Interstitial lung disease (ILD) is an umbrella term that encompasses a large number of disorders that are characterized by diffuse cellular infiltrates in a periacinar location. The spectrum of conditions included is broad, ranging from occasional self-limited inflammatory processes to severe debilitating fibrosis of the lungs. 

Terminology

Interstitial lung disease is considered a misnomer by some, as many of the diseases also involve the alveolar spaces.  

Diagnosis

This is the provenance of multi-disciplinary teams; clinical, functional laboratory and CT findings are integrated to reach a consensus diagnosis, if possible. Biopsy is only helpful if it might influence treatment decisions and outcome. Surgical lung biopsy carries significant morbidity and mortality; cryobiopsy is available in some centers.

Clinical presentation

Interstitial lung diseases classically produce the "3Cs": cough, clubbing of the nails, and fine crackles on auscultation ⁶.

Functional respiratory tests commonly show an abnormal restrictive pattern and reduced diffusing capacity. 

Pathology

Etiology

The radiological appearances are not specific for the underlying cause of diffuse lung disease in many cases. It is therefore key to determine whether there is an underlying cause for the changes. A number of precipitants can cause diffuse interstitial disease such as:

• smoking ¹

• organic dusts (causing hypersensitivity pneumonitis)

• inorganic dusts (causing pneumoconioses)

• gases or fumes

• drugs

• radiation

• infection

Eliciting a history of underlying systemic disease is also helpful since they may involve the lungs in a diffuse and infiltrative manner. Examples include:

• granulomatous diseases, e.g. sarcoidosis, Langerhans cell histiocytosis

• neoplasia

  • primary, e.g. lymphoma, other lymphoproliferative diseases

  • secondary, e.g. pulmonary metastases, lymphangitis carcinomatosis

• vasculitis

• inherited diseases, e.g. neurofibromatosis

• autoimmune and collagen vascular diseases (collagen vascular disease related interstitial pneumonitis) ³

  • systemic lupus erythematosus

  • rheumatoid arthritis

  • progressive systemic sclerosis

  • anti-Jo-1 antibody positive interstitial lung disease

    • dermatomyositis and polymyositis

    • antisynthetase syndrome

  • anti-SRP autoantibody associated interstitial lung disease

  • ankylosing spondylitis

  • Sjögren syndrome

  • mixed connective tissue disease

  • psoriasis - pulmonary manifestations of psoriasis  

  • interstitial pneumonia with autoimmune features

  • primary biliary cholangitis / primary biliary cirrhosis ⁷

• immune dysregulation 

  • e.g. HIV - HIV associated interstitial lung diseases ⁸

• miscellaneous, e.g. amyloidosis, alveolar proteinosis

Where a cause is not determined, the idiopathic interstitial pneumonia (IIP) should be considered:

• usual interstitial pneumonia (UIP): idiopathic pulmonary fibrosis

• non-UIP IIP

  • non-specific interstitial pneumonia (NSIP): non-smokers

  • cryptogenic organizing pneumonia (COP): previously termed BOOP

  • respiratory bronchiolitis-interstitial lung disease (RB-ILD): smokers

  • desquamative interstitial pneumonia (DIP): end-state of RB-ILD

  • lymphoid interstitial pneumonia (LIP): women

  • acute interstitial pneumonitis (AIP)

• other entities

  • combined pulmonary fibrosis and emphysema (CPFE)

  • idiopathic pleuroparenchymal fibroelastosis

Mnemonic: All Idiopathic Chronic Lung Diseases aRe Nonspecific

Radiographic features

The diffuse lung diseases tend to cause infiltrative opacification in the periphery of the lung, but patterns vary among the different etiologies. Please refer to the articles in each specific etiology listed above for specific details on their imaging pattern. 

Follow up

Follow up and monitoring will depend on a multitude of factors such as symptoms and other co-morbidities etc. While no strict consensus recommendations are available in relation to imaging follow-up for patients with progressive fibrosing forms, many consider an HRCT at the patient’s initial presentation and then every 12–18 months to assess for progression dependent on symptoms etc ¹¹.

Treatment and prognosis

Antifibrotics are approved for IPF and systemic sclerosis in the USA. Other fibrotic lung diseases only qualify if progression has occurred.

The extent of honeycombing and bronchiectasis, and pulmonary artery diameter appear to relate to higher mortality across all ILD subtypes whereas subpleural sparing is a favorable prognostic indicator ¹³.

Practical points

Interstitial lung disease is a misleading term for various diseases causing lung injury. The injury often begins within the alveoli, later spreading to the alveolar wall ¹².

See also

• interstitial lung abnormality

• interstitial lung pattern - radiograph