Associate Editor: Paul Foster
Remission of asthma: The next therapeutic frontier?

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Abstract

Asthma treatment goals focus on disease control rather than remission as a therapeutic aim. This is in contrast to diseases where remission is frequently discussed and has well-defined criteria. In this review, we consider the similarities and differences between remission in asthma and another chronic inflammatory disease, rheumatoid arthritis, where new therapies have made remission a realistic treatment goal. Clinical remission of asthma is often defined as prolonged absence of asthma symptoms without requirement for medication while others insist on the demonstration of normal lung function and airway responsiveness. Even in those who develop a symptomatic remission of asthma, persistent physiological abnormalities and airway inflammation are common. There is a clear need to develop a precise, internationally accepted, definition of asthma remission that can be used as a therapeutic endpoint in studies of new asthma treatments. Spontaneous remission of asthma symptoms is relatively common, especially during adolescence. It is more likely in males, those with mild symptoms and normal lung function and in those who quit smoking, and may be linked to normalisation of immune function. Remission is less likely in severe asthma, atopy, eosinophilia, airflow obstruction, continued smoking and weight gain. Studies of spontaneous remissions may provide insight into how remission might be induced with therapy. Remission is not identical to cure, there remains a risk of subsequent symptomatic relapse of asthma and there is little evidence that current asthma treatments can induce remission. Long-term remission should be regarded as the next therapeutic frontier in asthma management.

Introduction

Asthma is a chronic disease characterised by variable airflow obstruction, airway hyper-responsiveness (AHR) and airway inflammation, and risk of long-term airway remodeling and fixed airflow obstruction. Advances in asthma treatments, especially the introduction of inhaled corticosteroids and long-acting β-agonists, have improved the symptoms of asthma and reduced the frequency of severe life-threatening exacerbations of the disease. Asthma is now a treatable condition but is not curable. While it is logical to think that optimal management might minimize disease progression and increase the chances of inducing remission, there is little evidence that this is true.

Most discussion of asthma treatment goals revolves around disease control (Bateman et al., 2008, Taylor et al., 2008), and little attention is paid to remission as an achievable therapeutic goal. This is in contrast to other inflammatory diseases such as rheumatoid arthritis where remission is frequently discussed and has well-defined criteria. In this review, we consider rheumatoid arthritis (RA), a chronic inflammatory disease, in which new therapies have made remission a realistic treatment goal, and contrast this with remission in asthma. We discuss the issue of what constitutes an appropriate definition of an asthma remission, and review current evidence concerning spontaneous remission of asthma: its prevalence and the clinical, physiological and inflammatory features that are associated with remission. Finally, the influences of interventions on asthma remission are also considered.

Section snippets

Remission in another chronic inflammatory disease: lessons from rheumatoid arthritis

In considering remission in asthma, it is instructive to consider RA, another chronic disease in which the introduction of new therapies has made remission a realistic treatment goal. There are some parallels between asthma and RA: both are chronic inflammatory diseases with no known cure, and in both instances inadequate control of tissue inflammation is associated with chronic organ dysfunction.

In the past, both spontaneous remission and treatment-induced remission in RA were uncommon, but

Definitions of remission of asthma

Unlike RA, clinicians and researchers in asthma refer to the absence of symptoms and absence of pathology (shown by normal lung function and normal airway responsiveness) in response to therapy as ‘good control’ or ‘total control’ (Bateman et al., 2008, Taylor et al., 2008), rather than remission. Control in asthma has been well defined by consensus, but in contrast to RA, there is no clear consensus on what constitutes a remission of asthma. In RA, the term remission seems analogous to

Remission and the ‘natural history’ of asthma

Since the prevalence of asthma fluctuates across different age groups and because the term ‘asthma’ likely represents a spectrum of disease entities, it is important to consider remission in the context of the natural history and the heterogeneity of asthma.

Heterogeneity

There is no gold standard for the diagnosis of asthma. Large epidemiological studies, such as those reviewed above define asthma variably as: a history of wheeze (ever or in the last 12 months), asthma diagnosed by a doctor (ever), wheeze in the last 12 months AND airway hyper-responsiveness, doctor diagnosed asthma AND symptoms within the last 12 months AND/OR current use of treatment for asthma, or a combination of symptoms and a demonstrable bronchodilator response.

While the preceding studies

Can therapy influence remission in asthma?

While the preceding discussion has addressed spontaneous asthma remission, it is important to consider whether asthma therapy has an impact on remission. Though there is strong evidence that early introduction of effective therapy will induce a state of remission in RA, the same cannot be said at this time in asthma. Although inhaled steroids are generally very effective in asthma – they reduce symptoms, prevent exacerbations and improve lung function and airway responsiveness – it is widely

Summary and conclusions

Spontaneous remission of asthma symptoms is not uncommon. While it may occur at any age, it is most frequent during adolescence and early adulthood. However, mild airflow obstruction, AHR, and airway inflammation often persist, so that a definition of remission on the basis of symptoms and medication use alone will often overlook subclinical disease in which there is persistent airway inflammation and remodeling.

Although there is a lack of consistency in the definitions used to define asthma

Acknowledgments

The authors wish to thank Peta Grayson for administrative assistance in the preparation of the manuscript.

Sources of support: National Health & Medical Research Council of Australia, Asthma Foundation of Queensland, Princess Alexandra Hospital Foundation and Asthma Foundation of Western Australia.

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