Cryptogenic fibrosing alveolitis (CFA) (or idiopathic pulmonary fibrosis) is a disease of unknown aetiology which is characterised initially by a cellular alveolar infiltrate and later by fibrosis of the alveolar walls.
The mononuclear cell infiltration of the alveoli correlates with acute symptoms whereas the fibrosis correlates with the gradual decline in lung function.
Lung function deteriorates progressively, usually over a period of years; a rapidly progressive form of the disease leads to death within months and is termed the Hamman-Rich syndrome.
It is thought that in CFA there is an abnormal immune response to an unknown stimulus.
Awareness of clinical features of idiopathic pulmonary fibrosis (1)
- be aware of idiopathic pulmonary fibrosis when assessing a patient with the clinical features listed below and when considering requesting a chest X-ray or referring to a specialist:
- age over 45 years
- persistent breathlessness on exertion
- persistent cough
- bilateral inspiratory crackles when listening to the chest
- clubbing of the fingers
- normal spirometry or impaired spirometry usually with a restrictive pattern but sometimes with an obstructive pattern
It usually presents with progressive dyspnoea, reduced lung volumes, bilateral lower lobe reticular opacities, and a usual interstitial pneumonia pattern on histology.
There is no curative treatment and median survival is approximately 3 years (2)
- however, about 20% of people with the disease survive for more than 5 years. The rate of disease progression can vary greatly. A person's prognosis is difficult to estimate at the time of diagnosis and may only become apparent after a period of careful follow-up (1)
Antifibrotic agents in idiopathic pulmonary fibrosis:
- pirfenidone is an immunosuppressant that is thought to have anti-inflammatory and antifibrotic effects
- mechanism of action is not fully understood but it is likely that pirfenidone exerts its effects by suppressing fibroblast proliferation, reducing the production of fibrosis-associated proteins and cytokines and reducing the response to growth factors such as transforming growth factor-beta and platelet-derived growth factor
- NICE suggest (1) that "...pirfenidone is recommended as an option for treating idiopathic pulmonary fibrosis only if the person has a forced vital capacity (FVC) between 50% and 80% predicted.."
- serious liver injury has been reported during treatment with pirfenidone in the first year after initiation, including 2 cases with a fatal outcome. Measure alanine aminotransferase (ALT), aspartate aminotransferase (AST), and bilirubin levels before starting pirfenidone treatment, monthly for the first 6 months of treatment, and then every 3 months thereafter (3)
- monitor closely for signs of toxicity if pirfenidone is being used concomitantly with inhibitors of one or more other CYP isoenzymes involved in the metabolism of pirfenidone (3)
- nintedanib targets 3 growth factor receptors involved in pulmonary fibrosis. Nintedanib is thought to block the signalling pathways involved in fibrotic processes, and ma y reduce disease progression by slowing the decline of lung function. It is administered orally.
- NICE suggest (1) that "..Nintedanib is recommended as an option for treating idiopathic pulmonary fibrosis, only if: the person has a forced vital capacity (FV C) between 50% and 80% of predicted.."
- NICE suggest (4) that "Nintedanib is recommended, within its marketing authorisation, as an option for treating chronic progressive fibrosing interstitial lung diseases (PF-ILD) in adults."
- "...the clinical trial evidence suggests that nintedanib slows the decline of lung function compared with placebo. But, there are uncertainties in the evidence: it is unclear if nintedanib helps people to live longer, and the trial reflects how nintedanib would be used in the NHS in some but not all people with PF-ILD.."
- NICE (May 2017). Idiopathic pulmonary fibrosis: the diagnosis and management of suspected idiopathic pulmonary fibrosis
- Bhatti H et al. Approach to acute exacerbation of idiopathic pulmonary fibrosis.Ann Thorac Med. 2013 Apr;8(2):71-7.
- Drug Safety Update volume 14, issue 4: November 2020: 2.
- NICE (November 2021). Nintedanib for treating progressive fibrosing interstitial lung diseases