UPDATE ON INTERSTITIAL LUNG DISEASEdoencaspulmonaresdifusas.med.up.pt/.../UPdate_on_ILD.pdf · 2018. 1. 26. · Smoking, fibrosis and ILD . 1. UPDATE ON IDIOPATHIC PULMONARY FIBROSIS

UPDATE ON INTERSTITIAL LUNG DISEASE

Thomas V. Colby, M.D.

FINANCIAL DISCLOSURES

NONE

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

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

Am J Respir Crit Care Med 2011; 183: 788-824

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

2011

Emphasis on guidelines for clinical trials to find efficacious drugs for IPF

HRCT UIP PATTERN can be diagnostic in IPF

DEFINITE UIP DEFINITE UIP

Am J Respir Crit Care Med 2011; 183: 788-824 Some images courtesy Luca Richeldi

IPF shows a UIP pattern radiologically and histologically

Dense scar, honeycombing

Fibroblast foci

There has been no effective treatment for IPF

Peripheral accentuation

…ENROLLING PATIENTS IN IPF

TRIALS IS NOW EMPHASIZED “Confidence criteria” for radiologic and pathologic

diagnosis are used to select patients for clinical trials.

1989 2011 Image courtesy L Richeldi MDPirfenidone and Nintedanib have

emerged as potentially useful

“GOLD STANDARD” FOR IPF DIAGNOSIS

Multidisciplinary discussion (MDD) = clinical- radiologic-pathologic correlation

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.

Am J Respir Crit Care Med 2011; 183: 788-824 Slide courtesy Luca Richeldi

Multidisciplinary team (MDT) is a term also being used.

Pathologists are encouraged to be part of this discussion

MDD should change the following:

From Google images

Bx

Management Decisions

MDD

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)

Discrete cysts (multiple, bilateral, away from areas of honeycombing)

Diffuse mosaic attenuation / air-trapping (bilateral, in 3 or more lobes)

Consolidation in bronchopulmonary segment(s)/lobe(s)


DEFINITE UIP POSSIBLE UIP

These categories are being reassessed

HISTOPATHOLOGICAL CRITERIA FOR UIP PATTERN

Definite UIP (all four criteria)

Probable UIP Possible UIP (all three criteria)

Not UIP (any of the 6 criteria)

Evidence of marked fibrosis/architectural distortion, +/- honeycombing in a predominantly subpleural/paraseptal 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)

Evidence of marked fibrosis/architectural distortion, +/- honeycombing in a subpleural/paraseptal distribution

Absence of either patchy involvement or fibroblastic foci, but not both


Patchy or diffuse involvement of lung parenchyma by fibrosis, with or without interstitial inflammation

Absence of other criteria for UIP (see UIP pattern column)


Hyaline membranes Organizing

pneumonia Granulomas Marked interstitial

inflammatory cell infiltrate away from honeycombing

Predominant airway centered changes

Other features suggestive of an alternate diagnosis

OR Honeycomb

changes only


“Levels of confidence”

These are not meant for routine pathology reports

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 NoConsistent with UIP Definite UIP Yes Consistent with UIP Probable UIP Yes Consistent with UIP Possible UIP NoConsistent with UIP Not UIP NoSuggests alternative Dx Any Path No

From NIH IPFnet

Clear evidence of chronic scarring and architectural destruction/honeycombing

Normal area Scarring

Fibroblast foci

Definite UIP

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

Pathologic issues

Many biopsies are “possible” UIP

Features “against” UIP are slipperyDAD 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:

Airway centered changes

Acceptance of Acute Exacerbation of IPF

Acute exacerbation is defined clinically…

not on a biopsy.

Am J Respir Crit Care Med 2011; 183: 788-824

Am J Respir Crit Care Med 2011; 183: 788-824 (modified)

DIS

EASE

PR

OG

RES

SIO

N

TIME

NATURAL HISTORY OF IPF

RAPID

PROGRESSION

SLOW

PROGRESSION

STABLE

PROGRESSION ACUTE

WORSENING

Acute exacerbation of IPF is defined on the clinical, radiologic and functional findings, not pathologically

Slide courtesy Luca Richeldi

Histologically one see background UIP with superimposed acute injury, usually acute or organizing DAD

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

Acute exacerbation of IPF: Autopsy

DAD

UIP

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

2002 ATS/ERS CLASSIFICATION OF IDIOPATHIC INTERSTITIAL PNEUMONIAS*

Clinicopathologic Diagnosis Pathologic PatternIdiopathic pulmonary fibrosis (IPF) UIP Desquamative interstitial pneumonia (DIP) DIP Respiratory bronchiolitis interstitial

lung disease (RBILD) RBCryptogenic organizing pneumonia (COP) OP (BOOP) Acute interstitial pneumonia (AIP) DADNonspecific interstitial pneumonia (NSIP) NSIP Lymphocytic interstitial pneumonia (LIP) LIP

*ATS/ERS International Consensus Panel; Am J Respir Crit Care Med 2002; 165:277

Revised (2013) ATS/ERS IIP Classification (Clin-rad-path/CRP Diagnosis)

Travis WD et.al Am J Respir Crit Care Med 2013; 188: 733

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

*

Fibrotic NSIP

RB-ILD

DIP

Cellular NSIP

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

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

Pleuroparenchymal fibroelastosis (PPFE): the new lesion added to the IIPs

Cases courtesy Dr.s A. Nicholson and D. Hansell

Elastic stain

F>M, 6th decade, Upper lobe pleural/subpleural infiltrates radiologically, elastotic fibrosis on histology*

* “Apical cap gone wild”

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.

(Mod Pathol 2011; 24: 1633)

Good review of PPFEMay be associated with a variety of drugs Interesting factoid: PPFE is seen at autopsy in 1/3 of aged donkeys

Eur Respir J 2014; 44: 289

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 clinical- radiologic correlation

Lowest yield; Lowest morbidity Transbronchial cryobiopsies may change the entire paradigm; Architectural features can beappreciated

High yield (~80%); Lower morbidity than SLBx

Transbronchial cryobiopsy in IPF

Images courtesy Alberto Cavazza MD Honeycombing

Patchy fibrosis

Fibroblast foci

0.5 mm

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

High frequency of NSIP which varies among CTD’s.

ILD PATTERN IN CTD’s

UIP

NSIP

Other

Kim E J et al. Chest 2009;136:1397-1405

Different frequencies compared to IIP’s: IPF/UIP = 55%

Idiopathic NSIP = 25%)

: 50-100%

: 5-25%

NSI

P

NSI

P

NSI

P

NSI

P

NSI

P

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)

p=0.001

IPF/UIP

IPF vs. CTD-UIP

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

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

AKA: “undifferentiated CTD associated

ILD” “lung-dominant CTD”

“autoimmune-featured ILD”

IPAF concept provides standardized, multidisciplinary assessment criteria IPAF is not a clinical diagnosis

ERJ 2015; 46: 976

IPAF

Slide courtesy KO Leslie MD

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.


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 ofthese domains:

A. Clinical domain B. Serologic domain C. Morphologic domain


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)


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-CCP4. 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


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


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

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;186:314-24.

The prototype in the USA is “hot tub lung.”

This produces a granulomatous interstitial pneumonia distinct from classic HP

Aerosolized Mycobacteria and HP

Ag

Ag

For the pathologist the granulomas in hot tub lung differ from typical HP:

Perhaps this is related to antigenicity ?

They look more like sarcoid granulomas

Hot tub lung Classic HP

Chonic HP with UIP pattern Fibroblast foci

Clues to Chr. HP: Incr. inflammation, centrilobular inflam/fibrosis, granulomas

Chronic HP

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;131:405-15.

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; 61:1026-35.

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

How common is Chr HP ??

46 consecutive pts diagnosed with IPF (2011 guidelines) 20/46 reinterpreted as Chr HP (details available) The study implicated….

(Lancet Respir Med 2013; 1: 685.)

…Feathers pillows and beddingImages from Google

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)

Airway centered changes

Takemura T et.al. Histopathology. 2012; 61:1026-35.

DISCRIMINATORS Bronchiolitis 0.0003 Centrilobular fibrosis 0.0003 Bridging fibrosis 0.0042 Org pneumonia 0.0006 Granulomas 0.0002 Giant cells < 0.0001 Lymphocytic alveolitis 0.002

BRONCHIOLAR CHANGES Lymphocytic infilt. 0.0003 Fibrosis of RB 0.0011 Fibroblast foci 0.0013 Lymphoid follicles 0.0091 Granuloma/giant cell 0.0077

Centrilobular fibrosis

N= 22 Chr HP and 13 UIP/IPF

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

RECURRENCE OF LAM IN LUNG ALLOGRAFT

with recipient-derived cells

HMB45+ SMA+ Des+ ER+ PR+

HMB-45

SMA

DES

PR ER

Lymphangioleiomyomatosis (LAM)

* *

**

= lumen *Lymphatic spaces

© 2005 Lippincott Williams & Wilkins, Inc. Published by Lippincott Williams & Wilkins, Inc. 2

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 at the site and will generate LCC as shown in Fig. 5A. LCC, LAM cell cluster enveloped by LEC; LEC, lymphatic endothelial cells; BM, basement membrane.

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):1356-1366, October 2005.

Shedding of LAM cell clusters (LCC)

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 negative (smear, original magnification x400). C, The flattened monolayer cells (outer cells) were immunoreactive for VEGFR-3 (smear, original magnification x400). D, Immunofluorescent labeling of VEGFR-3 delineated a fine lymphatic network lined by lymphatic endothelial cells in a tissue specimen obtained from the inner marginal tissues of retroperitoneal lymphangioleiomyoma (smear preparation, original magnification x100). LAM cases presented were: A, LNF79; B, LRK84; C, LTM96; and D, LTM96.

© 2005 Lippincott Williams & Wilkins, Inc. Published by Lippincott Williams & Wilkins, Inc. 2

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):1356-1366, October 2005.

HMB-45 SMA

VEGFR-3

Cytologic diagnosis based on fluid analysis should replace many lung biopsies

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.

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

RBILD An exaggerated RB reaction with increased airspace

macrophages and greater extent of lung tissue affected

Desquamative Interstitial Pneumonia (DIP)

Pulmonary Langerhans Cell Histiocytosis LCH

Eosinophilic pneumonia in a young man who recently started smoking

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

Study of lung cancer resection specimens (Kawabata et al. Histopathology. 2008 53:707)

Resections: 587 smokers and 230 nonsmokers. CLE and airspace enlargement with fibrosis (AEF) were assessed grossly and histologically.

CLE

AEF

Airspace enlargement with fibrosis (AEF) Figures courtesy Y. Kawabata

Smoking-related changes in the background lung of specimens resected for lung cancer

(Kawabata et al. Histopathology. 2008 53:707)

Smoking Index

Nonsmokers <25 Mild

25-50Moderate

>50 Heavy

RB 2% 9% 33% 34%

CLE 9.5% 40% 57% 61%

AEF 0.5% 6.5% 18% 21%

RB = Respiratory bronchiolitis; CLE = Centrilobular emphysema;

AEF = airspace enlargement with fibrosis; UIP = usual interstitial pneumonia

Both CLE and AEF correlated with smoking

Lung volumes and emphysema in smokers with interstitial lung abnormalities

(Washko et.al. in NEJM 2011; 364:10)

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)

2416 lung CTs of smokers studied 194 (8%) had interstitial abnormalities (ILA)

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 -1444 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

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

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 ??

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

THANK-YOU FOR YOUR ATTENTION !

Documents

UPDATE ON INTERSTITIAL LUNG DISEASEdoencaspulmonaresdifusas.med.up.pt/.../UPdate_on_ILD.pdf · 2018. 1. 26. · Smoking, fibrosis and ILD . 1. UPDATE ON IDIOPATHIC PULMONARY FIBROSIS