inflammation with variable fibrosis • Progressive fibrosis, stabilisation a realistic goal • Inexorably progressive fibrosis

32. The art of pragmatic management is to place our patients with confidence in one of the five categories The rest is procedural

33. A 54 year old woman with “COP”

35. Is this …… • Major reversible disease with progression to irreversible disease? • Progressive irreversible disease, stabilisation a realistic goal? • Inexorably progressive irreversible disease?

36. FVC % Cyclophosphamide DLco % Cyclophosphamide Prednisolone 40mg IV methyl-prednisolone MMF & prednisolone

37. After treatment Before treatment After treatment

38. Follow up • June 2008 • Playing golf; working full-time • Much improved • 6MWT on RA 95% to 88% (375m) • Continued on prednisolone 10mg and mycophenolate (azathioprine not tolerated). • Diagnosis now “progressive irreversible disease, realistic to stabilise”

40. CTD-ILD: a poll (n=350). With regard to clinical utility, the IIP classification is: • Intuitive, user friendly and readily understood by patients • Is somewhat helpful to clinicians and patients although not always straightforward • Difficult to grasp, arduous to apply but worthwhile • Opaque, poorly understood by patients and of little clinical value

41. CTD-ILD: a poll (n=350). With regard to clinical utility, the IIP classification is: • Intuitive, user friendly and readily understood by patients • Is somewhat helpful to clinicians and patients although not always straightforward • Difficult to grasp, arduous to apply but worthwhile • Opaque, poorly understood by patients and of little clinical value 9% 17% 30% 43%

42. If correct in principle, the DBC should apply generally • NSIP • HP • Sarcoidosis • Drug-induced lung disease

43. A classification based on pragmatic management ... • Specific diagnosis: defines what behaviour patterns are possible • Cause: removal of cause may change the category • Predominant morphologic abnormality on HRCT (/biopsy) – reversible vs irreversible disease • Severity: in some scenarios, pivotal • Short-term serial behaviour ……

44. Histospecific diagnosis Informs as to what patterns of disease behaviour are possible

45. DIP COP Reversible disease with risk of progression/irreversible disease Treat for a response Do what is needed to preserve gains

46. Idiopathic pulmonary fibrosis • Progressive irreversible disease despite therapy

47. Non-specific interstitial pneumonia • Any of the five disease patterns! Any of the five management strategies

48. Cause

49. Respiratory bronchiolitis with associated ILD Self-limited/ reversible Remove cause, observe

50. Predominant morphologic abnormality • This should be distinguished from the histospecific diagnosis • Judgement based on review of HRCT in all cases, and on review of biopsy in some cases (but beware “sampling error”). • Simple assessment of predominance of inflammation and fibrosis