Diagnosis and monitoring

The diagnosis and classification of interstitial lung disease (ILD) is complex. ILDs may present with a variety of symptoms including breathlessness, fatigue, weight loss or cough; which can be similar to other conditions such as asthma, Chronic Obstructive Pulmonary Disease (COPD) and heart diseases. Many forms of ILD are progressive, so early and accurate diagnosis is important to optimise patient outcomes.

How is ILD diagnosed?

Detailed clinician history, examination findings, blood testing, lung function and imaging findings are critical to a timely and accurate diagnosis of ILD. In certain instances, histopathological sampling via bronchoscopy or surgical or endobronchial lung biopsy is also required to diagnose specific ILDs. The gold standard for ILD diagnosis is ultimately via an ILD specific multi-disciplinary meeting (MDM).

If ILD is suspected or confirmed, early referral to a respiratory physician is recommended for further investigation and management.

These detailed examinations and investigations to diagnose ILD are typically performed or arranged by respiratory physicians.

1. Clinical features suggestive of ILD:

Many of the clinical features of ILD may overlap with other cardiopulmonary conditions. While symptoms and signs may be subtle to begin with, they often progress with time prompting further investigation.

2. Clinical History:

The symptoms of ILD can include:

• Insidious onset breathlessness
• Dry, non-productive cough 
• Progressive deterioration in symptoms over months to years
• Fatigue, weight loss and deconditioning

Other characteristics associated with people with ILD can include:

• Typically older, male patients; although this is not true for connective tissue disease associated ILD
• History of smoking, occupational or environmental exposures
• Positive family history of lung fibrosis
• History of a connective tissue disease such as Rheumatoid Arthritis, Scleroderma or Myositis 
• History of smoking or occupational or environmental exposures which may be associated with development of ILD 
• History of medication or radiotherapy which may have predated and contributed to the development of ILD

3. Physical examination:

• Fine, velcro-like inspiratory crackles, particularly at the lung bases, are a hallmark of ILD.
• Pulse oximetry at rest on room air is recommended, although this is usually normal until the end stages of the disease
• Clubbing of the nails
• Peripheral examination may note signs of associated rheumatological or immune mediated conditions such as
  • Arthralgias, rash, eye changes, myalgia, serositis, sclerodactyly or nail changes  
• Evidence of Pulmonary Hypertension or Right Heart Failure (cor pulmonale) – peripheral oedema, loud second heart sound (P2).

4. Diagnostic investigations

Lung Function Tests

• Spirometry – Typical results for someone with ILD will demonstrate a proportionate reduction in FEV1 and FVC with a normal or elevated FEV1/FVC ratio. If the FEV1/FVC ratio is below the lower limit of normal, this is more suggestive of obstructive airways disease such as COPD or asthma. 
• Pulmonary Function Tests (PFT)
  • Lung volumes – may confirm the presence of a restrictive ventilatory deficit defined by a reduced total lung capacity. 
  • Gas diffusion studies – a reduction in gas transfer (measured by DLCO) is often an early indicator of parenchymal lung disease. Significant reduction is often observed in diffuse interstitial lung diseases. The KCO (DLCO/alveolar volume) will usually be normal or near-normal in ILD patients.  
• 6 Minute Walk Test – to assess exercise capacity and exertional hypoxaemia. Serial results help track patient progress and response to therapy. 

5. Imaging

Computed Tomography (CT) chest scan – The diagnosis of ILD is heavily reliant on good quality CT imaging. If ILD is suspected, a High Resolution Computed Tomography (HRCT) chest scan will be performed. This should include inspiratory/expiratory phases, and supine/prone images.

Note: Signs of early fibrotic lung disease (classically reticular markings) may not be noticeable on chest X-ray. Chest X-ray can be a reasonable screening test for other causes of breathlessness (for example a pleural effusion).

6. Blood tests

• Baseline screening blood work is important at the time of initial investigation and referral. Essential blood tests include:
  • Antinuclear antibody (ANA), anti-cyclic citrullinated peptide antibody (anti-CCP) and rheumatoid factor (RF)
• If a connective tissue disease is suspected, performing an extensive connective tissue disease panel is desirable. These tests include:
  • Antibodies to extractable nuclear antigens (ENA), double-stranded DNA antibody (Anti-dsDNA), anti-neutrophil cytoplasmic antibody (ANCA), proteinase 3/myeloperoxidase (PR3/MPO), Complement 3+4, creatinine kinase, and an extended myositis panel.  

7. Fibreoptic Bronchoscopy & Lung Biopsy

• Bronchoscopic lavage specimens can be taken to evaluate the cellular nature of a pulmonary infiltrate. Results are generally non-specific however can be used in confirming a suspected diagnosis, for example chronic hypersensitivity pneumonitis. 
• The decision to attain tissue for histological analysis should be ideally determined via multidisciplinary discussion. Risks of the proposed procedure need to be weighed against diagnostic uncertainty and available treatment options. For example, a biopsy can be considered in cases where the radiological pattern is indeterminate or inconsistent with UIP. Procedural options include:
  • A surgical lung biopsy; usually performed via video-assisted thoracoscopy. 
  • Transbronchial lung cryobiopsy, in experienced centres, which has now been demonstrated to have high diagnostic agreement with surgical lung biopsy .
  • Transbronchial lung biopsy (through standard bronchoscopy) is not recommended for ILD diagnosis.  

Common clinical features and investigation findings present in idiopathic pulmonary fibrosis (IPF)

History:

• Older age (median age at diagnosis = 66 years) The Interstitial Lung Disease Multi-Disciplinary Meeting
• Exertional dyspnoea (in 90% of patients)
• Non-productive cough (in >70% of patients)
• Absence of features suggestive of other causes of ILD such as connective tissue disease features, occupational, recreational or medication exposures

Examination findings:

• Finger clubbing (in 40-65% of patients)
• Bibasilar crackles
• Features of cor pulmonale (in advanced disease)

Investigations:

• Restrictive ventilatory deficit on spirometry
• Reduced diffusion capacity
• Six minute walk test with oximetry demonstrating reduced walk distance and oxygen desaturation
• High resolution computed tomography demonstrating usual interstitial pneumonia pattern of fibrosis
• Surgical lung biopsy (if required) demonstrating usual interstitial pneumonia pattern of fibrosis
• Serum and bronchoalveolar lavage biomarkers and genetic testing are not currently routinely available for clinical practice in Australia

The Interstitial Lung Disease Multi-Disciplinary Meeting

An ILD multi-disciplinary meeting (ILD-MDM) is considered best-practice standard of care in international guidelines.

How does an MDM work?

An ILD-MDM is a collaborative meeting of specialists with the purpose of accurately determining a consensus diagnosis, prognosis and management plan. The MDM process ideally involves two or more respiratory physicians (ideally one of which with expertise in ILD), at least one radiologist and a histopathologist. Patient data is collated, evaluated against standardised diagnostic criteria and discussion results are communicated with the healthcare team.

How to access an ILD-MDM

Most health jurisdictions have a respiratory service with access to a local ILD-MDM. In addition, there are established ILD centres in a number of states where expert consultation can be sought. Several larger centres (including Royal Prince Alfred Hospital (NSW), the Alfred Hospital (Victoria) and Prince Charles Hospital (Queensland) offer videoconferencing for regional centres to present their ILD cases.

The Interstitial Lung Disease Toolkit contains online resources for health professionals designed to aid in the presentation and discussion of cases to assist in the running of ILD-MDMs. The toolkit resources can be downloaded and saved for local use or used as an example to aid in the preparation of individualised templates.

Monitoring ILD

Ongoing monitoring is important for people living with ILD. Monitoring ILD commonly includes regular:

• Clinical assessment of symptoms and signs
• Pulmonary function tests
• Imaging including HRCT
• Oxygen saturation and function capacity assessment (such as 6-Minute Walk Tests)
• Blood testing dependent on medications prescribed as described in the relevant sections under management
• Echocardiography to determine whether patients have developed pulmonary hypertension

Progression of ILD

Many forms of ILD are progressive. While some forms of ILD may follow an indolent course, others may deteriorate much more rapidly. Even within one disease group such as IPF, there is a wide heterogeneity (figure) between individuals with some patients progressing slowly and others much more rapidly. Early symptom identification and diagnosis are important in optimising outcomes by ensuring the right therapy is commenced as early as possible to alter disease trajectory.

Helpful links

• Interstitial Lung Disease Multidisciplinary Meeting (ILD MDM) Toolkit 
• Connective Tissue-Related Interstitial Lung Disease Primer (2020) 
• Contemporary Concise Review 2023: Interstitial lung disease 
• Diagnosis and management of connective tissue disease-associated interstitial lung disease in Australia and New Zealand: A position statement from the Thoracic Society of Australia and New Zealand 
• Diagnosis and management of hypersensitivity pneumonitis in adults: A position statement from the Thoracic Society of Australia and New Zealand 
• Hypersensitivity Pneumonitis Primer (2021)
• Idiopathic Pulmonary Fibrosis Primer (2021)
• Treatment of idiopathic pulmonary fibrosis and progressive pulmonary fibrosis: A position statement from the Thoracic Society of Australia and New Zealand 2023 revision  
• Progressive Fibrosing Interstitial Lung Disease Primer (2020)

References

• Diagnostic accuracy of transbronchial lung cryobiopsy for interstitial lung disease diagnosis (COLDICE): A prospective, comparative study.
• Diagnostic criteria for idiopathic pulmonary fibrosis: a Fleischner Society White Paper.
• Essential features of an interstitial lung disease multidisciplinary meeting: An international Delphi survey.
• Idiopathic Pulmonary Fibrosis.
• Idiopathic Pulmonary Fibrosis (an Update) and Progressive Pulmonary Fibrosis in Adults: An Official ATS/ERS/JRS/ALAT Clinical Practice Guideline
• The natural history of progressive fibrosing interstitial lung diseases.
• What’s in a name? That which we call IPF, by any other name would act the same.