Idiopathic Pulmonary Fibrosis: Rare Disease with Severe Prognosis
Idiopathic pulmonary fibrosis (IPF) represents a diagnostic and therapeutic challenge. This rare diffuse primary fibroproliferative involvement of lung tissue is characterized by progressive exertional dyspnea, with antifibrotic treatment being the first-line therapeutic modality.
Definition and Epidemiological Characteristics
Idiopathic pulmonary fibrosis represents a specific form of chronic progressive interstitial pneumonia of unclear etiology, classified among usual interstitial pneumonias. The disease primarily appears in adult patients, with most being older than 50 years. The disease has not been described in individuals younger than 45 years. Men are more frequently affected. IPF affects only the lungs, and the diagnosis is made per exclusionem.
The prevalence of IPF worldwide ranges from 2–29/100,000 inhabitants, while in the Czech Republic, epidemiological studies report a prevalence of 7/100,000 inhabitants. Globally, about 5 million people suffer from the disease, with approximately 110 thousand cases on the European continent. It usually occurs sporadically, with familial cases being rare, estimated at 5%. The most likely form of transmission is autosomal dominant with variable penetrance.
The etiopathogenesis of the disease is complex, with risk factors including exposure to tobacco smoke, dust containing metals and stones, exposure to animal and plant antigens, as well as pinewood dust and viral antigens (CMV, EBV, influenza viruses, hepatitis B and C viruses).
Clinical Picture and Diagnosis
Idiopathic pulmonary fibrosis is characterized by an insidious and gradual onset of clinical symptoms, including chronic exertional dyspnea, easy fatigability, cough, and in later stages, cyanosis due to hypoxemia. The disease may be complicated by acute exacerbations with worsening clinical symptoms. In 75% of patients, typical clinical manifestations such as clubbing of the fingers with nails shaped like watch glasses and crepitations over the lung bases during auscultation are present.
Functionally, the disease is characterized by restrictive ventilatory impairment. High-resolution computed tomography (HRCT) of the chest plays a crucial role in diagnosis. Other diagnostic methods include bronchoalveolar lavage, recommended for every patient suspected of having this disease, while lung biopsy is indicated only in cases of diagnostic uncertainty based on clinical and imaging examinations.
Treatment Options
The disease is characterized by a progressive course with a median survival time of 2.5–3 years. There have been significant changes in treatment in recent years; patients were previously treated with corticosteroids, immunosuppressants, and possibly N-acetylcysteine, but these treatment methods have been found ineffective, sometimes even harmful, and are not recommended for patients with idiopathic pulmonary fibrosis. Focus has now shifted to antifibrotic drugs, which slow down the progression of the disease.
Pirfenidone has been designated by the U.S. Food and Drug Administration (FDA) as a breakthrough drug in the treatment of IPF. This substance was discovered several decades ago, but it has been available for the treatment of progressive lung disease in the Czech Republic only since 2011. Its mechanism of action is complex and not entirely elucidated. Pirfenidone reduces the production of fibroblasts and cytokines associated with the fibrosis process and is indicated for patients with mild to moderate IPF (it is reimbursed only for patients with forced vital capacity [FVC] 50–90%). The drug is administered in a dose of 3 capsules 3 times a day (total daily dose of 2403 mg).
Other drugs used in the treatment of IPF include nintedanib, a tyrosine kinase inhibitor targeting VEGFR, FGFR, and PDGFR receptors. Clinical studies are currently underway to evaluate additional potential antifibrotic drugs.
For patients with exertional or resting hypoxemia, long-term home oxygen therapy is recommended, and lung transplantation may be recommended for selected individuals. Pulmonary rehabilitation also plays an irreplaceable role, aiming to improve functional performance and alleviate dyspnea.
Conclusion
Idiopathic pulmonary fibrosis represents a rare but serious disease of the lung tissue primarily affecting adult patients. It is currently incurable, with first-line drugs that slow disease progression being antifibrotics pirfenidone and nintedanib. However, early diagnosis associated with the initiation of antifibrotic therapy is crucial to increase the chances of longer survival.
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Source: Vašáková M. Current Pharmacotherapy of Idiopathic Pulmonary Fibrosis. Clinical Pharmacology and Pharmacy 2016; 30 (1): 30–34.
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