NAVIGATING the NEW ERA in IPF:
Diagnosing Idiopathic Pulmonary Fibrosis
FACULTY
Title
Affiliation
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
Idiopathic
Interstitial
Pneumonias
Sarcoidosis
& Other
Granulomatous
Diseases
Other
Medications
LAM
Radiation
Pulmonary LCH
Connective Tissue
Disease
Eosinophilic
Pneumonias
Vasculitis & DAH
Alveolar Proteinosis
Hypersensitivity
Pneumonitis
Genetic Syndromes
Pneumoconioses
Adapted from: ATS/ERS Guidelines for IIP. AJRCCM. 2002;165:277-304.
Major Idiopathic Interstitial Pneumonias
Category
Chronic
fibrosing
Smokingrelated
Acute/
subacute
Clinical-Radiologic-Pathologic
Diagnosis
Associated Radiographic
and/or Pathologic pattern
IPF
UIP
Idiopathic nonspecific interstitial
Pneumonia (iNSIP)
NSIP
Respiratory bronchiolitis-ILD (RB-ILD)
Respiratory bronchiolitis
Desquamative interstitial pneumonia (DIP)
Desquamative interstitial
pneumonia
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
Rare
Unclassifiable
Clinical-Radiologic-Pathologic
Diagnosis
Associated Radiographic
and/or Pathologic pattern
Idiopathic lymphoid interstitial
pneumonia (iLIP)
Lymphoid interstitial pneumonia
Idiopathic pleuroparenchymal
fibroelastosis (IPPFE)
Pleuroparenchymal fibroelastosis
Unclassifiable IIP
Many
Travis et al. Am J Respir Crit Care Med. 2013;188:733-748.
Diffuse Parenchymal Lung Disease (DPLD)
Idiopathic
interstitial
pneumonias
DPLD of known cause, eg,
drugs or association, eg,
collagen vascular disease
Idiopathic
pulmonary
fibrosis
Granulomatous
DPLD, eg,
sarcoidosis
Other forms of
DPLD, eg, LAM,
HX, etc
IIP other than
idiopathic
pulmonary fibrosis
Desquamative interstitial
pneumonia
Respiratory bronchiolitis
interstitial lung disease
Acute interstitial pneumonia
Cryptogenic organizing
pneumonia
Nonspecific interstitial
pneumonia (provisional)
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)
Diagnosis Matters!
Cumulative Proportion Surviving
IPF/UIP Confers a Poor Prognosis
Parameter
IPF Dx
Time (years)
HR (95% CI)
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)
Correct diagnosis  appropriate management
Flaherty KR, et al. Eur Respir J. 2002;19:275-283.
Survival
Higher Mortality Associated With
Delays in Accessing Care
Years
Lamas DJ, et al. Am J Respir Crit Care Med. 2011;184:842-847.
2011 ATS/ERS Diagnostic Criteria for IPF
UIP pattern on HRCT without
surgical biopsy
Exclusion of known
causes of ILD*
AND
*also known as diffuse parenchymal lung disease, DPLD
Raghu G, et al. Am J Respir Crit Care Med. 2011;183:788-824.
OR
Definite/possible UIP pattern
on HRCT with a surgical lung
biopsy showing
definite/probable UIP
Idiopathic Pulmonary Fibrosis
Normal Lung
Usual Interstitial Pneumonia
Idiopathic Pulmonary Fibrosis
Normal Lung
Fibroblastic focus in
Usual Interstitial Pneumonia
Prevalence of IPF is Increasing
Medicare Beneficiaries Age ≥ 65 Years
• 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.
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.
Lowest
Highest
Medium
When Should I Suspect ILD?
One from Column A and one from Column B
Column A
Exertional Dyspnea
Column B
Abnormal CXR
Crackles
Non-productive
Cough
Exertional
Desaturation
Family History of ILD
Spirometry (low FVC)
or low DLCO
“ACES”
ILD Features
Similarities
• Dyspnea
•
•
•
•
•
– Progressive
– Exertional
Cough
– Non-productive
Bibasilar crackles
Restrictive ventilatory defect
Exertional desaturation
ILD on HRCT
Differences
• 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
Mnemonic for Diagnosing ILD
•
•
•
•
•
•
•
Infectious
Inhalational
Immunologic
Iatrogenic
Idiopathic
Cardiovascular
Neoplastic
What Should I Do if I Suspect ILD?
Radiologic
pattern (HRCT)
Pathologic
pattern
(lung biopsy)
Clinical
picture
Specific
diagnosis
http://www.pfdoc.org/2014/07/a-pulmonary-fibrosis-primer-for-doctors.html. Accessed August 2014.
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
traction
bronchiectasis
Hodnett PA, et al. Am J Respir Crit Care Med. 2013;188:141-149.
HRCT Criteria for UIP
UIP Pattern
Possible
UIP Pattern
Reticular abnormality
+
+
+
+
Honeycombing
(+/- traction bronchiectasis)
+
-
Absence of “inconsistent” features
+
+
Subpleural, basal predominance
Raghu G, et al. Am J Respir Crit Care Med. 2011;183:788-824.
Inconsistent With UIP
distinct
lobular
pattern
Hodnett PA, et al. Am J Respir Crit Care Med. 2013;188:141-149.
HRCT features inconsistent with IPF
Inconsistent 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?
Radiologic
pattern (HRCT)
Pathologic
pattern
(lung biopsy)
Clinical
picture
Specific
diagnosis
http://www.pfdoc.org/2014/07/a-pulmonary-fibrosis-primer-for-doctors.html. Accessed August 2014.
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
Reynen K, et al. N Engl J Med. 2000; 343:1235
NEJM, 2001
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
2011 ATS/ERS Diagnostic Criteria for IPF
UIP pattern on HRCT without
surgical biopsy
Exclusion of known
causes of ILD*
AND
*also known as diffuse parenchymal lung disease, DPLD
Raghu G, et al. Am J Respir Crit Care Med. 2011;183:788-824.
OR
Definite/possible UIP pattern
on HRCT with a surgical lung
biopsy showing
definite/probable UIP
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
Radiologic Pattern
Histopathologic Pattern
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
Raghu G, et al. Am J Respir Crit Care Med. 2011;183:788-824.
Putting it all Together
• Physiology
• Full PFTs
• Gas exchange
• 6MWT
• Radiology
• HRCT
• History
• Exam
• Labs
• ANA, RF, anti-CCP
• Pathology
Summary
Diagnosis
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