Idiopathic Interstitial Pneumonia

1. Idiopathic Interstitial Pneumonia Trying to make sense of the letters Michelle Thompson, MS4 February 2006

2. Idiopathic Interstitial Pneumonias (IIP’s) Group of uncommon parenchymal lung diseases Similar pattern of lung injury to those seen in collagen vascular disease, drug reactions, asbestosis and chronic hypersensitivity pneumonitis “Idiopathic” reserved for conditions in which the cause of lung injury pattern is unknown

3. Classification “So diverse are the different forms and so varied the conditions under which this change occurs that a proper classification is extremely difficult” Osler speaking of IIP (1892)

4. Classification A number of classification schemes, names and definitions have been associated with the IIP’s over the years leading to a great deal of confusion (and article titles referring to “alphabet soup”) American Thoracic Society and European Respiratory Society (ATS/ERS) met in 2002 to clarify nomenclature and describe the clinical, radiologic and histologic patterns of these conditions Participants included thoracic radiologists, pulmonologists and pulmonary pathologists

5. Idiopathic Interstitial Pneumonias(clinical nomenclature as proposed by ATS/ERS) Include (in order of frequency): Usual Interstitial Pneumonia (UIP) Non-specific Interstitial Pneumonia (NSIP) Cryptogenic Organizing pneumonia (COP) Acute Interstitial Pneumonia (AIP) Respiratory Bronchiolitis-Associated Interstitial Lung Disease (RB-ILD) Desquamative Interstital Pneumonia (DIP) Lymphoid Interstitial Pneumonia (LIP)

6. Diagnosis of IIP ATS/ERS guidelines emphasize the importance of combined clinical, radiologic and histologic diagnosis of IIP’s The MOST IMPORTANT distinction is between UIP and the other IIP’s due to prognostic and therapeutic implications

7. Diagnosis of IIP HIGHLIGHTS: If HRCT gives confident diagnosis of UIP, no lung biopsy needed and diagnostic process is done If equivocal findings on HRCT, then surgical lung biopsy considered Figure from UpToDate, adapted from ATS/ERS guidelines

8. Usual Interstitial Pneumonia (UIP)Also known as Idiopathic pulmonary fibrosis (IPF) Most common IIP Primarily a fibrotic condition

9. Clinical Findings in UIP Age >50 Slight male predominance Symptoms usually present 6 months prior to presentation Progressive shortness of breath, non-productive cough Physical exam: end-inspiratory crackles at lung bases “velcro” lung Lung function tests: restrictive pattern Decreased DLCO

10. Histologic Findings in UIP Histology: Fibroblastic foci at the edge of dense scars Subpleural, paraseptal and/or peribronchovascular distribution Dense fibrosis causes remodeling of lung architecture and frequent honeycomb fibrosis Two distinguishing characteristics from other IIP’s Temporal heterogeneity: fibrotic lesions of different stages within same biopsy specimen Spatial heterogeneity: patchy lung involvement

11. Histology of UIP Left to right: Patchy fibrosis, subpleural distribution. Some lymphoid aggregates (black arrow). Areas of normal lung also present. Fibroblastic focus (white arrow) adjacent to dense collagenous scar. Figures from Lynch et al. 2005

12. Radiographic features of UIP Radiographs Bilateral and basilar irregular linear opacities (close to 100% of cases) Ground glass opacities Honeycombing Loss of lung volumes Normal radiograph in 2-8% of cases

13. Early changes UIP: peripheral, irregular linear opacities and normal lung volumes Late features UIP: same patient 2 years later. Peripheral, irregular linear opacities and progressive loss of lung volume Images from McAdams et al., 1996

14. Late features UIP showing bilateral, coarse, reticular opacities with architectural distortion, volume loss and honeycombing Images from McAdams et al., 1996

15. CT features of UIP Reticular opacities with traction bronchiectasis Honeycombing (96% of cases) Ground glass opacity (less extensive than reticular pattern) Architectural distortion reflecting fibrosis Distribution: basal/peripheral and patchy

16. CT features of UIP Left: left lower lobe shows peripheral ground-glass opacity and reticular patterns with traction bronchiectasis (arrow) Right: same patient two years later with progression of ground-glass to reticular pattern and honeycombing and progression of traction bronchiectasis Images from Lynch et al., 2005

17. Clinical Course in UIP Gradual deterioration, with possible periods of rapid decline Mean survival is 2.5-3.5 years from time of diagnosis As UIP is predominantly a fibrotic condition, does not typically respond to steroid treatment

18. Non-specific Interstitial Pneumonia (NSIP) Second most frequently diagnosed IIP more favorable prognosis than IPF/UIP ATS/ERS guidelines stress that a finding of an NSIP pattern on biopsy should “prompt the clinician to redouble efforts to find potential causes” (collagen vascular disease, exposures)

19. Clinical findings in NSIP Mean age of onset is 40-50 No sexual predominance No association with cigarette smoking Gradual onset, some patients may have subacute course The median duration of symptoms before diagnosis is 6-31 mo in different series Symptoms: progressive SOB, cough, fatigue Half present with history of weight loss Physical Exam: crackles at lung bases Lung function tests: restrictive pattern with decreased DLCO

20. Histology of NSIP Because features are “non-specific”, histology is difficult to define Spatially homogenous alveolar wall thickening Temporal homogenous pattern Two main types: 1. Fibrotic: dense or loose interstitial fibrosis lacking temporal heterogeneity or patchy features 2. Cellular: Mild-moderate interstitial chronic inflammation Type II pneumocyte hyperplasia in areas of inflammation

21. Fibrotic NSIP NSIP with fibrosing pattern. Alveolar walls (arrows) show thickening caused by fibrosis. No fibroblastic foci are present. Image from Lynch et al., 2005

22. Cellular NSIP Photomicrograph showing NSIP with cellular pattern. Alveolar walls (arrows) are infiltrated by a chronic inflammatory infiltrate. Image from Lynch et al., 2005

23. Fibrotic vs. Cellular NSIP Main importance is prognostic. Patients with predominant fibrosis have a poorer prognosis than those with cellular NSIP Figure below shows survival curves for patients with UIP, fibrotic NSIP (FNSIP) and Cellular NSIP (CNSIP). Those with CNSIP are shown to have the best survival. Figure from Lynch et al., 2005

24. Radiographic Features of NSIP Irregular linear opacities Air space consolidation Bilateral and basilar pattern Radiograph normal in 14% of cases

25. Radiographic features of NSIP Basilar opacities and normal lung volumes Image from McAdams et al., 1996

26. CT features of NSIP Scattered ground glass opacities Basal predominance Consolidation uncommon and honeycombing rare Irregular linear opacities Fibrosis (lobar volume loss, reticular pattern, and/or traction bronchiectasis)

27. CT features of NSIP Top: Fibrotic NSIP. Ground glass opacity with traction bronchiectasis (arrows) Arrowhead indicating posterior displacement of left major fissure denoting volume loss Bottom: Cellular NSIP. Ground glass opacity with reticular pattern. Images from Lynch et al., 2005

28. Clinical Course of NSIP Significantly better prognosis than UIP Evidence for corticosteroid efficacy is from retrospective reviews of observational studies. (25-30% of patients improved)* Relapse may occur *Collard et al., 2003

29. Cryptogenic Organizing Pneumonia (COP)(IIP formerly known as BOOP) Third most common IIP Although process is primarily intraalveolar, it is included with IIP’s because of its idiopathic nature and because its appearance may overlap with other IIP’s

30. Organizing Pneumonia: (COP or BOOP) Histology: Organizing pneumonia-intraluminal organization in distal air spaces Patchy distribution Preservation of lung architecture Uniform temporal appearance Mild chronic interstitial inflammation Edematous granulation-type tissue within airspaces: bronchioles and alveolar ducts and alveoli

31. Clinical findings in COP Cough and shortness of breath Relatively short duration of symptoms (1-6 months) Patients often diagnosed first with pneumonia but fail to respond to antibiotics as not infectious etiology Physical exam: PFT’s: restrictive pattern equal sex distribution but nonsmokers outnumber smokers by 2:1. Mean age of onset is 55 yr Continuing weight loss, sweats, chills, intermittent fever, and myalgia are common. Localized or more widespread crackles are frequently present,

32. Histology of COP Patchy areas of consolidation Polypoid plugs of loose organizing connective tissue Architecture of lung is preserved All the connective tissue is the same age Mild to moderate inflammation

33. COP histology From left to right: low-power photomicrograph shows scattered areas of organizing pneumonia. Fibroblast plugs are identified as pale, round structures (arrows) High power photomicrograph shows fibroblast plug in small brochiole High power photomicrograph shows fibroblast plugs streaming from one alveolus to another gross specimen showing branching fibroblast plugs (arrowheads) Images from McAdams et al., 1996

34. Radiographic features of COP Bilateral or unilateral areas of consolidation Patchy distribution, but in minority of cases may be confined to the subpleural region Small nodular opacities are seen in 10–50% of cases. Lung volumes are normal in up to 75% of cases

35. Radiographic Features in COP Multifocal, bilateral, basilar consolidations Bilateral multifocal consolidations Images from McAdams et al, 1996

36. CT features of COP Consolidation present in 90% of patients Lower lung zones frequently involved Air bronchograms present with consolidation Mild bronchial dilatation in areas of consolidation

37. CT features in COP Bilateral pulmonary consolidation with subpleural and perbronchovascular predominance and right pleural effusion Images from Lynch et al., 2005

38. Clinical Course (COP) Majority of patients recover completely with oral corticosteroids Relapse common with steroid taper and/or cessation

39. Acute Interstitial Pneumonia (AIP) Rapidly evolving lesion (days-weeks) Histological findings of diffuse alveolar damage. Therefore, diagnosis of AIP should only be considered after the other causes of DAD (sepsis, shock, etc.) are ruled out.

40. Clinical Findings in AIP Patients often have prior illness suggestive of viral URI Constitutional symptoms: myalgias, arthralgias, fever, chills, malaise Severe dyspnea on exertion developing over days Median time from first symptom to presentation is 3 weeks Hypoxemia progressing rapidly to respiratory failure Mean age of 50 No sex predominance No association with smoking Physical exam: diffuse crackles Lung function tests: restrictive pattern Mechanical ventilation is usually required The majority of patients fulfill the diagnostic clinical criteria for ARDS

41. Histology of AIP Histology: Diffuse alveolar damage Acute phase: Edema and hyaline membranes Organizing phase: Organizing alveolar septal fibrosis and pneumocyte hyperplasia Uniform temporal appearance

42. Histology of AIP Left to right High power photomicrograph demonstrating interstitial widening by edema and inflammatory cells. Hyaline membrane formation also apparent. High power photomicrograph shows organization of the intraalveolar exudate and immature collagen deposition Images from Lynch et al., 2005

43. Radiographic features of AIP Diffuse bilateral opacities Left: Initial radiograph shows bilateral and basilar consolidation Right: Two weeks later with progressive, diffuse consolidation. Images from McAdams et al., 1996

44. CT features of AIP Early exudation phase: Ground glass opacity-bilateral and patchy Consolidation also evident Organizing stage: Distortion of bronchovascular bundles Traction bronchiectasis Although CT findings in AIP and ARDS overlap, patients with AIP are more likely to have symmetric lower lobe distribution and a greater prevelance of honeycombing

45. CT features of AIP Diffuse consolidation and air bronchograms Image from McAdams et al., 1996

46. Clinical Course AIP No proven treatment, corticosteroids often used Mortality rates high (>50%) Those patients who recover may experience recurrence and/or chronic, progressive lung disease

47. Respiratory Bronchiolitis Interstitial Disease (RB-ILD) Respiratory Bronchiolitis: Lesion found in cigarette smokers Characterized by pigmented macrophages in respiratory bronchioles Rarely symptomatic, minor airway dysfunction RB-ILD is defined as the combination of clinically significant pulmonary symptoms, abnormal pulmonary function and imaging abnormalities associated with the pathologic lesion of respiratory bronchiolitis

48. Clinical Findings in RB-ILD Heavy smokers with average exposure of more than 30 pack-years Gradual onset 40-50 years of age Generally mild symptoms of sob and cough (new or changed) Some patients may present with significant dyspnea and hypoxemia Male to female ratio of 2:1

49. Histology: RB-ILD Histology: Bronchiolocentric alveolar macrophage accumulation Mild bronchiolar/peribronchiolar fibrosis and chronic inflammation Macrophages with “dusty-brown” appearance Figure below: faintly pigmented alveolar macrophages (arrows) fill the lumen of respiratory bronchiole. Mild thickening of respiratory bronchiole wall. Image from Lynch et al., 1996

50. Radiographic Features of RB-ILD Wall thickening of central or peripheral bronchi (75% of patients) Ground glass opacity (60% of patients) Normal radiograph (14%) Centrilobular emphysema also commonly seen as patients are heavy smokers