Initial investigations

Pulmonary function testing

If ILD is suspected, perform spirometry and pulse oximetry.

Patients with ILD typically develop a restrictive defect in pulmonary function, characterised by reduced forced vital capacity (FVC), normal or reduced forced expiratory volume in 1 second (FEV1), and normal or increased FEV1/FVC ratio.

Complex pulmonary function testing (eg static lung volumes [including total lung capacity], diffusing capacity of the lung for carbon monoxide [DLCO]) may be ordered by the specialist.

Changes in pulmonary function tests over time can also be used to monitor ILD progression. A 10% decline in FVC or a 15% decline in DLCO is highly suggestive of progressive ILD.

Blood tests

Blood tests can help determine the cause of ILD. Initial blood tests may include full blood count (FBC) with eosinophil count, antinuclear antibodies (ANA), extractable nuclear antigens (ENA), double-stranded DNA (dsDNA), serum calcium and rheumatoid factor (RF).

Additional tests may be ordered by the specialist depending on the clinical scenario, such as antineutrophil cytoplasmic antibodies (ANCAs) if pulmonary vasculitis is suspected, or precipitins against environmental antigens (eg avian or mould precipitins) if hypersensitivity pneumonitis is suspected.

Imaging

Chest X-rays are often ordered to assess breathlessness and are useful in detecting a range of respiratory diseases, including ILD. However, in patients with early or mild ILD, chest X-ray may appear normal.

HRCT is a pivotal diagnostic test in ILD and is usually ordered if chest X-ray and spirometry reveal abnormalities. The clinical question or indication for ordering the HRCT scan should be clearly described in the request form for consideration by the radiology team. Consider the dose of radiation exposure to the patient from HRCT, especially as the specialist may need to repeat the scan for additional clarity. If there is any uncertainty about ordering HRCT, consult the radiologist. See also CT of the chest.

Sometimes prone HRCT images can help distinguish early or mild ILD from causes of gravity-dependent opacity (eg atelectasis).

While HRCT scans of the chest are usually performed at full inspiration, occasionally expiratory phase images are also performed to assess for small airways involvement and gas trapping that can be a feature of chronic hypersensitivity pneumonitis.

The HRCT pattern and distribution are important in distinguishing between the different ILDs. Upper-zone predominant diseases include sarcoidosis and chronic hypersensitivity pneumonitis, while lower-zone distribution diseases include idiopathic pulmonary fibrosis and nonspecific interstitial pneumonia. Specific features on HRCT, such as honeycombing, nodules or ground-glass opacity, can help define the ILD diagnosis. Examples of HRCT patterns that can be suggestive of specific ILDs include usual interstitial pneumonia pattern, nonspecific interstitial pneumonia pattern, organising pneumonia, pulmonary nodules and pulmonary cysts.

A usual interstitial pneumonia (UIP) pattern is the term used to describe a specific pattern on HRCT, and also a specific histological pattern on a lung biopsy specimen.

A UIP pattern can be seen in several conditions including idiopathic pulmonary fibrosis, rheumatoid arthritis–associated ILD, asbestosis, chronic hypersensitivity pneumonitis and drug-induced ILD.

A UIP pattern on HRCT is characterised by:

  • honeycombing, with or without traction bronchiectasis
  • subpleural, basal predominant reticulation
  • absence of or minimal ground-glass opacity
  • absence of nodules, cysts and other features (eg pleural plaques).

The histological features of a UIP pattern include:

  • marked fibrosis and honeycombing in a subpleural distribution
  • patchy involvement of lung parenchyma with fibrosis
  • presence of fibroblastic foci.

A nonspecific interstitial pneumonia (NSIP) pattern is the most frequently observed pattern in connective tissue disease–associated ILD, but may also occur in drug-induced lung injury or from unknown causes (idiopathic NSIP).

An NSIP pattern on HRCT is characterised by bilateral, often lower-zone ground-glass opacities with reticular changes (with or without traction bronchiectasis). Histological features include varying amounts of interstitial inflammation and fibrosis.

Assess for connective tissue disease and drug exposure if NSIP is identified on HRCT or lung biopsy.