biopsy is necessary for the diagnosis of ipf
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Biopsy is necessary for the diagnosis of IPF. Nesrin Moğulkoç Pulmonary Medicine. A TS /E RS International Multidisciplinary Consensus Classification Of Idiopathic Interstitial Pneumonias General Principles and Recommendations. Co-chairs: William D. Travis, M.D. - PowerPoint PPT PresentationTRANSCRIPT
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Biopsy is Biopsy is necessarynecessary for the for the diagnosis of IPFdiagnosis of IPF
NesrinNesrin MoğulkoçMoğulkoç
Pulmonary Medicine
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AATSTS/E/ERSRS International International Multidisciplinary Consensus Multidisciplinary Consensus
Classification Of Idiopathic Interstitial Classification Of Idiopathic Interstitial PneumoniasPneumonias
General Principles and RecommendationsGeneral Principles and Recommendations
Co-chairs: William D. Travis, M.D.
Talmadge King, Jr. M.D.
Am J Respir Crit Care Med 2002; 165: 277
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DPLD of known cause (e.g. drugs, dust exposure, collagen vasculardisease)
Idiopathic interstitial
pneumonias
Granulomatous DPLD (e.g. sarcoidosis)
Other forms of DPLD(e.g. LAM, HX, eosin. pneum.)
Diffuse Parenchymal Lung Disease
Idiopathic Iinterstitial Pneumonia other than IPF
Idiopathicpulmonary
fibrosis (IPF)
Desquamative interstitialpneumonia (DIP)
Acute interstitial pneumonia (AIP)
Lymphocytic interstitialpneumonia (LIP)
Nonspecific interstitialpneumonia (NSIP)
Cryptogenic organisingpneumonia (COP)
Respiratory bronchiolitis/Interst. lung dis. (RBILD)
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SeriesSeries IPF NSIP DIP/RBILD COPIPF NSIP DIP/RBILD COP
Bjoraker et al. 62% 14% 10% 2%1998
Nagai et al. 58% 28% - 14%1998
Travis et al. 55% 29% 16% -2000
Nicholson et al. 47% 36% 17% -2000
Proportion of patients with IPF, NSIP, Proportion of patients with IPF, NSIP, DIP/RBILD and COP among IIPsDIP/RBILD and COP among IIPs
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DPLD of known cause (e.g. drugs, dust exposure, collagen vasculardisease)
Idiopathic interstitial
pneumonias
Granulomatous DPLD (e.g. sarcoidosis)
Other forms of DPLD(e.g. LAM, HX,
eosin. pneum. etc.)
Diffuse Parenchymal Lung Disease
IIP other thanidiopathic
pulmonary fibrosis
Idiopathicpulmonary
fibrosis (IPF)
Desquamative interstitialpneumonia (DIP)
Acute interstitial pneumonia (AIP)
Lymphocytic interstitialpneumonia (LIP)
Nonspecific interstitialpneumonia (NSIP)
Cryptogenic organisingpneumonia (COP)
Respiratory bronchiolitis/Interst. lung dis. (RBILD)
%40-50%40-50
%47-64%47-64
%14-36%14-36
%10-17%10-17
%4-12%4-12<%2<%2
<%2<%2
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tto provide a specific diagnosiso provide a specific diagnosis
Biopsy is Biopsy is necessarynecessary in IPF in IPF
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History, physical exam, clinical chemistry, PFT, Chest Xray
Not IIP Possible IIP
HRCT
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Septal thickeningSeptal thickening
Irregular Irregular reticularreticular / / linear opacitieslinear opacities
Cystic airspacesCystic airspaces / / honeycombinghoneycombing
NodulesNodules
Ground-glass attentuationGround-glass attentuation
ConsolidationConsolidation
HRCTHRCTPathologyPathology
Lymphangitis carcinomatosaLymphangitis carcinomatosa
LymphomaLymphoma
SarcoidosisSarcoidosis
UIPUIP
Collagen vascular diseaseCollagen vascular disease
AsbestosisAsbestosis
Hypersensitivity pneumonitisHypersensitivity pneumonitis
LymphangioleiomyomatosisLymphangioleiomyomatosis
Langerhans’ cell histiocytosisLangerhans’ cell histiocytosis
Miliary TBMiliary TB
Fungal infectionFungal infection
DIPDIP
LIPLIP
Alveolar proteinosisAlveolar proteinosis
Chronic eosinophilic pneumoniaChronic eosinophilic pneumonia
BOOP/COPBOOP/COP
DAD/ARDSDAD/ARDS
NSIPNSIP
RB/ILDRB/ILD
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History, physical exam, clinical chemistry, PFT, Chest Xray
HRCT
Typical of IPF (~50%) ∅ IPF (~50%) suggestive of Other ILD ? specific ILD
Not IIP Possible IIP
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HRCT Criteria of IPFHRCT Criteria of IPF1. Reticular abnormality and/or traction
bronchiectasis with basal and peripheral predominance
2. Honeycombing with basal and peripheral predominance
3. Atypical features are absent – Micronodules are not present– Peribronchovascular nodules are not present– Consolidation is not present– Ground glass attenuation, if present, is less extensive than
reticular opacity – Mediastinal adenopathy, if present, is not extensive enough to be
visible on chest X-ray
Definite IPF: all 3 are metProbable IPF: 1 and 3 are met
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UIP: Progression UIP: Progression oof Fibrosis f Fibrosis oon n HRHRCCTT
Early:Early:
ReticularReticular
Late:Late:ExtensiveExtensive
HoneycombingHoneycombingModerate:Moderate:SubpleuralSubpleural
HoneycombingHoneycombing
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Honeycombing
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Honeycombing (5%)
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Honeycombing (5%)
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Rating of κ scores
Landis JR, Koch GG. 1977
agreement κ score
•perfect
•substantial
•moderate
•fair
•slight
•poor
> 0.8
0.6 - 0.8
0.4 - 0.6
0.2 - 0.4
0.0 - 0.2
= 0.0
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Kappa coefficients of agreement between 11 radiologists for HRCT diagnosis
(Aziz et al. Thorax 2004)
DiagnosisDiagnosisKappa Kappa ((of first choiceof first choice
diagnosisdiagnosis))
IPFIPF 0.500.50
NSIPNSIP 0.380.38
RBILD/DIPRBILD/DIP 0.300.30
COPCOP 0.370.37
EAAEAA 0.590.59
SarcoidosisSarcoidosis 0.620.62
OverallOverall 0.480.48
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Accuracy of Clinical & Radiological Diagnosis of IPF
• 59 patients with surgical biopsies
• clinical diagnosis or radiological diagnosis
• clinical diagnosis of IPF
- 97% specific
- 62% sensitive
• HRCT diagnosis of IPF
- 90% specific
- 79% sensitive Raghu et al, 1999
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Accuracy of HRCT Diagnosis in IPF
A confident diagnosis is made in only about two-thirds of patients with IPF
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History, physical exam, clinical chemistry, PFT, Chest Xray
HRCT
Typical of IPF (~50%) ∅ IPF (~50%) suggestive of Other ILD ? specific ILD
Ø IPF No TBBx TBBx TBBx diagnosis BAL BAL BAL
Surgical lung biopsy (3 locations, min. 2cm3)
UIP NSIP RB-ILD DIP DAD COP LIP ∅ IIP
Not IIP Possible IIP
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tto assess disease activityo assess disease activity
Biopsy is Biopsy is necessarynecessary in IPF in IPF
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UIP: fibroblast foci
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• Extent Of Fibroblastic foci Predict Mortality In Idiopathic Pulmonary Fibrosis T.E. King Jr., AJRCCM 2001:164;1025-32.
• The frequency of fibroblastic foci in usual interstitial pneumonia and their relationship to disease progression Nicholson AG, AJRCCM 2002; 166: 173-7.
• Relationship between histopathologic features and course of IPF/UIP Titto L, Thorax 2006:61:1091-5.
Fibroblastic foci in UIP
Site of initial injury that triggers fibrosing process?
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Survival in IPF patients categorised by fibroblastic Survival in IPF patients categorised by fibroblastic foci score in the lung biopsyfoci score in the lung biopsy
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tto o predict prognosis and to predict prognosis and to identify a identify a more treatable process than more treatable process than
originally suspectedoriginally suspected
Biopsy is Biopsy is necessarynecessary in IPF in IPF
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IPF: worst case of an ILD
100
Bjoraker JA Am J Respir Crit Care Med. 1998;157:199
80
60 Other
40 NSIP
20
IPF
0 0 2 4 6 8 10 12 14 16 18
Years
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Flaherty et al., Thorax, 2003
0 6 8 102 4
0
20
40
60
80
100 BBypyp=NSIP &=NSIP &HRCT=NSIP/HRCT=NSIP/UdtmUdtm
BBypyp=UIP &=UIP &, , HRCT=NSIP/HRCT=NSIP/UdtmUdtm
BBypyp=UIP &=UIP &HRCT=UIPHRCT=UIP
Follow up Time (years)
Cum
ulat
ive
prop
ortio
n su
rviv
ing
BBx-Diagnosisx-Diagnosis::NSIP: n = 23, UIP: n = 73
HRCTHRCT-Diagnosis:-Diagnosis:NSIP: n = 44, UIP: n = 27
Udtm: n = 25
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UIP pattern (histology vs HRCT) Flaherty et al Thorax 2003
• HRCT UIP 2.08• SLBx UIP 3.99• SLBx of UIP and HRCT of other/NSIP 5.76• HRCT of NSIP and SLBx of NSIP >9
• Pattern of UIP on HRCT or Bx = poorer prognosis in IPF
(median survival in years)
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to rto recognise ecognise purerpurer cohorts of cohorts of patients with regard patients with regard
investigation of cause and investigation of cause and treatment strategiestreatment strategies
Biopsy is Biopsy is necessarynecessary in IPF in IPF
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‘Importance of the lung biopsy for drug trials’
Stricter criteria for IPF, greater
understanding of the ‘entity’ NSIP and
problems with overlap, need for confident
diagnosis of UIP/IPF for international drug
trials
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Biopsy may be Biopsy may be necessarynecessary in in ILDILD
tto exclude neoplastic and o exclude neoplastic and infectious processes that infectious processes that
occasionally mimic chronic, occasionally mimic chronic, progressive interstitial diseaseprogressive interstitial disease
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Conditions mistaken for ILD
• Infection
• Cancer– Lymphoma– BAC– lymphangitis carcinomatosa
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Am J Respir Crit Care Med Vol 170. pp 904–910, 2004
Does the interactive diagnostic process improve Does the interactive diagnostic process improve the interobserver agreement?the interobserver agreement?
Idiopathic Interstitial PneumoniaWhat Is the Effect of a Multidisciplinary Approach to Diagnosis?
Kevin R. Flaherty, Talmadge E. King, Jr., Ganesh Raghu, Joseph P. Lynch III, Thomas V. Colby,William D. Travis, Barry H. Gross, Ella A. Kazerooni, Galen B. Toews, Qi Long, Susan Murray,Vibha N. Lama, Steven E. Gay, and Fernando J. Martinez
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Information provided
Type of decision
Participants Output
Step 1 HRCT InvidualCliniciansClinicians
RadiologistsRadiologistsFirst Diagnosis & Confidence
Step 2HRCT +
clinical dataInvidual
CliniciansClinicians
RadiologistsRadiologistsDiagnosis & Diagnosis & ConfidenceConfidence
Step 3HRCT +
clinical dataGroup
CliniciansClinicians
RadiologistsRadiologistsDiagnosis & Diagnosis & ConfidenceConfidence
Step 4
HRCT +
clinical data + surgical biopsy
Group
CliniciansClinicians
RadiologistsRadiologists
Pathologists
Diagnosis & Diagnosis & ConfidenceConfidence
Step 5HRCT+
clinical data + surgical biopsy
Group
CliniciansClinicians
RadiologistsRadiologists
Pathologists
Consensus Consensus Diagnosis & Diagnosis & ConfidenceConfidence
Organisational Scheme(Review of 58 cases)
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Interobserver agreement at each diagnostic step
Step
Clinicians
[κ (95% CI) ]
Radiologists
[ κ (95% CI)]
Clinicians–Radiologists
[κ (95% CI)]
All Observers
[κ (95% CI)]
1 0.41 (0.29, 0.52) 0.72 (0.57, 0.86) 0.39 (0.29, 0.49) NA
2 0.51 (0.37, 0.64) 0.80 (0.67, 0.93) 0.44 (0.34, 0.54) NA
3 0.67 (0.54, 0.79) 0.78 (0.65, 0.91) 0.55 (0.44, 0.66) NA
4 0.75 (0.64, 0.86) 0.84 (0.72, 0.96) 0.78 (0.70, 0.86) 0.79 (0.71, 0.86)
5 0.86 (0.76, 0.95) 0.90 (0.80, 0.99) 0.88 (0.81, 0.96) 0.88 (0.81, 0.94)
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Interobserver agreement at each diagnostic step
Step
Clinicians
[κ (95% CI) ]
Radiologists
[ κ (95% CI)]
Clinicians–Radiologists
[κ (95% CI)]
All Observers
[κ (95% CI)]
1 0.41 (0.29, 0.52) 0.72 (0.57, 0.86) 0.39 (0.29, 0.49) NA
2 0.51 (0.37, 0.64) 0.80 (0.67, 0.93) 0.44 (0.34, 0.54) NA
3 0.67 (0.54, 0.79) 0.78 (0.65, 0.91) 0.55 (0.44, 0.66) NA
4 0.75 (0.64, 0.86) 0.84 (0.72, 0.96) 0.78 (0.70, 0.86) 0.79 (0.71, 0.86)
5 0.86 (0.76, 0.95) 0.90 (0.80, 0.99) 0.88 (0.81, 0.96) 0.88 (0.81, 0.94)
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AJRCCM 2007; 175: 1054 – 1060
Idiopathic Interstitial PneumoniaDo Community and Academic Physicians
Agree on Diagnosis?
Kevin R. Flaherty, Adin-Cristian Andrei, Talmadge E. King, Jr., Ganesh Raghu, Thomas V. Colby, Athol Wells, Nadir Bassily, Kevin Brown, Roland
du Bois, Andrew Flint, Steven E. Gay, Barry H. Gross, Ella A. Kazerooni, Robert Knapp, Edmund Louvar, David Lynch, Andrew G. Nicholson, John Quick, Victor J. Thannickal, William D. Travis, James Vyskocil, Frazer A.
Wadenstorer, Jeffrey Wilt, Galen B. Toews, Susan Murray, and Fernando J. Martinez
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Final Diagnosis Agreement:Different among Community/Academic
Physicians?
Flaherty KR, et al. AJRCCM 2007; 175: 1054
• n = 39 pat. with ILD, retrospective review
• Agreement in final diagnosis among 6 groups
academic/community
clinicians/radiologists/pathologists
• Final agreement was better within academic
centers (kappa = 0.55 to 0.71) than within
community centers (kappa = 0.32 to 0.44)
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Surgical Lung BiopsySpecial risk in IPF!
• 60 pat with UIP (46 idiopathic, 14 associated with collagen/vasc dis) from Mayo Clinic 1986 - 1995
• 10/60 (=17%) died within 30 days after surgical biopsy
3/16 (19%) after VATS
7/44 (16%) after thoracotomy and biopsy
• All 10 who died had IPF, 5 of these were biopsied for accelerated progress
Utz et al, ERJ 2001; 17: 175
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Mortality and Risk Factors for Surgical Lung Biopsy in IIP
• 200 pat. with IIP (140 IPF, 46 NSIP, 14 COP), retrospective study
• 4.3% died within 30 days after surgical biopsy, no difference between VATS or OLB
no difference between IPF and other IIPs
• Biopsy at time of acute exacerbation: mortality 29% vs 3%
• DLCO<50%: mortality 11% vs 1.4% Park JH et al, Eur J Cardiothorac Surg 2007
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sarcoid
UIP
NSIP
EAAother
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sarcoid
UIP
NSIP
EAAother
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sarcoid
UIP
NSIP
EAAother
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UIP
NSIP
EAAother
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UIP
NSIP
EAAother
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UIP: HRCTUIP
NSIP
EAAother
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UIP: HRCT
UIP
NSIP
EAAother
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UIP: HRCT
UIP
NSIP
EAAotherLCH
LAM
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UIP
NSIP
EAAother
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Biopsy is Biopsy is necessarynecessary for the for the diagnosis of IPFdiagnosis of IPF
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