Diagnostic criteria and diagnostic algorithm for IPF

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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 

Early diagnosis is essential for timely referral to a lung transplant center for patients with advanced disease4

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.

Diagnostic criteria for IPF

 

Current diagnostic criteria

According to the 2011 ATS/ERS/JRS/ALAT guideline criteria, diagnosing IPF requires the following5:

1. Exclusion of other known causes of ILD
2. A UIP pattern on HRCT in patients without SLB
3. Specific combinations of HRCT and SLB pattern (in patients who undergo an SLB)

ILD, interstitial lung disease; HRCT, high-resolution computed tomography; SLB, surgical lung biopsy.

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

Diagnostic algorithm

When you suspect a patient has an ILD, the first things to do are5,6:
-Perform a physical exam
-Take a complete history, including exposures
-Evaluate pulmonary function through PFTs

PFT, pulmonary function test

5. Raghu G et al. Am J Respir Crit Care Med. 2011;183:788-824.
6. Ley B et al. Am J Respir Crit Care Med. 2011;183(4):431-440.
 

Diagnostic algorithm

Signs of IPF on physical exam:5
  • Typically affects adults >50 years of age
  • Chronic exertional dyspnea
  • Dry, nonproductive cough
  • Crackles or rales on auscultation
  • May show signs of digital clubbing
Reprinted with permission of the American Thoracic Society. Copyright © 2014 American Thoracic Society. Raghu G, Collard HR, Egan JJ, et al. An official ATS/ERS/JRS/ALAT statement: idiopathic pulmonary fibrosis: evidence-based guidelines for diagnosis and management. Am J Respir Crit Care Med. 2011;183:788-824. Official Journal of the American Thoracic Society. Note: this document was published in 2011 and is currently in revision. Certain aspects of this document may be out of date and caution should be used when applying these in clinical practice or other usages

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

Diagnostic algorithm

Signs of IPF based on history:5
  • Current or former smoker
  • Exposure to any number of dusts (eg, stone, silica, wood)
  • Agriculture and/or bird exposures
  • Viral exposures (eg, Hepatitis C)
  • Family history of pulmonary fibrosis
Reprinted with permission of the American Thoracic Society. Copyright © 2014 American Thoracic Society. Raghu G, Collard HR, Egan JJ, et al. An official ATS/ERS/JRS/ALAT statement: idiopathic pulmonary fibrosis: evidence-based guidelines for diagnosis and management. Am J Respir Crit Care Med. 2011;183:788-824. Official Journal of the American Thoracic Society. Note: this document was published in 2011 and is currently in revision. Certain aspects of this document may be out of date and caution should be used when applying these in clinical practice or other usages

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

Diagnostic algorithm

Signs of IPF on PFTs:7,8
  • Restrictive physiology
    • Reduced TLC
    • Increased FEV1/FVC ratio
  • Reduced DLco
  • Reduced predicted FVC
  • Desaturation on exertion
Reprinted with permission of the American Thoracic Society. Copyright © 2014 American Thoracic Society. Raghu G, Collard HR, Egan JJ, et al. An official ATS/ERS/JRS/ALAT statement: idiopathic pulmonary fibrosis: evidence-based guidelines for diagnosis and management. Am J Respir Crit Care Med. 2011;183:788-824. Official Journal of the American Thoracic Society. Note: this document was published in 2011 and is currently in revision. Certain aspects of this document may be out of date and caution should be used when applying these in clinical practice or other usages

7. Pellegrino R et al. Eur Respir J. 2005;26(5):948-968.
8. Meltzer EB et al. Orphanet J Rare Dis. 2008;3:1-15.

Diagnostic algorithm

Identifiable Cause?

Reprinted with permission of the American Thoracic Society. Copyright © 2014 American Thoracic Society. Raghu G, Collard HR, Egan JJ, et al. An official ATS/ERS/JRS/ALAT statement: idiopathic pulmonary fibrosis: evidence-based guidelines for diagnosis and management. Am J Respir Crit Care Med. 2011;183:788-824. Official Journal of the American Thoracic Society. Note: this document was published in 2011 and is currently in revision. Certain aspects of this document may be out of date and caution should be used when applying these in clinical practice or other usages

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

Diagnostic algorithm

Many ILDs have identifiable causes:9
  • Hypersensitivity pneumonitis
  • Asbestosis
  • Silicosis
  • Post-infectious ILD
  • Drug-induced ILD
Reprinted with permission of the American Thoracic Society. Copyright © 2014 American Thoracic Society. Raghu G, Collard HR, Egan JJ, et al. An official ATS/ERS/JRS/ALAT statement: idiopathic pulmonary fibrosis: evidence-based guidelines for diagnosis and management. Am J Respir Crit Care Med. 2011;183:788-824. Official Journal of the American Thoracic Society. Note: this document was published in 2011 and is currently in revision. Certain aspects of this document may be out of date and caution should be used when applying these in clinical practice or other usages

9. European Respiratory Society. White Book: ILDs. http://www.erswhitebook.org/chapters/interstitial-lung-diseases/

Diagnostic algorithm

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 © 2014 American Thoracic Society. Raghu G, Collard HR, Egan JJ, et al. An official ATS/ERS/JRS/ALAT statement: idiopathic pulmonary fibrosis: evidence-based guidelines for diagnosis and management. Am J Respir Crit Care Med. 2011;183:788-824. Official Journal of the American Thoracic Society. Note: this document was published in 2011 and is currently in revision. Certain aspects of this document may be out of date and caution should be used when applying these in clinical practice or other usages

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

Diagnostic algorithm

CTD on serologic testing?
 
Reprinted with permission of the American Thoracic Society. Copyright © 2014 American Thoracic Society. Raghu G, Collard HR, Egan JJ, et al. An official ATS/ERS/JRS/ALAT statement: idiopathic pulmonary fibrosis: evidence-based guidelines for diagnosis and management. Am J Respir Crit Care Med. 2011;183:788-824. Official Journal of the American Thoracic Society. Note: this document was published in 2011 and is currently in revision. Certain aspects of this document may be out of date and caution should be used when applying these in clinical practice or other usages

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

Diagnostic algorithm

The next step is to consider performing serologic testing to evaluate for CTD5
  • Screens include: RF, anti-CCP, ANA
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.

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

Diagnostic algorithm

If there are no elevations in CTD markers, you should continue to suspect IPF.
 
Reprinted with permission of the American Thoracic Society. Copyright © 2014 American Thoracic Society. Raghu G, Collard HR, Egan JJ, et al. An official ATS/ERS/JRS/ALAT statement: idiopathic pulmonary fibrosis: evidence-based guidelines for diagnosis and management. Am J Respir Crit Care Med. 2011;183:788-824. Official Journal of the American Thoracic Society. Note: this document was published in 2011 and is currently in revision. Certain aspects of this document may be out of date and caution should be used when applying these in clinical practice or other usages

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

Diagnostic algorithm

HRCT results

Reprinted with permission of the American Thoracic Society. Copyright © 2014 American Thoracic Society. Raghu G, Collard HR, Egan JJ, et al. An official ATS/ERS/JRS/ALAT statement: idiopathic pulmonary fibrosis: evidence-based guidelines for diagnosis and management. Am J Respir Crit Care Med. 2011;183:788-824. Official Journal of the American Thoracic Society. Note: this document was published in 2011 and is currently in revision. Certain aspects of this document may be out of date and caution should be used when applying these in clinical practice or other usages

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

Diagnostic algorithm

Next, patients should have an HRCT performed5
  • The positive predictive value of a definite UIP pattern on HRCT is 90%-100%10-15
  • Definite UIP should be paired with an exclusion of other causes of ILD before reaching a diagnosis of IPF5
Reprinted with permission of the American Thoracic Society. Copyright © 2014 American Thoracic Society. Raghu G, Collard HR, Egan JJ, et al. An official ATS/ERS/JRS/ALAT statement: idiopathic pulmonary fibrosis: evidence-based guidelines for diagnosis and management. Am J Respir Crit Care Med. 2011;183:788-824. Official Journal of the American Thoracic Society. Note: this document was published in 2011 and is currently in revision. Certain aspects of this document may be out of date and caution should be used when applying these in clinical practice or other usages

5. Raghu G et al. Am J Respir Crit Care Med. 2011;183:788-824.
10. Mathieson JR et al. Radiol. 1989;171(1):111-116.
11. Hunninghake GW et al. Am J Respir Crit Care Med. 2001;164(2):193-196.
12. Raghu G et al. Chest. 1999;116(5):1168-1174.
13. Grenier P et al. Radiology. 1991;179(1):123-132.
14. Lee KS et al. Radiology. 1994;191(3):669-673.
15. Swensen SJ et al. Radiology. 1997;205(1):229-234.

Diagnostic algorithm

HRCT: Definite UIP pattern5
  1. Subpleural, basal predominance
  2. Reticulation
  3. Honeycombing
  4. Absence/paucity of:
    • Micronodules
    • Discrete cysts
    • Consolidation
    • Mosaic attenuation/air trapping
    • Ground glass opacity
Reprinted with permission of the American Thoracic Society. Copyright © 2014 American Thoracic Society. Raghu G, Collard HR, Egan JJ, et al. An official ATS/ERS/JRS/ALAT statement: idiopathic pulmonary fibrosis: evidence-based guidelines for diagnosis and management. Am J Respir Crit Care Med. 2011;183:788-824. Official Journal of the American Thoracic Society. Note: this document was published in 2011 and is currently in revision. Certain aspects of this document may be out of date and caution should be used when applying these in clinical practice or other usages

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

Diagnostic algorithm

A definite UIP pattern on HRCT, paired with a lack of identifiable cause, is sufficient to diagnose IPF.5

Reprinted with permission of the American Thoracic Society. Copyright © 2014 American Thoracic Society. Raghu G, Collard HR, Egan JJ, et al. An official ATS/ERS/JRS/ALAT statement: idiopathic pulmonary fibrosis: evidence-based guidelines for diagnosis and management. Am J Respir Crit Care Med. 2011;183:788-824. Official Journal of the American Thoracic Society. Note: this document was published in 2011 and is currently in revision. Certain aspects of this document may be out of date and caution should be used when applying these in clinical practice or other usages

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

Diagnostic algorithm

HRCT: Possible UIP pattern5
  1. Subpleural, basal predominance
  2. Reticulation
  3. Absence/paucity of:
    • Micronodules
    • Discrete cysts
    • Consolidation
    • Mosaic attenuation/air trapping
    • Ground glass opacity
Reprinted with permission of the American Thoracic Society. Copyright © 2014 American Thoracic Society. Raghu G, Collard HR, Egan JJ, et al. An official ATS/ERS/JRS/ALAT statement: idiopathic pulmonary fibrosis: evidence-based guidelines for diagnosis and management. Am J Respir Crit Care Med. 2011;183:788-824. Official Journal of the American Thoracic Society. Note: this document was published in 2011 and is currently in revision. Certain aspects of this document may be out of date and caution should be used when applying these in clinical practice or other usages

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

Diagnostic algorithm

HRCT: Not UIP pattern5
  1. Upper/mid-lung predominance
  2. Peribronchovascular predominance
  3. Extensive ground glass abnormality (extent > reticular abnormality)
  4. Substantial extent of any of the following:
    • Consolidation
    • Micronodules
    • Discrete cysts
    • Mosaic attenuation/air trapping
Reprinted with permission of the American Thoracic Society. Copyright © 2014 American Thoracic Society. Raghu G, Collard HR, Egan JJ, et al. An official ATS/ERS/JRS/ALAT statement: idiopathic pulmonary fibrosis: evidence-based guidelines for diagnosis and management. Am J Respir Crit Care Med. 2011;183:788-824. Official Journal of the American Thoracic Society. Note: this document was published in 2011 and is currently in revision. Certain aspects of this document may be out of date and caution should be used when applying these in clinical practice or other usages

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

Diagnostic algorithm

Cases of possible or inconsistent with UIP pattern should undergo biopsy (when possible) and MDD to ensure a more accurate diagnosis.5

MDD, multidisciplinary discussion

Reprinted with permission of the American Thoracic Society. Copyright © 2014 American Thoracic Society. Raghu G, Collard HR, Egan JJ, et al. An official ATS/ERS/JRS/ALAT statement: idiopathic pulmonary fibrosis: evidence-based guidelines for diagnosis and management. Am J Respir Crit Care Med. 2011;183:788-824. Official Journal of the American Thoracic Society. Note: this document was published in 2011 and is currently in revision. Certain aspects of this document may be out of date and caution should be used when applying these in clinical practice or other usages

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

Diagnostic algorithm

Histopathology: UIP pattern5
  1. Evidence of marked fibrosis/architectural distortion ± honeycombing in a predominantly subpleural/paraseptal distribution
  2. Presence of patchy involvement of lung parenchyma by fibrosis
  3. Presence of fibroblast foci
  4. Absence of features against a diagnosis of UIP, suggesting an alternate diagnosis (see Not UIP section)
Reprinted with permission of the American Thoracic Society. Copyright © 2014 American Thoracic Society. Raghu G, Collard HR, Egan JJ, et al. An official ATS/ERS/JRS/ALAT statement: idiopathic pulmonary fibrosis: evidence-based guidelines for diagnosis and management. Am J Respir Crit Care Med. 2011;183:788-824. Official Journal of the American Thoracic Society. Note: this document was published in 2011 and is currently in revision. Certain aspects of this document may be out of date and caution should be used when applying these in clinical practice or other usages

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

Diagnostic algorithm

Histopathology: Not UIP pattern5
  1. Organizing pneumonia
  2. Hyaline membranes
  3. Predominant airway-centered changes
  4. Marked interstitial inflammatory cell infiltrate apart from honeycombing
  5. Granulomas
  6. Other features suggestive of an alternate diagnosis
Reprinted with permission of the American Thoracic Society. Copyright © 2014 American Thoracic Society. Raghu G, Collard HR, Egan JJ, et al. An official ATS/ERS/JRS/ALAT statement: idiopathic pulmonary fibrosis: evidence-based guidelines for diagnosis and management. Am J Respir Crit Care Med. 2011;183:788-824. Official Journal of the American Thoracic Society. Note: this document was published in 2011 and is currently in revision. Certain aspects of this document may be out of date and caution should be used when applying these in clinical practice or other usages

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

Diagnostic algorithm

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
 
Reprinted with permission of the American Thoracic Society. Copyright © 2014 American Thoracic Society. Raghu G, Collard HR, Egan JJ, et al. An official ATS/ERS/JRS/ALAT statement: idiopathic pulmonary fibrosis: evidence-based guidelines for diagnosis and management. Am J Respir Crit Care Med. 2011;183:788-824. Official Journal of the American Thoracic Society. Note: this document was published in 2011 and is currently in revision. Certain aspects of this document may be out of date and caution should be used when applying these in clinical practice or other usages

MDD, multidisciplinary discussion

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

Diagnostic algorithm

Reprinted with permission of the American Thoracic Society. Copyright © 2014 American Thoracic Society. Raghu G, Collard HR, Egan JJ, et al. An official ATS/ERS/JRS/ALAT statement: idiopathic pulmonary fibrosis: evidence-based guidelines for diagnosis and management. Am J Respir Crit Care Med. 2011;183:788-824. Official Journal of the American Thoracic Society. Note: this document was published in 2011 and is currently in revision. Certain aspects of this document may be out of date and caution should be used when applying these in clinical practice or other usages

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

References

1.Wells AU. Eur Respir Rev. 2013;22(128):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(5):538-542.
5.Raghu G et al. Am J Respir Crit Care Med. 2011;183(6):788-824.
6.Ley B et al. Am J Respir Crit Care Med. 2011;183(4):431-440.
7.Pellegrino R et al. Eur Respir J. 2005;26(5):948-968.
8.Meltzer EB et al. Orphanet J Rare Dis. 2008;3:1-15.
9.European Respiratory Society. White Book: ILDs. http://www.erswhitebook.org/chapters/interstitial-lung-diseases/
10.Mathieson JR et al. Radiol. 1989;171(1):111-116.
11.Hunninghake GW et al. Am J Respir Crit Care Med. 2001;164(2):193-196.
12.Raghu G et al. Chest. 1999;116(5):1168-1174.
13.Grenier P et al. Radiology. 1991;179(1):123-132.
14.Lee KS et al. Radiology. 1994;191(3):669-673.
15.Swensen SJ et al. Radiology. 1997;205(1):229-234.