UPDATE ON INTERSTITIAL LUNG DISEASE. Thomas V. Colby, M.D.

Transcription

1 UPDATE ON INTERSTITIAL LUNG DISEASE Thomas V. Colby, M.D.

2 FINANCIAL DISCLOSURES NONE

3 Topics Discussed 1. Idiopathic pulmonary fibrosis (IPF) 2. Idiopathic interstitial pneumonias (IIPs) 3. Interstitial lung disease (ILD) in connective tissue disease (CTD) 4. Hypersensitivity pneumonitis (HP) 5. Lymphangioleiomyomatosis (LAM) 6. Smoking, fibrosis and ILD

4 1. UPDATE ON IDIOPATHIC PULMONARY FIBROSIS (IPF) Radiologic diagnosis of UIP is possible Multidisciplinary discussion is the gold standard Emphasis on enrolling patients in clinical trials Recognition of acute exacerbation of IPF

5 2011 Emphasis on guidelines for clinical trials to find efficacious drugs for IPF 2011: IPF is defined as a specific form of chronic, progessive fibrosing interstitial pneumonia of unknown cause, occurring primarily in older adults, limited to the lungs, and associated with the histopathologic and/or radiologic pattern of UIP. Slide courtesy Luca Richeldi Am J Respir Crit Care Med 2011; 183:

6 HRCT UIP PATTERN can be diagnostic in IPF DEFINITE UIP Some images courtesy Luca Richeldi DEFINITE UIP Am J Respir Crit Care Med 2011; 183:

7 IPF shows a UIP pattern radiologically and histologically Fibroblast foci Peripheral accentuation Dense scar, honeycombing There has been no effective treatment for IPF

8 ENROLLING PATIENTS IN IPF TRIALS IS NOW EMPHASIZED Confidence criteria for radiologic and pathologic diagnosis are used to select patients for clinical trials. Pirfenidone and Nintedanib have Image courtesy L Richeldi MD emerged as potentially useful

9 GOLD STANDARD FOR IPF DIAGNOSIS The accuracy of the diagnosis of IPF increases with multidisciplinary discussion (MDD) between pulmonologists, radiologists, and pathologists experienced in the diagnosis of interstitial lung disease. Slide courtesy Luca Richeldi Multidisciplinary discussion (MDD) = clinicalradiologic-pathologic correlation Multidisciplinary team (MDT) is a term also being used. Pathologists are encouraged to be part of this discussion Am J Respir Crit Care Med 2011; 183:

10 MDD should change the following: Management Decisions Bx MDD From Google images

11 HRCT CRITERIA FOR UIP PATTERN Definite UIP (all four features) Possible UIP (all three features) Inconsistent with UIP (any of the seven features ) Subpleural, basal predominance Reticular abnormality Honeycombing with or without traction bronchiectasis Absence of features listed as inconsistent with UIP pattern (see third column ) Subpleural, basal predominance Reticular abnormality Absence of features listed as inconsistent with UIP pattern (see third column) Upper or mid lung predominance Peribronchovascular predominance Extensive ground glass abnormality (extent > reticular abnormality) Profuse micronodules (bilateral, predominantly upper lobes) These categories are being reassessed DEFINITE UIP Slide courtesy Luca Richeldi POSSIBLE UIP Discrete cysts (multiple, bilateral, away from areas of honeycombing) Diffuse mosaic attenuation / airtrapping (bilateral, in 3 or more lobes) Consolidation in bronchopulmonary segment(s)/lobe(s) Am J Respir Crit Care Med 2011; 183:

12 HISTOPATHOLOGICAL CRITERIA FOR UIP PATTERN Definite UIP (all four criteria) Evidence of marked fibrosis/architectural distortion, +/- honeycombing in a predominantly subpleural/parasepta l distribution Presence of patchy involvement of lung parenchyma by fibrosis Presence of fibroblast foci Absence of features against a diagnosis of UIP suggesting an alternate diagnosis (see fourth column) Slide courtesy Luca Richeldi Probable UIP Evidence of marked fibrosis/architectural distortion, +/- honeycombing in a subpleural/parasepta l distribution Absence of either patchy involvement or fibroblastic foci, but not both Absence of features against a diagnosis of UIP suggesting an alternate diagnosis (see fourth column) OR Honeycomb changes only Possible UIP (all three criteria) Patchy or diffuse involvement of lung parenchyma by fibrosis, with or without interstitial inflammation Absence of other criteria for UIP (see UIP pattern column) Absence of features against a diagnosis of UIP suggesting an alternate diagnosis (see fourth column) Not UIP (any of the 6 criteria) Hyaline membranes Organizing pneumonia Granulomas Marked interstitial inflammatory cell infiltrate away from honeycombing Predominant airway centered changes Other features suggestive of an alternate diagnosis Levels of confidence These are not meant for routine pathology reports Am J Respir Crit Care Med 2011; 183:

13 Combining HRCT and Pathology interpretations to determine if IPF is present (for clinical trials) HRCT Diagnosis Pathology IPF Present? Definite UIP Definite UIP Yes Definite UIP Probable UIP Yes Definite UIP Possible UIP Yes Definite UIP Not UIP No Consistent with UIP Definite UIP Yes Consistent with UIP Probable UIP Yes Consistent with UIP Possible UIP No Consistent with UIP Not UIP No Suggests alternative Dx Any Path No From NIH IPFnet

14 Clear evidence of chronic scarring and architectural destruction/honeycombing Normal area Scarring Fibroblast foci Definite UIP

15 I called this: PROBABLE UIP 1. Clear evidence of chronic scarring and architectural destruction 2. Evidence of active fibrosis as fibroblast foci 3. Typically patchy, subpleural or paraseptal 4. Absence of features suggesting an alternative diagnoses Not well shown

16 Pathologic issues Many biopsies are possible UIP Features against UIP are slippery DAD and OP may be focal changes in UIP - Usually not an issue unless widespread (? AE) Granulomas: definition, number present? Airway-centering: how widespread? Inflammation: how much is too much? Example:

17 Airway centered changes

18 Acceptance of Acute Exacerbation of IPF Am J Respir Crit Care Med 2011; 183: Acute exacerbation is defined clinically not on a biopsy.

19 NATURAL HISTORY OF IPF STABLE DISEASE PROGRESSION RAPID PROGRESSION ACUTE WORSENING SLOW PROGRESSION Acute exacerbation of IPF is defined on the clinical, radiologic and functional findings, not pathologically Histologically one see background UIP with superimposed acute injury, usually acute TIME or organizing DAD Slide courtesy Luca Richeldi Am J Respir Crit Care Med 2011; 183: (modified)

20 When do pathologists encounter acute exacerbation?? At autopsy of patients with IPF On biopsies of patients with IPF when there is sudden deterioration On biopsies of patients with IPF when there is concern for pneumonia On biopsies when clinically occult IPF presents an acute ILD Sudden deterioration in patients with other chronic interstitial pneumonias: CTD/ILD, Chr. HP, fibrotic NSIP

21 Acute exacerbation of IPF: Autopsy DAD UIP

22 2. The Idiopathic Interstitial Pneumonias (IIPs) Not all are idiopathic Not all are solely interstitial pathologically Grouped together for convenience and historical reasons *ATS/ERS International Consensus Panel; Am J Respir Crit Care Med 2002; 165:277

23 2002 ATS/ERS CLASSIFICATION OF IDIOPATHIC INTERSTITIAL PNEUMONIAS* Clinicopathologic Diagnosis Idiopathic pulmonary fibrosis (IPF) Desquamative interstitial pneumonia (DIP) Respiratory bronchiolitis interstitial lung disease (RBILD) Cryptogenic organizing pneumonia (COP) Acute interstitial pneumonia (AIP) Nonspecific interstitial pneumonia (NSIP) Lymphocytic interstitial pneumonia (LIP) Pathologic Pattern UIP DIP RB OP (BOOP) DAD NSIP LIP *ATS/ERS International Consensus Panel; Am J Respir Crit Care Med 2002; 165:277

24 Revised (2013) ATS/ERS IIP Classification (Clin-rad-path/CRP Diagnosis) Major Idiopathic Interstitial Pneumonias Idiopathic pulmonary fibrosis (IPF) Idiopathic nonspecific interstitial pneumonia (NSIP) Respiratory bronchiolitis interstitial lung disease (RBILD) Desquamative interstitial pneumonia (DIP) Cryptogenic organizing pneumonia (COP) Acute interstitial pneumonia (AIP) Rare Idiopathic Interstitial Pneumonias Idiopathic lymphocytic interstitial pneumonia (LIP) Idiopathic pleuropulmonary fibroelastosis (PPFE) Unclassifiable idiopathic interstitial pneumonias * Travis WD et.al Am J Respir Crit Care Med 2013; 188: 733

25 Fibrotic NSIP DIP Cellular NSIP RB-ILD

26 AIP (acute and org DAD) COP (Idiopathic BOOP)

27 2013 IIP CLASSIFICATION Cases are also categorized as follows: 1. Chronic fibrosing IIP s (IPF/NSIP) 2. Smoking-related IIP s (RBILD, DIP) 3. Acute/subacute IIP s (COP, AIP) Travis WD et.al Am J Respir Crit Care Med 2013; 188: 733

28 Pleuroparenchymal fibroelastosis (PPFE): the new lesion added to the IIPs * Apical cap gone wild Elastic stain F>M, 6 th decade, Upper lobe pleural/subpleural infiltrates Cases courtesy Dr.s A. Nicholson and D. Hansell radiologically, elastotic fibrosis on histology*

29 Pleuroparenchymal fibroelastosis (PPFE): gross from an explant Sometime other ILD patterns (UIP and/os NSIP are seen along with PPFE, sometimes in the lower lobes.

30 (Mod Pathol 2011; 24: 1633)

31 Eur Respir J 2014; 44: 289 Good review of PPFE May be associated with a variety of drugs Interesting factoid: PPFE is seen at autopsy in 1/3 of aged donkeys

32 PATHOLOGIC DIAGNOSIS OF INTERSTITIAL PNEUMONIAS The current dogma: Surgical/VATS lung biopsies required to recognize patterns; esp. UIP, NSIP Highest yield (>95%); Appreciable morbidity Transbronchial occasionally useful with clinicalradiologic correlation Lowest yield; Lowest morbidity Transbronchial cryobiopsies may change the entire paradigm; Architectural features can be appreciated High yield (~80%); Lower morbidity than SLBx

33 Transbronchial cryobiopsy in IPF 0.5 mm Patchy fibrosis Honeycombing Fibroblast foci Images courtesy Alberto Cavazza MD

34 3. INTERSTITIAL LUNG DISEASE IN PATIENTS WITH CONNECTIVE TISSUE DISEASE (CTD/ILD) CTD/ILD shows a number of patterns, paralleling those seen in the idiopathic interstitial pneumonias Overall CTD/ILD has a favorable prognosis compared to IPF The frequency of NSIP pattern is more common in CTD/ILD than IIP UIP pattern in some CTD s has a better prognosis than IPF -----The exception may be RA

35 ILD PATTERN IN CTD s High frequency of NSIP which varies among CTD s. Different frequencies compared to IIP s: IPF/UIP = 55% NSIP Idiopathic NSIP = 25%) NSIP NSIP NSIP NSIP Other UIP : 5-25% NSIP : % Kim E J et al. Chest 2009;136:

36 Prognosis of Fibrotic IPs (NSIP and UIP): Idiopathic vs CTD-Related (Park JH et. Al AJRCCM 2007; 175: 705) IIP 269 pts (203 UIP, 66 NSIP) CTD-IP 93 pts (36 UIP, 57 NSIP) IPF vs. CTD-UIP p=0.001 IPF/UIP

37 PATHOLOGY OF CTD/ILD Are there morphologic clues to a CTD? Yes: Increased overall inflammation, especially lymphoid follicles with germinal centers are statistically associated with CTD/ILD.

38 CTD/ILD AND IIP ADDITIONAL CAVEATS Patients with IPF who have positive auto-antibodies have some pathologic similarities to CTD/UIP The presence of auto-antibodies in IIP is a predictor for subsequent development of UCTD In some studies, up to 50% of patients with idiopathic NSIP develop definable autoimmune disease at follow-up The relationship between the IIPs and CTDs is a complicated developing story

39 ERJ 2015; 46: 976 IPAF AKA: undifferentiated CTD associated ILD lung-dominant CTD autoimmune-featured ILD IPAF concept provides standardized, multidisciplinary assessment criteria IPAF is not a clinical diagnosis Slide courtesy KO Leslie MD

40 IPAF Definition Patients with idiopathic interstitial lung disease having combined clinical, laboratory and morphologic attributes suggesting a systemic autoimmune disorder, but who fail to meet criteria for a defined connective tissue disease. A priori requirement: HRCT and/or lung biopsy documenting the presence of ILD. Slide courtesy KO Leslie MD

41 Classification Criteria 1. Presence of an interstitial pneumonia (by HRCT or surgical lung biopsy) AND 2. Exclusion of alternative etiologies AND 3. Does not meet criteria of a defined connective tissue disease AND, 4. At least one feature from at least two of these domains: A. Clinical domain B. Serologic domain C. Morphologic domain Slide courtesy KO Leslie MD

42 Clinical Domain 1. Distal digital fissuring (i.e. mechanic hands ) 2. Distal digital tip ulceration 3. Inflammatory arthritis or polyarticular morning joint stiffness 60 min 4. Palmar telangiectasia 5. Raynaud s phenomenon 6. Unexplained digital edema 7. Unexplained fixed rash on the digital extensor surfaces (Gottron s sign) Slide courtesy KO Leslie MD

43 Serologic Domain 1. ANA 1:320 titre, diffuse, speckled, homogeneous patterns or a. ANA nucleolar pattern (any titre) or b. ANA centromere pattern (any titre) 2. Rheumatoid factor 2 upper limit of normal 3. Anti-CCP 4. Anti-dsDNA 5. Anti-Ro (SS-A) 6. Anti-La (SS-B) 7. Anti-ribonucleoprotein 8. Anti-Smith 9. Anti-topoisomerase (Scl-70) 10. Anti-tRNA synthetase (eg. Jo-1, PL-7, PL-12; others are: EJ, OJ, KS, Zo, trs) 11. Anti-PM-Scl 12. Anti-MDA-5 Slide courtesy KO Leslie MD

44 Morphologic Domain 1. Suggestive radiology patterns by HRCT (see text for descriptions): NSIP, OP, NSIP with OP overlap, LIP 2. Histopathology patterns or features by surgical lung biopsy: NSIP, OP, NSIP with OP overlap, LIP, Interstitial lymphoid aggregates with germinal centers, Diffuse lymphoplasmacytic infiltration (with/wo lymphoid follicles) {UIP may be seen but it is not a suggestive pattern by itself} 3. Multi-compartment involvement (in addition to interstitial pneumonia): Unexplained pleural or pericardial effusion or thickening Unexplained intrinsic airways disease (by PFT, imaging or path) Unexplained pulmonary vasculopathy Slide courtesy KO Leslie MD

45 Interstitial Pneumonitis with Autoimmune Features (IPAF) IPAF provides a framework to collect and categorize these cases some more can be learned about them. -- It is not a clinical diagnosis The relationship between the IIPs and CTDs is a complicated developing story

46 4. HYPERSENSITIVITY PNEUMONITIS UPDATE Two-hit hypothesis: 1. Genetic predisposition; 2. Exposure to sensitizing antigen Atypical mycobacteria in aerosolized water as an inciting antigen with better defined granulomas Usefulness of BAL in cases of HP: lymphocytosis Some antigens are associated with more aggressive disease (esp. bird fancier s lung) Chronic HP can have a UIP pattern Is IPF a form of Chr HP?? Selman M, Pardo A, King TE Jr. Hypersensitivity pneumonitis: insights in diagnosis and pathobiology. Am J Respir Crit Care Med. 2012;186:

47 Aerosolized Mycobacteria and HP The prototype in the USA is hot tub lung. This produces a granulomatous interstitial pneumonia distinct from classic HP Ag Ag

48 For the pathologist the granulomas in hot tub lung differ from typical HP: They look more like sarcoid granulomas Hot tub lung Classic HP Perhaps this is related to antigenicity?

49 Chronic HP Chonic HP with UIP pattern Fibroblast foci Clues to Chr. HP: Incr. inflammation, centrilobular inflam/fibrosis, granulomas

50 CHRONIC HP HISTOLOGIC STUDIES Some chronic HP shows UIP indistinguishable from that in IPF Clues to chronic HP: centrilobular fibrosis/fibroblast foci; bridging fibrosis; bronchiolitis; granulomas; giant cells Akashi T, Takemura T, Ando N, Eishi Y, Kitagawa M, Takizawa T, Koike M, Ohtani Y, Miyazaki Y, Inase N, Yoshizawa Y. Histopathologic analysis of sixteen autopsy cases of chronic hypersensitivity pneumonitis and comparison with idiopathic pulmonary fibrosis/usual interstitial pneumonia. Am J Clin Pathol. 2009;131: Takemura T, Akashi T, Kamiya H, Ikushima S, Ando T, Oritsu M, Sawahata M, Ogura T. Pathological differentiation of chronic hypersensitivity pneumonitis from idiopathic pulmonary fibrosis/usual interstitial pneumonia. Histopathology. 2012; 61:

51 THE EFFECT OF FIBROSIS ON SURVIVAL IN PATIENTS WITH HP (Voulekis in Am J Med 2004; 116: 662) 46 of 72 pts identified were classified as fibrotic No correlation of degree of fibrosis with implicated antigen

52 How common is Chr HP?? (Lancet Respir Med 2013; 1: 685.) 46 consecutive pts diagnosed with IPF (2011 guidelines) 20/46 reinterpreted as Chr HP (details available) The study implicated. Feathers pillows and bedding Images from Google

53 What does this mean for pathologists? Chr. HP should be on their radar How to recognize? Radiologic clues (upper lobe, centrilobular nodules, air trapping) Histologic clues (granulomas, centrilobular changes)

54 Airway centered changes

55 Takemura T et.al. Histopathology. 2012; 61: N= 22 Chr HP and 13 UIP/IPF DISCRIMINATORS Bronchiolitis Centrilobular fibrosis Bridging fibrosis Org pneumonia Granulomas Giant cells < Lymphocytic alveolitis BRONCHIOLAR CHANGES Lymphocytic infilt Fibrosis of RB Fibroblast foci Lymphoid follicles Granuloma/giant cell Centrilobular fibrosis

56 5. LYMPHANGIOLEIOMYOMATOSIS (LAM) UPDATE There has been a paradigm shift in the conceptual approach to LAM. It is considered to be a low-grade destructive metastasizing neoplasm based on: Loss of heterozygosity for tuberous sclerosis complex genes Similar clonality of lesions at multiple sites Uncontrolled growth Ability to recur ( metastasize to ) in allografts Invasion Angiogenesis, including lymphangiogenesis Ability to disseminate via blood stream and lymphatics One study implicated the uterus as a primary site for LAM cells VEGF levels in the serum and LAM cell clusters in effusion as new means of diagnosis

57 RECURRENCE OF LAM IN LUNG ALLOGRAFT with recipient-derived cells HMB45+ SMA+ Des+ ER+ PR+

58 SMA HMB-45 DES PR ER

59 Lymphangioleiomyomatosis (LAM) * * * * Lymphatic spaces * = lumen

60 Lymphangiogenesis-Mediated Shedding of LAM Cell Clusters as a Mechanism for Dissemination in Lymphangioleiomyomatosis. Kumasaka, t et al. American Journal of Surgical Pathology. 29(10): , October Shedding of LAM cell clusters (LCC) FIGURE 5. Schematic illustration of a postulated lymphangiogenesis-mediated fragmentation of LAM lesion and shedding of LCC. A, Lymphangiogenesis occurs in association with proliferation of LAM cells. As LAM-associated lymphangiogenesis progresses, a fine lymphatic network demarcates and separates the LAM lesions. Eventually LAM lesion fragments into LCC shedding into lymphatic circulation or extralymphatic spaces. B, LCC enters the lymphatic circulation and anchor inside the lymphatic vessel through homotypic cell interaction between LEC of the lymphatic vessel and LCC. Once LAM cells are free of LEC and exposed to the extracellular matrix, LAM cells proliferate to generate a new LAM lesion. The resultant new LAM lesion will induce lymphangiogenesis 2005 at the Lippincott site and Williams will generate & Wilkins, LCC as Inc. shown Published in Fig. by 5A. Lippincott LCC, LAM Williams cell cluster & Wilkins, enveloped Inc. by LEC; LEC, lymphatic endothelial 2 cells; BM, basement membrane.

61 Lymphangiogenesis-Mediated Shedding of LAM Cell Clusters as a Mechanism for Dissemination in Lymphangioleiomyomatosis. Kumasaka, t et al. American Journal of Surgical Pathology. 29(10): , October HMB-45 SMA VEGFR-3 FIGURE 1. Immunocytochemistry for LCC in chylous effusion. A, HMB45 was granularly positive on the cytoplasm of cells inside the LCC surrounded by lymphocytes and histiocytes. Note that flattened cells covering LCC were not immunoreactive for HMB45 (smear, original magnification x100). B, LAM cells in the clusters were strongly positive for [alpha]-sma, but the flattened cells were Cytologic negative (smear, original diagnosis magnification x400). C, The flattened based monolayer on cells (outer fluid cells) were analysis immunoreactive for VEGFR-3 (smear, original magnification x400). D, Immunofluorescent 2005 Lippincott labeling Williams of VEGFR-3 & Wilkins, delineated Inc. Published a fine by Lippincott lymphatic Williams network & lined Wilkins, by Inc. lymphatic endothelial cells in a tissue 2 specimen obtained from the inner marginal tissues of retroperitoneal should lymphangioleiomyoma replace (smear preparation, many original magnification lung biopsies x100). LAM cases presented were: A, LNF79; B, LRK84; C, LTM96; and D, LTM96.

62 Pathologist Diagnosis of LAM (In patients with cystic lung disease) Diagnostic lung biopsy (TBBx, SLBx) Explanted lungs Review of blebs for pneumothorax In real time or retrospectively Extrathoracic tissues eg. Retroperitoneal lymphangiomyoma Cytologic analysis of pleural/peritoneal fluids In all of these situations we are aided by knowledge that LAM is suspected.

63 6. SMOKING, FIBROSIS, AND ILD UPDATE Well-known clinical conditions associated with smoking: PLCH, RBILD, DIP, eos pneumonia Histologic changes associated with smoking: Airspace enlargement with fibrosis (AEF) Smoking-related interstitial fibrosis (SRIF) RBILD with fibrosis Subclinical radiologic interstitial lung abnormalities (ILA) in ~10% of smokers

64 RBILD An exaggerated RB reaction with increased airspace macrophages and greater extent of lung tissue affected

65 Desquamative Interstitial Pneumonia (DIP)

66 Pulmonary Langerhans Cell Histiocytosis LCH

67 Eosinophilic pneumonia in a young man who recently started smoking

68 MICROSCOPIC FIBROSIS CAN BE RELATED TO SMOKING Pathologic studies (Yousem SA. Mod Pathol 2006;19:1474) 30 lobectomies from smokers: 13 (43%) with some fibrosis (No fibrosis in lobectomies from 16 nonsmokers) (Katzenstein et al in Hum Pathol 2010) 20 lobectomies from smokers: 9 (45%) with fibrosis labelled: Smoking-related interstitial fibrosis Can this smoking-related fibrosis be clinically recognized?? ---Interstitial lung abnormalities (ILA) in CT studies

69 Study of lung cancer resection specimens (Kawabata et al. Histopathology :707) Resections: 587 smokers and 230 nonsmokers. CLE and airspace enlargement with fibrosis (AEF) were assessed grossly and histologically. AEF CLE Airspace enlargement with fibrosis (AEF) Figures courtesy Y. Kawabata

70 Smoking-related changes in the background lung of specimens resected for lung cancer (Kawabata et al. Histopathology :707) Smoking Index Nonsmokers <25 Mild Moderate >50 Heavy RB 2% 9% 33% 34% CLE 9.5% 40% 57% 61% AEF 0.5% 6.5% 18% 21% Both CLE and AEF correlated with smoking RB = Respiratory bronchiolitis; CLE = Centrilobular emphysema; AEF = airspace enlargement with fibrosis; UIP = usual interstitial pneumonia

71 Lung volumes and emphysema in smokers with interstitial lung abnormalities (Washko et.al. in NEJM 2011; 364:10) 2416 lung CTs of smokers studied 194 (8%) had interstitial abnormalities (ILA) Compared to those without Interstitial abnormalities (ILA) those with ILA showed: Restriction/reduced TLC (p<0.001) Lesser amount of emphysema (p<0.001) Greater tobacco smoke exposure (p<0.01)

72 Cigarette smoking is associated with subclinical parenchymal lung disease: the Multi-Ethnic Study of Atherosclerosis (MESA)-lung study. (Lederer DJ, et.al. Am J Respir Crit Care Med. 2009;180:407-14) 2563 adults without airflow obstruction never smokers; 1119 smokers CONCLUSIONS: Smoking may cause subclinical parenchymal lung disease detectable by spirometry and CT imaging, even among a generally healthy cohort. Is appealing to think this correlates with the changes seen microscopically in smokers

73 Interstitial lung abnormalities (ILA) in a CT lung cancer screening population (Jin GY et.al. Radiology 2013; 268: 563) 86 (9.7%) of 884 subjects had ILA Nonfibrotic in 5.9%, Fibrotic in 2.1%, mixed in 1.7% 37% of those with fibrotic ILA showed progression

74 SUMMARY We have a lot to learn about the subclinical radiologic (ILA) and pathologic changes (eg. SRIF) in the lungs of smokers. Are they incidental findings or something that can progress to clinical disease?? like UIP/IPF??

75 Topics Discussed 1. Idiopathic pulmonary fibrosis (IPF) 2. Idiopathic interstitial pneumonias (IIPs) 3. Interstitial lung disease (ILD) in connective tissue disease (CTD) 4. Hypersensitivity pneumonitis (HP) 5. Lymphangioleiomyomatosis (LAM) 6. Smoking, fibrosis and ILD

76 THANK-YOU FOR YOUR ATTENTION!