Interstitial Lung Diseases for CMTs

Dr Laura-Jane SmithRespiratory Registrar, Whittington Hospital

Honorary Clinical Lecturer in Medical Education, UCL@drlaurajane

http://www.slideshare.net/_elljay_

June 2015

Objectives

• Describe what ILDs are• Explain the basis of the classification of ILDs• List the steps in diagnosis of ILDs• Update evidence for treatment of IPF• List the specific features of some interesting

ILDs

pneumonia ≠ infection

Task 1

Interstitial Lung Diseases – what are they?

ILD = DPLDNon-infective infiltrations

of interstitium and alveoli

Progressive

breathlessness

Restrictive lung function

Reduced

transfer factor

Clinical

RadiologicalPathological

Speed of progressionSymptoms

Associated conditionsAgeSex

Ethnicity

UIP vs NSIPGranuloma

FibrosisInflammation

UIP-like patternNSIP-like patternDistributionHoneycombingGround glassNodulesCysts

UIP NSIP

Interstitial lung diseases

Sarcoidosis

Idiopathic(IPF)

Associated with

connective tissue

disease

RadiotherapyDrugs Post-ARDS

Pulmonary fibrosis Hypersensitivity pneumonitis Rare / infiltrations

(Lymphangitis carcinomatosis)

LIP

Eosinophilicpneumonias

Organising pneumonia

LAMHistiocytosis X

Pneumoconiosis

amyloid

Histology can be UIP or NSIPEnd stage of many ILDs have similar appearances to UIP Alveolar

proteinosis

ILD: classification

Other

RB-ILDDIP

Dear colleague,

I’d be grateful if you would see this 76 year old actor who has a 7 month history of breathlessness and cough.

Heart sounds are normal and he has no peripheral oedema. Chest expansion equal. There are bibasal crackles. Sats 95% on air.

PMH: HTNMeds: amlodipine 5mg ODLives with husband. Smokes occasional cigar but no cigarettes.

Best wishes, Dr GP

Investigations

FEV1 2.25L (59% predicted) FVC 2.74L (65% predicted) ratio 0.82Total lung volume 79% predicted, TLCO 48% predicted.

CXRCT

Interstitial lung diseases

Sarcoidosis

Idiopathic(IPF)

Associated with

connective tissue

disease

RadiotherapyDrugs Post-ARDS

Pulmonary fibrosis Hypersensitivity pneumonitis Rare / infiltrations

RB-ILD

Eosinophilicpneumonias

Organising pneumonia

LAMHistiocytosis X

Pneumoconiosis

Alveolar proteinosis

ILD: classification

60% ILDs

LIP10-20% ILDs

Usually UIP Usually NSIPAsbestosis

End stage of many ILDs is fibrosis

5-15% RTX pts within 1-3/12, progresses over 6-12/12

Lymphangitis carcinomatosis

Other

Eosinophilicpneumonias

Chronic aspiration

Organising pneumonia

LAMHistiocytosis X

amyloid

Alveolar proteinosis

DIP

Idiopathic Pulmonary Fibrosis

• Incidence 14-43/100000 worldwide• 2000 new cases/yr in UK• Median age of presentation 70yrs• Progressive breathlessness over months-yrs• Dry cough• Finger clubbing 15-20%• Fine, late inspiratory ‘Velcro’ crackles

Idiopathic Pulmonary Fibrosis

Genes and epigenetics

Environment

Abberant

response to

injury

Inflammation Abnormal repair

Repeated injury

Fibroblast proliferation and migration

Alveolar

epithelium

damage

Activation of coagulation

Extracellular matrix deposition

Epithelial

mesenchymal

transition

Adapted from: Camelo, Ana, et al. "The epithelium in idiopathic pulmonary fibrosis: breaking the barrier." Frontiers in pharmacology 4 (2013).

InvestigationsBloods: exclude specific causes

Lung function tests: restrictive defect, small lung volumes, reduced transfer factor

Imaging: thickened interlobular septa, ground glass infiltration, and honeycombing in a sub-pleural and basal distribution

Bronchoscopy: BAL/EBUS helps exclude other diagnoses and infection

Lung biopsy: Surgical/VATS biopsy is considered only if the diagnosis is unclear and will change management

Table from Eureka: Respiratory Medicine. Smith, Brown, Quint. 2015.

Prognosis

• Insidious disease progression– Rate of decline in FVC ~150-200mL/yr– Periods of acute deterioration, unpredictable

• Prognosis very poor– Most die within 5-10 years– 20-30% alive at 5 years after diagnosis

Treatment

Task 2

Treatment

• Stop smoking• Treat contributors – drugs, reflux • Oral corticosteroids• NAC• Immunosuppresion: azathioprine,

cyclophosphamide• Newer drugs: perfenidone, nintedanib

Specialist ILD MDT decision-making

Treatment

• 1999 ATS/ERS statement recommended ‘standard therapy’ for IPF based on expert opinion and several small cohort studies – Azathioprine and Prednisolone

• IFIGENIA – Idiopathic Pulmonary Fibrosis International Group exploring N-acetylcysteine I Annual– 3 Drug Regimen (PAN) preserved Pulmonary

Function > 2 Drug Regimen (PN)

N Engl J Med 2005;353:2229-42.

Prednisone, Azathioprine, and N-Acetylcysteine for Pulmonary Fibrosis. (2012). New England Journal of Medicine, 366(21), 1968–1977. doi:10.1056/NEJMoa1113354

RCT of NAC

Martinez, Fernando J., et al. "Randomized Trial of N-acetylcysteine in Idiopathic Pulmonary Fibrosis." The New England journal of medicine 370.22 (2014): 2093.

Recent trials• The ASCEND trial: A Phase 3 Trial of Pirfenidone in Patients with

Idiopathic Pulmonary Fibrosis; N Engl J Med 2014;370:2083-92.– Oral Anti-fibrotic Therapy– Reduced Disease Progression (Lung Function, Exercise Tolerance,

Progression Free Survival)– Fewer Deaths

• Efficacy & Safety of Nintedanib in Idiopathic Pulmonary Fibrosis; N Engl J Med 2014;370:2071-82.– Intracellular Inhibitor of Multiple Tyrosine Kinases– Reduced Decline in FVC – Slowing of Disease Progression– Associated with Diarrhoea, < 5% Drop Out

From: Adamali, Huzaifa I., and Toby M. Maher. "Current and novel drug therapies for idiopathic pulmonary fibrosis." Drug design, development and therapy 6 (2012): 261.

https://adventuresofabluegirl.wordpress.com/2015/05/27/adventures-galore/

“It's frightening, life changing. Life becomes very small, stuck in house. Breathlessness is

terrifying.”

Interstitial lung diseases

Sarcoidosis

Idiopathic(IPF)

Associated with

connective tissue

disease

RadiotherapyDrugs Post-ARDS

Pulmonary fibrosis Hypersensitivity pneumonitis Rare / infiltrations

RB-ILD

Eosinophilicpneumonias

Organising pneumonia

LAMHistiocytosis X

Pneumoconiosis

Alveolar proteinosis

ILD: classification

60% ILDs10-20% ILDs

Usually UIP Usually NSIP

End stage of many ILDs is fibrosis

5-15% RTX pts within 1-3/12, progresses over 6-12/12

Lymphangitis carcinomatosis

Other

LIPChronic

aspiration

Asbestosis

Eosinophilicpneumonias

Organising pneumonia

LAMHistiocytosis X

amyloid

Alveolar proteinosis

DIP

Task 3

Table from Eureka: Respiratory Medicine. Smith, Brown, Quint. 2015.

Interstitial lung diseases

Sarcoidosis

Idiopathic(IPF)

Associated with

connective tissue

disease

RadiotherapyDrugs Post-ARDS

Pulmonary fibrosis Hypersensitivity pneumonitis Rare / infiltrations

Lymphangitis carcinomatosis

LIP

Eosinophilicpneumonias

Organising pneumonia

LAMHistiocytosis X

Pneumoconiosis

amyloid

Alveolar proteinosis

ILD: classification

Other

RB-ILDDIP

acute vs chronic

Examples

Interstitial lung diseases

Sarcoidosis

Idiopathic(IPF)

Associated with

connective tissue

disease

RadiotherapyDrugs Post-ARDS

Pulmonary fibrosis Hypersensitivity pneumonitis Rare / infiltrations

Lymphangitis carcinomatosis

LIP

Eosinophilicpneumonias

Organising pneumonia

LAMHistiocytosis X

Pneumoconiosis

amyloid

Alveolar proteinosis

ILD: classification

Other

RB-ILDDIP

Examples of rare ILDs

QUESTIONS?

Key points

• Interstitial lung diseases are a heterogenous group of diseases featuring non-infective infiltrations of the interstitium and alveoli

• Patients present with breathlessness and cough• Patients have a restrictive deficit on spirometry and

reduced transfer factor• Some patterns on HRCT are characteristic • The key to diagnosis is clinical, radiological and

histological correlation • IPF is a distinct disease which is incurable and often has

a poor prognosis, but new treatments are emerging

Dr Laura-Jane Smith@drlaurajane

http://www.slideshare.net/_elljay_

Task 1

UIP: usual interstitial pneumoniaILD: interstitial lung diseaseIPF: idiopathic pulmonary fibrosisNSIP: non-specific interstitial pneumoniaDPLD: diffuse parenchymal lung diseaseCFA: cryptogenic fibrosing alveolitis

LIP: lymphocytic interstitial pneumoniaDIP: desquamative interstitial pneumoniaCOP: chronic organising pneumoniaHP: hypersensitivity pneumonitisRB-ILD: respiratory bronchiolitis ILDARDS: acute resp distress syndrome

UIPILDIPF

LIPDIPCOP

HPNSIP

ARDSRB-ILD

CFADPLD