THE DIAGNOSIS OF IPF
Steven A. Sahn, MD
Professor of Medicine and Director
Division of Pulmonary, Critical Care,
Allergy and Sleep Medicine
Medical University of South Carolina
Current Definition of IPF
• Distinct chronic fibrosing
interstitial pneumonia
• Unknown cause
• Limited to the lungs
• Has typical HRCT findings
• Associated with a
histologic pattern of UIP
ATS/ERS Consensus Statement. Am J Respir Crit Care Med.
2002;165:277-304.
Demographics and Risk Factors for IPF
•
US Demographics
• Incidence: > 30,000 patients/year
• Prevalence: > 80,000 current patients
• Age of onset: 40–70 years
• Two-thirds > 60 years old at presentation
• Males > females
•
Risk Factors
• Familial
• Smoking
• Environment (eg, wood or metal dust)
• Gastroesophageal reflux disease (GERD)
• Infectious agents
ATS/ERS. Am J Respir Crit Care Med. 2000;161:646-664.
Raghu G, et al. Am J Respir Crit Care Med. 2006;174:810-816.
Pulmonary Function Tests
• Normal PFTs or resting ABG do not exclude IPF
• Restriction (not always seen)
• Reduced FVC and TLC
• Normal or increased FEV1/FVC ratio
• Impaired gas exchange
• Decreased DLCO, PaO2
• Desaturation on exercise oximetry
• Increased P(A-a)O2 gradient
ATS/ERS. Am J Respir Crit Care Med. 2000;161:646-664.
Diagnosing Chronic Exertional Dyspnea
Differential Diagnosis
Neuromuscular
Pulmonary
Pulmonary Hypertension
AVM
NM disease,
malnutrition,
diaphragm dysfunction
COPD, ILD, Asthma
Anemia,
Anxiety, Obesity,
Deconditioning,
hyperthyroidism
Cardiomyopathy, R-to-L Shunt
YES
No
Basilar Velcro Crackles
HRCT SCAN
IPF
Image courtesy of Steven A. Sahn, MD.
Others
Vascular
Cardiac
Serologic Tests Can Help Exclude Other
Conditions
Connective tissue
diseases
Sarcoid
Hypersensitivity
pneumonitis
ESR
ANA
RF
CK
Aldolase
Anti-myositis panel with Jo-1 antibody
ENA panel
p-ANCA
ACE
Hypersensitivity panel
(exposure history)
ATS/ERS. Am J Respir Crit Care Med. 2000;161:646-664.
Chest Radiograph in IPF
Reduced lung volume
Images courtesy of W. Richard Webb, MD.
Basal and peripheral reticulation
Early/Low Burden IPF HRCT
Reticular opacities with a subpleural and basal predominance
No honeycombing or traction bronchiectasis
Image courtesy of W. Richard Webb, MD.
Classic IPF HRCT
Basal and subpleural predominance
Reticular opacities
Image courtesy of W. Richard Webb, MD.
Traction
bronchiectasis
Honeycombing
Advanced IPF HRCT
Extensive
honeycombing
Traction
bronchiectasis
Reticular opacities
Basal and subpleural predominance
Image courtesy of W. Richard Webb, MD.
Diagnostic Criteria for IPF Without a
Surgical Lung Biopsy
Major Criteria
Minor Criteria
Exclusion of other known causes of ILD
Age > 50 years
Evidence of restriction and/or impaired
gas exchange
Insidious onset of otherwise
unexplained dyspnea on exertion
HRCT: bibasilar reticular abnormalities
with minimal ground-glass opacities
(Honeycombing is characteristic1)
Duration of illness > 3 months
TBB or BAL that does not support an
alternative diagnosis
Bibasilar, inspiratory, Velcro®
crackles
All major criteria and at least 3 minor criteria must be present
to increase the likelihood of an IPF diagnosis
1. Not included in current guidelines
ATS/ERS. Am J Respir Crit Care Med. 2000;161:646-664.
Radiologic Diagnosis Inconclusive
Subpleural reticular opacities
Both scans show subpleural reticulation.
This appearance may represent early UIP/IPF or fibrotic NSIP.
Biopsy is needed for their differentiation.
Images courtesy of W. Richard Webb, MD.
Video-Assisted Thoracic Surgery (VATS)
• High diagnostic accuracy
• Less morbidity and mortality than open lung biopsy
• Ideal biopsy
• Two or more surgical wedge biopsies with areas of normal lung from
different sites of the lung
• Samples 3–5 cm in length and 2–3 cm in depth
• Outpatient thoracoscopic lung biopsy in patients with
interstitial or focal lung disease
• Diagnosis in 61/62 patients
• 72% discharged within 8 hours
• 22% discharged within 23 hours
Rena O, et al. Eur J Cardiothorac Surg. 1999;16:624-627.
Chang AC, et al. Ann Thorac Surg. 2002;74:1942-1946.
Pathological Sections Demonstrating UIP
a. Peripheral accentuation of disease
Fibrosis
Normal lung
b. Transition into uninvolved lung
Fibroblast
focus
Normal lung
Normal lung
c. Microscopic honeycombing
d. High power image of fibroblastic foci
Myofibroblasts
Chronic inflammation
Minimal chronic
Chronic inflammation
inflammation
Mucus-filled cysts
Courtesy of Kevin O. Leslie, MD.
Images courtesy of Kevin O. Leslie, MD.
Pleura
Points to Remember
• Typical clinical features: male > 50 years,
smoker, insidious onset of dyspnea, nonproductive cough and bibasilar Velcro
crackles
• Other diseases, such as CTD and sarcoidosis
need to be excluded
• Surgical lung biopsy necessary when typical
clinical and HRCT findings of IPF not present
• IPF: characteristic UIP histology enables
definitive diagnosis when clinical/radiologic
findings not conclusive