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People with mild asthma often have two inhalers. One (usually blue) inhaler contains reliever medicine to treat symptoms when they occur. The other contains steroids to make the airways less sensitive. New research tested a single inhaler, combining both drugs and used only when people have symptoms. The study found it is an effective treatment for mild asthma.

Asthma is a common lung condition that causes breathing difficulties. Even people with mild asthma experience occasional wheezing, tightness of the chest and breathlessness. There is no cure, but treatments reduce symptoms.

Inhaled steroids reduce inflammation in the airways. But fear of side effects can put people off taking them, especially if they rarely have symptoms. However, not taking this medication regularly can lead to worsening asthma and an increased chance of a serious asthma attack.

The combination inhaler (an inhaler including both steroids and reliever medicines) is currently only licensed for use in the UK for moderate asthma. This study looked at its effect on people with mild asthma.

Researchers pooled the results from 6 studies that compared separate inhalers with a combination inhaler. They found that the combination inhaler was an effective treatment for mild asthma.

Further information on asthma is available on the NHS website.

What’s the issue?

Asthma affects around 350 million people worldwide. Many (between 45% and 70%) have mild disease. Symptoms include wheezing (a whistling sound while breathing), breathlessness, a tight feeling in the chest and coughing. When these symptoms temporarily get worse, it is called an asthma attack . There is no cure, but simple treatments can keep the symptoms under control.

People with asthma are prescribed an inhaler containing reliever medication called a fast-acting beta agonist. This relaxes the muscles of the airways and is used as needed when symptoms occur. A second inhaler contains a steroid. It should be taken regularly to reduce inflammation in the airways. This helps control the disease and reduces the risk of asthma attacks and of dying.

Inhaled steroids are associated with side effects such as an increased risk of osteoporosis (weakened bones), diabetes and mood or sleep disorders. People may be reluctant to take the steroids, and many are tempted to rely only on their reliever medication. However, their symptoms can get worse when they don’t use steroid inhalers regularly. This increases their risk of asthma attacks.

During an asthma attack, people may need oral or injected steroids, and they may be admitted to hospital. Severe attacks can result in death. Most people in the UK who die of asthma have mild or moderate disease. Death is more common among those who do not use their inhaled steroids as directed.

The combination inhaler is used in moderate asthma. Researchers explored whether it is safe and effective for mild asthma.

What’s new?

This review pooled data from studies of people with mild asthma, aged 12 and over. The studies lasted at least 12 weeks and were carried out all over the world. They explored the use of a combination inhaler, used as needed. It contained reliever medicine (formoterol) and steroid (dry-powder budesonide).

The first analysis included 2,997 people. It compared the combination inhaler (used as needed) with reliever-only treatment (which reflects how people tend to use their inhalers in the real world). Evidence was ranked according to how certain the finding was. Certainty depends on the size of studies, and their  design.

The analysis found that, compared with reliever-only treatment, the combination inhaler:

    • reduced attacks needing emergency oral or injected steroids by over half in one year (high certainty)
    • was linked with fewer adverse events (moderate certainty)
    • was as effective at controlling symptoms; its use led to a similar number of symptom-free days (moderate certainty).

The second analysis included 8,065 people and compared the combination inhaler with treatment as prescribed. That is, regular inhaled steroid with reliever medication as required.

This analysis found that, compared with treatment as prescribed, the combination inhaler:

    • was as effective at controlling symptoms (high certainty)
    • had a similar rate of adverse events (moderate certainty)
    • was linked with less use of inhaled steroid (moderate certainty).

Both analyses found low certainty evidence that the combined inhaler reduced the chance of an emergency hospital or urgent care visit for asthma.

The combined inhaler used as required is effective for mild asthma, the researchers say.

Why is this important?

The study compared the combination inhaler to reliever-only treatment (which reflects how people tend to use their inhalers in the real world). It found that in mild asthma, the combination inhaler dramatically reduced the need for emergency steroids for asthma attacks. It was similarly effective in controlling symptoms but linked with fewer side effects.

When compared to treatment as prescribed, the combination inhaler reduced the amount of inhaled steroid used, without reducing asthma control. A reduction in inhaled steroids could limit long-term side effects and improve people’s quality of life.

The combination inhaler is used only when people feel their symptoms are worsening. It means that people automatically get the inhaled steroid when they use their reliever. This approach simplifies asthma treatment and could make the disease easier for people to manage.

International guidelines were recently updated to recommend combination inhalers in mild asthma. This research supports the change. The researchers hope that their findings will inform the forthcoming draft of the British Thoracic Society (BTS) guidelines.

The researchers say that the combination inhaler empowers people and could be critical to improving asthma treatment. This is important since asthma is a major cause of chronic ill health and a largely preventable cause of death for 400,000 people per year globally.

What’s next?

The study was too small to find a reduction in death rates with the combination inhaler; larger studies would be needed. In addition, the researchers recommend a cost-effectiveness analysis. They also say that reliever medications (other than those in this study) could be tested.

Exploring this treatment in children younger than 12 will be an important next step.

You may be interested to read

The paper this NIHR Alert is based on: Crossingham I, and others. Combination fixed-dose β agonist and steroid inhaler as required for adults or children with mild asthma: a Cochrane systematic review. BMJ Evidence-Based Medicine 2021; doi:10.1136/bmjebm-2021-111764

Global Strategy for Asthma Management and Prevention: the 2021 update from the Global Initiative for Asthma.

Why asthma still kills: a report from the National Review of Asthma Deaths into the circumstances surrounding deaths from asthma in the UK.

 

Photo: Asthma + Lung UK.

Funding: This project was funded by the NIHR Cochrane Incentive Awards 2019 and the Wellcome Trust.

Conflicts of Interest: Several of the authors have reported a conflict of interest.

Disclaimer: NIHR Alerts are not a substitute for professional medical advice. They provide information about research which is funded or supported by the NIHR. Please note that views expressed in NIHR Alerts are those of the author(s) and reviewer(s) and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care.


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Commentaries

Study author

Three people die each day of asthma in the UK. Some have mild disease. This work shows that simplifying the treatments and empowering patients to decide for themselves when they need to use their inhaler will improve their condition.A lot of studies have been published recently. International guidelines have been changed and British Thoracic Society (BTS) guidelines are being rewritten now. It was the right time to do an objective review of the evidence.Timothy Hinks, Senior Research Fellow and Honorary Consultant, Nuffield Department of Medicine, University of Oxford 

British Thoracic Society

This review is timely and informative. It reinforces the use of inhaled steroids as soon as the diagnosis of asthma is made, even in patients who are typically classified as having ‘mild’ asthma. However, adherence to inhaled therapy can be poor and many patients only take their treatment when they are symptomatic.This review has shown that symptom-directed therapy (i.e. as and when required use of combination steroid/reliever) is just as effective as regular inhaled steroid therapy, and is associated with fewer asthma-related hospital admissions. Clinically, this is very relevant as severe asthma exacerbations are associated with considerable morbidity.For the patient, it represents a more simplified treatment regime, enables timely delivery of anti-inflammatory therapy into the lung, and will help reduce over-reliance on reliever therapy. However, optimising inhaler technique, ensuring patients have a personalised self-management plan and supporting smoking cessation (when relevant) remain important components of asthma care.Hitasha Rupani, Consultant Respiratory Physician, University Hospital Southampton NHS Foundation Trust and Chair of the British Thoracic Society (BTS) Asthma Specialist Advisory Group 

Primary care clinical academic 

This well-conducted review adds weight to recent changes in national and international asthma guidelines. The guidelines have moved away from recommending relievers as the first step in asthma management. Inhaled steroids (either in combination with reliever medication, or in separate inhalers) are convincingly superior to reliever medication alone.Combination steroid/reliever inhalers were more convenient and slightly more effective than separate inhalers in this review. These inhalers are used as required, which is in line with the preference of many people with mild asthma only to take medication ‘when they need it'. It is a bonus that the overall steroid dose is lower when used as required.Cost will be a barrier to using combination inhalers. Decisions will need to consider some practical factors. Although separate inhalers are similarly effective in trials, the combination inhaler means that in the real world, people cannot default to just using the reliever.Hilary Pinnock, Professor of Primary Care Respiratory Medicine, Asthma UK Centre for Applied Research, The University of Edinburgh 

Researcher in the same field

This work should help shift asthma guidelines towards earlier use of a single inhaler containing both steroid and reliever medication. Although this approach is not licensed in the UK at the moment for mild asthma, the research will inform my practice.Dominick Shaw, Researcher and Clinician, University of Nottingham 
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