Background Information
Definitions
Interstitial lung disease (ILD): group of lung disordersinclude lung disorders of unknown cause such as IPF and of known causes including connective tissue disease-associated ILD (i.e., related to rheumatoid arthritis, systemic sclerosis...), hypersensitivity pneumonitis and drug-induced ILD characterised by inflammation and/or fibrosis of the lung parenchyma – specifically affecting the interstitiumtissue and space surrounding the alveoli – leading to impaired gas exchange and progressive dyspnoea. [Ref]
Idiopathic pulmonary fibrosis (IPF): most common type of ILD, that is of unknown cause (idiopathic), diagnosed by characteristic clinical, radiologic and/or histopathologic features, and by the exclusion of secondary causesExclusion of secondary causes is a mandatory step in the diagnosis of IPF. This involves a thorough clinical evaluation to rule out known causes of interstitial lung disease, including environmental or occupational exposures (e.g., mold, birds, asbestos), connective tissue diseases (e.g., rheumatoid arthritis, systemic sclerosis) and drug toxicity (e.g., amiodarone, methotrexate) among others.. [Ref]
Usual interstitial pneumonia (UIP) pattern: hallmark radiologic and histopathologic pattern required for the diagnosis of IPF. Radiologically, this includes subpleural & basal lung zone predominant honeycombing (clustered cystic airspaces), traction bronchiectasis and ground-glass opacities. The histological pattern includes a patchy, heterogenous fibrosis of the interstitium. [Ref]
Epidemiology
Risk Factors
Although the cause of IPF is unknown, there are several risk factors:
- ↑ Age
- Male sex
- Environmental and occupational exposures: [Ref] ↑ risk with metal dust, wood dust, pesticides, farrming/agricultural work, asbestos exposure
- Family History
- Conditions (may contribute to disease risk / progression)
- GORD
- OSA
- Lung disease → emphysema / pulmonary hypertension
Clinical Features
IPF presents with typical interstitial lung disease features:
Symptoms
- Onset → Insidious (over months – years)
- Progressive dyspnoea
- Initially → extertional
- Progresses to dyspnoea at rest
- Progressive nonproductive cough
- Nonspecific → weight loss, fatigue
Signs / Examination findings
- Inspection → digital clubbing (30-50% of cases), cyanosis (advanced disease)
- Chest auscultation
- Fine-inspiratory crackles (velcro-like rales) → indication of pulmonary fibrosis
- Distribution → bibasal
- Loud inspiratory wheeze (advanced)
- Fine-inspiratory crackles (velcro-like rales) → indication of pulmonary fibrosis
Being an ILD, IPF manifests similar to other types of ILD; however, IPF is distinguished by its older age at onset, male predominance and lack of identifiable cause.
Complications
- Complications overlap between different types of ILD and include: [Ref]
- Acute exacerbations
- Progressive hypoxaemic (type 1) respiratory failure → leading cause of death
- Pulmonary hypertension → Cor pulmonale
- ↑ risk of lung cancer
Prognosis
Diagnosis Guidelines
1st Line Tests
Perform ALL the following tests if IPF is suspected.
| Test | Purpose | Typical findings in IPF |
|---|---|---|
| Lung function test – spirometry | To distinguish between obstructive vs restrictive lung disease | IPF causes a restrictive pattern:
|
| Lung function test – gas transfer (DLCODiffuse capacity of the lungs for carbon monoxide) | Assess gas exchange efficiency | ↓ DLCODiffusion capacity of the lungs for carbon monoxide is typical of fibrosis |
| Chest X-ray | Non-specific findings:
|
|
| HRCTHigh-resolution CT thorax | Gold standard imaging | Usual interstitial pneumonia pattern:
Changes are predominantly in basal and peripheral areas |
Further Tests (Specialist)
Specialist tests if diagnosis remains uncertain after 1st line tests:
- Bronchoalveolar lavage
- Useful to exclude hypersensitivity pneumonitis
- Trans-bronchial biopsy (via bronchoscopy)
- Surgical lung biopsy (usually via VATSVideo-assisted thoracoscopic surgery) – most definitive testing
- Histology: usual interstitial pneumonia pattern
Management Guidelines
General Conservative Management
- Smoking cessation advice
- Offer pulmonary rehabilitation if appropriate
- Oxygen therapy as needed
- Ventilatory support if respiratory failure develops
Pharmacological Management
Symptomatic Management
Management of cough:
- Treat other causes of cough (e.g. GORDGastro-oesophageal reflux disease, post-nasal drip)
- Opioids, if the cough is debilitating
- Thalidomide – to be considered by a specialist if the cough is intractable
It is important to optimise treatment of GORDGastro-oesophageal reflux disease in IPF as it is common in IPF patients and can cause microaspiration of gastric contents into the lungs.
Disease-Modifying
Recommended treatment (FVCForced vital capacity 50-80% of predicted)
- Nintedanib (small molecule tyrosine kinase inhibitor)
- Pirfenidone (anti-fibrotic and anti-inflammatory agent – via inhibition of TGF-β1)
Oral N‑acetylcysteine is used for managing IPF, but its benefits are uncertain
The following are NOT recommended to modify disease progression in IPF:
- Immunosuppressant (prednisolone, mycophenolate mofetil, azathioprine)
- Co-trimoxazole
- Pulmonary vasodilators
- Endothelin receptor antagonist (bosentan, ambrisentan)
- Sildenafil
- Warfarin
Lung Transplantation
All patients with IPF should be considered for lung transplantation if there are no contraindications
- Discussion and referral should take place 3-6 months after diagnosis or sooner
Most patients with IPF will eventually require lung transplantation if they are eligible, as IPF is a progressive, fatal disease with a median survival of ~3 years after diagnosis without transplant.
Lung transplantation offers a substantial improvement in survival (5-year post-transplant survival is ~50-55%).