NAVIGATING the NEW ERA in IPF:

Diagnosing Idiopathic Pulmonary FibrosisFACULTY

TitleAffiliation

Learning Objectives

• Explain the considerations associated with clinical evaluation, imaging, and biopsy, in terms of differentially diagnosing IPF

• Identify opportunities for interdisciplinary collaboration and consultation and key aspects of guideline recommendations that can facilitate early and accurate IPF diagnosis

Interstitial Lung Diseases

• Diverse group of disorders that involve the distal pulmonary parenchyma

• Typical presentation– Progressive dyspnea and dry cough– Abnormal pulmonary physiology– Abnormal CXR and/or HRCT

• Etiology– Idiopathic – Systemic diseases (connective tissue disorders) – Toxic, radiologic, environmental, occupational exposures

Interstitial Lung Diseases

ILD of Known Cause or

Association

Medications

Radiation

Connective Tissue Disease

Vasculitis & DAH

Hypersensitivity Pneumonitis

Pneumoconioses

Idiopathic Interstitial

Pneumonias

Sarcoidosis & Other

Granulomatous Diseases

Other

LAM

Pulmonary LCH

Eosinophilic Pneumonias

Alveolar Proteinosis

Genetic Syndromes

Adapted from: ATS/ERS Guidelines for IIP. AJRCCM. 2002;165:277-304.

Major Idiopathic Interstitial Pneumonias

Category Clinical-Radiologic-Pathologic Diagnosis

Associated Radiographic and/or Pathologic pattern

Chronic fibrosing

IPF UIP

Idiopathic nonspecific interstitial Pneumonia (iNSIP) NSIP

Smoking-related

Respiratory bronchiolitis-ILD (RB-ILD) Respiratory bronchiolitis

Desquamative interstitial pneumonia (DIP) Desquamative interstitial pneumonia

Acute/ subacute

Cryptogenic organizing pneumonia (COP) Organizing pneumonia

Acute interstitial pneumonia (AIP) Diffuse alveolar damage

Travis et al. Am J Respir Crit Care Med. 2013;188:733-748.

Other Idiopathic Interstitial Pneumonias

Category Clinical-Radiologic-Pathologic Diagnosis

Associated Radiographic and/or Pathologic pattern

Rare

Idiopathic lymphoid interstitial pneumonia (iLIP) Lymphoid interstitial pneumonia

Idiopathic pleuroparenchymal fibroelastosis (IPPFE) Pleuroparenchymal fibroelastosis

Unclassifiable Unclassifiable IIP Many

Travis et al. Am J Respir Crit Care Med. 2013;188:733-748.

Diffuse Parenchymal Lung Disease (DPLD)

DPLD of known cause, eg, drugs or association, eg, collagen vascular disease

Idiopathic interstitial

pneumonias

Granulomatous DPLD, eg,

sarcoidosis

Other forms of DPLD, eg, LAM,

HX, etc

Idiopathic pulmonary

fibrosis

IIP other than idiopathic

pulmonary fibrosis

Desquamative interstitial pneumonia

Acute interstitial pneumonia

Nonspecific interstitial pneumonia (provisional)

Respiratory bronchiolitis interstitial lung disease

Cryptogenic organizing pneumonia

Lymphocytic interstitial pneumonia

Pleuroparenchymal fibroelastosis

Travis WD, et al; ATS/ERS Committee on Idiopathic Interstitial Pneumonias. Am J Respir Crit Care Med. 2013;188(6):733-748.

Idiopathic Pulmonary Fibrosis

Normal Lungs Usual Interstitial Pneumonia

Idiopathic Pulmonary Fibrosis

• Peripheral lobular fibrosis of unknown cause• Clinical impact

– Exertional dyspnea– Cough– Functional and exercise limitation– Impaired quality-of-life– Risk for acute respiratory failure and death

• Median survival time of 3-5 years• Two new drugs approved by the FDA in October 2014

‒ Nintedanib (Ofev)‒ Pirfenidone (Esbriet)

Parameter HR (95% CI)IPF Dx 28.46 (5.5, 147)Age 0.99 (0.95, 1.03)Female sex 0.31 (0.13, 0.72)Smoker 0.30 (0.13, 0.72)Physio CRP 1.06 (1.01, 1.11)Onset Sx (yrs) 1.02 (0.93, 1.12)CTfib score ≥ 2 0.77 (0.29, 2.04)

Diagnosis Matters!IPF/UIP Confers a Poor Prognosis

Flaherty KR, et al. Eur Respir J. 2002;19:275-283.

Correct diagnosis appropriate management

Cum

ulati

ve P

ropo

rtion

Sur

vivi

ng

Time (years)

Higher Mortality Associated With Delays in Accessing Care

Lamas DJ, et al. Am J Respir Crit Care Med. 2011;184:842-847.

Years

Surv

ival

Raghu G, et al. Am J Respir Crit Care Med. 2011;183:788-824.

2011 ATS/ERS Diagnostic Criteria for IPF

*also known as diffuse parenchymal lung disease, DPLD

Exclusion of known causes of ILD*

UIP pattern on HRCT without surgical biopsy

ORDefinite/possible UIP pattern on HRCT with a surgical lung

biopsy showing definite/probable UIP

AND

Idiopathic Pulmonary Fibrosis

Normal Lung Usual Interstitial Pneumonia

Idiopathic Pulmonary Fibrosis

Normal Lung Fibroblastic focus inUsual Interstitial Pneumonia

• Median survival = 3.8 years• Factors associated with lower survival

– Age, index year, male sex

Raghu G, et al. Lancet Respir Med. 2014;2(7):566-572.

Prevalence of IPF is IncreasingMedicare Beneficiaries Age ≥ 65 Years

Incidence of IPF

Risk factors for higher incidence• Age • Male sex • Hispanic

ethnic origin• Geography

Raghu G, et al. Lancet Respir Med. 2014;2(7):566-572.

Highest Medium

Lowest

When Should I Suspect ILD?

Column A

Exertional Dyspnea

Non-productive Cough

Family History of ILD

Column BAbnormal CXR

Crackles

Exertional Desaturation

Spirometry (low FVC) or low DLCO

One from Column A and one from Column B

“ACES”

ILD FeaturesSimilarities Differences

• Dyspnea– Progressive– Exertional

• Cough– Non-productive

• Bibasilar crackles• Restrictive ventilatory defect• Exertional desaturation• ILD on HRCT

• Prior/current exposures• Extrapulmonary findings

– Sarcoidosis– Connective tissue disease– Joint involvement

• Serologies• HRCT

– Honeycombing– Ground glass – Distribution of abnormalities

• Histopathology

Pulmonary Function Tests

• Spirometry – Reduced FVC and TLC

– Normal or increased FEV1/FVC ratio

• Restriction often accompanied by some obstruction

• Impaired gas exchange

– Decreased DLCO, PaO2

– Desaturation on exercise oximetry

– Increased A-aPO2 gradient

• Normal PFTs do not exclude ILD– Emphysema + Interstitial Lung Disease

• Infectious• Inhalational• Immunologic• Iatrogenic• Idiopathic• Cardiovascular• Neoplastic

Mnemonic for Diagnosing ILD

What Should I Do if I Suspect ILD?

http://www.pfdoc.org/2014/07/a-pulmonary-fibrosis-primer-for-doctors.html. Accessed August 2014.

Specific diagnosis

Clinical picture

Radiologic pattern (HRCT)

Pathologic pattern

(lung biopsy)

High Resolution CT scan

• Inspiratory supine and expiratory supine• < 1.25mm axial reconstruction• High spatial frequency reconstruction (“bone”)

algorithm • Prone imaging in select cases• No IV contrast

http://www.pfdoc.org/2013/08/should-i-undergo-lung-biopsy-to.html. Accessed August 2014.

UIP Pattern

Hodnett PA, et al. Am J Respir Crit Care Med. 2013;188:141-149.

Possible UIP Pattern

Hodnett PA, et al. Am J Respir Crit Care Med. 2013;188:141-149.

traction bronchiectasis

HRCT Criteria for UIP

UIP Pattern Possible UIP Pattern

Subpleural, basal predominance + +Reticular abnormality + +Honeycombing (+/- traction bronchiectasis) + -

Absence of “inconsistent” features + +

Raghu G, et al. Am J Respir Crit Care Med. 2011;183:788-824.

Inconsistent With UIP

Hodnett PA, et al. Am J Respir Crit Care Med. 2013;188:141-149.

distinctlobular pattern

HRCT features inconsistent with IPFInconsistent Features

Upper lobe predominant

Peribronchovascular predominance

Ground-glass > extent of reticular abnormality

Profuse micronodules

Discrete cysts

Diffuse mosaic attenuation/gas-trapping

Consolidation

Raghu G, et al. Am J Respir Crit Care Med. 2011;183:788-824.

What Should I Do if HRCT Confirms ILD?

http://www.pfdoc.org/2014/07/a-pulmonary-fibrosis-primer-for-doctors.html. Accessed August 2014.

Specific diagnosis

Clinical picture

Radiologic pattern (HRCT)

Pathologic pattern

(lung biopsy)

Known Causes of ILD: History & Physical Exam • Drugs

– eg, Amiodarone, bleomycin, nitrofurantoin

– www.pneumotox.com

• Radiation‒ External beam radiation

therapy to thorax

• Connective Tissue Diseases– Rheumatoid arthritis– Systemic sclerosis

(scleroderma)– Idiopathic inflammatory

myopathies– Vasculitis

• Occupational/Environmental– Inorganic antigens

(Pneumoconioses)• Asbestosis• Coal worker’s pneumoconiosis• Silicosis

– Organic antigens (Hypersensitivity Pneumonitis)

• Birds• Mold

Gottron's Papules in Dermatomyositis

http://images.rheumatology.org. Accessed July 2014.

Mechanic's Hands in Anti-Synthetase Syndrome

http://images.rheumatology.org. Accessed July 2014.

Raynaud's Phenomenon

http://images.rheumatology.org. Accessed July 2014.

Puffy Fingers in Early Scleroderma or Mixed CTD

http://images.rheumatology.org. Accessed July 2014.

Advanced Sclerodactyly

http://images.rheumatology.org. Accessed July 2014.

Digital Clubbing

NEJM, 2001

Reynen K, et al. N Engl J Med. 2000; 343:1235

Serological Evaluation

• Minimum: ANA, RF, CCP (ATS/ERS guidelines)• Based on history & physical exam, consider:

– Extractable nuclear antigen (ENA) autoantibody panel– Anti-centromere antibody– ESR & CRP– MPO/PR3 (ANCA) antibodies– Anti-cardiolipin antibodies, lupus anticoagulant– Creatine kinase, aldolase– Hypersensitivity pneumonitis panel

• Should be performed before a biopsy

Raghu G, et al. Am J Respir Crit Care Med. 2011;183:788-824.

2011 ATS/ERS Diagnostic Criteria for IPF

*also known as diffuse parenchymal lung disease, DPLD

Exclusion of known causes of ILD*

UIP pattern on HRCT without surgical biopsy

ORDefinite/possible UIP pattern on HRCT with a surgical lung

biopsy showing definite/probable UIP

AND

Before You Biopsy…

• Can you confirm the diagnosis without a biopsy?• Is it safe?

– Extensive honeycombing– Pulmonary hypertension– High oxygen requirements– Progressive disease

• Avoid a “diagnostic trial” of steroids if possible• Consider referral to an ILD center

Diagnosis of IPF by Lung Biopsy

Raghu G, et al. Am J Respir Crit Care Med. 2011;183:788-824.

UIP Probable UIP

Possible UIP Not UIP Not

performed

UIP IPF IPF IPF Not IPF IPF

Possible UIP IPF IPF +/- IPF Not IPF Not IPF

Inconsistent with UIP +/- IPF Not IPF Not IPF Not IPF Not IPF

Histopathologic Pattern

Radi

olog

ic P

atter

n

Summary Diagnosis

Putting it all Together

• Physiology• Full PFTs

• Gas exchange• 6MWT

• Radiology• HRCT

• History• Exam• Labs

• ANA, RF, anti-CCP

• Pathology

Conclusions: Diagnosing IPF

• IPF is a fibrotic ILD• No identifiable cause for fibrosis

–Exposure/CTD are absent

• Either…–Characteristic HRCT pattern–UIP-pattern on surgical lung biopsy

• Multidisciplinary approach enables an accurate diagnosis

QUESTIONS and ANSWERS