Chai Gin Tsen Dept of Respiratory and Critical Care Medicine Chai Gin Tsen Dept of Respiratory and Critical Care Medicine . Scope •Introduction •Classification of interstitial

Advances in Interstitial lung

disease - New disease

perspectives

Chai Gin Tsen

Dept of Respiratory and Critical Care Medicine

Scope

• Introduction

• Classification of interstitial lung disease (ILD)/diffuse lung disease

• Idiopathic pulmonary fibrosis (IPF) – diagnosis and treatment

• Issues with ILD guidelines

• Disease behaviour classification

• Case studies

• Summary

Scope

• We are not going to talk about specific ILD

entities

• Introduce a different way to approach this group

of complicated disease entities

Introduction

• Please forget about these terms:

– Pulmonary fibrosis

– Fibrosing alveolitis

• Group of disease that affects the lung

parenchyma diffusely, which includes PCP,

miliary TB, lymphangitis carcinomatosis or

ARDS

• Not all ILDs have fibrosis

• Instead use the phrase interstitial lung disease

(ILD) or diffuse lung disease

Old classification - 2002

AJRCCM 2002

Old classification - 2002

AJRCCM 2002

Travis W et al. AJRCCM 2013

Revised criteria 2013

Idiopathic interstitial pneumonia

(IIP) • The key issue is to differentiate idiopathic

pulmonary fibrosis (IPF) from the rest

• Diagnosis is prognosis

C Ryerson ERJ 2013

Idiopathic Pulmonary Fibrosis

(IPF)

Changes in IPF diagnosis over

the years 1999 ATS guidelines

All major + 3 out of 4 minor (No SLBx)

2011 ATS guidelines

HRCT features – usual

interstitial pneumonia (UIP)

2011 ATS/ERS/JRS/ALAT IPF guidelines

2011 ATS/ERS/JRS/ALAT IPF guidelines

IPF Treatment 1999 ATS IPF guidelines 2011 ATS/ERS/JRS/ALAT IPF guidelines

2012: In comes the PANTHER

Combination of prednisolone + azathioprine + NAC

vs

placebo

Raghu G et al. NEJM 2012

CAPACITY

P Noble et al. Lancet 2011

ASCEND

King TE et al. NEJM 2014

A New Hope: Pirfenidone vs

placebo trials

IMPULSIS: Nintedanib vs

placebo

Richeldi L et al. NEJM 2014

2015 ATS/ERS/JRS/ALAT updated IPF guidelines

Diagnosis of ILD

How do we diagnose and

manage ILD in 2016?

A. HRCT provides “truth data”. Other clinical information has no role

B. Biopsy all patients: therein lies the truth. Clinical reasoning has no role

C. View all IIP as essentially the same disorder and treat with steroids

D. Apply guidelines and treat according to recommendations

E. I disagree with all of the above

Traditional approach

Why traditional guidelines fail in

ILD? 1. Unlike medical oncology or pulmonary

hypertension, there is no gold standard in

diagnosing many ILDs

2. Up to 5-15% of ILDs are “unclassifiable” even

in expert centres. (CJ Ryerson et al. ERJ

2013; Skolnik K et al. Respirology 2015)

3. Confusing terminology

Walsh S et al. Lancet Respir Med 2016

Pathological dx of IPF is not the

gold standard

Issues with sampling

Too many patients fall outside the

trials and guidelines!

377 patients with working dx of IPF in Edinburgh:

- 77% excluded for CAPACITY

- 92% excluded for ASCEND

- 71% excluded for PANTHER

Lisa Nicol et al. ERS 2015 abstract

Confusing terminologies

Obliterative bronchiolitis, proliferative

bronchiolitis, constrictive bronchiolitis,

bronchiolitis obliterans organizing pneumonia,

cellular bronchiolitis, lymphocytic bronchiolitis,

diffuse panbronchiolitis, respiratory

bronchiolitis, cryptogenic constrictive

bronchiolitis, airway centered interstitial fibrosis

A different question is needed

• Historically, the primary question has been

“what is the diagnosis”?

• Pragmatically, the primary question should be

“what are you going to do about it”?

A metaphor for diagnostic

practice

Warp = the basic ILD knowledge

Weft = everything that is individual in patients including disease behavior

Integrate into a multi disciplinary discussion

The “warp” – basic ILD knowledge

• Complete history, physical examination, age, co-

morbidities, smoking history, reflux, CTD history,

family history

• Precipitating causes: occupational, drugs,

environmental exposures

• Severity of disease – lung function, 6MWT

• HRCT

• Other investigations: echocardiogram,

autoimmune markers, bronchoscopy, surgical

lung biopsy

The weft - “disease behaviour”

• How does the disease progress over a period of

time?

• Is it acute? Is it stable over many years? Are

there intermittent exacerbations?

• How does it respond to previous treatments e.g.

steroid responsiveness?

• Subjective assessment: Symptoms

• Objective assessments: Lung function tests,

HRCT pattern (is it predominantly ground glass,

fibrotic) and their trend

Reversible, self limiting or

irreversible, stable:

Do we need to treat it? e.g. smoking related ILDs, mild

drug induced ILD

Can the disease be

reversed? Reversible with risk of

progression e.g. NSIP, OP

Can the disease be

stabilized? Reversible with potential to

stabilize e.g. some fibrotic NSIP

Irreversible and progressive:

How do we slow it down? e.g. IPF, some fibrotic HP, NSIP

Yes

Yes

MICO (masterly inactivity

with cat-like observation)

Yes

Yes

No

No

No

Treat high to achieve

response e.g. IV methylpred,

long term maintenance to

preserve gains.

Treat to maintain stability

Anti-fibrotics in selected

patients, consider effective

palliation, lung transplant

Travis W et al. AJRCCM 2013

Integrate into a multi

disciplinary meeting (MDM)

Jo et al. BMC Pulmonary

Medicine 2016

Components of MDM

Some case examples to

illustrate how it works

Case 1

• 71 year old man, ex-smoker

• Breathlessness for 3 years but progressively

worse last 1 year

• Given trial of steroids for 6 months without any

improvement

• No CTD symptoms

• No other exposures

Lung function

FVC DLCO

Sep 2013 1.45L (62%) 3.8 (65%)

May 2014 1.21L 2.8 (50%)

May 2015

1.1L 2.1 (36%)

May 2016 0.94L (47%) Not done as

FVC < 1L

G Raghu et al. AJRCCM

2010

What would you do?

A. Send for surgical lung biopsy since the

guideline says so

B. Treat as unclassifiable ILD as patient is

too high risk for a lung biopsy due to

poor lung function

C. Do bronchoscopy and TBLB

D. Treat as IPF and consider anti-fibrotics,

effective palliation and lung transplant

Can we diagnose IPF in patients without

honeycombing on HRCT in the absence of a

surgical lung bx?

CD Fell et al. AJRCCM 2010

71 year old

Diffuse lung fibrosis

Reversible, self limiting or

irreversible, stable:

Do we need to treat it? e.g. smoking related ILDs, mild

drug induced ILD

Can the disease be

reversed? Reversible with risk of

progression e.g. NSIP, OP

Can the disease be

stabilized? Reversible with potential to

stabilize e.g. some fibrotic NSIP

Irreversible and progressive:

How do we slow it down? e.g. IPF, some fibrotic HP, NSIP

Yes

Yes

MICO (masterly inactivity

with cat-like observation)

Yes

Yes

No

No

No

Treat high to achieve

response e.g. IV methylpred,

long term maintenance to

preserve gains.

Treat to maintain stability

Anti-fibrotics in selected

patients, consider effective

palliation, lung transplant

Case 1

• Clinical history fits

• Disease behaving like IPF

• MDM discussion and manage as per IPF

algorithm

Case 2

• 57 year old lady, non-smoker

• Worsening breathlessness over 4-5 months

• Hx of hypertension, hyperlipidemia, bilat ovarian cysts and fibroids s/p THBSO

• Treated as pneumonia with antibiotics without any improvement

• Mechanic’s hand, fine crackles at lung bases

Case 2

• CK normal

• ANA negative

• Other autoimmune markers pending

• FVC 1.15L (47%), DLCO 2.9 (47%)

What will you do?

A. Observe, wait for autoimmune markers

and repeat a CXR and lung function test

in 3 month’s time

B. Oral prednisolone at 0.5mg/kg/day

C. IV methylprednisolone 15mg/kg/day x 3

days followed by IV cyclophosphamide

D. Start Pirfenidone

The “weft” and “warp”

• Female, mechanic’s hands, NSIP pattern

on CT with no evidence of fibrosis… yet

• Fairly rapid progression

• Severe impairment in lung function - FVC

47% predicted

Reversible, self limiting or

irreversible, stable:

Do we need to treat it? e.g. smoking related ILDs, mild

drug induced ILD

Can the disease be

reversed? Reversible with risk of

progression e.g. NSIP, OP

Can the disease be

stabilized? Reversible with potential to

stabilize e.g. some fibrotic NSIP

Irreversible and progressive:

How do we slow it down? e.g. IPF, some fibrotic HP, NSIP

Yes

Yes

MICO (masterly inactivity

with cat-like observation)

Yes

Yes

No

No

No

Treat high to achieve

response e.g. IV methylpred,

long term maintenance to

preserve gains.

Treat to maintain stability

Anti-fibrotics in selected

patients, consider effective

palliation, lung transplant

What we did

• IV hydrocortisone, converted to tapering doses of oral prednisolone 1mg/kg/day

• IV cyclophosphamide

• Further blood results: anti Jo1 positive

• After 3# of IV cyclophosphamide

– FVC 1.15L 1.61L (66%)

• To complete total 6# of IV cyclo and transition to azathioprine and prednisolone to maintain gains

Summary

• IPF diagnosis = prognosis

• ILD diagnosis: biopsy does not provide truth data

• MDM is essential for diagnosis of ILDs

• Integration of clinical reasoning, morphologic (CT and pathology) pattern recognition, examined against the disease behaviour will help guide management even in unclassifiable cases

Thank you

Email:

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