Precision medicine has become a commonplace term in modern healthcare and is the opposite of a one-size-fits-all approach to diagnosing health conditions and developing individual care pathways. But how is it being used in the arena of respiratory health and what are the implications for diseases such as asthma and COPD?
To find out more, we spoke with Dr Rory Chan, a senior respiratory registrar who has recently completed a PhD about Precision Medicine in Severe Asthma.
What is meant by the term precision medicine?
Precision medicine involves the collection of a wide array of clinical, biomarker, imaging, genetic, and lifestyle data. The ultimate aim is to optimise patient outcomes. This method of patient evaluation and treatment contrasts with the more conventional and less precise one-size-fits-all approach in medicine.
For example when it comes to asthma, traditionally, clinicians have used an escalating combination of inhaled corticosteroids, bronchodilators, leukotriene receptor antagonists, and theophylline to treat patients according to their disease severity. However, this does not take into account a patient’s underlying disease phenotype.
The identification and targeting of so-called treatable traits have been shown to improve patient outcomes. Broadly speaking, treatable traits in severe asthma can be categorised into pulmonary, extra-pulmonary and behavioural factors. In one randomised controlled trial, it was found that severe asthma patients have an average of 10 treatable traits and a focused approach that targeted these traits conferred greater improvements in quality of life and asthma control compared to standard of care.
What are the benefits of a precision medicine approach?
For heterogeneous conditions, the benefit of precision medicine lies within its prognostic implications. For instance, In lung cancer, the identification of programmed death ligand 1 (PD-L1) resulted in the development of immunotherapy agents such as nivolumab and pembrolizumab. These treatments have significantly improved survival rates compared to traditional chemotherapy. In infectious diseases, we know that establishing a causative organism allows the administration of targeted antimicrobial(s), and identified sensitivities whilst also mitigating the problem of drug resistance.
In severe asthma, practicing precision medicine also reduces long-term adverse effects of drugs such as oral corticosteroids that are subsequently not indicated after further phenotyping. In this regard, there will also be a time-saving benefit as a result of avoiding the prescription and administration of non-indicated medications.
What are the challenges of precision medicine?
Precision medicine is an ambitious goal but it can be challenging for a multitude of reasons. Firstly, the proposed investigations must be both accessible to clinicians and acceptable for patients. For instance, in asthma, not every patient is capable of expectorating sputum or tolerating an invasive bronchoscopy, both of which might be used as part of a precision medicine approach. Therefore, although sputum analysis is promising, it is not routinely used in clinical practice. Physically performing a vast array of investigations can also be both time-consuming and labour-intensive. This means clinicians need to be able to justify whether these tests will change asthma management.
Secondly, the amalgamation and interpretation of such a large body of data requires specialist input.
Thirdly, the adoption of aspects of precision medicine into local, national, and international guidelines takes time, resources, and keen individuals who are motivated in service development.
Let’s get specific, what sorts of challenges are there in treating patients with severe asthma?
Conventionally, clinicians who treat severe asthma have been quite reactive in the sense that we typically make biologic decisions after patients have experienced multiple severe exacerbations requiring oral corticosteroids or hospital admissions. This is suboptimal as exacerbations are linked to lung function decline whilst cumulative oral corticosteroid exposure is associated with severe long-term complications. Instead, clinicians might wish to take a more proactive approach by predicting the at-risk severe asthma patient early and preventing them from experiencing critical exacerbations. This paradigm requires the practice of precision medicine.
Severe asthma is also challenging to treat because the pathophysiology and clinical presentation is both heterogenous and complex. As a result, underdiagnosis of severe asthma is a significant problem and this notion is supported by the 2014 National Review of Asthma Deaths (NRAD) report. Pointedly, 61% of asthma deaths in the NRAD report were attributed to mild-to-moderate disease. It was more plausible that severe asthma was simply under-recognised. This underpins the importance of educating patients to seek help when their symptoms are uncontrolled. Additionally, clinicians may wish to ask themselves whether the current basic investigation panel is sufficient in providing optimal care for our patients.
Linked to the underdiagnosis of severe asthma is the over-reliance on reliever therapies such as short-acting beta agonists (SABA). Individual patient circumstances vary widely but as an approximate guide, patients requiring more than 3 SABA cannisters in the preceding 12 months should be reviewed urgently to improve inhaler technique and compliance and to optimise basic asthma treatment.
Another challenging area is the rapid identification and treatment of common asthma comorbidities such as chronic rhinosinusitis with nasal polyps (CRSwNP), obesity, and gastro-oesophageal reflux. For example, we know that patients with concomitant CRSwNP and asthma, have a greater type 2 inflammatory burden than those with asthma alone. Interestingly, these patients also experience greater benefits in terms of asthma exacerbation reduction with eosinophil-depleting biologics. Equally, those with co-existing obesity and asthma have worse pulmonary function than those with asthma alone.
How does precision medicine help overcome these challenges?
It is perhaps intuitive that performing a variety of targeted and relevant investigations might increase the likelihood of identifying unique asthma phenotypes and decrease the underdiagnosis of severe asthma. For example, checking blood eosinophils in addition to fractional exhaled nitric oxide before starting a patient on anti-IL4Rα therapy allows better characterisation of their risk of hyper-eosinophilia.
Likewise, the use of airway oscillometry as an adjunct to spirometry offers higher sensitivity in regard to changes in airway geometry resulting from obesity. All of these cumulative improvements, also known as practising precision medicine, culminate in continual marginal gains for our patients with severe asthma.
About our Vital Insights guest
Rory Chan (MBChB, MRCP(UK), PhD) is a senior respiratory registrar currently working in Ninewells Hospital, Dundee, United Kingdom. He recently completed his PhD relating to Precision Medicine in Severe Asthma and has published more than 20 first-author peer reviewed papers in various high impact factor journals. He is also a Honorary Clinical Lecturer at the University of Dundee, an Early Career Editor at CHEST, and the Principal Investigator of two phase IV biologic clinical trials in severe asthma.
