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Hamlet’s DelightNew Guidelines for IPF
CRC 2011
Ted Marras, MD FRCPC
Toronto Western Hospital / University Health Network
Potential conflicts of interestFinancial– Study participation: Actelion, Boehringer-
Ingelheim, Gilead, Intermune– Grant support: CPFF, CIHROther– Clinical and academic interest in ILD
Off label use of therapiesNone of the medications mentioned have a
formal indication for treating IPF
Declarations
Objectives
Considering revised guidelines for idiopathic pulmonary fibrosis (IPF):
1. Consider appropriate investigations and diagnostic algorithm for IPF
2. Select a management strategy that is most appropriate for a given IPF patient
3. Select an appropriate strategy of clinical follow-up for a given IPF patient
IPFWhat is it?• Chronic, progressive fibrosis of the lung• Unknown cause
Why is it bad?• Stiff lung dyspnea• Scarred lung poor gas exchange• Poor prognosis (difficult to quantify)
IPF - HRCTPeripheral, basal predominant:
• Reticulations, interlobular septal thickening, intralobular reticulations• Honeycombing
IPF - Histology = UIP
A) Heterogeneity, traction emphysema
B) Subpleural fibrosis, fibroblast foci
C) Fibroblast focus
D) Microscopic honeycombing
Raghu. Clin Chest Med 2004. 25(4)621-36.
ATS / ERS / JRS / ALATProvide evidence- based recommendations
on diagnosis and management of IPF
Joint Taskforce• 22 Pulmonary physicians
• 4 Chest radiologists • 4 Lung pathologists• 3 Health care librarians• 1 Expert methodologist (respirologist)
Raghu et al. AJRCCM 2011, 183:788-824
Recommendations
Reviewed published data
Recommendations on questions• Direction – yes / no
• Strength – strong / weak • Evidence quality
Voted on by committee members
Objectives
Considering revised guidelines for idiopathic pulmonary fibrosis (IPF):
1. Consider appropriate investigations and diagnostic algorithm for IPF
2. Select a management strategy that is most appropriate for a given IPF patient
3. Select an appropriate strategy of clinical follow-up for a given IPF patient
Diagnosis Excluding Connective Tissue Disease
• Should a CTD serologic evaluation be performed in all people with suspected IPF?
• No reliable data
Diagnosis Excluding Connective Tissue Disease
• Should a CTD serologic evaluation be performed in all people with suspected IPF?
• No reliable data
Question
RecommendationVote
Yes/No/AbsDirection StrengthEvidence
quality
CTD serology?
Yes Weak Very low 23/0/0
Even in absence of overt CTD: RF, anti-CCP, ANA
(ENA – Jo-1, Scl-70, etc. may be helpful)
Diagnosis Utility of BAL / TBBx
• BAL may help differentiate HP• TBBx may help with granulomatous disorders• Should BAL / TBBx be performed in all people with
suspected IPF?
Diagnosis Utility of BAL / TBBx
• BAL may help differentiate HP• TBBx may help with granulomatous disorders• Should BAL / TBBx be performed in all people with
suspected IPF?
Question
RecommendationVote
Yes/No/AbsDirection StrengthEvidence
quality
BAL? No Weak Low 4/18/1
TBBx? No Weak Low 0/23/0
Diagnosis Multi-disciplinary discussion (MDD)
• IPF diagnosis usually requires expertise from clinicians, radiologists, pathologists
• Proper communication increases inter-observer agreement
• Should MDD be used in evaluating suspected IPF?
Diagnosis Multi-disciplinary discussion (MDD)
• IPF diagnosis usually requires expertise from clinicians, radiologists, pathologists
• Proper communication increases inter-observer agreement
• Should MDD be used in evaluating suspected IPF?
Question
RecommendationVote
Yes/No/AbsDirection StrengthEvidence
quality
MDD? Yes Strong Low 0/23/0
• Not possible for many practitioners• Efforts to promote verbal communication should be made
Diagnosis HRCT
Relevant features1. Distribution subpleural / basal predominant2. Reticulation3. Honeycombing + traction bronchiectasis4. Absence of inconsistent features:
– Upper lobe predominant– Peribronchial predominant– GGO > reticulation– Profuse micronodules– Discrete cysts – multiple, bilateral, away from HC– Diffuse mosaicism– Consolidation
Diagnosis HRCT
HRCT classification for suspected IPF• UIP pattern (1,2,3,4)• Possible UIP pattern (1,2,4)• Inconsistent with UIP (4 not fulfilled)
1. Subpleural / basal2. Reticulation3. Honeycombing + traction bronchiectasis4. Absence of inconsistent features
Diagnosis Histology
Relevant features1. Fibrosis + subpleural / paraseptal HC 2. Patchy3. Fibroblast foci4. Absence of inconsistent features:
– Hyaline membranes– Organizing pneumonia– Granulomas– Marked inflammation away from HC– Predominantly airway centred
Diagnosis Histology
Histologic classification for suspected IPF• UIP pattern (1,2,3,4)• Probable UIP pattern (1 and [2 or 3] and 4) or
HC only• Possible UIP pattern (1,4)• Not UIP pattern (4 not fulfilled)
1. Fibrosis + subpleural / paraseptal HC2. Patchy3. Fibroblast foci4. Absence of inconsistent features
Diagnosis HRCT / Histology
HRCT Surgical biopsy IPF?
UIP Not done (clinically typical)
UIP / Probable / Possible
Not UIP
Yes
Yes
No
Consistent with UIP
(lack HC / traction bronchiectasis)
UIP / Probable
Possible UIP
Not UIP
Yes
Probable*
No
Inconsistent with UIP
(inconsistent features)
UIP
All others
Possible*
No
* Multidisciplinary discussion recommended
Diagnosis HRCT / Histology
HRCT Surgical biopsy IPF?
UIP Not done (clinically typical)
Not UIP
Yes
Yes
No
Consistent with UIP
(lack HC / traction bronchiectasis)
UIP / Probable
Possible UIP
Not UIP
Yes
Probable*
No
Inconsistent with UIP
(inconsistent features)
UIP
All others
Possible*
No
* Multidisciplinary discussion recommended
Diagnosis HRCT / Histology
HRCT Surgical biopsy IPF?
UIP Not done (clinically typical)
UIP / Probable / Possible
Not UIP
Yes
Yes
Consistent with UIP
(lack HC / traction bronchiectasis)
UIP / Probable
Possible UIP
Not UIP
Yes
Probable*
No
Inconsistent with UIP
(inconsistent features)
UIP
All others
Possible*
No
* Multidisciplinary discussion recommended
Diagnosis HRCT / Histology
HRCT Surgical biopsy IPF?
UIP Not done (clinically typical)
UIP / Probable / Possible
Not UIP
Yes
Yes
No
Consistent with UIP
(lack HC / traction bronchiectasis)
UIP / Probable
Possible UIP
Not UIP
Yes
Probable*
No
Inconsistent with UIP
(inconsistent features)
UIP
All others
Possible*
No
* Multidisciplinary discussion recommended
Diagnosis HRCT / Histology
HRCT Surgical biopsy IPF?
UIP Not done (clinically typical)
UIP / Probable / Possible
Not UIP
Yes
Yes
No
Possible UIP
(lack HC)
UIP / Probable
Possible UIP
Not UIP
Yes
Probable*
No
Inconsistent with UIP
(inconsistent features)
UIP
All others
Possible*
No
* Multidisciplinary discussion recommended
Diagnosis HRCT / Histology
HRCT Surgical biopsy IPF?
UIP Not done (clinically typical)
UIP / Probable / Possible
Not UIP
Yes
Yes
No
Possible UIP
(lack HC)
UIP / Probable
Possible UIP
Not UIP
Yes
Probable*
No
Inconsistent with UIP
(inconsistent features)
UIP
All others
Possible*
No
* Multidisciplinary discussion recommended
Diagnosis HRCT / Histology
HRCT Surgical biopsy IPF?
UIP Not done (clinically typical)
UIP / Probable / Possible
Not UIP
Yes
Yes
No
Possible UIP
(lack HC)
UIP / Probable
Possible UIP
Not UIP
Yes
Probable*
No
Inconsistent with UIP
(inconsistent features)
UIP
All others
Possible*
No
* Multidisciplinary discussion recommended
Diagnosis HRCT / Histology
HRCT Surgical biopsy IPF?
UIP Not done (clinically typical)
UIP / Probable / Possible
Not UIP
Yes
Yes
No
Possible UIP
(lack HC)
UIP / Probable
Possible UIP
Not UIP
Yes
Probable*
No
Inconsistent with UIP
(inconsistent features)
UIP
All others
Possible*
No
* Multidisciplinary discussion recommended
Diagnosis HRCT / Histology
HRCT Surgical biopsy IPF?
UIP Not done (clinically typical)
UIP / Probable / Possible
Not UIP
Yes
Yes
No
Possible UIP
(lack HC)
UIP / Probable
Possible UIP
Not UIP
Yes
Probable*
No
Inconsistent with UIP
(inconsistent features)
UIP
All others
Possible*
No
* Multidisciplinary discussion recommended
Diagnosis HRCT / Histology
HRCT Surgical biopsy IPF?
UIP Not done (clinically typical)
UIP / Probable / Possible
Not UIP
Yes
Yes
No
Possible UIP
(lack HC)
UIP / Probable
Possible UIP
Not UIP
Yes
Probable*
No
Inconsistent with UIP
(inconsistent features)
UIP
All others
Possible*
No
* Multidisciplinary discussion recommended
DiagnosisSuspected IPF
Identifiable cause? Not IPFyes
no
HRCT
IPF
UIP
possible UIP or inconsistent with UIP
Surgical Biopsy
DiagnosisSuspected IPF
Identifiable cause? Not IPFyes
no
HRCT
IPF
UIP
possible UIP or inconsistent with UIP
Surgical Biopsy
Not UIP
DiagnosisSuspected IPF
Identifiable cause? Not IPFyes
no
HRCT
IPF
UIP
possible UIP or inconsistent with UIP
Surgical Biopsy
Not UIP
UIP, probable, possible
See table
Objectives
Considering revised guidelines for idiopathic pulmonary fibrosis (IPF):
1. Consider appropriate investigations and diagnostic algorithm for IPF
2. Select a management strategy that is most appropriate for a given IPF patient
3. Select an appropriate strategy of clinical follow-up for a given IPF patient
Treatment
RecommendationVote
Yes/No/AbsDirection StrengthEvidence
quality
Steroids alone No Strong Very low 0 / 21 / 2
Colchicine No Strong Very low 0 / 21 / 2
Cyclosporine No Strong Very low 0 / 18 / 4
Steroid + Aza / CY No Strong Low 0 / 21 / 2
Steroid + Aza + NAC No Weak Low 3 / 17 / 3
NAC alone No Weak Low 5 / 15 / 3
IFN gamma No Strong High 0 / 17 / 6
Bosentan No Strong Moderate 0 / 10 / 13
Etanercept No Strong Moderate 0 / 18 / 4
Anticoagulation No Weak Very low 1 / 20 / 2
Pirfenidone No Weak Low-mod 4 / 10 / 17
IPF Treatment
Treatment
RecommendationVote
Yes/No/AbsDirection StrengthEvidence
quality
Steroids alone No Strong Very low 0 / 21 / 2
Colchicine No Strong Very low 0 / 21 / 2
Cyclosporine No Strong Very low 0 / 18 / 4
Steroid + Aza / CY No Strong Low 0 / 21 / 2
Steroid + Aza + NAC No Weak Low 3 / 17 / 3
NAC alone No Weak Low 5 / 15 / 3
IFN gamma No Strong High 0 / 17 / 6
Bosentan No Strong Moderate 0 / 10 / 13
Etanercept No Strong Moderate 0 / 18 / 4
Anticoagulation No Weak Very low 1 / 20 / 2
Pirfenidone No Weak Low-mod 4 / 10 / 17
IPF Treatment
Treatment
RecommendationVote
Yes/No/AbsDirection StrengthEvidence
quality
Steroids alone No Strong Very low 0 / 21 / 2
Colchicine No Strong Very low 0 / 21 / 2
Cyclosporine No Strong Very low 0 / 18 / 4
Steroid + Aza / CY No Strong Low 0 / 21 / 2
Steroid + Aza + NAC* No Weak Low 3 / 17 / 3
NAC alone No Weak Low 5 / 15 / 3
IFN gamma No Strong High 0 / 17 / 6
Bosentan No Strong Moderate 0 / 10 / 13
Etanercept No Strong Moderate 0 / 18 / 4
Anticoagulation No Weak Very low 1 / 20 / 2
Pirfenidone No Weak Low-mod 4 / 10 / 17
IPF Treatment
* Small physiologic benefit, may have significant toxicities
Treatment
RecommendationVote
Yes/No/AbsDirection StrengthEvidence
quality
Steroids alone No Strong Very low 0 / 21 / 2
Colchicine No Strong Very low 0 / 21 / 2
Cyclosporine No Strong Very low 0 / 18 / 4
Steroid + Aza / CY No Strong Low 0 / 21 / 2
Steroid + Aza + NAC No Weak Low 3 / 17 / 3
NAC alone* No Weak Low 5 / 15 / 3
IFN gamma No Strong High 0 / 17 / 6
Bosentan No Strong Moderate 0 / 10 / 13
Etanercept No Strong Moderate 0 / 18 / 4
Anticoagulation No Weak Very low 1 / 20 / 2
Pirfenidone No Weak Low-mod 4 / 10 / 17
IPF Treatment
* Limited data, safe, maybe cheap; preparation not standardized
Treatment
RecommendationVote
Yes/No/AbsDirection StrengthEvidence
quality
Steroids alone No Strong Very low 0 / 21 / 2
Colchicine No Strong Very low 0 / 21 / 2
Cyclosporine No Strong Very low 0 / 18 / 4
Steroid + Aza / CY No Strong Low 0 / 21 / 2
Steroid + Aza + NAC No Weak Low 3 / 17 / 3
NAC alone No Weak Low 5 / 15 / 3
IFN gamma No Strong High 0 / 17 / 6
Bosentan No Strong Moderate 0 / 10 / 13
Etanercept No Strong Moderate 0 / 18 / 4
Anticoagulation* No Weak Very low 1 / 20 / 2
Pirfenidone No Weak Low-mod 4 / 10 / 17
IPF Treatment
* Supportive study, several limitations
Treatment
RecommendationVote
Yes/No/AbsDirection StrengthEvidence
quality
Steroids alone No Strong Very low 0 / 21 / 2
Colchicine No Strong Very low 0 / 21 / 2
Cyclosporine No Strong Very low 0 / 18 / 4
Steroid + Aza / CY No Strong Low 0 / 21 / 2
Steroid + Aza + NAC No Weak Low 3 / 17 / 3
NAC alone No Weak Low 5 / 15 / 3
IFN gamma No Strong High 0 / 17 / 6
Bosentan No Strong Moderate 0 / 10 / 13
Etanercept No Strong Moderate 0 / 18 / 4
Anticoagulation No Weak Very low 1 / 20 / 2
Pirfenidone No Weak Low-mod 4 / 10 / 17
IPF Treatment
Treatment
RecommendationVote
Yes/No/AbsDirection StrengthEvidence
quality
Steroids alone No Strong Very low 0 / 21 / 2
Colchicine No Strong Very low 0 / 21 / 2
Cyclosporine No Strong Very low 0 / 18 / 4
Steroid + Aza / CY No Strong Low 0 / 21 / 2
Steroid + Aza + NAC No Weak Low 3 / 17 / 3
NAC alone No Weak Low 5 / 15 / 3
IFN gamma No Strong High 0 / 17 / 6
Bosentan No Strong Moderate 0 / 10 / 13
Etanercept No Strong Moderate 0 / 18 / 4
Anticoagulation No Weak Very low 1 / 20 / 2
Pirfenidone No Weak Low-mod 4 / 10 / 17
IPF Treatment
Treatment
RecommendationVote
Yes/No/AbsDirection StrengthEvidence
quality
Steroids alone No Strong Very low 0 / 21 / 2
Colchicine No Strong Very low 0 / 21 / 2
Cyclosporine No Strong Very low 0 / 18 / 4
Steroid + Aza / CY No Strong Low 0 / 21 / 2
Steroid + Aza + NAC No Weak Low 3 / 17 / 3
NAC alone No Weak Low 5 / 15 / 3
IFN gamma No Strong High 0 / 17 / 6
Bosentan No Strong Moderate 0 / 10 / 13
Etanercept No Strong Moderate 0 / 18 / 4
Anticoagulation No Weak Very low 1 / 20 / 2
Pirfenidone No Weak Low-mod 4 / 10 / 17
IPF Treatment
Treatment
RecommendationVote
Yes/No/AbsDirection StrengthEvidence
quality
Steroids alone No Strong Very low 0 / 21 / 2
Colchicine No Strong Very low 0 / 21 / 2
Cyclosporine No Strong Very low 0 / 18 / 4
Steroid + Aza / CY No Strong Low 0 / 21 / 2
Steroid + Aza + NAC No Weak Low 3 / 17 / 3
NAC alone No Weak Low 5 / 15 / 3
IFN gamma No Strong High 0 / 17 / 6
Bosentan No Strong Moderate 0 / 10 / 13
Etanercept No Strong Moderate 0 / 18 / 4
Anticoagulation No Weak Very low 1 / 20 / 2
Pirfenidone No Weak Low-mod 4 / 10 / 17
IPF Treatment
Treatment
RecommendationVote
Yes/No/AbsDirection StrengthEvidence
quality
Pulmonary rehabilitation
Yes Weak Low 19 / 0 / 3
Oxygen Yes Strong Very low 18 / 0 / 4
Transplantation Yes Strong Low 21 / 0 / 1
“Nonpharmacologic” Treatment
Transplant Who to consider?Discuss at diagnosis
Detailed evaluation:• Advanced at diagnosis• With objective deterioration
Transplant Who to consider?
Baseline• Severe dyspnea• DLCO<40%• 6MW SaO2 < 88%• Extensive HC on HRCT
Longitudinal• Increasing dyspnea• FVC decrease >10%*• DLCO decrease >15%*• Progression on HRCT
Discuss at diagnosis
Detailed evaluation:• Advanced at diagnosis• With objective deterioration
* Absolute measure
AEIPF - Definition• “Acute, clinically significant deterioration of
unidentifiable cause in a patient with underlying IPF”
Diagnostic Criteria• IPF with unexplained worsening < 30 days• HRCT new bilateral GGO and/or consolidation
superimposed on typical IPF pattern• No infection by tracheal aspirate or BAL• Exclude: CHF, PE, identifiable acute lung injury
cause
Additional Treatment- Acute exacerbations
Treatment
RecommendationVote
Yes/No/AbsDirection StrengthEvidence
quality
Steroids in AEIPF Yes Weak Very Low 14 / 5 / 1
Mechanical ventilation
No Weak Low 2 / 19 / 1
Pulmonary hypertension
No Weak Very low 8 / 14 / 1
Asymptomatic GERD
Yes Weak Very low 15 / 8 / 0
Additional Treatment
Objectives
Considering revised guidelines for idiopathic pulmonary fibrosis (IPF):
1. Consider appropriate investigations and diagnostic algorithm for IPF
2. Select a management strategy that is most appropriate for a given IPF patient
3. Select an appropriate strategy of clinical follow-up for a given IPF patient
Monitoring for progression
Routine PFT• Sustained change in absolute:
– FVC of 10% (e.g. 2L1.8L)*– DLCO of 15%
(Both associated with mortality, suggestive of progression)
• *Smaller progressive, sustained changes MAY be relevant (e.g. 5-10% FVC decline)
Recommended