INTERSTITIAL LUNG DISEASE Pattern Approach main.pptx

APPROACH TO ILD

1. Interstitial Lung Disease Pattern Approach

2. Interstitial Lung Diseases (ILDs) ILDs are a heterogeneous group of disorders that affect the pulmonary interstitium comprising of interalveolar connective tissue, peribronchovascular and perilymphatic tissues including the alveolar epithelium, capillary endothelium and basement membranes. Affected by inflammation, infiltration, and fibrosis These are acute or chronic ILDs are idiopathic or caused by a number of etiologies

3. Interstitial Lung Diseases (ILDs) The term ILD is often used interchangeably with diffuse lung diseases (DLDs); however, neither all DLDs involve interstitium (diffuse alveolar hemorrhage) nor all ILDs are diffuse (IPF) HRCT is the modality of choice in the evaluation of ILDs Diagnosis of ILD is achieved through a multidisciplinary approach which includes a team of physician, radiologist and pathologist

4. Idiopathic Interstitial Pneumonias Category Clinical-radiologic-pathologic diagnosis Associated radiologic and/or pathologic-morphologic patterns Chronic fibrosing IP Idiopathic pulmonary fibrosis Usual interstitial pneumonia (UIP) Idiopathic non-specific interstitial pneumonia Non-specific interstitial pneumonia (NSIP) Smoking related IP Respiratory bronchiolitis-Interstitial lung disease Respiratory bronchiolitis Desquamative interstitial pneumonia Desquamative interstitial pneumonia (DIP) Acute/subacute Cryptogenic organizing pneumonia Organizing pneumonia Acute interstitial pneumonia Diffuse alveolar damage Rare IP Lymphoid interstitial pneumonia - Idiopathic pleuropulmonary fibroelastosis - Updated ATS-ERS classification of IIPs (2002-13)

5. History Clinical presentation is often non-specific Onset of symptoms: Acute (days to weeks) Subacute (weeks to months) Chronic (months to years) Episodic (symptomatic f/b asymptomatic) Dyspnoea – most common symptom (insidious, progressive) – correlates with severity of disease Cough – second most common (non-productive) – airway centered ILDs Uncommon – hemoptysis and chest pain

6. History Checklist: Connective tissue disorder – CTD-ILD AKI/CKD – CTD-ILD Atopy – Hypersensitivity pneumonitis HIV – Lymphocytic interstitial pneumonia (LIP) Occupational – Pneumoconiosis Smoking – IPF, DIP, RB-ILD Radiation – Radiation induced lung injury Drugs – Amiodarone, Bleomycin, Busulfan, Cyclophosphamide, Nitrofurantoin, Sulfa drugs

7. Pulmonary function tests PFTs – determine severity, progression, response to t/t and prognosis Restrictive pattern more common (decreased lung compliance) Reduction of total lung capacity (TLC), functional residual capacity (FRC) and residual volume (RV) FEV1/FVC ratio is usually normal /increased A reduction in the diffusing capacity of the lung for carbon monoxide (DLCO) is common in most ILDs Presence of obstructive pattern – airway-centered ILD and concomitant obstructive lung disease (COPD)

8. Imaging Chest radiograph is part of the initial assessment of ILD; however, Radiographic pattern is often non-specific Observer variation is considerable Relatively insensitive to early ILDs High-resolution computed tomography ( HRCT ) enables Early detection of disease Provides insight into disease reversibility and prognosis

9. Chest X-Ray Non-specific Bibasilar reticular pattern Mixed reticulonodular pattern Volume loss, tractional bronchiectasis Poor correlation with clinical and histopathological findings

10. HRCT High-resolution CT is performed by using thin-collimation during acquisition of data and then high resolution reconstruction algorithm is used to generate the image Provides exquisite details about pulmonary architecture Can detect subtle ground glass attenuation (GGOs) which are occasionally the only abnormality

11. Indications of HRCT Confirming presence , pattern , distribution , and activity of interstitial lung disease Assessment of progression of disease Suspected small airway disease Response assessment Evaluating associated conditions like emphysema, bronchiectasis, and bronchiolitis Assessment of complications Selection of site and type of biopsy

12. HRCT – Acquisition SPACED AXIAL IMAGING Acquired at 0.5-2 cm interval Lower radiation dose (interval between two slices) Adequate representative sampling of the lung in ILD Sampling error may limit assessment of longitudinal changes May miss focal abnormalities like pneumonia or carcinoma VOLUMETRIC IMAGING Superior in imaging the entirety of lung parenchyma with MPR Particularly advantageous in the serial follow-up of ILDs Subtle changes easier to appreciate when whole lung is imaged Quantitative CT can be performed In current practice, volumetric imaging is more commonly employed

13. HRCT Parameters Parameters Recommended value Section thickness 0.625-1.5 mm kVp 120 mAs 100-240 Gantry rotation time < 1 sec Matrix size 512 x 512 or largest available Reconstruction algorithm High spatial frequency (High resolution algorithm – bone algorithm) Viewing window setting Lung window

14. CT Chest – B80f CT Chest – B30f

15. Prone Imaging : Performed with 1–1.5 mm collimation at 2 cm intervals in full inspiration as noted above. Expiratory Views : 3 postexpiratory views are routinely performed at the level of the: • aortic arch, • at the tracheal carina, and • above the diaphragm. If possible, dynamic expiratory imaging is performed. Dynamic expiratory imaging employs 1 mm collimation while scanning in cine mode (no table increment), during a forced vital capacity maneuver, in the supine position. These images are performed as a 6 image set using the fastest possible tube rotation time.

16. Expiratory scan How to identify? Posterior margin of trachea flat or concave Lung volume smaller Increased attenuation of lung at end expiration Standard HRCT protocol includes inspiratory scan; however, expiratory scan is done in certain cases Indications: Air trapping Small airway disease Tracheobronchomalacia Full inspiration End maximal expiration

17. Supine vs Prone scan Most of the scans are acquired in supine position Prone scan helpful in separating gravity dependent densities from disease in subpleural interstitium Smokers and age-related subpleural changes in dependent portion of lung can be picked up on prone imaging Only area of interest can be imaged

18. Normal lung anatomy

19. Secondary pulmonary lobule Also simply known as a pulmonary lobule Basic anatomic unit of lung Polyhedral in shape; 1-2.5 cm in size Marginated by connective tissue interlobular septa containing pulmonary veins and lymphatics Central portion contains pulmonary artery and bronchiole

20. HRCT appearance Lung appears homogeneous in attenuation Fissures are smooth and unform in thickness Vessels are smooth and sharply demarcated The most peripheral vessels visible are 5-10 mm away from the pleural surface – represent centrilobular arteries Centrilobular bronchioles and interlobular septae are usually not seen

21. HRCT appearance Centrilobular artery Interlobular septa

22. Systematic approach to interpreting an HRCT in ILD

23. General considerations By definition, ILDs are diffuse and bilateral They may be asymmetric and heterogeneous on occasion However, all bilateral, diffuse diseases are not ILDs An attempt should be made to rule out other conditions such as metastasis, infection, emphysema, bronchiectasis.

24. HRCT Patterns Increased attenuation Reticulations and linear opacities Nodules Airspace -Ground glass opacities (GGOs) and Consolidation Decreased attenuation Cystic

25. Reticulations & linear opacities Appear as linear densities on HRCT These occur due to thickening of the interlobular septae (peripheral interstitium) which can later lead to thickening of central interstitium Three patterns are seen: Smooth Nodular Irregular

26. Reticular pattern - Smooth Occurs due to edema or infiltration of interlobular septum Seen in pulmonary edema

27. Reticular pattern - Nodular Nodular densities seen on reticulations Seen in sarcoidosis and lymphangitic carcinomatosis

28. Reticular pattern - Irregular Fibrosing ILDs such as in UIP pattern (IPF), NSIP pattern and chronic HSP

29. Honeycombing Air-filled (black) cystic structures Thick, easily seen walls Usually 3-10 mm in diameter Immediate subpleural location Occur in clusters or layers and share walls Multiple layers seen in late disease Non-branching Associated with other fibrotic changes

30. Honeycombing One or more layers Thick-walled Lower lobe predominance Decreased lung volume, traction bronchiectasis are associated findings Paraseptal emphysema One layer Thin-walled Upper lobe predominance Increased lung volume, centrilobular emphysema are associated findings

31. Honeycombing Subpleural Posterior Lower lobe predominant No atypical findings Atypical findings also seen (GGOs, nodules, consolidation, cysts, mosaic perfusion, air trapping) Upper, mid-lung or peribronchial predominance IPF (70%) Collagen vascular disease Drug-related fibrosis Asbestosis Chronic HSP Chronic HSP Sarcoidosis Radiation Fibrotic ARDS Interstitial pneumonias other than UIP (NSIP, OP, LIP, DIP) Chronic HSP Sarcoidosis Cystic lung disease

32. Differentials of fibrotic pattern UIP pattern ilds NSIP pattern ilds Chronic HSP

33. Differentiating featues Distribution Homogenous vs heterogenous Honeycombing Subpleural sparing Ground glass opacities Mosaic attenuation Ancillary features like dilated esophagus, pleural plaques, arthropathy, subcutaneous calcifications History

34. UIP is a histopathological and radiological pattern If cause is unknown (i.e. idiopathic), the disease is called idiopathic pulmonary fibrosis (IPF) IPF accounts for about 70% of cases of UIP with a poor 5-year survival rate Elderly male , > 60 years with no h/o collagen-vascular disease, asbestosis exposure, drug toxicity, radiation, chronic hypersensitivity pneumonitis USUAL INTERSTITIAL PNEUMONIA (UIP)- IPF Spatial and temporal heterogeneity is characteristic of UIP (on histopathology) C/O progressive dyspnoea , cough, weight loss and finger clubbing Pulmonary function tests show restrictive pattern

35. ATS/ERS criteria for diagnosis of idiopathic pulmonary fibrosis

36. UIP Honeycombing – must be present and is the distinguishing feature. Typical UIP pattern occurs only in one third of IPF patients ; two thirds of the patients have other patterns (probable UIP and indeterminate for UIP). Biopsy is not required PPV of HRCT diagnosis of UIP with pathology is 90-100%

37. Absence of honeycombing . Probable UIP pattern in the absence of an etiology and in the typical clinical setting is highly suggestive of IPF and obviates the need for a biopsy Probable UIP

38. Subtle reticulations with GGOs Requires biopsy ~ 50% of cases have UIP on histopathology. Indeterminate for UIP

39. Multidisciplinary Discussion (MDD) Pulmonologist/Rheumatologist Chest radiologist Pulmonary pathologist Diagnosis of idiopathic pulmonary fibrosis: An official ATS/ERS/JRS/ALAT clinical practice guideline. Am J Respir Crit Care Med. 2018; 198(5):e44-68.

40. IPF- What else to look for on HRCT? Mild mediastinal lymph node enlargement with short axis diameter up to 1.5 cm is evident on CT in approximately 70% cases of UIP* Main and branch pulmonary enlargement- pulmonary hypertension IPF is a risk factor for lung cancer *Niimi H, Kang EY, Kwong JS, Carignan, Muller NL. CT of chronic infiltrative lung disease: prevalence of mediastinal lymphadenopathy. J Comput Assist Tomogr. 1996;20(2):305-8.

41. Connective tissue disease-related ILDs CTD – one of most common causes among systemic diseases causing ILD ILD- seen in 40-50% of patients with CTDs – main cause of morbidity and mortality Higher frequency of ILD in SSc, PM - DM , lower frequency in SLE

42. Patterns of ILD encountered in CTD-ILD Most common pattern across all CTDs is fibrotic NSIP Rheumatoid arthritis – UIP > NSIP=OP>LIP Scleroderma – NSIP >> UIP Sjogren syndrome – NSIP > UIP=LIP= OP Polymyositis/dermatomyositis – NSIP = OP > UIP Mixed connective tissue disease - NSIP >OP =UIP ILD can precede extrathoracic manifestation of CTD by years – differentiation from IIP difficult

43. Patterns of ILD encountered in CTD-ILD NSIP – Systemic sclerosis UIP – Rheumatoid arthritis

44. Significance in management Impact on prognosis – CTD-ILD better prognosis than IPF Treatment options vary (steroids and immunomodulators) Need to search for evidence in newly diagnosed cases of ILD (as ILDs may precede extrathoracic manifestations)

45. It occurs both as an idiopathic condition (less common) or as part of other conditions like collagen vascular diseases Have cellular (more ground-glass areas) and fibrotic types Typically occurs in relatively younger patients than UIP (<50 years) Common in women Usually due to an underlying etiology like connective tissue disease (CTD), collagen vascular disease (CVD) and drugs known to cause lung toxicity Treatment ( steroids ) usually effective (cellular phase) Non-specific interstitial pneumonia (NSIP)

46. HRCT findings: Ground glass opacities (GGOs), with reticulation Irregular, patchy consolidation Honeycombing – absent, inconspicuous, or minimal Basal predominance Subpleural sparing (20-60% cases) – used to differentiate from UIP pattern Fibrotic NSIP will show the presence of reticulations and traction bronchiectasis Non-specific interstitial pneumonia (NSIP)

47. Non-specific interstitial pneumonia Cellular NSIP Fibrotic NSIP

48. UIP NSIP Age >60 yrs 40-50 yrs Sex Male > Female Female > Male Distribution Peripheral basal Peripheral basal ± subpleural sparing Honeycombing Present (characteristic) Absent Predominant pattern Honeycombing Reticulation Ground glass Reticulation UIP VS NSIP

49. Treatment – Anti-fibrotic drugs Pirfenidone (pyridone) – downregulation of production of growth factors and procollagens I and II Nintedanib (tyrosine kinase inhibitor) – Targets VEGF, FGR and PDGF receptors

50. Hypersensitivity Pneumonitis (HP) Immune-mediated disease, recurrent exposure to offending inducers in genetically susceptible individuals A high index of suspicion is required to make a diagnosis Begins as an airway-based disease More common in women Predominantly in non-smokers Etiology : Microbial agents, animal/bird proteins, haptens in paints No identifiable cause in 40% cases Classification: Old – Acute, subacute, chronic New – Acute inflammatory/non-fibrotic (< 6m), chronic/fibrotic (> 6m)* Raghu G, Remy-Jardin M, Ryerson CJ, Myers JL, Kreuter M, Vasakova M, et al. Diagnosis of Hypersensitivity Pneumonitis in Adults: An Official ATS/JRS/ALAT Clinical Practice Guideline. Am J Respir Crit Care Med. 2020;202(3):e36–69.

51. Hypersensitivity Pneumonitis (HP) Ground glass centrilobular nodules Mosaic attenuation Air-trapping Three-density pattern (formerly known as headcheese sign) Non-fibrotic Fibrotic Peribronchovascular and/or subpleural reticulations +/- honeycombing Architectural distortion Traction bronchiectasis Superimposed findings of non-fibrotic HP

52. Hypersensitivity Pneumonitis (HP) Fibrotic Peribronchial fibrosis with reticulations Peribronchial fibrosis with honeycombing

53. Nodular pattern Nodule is defined as a rounded pulmonary density , well-defined or ill-defined, and not more than 3 cm in diameter. Description of a nodule: Size (small < 1 cm; large > 1 cm) Appearance (well-defined; ill-defined) Attenuation (Soft tissue; ground glass) Distribution (Centrilobular, perilymphatic or random)

54. Nodular pattern Interstitial nodule is usually well-defined , of soft tissue attenuation and obscure the edges of vessels or other structures that it comes in contact with Air space nodule is more likely to be ill-defined , can be of soft tissue or ground glass attenuation Despite these differences in appearance, a distinction between airspace and interstitial nodules on HRCT is arbitrary Interstitial Air-space

55. Nodular pattern - Margins Well-defined Ill-defined Sarcoidosis Metastasis Miliary infections Amyloidosis Aspiration Pulmonary edema Pulmonary haemorrhage Vasculitis Organizing pneumonia RB and RB-ILD Hypersensitivity Pneumonitis

56. Nodular pattern - Margins Well-defined Ill-defined

57. Nodular pattern - Distribution Centrilobular Perilymphatic Random

58. Nodular pattern - Distribution Centrilobular Perilymphatic Random

59. Sarcoidosis Systemic chronic granulomatous disease characterized by non-caseating granulomas in multiple organs Unknown etiology Adults < 40 years of age Adenopathy – Bilateral hilar + mediastinal Typically non-necrotic ; calcification +/- 1-2-3 sign or Lambda sign, 1-2-3-4 sign Sharply defined nodules – Perilymphatic in distribution, upper lobe predominance Large nodules form masses Galaxy sign (masses with satellite nodules) Alveolar sarcoid Late stages – Fibrosis – Upper lobe predominant Bronchial/bronchiolar abnormalities may be seen

60. Sarcoidosis Hilar & Mediastinal lymphadenopathy

61. Sarcoidosis Perilymphatic nodules, nodular interlobular septal thickening Perilymphatic nodules Perilymphatic nodules, alveolar sarcoid and Galaxy sign

62. Sarcoidosis End-stage fibrosis

63. Lymphangitic cancer

64. Random Miliary tb Lung ca with metastasis

65. Centrilobular

66. Hypersensitivity Pneumonitis (HP) Non-fibrotic Ground glass centrilobular nodules GGOs with mosaic attenuation

67. Hypersensitivity Pneumonitis (HP)

68. Respiratory bronchiolitis – ILD (RB-ILD) Cellular bronchiolitis seen in smokers Mild to moderate chronic inflammation (pigmented macrophages) around bronchioles and alveolar septae Centrilobular micronodules Ground glass attenuation > solid (MIP helpful) Ground glass opacities Bronchial wall thickening Co-existent emphysema Best diagnostic clue – GGOs + centrilobular nodules + upper lobe predominance

69. Respiratory bronchiolitis – ILD (RB-ILD)

70. Endobronchial spread Nearly always indicates infection. Bronchilar impaction. Bacterial>mycobacterial>others.

71. Increased lung attenuation Ground glass opacities Consolidation

72. Ground glass opacities & Consolidation Abnormal increase in lung density Non-obscuration of pulmonary vessels – GGOs Obscuration of pulmonary vessels – Consolidation There is opacification of the alveolar spaces with or without affecting the interstitium Ground glass opacities + reticular pattern = Crazy paving pattern

73. Ground glass opacities & Consolidation GGOs with interlobular septal thickening GGOs with consolidation and interlobular septal thickening

74. Crazy Paving Pattern GGO + superimposition of reticular pattern on HRCT Differential diagnosis: ARDS Pulmonary edema/hemorrhage Pneumonia Radiation pneumonitis Idiopathic interstitial pneumonias Lipoid pneumonia Alveolar proteinosis

75. Organizing Pneumonia (OP) Polypoidal intraluminal plugs of loose organizing connective tissue in distal airways Formerly known as bronchiolitis obliterans organizing pneumonia (BOOP) Idiopathic cases – Cryptogenic OP Patients can have systemic symptoms OP - Bilateral peripheral or peribronchial consolidations Reversed halo (or Atoll sign) AFOP – Acute fibrinous and organizing pneumonia Nodule/mass +/- air bronchograms Multifocal ground glass opacities or consolidation Cysts – small (2-4 mm), round, thin-walled

76. Organizing Pneumonia (OP) Bilateral GGOs with Atoll sign Crescentic consolidation surrounding focal GGOs – Atoll sign Irregular nodular opacities with focal consolidation in relation to bronchus

77. Desquamative Interstitial Pneumonitis (DIP) ILD characterized by the accumulation of pigmented macrophages within alveoli and distal pulmonary airspaces Associated with smoking 40-60 years of age M > F (2:1) Ground glass opacities +/- Associated consolidation Bilateral and moderately symmetric Lower lobe > peripheral > patchy > diffuse Intralobular lines or reticular opacities Subpleural predominance Associated with GGOs Cysts – small (2-4 mm), round, thin-walled Best diagnostic clue – Bilateral, lower zone predominance GGOs +/- subpleural intralobular lines and thin-walled cysts

78. Desquamative Interstitial Pneumonitis (DIP) GGOs, small thin-walled cysts GGOs, small thin-walled cysts, subpleural intralobular lines

79. Desquamative Interstitial Pneumonitis (DIP)

80. Acute intersitital pneumonia (AIP) Fulminant disease of unknown cause Histologically – diffuse alveolar damage with alveolar hyaline membrane and diffuse, active interstitial fibrosis If cause is known – ARDS Mean age – 50 years Diffuse or patchy consolidation Diffuse or patchy GGOs Posterior, lower lobe predominance

81. Acute interstitial pneumonia (AIP) Bilateral lower lobe consolidation with GGOs, posterior lung predominance Bilateral lung consolidation, progressed within a period of days

82. Decreased lung attenuation Lung cysts Emphysema

83. Thank you

84. References Thoracic Imaging, Pulmonary and Cardiovascular Radiology, 3 rd edition – W. Richard Webb, Charles B. Higgins. CT of Interstitial Lung Diseases – Bhavin Jankharia Imaging of Interstitial Lung diseases, clinicoradiological series – Ashu Seith Bhalla, Manisha Jana. Diagnosis of idiopathic pulmonary fibrosis: An official ATS/ERS/JRS/ALAT clinical practice guideline. Am J Respir Crit Care Med. 2018; 198(5):e44-68. Niimi H, Kang EY, Kwong JS, Carignan, Muller NL. CT of chronic infiltrative lung disease: prevalence of mediastinal lymphadenopathy. J Comput Assist Tomogr. 1996;20(2):305-8. Raghu G, Remy-Jardin M, Ryerson CJ, Myers JL, Kreuter M, Vasakova M, et al. Diagnosis of Hypersensitivity Pneumonitis in Adults: An Official ATS/JRS/ALAT Clinical Practice Guideline. Am J Respir Crit Care Med. 2020;202(3):e36–69.

85. Distribution of the disease Basal predominance (UIP)

86. Acute, rapid, clinical deterioration within 1 month without obvious clinical cause ( cardiac failure, pulmonary embolism etc) Imaging- Extensive, new GGOs +/- consolidation D/D – congestive cardiac failure, infection Triggers - infection, micro aspiration, air pollution, drugs Path- acute or organising diffuse alveolar damage Prognosis- poor , high mortality Acute exacerbation of IPF HRCT Chest following clinical deterioration (after 20 days) Baseline HRCT Chest at the time of diagnosis