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.

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.

Epidemiology

IPF is the most common interstitial lung disease, with an estimated incidence in the UK of around 7.44 per 100,000 population.¹

IPF is rare in people younger than 45 years and in the UK the median age of presentation is 70 years. The prevalence is around 15 to 25 cases per 100,000 people and increases with age. Most people with IPF smoke or have a history of smoking. IPF often co-exists with chronic obstructive pulmonary disease.²

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.³ Genetic 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 factors³

• 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.

• 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. The effect of the COVID-19 pandemic on the long-term burden of pulmonary fibrosis has yet to be determined.⁴

• Gastro-oesophageal reflux disease with micro-aspiration.

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:^{5 6}

• 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.

Investigations⁵

• 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).

• Performing CT scans of the thorax (including high-resolution images - HRCT). 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 erythematosis

Management^{3 7}

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.⁸

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.⁵

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 should be considered in all and has been associated with stabilisation in lung function.³

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

Pulmonary rehabilitation seems to be safe for people with pulmonary fibrosis and improvements in functional exercise capacity, dyspnoea and quality of life immediately following pulmonary rehabilitation have been shown. There is little evidence regarding longer-term effects of pulmonary rehabilitation.⁸

Medical³

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:⁹

  • 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 has the same restrictions in its use.^{10 5}

Neither pirfenidone nor nintedanib is a cure for IPF and disease severity for most patients continues to progress despite treatment.¹²

Surgical^{1 13}

Lung transplant may be required for patients who fail to respond to medical therapy. Lung transplantation offers survival benefits in carefully selected patients. 23% of lung transplants worldwide are performed on patients with IPF.

Patient selection is important and it is recommended to refer patients with IPF for consideration of transplant when they demonstrate a 10% or greater reduction in FVC over six months and a decrease in oxygen saturations to below 89% or the need for oxygen at rest.

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

These may include:³

• 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 2.5 years from the time of diagnosis.¹⁴

However, the rate of disease progression varies and about 20% of people with the disease survive for more than five years.² The prognosis for other causes of pulmonary fibrosis will depend on the cause and comorbidity.¹⁵