Knowledge on rare diseases and orphan drugs

Idiopathic pulmonary fibrosis (IPF) incidence appears to be increasing. Reported incidences range from 0.2 per 100.000 per year to 94 per 100.000 per year. The prevalence is estimated to be higher in men than in women.

The mean age at presentation is 66 years. IPF initially usually manifests with symptoms of breathlessness on exertion and dry coughing. Auscultation of the lungs reveals early inspiratory crackles, predominantly located in the lower posterior lung zones. Clubbing is found in approximately 50% of IPF patients typically exertional dyspnea progresses over a period of months to years. In practice patients are often misdiagnosed.

The etiology is not yet completely understood. The current conceptual model is that environmental factors may cause microscopic damage in the lungs and that in susceptible people this may lead to a disturbed healing reaction that will result in an ongoing process of scar formation in the lung. This will ultimately lead to loss of lung function.

IPF is recognized on high-resolution computed tomography by peripheral, subpleural lower lobe reticular opacities in association with subpleural honeycomb changes. IPF is associated with a pathological lesion known as usual interstitial pneumonia (UIP). The UIP pattern consists of normal lung alternating with patches of dense fibrosis, taking the form of collagen sheets. The diagnosis of IPF requires correlation of the clinical setting with radiographic images. If these are non-conclusive a lung biopsy can be considered, though potential implications and associated risks should always be weighed and discussed. The diagnosis of IPF can be made by defined criteria that have been published in guidelines endorsed by several professional societies.

Differential diagnosis includes other idiopathic interstitial pneumonias, connective tissue diseases (systemic sclerosis, polymyositis, rheumatoid arthritis), forme fruste of autoimmune disorders, chronic hypersensitivity pneumonitis + and other environmental (sometimes occupational) exposures. In a subgroup of patients with pulmonary fibrosis, despite thorough investigations, no definite diagnosis can be made and this group is than labeled as unclassifiable- pulmonary fibrosis.

In patients that present one or more family members with pulmonary fibrosis, genetic counseling should be considered.

Pharmacological management: Two medications, pirfenidone and nintedanib, are recommended in the current international guidelines for the treatment of IPF. These medication slow down disease progression, as measured by decline in forced vital capacity by approximately 50% and are safe. Besides these, multiple new molecular therapeutic targets have been identified and several clinical trials are investigating the efficacy of novel medications. These non pharmacological management approaches aim to improve or maintain quality of life and sometimes also life longer. Preventative measures as smoking cessation, influenza and pneumococcal vaccination are recommended. Supplemental oxygen is recommended for patients with an oxyhemoglobin saturation of less than 88% and reduces exertional dyspnea and improves exercise capacity for patients. Pulmonary rehabilitation and measures aimed at symptom relieve improve health related quality of life for patients. In a subgroup of patient lung transplantation may be an option.

The median survival without treatment is 2 to 5 years from the time of diagnosis.

Last update: July 2020 - Expert reviewer(s): Pr María MOLINA-MOLINA - Dr M.S. [Marlies] WIJSENBEEK