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Diagnostic criteria and diagnostic algorithm for IPF
Diagnostic criteria and diagnostic algorithm for IPF
An early and accurate diagnosis of IPF is critical
Early diagnosis of IPF allows for appropriate management of symptoms and quality-of-life issues in patients with this disease1-3
1. Wells AU. Eur Respir Rev. 2013;22:158-162. 2. du Bois RM. Eur Respir Rev. 2012;21(124):141-146. 3. Lamas DJ et al. Am J Respir Crit Care Med. 2011;184(7):842-847. 4. Collard HR et al. Am J Respir Crit Care Med2003;168:538-542.
Early diagnosis is essential for timely referral to a lung transplant center for patients with advanced disease4
2
Diagnostic criteria for IPF
Current diagnostic criteria
According to the 2018 ATS/ERS/JRS/ALAT guideline criteria, diagnosing IPF requires the following5:
5. Raghu G et al. Am J Respir Crit Care Med. 2018;198(5):e44-e68.
1
Exclusion of other known causes of ILD and either #2 or #3
2
A UIP pattern on HRCT
3
Specific combinations of HRCT and histopathology patterns (in patients who undergo an SLB)
ILD, interstitial lung disease; HRCT, high-resolution computed tomography; SLB, surgical lung biopsy.
4
Diagnostic algorithm
Suspected ILD
5. Raghu G et al. Am J Respir Crit Care Med. 2018;198(5):e44-e68. 6. Raghu G et al. Am J Respir Crit Care Med. 2011;183(6):788-824. 7. Ley B et al. Am J Respir Crit Care Med. 2011;183(4):431-440.
When you suspect a patient has an ILD, the first things to do are5-7:
PFT, pulmonary function test
5
Diagnostic algorithm
Signs of IPF on physical exam:5
Reprinted with permission of the American Thoracic Society. Copyright © 2018 American Thoracic Society. Raghu G, Remy-Jardin M, et al. Diagnosis of Idiopathic Pulmonary Fibrosis. An Official ATS/ERS/JRS/ALAT Clinical Practice Guideline. Am J Respir Crit Care Med. 2018;198(5):e44-e68.Official Journal of the American Thoracic Society.
5. Raghu G et al. Am J Respir Crit Care Med. 2018;198(5):e44-e68.
Suspected ILD
6
Diagnostic algorithm
Signs of IPF based on history:5
5. Raghu G et al. Am J Respir Crit Care Med. 2018;198(5):e44-e68.
Suspected ILD
7
Reprinted with permission of the American Thoracic Society. Copyright © 2018 American Thoracic Society. Raghu G, Remy-Jardin M, et al. Diagnosis of Idiopathic Pulmonary Fibrosis. An Official ATS/ERS/JRS/ALAT Clinical Practice Guideline. Am J Respir Crit Care Med. 2018;198(5):e44-e68.Official Journal of the American Thoracic Society.
Diagnostic algorithm
Signs of IPF on PFTs:8,9
8. Pellegrino R et al. Eur Respir J. 2005;26(5):948-968. 9. Meltzer EB et al. Orphanet J Rare Dis. 2008;3:1-15.
Suspected ILD
8
Reprinted with permission of the American Thoracic Society. Copyright © 2018 American Thoracic Society. Raghu G, Remy-Jardin M, et al. Diagnosis of Idiopathic Pulmonary Fibrosis. An Official ATS/ERS/JRS/ALAT Clinical Practice Guideline. Am J Respir Crit Care Med. 2018;198(5):e44-e68.Official Journal of the American Thoracic Society.
Probable UIP, Indeterminate for UIP, or Alternative diagnosis
Diagnostic algorithm
5. Raghu G et al. Am J Respir Crit Care Med. 2018;198(5):e44-e68.
9
Identifiable cause/ associated condition?
CTD on serologic testing?
HRCT results
IPF
YES
YES
Not UIP
UIP
Biopsy
Not
IPF
NO
NO
Suspected ILD
Further evaluation
YES
NO
Specific Diagnosis
MDD
BAL
MDD
Alternative Diagnosis
Reprinted with permission of the American Thoracic Society. Copyright © 2018 American Thoracic Society. Raghu G, Remy-Jardin M, et al. Diagnosis of Idiopathic Pulmonary Fibrosis. An Official ATS/ERS/JRS/ALAT Clinical Practice Guideline. Am J Respir Crit Care Med. 2018;198(5):e44-e68.Official Journal of the American Thoracic Society.
Diagnostic algorithm
5. Raghu G et al. Am J Respir Crit Care Med. 2018;198(5):e44-e68. 10. European Respiratory Society. White Book: ILDs. http://www.erswhitebook.org/chapters/interstitial-lung-diseases/
10
Identifiable cause/ associated condition?
CTD on serologic testing?
HRCT results
IPF
YES
YES
Not UIP
UIP
Probable UIP, Indeterminate for UIP, or Alternative diagnosis
Biopsy
Not
IPF
NO
NO
Suspected ILD
Further evaluation
YES
NO
Specific Diagnosis
MDD
BAL
MDD
Alternative Diagnosis
Many ILDs have identifiable causes:10
Reprinted with permission of the American Thoracic Society. Copyright © 2018 American Thoracic Society. Raghu G, Remy-Jardin M, et al. Diagnosis of Idiopathic Pulmonary Fibrosis. An Official ATS/ERS/JRS/ALAT Clinical Practice Guideline. Am J Respir Crit Care Med. 2018;198(5):e44-e68.Official Journal of the American Thoracic Society.
Probable UIP, Indeterminate for UIP, or Alternative diagnosis
Identifiable cause/ associated condition?
CTD on serologic testing?
HRCT results
IPF
YES
YES
Not UIP
UIP
Biopsy
Not
IPF
NO
NO
Suspected ILD
Further evaluation
YES
NO
Specific Diagnosis
MDD
BAL
MDD
Alternative Diagnosis
Diagnostic algorithm
5. Raghu G et al. Am J Respir Crit Care Med. 2018;198(5):e44-e68.
11
If there are no obvious causes of ILD based on patient history, you should continue to suspect IPF.
Reprinted with permission of the American Thoracic Society. Copyright © 2018 American Thoracic Society. Raghu G, Remy-Jardin M, et al. Diagnosis of Idiopathic Pulmonary Fibrosis. An Official ATS/ERS/JRS/ALAT Clinical Practice Guideline. Am J Respir Crit Care Med. 2018;198(5):e44-e68.Official Journal of the American Thoracic Society.
Probable UIP, Indeterminate for UIP, or Alternative diagnosis
Identifiable cause/ associated condition?
CTD on serologic testing?
HRCT results
IPF
YES
YES
Not UIP
UIP
Biopsy
Not
IPF
NO
NO
Suspected ILD
Further evaluation
YES
NO
Specific Diagnosis
MDD
BAL
MDD
Alternative Diagnosis
Diagnostic algorithm
5. Raghu G et al. Am J Respir Crit Care Med. 2018;198(5):e44-e68. 6. Raghu G et al. Am J Respir Crit Care Med. 2011;183(6):788-824.
12
The next step is to consider performing serologic testing to evaluate for CTD5,6
These tests should be paired with clinical signs of CTD (eg, arthralgia/synovitis, proximal muscle weakness, Raynaud’s phenomenon).
CTD, connective tissue disorder; HP, hypersensitivity pneumonitis; RF, rheumatoid factor; CCP, cyclic citrullinated peptide; ANA, anti-nuclear antibody.
Probable UIP, Indeterminate for UIP, or Alternative diagnosis
Identifiable cause/ associated condition?
CTD on serologic testing?
HRCT results
IPF
YES
YES
Not UIP
UIP
Biopsy
Not
IPF
NO
NO
Suspected ILD
Further evaluation
YES
NO
Specific Diagnosis
MDD
BAL
MDD
Alternative Diagnosis
Diagnostic algorithm
5. Raghu G et al. Am J Respir Crit Care Med. 2018;198(5):e44-e68.
13
Reprinted with permission of the American Thoracic Society. Copyright © 2018 American Thoracic Society. Raghu G, Remy-Jardin M, et al. Diagnosis of Idiopathic Pulmonary Fibrosis. An Official ATS/ERS/JRS/ALAT Clinical Practice Guideline. Am J Respir Crit Care Med. 2018;198(5):e44-e68.Official Journal of the American Thoracic Society.
Probable UIP, Indeterminate for UIP, or Alternative diagnosis
Identifiable cause/ associated condition?
CTD on serologic testing?
HRCT results
IPF
YES
YES
Not UIP
UIP
Biopsy
Not
IPF
NO
NO
Suspected ILD
Further evaluation
YES
NO
Specific Diagnosis
MDD
BAL
MDD
Alternative Diagnosis
Diagnostic algorithm
5. Raghu G et al. Am J Respir Crit Care Med. 2018;198(5):e44-e68.
14
If there are no elevations in CTD markers, you should continue to suspect IPF.
Reprinted with permission of the American Thoracic Society. Copyright © 2018 American Thoracic Society. Raghu G, Remy-Jardin M, et al. Diagnosis of Idiopathic Pulmonary Fibrosis. An Official ATS/ERS/JRS/ALAT Clinical Practice Guideline. Am J Respir Crit Care Med. 2018;198(5):e44-e68.Official Journal of the American Thoracic Society.
Probable UIP, Indeterminate for UIP, or Alternative diagnosis
Identifiable cause/ associated condition?
CTD on serologic testing?
HRCT results
IPF
YES
YES
Not UIP
UIP
Biopsy
Not
IPF
NO
NO
Suspected ILD
Further evaluation
YES
NO
Specific Diagnosis
MDD
BAL
MDD
Alternative Diagnosis
Diagnostic algorithm
5. Raghu G et al. Am J Respir Crit Care Med. 2018;198(5):e44-e68. 11. Mathieson JR et al. Radiol. 1989;171(1):111-116. 12. Hunninghake GW et al. Am J Respir Crit Care Med. 2001;164(2):193-196. 13. Raghu G et al. Chest. 1999;116(5):1168-1174. 14. Grenier P et al. Radiology. 1991;179(1):123-132. 15. Lee KS et al. Radiology. 1994;191(3):669-673. 16. Swensen SJ et al. Radiology. 1997;205(1):229-234.
Next, patients should have an HRCT performed5
15
Reprinted with permission of the American Thoracic Society. Copyright © 2018 American Thoracic Society. Raghu G, Remy-Jardin M, et al. Diagnosis of Idiopathic Pulmonary Fibrosis. An Official ATS/ERS/JRS/ALAT Clinical Practice Guideline. Am J Respir Crit Care Med. 2018;198(5):e44-e68.Official Journal of the American Thoracic Society.
Diagnostic algorithm
5. Raghu G et al. Am J Respir Crit Care Med. 2018;198(5):e44-e68.
16
Identifiable cause/ associated condition?
CTD on serologic testing?
HRCT results
IPF
YES
YES
Not UIP
UIP
Biopsy
Not
IPF
NO
NO
Suspected ILD
Further evaluation
YES
NO
Specific Diagnosis
MDD
BAL
MDD
Alternative Diagnosis
Reprinted with permission of the American Thoracic Society. Copyright © 2018 American Thoracic Society. Raghu G, Remy-Jardin M, et al. Diagnosis of Idiopathic Pulmonary Fibrosis. An Official ATS/ERS/JRS/ALAT Clinical Practice Guideline. Am J Respir Crit Care Med. 2018;198(5):e44-e68.Official Journal of the American Thoracic Society.
Probable UIP, Indeterminate for UIP, or Alternative diagnosis
Probable UIP, Indeterminate for UIP, or Alternative diagnosis
Diagnostic algorithm
5. Raghu G et al. Am J Respir Crit Care Med. 2018;198(5):e44-e68. 17. Lynch DA et al. Lancet. 2018;6(2):138-153.
17
Identifiable cause/ associated condition?
CTD on serologic testing?
HRCT results
IPF
YES
YES
Not UIP
UIP
Biopsy
Not
IPF
NO
NO
Suspected ILD
Further evaluation
YES
NO
Specific Diagnosis
MDD
BAL
MDD
Alternative Diagnosis
HRCT: UIP pattern5,17
UIP
Image courtesy of and used with permission from Sudhakar Pipavath, MD.
Reprinted with permission of the American Thoracic Society. Copyright © 2018 American Thoracic Society. Raghu G, Remy-Jardin M, et al. Diagnosis of Idiopathic Pulmonary Fibrosis. An Official ATS/ERS/JRS/ALAT Clinical Practice Guideline. Am J Respir Crit Care Med. 2018;198(5):e44-e68.Official Journal of the American Thoracic Society.
Probable UIP, Indeterminate for UIP, or Alternative diagnosis
Diagnostic algorithm
5. Raghu G et al. Am J Respir Crit Care Med. 2018;198(5):e44-e68. 17. Lynch DA et al. Lancet. 2018;6(2):138-153.
18
Identifiable cause/ associated condition?
CTD on serologic testing?
HRCT results
IPF
YES
YES
Not UIP
UIP
Biopsy
Not
IPF
NO
NO
Suspected ILD
Further evaluation
YES
NO
Specific Diagnosis
MDD
BAL
MDD
Alternative Diagnosis
A UIP pattern on HRCT, paired with a lack of identifiable cause, is sufficient to diagnose IPF.5,17
Reprinted with permission of the American Thoracic Society. Copyright © 2018 American Thoracic Society. Raghu G, Remy-Jardin M, et al. Diagnosis of Idiopathic Pulmonary Fibrosis. An Official ATS/ERS/JRS/ALAT Clinical Practice Guideline. Am J Respir Crit Care Med. 2018;198(5):e44-e68.Official Journal of the American Thoracic Society.
Probable UIP, Indeterminate for UIP, or Alternative diagnosis
Identifiable cause/ associated condition?
CTD on serologic testing?
HRCT results
IPF
YES
YES
Not UIP
UIP
Biopsy
Not
IPF
NO
NO
Suspected ILD
Further evaluation
YES
NO
Specific Diagnosis
MDD
BAL
MDD
Alternative Diagnosis
Diagnostic algorithm
5. Raghu G et al. Am J Respir Crit Care Med. 2018;198(5):e44-e68. 6. Raghu G et al. Am J Respir Crit Care Med. 2011;183(6):788-824. 17. Lynch DA et al. Lancet. 2018;6(2):138-153.
19
HRCT: Probable UIP pattern5,17
Probable UIP
Image courtesy of and used with permission from Sudhakar Pipavath, MD.
Reprinted with permission of the American Thoracic Society. Copyright © 2018 American Thoracic Society. Raghu G, Remy-Jardin M, et al. Diagnosis of Idiopathic Pulmonary Fibrosis. An Official ATS/ERS/JRS/ALAT Clinical Practice Guideline. Am J Respir Crit Care Med. 2018;198(5):e44-e68.Official Journal of the American Thoracic Society.
Image used with permission from the American Thoracic Society. © 2014. Raghu G et al.6
Probable UIP, Indeterminate for UIP, or Alternative diagnosis
Identifiable cause/ associated condition?
CTD on serologic testing?
HRCT results
IPF
YES
YES
Not UIP
UIP
Biopsy
Not
IPF
NO
NO
Suspected ILD
Further evaluation
YES
NO
Specific Diagnosis
MDD
BAL
MDD
Alternative Diagnosis
Diagnostic algorithm
5. Raghu G et al. Am J Respir Crit Care Med. 2018;198(5):e44-e68. 17. Lynch DA et al. Lancet. 2018;6(2):138-153.
20
HRCT: Indeterminate pattern5,17
Indeterminate
Reprinted with permission of the American Thoracic Society. Copyright © 2018 American Thoracic Society. Raghu G, Remy-Jardin M, et al. Diagnosis of Idiopathic Pulmonary Fibrosis. An Official ATS/ERS/JRS/ALAT Clinical Practice Guideline. Am J Respir Crit Care Med. 2018;198(5):e44-e68.Official Journal of the American Thoracic Society.
Image courtesy of and used with permission from Robert Suh, MD.
Probable UIP, Indeterminate for UIP, or Alternative diagnosis
Identifiable cause/ associated condition?
CTD on serologic testing?
HRCT results
IPF
YES
YES
Not UIP
UIP
Biopsy
Not
IPF
NO
NO
Suspected ILD
Further evaluation
YES
NO
Specific Diagnosis
MDD
BAL
MDD
Alternative Diagnosis
Diagnostic algorithm
5. Raghu G et al. Am J Respir Crit Care Med. 2018;198(5):e44-e68. 17. Lynch DA et al. Lancet. 2018;6(2):138-153.
21
HRCT: Alternative Diagnosis5,17
Alternative Diagnosis
Image courtesy of and used with permission from Sudhakar Pipavath, MD.
Image courtesy of and used with permission from Jonathan Goldin, MD, PhD.
Reprinted with permission of the American Thoracic Society. Copyright © 2018 American Thoracic Society. Raghu G, Remy-Jardin M, et al. Diagnosis of Idiopathic Pulmonary Fibrosis. An Official ATS/ERS/JRS/ALAT Clinical Practice Guideline. Am J Respir Crit Care Med. 2018;198(5):e44-e68.Official Journal of the American Thoracic Society.
Probable UIP, Indeterminate for UIP, or Alternative diagnosis
Identifiable cause/ associated condition?
CTD on serologic testing?
HRCT results
IPF
YES
YES
Not UIP
UIP
Biopsy
Not
IPF
NO
NO
Suspected ILD
Further evaluation
YES
NO
Specific Diagnosis
MDD
BAL
MDD
Alternative Diagnosis
Diagnostic algorithm
5. Raghu G et al. Am J Respir Crit Care Med. 2018;198(5):e44-e68. 17. Lynch DA et al. Lancet. 2018;6(2):138-153.
Cases of probable UIP pattern, indeterminate, or potential alternative diagnosis should undergo biopsy (when possible) and MDD to ensure a more accurate diagnosis.5,17
MDD, multidisciplinary discussion
22
Reprinted with permission of the American Thoracic Society. Copyright © 2018 American Thoracic Society. Raghu G, Remy-Jardin M, et al. Diagnosis of Idiopathic Pulmonary Fibrosis. An Official ATS/ERS/JRS/ALAT Clinical Practice Guideline. Am J Respir Crit Care Med. 2018;198(5):e44-e68.Official Journal of the American Thoracic Society.
Probable UIP, Indeterminate for UIP, or Alternative diagnosis
Identifiable cause/ associated condition?
CTD on serologic testing?
HRCT results
IPF
YES
YES
Not UIP
UIP
Biopsy
Not
IPF
NO
NO
Suspected ILD
Further evaluation
YES
NO
Specific Diagnosis
MDD
BAL
MDD
Alternative Diagnosis
Diagnostic algorithm
5. Raghu G et al. Am J Respir Crit Care Med. 2018;198(5):e44-e68. 17. Lynch DA et al. Lancet. 2018;6(2):138-153.
23
Histopathology: UIP pattern5,17
Image used with permission from the American Thoracic Society. © 2018. Raghu G et al.5
UIP
Probable UIP, Indeterminate for UIP, or Alternative diagnosis
Identifiable cause/ associated condition?
CTD on serologic testing?
HRCT results
IPF
YES
YES
Not UIP
UIP
Biopsy
Not
IPF
NO
NO
Suspected ILD
Further evaluation
YES
NO
Specific Diagnosis
MDD
BAL
MDD
Alternative Diagnosis
Diagnostic algorithm
5. Raghu G et al. Am J Respir Crit Care Med. 2018;198(5):e44-e68. 17. Lynch DA et al. Lancet. 2018;6(2):138-153.
24
Histopathology: Probable UIP pattern5,17
Image used with permission from the American Thoracic Society. © 2018. Raghu G et al.5
AND
OR
Probable UIP
Probable UIP, Indeterminate for UIP, or Alternative diagnosis
Identifiable cause/ associated condition?
CTD on serologic testing?
HRCT results
IPF
YES
YES
Not UIP
UIP
Biopsy
Not
IPF
NO
NO
Suspected ILD
Further evaluation
YES
NO
Specific Diagnosis
MDD
BAL
MDD
Alternative Diagnosis
Diagnostic algorithm
5. Raghu G et al. Am J Respir Crit Care Med. 2018;198(5):e44-e68. 17. Lynch DA et al. Lancet. 2018;6(2):138-153.
25
Histopathology: Indeterminate for pattern5,17
Image used with permission from the American Thoracic Society. © 2018. Raghu G et al.5
Indeterminate for UIP
Probable UIP, Indeterminate for UIP, or Alternative diagnosis
Reprinted with permission of the American Thoracic Society. Copyright © 2018 American Thoracic Society. Raghu G, Remy-Jardin M, et al. Diagnosis of Idiopathic Pulmonary Fibrosis. An Official ATS/ERS/JRS/ALAT Clinical Practice Guideline. Am J Respir Crit Care Med. 2018;198(5):e44-e68.Official Journal of the American Thoracic Society.
Diagnostic algorithm
5. Raghu G et al. Am J Respir Crit Care Med. 2018;198(5):e44-e68. 17. Lynch DA et al. Lancet. 2018;6(2):138-153.
26
Identifiable cause/ associated condition?
CTD on serologic testing?
HRCT results
IPF
YES
YES
Not UIP
UIP
Biopsy
Not
IPF
NO
NO
Suspected ILD
Further evaluation
YES
NO
Specific Diagnosis
MDD
BAL
MDD
Alternative Diagnosis
Histopathology: Alternative diagnosis5,17
Image courtesy of and used with permission from Kirk Jones, MD.
Alternative diagnosis
Probable UIP, Indeterminate for UIP, or Alternative diagnosis
Diagnostic algorithm
5. Raghu G et al. Am J Respir Crit Care Med. 2018;198(5):e44-e68. 17. Lynch DA et al. Lancet. 2018;6(2):138-153.
MDD, multidisciplinary discussion
27
Identifiable cause/ associated condition?
CTD on serologic testing?
HRCT results
IPF
YES
YES
Not UIP
UIP
Biopsy
Not
IPF
NO
NO
Suspected ILD
Further evaluation
YES
NO
Specific Diagnosis
MDD
BAL
MDD
Alternative Diagnosis
An MDD provides a sounding board to evaluate all evidence to come up with a consensus diagnosis, whether that is IPF or another ILD.5,17
Reprinted with permission of the American Thoracic Society. Copyright © 2018 American Thoracic Society. Raghu G, Remy-Jardin M, et al. Diagnosis of Idiopathic Pulmonary Fibrosis. An Official ATS/ERS/JRS/ALAT Clinical Practice Guideline. Am J Respir Crit Care Med. 2018;198(5):e44-e68.Official Journal of the American Thoracic Society.
Diagnostic algorithm – designating the HRCT and histopathology pattern
28
Suspected Case of IPF
Histopathology
UIP
Probable UIP
Indeterminate UIP
Alternative Diagnosis
HRCT results
UIP
IPF
IPF
IPF
Not IPF
Probable UIP
IPF
IPF
IPF Likely
Not IPF
Indeterminate UIP
IPF
IPF Likely
Indeterminate
Not IPF
Alternative Diagnosis
IPF (likely) or non-IPF
Not IPF
Not IPF
Not IPF
Adapted from Raghu G et al. Am J Respir Crit Care Med. 2018;198(5):e44-e68.
5. Raghu G et al. Am J Respir Crit Care Med. 2018;198(5):e44-e68.
Likely IPF:
Indeterminate:
Probable UIP, Indeterminate for UIP, or Alternative diagnosis
Diagnostic algorithm
5. Raghu G et al. Am J Respir Crit Care Med. 2018;198(5):e44-e68.
29
Identifiable cause/ associated condition?
CTD on serologic testing?
HRCT results
IPF
YES
YES
Not UIP
UIP
Biopsy
Not
IPF
NO
NO
Suspected ILD
Further evaluation
YES
NO
Specific Diagnosis
MDD
BAL
MDD
Alternative Diagnosis
Reprinted with permission of the American Thoracic Society. Copyright © 2018 American Thoracic Society. Raghu G, Remy-Jardin M, et al. Diagnosis of Idiopathic Pulmonary Fibrosis. An Official ATS/ERS/JRS/ALAT Clinical Practice Guideline. Am J Respir Crit Care Med. 2018;198(5):e44-e68.Official Journal of the American Thoracic Society.
References
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