Researchers have identified a promising alternative to steroid therapy for chronic obstructive pulmonary disease (COPD) by repurposing Pirfenidone, a drug currently used to treat lung fibrosis. The breakthrough study, conducted at Hudson Institute of Medical Research in collaboration with Monash Health and the Monash Biomedicine Discovery Institute, demonstrates that Pirfenidone effectively addresses key limitations of current COPD treatments.
Current COPD Treatment Challenges
COPD, an umbrella term encompassing emphysema and chronic bronchitis, affects approximately 2 million Australians and represents a significant cause of morbidity and mortality, particularly in individuals over 40 years of age. The disease makes breathing difficult and typically worsens over time, often complicated by sudden severe attacks called exacerbations.
Current standard care relies heavily on steroids, which effectively reduce inflammation but create a therapeutic paradox. "Sudden attacks of COPD (called exacerbations) are usually caused by viruses and steroids encourage their replication, making things worse," explained Dr. Belinda Thomas from the Respiratory and Lung Research group. "Steroids can fix one problem (inflammation) – but cause another."
Pirfenidone's Dual Benefits
Using a laboratory pre-clinical model that mimics COPD, researchers tested Pirfenidone and found superior results compared to steroids. "Compared to steroids, Pirfenidone reduced disease severity, lowering both virus replication and airway inflammation, without reducing the immune response, which is what the steroids do," Dr. Thomas reported.
Professor Philip Bardin, Professor of Respiratory Medicine and Emeritus Director of Monash Lung Sleep Allergy & Immunology, who oversaw the research, highlighted the drug's unique mechanism. "Pirfenidone had the opposite effect to steroids, in a way, because it dampened down infection and it helped with inflammation, whereas with steroids the infection was made worse, though it helped somewhat with inflammation."
Addressing Steroid-Related Side Effects
The potential to replace steroids represents a significant advancement given their extensive adverse effects profile. Professor Bardin described the side effects as "horrendous - diabetes, hypertension, heart disease, osteoporosis, obesity, skin changes and effects on sleep." He noted that while steroids are "wonderful for inflammation, it comes at a price."
"The great benefit if this treatment is translated into the clinic is that people could come off steroids," Professor Bardin explained. "Detrimental effects of steroids build up over time so that by the age of 60 many people start having severe side effects such as cardiac disease, hypertension, diabetes, skin problems and osteoporosis."
Clinical Translation Potential
Pirfenidone is already registered for use in idiopathic pulmonary fibrosis in Australia and worldwide, potentially facilitating its transition to COPD treatment. The research team has published their findings in the American Journal of Respiratory Cell and Molecular Biology, with additional recognition through an editorial comment in Lancet Respiratory Medicine.
"We have a robust pre-clinical model showing that it works and there is likely to be a lot of interest in repurposing Pirfenidone in COPD," Dr. Thomas stated. She emphasized that the drug was "really hiding in plain sight - people were excited that it was stopping or slowing lung fibrosis, but until now no-one had anticipated that it could have this important extra benefit."
The research addresses a critical unmet need in COPD management, particularly regarding exacerbations. "It can prevent and treat flares of COPD, the event that can lead to premature death in COPD - when people get severe infections is when they can die," Dr. Thomas concluded.
