Professor Ramesh Kurukulaaratchy, professor of respiratory medicine and allergy at the University of Southampton, explains how his team’s recent work recognising distinct patterns of multimorbidity in severe asthma may help clinicians move beyond an airway-centred approach towards more holistic, multidisciplinary care
Asthma is traditionally regarded as a lung disease treated with inhalers, oral corticosteroids or biologics that target airway inflammation to improve symptoms. However, many patients with severe asthma fail to achieve adequate disease control with these treatments
Most people with severe asthma also live with an average of three to four other chronic conditions within a model of multimorbidity. Emerging evidence has suggested that these additional health conditions can be associated with a range of adverse asthma outcomes. However, little was known about the association of multimorbidity and severe asthma until recently
From MiDAS to multimorbidity phenotypes
In our previous work, published in The Lancet Respiratory Medicine, our group at Southampton developed the novel Multimorbidity in Difficult Asthma Score (MiDAS) to quantify the impact of multimorbidity on individual patients
MiDAS can be used in the clinic to assess the impact of multimorbidity on an individual patient. Building on that work, we have now investigated whether distinct patterns of multimorbidity exist in severe asthma and whether these patterns are associated with different clinical outcomes
Our hope was that understanding those different patterns of multimorbidity would support more holistic treatment addressing the whole patient and ultimately lead to better patient outcomes
SHARP in driving collaborative research
This research is set within the context of a European Respiratory Society clinical research collaboration known as Severe Heterogeneous Asthma Research collaboration: Patient-centred (SHARP)
Established in 2018 to improve the lived experience of people with severe asthma, its overarching vision is to end dependence on oral corticosteroids for disease control, end asthma exacerbations, ensure all patients across Europe have access to severe asthma specialists, and improve understanding of the heterogeneous mechanisms underlying severe asthma. The ultimate goal is preventing the disease
SHARP provides a framework for linking national severe asthma registries, supporting countries without existing registries and promoting standardised approaches to research and clinical practice
It also aims to build a catalogue of European asthma research centres and support comprehensive characterisation of patient characteristics, phenotypes, treatment strategies, treatment responses and the burden of severe asthma across Europe
Through its Rising Stars programme, SHARP also supports the education and development of early-career researchers to strengthen research capability and improve patient care
Understanding patterns of multimorbidity
In our recent study, published in The Lancet Regional Health Europe, we assessed data from 2,690 patients with severe asthma and 23 comorbidities from 11 countries in the SHARP database and used a clustering approach to understand how the most common comorbidities in severe asthma are associated with one another
From this, we identified three paired comorbidity clusters. One was associated with corticosteroid-related complications, including weight gain and osteoporosis. Another was linked to allergic diseases, including eczema and rhinitis. The third comprised chronic sinus disease and nasal polyps
Other conditions, including obesity, bronchiectasis, psychological distress and gastric reflux, did not consistently fit into these clusters. We also found that individual patients may exhibit features of more than one cluster
On that basis, we created eight multimorbidity phenotypes. Some were associated with a milder disease burden, particularly those linked to allergic and sinonasal disease. This suggests that those comorbidities may be more ‘treatable traits’
Other phenotypes showed greater severity, particularly those associated with corticosteroid-related complications. One phenotype had almost all the common comorbidities and particularly poor clinical outcomes
Recognising these phenotypes and their clinical implications provides a starting point for clinicians to apply their understanding of multimorbidity in severe asthma and more holistically address the needs of the individual patient
Holistic and multidisciplinary approach to multimorbidity
A key message from our study is that multimorbidity is very common and that certain patterns of multimorbidity are associated with worse clinical outcomes
These findings suggest that clinicians need to consider the wider clinical picture in patients with severe asthma, actively identify comorbidities and incorporate them into their management plans. This may require a significant change in approach for many clinicians, whereas many patients understand this point well
One patient colleague in SHARP commented that, for most of her life, she had been treated as ‘an asthmatic pair of lungs’, when she was actually a person living with many different medical conditions
Multidisciplinary approaches are therefore fundamental to addressing patterns of multimorbidity in severe asthma. Some of that care can be delivered within the framework of a multidisciplinary severe asthma team itself, ideally involving respiratory physicians, asthma nurse specialists, psychologists, physiotherapists, dietitians and pharmacists
Close collaboration with allergists, ear, nose and throat specialists, gastroenterologists and endocrinologists is also important
Reducing corticosteroid burden in severe asthma
Several more severe phenotypes were characterised by high corticosteroid exposure and associated treatment-related complications, highlighting the importance of minimising oral corticosteroid exposure wherever possible
A holistic approach that addresses clinical factors beyond asthma can help to reduce inappropriate reliance on long-term corticosteroids. Newer biologics also offer an effective route to clinical improvement for many patients and can help spare oral corticosteroid exposure
Where funded access is available, initiating prompt access for appropriately selected patients. In that setting, long-term corticosteroids should increasingly be regarded as ‘yesterday’s asthma treatment’ and ideally consigned to the dustbin of history
Although biologics provide a significant clinical improvement in around 70% of appropriate patients, only about 30% achieve what is described as a ‘super-response’ to those agents
Multimorbidity is likely to influence these treatment responses and should therefore be considered alongside decisions about biologic therapy
Conclusion
There is a growing recognition that multimorbidity is highly relevant across many chronic diseases and healthcare systems are increasingly recognising this. Future severe asthma guidelines must therefore incorporate a focus on addressing multimorbidity alongside traditional airway-centred approaches
Our findings, together with tools such as MiDAS and recognition of the core multimorbidity phenotypes, may contribute to this development. Achieving this will require multidisciplinary team reure severe asthma care pathways
Future research should broaden investigation of multimorbidity in severe asthma and assess multidisciplinary and multimodal approaches designed to address its impact
Author
Ramesh Kurukulaaratchy BM DM FRCP
Professor of respiratory medicine and allergy at the University of Southampton, and respiratory consultant at University Hospital Southampton NHS Trust, UK
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