Fundamental changes in asthma management guidelines aim to reduce severe attacks

New asthma guidelines were recently released by the Asthma and Respiratory Foundation NZ. Treatment for adults and adolescents (ie, people aged 12 and over) is the same and the recommendations are now together in one guideline.¹ The child guidelines have also been reviewed and updated.² These guidelines are based on the new recommendations by the Global Initiative for Asthma (GINA).

The GINA Assembly includes members from 45 countries. Every year, they publish a report³ and a pocket guide,⁴ with the intent to provide a comprehensive international approach to management of asthma and to provide clear guidelines and feasible tools for clinical practice, using a strong evidence base.

In 2019/2020, there were major changes to GINA’s recommendations for asthma treatment. The large, double-blind study used to support the GINA recommendations investigated the combined inhaled corticosteroid (ICS)/long-acting beta2 agonist (LABA) budesonide/formoterol, used either as needed or regularly plus as needed.

It is important to note that these recommendations apply only to people with asthma, not to people with chronic obstructive pulmonary disease (COPD). The inhaler regimens for COPD are different from asthma, but people can have both asthma and COPD at the same time. New Zealand’s first-ever COPD guidelines will be published later this year.

Another important reminder is that people with asthma should continue taking all prescribed asthma medications during the COVID-19 pandemic.

Why have the recommendations changed?

Previous recommendations date back many years and were based on the belief that mild asthma was primarily bronchoconstriction. We now know that inflammation of the airways is found in most people with asthma, even if they only have symptoms intermittently.

Clinical studies have shown that treatment with an ICS significantly reduces the frequency and severity of asthma symptoms, and markedly reduces the risk of experiencing, or even dying from, an asthma attack.

There is strong evidence that, although short-term relief of asthma is achieved with short-acting beta2 agonist (SABA)-only treatment, this does not protect from severe exacerbations. In fact, regular or frequent use of SABA treatment actually increases the risk of exacerbations, worsening airway inflammation and lung function, and increasing allergic reaction.

The GINA report states that overuse of SABA treatment (eg, three or more canisters per year) is associated with an increased risk of severe exacerbations, and 12 or more canisters per year is associated with increased risk of asthma-related death.³

The new recommendations aim to:

• reduce the risk of serious exacerbations
• reduce the pattern of people depending on SABA-only treatment to manage their asthma
• provide consistent treatment plans across the whole range of asthma severity.

Have you heard of ‘AIR’ therapy?

Anti-inflammatory reliever (AIR) therapy is the use of a combination budesonide/formoterol inhaler as a reliever medication. It can be used either only as needed or regularly plus as needed. This approach includes and extends the “single combination ICS/LABA inhaler maintenance and reliever therapy” (SMART) approach previously recommended.

• AIR therapy requires an ICS in combination with a fast-onset beta2-agonist – the only such combination currently available in New Zealand is budesonide/formoterol.
• Remember, formoterol and eformoterol are alternative names for the same medication.
• Other combinations of ICS/LABA should not be used in this way.
• When using budesonide/formoterol as maintenance and reliever therapy, a SABA reliever should not be prescribed.
• For people using a combination ICS/LABA maintenance inhaler that is not budesonide/formoterol, a SABA reliever should still be used.
• The budesonide/formoterol reliever combination should not be prescribed in addition to other ICS/LABA preparations.
• A LABA should not be prescribed without an ICS for people with asthma.
• Note that the budesonide/formoterol 400μg/12μg formulation should not be used as a reliever.

AIR therapy in New Zealand – the only ICS/fast-onset beta2-agonist combination currently available in New Zealand is budesonide/formoterol, and the only preparations approved for reliever use are the Symbicort Turbuhaler and DuoResp Spiromax dry powder inhalers.

A budesonide/formoterol pressurised metered dose inhaler is available, but this would represent an off-label prescription.

What has changed for treatment of adults and adolescents?

Starting asthma treatment with a SABA (ie, salbutamol orterbutaline) alone is no longer recommended. Instead, it is recommended that an ICS should be initiated from first diagnosis.

This can be done either by introducing AIR treatment or by using traditional ICS/SABA therapy. One of the risks of traditional ICS/SABA therapy is that people do not use the ICS and rely solely on the SABA. AIR therapy removes this risk as the ICS is included in the reliever treatment as well as maintenance treatment.

Stepwise AIR-based algorithm using budesonide/formoterol 200μg/6μg:¹

• Step 1 – one inhalation as required to relieve symptoms.This results in a similar short-term bronchodilator response as a 200μg dose of salbutamol and, in adults and adolescents with mild asthma, reduces the risk of a severe asthma exacerbation by at least 60 per cent compared with SABA reliever alone.
• Step 2 – regular maintenance treatment is implemented as either one inhalation twice daily or two inhalations once daily, depending on patient preference.
• Step 3 – maintenance treatment is stepped up to two inhalations twice daily.

In adults and adolescents taking maintenance ICS/LABA therapy, budesonide/formoterol used as a reliever reduces the risk of a severe asthma exacerbation by about one-third compared with using a SABA reliever. Thus, budesonide/formoterol used both as a reliever plus regularly as maintenance therapy is the preferred treatment for patients with moderate to severe asthma.

Stepwise ICS/SABA-based algorithm for asthma management:¹

• Step 1 – introduce standard-dose ICS as maintenance treatment plus a SABA as needed.
• Step 2 – use standard-dose ICS/LABA as maintenance treatment plus a SABA as needed.
• Step 3 – use high-dose ICS/LABA as maintenance treatment plus a SABA as needed.

Note the recommendation that if a severe exacerbation of asthma occurs, consider switching to AIR therapy.

ICS doses

For most people, most of the clinical benefit is obtained with low-dose ICS. Some people will need standard-dose ICS if their asthma is not well controlled with low-dose ICS,but adherence and inhaler technique should be checked first. A few will need high-dose ICS.

When an ICS is initiated as maintenance therapy together with a SABA reliever, a standard dose of ICS should be used. The recommended standard daily dose of different ICS preparations for adults is as follows: beclomethasone dipropionate 400–500μg/day, beclomethasone dipropionate extra fine 200μg/day, budesonide 400μg/day, fluticasonepropionate 200–250μg/day, or fluticasone furoate100μg/day.¹

What if optimal inhaled therapy doesn’t work?

Long-acting muscarinic antagonists – are not subsidised in New Zealand for treatment of asthma, although tiotropium is a Medsafe approved indication. Note that LAMAs are funded for patients with COPD, and there will be a significant cohort who have coexisting asthma and COPD.

Montelukast – is a leukotriene receptor antagonist. In New Zealand, it is indicated for adults and children over the age of two for prophylaxis of asthma or relief of allergic rhinitis (seasonal or perennial). Montelukast should be considered as add-on therapy when control is not achieved with optimal standard treatment; for everyone with respiratory conditions exacerbated by asthma; and may be useful in exercise-induced asthma or people with coexisting rhinitis.⁵

Note the precaution around neuropsychiatric side effects with montelukast:⁶ “Contact your doctor if you experience sleeping problems, strange dreams, changes in behaviour,hallucinations, anxiousness or agitation, confusion or suicidal thoughts.”⁷

Mast cell stabilisers – sodium cromoglycate and nedocromil inhalers are approved for use in mild asthma, but there have been recent notifications of discontinuation of supply in New Zealand. As of 1 July 2020, sodium cromoglycate and nedocromil inhalers are no longer funded for new patients– these patients should be managed on alternative treatments, in line with current asthma guidelines.⁸

Other treatments – include high-dose ICS, oral corticosteroids, theophylline, azithromycin and monoclonal antibodies, many of which will only be used following specialist review.

Children aged under 12

The New Zealand Child Asthma Guidelines were updated in June. These guidelines include important ways that all health professionals can help children with asthma, apart from prescribing medicines (see panel).

The guidelines also summarise the medication approaches for children of different ages (see below). The goal is for all children to use an inhaler device that is appropriate for their development, including consideration of whether a spacer or mask is appropriate.

It is important that children’s treatment includes regular review to allow step-up or step-down through treatment options as appropriate for symptom control.

Children aged one to four years – who wheeze are considered in a different way from children aged five to 11, as many preschool children with post-viral wheeze do not have asthma or go on to develop asthma.

The current recommendations are:²

• Step 1 – SABA reliever alone (one to two puffs when needed).
• Step 2 – add maintenance low-dose ICS.
• Step 3 – add montelukast.
• Step 4 – refer to a paediatrician.

Note that if SABA, ICS and montelukast are insufficient, Step 4 is referral to a paediatrician. This means that LABAs are not part of the routine management of wheeze or asthma in this age group.

Children aged five to 11 years – assessment of inhaler technique and adherence to treatment remains key in this age group.

The current recommendations are:²

• Step 1 – SABA reliever alone (one to two puffs when needed).
• Step 2 – add maintenance low-dose ICS.
• Step 3 – add LABA.
• Step 4 – increase to standard dose of maintenance ICS/LABA; add montelukast; consider referral to a paediatrician.
• Step 5 – consider high-dose ICS/LABA; refer to a paediatrician.

At Step 5, the child will likely be having frequent oral steroids and should definitely be referred to a paediatrician.

SMART using budesonide/formoterol 100μg/6μg (eg, Turbuhaler) may be considered on specialist advice in select children who are poorly controlled at Steps 3 to 5. Currently, there is insufficient evidence to recommend SMART as first-line therapy in children aged 11 years and younger.

Review treatments with your patients

In New Zealand at the moment, many people will be using SABA-only treatment for mild asthma.In 2018, over two million salbutamol inhaler devices were dispensed in the community setting in New Zealand,making it the eighth most dispensed Pharmac-funded drug (Pharmac data: https://bit.ly/2SM2dRN, https://bit.ly/2yCl7nq).

Asthma attacks can be very serious, even fatal. They are more common and more severe in people with poorly controlled asthma and in high-risk people, but they can occur in anyone with asthma. It is worth asking people how much SABA they are actually using – inhalers do tend to get lost or given to someone else, and some people will want to have inhalers in different rooms of the house, in the car, etc.

Many people who are prescribed an ICS don’t collect their ICS prescriptions. Having one combined ICS/LABA for as-needed use, and for regular use if required, not only ensures that the ICS is taken more regularly but also provides safer treatment right from the start.

Inhaler technique – now is a great opportunity to encourage review and optimisation of treatment, and to provide education. Worldwide, it is estimated that up to 80 per cent of people do not use their inhaler correctly, and at least 50 per cent do not use their maintenance medications as prescribed. Inhaler technique remains critical to optimal therapy, no matter which inhaler device is being used. Ensure patients are getting the best out of their treatment by checking their inhaler technique.

Asthma plans – people with asthma should still be encouraged to have an asthma action plan (https://bit.ly/2CvmPsj). Of course, everyone is different, and the treatment plan should be individualised for each patient. Choice of treatment will depend on many factors, such as severity of asthma, other lung conditions, personal preference, ability to use devices and other health conditions.

What does good control of asthma look like?

People with well-controlled asthma:

• have no or minimal symptoms both during the day and at night.
• need little or no as-needed medication
• can participate in physical activities without restriction
• have normal or near-normal lung function
• avoid serious asthma exacerbations, including the need for hospitalisation.

Helen Cant is a pharmacist prescriber working in general practices in Tokoroa