By Kimberley Wang, Manager, Media and Publications, Communications and Outreach
Faced with the rising prevalence of multiple chronic diseases among Singaporeans and a rapidly ageing population, how can we work towards a healthier Singapore?
In March, the Ministry of Health launched the Healthier SG strategy to focus efforts upstream on keeping individuals healthy, driving preventive health and early intervention.1
With an emphasis on population health, Healthier SG will potentially tackle the challenges faced by our healthcare system, including increasing chronic disease burden and rising healthcare costs. This will require further research into chronic diseases such as diabetes, asthma and dementia among the local population.
Although Asia is home to almost 60 per cent of the global population, with a high population density that far exceeds that of other regions, Asians tend to be underrepresented in international biomedical research. One reason for this is that currently, most healthcare institutions studying global health exist outside Asia.
In a 2020 analysis of the global participation in clinical trials, the U.S. Food and Drug Administration highlighted the vast difference between the enrolled participants and the global population. In clinical trials globally, the vast majority (76 per cent) were white and only 11 per cent were Asian.2 The researchers pointed out that representative and diverse research participation is necessary to establish fair standards of care and minimise outcome disparities between populations.
Furthermore, factoring in Asian phenotypes is essential for the medical research community and the development of improved clinical practice guidelines across disciplines that will translate to better human health globally.3
New research initiatives focusing on Asian populations
In line with its transformative research strategic thrust to pioneer impactful research outcomes, the School recently established two initiatives with a strong focus on Asian populations to add to several ongoing projects at LKCMedicine. Launched in September, the Centre for Microbiome Medicine (CMM) studies the microbiome of the local and regional population and the diseases they are linked to while the Singapore Severe Asthma Registry (SSAR) aims to find targeted treatment for Asian patients with severe asthma.
The CMM is a research facility that sets out to improve human health and find new ways to treat diseases by leveraging the microbiome, which are naturally present microorganisms that play a vital role in our wellbeing.
Thousands of different species of microbes including bacteria and fungi live in and on the human body. In healthy individuals, the microbes exist peacefully while in unhealthy individuals, the imbalance of the microbes causes the body to be more susceptible to disorders.
Led by Programme Director LKCMedicine Associate Professor Sunny Wong and working with partners including the National Healthcare Group (NHG), Imperial College London, and the Singapore-based precision gut microbiome company AMILI, the research centre will unravel the mechanisms behind microbiome and diseases.
The facility will focus its research in the areas of Nutrition and Metabolism, Airway and Environment, Cancers, as well as infections and other neurological and skin diseases. Using human sample collections, advanced DNA sequencing, and laboratory experiments, researchers will look at how microbiome causes a range of diseases such as obesity, diabetes, fatty liver, and chronic lung diseases like bronchiectasis.
With a deepened understanding of how microbiome is related to these diseases, researchers hope to translate their discoveries into improved diagnostics and new treatments for patients.
One of these diseases is obesity, which is on the rise in Singapore and globally. A staggering 8.9 per cent of the adult population in Singapore is obese4 and the rate of obesity in the country is also at its highest level since 20105. Associated increased health risks including diabetes, fatty liver, cardiovascular diseases, and even some cancers. Tackling obesity through the microbiome may be a new way forward.
While the disease is commonly associated with unhealthy diets and low physical activity, the gut microbiome is an important interface. Studies have suggested that microbes in the gut can affect our eating habits and our ability to lose or gain weight.
One of the centre’s focus areas is studying how ‘good’ and ‘bad’ bugs in the microbiome can be harnessed to combat the rise in obesity and its associated diseases. Through identifying beneficial microbes and its effects on obesity, researchers aim to alleviate obesity and its related conditions. Discovery of new treatments, diagnostic tools, and prevention strategies are on the horizon.
“Studies have established that gut microbes can be detrimental for metabolic health, causing obesity. As the microbiome can be readily modified by diet, exercise, and drugs, it represents an untapped opportunity for therapeutic manipulation to treat diseases like obesity and more. Our research centre aims to investigate the mechanisms by which such microbes work to help tackle some of Asia’s pressing health challenges,” said A/Prof Wong.
Studies have also shown that obesity is linked to cancer.6 The centre is currently working on understanding the role of the microbes in obesity-related cancers such as colon and other digestive cancers.
Professor Joseph Sung, LKCMedicine Dean and NTU Senior Vice-President (Health & Life Sciences) said, “NTU’s initiative to advance research into microbiome is important as microbes play a vital role in our health and influences a range of disorders from obesity to chronic obstructive airway diseases and fatty liver disease. I believe that microbiome medicine is going to dramatically change our future therapy for metabolic diseases and obesity, lung disease and even therapy for cancer.”
Besides working closely with local healthcare institutions and international partners, the CMM will also foster collaborations among scientists from many disciplines at NTU to develop innovative solutions for microbiome related diseases.
September also saw the launch of a new research network – the Singapore Severe Asthma Registry (SSAR), the first of its kind in the country. Formed by LKCMedicine, Changi General Hospital (CGH), Singapore General Hospital (SGH), and Tan Tock Seng Hospital (TTSH), this national registry joins the International Severe Asthma Registry (ISAR), making it the largest international research collaboration in the history of respiratory medicine in Singapore.
The first multi-centre, large-scale registry of severe asthma patients in Singapore, SSAR aims to improve understanding of severe asthma, collect evidence of treatment effectiveness and safety, and identify predictors of treatment success. The registry will be managed by The Academic Respiratory Initiative for Pulmonary Health (TARIPH), a research network spearheaded by LKCMedicine.
Co-Chair of TARIPH and LKCMedicine Assistant Dean (Faculty Affairs) Associate Professor Sanjay H. Chotirmall said, “Severe asthma affects one in 20 individuals with asthma. This group of patients experience higher treatment burden and differing clinical trajectories, necessitating us to evaluate if and how Asian patients may be different and whether there are better ways to manage and treat this important condition.”
“Developing a national registry of this kind fulfils a key mission of TARIPH to bring research to patients through partnerships. Being part of an international registry gives us rich data upon which to improve outcomes for Singaporeans with severe asthma,” added A/Prof Chotirmall, who is also Provost’s Chair in Molecular Medicine.
Associate Professor Mariko Koh, Senior Consultant in the Department of Respiratory and Critical Care Medicine at SGH, chairs the SSAR workgroup within TARIPH. She said, “SGH has over the years piloted various initiatives to improve asthma care for patients, especially those with severe asthma, as a number of them return frequently to the Emergency Department when they get an attack. Like other chronic respiratory diseases, severe asthma presents differently across patients in its underlying inflammation and response to treatment.
“There is no one treatment or intervention that works for all patients. The formation of SSAR will not only enable us to find better ways to deliver more personalised, targeted, and effective treatment plans for patients, but we will also better understand the burden of severe asthma in Singapore and introduce interventions to address issues at a systemic level.”
Noting that this joint initiative to advance research into severe asthma is timely as the burden of disease is high, Prof Sung said, “By partnering with hospitals and respiratory medicine specialists to set up the Singapore Severe Asthma Registry, we can find better solutions to treat severe asthma. At the same time, the Registry gives us a unique opportunity to look at how severe asthma affects the Asian population differently, thereby leading to strategies tailored for our population.”
Set up since April this year, the SSAR aims to understand the burden of severe asthma in Singapore, address clinical and knowledge gaps of severe asthma, reduce complications and improve care and outcomes. The real-world evidence gathered has the potential to inform policy decision-making and guideline implementation.
The registry has collected data from 139 severe asthma patients to date and aims to register 200 patients by the end of the year. The anonymised data that is collected comprise demography, medical history, exacerbation history, treatment plan and biomarkers such as lung spirometry test results, full blood count and other clinical parameters. Crucially, the researchers will be able to compare the data of Asian patients with non-Asian patients from other countries.
“Current clinical guidelines for treatment have been derived from evidence predominantly from non-Asian patients,” said A/Prof Chotirmall. “There is emerging evidence from a range of lung diseases that Asian and non-Asian patients respond differently to treatment and have lung diseases that behave differently. This is likely due to differences in genetics, environmental exposures (such as allergens, air quality and climate), health-seeking behaviours, and practices in health systems.”
TARIPH researchers can tap on SSAR’s data to address important research questions in severe asthma, improve early diagnosis for patients and promote best practices in severe asthma care.
One key research focus is the choice of treatment for severe asthma patients. An area of concern is the high oral corticosteroid use among severe asthmatics in Singapore.
Oral corticosteroids are commonly used for acute asthma flare-ups and as maintenance for patients with severe asthma. However, long-term and frequent oral corticosteroid use is associated with side effects such as the development of diabetes, osteoporosis, and kidney disease, along with increased risk of heart attack, strokes, pneumonia, and glaucoma.
Through the data collected, the researchers aim to understand how the high oral steroid usage is affecting the local severe asthmatic population and identify ways to minimise steroid burden and reduce complications.
Associate Professor John Arputhan Abisheganaden, Head and Senior Consultant in the Department of Respiratory and Critical Care Medicine at TTSH and TARIPH’s co-chair, explained, “The Singapore Severe Asthma Registry will go a long way towards identifying asthma patients who are at high risk, and providing us with deeper insights from bench to bedside in improving the care and management of these patients. Linking up with the international registry will also help enhance our global perspective and understanding of the condition in the Singapore context.”
Other research topics to be investigated include determining the predictors of treatment success, outcomes of personalised therapies, the use of biologics for treatment, and studying undiagnosed severe asthma in primary care.
Ongoing studies to improve local care outcomes
These new research initiatives complement ongoing studies at the School that aim to improve care outcomes for Singaporeans.
One such study is the Biomarker and Cognitive Impairment Study by LKCMedicine’s Dementia Research Centre (Singapore). A five-year longitudinal study, it looks at what is happening to the brain at the very earliest stages of dementia and even before brain changes set in to shed light on ‘Asian dementia’.
The study aims to recruit 1,500 Singapore participants aged between 30 and 95 and is partnering hospitals here, including the Institute of Mental Health and Khoo Teck Puat Hospital, to recruit patients with mild cognitive impairment.
Participants go through a comprehensive cognitive assessment, which includes brain MRI scans, a neuropsychological assessment, and blood sample collection to measure markers in blood that are associated with cognition. These participants will be followed up over a five-year period to identify changes in cognition and health status.
A combination of these tests and the blood biomarkers, digital biomarkers and neuroimaging markers can help researchers detect early brain changes and determine whether a person is at risk of developing dementia.
Another study established and led by LKCMedicine, the Health for Life in Singapore (HELIOS) study, aims to understand the health of the Singaporean population by collecting deep phenotypic data regarding lifestyle, environment, and genes that may influence health.
Launched in 2018, HELIOS has captured insightful data from 10,000 participants which will be a powerful resource to investigate a broad range of diseases, including atherosclerosis, diabetes, cardiometabolic disease, coronary artery disease, non-alcoholic fatty liver disease, non-alcoholic steatohepatitis, cancer, Alzheimer’s disease, Parkinson’s disease, frailty, aging, osteoporosis, asthma, and chronic obstructive pulmonary disease.
In Phase 2 of HELIOS, LKCMedicine will be leading and partnering with cohorts from National University of Singapore (Multi-ethnic Cohort), Singapore Eye Research Institute (Singapore Epidemiology of Eye Diseases) and National Heart Centre Singapore (SingHEART) to form SG100K. The programme aims to form a bio-resource comprising samples and data from 100,000 residents. This sample size will be powered to look into many diseases that are prevalent to the Asian population.
At the same time, HELIOS has partnered with Metabolon, Inc., a global leader in providing metabolomics solutions.
Metabolon will leverage HELIOS samples to identify biomarkers to support the prevention, diagnosis, and treatment of a wide range of health conditions, such as heart disease, diabetes, cancer, and other chronic diseases. Data from this collaboration and subsequent follow-ups of the participants will enable identification of critical environment, lifestyle and genetic factors that lead to subsequent disease.
In addition, LKCMedicine hosts the Brain Bank Singapore, which provides a national resource of post-mortem brain and spinal cord tissues for vital research into disorders affecting the human brain A joint partnership between LKCMedicine, the National Neuroscience Institute, NHG and the NUS Yong Loo Lin School of Medicine, it will open up research possibilities that will generate new knowledge of brain diseases.
The research centre serves as a platform through which neuroscientists and clinician-scientists can work together to find solutions that will address debilitating brain diseases in Singapore. To achieve this, it is essential that neuroscientists in Singapore have access to brains from patients with the appropriate genetic and ethnic background.
With greater awareness and education, more patients with brain conditions and their family members are pledging their brains for medical research. To date, over 200 donors have registered to donate their brains after death to aid in the development of new therapeutic treatments for future generations.
Collectively, these centres and facilities will support the School’s key research programmes and cross-cutting themes for which we have unique strengths. In tandem with Healthier SG, LKCMedicine will continue to work towards enhancing human health and potential by advocating health protection and disease prevention, and ultimately, to realise our vision of redefining medicine and transforming healthcare.