Asthma represents one of the pillars of the MRINZ. The primary focus is to investigate novel approaches to management and prevention of asthma.

Anti-inflammatory reliever therapy in asthma

There have been longstanding concerns that the traditional approach of using a short-acting beta-agonist (SABA) as reliever therapy in asthma may be associated with risk, across the spectrum of asthma severity. These concerns have led to a novel treatment approach in which an inhaled corticosteroid (ICS) is combined with a beta-agonist within the same inhaler device, which is used as-needed for relief of symptoms. The MRINZ has led three large randomised controlled trials of patients with asthma which have shown that this novel regimen of a combination ICS/long-acting beta agonist (LABA) inhaler taken as required for relief of symptoms is superior to SABA reliever therapy in reducing the risk of severe attacks.

The SMART study, which was undertaken in New Zealand, and published in the Lancet Respiratory Medicine, showed that in high-risk adults with severe asthma on maintenance ICS/LABA therapy, the use of budesonide-formoterol (ICS/fast onset LABA) as a reliever markedly reduced the risk of severe exacerbations compared with the use of the SABA salbutamol as a reliever. This was the first independent clinical trial of this regimen, and was funded by the Health Research Council of New Zealand. It was the first major asthma study that incorporated electronic monitors to record the date and time of inhaler actuations, thereby allowing patterns of use to be determined, and as a result the assessment of acute and long term medication side effects.

The Novel START study, which was undertaken in the United Kingdom, Italy, Australia and New Zealand, and was published in the New England Journal of Medicine, showed that in adults with mild asthma, as-needed budesonide-formoterol taken for relief of symptoms markedly reduced the risk of severe asthma attacks compared with as-needed salbutamol (SABA). As-needed budesonide/formoterol also markedly reduced the risk of severe asthma attacks compared with regular budesonide (ICS) and as-needed salbutamol, despite a lower total dose of ICS being taken. Budesonide/formoterol reduced the FeNO, a measure of airways inflammation, indicating that this regimen can be referred to as ‘anti-inflammatory reliever (AIR) therapy’.

The PRACTICAL study, which was undertaken in New Zealand, and was published in The Lancet, confirmed that as-needed budesonide/formoterol reduced the rate of severe asthma attacks compared with regular scheduled budesonide and the SABA terbutaline, in adults with mild to moderate asthma. This independent study was funded by the Health Research Council of New Zealand.

The findings have been incorporated into New Zealand and international guidelines which now recommend that anti-inflammatory reliever therapy with ICS/formoterol is preferred to a SABA in the management of asthma across the spectrum of asthma severity. The translation of the findings have led to a major shift in clinical practice in New Zealand and internationally, which will undoubtedly improve outcomes in patients with asthma and reduce the global burden of disease.

There is an evidence gap on whether anti-inflammatory reliever therapy is also suitable for children. We have designed the CARE study to determine if 2 in 1 combined reliever therapy is also the best way to treat children with mild asthma. Recruitment is currently underway, and you can learn more here if interested.

Precision Medicine

The MRINZ is part of an international collaborative group which has proposed a paradigm shift in the approach to the management of asthma and COPD. It is based on the concept that asthma and COPD represent a continuum of different diseases that share biological mechanisms and present with distinct clinical, pathophysiological and psychosocial features that can be observed and which require individualised treatment. This allows treatments to be targeted to the needs of individual patients on the basis of such clinical characteristics that distinguish a given patient from other patients. The main publication in this field has been ‘The Lancet Commission on Asthma’, a major treatise which challenges the current management approach to asthma, and proposes a revolution in thinking about asthma. Recommendations made in The Lancet Commission on asthma have the potential to lead to a paradigm shift in the assessment and management of asthma worldwide.

Prevention of asthma

Paediatric asthma is a major public health problem in New Zealand. Prevalence rates for childhood asthma are amongst the highest in the world. There is an urgent need for research that leads to evidence-based primary prevention strategies to reduce the prevalence of asthma. This has led to consideration of the role of novel risk factors that may increase the susceptibility to the development of asthma, and may be amenable to simple public health intervention programmes. One such risk factor for which there is substantive evidence for a potential causative role is the frequent use of paracetamol. The first ever randomised controlled trial investigating whether paracetamol increases the risk of childhood asthma has begun, and recruitment is on track, with over one-third of participants having been recruited. This study, led by Professor Stuart Dalziel from the University of Auckland, in collaboration with the MRINZ, is funded by the Health Research Council of New Zealand.

This study not only has the potential to determine whether increasing use of paracetamol over recent decades has contributed to the higher asthma rates, but also could lead to primary intervention strategies.