Interstitial Lung Disease

Dr. Ian Forrest

Consultant Respiratory Physician

Clinical Lead NILDS

Royal Victoria Infirmary

ILD – The Confusing Land of the TLA?

• Take it back to basics

• Focus on

– idiopathic pulmonary fibrosis (IPF)– connective tissue disease (CTD) – chronic hypersensitivity pneumonitis (CHP)

• Discuss the challenges of clinical practice and emerging clinical science

• Questions

Interstitium

Fibrosis

A

B

ILDs>200

Known Causeeg. CTD/Drugs/

Asbestos

Idiopathic Interstitial

Pneumonias

Granulomatous Disease eg. Sarcoid and Hypersensitivity

Pneumonitis

Otherseg. LAM /LCH

OthersIdiopathic Pulmonary

Fibrosis

DIP RBILD

NSIP AIPLIP COP

ILDs>200

CTD - ILD

ChronicHypersensitivity

Pneumonitis

Idiopathic Pulmonary

Fibrosis

Idiopathic Pulmonary Fibrosis (IPF)

One in a hundred people in the UK will die of IPF

Pathogenesis of IPF

Goodwin AT, Jenkins G. CHEST 2016; 149(1):228-237

Familial ILD• 2-20% of cases in UK

• Autosomal dominant inheritance with incomplete penetrance

• Phenotypic heterogeneity in families

• 100,000 genomes study

Pathogenesis of IPF

Goodwin AT, Jenkins G. CHEST 2016; 149(1):228-237

GORD

• Common

• Often proximal and non acid

• Fundoplication helps?

• PPI helps?

• Populates lung microbiome?

Pathogenesis of IPF

Goodwin AT, Jenkins G. CHEST 2016; 149(1):228-237

Natural History of IPF

Ley et al. Am J Respir Crit Care Med 2011, 183:431–440

Early Detection?Medical students Clinical Physiologists

Crep = French Pancake ≠ Crackle

Treatment of IPF

Nothing (much of previous treatment was harmful)

Steroids in IPF

Now the drugs don't work

They just make you worse

But I know I'll see your face again……

The Verve 1997

Trials in IPF

Treatment of IPF• Nothing (much of previous treatment was harmful)

• Best Supportive Care ie: Oxygen / ILD rehabilitation

• Palliative Care

• Transplantation

• Recruit to Clinical Trials

• Antifibrotic therapies

Treatment of IPF• Nothing (much of previous treatment was harmful)

• Best Supportive Care ie: Oxygen / ILD rehabilitation

• Palliative Care

• Transplantation

• Recruit to Clinical Trials

• Antifibrotic therapies

Integrated Palliative Care

Murray SA et al. BMJ.2005; 330(7498): 1007–1011

Treatment of IPF• Nothing (much of previous treatment was harmful)

• Best Supportive Care ie:oxygen/rehabilitation

• Palliative Care

• Transplantation

• Recruit to Clinical Trials

• Antifibrotic therapies

Treatment of IPF• Nothing (much of previous treatment was harmful)

• Best Supportive Care ie:oxygen/rehabilitation

• Palliative Care

• Transplantation

• Recruit to Clinical Trials

• Antifibrotic therapies

Treatment of IPF• Nothing (much of previous treatment was harmful)

• Best Supportive Care ie:oxygen/rehabilitation

• Palliative Care

• Transplantation

• Recruit to Clinical Trials

• Antifibrotic therapies

Anti-fibrotic Therapies(If MDT ratified IPF and VC 50-80%)

• Pirfenidone

• Nintedanib

• Probably suppresses fibroblast proliferation via TGF- inhibition

• Side effects: GI upset, weight loss, photosensitive rash, hepatotoxicity

• C/I: renal impairment eGFR <30

Pirfenidone

Pirfenidone rash

Nintedanib

• Triple TKI

• Side effects: GI upset, diarrhoea, hepatotoxicity

• Cautions: anticoagulants, cardiac disease, surgery, liver disease

Nintedanib Diarrhoea

Practical Points• These drugs are not immunosuppressive and don’t need

to be stopped with infection

• If you think there is a side effect, feel free to stop the drug in short term….bad things don’t happen

• There is (should be) an ILD nurse specialist at the end of the ‘phone…please call

• Emphysema • Lung Cancer• Pulmonary hypertension • Venous thromboembolism• Sleep-disordered breathing • Gastroesophageal reflux disease • Coronary artery disease • Depression and anxiety• Deconditioning • Frailty and Sarcopenia

Co-Morbidities

Combined Pulmonary Fibrosis and Emphysema (CPFE)

• Spirometry can be normal precluding antifibrotics

• Gas transfer very low / desaturate++

• Pulmonary hypertension common

• Poor prognosis

Lung cancer

• Increased risk in IPF (7x)

• Independent of smoking

• Treatment can trigger AE-IPF

Acute Exacerbations of IPF (AE-IPF)

AE-IPF

• 1 in 7 patients/year

• 20-40% fatality

• Treatment?

AE-IPF• Exclude PE

• Exclude heart failure

• Exclude infection

• Support with oxygen

• Steroid

• Co-trimoxazole

• Palliative care / EOLC

• Do not intubate /ventilate

Enomoto N et al. BMC Pulmonary Medicine 2015 15:15

Treatment of acute exacerbation of idiopathic pulmonary fibrosis with direct

hemoperfusion using a polymyxin B-immobilized fibre column improves survival

Haemoperfusion

CTD-ILD PatternsUIP NSIP COP Diffuse Alveolar

DamageLymphocyticInterstitial Pneumonia

Diffuse AlvelolarHaemorrhage

Systemic sclerosis

++ ++++ + + - -

RA ++ + - + - -

MCTD ++ +++ - - + -

SLE + + + ++ - +++

PM/DM ++ ++++ ++ + - -

Sjogren’s + + + - +++ -

Immunosuppression?

NSIP (Often SSc)

• Ground glass predominant

• Peripheral, subpleural

• Basal predominant

• No honeycombing

UIP (Often RA)

• Little ground glass

• Peripheral, subpleural

• Basal predominant

• Honeycombing - key feature

Anti-synthetase ILD

• High index of suspicion

• Requires specific antibody testing

• Work closely with your Rheumatologist / Neurologist

Why HP not EAA?

• Type III (immune complex) and Type IV (T-lymphocyte) DTH• Affects distal airways, alveoli and interstitium

Protocolised HRCT1mm helix done prone with sharpened protocol

In both full inspiration and expirationNo contrast

Inspiratory Expiratory

Look Carefully

Look Carefully

Look Carefully

Look Carefully

Look Carefully

Listen Carefully

HP TreatmentRemove antigen exposure

Immunosuppression

Fibrotic HP…challenging

At the ILD MDT….

IPF

CTD-ILD

CHP

Possible IPF

Possible fibroticHP

Interstitial Pneumonia with autoimmune features

(IPAF)

Unclassifiable?

At the ILD MDT….

Lung Biopsy ?

Future Fibrotic ILD Treatment (after Dr Toby Maher)

Manage disease complications

Treat Underlying Cause (where known)

Anti-fibrotic therapy

If disease progression

In Conclusion1. One in a hundred of us will die of IPF

2. Your stethoscope remains useful

3. It’s often tricky…..MDT working is vital

4. Genetics /translational science informing treatment

5. Get rid of your feather bedding

Questions…..?