Pulmonary fibrosis

What is pulmonary fibrosis?

Pulmonary fibrosis describes a group of diseases which produce interstitial lung damage and ultimately fibrosis and loss of the elasticity of the lungs. It is a chronic condition characterised by shortness of breath, diffuse infiltrates on CXR and inflammation and/or fibrosis on biopsy. Pulmonary fibrosis may be secondary to a wide range of diseases or may be idiopathic with no known underlying cause. There are three types of lung fibrosis:

• Replacement fibrosis secondary to lung damage - eg, infarction, tuberculosis and pneumonia.

• Focal fibrosis in response to irritants - eg, coal dust and silica.

• Diffuse parenchymal lung disease (DPLD), which occurs in idiopathic pulmonary fibrosis (IPF) and hypersensitivity pneumonitis.

Pulmonary fibrosis of known cause is sometimes called interstitial or non-idiopathic pulmonary fibrosis.

How common is pulmonary fibrosis? (Epidemiology)

IPF is the most common interstitial lung disease, with an estimated incidence in the UK of around 7.44 per 100,000 population. It is estimated that there are over 32,000 people in the UK who live with IPF. ¹²

IPF is rare in people younger than 45 years and in the UK the median age of presentation is 74 years. The prevalence is around 15 to 25 cases per 100,000 people and increases with age. Around two-thirds of people with IPF smoke or have a history of smoking. IPF often co-exists with chronic obstructive pulmonary disease.^{3 2}

Causes of pulmonary fibrosis (aetiology)

• The aetiology and pathogenesis of IPF is unknown. The condition is part of a spectrum of conditions known as interstitial lung diseases.

• Pulmonary fibrosis can occur in association with a number of connective tissue diseases, including rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis and Sjögren's syndrome.

• Pulmonary fibrosis can also result from certain occupational exposures, including asbestos, coal dust and silica. Some medications may also cause lung fibrosis, including amiodarone, nitrofurantoin and bleomycin.

• Pulmonary fibrosis may also occur following inhalation of irritant substances, such as with hypersensitivity pneumonitis caused by exposure to birds or moulds.

• IPF may show familial clusters (<5% of all cases) but the genetic reason for this is not yet fully understood, as it does not occur in a predictable fashion. ⁴Genetic predisposing factors known to increase the risk of pulmonary fibrosis have been detected in at least 30% of patients who have sporadic or familial pulmonary fibrosis

Risk factors ⁴

• Smoking - risk factor in familial and sporadic cases, especially if there is a smoking history of >20 pack years.

• The condition is common in certain occupations - for example, in people who work with silica, asbestos, heavy metals or mouldy foliage and in hairdressers.

• Environmental factors include pigeon breeding and contaminated ventilation systems.

• Chronic viral infections have been investigated as potential risk factors, with a focus on hepatitis C and Epstein-Barr viruses. COVID-19 is now recognised as a cause of long-term pulmonary fibrosis. ⁵⁶

• Gastro-oesophageal reflux disease with micro-aspiration.

Symptoms of pulmonary fibrosis (presentation)

The diagnosis of pulmonary fibrosis should be considered in any patient presenting with breathlessness, especially if there is a pre-existing medical history or environmental exposure possibly associated with pulmonary fibrosis (see above).

Features suggesting the possibility of IPF include:^{7 8}

• Age over 45 years.

• Persistent breathlessness on exertion.

• Persistent dry cough.

• Bilateral inspiratory crackles on auscultation of the chest.

• Clubbing of the fingers

• Normal spirometry or impaired spirometry usually with a restrictive pattern but sometimes with an obstructive pattern.

Patients may be systemically unwell and may have a flu-like illness, fatigue or weight loss at presentation. Extrapulmonary features may include arthralgia, muscle pains and skin rashes. Obstructive sleep apnoea may be a common presenting feature.

Other signs on examination may include tachypnoea, cyanosis and also signs of cor pulmonale and right heart failure in the later stages.

Investigations⁷

• Initial assessment should include a detailed history, carrying out a clinical examination and performing blood tests (eg, FBC, ESR, CRP, autoantibodies) to assess environmental and occupational exposure, connective tissue diseases and with drug history.

• CXR.

• Lung function testing (spirometry and gas transfer).

• A CT scan of the thorax (including high-resolution images - HRCT) will usually be done in secondary care. HRCT reveals pattern of usual interstitial pneumonia (subpleural basal predominance, reticular pattern, honeycombing, and absence of inconsistent features - eg, micronodules or cysts.

• If a confident diagnosis cannot be made on the basis of clinical features, lung function and radiological findings, bronchoalveolar lavage or transbronchial biopsy and/or surgical lung biopsy should be considered.

Differential diagnosis

Due to the nonspecific nature of the presenting symptoms and signs, there are many other diagnoses which must be considered, ranging from very common disorders such as heart failure through to much rarer diseases. Other diagnoses to be considered include:

• Heart failure.

• Chronic obstructive pulmonary disease.

• Sarcoidosis.

• Pulmonary embolism.

• Lung cancer.

• Hypersensitivity pneumonitis.

• Pneumonia.

• Asbestosis.

Associated diseases

IPF may be found in association with several autoimmune disorders such as:

• Thyroid disease.

• Systemic sclerosis.

• Rheumatoid arthritis.

• Autoimmune liver disease.

• Systemic lupus erythematosus.

Management of pulmonary fibrosis ⁴⁹

Management should be under a multidisciplinary team and include the management of any underlying cause associated with pulmonary fibrosis and an assessment for pulmonary rehabilitation. ¹⁰

Assessments for pulmonary rehabilitation should be made at the time of diagnosis and repeated at 6-month or 12-month intervals. Pulmonary rehabilitation including exercise and educational components should be tailored to the needs of each individual patient.⁷

Supportive

• Supportive therapy with oxygen is recommended for those with significant resting hypoxaemia.

• Physiotherapy may be helpful.

• Regular exercise and weight control should be encouraged.

• Vaccinate against influenza and pneumococcus.

• Encourage the patient to stop smoking if he or she continues to do so.

• Proton pump inhibitor therapy was recommended in previous guidelines, but more recent research suggests that they are not associated with reduced mortality or admission. ¹¹

• In end-stage disease, opiates may help excessive cough.

Pulmonary rehabilitation seems to be safe for people with pulmonary fibrosis and probably reduces dyspnoea, improving quality of life and functional exercise capacity in the short and long term.¹⁰

Medical ⁴

It has been acknowledged for some time that the effectiveness of medical therapies has been disappointing. Medication should be initiated under specialist supervision. The management will include treatment of any underlying cause, oxygen therapy and other supportive treatments for symptoms.

• Pirfenidone is recommended by the National Institute for Health and Care Excellence (NICE) as an option for treating IPF but only if:¹²

  • The person has a forced vital capacity (FVC) between 50% and 80% predicted.

  • Treatment is stopped if there is evidence of disease progression (an absolute decline of 10% or more in predicted FVC within any 12‑month period).

  • The agreed pricing structure is followed.

• Nintedanib, an intracellular tyrosine kinase inhibitor with antifibrotic and anti-inflammatory properties, is newly licensed for the treatment of IPF and has been approved by NICE. It has been shown in clinical trials to slow the rate of decline of pulmonary function tests similar to pirfenidone. It initially had the same restrictions, but in 2023 was approved by NICE for those with an FVC of above 80%, if the agreed pricing structure is followed. It has been shown to slow the decrease of lung function in this group. ⁷¹³

Neither pirfenidone nor nintedanib is a cure for IPF - they slow rather than stopping progression. ¹⁴

Surgical^{1 15}

Lung transplant may be required for patients who fail to respond to medical therapy. Lung transplantation offers survival benefits in carefully selected patients. 32% of lung transplants worldwide are performed on patients with IPF and 41% are for some type of interstitial lung disease.

Patient selection is important - considerations might include the risk of death without transplant, co-morbidities, age and previous surgery.

Other treatments which may need to be considered

• Acute exacerbations - corticosteroids are recommended.

• Pulmonary hypertension - treatment is not recommended in the majority but clinicians need to review each case individually.

Complications of pulmonary fibrosis

These may include: ⁴

• Pulmonary hypertension.

• Lung cancer.

• Pulmonary embolism.

• Right ventricular heart failure.

• Coronary heart disease.

Prognosis

The median survival for people with IPF in the UK is approximately 3 -5 years from the time of diagnosis. Survival is reduced in the presence of co-morbidities, with one prospective study of 3,580 patients showing that five-year survival was 53.7% in those with no comorbidities but dropped to 41.1% for those with four or more comorbidities. ²¹⁶¹⁷