Medicine – Interstitial Lung Disease (Pulmonary Fibrosis)

Interstitial lung disease (ILD) refers to a broad group of disorders that affect the pulmonary interstitium and may lead to inflammation, scarring, and progressive pulmonary fibrosis. Patients commonly present with progressive exertional breathlessness, dry cough, fine inspiratory crackles, restrictive lung physiology, and reduced gas transfer.

A useful way to remember the differential diagnosis is by the predominant radiological distribution, particularly whether fibrosis mainly affects the upper or lower lobes.

1. Predominantly Upper-Lobe Disease

Upper-lobe or upper-zone predominance is seen in several granulomatous, occupational, infectious, and inflammatory lung disorders.

Sarcoidosis

Sarcoidosis can produce chronic interstitial lung disease with fibrosis, particularly in longstanding pulmonary disease.

The fibrotic changes tend to involve the upper and mid zones and may be associated with hilar or mediastinal lymphadenopathy, traction bronchiectasis, and architectural distortion.

Tuberculosis

Pulmonary tuberculosis, particularly chronic or previously treated disease, can leave residual upper-lobe fibrosis, volume loss, scarring, and cavitation.

The fibrosis often reflects previous destruction of lung tissue rather than a primary diffuse interstitial fibrotic process.

Pneumoconiosis

Several forms of pneumoconiosis can produce upper-zone nodular and fibrotic changes, especially when exposure has been prolonged.

Coal workers’ pneumoconiosis, for example, may progress from small nodular opacities to progressive massive fibrosis, usually affecting the upper lungs.

Silicosis

Silicosis classically produces multiple small nodules predominantly in the upper lobes.

Advanced disease may result in progressive massive fibrosis with large fibrotic masses and severe distortion of normal lung architecture. Hilar lymph nodes may show characteristic eggshell calcification.

Ankylosing Spondylitis

Ankylosing spondylitis can rarely cause upper-lobe pulmonary fibrosis, usually in longstanding disease.

The fibrosis may be associated with apical scarring, volume loss, and occasionally cavitation. These abnormal upper-lobe spaces can predispose to colonisation by organisms such as Aspergillus.

Allergic Bronchopulmonary Aspergillosis

Allergic bronchopulmonary aspergillosis (ABPA) occurs mainly in patients with asthma or cystic fibrosis and is characterised by hypersensitivity to Aspergillus antigens.

It is more typically associated with central bronchiectasis, mucus plugging, and upper-lobe-predominant infiltrates rather than being a classic primary fibrosing ILD. Chronic or severe disease can nevertheless produce bronchiectatic and fibrotic change.

2. Predominantly Lower-Lobe Disease

Lower-zone or basal predominance is particularly characteristic of several fibrotic and connective tissue-related lung diseases.

Bronchiectasis

Bronchiectasis itself is primarily an airway disorder rather than a true interstitial lung disease.

However, chronic lower-lobe bronchiectasis may produce scarring and fibrotic change around damaged airways, especially when associated with recurrent infection.

Asbestosis

Asbestosis is a diffuse interstitial pulmonary fibrosis caused by significant asbestos exposure.

Fibrosis predominantly affects the lower lobes and subpleural regions. Patients may have dry cough, exertional breathlessness, bibasal inspiratory crackles, finger clubbing, restrictive lung function, and reduced gas transfer.

Usual Interstitial Pneumonia

Usual interstitial pneumonia (UIP) is the characteristic radiological and histological pattern associated with idiopathic pulmonary fibrosis when no secondary cause is identified.

It predominantly affects the subpleural and basal regions and is characterised by reticulation, traction bronchiectasis, and honeycombing.

Rheumatoid Arthritis

Rheumatoid arthritis can cause interstitial lung disease, and the UIP pattern is common.

Patients may develop progressive dry cough and exertional breathlessness with bibasal fibrotic changes on imaging. RA can also cause pleural disease, pulmonary nodules, and bronchiectasis.

Systemic Sclerosis

Systemic sclerosis is strongly associated with interstitial lung disease, typically with a lower-lobe and peripheral predominance.

The most common imaging pattern is nonspecific interstitial pneumonia (NSIP), although UIP can also occur. Pulmonary arterial hypertension is another major pulmonary complication of systemic sclerosis.

3. Drug- and Treatment-Induced Interstitial Lung Disease

Several medications and therapeutic interventions can cause inflammatory pneumonitis, pulmonary fibrosis, or both.

Amiodarone

Amiodarone can cause pulmonary toxicity ranging from mild pneumonitis to severe interstitial fibrosis.

Patients may develop progressive dry cough, dyspnoea, diffuse pulmonary infiltrates, restrictive lung function, and impaired gas transfer.

Methotrexate

Methotrexate can cause drug-induced pneumonitis, often presenting with dry cough, fever, breathlessness, and diffuse infiltrates.

This is usually an inflammatory hypersensitivity-type reaction rather than slowly progressive dose-related fibrosis, although distinguishing drug toxicity from underlying rheumatological lung disease can sometimes be difficult.

Nitrofurantoin

Nitrofurantoin can cause both acute and chronic pulmonary reactions.

Acute disease may resemble hypersensitivity pneumonitis, while prolonged exposure can lead to chronic interstitial inflammation and pulmonary fibrosis.

Bleomycin

Bleomycin is a well-known cause of dose-related pulmonary toxicity.

It can produce interstitial pneumonitis followed by progressive pulmonary fibrosis, and the risk increases with greater cumulative exposure and certain additional risk factors.

Radiotherapy

Thoracic radiotherapy can produce lung injury in two main stages.

An earlier radiation pneumonitis may develop within months of treatment, followed later by permanent radiation fibrosis. The abnormalities often correspond geographically to the irradiated portion of lung.

Key Clinical Pattern

For exam purposes, a useful distribution is:

Upper-lobe predominant: sarcoidosis, TB-related scarring, pneumoconiosis, silicosis, ankylosing spondylitis, and chronic ABPA-related change.

Lower-lobe predominant: asbestosis, UIP/IPF, rheumatoid arthritis-associated ILD, and systemic sclerosis-associated ILD.

Important causes of drug- or treatment-induced ILD include amiodarone, methotrexate, nitrofurantoin, bleomycin, and thoracic radiotherapy.

A useful correction is that bronchiectasis and ABPA are primarily airway diseases rather than classic interstitial lung diseases, although both may produce associated fibrosis in chronic disease.