1

What is interstitial lung disease?

Interstitial lung disease (ILD) is a heterogeneous group of disorders that predominantly affect the lung parenchyma and vary widely in aetiology, clinical course, radiological presentation and histopathological features.

ILD is also known as diffuse parenchymal lung disease.

2

What is the pathophysiology of interstitial lung disease?

ILD is characterised by the infiltration of cellular or non-cellular material into the lung parenchyma.

This acute injury to the pulmonary parenchyma results in chronic interstitial inflammation, fibroblast activation and proliferation, and eventually pulmonary fibrosis and tissue destruction.

The distribution of this infiltrative process may affect the interstitial compartment, alveolar air spaces, blood vessels and distal airways.

The major physiological consequence of ILD is impaired gas exchange, resulting in progressively worsening respiratory function and ultimately death due to respiratory failure.

3

What is the classification of interstitial lung diseases?

ILD is divided into those with a ‘known’ or ‘unknown’ (idiopathic) cause.

Patients in the idiopathic group are subclassified as:

a)

idiopathic interstitial pneumonia:

i)

idiopathic pulmonary fibrosis (IPF)/usual interstitial pneumonia (UIP)/cryptogenic fibrosing alveolitis (CFA);

ii)

desquamative interstitial pneumonia (DIP);

iii)

respiratory bronchiolitis interstitial lung disease (RBILD);

iv)

acute interstitial pneumonia (AIP);

v)

non-specific interstitial pneumonia (NSIP);

vi)

cryptogenic organising pneumonia (COP) (also known as bronchiolitis obliterans organising pneumonia, BOOP);

vii)

lymphocytic interstitial pneumonia (LIP);

b)

granulomatous diseases:

i)

sarcoidosis;

ii)

hypersensitivity pneumonitis (HSP);

c)

eosinophilic pneumonia;

d)

pulmonary Langerhans cell histiocytosis;

e)

lymphangioleiomyomatosis.

Idiopathic pulmonary fibrosis is the most commonly diagnosed ILD and accounts for approximately 25-35% of all ILD cases.

4

What is the aetiology of interstitial lung disease of ‘known’ cause?

Environmental:

a)

inhaled substances, such as silicosis, asbestosis;

b)

radiation exposure;

c)

protein antigens, such as from pigeons, exotic birds;

d)

tobacco smoke.

Connective tissue disorders:

a)

scleroderma;

b)

systemic lupus erythematosus;

c)

rheumatoid arthritis.

Drug-induced:

a)

cytotoxic agents, such as methotrexate, bleomycin;

b)

antibiotics, such as nitrofurantoin, sulfasalazine;

c)

anti-arrhythmic medications, such as amiodarone;

d)

anti-inflammatory medications, such as penicillamine, gold;

e)

narcotics, such as cocaine, heroin.

Infection:

a)

pneumocystis pneumonia;

b)

tuberculosis;

c)

respiratory syncytial virus.

Malignancy, such as lymphangitis carcinomatosis.

Approximately 75% of patients diagnosed with ILD have interstitial pulmonary fibrosis, sarcoidosis or a connective tissue disorder-related ILD.

5

What is the epidemiology of interstitial lung disease?

Although less frequent than COPD and asthma, ILD accounts for 15% of respiratory diseases.

It has a prevalence of approximately 10-20 cases per 100,000 population.

ILD has an increased incidence in males (ratio 1.5:1).

It is more prevalent in older adults, with most patients aged >50 years.

As regards the subtypes of ILD:

a)

patients with idiopathic pulmonary fibrosis are typically older and male;

b)

patients with connective tissue disease-associated ILD are younger and female;

c)

patients with sarcoidosis are younger, with a higher prevalence and more progressive disease process amongst African Americans.

Genetic associations only modestly increase the risk for the more common forms of ILD, such as sarcoidosis and idiopathic pulmonary fibrosis.

Smoking slightly increases the risk of idiopathic pulmonary fibrosis.

6

What are the symptoms of interstitial lung disease?

Dyspnoea is the most common symptom.

Other respiratory symptoms include wheezing, chronic cough, chest pain or haemoptysis.

The clinical course of the different forms of ILD can vary:

a)

chronic, insidious, slowly progressive course, such as idiopathic pulmonary fibrosis;

b)

subacute course, with relapses and remissions, such as cryptogenic organising pneumonia;

c)

acute, fulminant, rapidly progressive course, such as acute interstitial pneumonitis.

When obtaining a clinical history, it is important to elicit information regarding occupational and environmental exposures, medications, smoking status and history of connective tissue diseases.

7

What are the signs of interstitial lung disease?

Dyspnoea or wheezing may be present at rest.

Bibasal fine end-inspiratory (‘velcro-like’) crackles on auscultation are universal in idiopathic pulmonary fibrosis, maybe present in other ILD but are rare in sarcoidosis.

The presence of a right ventricular heave, right-sided gallop rhythm (S3) and a fixed or paradoxically split P2 may suggest cor pulmonale.

Clubbing is a relative late sign and may suggest advanced disease.

Other signs may be related to the underlying aetiology, such as:

a)

lymphadenopathy with sarcoidosis;

b)

recurrent pneumothoraces with lymphangioleiomyomatosis and Langerhans cell histiocytosis.

8

Which blood tests are useful in the diagnosis of interstitial lung disease?

Although radiological imaging and histological analysis are the mainstay in the diagnosis of ILD, serologic testing may be useful to help detect or confirm underlying pathology or connective tissue disorder:

a)

antinuclear antibodies (ANA) – systemic lupus erythematosus, scleroderma;

b)

rheumatoid factor (RhF) – rheumatoid arthritis;

c)

anti-citrullinated protein antibodies (ACPA) – rheumatoid arthritis;

d)

anti-neutrophil cytoplasmic antibodies (ANCA) – systemic lupus erythematosus, vasculitis;

e)

angiotensin-converting enzyme (ACE) – sarcoidosis.

9

What are the radiological features of a patient with interstitial lung disease?

Chest radiograph (CXR) (Figure 1):

a)

reticular or nodular interstitial opacities;

b)

findings may be normal in up to 10% of patients;

c)

specific findings related to the underlying aetiology, such as bilateral hilar enlargement with sarcoidosis.

High-resolution computed tomography (HRCT) scan (Figure 2):

a)

reticular pattern (interlacing linear opacities) – especially with idiopathic pulmonary fibrosis;

b)

nodular pattern – especially with sarcoidosis;

c)

diffuse cystic pattern – especially with lymphangioleiomyomatosis and pulmonary Langerhans cell histiocytosis;

d)

scattered cystic air spaces – especially with desquamative interstitial pneumonia, hypersensitivity pneumonitis and lymphocytic interstitial pneumonia;

e)

ground-glass opacity;

f)

subpleural honeycombing (cluster of cysts, usually <5mm in diameter, with shared walls) is suggestive of advanced disease.

The site of the lesions within the lung can help to distinguish the different types of ILD:

a)

upper and middle lobes – sarcoidosis, pulmonary Langerhans cell histiocytosis, silicosis;

b)

lower lobes – idiopathic pulmonary fibrosis, asbestosis, most connective tissue disorder-related ILD;

c)

peripheral lung zones – chronic eosinophilic pneumonia, idiopathic pulmonary fibrosis, cryptogenic organising pneumonia;

d)

central lung zones (particularly along the bronchovascular bundles) – sarcoidosis, berylliosis.