Hamlet’s Delight New Guidelines for IPF CRC 2011 Ted Marras, MD FRCPC Toronto Western Hospital / University Health Network

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.

Raghu AJRCCM 183.788-824. 2011

IPF - Natural history

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

Recommendations


Recommendations


Objectives





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


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


quality

MDD? Yes Strong Low 0/23/0

• Not possible for many practitioners• Efforts to promote verbal communication should be made

Diagnosis

Consider:• Clinical

• Radiology - HRCT

• Histology - surgical lung biopsy

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




Not UIP

Yes

Yes

No

Consistent with UIP


UIP / Probable

Possible UIP

Not UIP

Yes

Probable*

No



UIP

All others

Possible*

No






Not UIP

Yes

Yes

Consistent with UIP


UIP / Probable

Possible UIP

Not UIP

Yes

Probable*

No



UIP

All others

Possible*

No






Not UIP

Yes

Yes

No

Consistent with UIP


UIP / Probable

Possible UIP

Not UIP

Yes

Probable*

No



UIP

All others

Possible*

No






Not UIP

Yes

Yes

No

Possible UIP

(lack HC)

UIP / Probable

Possible UIP

Not UIP

Yes

Probable*

No



UIP

All others

Possible*

No






Not UIP

Yes

Yes

No

Possible UIP

(lack HC)

UIP / Probable

Possible UIP

Not UIP

Yes

Probable*

No



UIP

All others

Possible*

No






Not UIP

Yes

Yes

No

Possible UIP

(lack HC)

UIP / Probable

Possible UIP

Not UIP

Yes

Probable*

No



UIP

All others

Possible*

No






Not UIP

Yes

Yes

No

Possible UIP

(lack HC)

UIP / Probable

Possible UIP

Not UIP

Yes

Probable*

No



UIP

All others

Possible*

No






Not UIP

Yes

Yes

No

Possible UIP

(lack HC)

UIP / Probable

Possible UIP

Not UIP

Yes

Probable*

No



UIP

All others

Possible*

No






Not UIP

Yes

Yes

No

Possible UIP

(lack HC)

UIP / Probable

Possible UIP

Not UIP

Yes

Probable*

No



UIP

All others

Possible*

No


DiagnosisSuspected IPF

Identifiable cause? Not IPFyes



no

HRCT

IPF

UIP



no

HRCT

IPF

UIP

possible UIP or inconsistent with UIP

Surgical Biopsy



no

HRCT

IPF

UIP


Surgical Biopsy

Not UIP



no

HRCT

IPF

UIP


Surgical Biopsy

Not UIP

UIP, probable, possible

See table

Objectives





Treatment

RecommendationVote


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


quality












IPF Treatment

Treatment

RecommendationVote


quality





Steroid + Aza + NAC* No Weak Low 3 / 17 / 3







IPF Treatment

* Small physiologic benefit, may have significant toxicities

Treatment

RecommendationVote


quality






NAC alone* No Weak Low 5 / 15 / 3






IPF Treatment

* Limited data, safe, maybe cheap; preparation not standardized

Treatment

RecommendationVote


quality










Anticoagulation* No Weak Very low 1 / 20 / 2


IPF Treatment

* Supportive study, several limitations

Treatment

RecommendationVote


quality












IPF Treatment

Treatment

RecommendationVote


quality












IPF Treatment

Treatment

RecommendationVote


quality












IPF Treatment

Treatment

RecommendationVote


quality












IPF Treatment

Treatment

RecommendationVote


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


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





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)

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)

6MW distance / oximetry too variable over long time periods (good discriminative test, not a good evaluative test)

Documents

Hamlet’s Delight New Guidelines for IPF CRC 2011 Ted Marras, MD FRCPC Toronto Western Hospital / University Health Network