© 2023 Edmund Blok and St Peter's College, Oxford University
Sanjay Ramakrishnan believes a lot of his career turns have been down to pure chance, and each time he fully grasped that opportunity. Born in a small country town in Malaysia, he had medicine in the family as his dad was a gynaecologist. He had been indifferent to science at high school until he visited a roadshow by the British Council at the Malaysian National Science Centre. It was his first exposure to research, the history of science, and global universities. “From then on, I was captivated”, says Ramakrishnan.
He successfully applied for a scholarship to study Medicine at the University of Western Australia (UWA; Perth, WA, Australia). He had wanted to be a surgeon, working in plastic or ear, nose, and throat surgery. Then during one rotation of his medical intern year, a pregnant fellow intern had wanted to swap out of a respiratory rotation to avoid flu infection, and Ramakrishnan took her place. This was to be the sliding doors moment of his life—by working with mentor Gary Lee at Sir Charles Gairdner Hospital, Perth, and the UWA on pleural research, Ramakrishnan quickly realised that there were so many challenges in respiratory medicine, and he completed specialist training in Perth. “When it came to deciding where to sub-specialise, I chose chronic obstructive pulmonary disease (COPD)”, he explains. “The burden of COPD is so high and there was lack of research due to the continuous blaming of smokers for developing the condition”, he explains.
There were also not enough resources directed at COPD and patients with the condition were not prioritised. He explains, “Some doctors and nurses just reacted more negatively to patients with COPD due to the stigma around smoking.” He also adds that 40% of patients with a COPD exacerbation will be back in hospital within 3 months. “Imagine how many hospitalisations could be avoided if we could focus on preventing these exacerbations”, he says. Although smoking is a huge factor in COPD, “where you are born can have a huge determinant of poverty, poor living standards, smoking, and subsequent COPD”.
His next big break came when Ian Pavord, of Oxford University (Oxford, UK), chatted with Lee at a European Respiratory Society conference, and Pavord said he was looking for a fellow. After this meeting, a visit was arranged for Ramakrishnan to meet the Oxford COPD research group led by Mona Bafadhel. “I am so lucky Mona had faith in me and took me on. Working with her has really made me look at the bigger picture relating to COPD”, he explains. “Moving to the UK was tough. It is a big financial, familial, and time commitment to postpone your specialist career for a PhD. I am lucky and grateful that my wife, Petia, is very supportive.”
Like most respiratory specialists, his research and academic training had to pivot towards the COVID-19 pandemic. Working with Bafadhel, Ramakrishnan led the STOIC trial, in which inhaled budesonide was shown to reduce the risk of deterioration in patients with early COVID-19 versus usual care. “I'm particularly proud of the immunological work we did during the trial. We were the first to sample the airway compartment to understand the immune disturbance in early COVID-19”, he explains. On the mechanism, Ramakrishnan says the corticosteroids helped the body to regulate COVID-19 inflammation and dampened the effects of the virus. Both the STOIC trial and the larger PRINCIPLE trial, which replicated the findings across a larger UK patient population, have been published. Bafadhel and Ramakrishnan are working with collaborators in India to see if the benefit can be replicated in a resource-restricted setting.
Ramakrishnan is also attempting to use monoclonal antibodies in patients with COPD. With Bafadhel, he is currently investigating exacerbations in both COPD and asthma. They aim to see if the monoclonal antibodies that have been pivotal in asthma can have the same positive effect in COPD, when given at the start of an exacerbation, instead of systemic corticosteroids. “If the biology and the treatment of asthma and COPD exacerbations are, in fact, the same, then why are we labelling them differently?” says Ramakrishnan. While monoclonal antibodies are far more expensive than current medications used for COPD exacerbations, if they avoid a single COPD-related hospitalisation, then these expensive drugs would pay for themselves.
For his post-doctoral research career, Ramakrishnan believes several areas of COPD care require increased focus. “First, more attention must be focused on correctly diagnosing COPD exacerbations in primary and secondary care. Second, every exacerbation is a potential point at which we can make a difference. Respiratory physicians need to start accepting that no exacerbation is inevitable, too mild, or too simple for them. Every chance we get, we should try to intervene and prevent that event from ever occurring.”
“Finally, what is going on in the days leading up to an exacerbation, those 4 or 5 days where the patient is deteriorating? Our colleagues in rheumatology and gastroenterology, for example, have tests to help predict when a joint or gut exacerbation is likely to occur and be ready to deal with it. We must do the same in respiratory medicine. If we can predict whether an exacerbation will happen in 3 days or 5 days, and intervene before the patient is in crisis, this could transform COPD exacerbation care.”