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Idiopathic Pulmonary Fibrosis
Evidence Based Guidelines for Diagnosis and Management*
Clinical presentation
– Older age (6th – 7th decades of life)
– Men > women
– Unexplained chronic exertional dyspnea, crackles, finger
clubbing
Incidence and prevalence
– No large-scale studies to base formal estimates
– Incidence = 6.8-16.3/100,000
– Prevalence = 14-42.7/100,00
Large database of health care
claims in health plan
(Raghu 2006)
Idiopathic Pulmonary Fibrosis
Idiopathic Pulmonary Fibrosis
Evidence Based Guidelines for Diagnosis and Management*
Specific form of chronic, progressive fibrosing interstitial
pneumonia of unknown cause
Occurring in adults; limited to the lungs
Histologic and/or radiologic pattern of Usual Interstitial
Pneumonia (UIP)
Requirement
– Exclusion of other forms of Idiopathic interstitial
pneumonia and Interstitial lung diseases associated with
environmental exposure, medication, or systemic disease
Definition: Idiopathic Pulmonary Fibrosis
Idiopathic Pulmonary Fibrosis
Evidence Based Guidelines for Diagnosis and Management*
Careful history and physical exam
Focus on environmental exposures, medication use, co morbidities
Family medical history
Use questionnaires (e.g., ILD questionnaire –
http://www.chestnet.org)
No validated questionnaires to exclude known cause(s) for ILD
Exclude connective tissue (CT) diseases
– Established criteria for specific CT disease
– Index of clinical suspicion for CT disease in patients <50 yrs (esp.
women)
Exclusion of Other Known Causes for Pulmonary Fibrosis
Idiopathic Pulmonary Fibrosis
Evidence Based Guidelines for Diagnosis and Management*
Summary of evidence
-No reliable data on the role of screening serologies in patients with
suspected IPF.
-Connective tissue disease (CTD) can present with a UIP
-ILD has been described as the sole clinical manifestation of CTD
and can precede the overt manifestation of a specific connective
tissue disease
Question: Should serological testing for connective tissues
disease be used in the evaluation of suspected IPF?
Idiopathic Pulmonary Fibrosis
Evidence Based Guidelines for Diagnosis and Management*
Recommendation: Serological testing for connective tissue disease
should be performed in the evaluation of IPF (weak recommendation,
very low quality evidence). (votes : 23 for the use of serological testing,
none against, no abstentions)
Values: A high value on distinguishing connective tissue disease from
IPF and low value on cost.
Remarks:
– Serological evaluation should be performed even in the absence of
signs or symptoms of connective tissue disease( include rheumatoid
factor, anti-cyclic citrullinated peptide, and anti-nuclear antibody titer
and pattern
– The routine use of other serological tests is of unclear benefit
Question: Should serological testing for connective tissues
disease be used in the evaluation of suspected IPF?
Idiopathic Pulmonary Fibrosis
Evidence Based Guidelines for Diagnosis and Management*
Summary of evidence
-Prominent lymphocytosis (>40%) in BAL suggests diagnosis of
chronic hypersensitivity pneumonitis
-8% of patients with UIP pattern on HRCT may have BAL findings
suggestive of dx other than IPF (Ohshimo et al. AJRCCM 2009)
-Unclear whether BAL adds significant diagnostic specificity to a
careful exposure history and clinical evaluation
Question: Should BAL Cellular Analysis be Performed
in the Diagnostic Evaluation of Suspected IPF?
Idiopathic Pulmonary Fibrosis
Evidence Based Guidelines for Diagnosis and Management*
Recommendation: BAL cellular analyses should not be
performed in the dx evaluation of IPF (weak
recommendation; low quality of evidence) (votes : 4 for
the use of BAL; 18 against the use of BAL; 1 abstention)
Values: High value on additional risk and cost; low value
on possible improved specificity of dx
Remarks: BAL cellular analysis should be considered at
the discretion of the treating physician based on
availability and experience at their center
Question: Should BAL Cellular Analysis be Performed
in the Diagnostic Evaluation of Suspected IPF?
Idiopathic Pulmonary Fibrosis
Evidence Based Guidelines for Diagnosis and Management*
Summary of evidence
-the specificity and positive predictive value of UIP pattern
identified by transbronchial biopsy has not been rigorously
studied.
-The sensitivity and specificity of this approach for the diagnosis
for UIP pattern is unknown.
-it is also unknown how many and from where transbronchial
biopsies should be obtained.
Question: Should transbronchial lung biopsy be used
in the evaluation of suspected IPF?
Idiopathic Pulmonary Fibrosis
Evidence Based Guidelines for Diagnosis and Management*
Recommendation: Trans bronchial biopsy should not be
used in the evaluation of IPF (weak recommendation,
low quality evidence). (Votes: none for the use of trans
bronchial biopsy, 23 against the use of trans bronchial
biopsy, no abstentions)
Values: This recommendation places a high value on
the additional morbidity of trans bronchial lung biopsy in
patients with IPF and low value on possible diagnostic
specifcity.
Question: Should transbronchial lung biopsy be used
in the evaluation of suspected IPF?
Idiopathic Pulmonary Fibrosis
Evidence Based Guidelines for Diagnosis and Management*
Usual Interstitial pneumonia (UIP)
HRCT images of lung :
UIP pattern
Consistent with UIP pattern
Inconsistent with UIP pattern
Histopathology on surgical lung biopsy :
UIP pattern
Probable UIP pattern
Possible UIP pattern
Not UIP pattern
Idiopathic Pulmonary Fibrosis
Evidence Based Guidelines for Diagnosis and Management*
UIP Pattern (All four features)
Subpleural, basal predominance
Reticular abnormality
Honeycombing with or without traction
bronchiectasis
Absence of features listed as inconsistent with
UIP pattern
HRCT Criteria for UIP Pattern
Idiopathic Pulmonary Fibrosis
Evidence Based Guidelines for Diagnosis and Management*
HRCT Images: UIP Pattern (Extensive honeycombing)
A B
Idiopathic Pulmonary Fibrosis
Evidence Based Guidelines for Diagnosis and Management*
D
HRCT Images: UIP Pattern (Less severe honeycombing)
C
Idiopathic Pulmonary Fibrosis
Evidence Based Guidelines for Diagnosis and Management*
HRCT Images: UIP Pattern
(Extensive honeycombing)
A C
B D
HRCT Images: UIP Pattern
(Less severe honeycombing)
Honeycombing (HRCT)
Clustered cystic air
spaces
Well defined walls
Typically comparable
diameters (3-10 mm;
occasionally as large
as 2.5 cm)
Sub pleural
Idiopathic Pulmonary Fibrosis
Evidence Based Guidelines for Diagnosis and Management*
Consistent with UIP Pattern (All three features)
Subpleural, basal predominance
Reticular abnormality
Absence of features listed as inconsistent with
UIP pattern
(NO HONEY COMBING)
HRCT Criteria for UIP Pattern
Idiopathic Pulmonary Fibrosis
Evidence Based Guidelines for Diagnosis and Management*
FE
HRCT Images: Consistent with UIP pattern (no honeycombing)
Idiopathic Pulmonary Fibrosis
Evidence Based Guidelines for Diagnosis and Management*
HRCT Images: UIP Pattern
(Extensive honeycombing)
A C
B D F
E
HRCT Images: UIP Pattern
(Less severe honeycombing)
HRCT Images: Consistent
with UIP pattern
Idiopathic Pulmonary Fibrosis
Evidence Based Guidelines for Diagnosis and Management*
Inconsistent with UIP pattern (any of the seven features)
– Upper or mid lung predominance
– Peribronchovascular predominance
– Extensive ground glass abnormality (extent > reticular
abnormality
– Profuse micro nodules (bilateral, predominantly upper lobes)
– Discrete cysts (multiple, bilateral, away from areas of
honeycombing)
– Diffuse mosaic attenuation/air trapping (bilateral, in 3 or more
lobes)
– Consolidation in bronchopulmonary segment (s) / lobe(s)
HRCT Criteria for UIP Pattern
Idiopathic Pulmonary Fibrosis
Evidence Based Guidelines for Diagnosis and Management*
Surgical Lung Biopsy Specimens: Histopathology of UIP Pattern
*
Honeycomb
spacesPreserved lung
tissue
Chronic
fibrosis
Fibroblast focus
Idiopathic Pulmonary Fibrosis
Evidence Based Guidelines for Diagnosis and Management*
Histopathological Criteria for UIP Pattern
UIP pattern (all four criteria)
– Evidence of marked fibrosis/architectural distortion, +/-
honeycombing in a predominantly subpleural/paraseptal
distribution
– Presence of patchy involvement of lung parenchyma by
fibrosis
– Presence of fibroblast foci
– Absence of features against a diagnosis of UIP suggesting
an alternate diagnosis
Idiopathic Pulmonary Fibrosis
Evidence Based Guidelines for Diagnosis and Management*
Histopathological Criteria for UIP Pattern
Probable UIP pattern
– Evidence of marked fibrosis/architectural distortion, +/-
honeycombing in a sub pleural /para septal distribution
– Absence of either patchy involvement or fibroblastic
foci, but not both
– Absence of features against a diagnosis of UIP
suggesting an alternate diagnosis
OR
– Honeycomb changes only**
** This scenario usually represents end-stage fibrotic lung disease where honeycombed
segments have been sampled but where a UIP pattern might be present in other areas.
Such areas are usually represented by overt honeycombing on HRCT and can be avoided
by pre-operative targeting of biopsy sites away from these areas using HRCT.
Idiopathic Pulmonary Fibrosis
Evidence Based Guidelines for Diagnosis and Management*
Histopathological Criteria for UIP Pattern
Possible UIP pattern (all three criteria)
– Patchy or diffuse involvement of lung parenchyma by
fibrosis, with or without interstitial inflammation
– Absence of other criteria for UIP
– Absence of features against a diagnosis of UIP
suggesting an alternate diagnosis
Idiopathic Pulmonary Fibrosis
Evidence Based Guidelines for Diagnosis and Management*
Histopathological Criteria for UIP Pattern
Not UIP pattern (any of the six criteria)
– Hyaline membranes *
– Organizing pneumonia *†
– Granulomas †
– Marked interstitial inflammatory cell infiltrate away from
honeycombing
– Predominant airway centered changes
– Other features suggestive of an alternate diagnosis
* Can be associated with acute exacerbation of IPF
† An isolated or occasional granuloma and /or a mild component of organizing pneumonia
pattern may rarely be coexisting in lung biopsies with an otherwise UIP pattern
Idiopathic Pulmonary Fibrosis
Evidence Based Guidelines for Diagnosis and Management*
DIAGNOSIS OF IPF : Combination of HRCT and Histopathology
requires multidisciplinary discussion (MDD)
UIP
** Non-classifiable fibrosis: a pattern of fibrosis that does not meet the above criteria for UIP pattern and
the other idiopathic interstitial pneumonias
† The accuracy of the diagnosis increases with MDD. This is particularly relevant in cases where the
radiologic and histopathologic patterns are discordant (e.g. HRCT is inconsistent with UIP and
histopathology is UIP). The accuracy of diagnosis is improved with MDD among interstitial lung disease
experts compared to clinician-specialists in the community setting.
UIP
Probable UIP
Possible UIP
Non-classifiable
fibrosis**
Not UIP
Yes
No
HRCT Pattern Histopathology Pattern
(when Surgical lung bx performed)
Dx of IPF ?†
Idiopathic Pulmonary Fibrosis
Evidence Based Guidelines for Diagnosis and Management*
Consistent
with UIP
†† MDD among interstitial lung disease experts should include discussions of the
potential for sampling error and a re-evaluation of adequacy of technique of
HRCT.
UIP
Probable UIP
Possible UIP
Non-classifiable
fibrosis
Not UIP
Yes
Probable††
No
HRCT Pattern
Histopathology Pattern
(when Surgical lung bx performed) Dx of IPF ?
DIAGNOSIS OF IPF : Combination of HRCT and Histopathology
requires multidisciplinary discussion (MDD)
Idiopathic Pulmonary Fibrosis
Evidence Based Guidelines for Diagnosis and Management*
Combination of HRCT and surgical lung biopsy for the diagnosis of IPF
(requires multidisciplinary discussion)
Inconsistent
with UIP
†† MDD among interstitial lung disease experts should include discussions of the
potential for sampling error and a re-evaluation of adequacy of technique of
HRCT.
UIP
Probable UIP
Possible UIP
Non-classifiable
fibrosis
Not UIP
Possible ††
No
HRCT Pattern
Histopathology Pattern
(When surgical lung bx performed) Dx of IPF?
Idiopathic Pulmonary Fibrosis
Evidence Based Guidelines for Diagnosis and Management*
Summary of evidence
-the diagnosis of IPF is, by definition, multidisciplinary,
drawing on the expertise of experienced clinicians, radiologists,
and pathologists.
-proper communication between the various disciplines
involved in the diagnosis of IPF (pulmonary, radiology,
pathology) has been shown to improve inter-observer
agreement among experienced clinical experts as to the
ultimate diagnosis (Flaherty et al. 2004 and 2007)
Question: Should a multi-disciplinary discussion be used
in the evaluation of suspected IPF?
Idiopathic Pulmonary Fibrosis
Evidence Based Guidelines for Diagnosis and Management*
Recommendation: A MDD should be used in the evaluation of IPF (strong
recommendation, low quality evidence). (Votes: 23 for the use of MDD, none against,
no abstentions)
Values: A high value on the accurate diagnosis of IPF and a low value on the access
to and availability of experts for MDD.
Remarks:
–It is recognized that a formal MDD between the treating pulmonologist, radiologist
and pathologist is not possible for many practitioners.
–Effort should be made, however, to promote verbal communication between
specialties during the evaluation of the case
–Accuracy of diagnosis is improved through MDD among interstitial lung disease
(ILD) experts compared to MDD among specialists in the community setting
(Flaherty et al. 2007)
–Timely referral to ILD experts is encouraged.
Question: Should a multi-disciplinary discussion (MDD) be used in
the evaluation of suspected IPF?
Idiopathic Pulmonary Fibrosis
Evidence Based Guidelines for Diagnosis and Management*
Exclusion of known causes of ILD (e.g., environmental
exposure, connective tissue disease, and drug toxicity
UIP pattern or HRCT and/or histopathology (surgical
lung biopsy)
Or
Specific combinations of HRCT and histopathological
patterns (surgical lung biopsy)
Diagnostic Criteria for IPF
Idiopathic Pulmonary Fibrosis
Evidence Based Guidelines for Diagnosis and Management*
Diagnostic Algorithm for IPF
Suspected IPF
Identifiable causes for ILD?
HRCT
Surgical Biopsy
MDD
IPF/Not IPF per TableIPF Not IPF
Yes
Not UIP
UIP Consistent with UIP
Inconsistent with UIP
UIP
Probable UIP/Possible UIP
Non-classifiable fibrosis
No
Idiopathic Pulmonary Fibrosis
Evidence Based Guidelines for Diagnosis and Management*
IPF ; natural history is variable and unpredictable
Usual interstitial pneumonia (UIP)pattern for both
HRCT and histopathology (surgical lung biopsy)
features
The pattern of UIP : “consistent” and “inconsistent” on
HRCT
The histopathologic features of “probable”, “possible”
patterns for UIP and those that are “not UIP”
Summary :
Precise Definitions
Idiopathic Pulmonary Fibrosis
Evidence Based Guidelines for Diagnosis and Management*
In the appropriate clinical setting
– The diagnosis of IPF is ascertained if the HRCT images
reveal pattern of UIP (surgical lung biopsy is not required)
– Histological features of UIP in surgical lung biopsy is
required for diagnosis of IPF if HRCT images are different
than the UIP pattern
– Combinations of HRCT and histopathological criteria are
required to diagnose and/or exclude IPF
– Accuracy of diagnosis increases with multidisciplinary
discussions between pulmonologists, radiologists, and
pathologists experienced in the diagnosis of ILD
Summary : Diagnosis
Idiopathic Pulmonary Fibrosis
Evidence Based Guidelines for Diagnosis and Management*
Natural History
of IPF
ClinicalCourse
Time
Stable
Slow
progression
Rapid
progression
Acute
worsening
Idiopathic Pulmonary Fibrosis
Evidence Based Guidelines for Diagnosis and Management*
American Thoracic Society
European Respiratory Society
Japanese Respiratory Society
Latin American Thoracic Association
Staffs
– University College, Dublin, Ireland
– University of Modena and Reggio Emilia, Italy
– Mr. Lance Lucas (ATS)
Peer Reviewers
Community and Academic pulmonologists
Acknowledgments

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Raghu nieuw

  • 1. Idiopathic Pulmonary Fibrosis Evidence Based Guidelines for Diagnosis and Management* Clinical presentation – Older age (6th – 7th decades of life) – Men > women – Unexplained chronic exertional dyspnea, crackles, finger clubbing Incidence and prevalence – No large-scale studies to base formal estimates – Incidence = 6.8-16.3/100,000 – Prevalence = 14-42.7/100,00 Large database of health care claims in health plan (Raghu 2006) Idiopathic Pulmonary Fibrosis
  • 2. Idiopathic Pulmonary Fibrosis Evidence Based Guidelines for Diagnosis and Management* Specific form of chronic, progressive fibrosing interstitial pneumonia of unknown cause Occurring in adults; limited to the lungs Histologic and/or radiologic pattern of Usual Interstitial Pneumonia (UIP) Requirement – Exclusion of other forms of Idiopathic interstitial pneumonia and Interstitial lung diseases associated with environmental exposure, medication, or systemic disease Definition: Idiopathic Pulmonary Fibrosis
  • 3. Idiopathic Pulmonary Fibrosis Evidence Based Guidelines for Diagnosis and Management* Careful history and physical exam Focus on environmental exposures, medication use, co morbidities Family medical history Use questionnaires (e.g., ILD questionnaire – http://www.chestnet.org) No validated questionnaires to exclude known cause(s) for ILD Exclude connective tissue (CT) diseases – Established criteria for specific CT disease – Index of clinical suspicion for CT disease in patients <50 yrs (esp. women) Exclusion of Other Known Causes for Pulmonary Fibrosis
  • 4. Idiopathic Pulmonary Fibrosis Evidence Based Guidelines for Diagnosis and Management* Summary of evidence -No reliable data on the role of screening serologies in patients with suspected IPF. -Connective tissue disease (CTD) can present with a UIP -ILD has been described as the sole clinical manifestation of CTD and can precede the overt manifestation of a specific connective tissue disease Question: Should serological testing for connective tissues disease be used in the evaluation of suspected IPF?
  • 5. Idiopathic Pulmonary Fibrosis Evidence Based Guidelines for Diagnosis and Management* Recommendation: Serological testing for connective tissue disease should be performed in the evaluation of IPF (weak recommendation, very low quality evidence). (votes : 23 for the use of serological testing, none against, no abstentions) Values: A high value on distinguishing connective tissue disease from IPF and low value on cost. Remarks: – Serological evaluation should be performed even in the absence of signs or symptoms of connective tissue disease( include rheumatoid factor, anti-cyclic citrullinated peptide, and anti-nuclear antibody titer and pattern – The routine use of other serological tests is of unclear benefit Question: Should serological testing for connective tissues disease be used in the evaluation of suspected IPF?
  • 6. Idiopathic Pulmonary Fibrosis Evidence Based Guidelines for Diagnosis and Management* Summary of evidence -Prominent lymphocytosis (>40%) in BAL suggests diagnosis of chronic hypersensitivity pneumonitis -8% of patients with UIP pattern on HRCT may have BAL findings suggestive of dx other than IPF (Ohshimo et al. AJRCCM 2009) -Unclear whether BAL adds significant diagnostic specificity to a careful exposure history and clinical evaluation Question: Should BAL Cellular Analysis be Performed in the Diagnostic Evaluation of Suspected IPF?
  • 7. Idiopathic Pulmonary Fibrosis Evidence Based Guidelines for Diagnosis and Management* Recommendation: BAL cellular analyses should not be performed in the dx evaluation of IPF (weak recommendation; low quality of evidence) (votes : 4 for the use of BAL; 18 against the use of BAL; 1 abstention) Values: High value on additional risk and cost; low value on possible improved specificity of dx Remarks: BAL cellular analysis should be considered at the discretion of the treating physician based on availability and experience at their center Question: Should BAL Cellular Analysis be Performed in the Diagnostic Evaluation of Suspected IPF?
  • 8. Idiopathic Pulmonary Fibrosis Evidence Based Guidelines for Diagnosis and Management* Summary of evidence -the specificity and positive predictive value of UIP pattern identified by transbronchial biopsy has not been rigorously studied. -The sensitivity and specificity of this approach for the diagnosis for UIP pattern is unknown. -it is also unknown how many and from where transbronchial biopsies should be obtained. Question: Should transbronchial lung biopsy be used in the evaluation of suspected IPF?
  • 9. Idiopathic Pulmonary Fibrosis Evidence Based Guidelines for Diagnosis and Management* Recommendation: Trans bronchial biopsy should not be used in the evaluation of IPF (weak recommendation, low quality evidence). (Votes: none for the use of trans bronchial biopsy, 23 against the use of trans bronchial biopsy, no abstentions) Values: This recommendation places a high value on the additional morbidity of trans bronchial lung biopsy in patients with IPF and low value on possible diagnostic specifcity. Question: Should transbronchial lung biopsy be used in the evaluation of suspected IPF?
  • 10. Idiopathic Pulmonary Fibrosis Evidence Based Guidelines for Diagnosis and Management* Usual Interstitial pneumonia (UIP) HRCT images of lung : UIP pattern Consistent with UIP pattern Inconsistent with UIP pattern Histopathology on surgical lung biopsy : UIP pattern Probable UIP pattern Possible UIP pattern Not UIP pattern
  • 11. Idiopathic Pulmonary Fibrosis Evidence Based Guidelines for Diagnosis and Management* UIP Pattern (All four features) Subpleural, basal predominance Reticular abnormality Honeycombing with or without traction bronchiectasis Absence of features listed as inconsistent with UIP pattern HRCT Criteria for UIP Pattern
  • 12. Idiopathic Pulmonary Fibrosis Evidence Based Guidelines for Diagnosis and Management* HRCT Images: UIP Pattern (Extensive honeycombing) A B
  • 13. Idiopathic Pulmonary Fibrosis Evidence Based Guidelines for Diagnosis and Management* D HRCT Images: UIP Pattern (Less severe honeycombing) C
  • 14. Idiopathic Pulmonary Fibrosis Evidence Based Guidelines for Diagnosis and Management* HRCT Images: UIP Pattern (Extensive honeycombing) A C B D HRCT Images: UIP Pattern (Less severe honeycombing) Honeycombing (HRCT) Clustered cystic air spaces Well defined walls Typically comparable diameters (3-10 mm; occasionally as large as 2.5 cm) Sub pleural
  • 15. Idiopathic Pulmonary Fibrosis Evidence Based Guidelines for Diagnosis and Management* Consistent with UIP Pattern (All three features) Subpleural, basal predominance Reticular abnormality Absence of features listed as inconsistent with UIP pattern (NO HONEY COMBING) HRCT Criteria for UIP Pattern
  • 16. Idiopathic Pulmonary Fibrosis Evidence Based Guidelines for Diagnosis and Management* FE HRCT Images: Consistent with UIP pattern (no honeycombing)
  • 17. Idiopathic Pulmonary Fibrosis Evidence Based Guidelines for Diagnosis and Management* HRCT Images: UIP Pattern (Extensive honeycombing) A C B D F E HRCT Images: UIP Pattern (Less severe honeycombing) HRCT Images: Consistent with UIP pattern
  • 18. Idiopathic Pulmonary Fibrosis Evidence Based Guidelines for Diagnosis and Management* Inconsistent with UIP pattern (any of the seven features) – Upper or mid lung predominance – Peribronchovascular predominance – Extensive ground glass abnormality (extent > reticular abnormality – Profuse micro nodules (bilateral, predominantly upper lobes) – Discrete cysts (multiple, bilateral, away from areas of honeycombing) – Diffuse mosaic attenuation/air trapping (bilateral, in 3 or more lobes) – Consolidation in bronchopulmonary segment (s) / lobe(s) HRCT Criteria for UIP Pattern
  • 19. Idiopathic Pulmonary Fibrosis Evidence Based Guidelines for Diagnosis and Management* Surgical Lung Biopsy Specimens: Histopathology of UIP Pattern * Honeycomb spacesPreserved lung tissue Chronic fibrosis Fibroblast focus
  • 20. Idiopathic Pulmonary Fibrosis Evidence Based Guidelines for Diagnosis and Management* Histopathological Criteria for UIP Pattern UIP pattern (all four criteria) – Evidence of marked fibrosis/architectural distortion, +/- honeycombing in a predominantly subpleural/paraseptal distribution – Presence of patchy involvement of lung parenchyma by fibrosis – Presence of fibroblast foci – Absence of features against a diagnosis of UIP suggesting an alternate diagnosis
  • 21. Idiopathic Pulmonary Fibrosis Evidence Based Guidelines for Diagnosis and Management* Histopathological Criteria for UIP Pattern Probable UIP pattern – Evidence of marked fibrosis/architectural distortion, +/- honeycombing in a sub pleural /para septal distribution – Absence of either patchy involvement or fibroblastic foci, but not both – Absence of features against a diagnosis of UIP suggesting an alternate diagnosis OR – Honeycomb changes only** ** This scenario usually represents end-stage fibrotic lung disease where honeycombed segments have been sampled but where a UIP pattern might be present in other areas. Such areas are usually represented by overt honeycombing on HRCT and can be avoided by pre-operative targeting of biopsy sites away from these areas using HRCT.
  • 22. Idiopathic Pulmonary Fibrosis Evidence Based Guidelines for Diagnosis and Management* Histopathological Criteria for UIP Pattern Possible UIP pattern (all three criteria) – Patchy or diffuse involvement of lung parenchyma by fibrosis, with or without interstitial inflammation – Absence of other criteria for UIP – Absence of features against a diagnosis of UIP suggesting an alternate diagnosis
  • 23. Idiopathic Pulmonary Fibrosis Evidence Based Guidelines for Diagnosis and Management* Histopathological Criteria for UIP Pattern Not UIP pattern (any of the six criteria) – Hyaline membranes * – Organizing pneumonia *† – Granulomas † – Marked interstitial inflammatory cell infiltrate away from honeycombing – Predominant airway centered changes – Other features suggestive of an alternate diagnosis * Can be associated with acute exacerbation of IPF † An isolated or occasional granuloma and /or a mild component of organizing pneumonia pattern may rarely be coexisting in lung biopsies with an otherwise UIP pattern
  • 24. Idiopathic Pulmonary Fibrosis Evidence Based Guidelines for Diagnosis and Management* DIAGNOSIS OF IPF : Combination of HRCT and Histopathology requires multidisciplinary discussion (MDD) UIP ** Non-classifiable fibrosis: a pattern of fibrosis that does not meet the above criteria for UIP pattern and the other idiopathic interstitial pneumonias † The accuracy of the diagnosis increases with MDD. This is particularly relevant in cases where the radiologic and histopathologic patterns are discordant (e.g. HRCT is inconsistent with UIP and histopathology is UIP). The accuracy of diagnosis is improved with MDD among interstitial lung disease experts compared to clinician-specialists in the community setting. UIP Probable UIP Possible UIP Non-classifiable fibrosis** Not UIP Yes No HRCT Pattern Histopathology Pattern (when Surgical lung bx performed) Dx of IPF ?†
  • 25. Idiopathic Pulmonary Fibrosis Evidence Based Guidelines for Diagnosis and Management* Consistent with UIP †† MDD among interstitial lung disease experts should include discussions of the potential for sampling error and a re-evaluation of adequacy of technique of HRCT. UIP Probable UIP Possible UIP Non-classifiable fibrosis Not UIP Yes Probable†† No HRCT Pattern Histopathology Pattern (when Surgical lung bx performed) Dx of IPF ? DIAGNOSIS OF IPF : Combination of HRCT and Histopathology requires multidisciplinary discussion (MDD)
  • 26. Idiopathic Pulmonary Fibrosis Evidence Based Guidelines for Diagnosis and Management* Combination of HRCT and surgical lung biopsy for the diagnosis of IPF (requires multidisciplinary discussion) Inconsistent with UIP †† MDD among interstitial lung disease experts should include discussions of the potential for sampling error and a re-evaluation of adequacy of technique of HRCT. UIP Probable UIP Possible UIP Non-classifiable fibrosis Not UIP Possible †† No HRCT Pattern Histopathology Pattern (When surgical lung bx performed) Dx of IPF?
  • 27. Idiopathic Pulmonary Fibrosis Evidence Based Guidelines for Diagnosis and Management* Summary of evidence -the diagnosis of IPF is, by definition, multidisciplinary, drawing on the expertise of experienced clinicians, radiologists, and pathologists. -proper communication between the various disciplines involved in the diagnosis of IPF (pulmonary, radiology, pathology) has been shown to improve inter-observer agreement among experienced clinical experts as to the ultimate diagnosis (Flaherty et al. 2004 and 2007) Question: Should a multi-disciplinary discussion be used in the evaluation of suspected IPF?
  • 28. Idiopathic Pulmonary Fibrosis Evidence Based Guidelines for Diagnosis and Management* Recommendation: A MDD should be used in the evaluation of IPF (strong recommendation, low quality evidence). (Votes: 23 for the use of MDD, none against, no abstentions) Values: A high value on the accurate diagnosis of IPF and a low value on the access to and availability of experts for MDD. Remarks: –It is recognized that a formal MDD between the treating pulmonologist, radiologist and pathologist is not possible for many practitioners. –Effort should be made, however, to promote verbal communication between specialties during the evaluation of the case –Accuracy of diagnosis is improved through MDD among interstitial lung disease (ILD) experts compared to MDD among specialists in the community setting (Flaherty et al. 2007) –Timely referral to ILD experts is encouraged. Question: Should a multi-disciplinary discussion (MDD) be used in the evaluation of suspected IPF?
  • 29. Idiopathic Pulmonary Fibrosis Evidence Based Guidelines for Diagnosis and Management* Exclusion of known causes of ILD (e.g., environmental exposure, connective tissue disease, and drug toxicity UIP pattern or HRCT and/or histopathology (surgical lung biopsy) Or Specific combinations of HRCT and histopathological patterns (surgical lung biopsy) Diagnostic Criteria for IPF
  • 30. Idiopathic Pulmonary Fibrosis Evidence Based Guidelines for Diagnosis and Management* Diagnostic Algorithm for IPF Suspected IPF Identifiable causes for ILD? HRCT Surgical Biopsy MDD IPF/Not IPF per TableIPF Not IPF Yes Not UIP UIP Consistent with UIP Inconsistent with UIP UIP Probable UIP/Possible UIP Non-classifiable fibrosis No
  • 31. Idiopathic Pulmonary Fibrosis Evidence Based Guidelines for Diagnosis and Management* IPF ; natural history is variable and unpredictable Usual interstitial pneumonia (UIP)pattern for both HRCT and histopathology (surgical lung biopsy) features The pattern of UIP : “consistent” and “inconsistent” on HRCT The histopathologic features of “probable”, “possible” patterns for UIP and those that are “not UIP” Summary : Precise Definitions
  • 32. Idiopathic Pulmonary Fibrosis Evidence Based Guidelines for Diagnosis and Management* In the appropriate clinical setting – The diagnosis of IPF is ascertained if the HRCT images reveal pattern of UIP (surgical lung biopsy is not required) – Histological features of UIP in surgical lung biopsy is required for diagnosis of IPF if HRCT images are different than the UIP pattern – Combinations of HRCT and histopathological criteria are required to diagnose and/or exclude IPF – Accuracy of diagnosis increases with multidisciplinary discussions between pulmonologists, radiologists, and pathologists experienced in the diagnosis of ILD Summary : Diagnosis
  • 33. Idiopathic Pulmonary Fibrosis Evidence Based Guidelines for Diagnosis and Management* Natural History of IPF ClinicalCourse Time Stable Slow progression Rapid progression Acute worsening
  • 34. Idiopathic Pulmonary Fibrosis Evidence Based Guidelines for Diagnosis and Management* American Thoracic Society European Respiratory Society Japanese Respiratory Society Latin American Thoracic Association Staffs – University College, Dublin, Ireland – University of Modena and Reggio Emilia, Italy – Mr. Lance Lucas (ATS) Peer Reviewers Community and Academic pulmonologists Acknowledgments