Asthma Management Handbook

Prescribing relievers for adults

Recommendations

Advise all patients with asthma to carry a reliever containing a rapid-onset inhaled beta2 agonist at all times and use it when they experience difficulty breathing.

Rapid-onset beta2 agonist relievers include:

  • short-acting beta2 agonists (salbutamol, terbutaline)
  • low-dose budesonide/formoterol (for people using budesonide/formoterol as both maintenance and reliever).
  • Formoterol alone should not be prescribed as a reliever inhaler.
  • For all inhalers: Train the patient how to use their inhaler correctly (including spacer, if used). A physical demonstration is essential.
How this recommendation was developed

Consensus

Based on clinical experience and expert opinion (informed by evidence, where available).

Short-acting beta2 agonists should be used only on an as-needed basis for asthma symptoms (e.g. wheezing or breathlessness), and at the lowest dose and frequency required.

Warn patients:

  • that frequent use of short-acting beta2 agonists is a sign of poorly controlled asthma, and may indicate or increase risk of asthma flare-ups
  • not to take their reliever when they do not have asthma symptoms (except before exercise, if indicated).
How this recommendation was developed

Consensus

Based on clinical experience and expert opinion (informed by evidence, where available), with particular reference to the following source(s):

  • Frey et al. 20051
  • Global Initiative for Asthma, 20122
  • Hancox, 20063
  • Suissa et al. 19944
  • Taylor, 20095
  • Taylor et al. 19986
  • Walters et al. 20037

Where more than one reliever option is appropriate, explain the options and take into consideration:

  • the person’s preference
  • the person’s ability to use the device
  • cost
  • potential adverse effects.
How this recommendation was developed

Consensus

Based on clinical experience and expert opinion (informed by evidence, where available).

More information

Correct use of inhaler devices

Checking and correcting inhaler technique is essential to effective asthma management.

Most patients with asthma or COPD do not use their inhalers properly,8, 9,1010, 11 and most have not had their technique checked or corrected by a health professional.

Incorrect inhaler technique when using maintenance treatments increases the risk of severe flare-ups and hospitalisation for people with asthma or COPD.8, 9, 12, 13, 14, 15

Poor asthma symptom control is often due to incorrect inhaler technique.16, 17

Incorrect inhaler technique when using inhaled corticosteroids increases the risk of local side effects like dysphonia and oral thrush.

The steps for using an inhaler device correctly differ between brands. Checklists of correct steps for each inhaler type and how-to videos are available from the National Asthma Council website.

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Short-acting beta-2 agonist relievers for adults and adolescents

Short-acting beta2 agonists are used to:

  • relieve asthma symptoms
  • prevent exercise-induced bronchoconstriction
  • relieve exercise-induced bronchoconstriction.

The duration of therapeutic effect is approximately 4 hours.

When using a pressurised metered-dose inhaler for salbutamol, the use of a large-volume spacer increases the proportion of drug delivered to the lung.18 For adults, it is not essential to use a spacer with salbutamol for day-to-day symptoms if adequate relief is obtained with a pressurised metered dose inhaler alone.

Patients with well-controlled asthma do not need to use their reliever on more than 2 days per week, not counting doses taken before exercise to prevent exercise-induced bronchoconstriction.

Increased use of short-acting beta2 agonists for relief of asthma symptoms, especially daily use, indicates worsening asthma control.

Dispensing of three or more canisters in a year (average 1.6 puffs per day) is associated with increased risk of flare-ups.19 Dispensing 12 or more canisters in a year (average 6.6 puffs per day) is associated with increased risk of asthma death.20

Note: Routine preventive doses of short-acting beta2 agonist taken before exercise are not counted when assessing recent asthma symptom control. However, persistent exercise-induced bronchoconstriction generally indicates inadequate asthma control.

Table. Definition of levels of recent asthma symptom control in adults and adolescents (regardless of current treatment regimen)

Good control

Partial control

Poor control

All of:

  • Daytime symptoms ≤2 days per week
  • Need for SABA reliever ≤2 days per week
  • No limitation of activities
  • No symptoms during night or on waking

One or two of:

  • Daytime symptoms >2 days per week
  • Need for SABA reliever >2 days per week
  • Any limitation of activities
  • Any symptoms during night or on waking

Three or more of:

  • Daytime symptoms >2 days per week
  • Need for SABA reliever >2 days per week
  • Any limitation of activities
  • Any symptoms during night or on waking

SABA: short-acting beta2-agonist

† SABA, not including doses taken prophylactically before exercise. (Record this separately and take into account when assessing management.)

Note: Recent asthma symptom control is based on symptoms over the previous 4 weeks.

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Over-use of short-acting beta-2 agonists

High use of short-acting beta2 agonists may, itself, increase the risk of asthma flare-ups:45

Regular use of short-acting beta2 agonists leads to receptor tolerance (down-regulation) to their bronchoprotective and bronchodilator effects. Tolerance becomes more apparent with worsening bronchoconstriction. In severe asthma, this could result in a poor response to emergency treatment.3

  • Data from population and case-control studies has led to concerns that the frequent use of short-acting beta2 agonists, including salbutamol, is associated with increased risk of asthma deaths.7 The risk of asthma deaths was greatest for fenoterol, which has since been withdrawn from use.4 For salbutamol, the risk is greatest for doses above 1000 microg/day (10 puffs).
  • Dispensing of 3 or more canisters of short-acting beta2 agonist in a year (average 1.6 puffs per day) is associated with increased risk of flare-ups21 Dispensing 12 or more canisters in a year (average 6.6 puffs per day) is associated with increased risk of asthma death.20

When high doses of short-acting beta2 agonist are needed (e.g. dose repeated at intervals of less than 4 hours in a person with acute severe asthma), the patient should be under medical supervision and should usually also be receiving systemic corticosteroids.

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Combination budesonide/formoterol maintenance-and-reliever regimen in adults and adolescents: overview of efficacy

Low-dose budesonide/formoterol combination can be used as reliever for asthma symptoms (instead of using a short-acting beta2 agonist reliever), in addition to its use as regular long-term preventer treatment.22, 23,  24,  2526, 27 The following formulations can be used in maintenance-and-reliever regimens:

  • dry-powder inhaler (Symbicort Turbuhaler) 100/6 microg or 200/6 microg
  • pressurised metered-dose inhaler (Symbicort Rapihaler) 50/3 microg or 100/3 microg.

Neither the 400/12 microg dry-powder inhaler nor the 200/6 microg pressurised metered-dose inhaler should be used in this way.

Overall, clinical trials show that budesonide/formoterol combination as maintenance and reliever reduces the risk of flare-ups that require oral corticosteroids, compared with other current preventer regimens and compared with a fixed higher dose of inhaled corticosteroids.28

Pooled data from five randomised controlled trials assessing budesonide/formoterol maintenance-and-reliever regimens showed that similar or better levels of asthma control were achieved with budesonide/formoterol maintenance-and-reliever compared with the conventional maintenance regimen comparators:24

  • higher-dose budesonide
  • same dose budesonide/formoterol
  • higher-dose inhaled corticosteroid/long-acting beta2 agonist (budesonide/formoterol or fluticasone propionate/salmeterol).

In randomised clinical trials in patients with a history of asthma flare-up within the previous 12 months (and therefore at greater risk of flare-up in the next 12 months), the use of formoterol/budesonide as maintenance-and-reliever regimen reduced the risk of asthma flare-ups that required treatment with oral corticosteroids, compared with the use of any of the following (plus a short-acting beta2 agonist reliever as needed):242930

  • the same combination as maintenance treatment only
  • higher-dose combination as maintenance treatment only
  • higher-dose inhaled corticosteroids.

Meta-analysis of six randomised controlled trials found that maintenance-and-reliever treatment with budesonide/formoterol reduced the risk of severe asthma flare-ups (use of oral corticosteroids for 3 days or more, hospitalisation or emergency department visits), compared with higher-dose inhaled corticosteroid alone, or in combination with a long-acting beta2 agonist.31

In open-label studies in which patients were not selected for a previous history of flare-ups, there was no overall difference in time to first flare-up between budesonide/formoterol as maintenance-and-reliever regimen and conventional maintenance regimens (including inhaled corticosteroid or inhaled corticosteroid/long-acting beta2 agonist combinations, leukotriene receptor antagonists, xanthines or any other asthma medicines) with rapid-onset beta2 agonist reliever (selected according to clinician’s choice).32 However, the inhaled corticosteroid dose was higher with conventional maintenance regimens.

Note: The fluticasone propionate/formoterol combination is approved by the Therapeutic Goods Administration only for regular maintenance therapy.

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Technical notes: pressurised metered-dose inhalers with spacers

Manufacturers of most pressurised metered-dose delivery devices recommend shaking the device before actuating. The physical characteristics of each formulation, including the effects of shaking, differ widely,33 but for simplicity it is best always to recommend shaking of pressurised metered-dose inhalers.

Pressurised metered-dose inhalers (except for those that are breath-actuated) can be used with a spacer. When a spacer is used with a pressurised metered-dose inhaler, delivery of the medicine to the patient’s airways is maximised when the patient takes a slow, deep breath from the spacer after each actuation.3435 Multiple actuations of a pressurised metered-dose inhaler into a spacer can reduce the amount of respirable medicine available because aerosol particles can agglomerate into larger particles or become attached to the spacer walls.34

Therefore, the ideal way to deliver inhaled medicines via pressurised metered-dose inhaler and spacer is to shake the device, ask the person to breathe out all the way into the spacer, actuate a single puff into the spacer, and have the person immediately take a slow deep breath from the spacer, then hold their breath for 5 seconds. This process should be repeated until the total intended number of actuations is taken. Patients should be trained to follow these instructions when using their inhalers. Inhaling slowly with a single breath maximises delivery of the medicine to the lungs and minimises deposition in the upper airways when using a manually actuated pressurised metered-dose inhaler with or without a spacer, or when using a breath-actuated pressurised metered-dose inhaler.36 However, slow breathing may not be possible for patients with acute asthma. Tidal breathing through the spacer (e.g. four breaths in and out without removing the spacer) is used in acute asthma and for very young children. First aid instructions should include how to use inhaler and spacer.

In practice, optimal delivery of inhaled medicines involves a balance between maximising the proportion of respirable medicine and maximising efficiency of inhalation by the patient within real-world constraints. The optimal delivery of salbutamol in real-world circumstances is not well defined. For day-to-day use of salbutamol, most adults gain sufficient relief from symptoms when using a pressurised metered-dose inhaler on its own. A spacer may only be needed during a flare-up. By contrast, the use of a spacer is always recommended for inhaled corticosteroids delivered by manually actuated pressurised metered-dose inhalers, to reduce the risk of local adverse effects and increase delivery to the airways.

Many available in vitro studies of aerosol particle deposition in the airways were performed using older CFC-propelled formulations, which are now obsolete. Similar studies have not been performed for current non-CFC pressurised metered-dose inhalers.

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Ipratropium for adults

Regular ipratropium bromide in addition to as-needed short-acting beta2 agonist does not appear to provide clinically significant benefit over as-needed short-acting beta2 agonists alone.37

Note: Ipratropium bromide may be used in the management of severe acute asthma.

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References

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  2. Global Initiative for Asthma (GINA). Global strategy for asthma management and prevention. GINA, 2012. Available from: http://www.ginasthma.org
  3. Hancox RJ. Concluding remarks: can we explain the association of beta-agonists with asthma mortality? A hypothesis. Clin Rev Allergy Immunol. 2006; 31: 279-88. Available from: http://www.ncbi.nlm.nih.gov/pubmed/17085800
  4. Suissa S, Blais L, Ernst P. Patterns of increasing beta-agonist use and the risk of fatal or near-fatal asthma. Eur Respir J. 1994; 7: 1602-1609. Available from: http://erj.ersjournals.com/content/7/9/1602.abstract
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  15. Giraud, V., Roche, N.. Misuse of corticosteroid metered-dose inhaler is associated with decreased asthma stability. The European respiratory journal. 2002; 19: 246-51. Available from: https://www.ncbi.nlm.nih.gov/pubmed/11866004
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  17. Hardwell, A., Barber, V., Hargadon, T., et al. Technique training does not improve the ability of most patients to use pressurised metered-dose inhalers (pMDIs). Prim Care Respir J. 2011; 20: 92-6. Available from: http://www.nature.com/articles/pcrj201088
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  33. Cyr TD, Graham SJ, Li KY, Levering EG. Low first-spray drug content in albuterol metered-dose inhalers. Pharm Res. 1991; 8: 658-660. Available from: http://link.springer.com/article/10.1023/A:1015825311750
  34. Barry PW, O'Callaghan C. Multiple actuations of salbutamol MDI into a spacer device reduce the amount of drug recovered in the respirable range. Eur Respir J. 1994; 7: 1707-1709. Available from: http://www.ncbi.nlm.nih.gov/pubmed/7995401
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  37. Westby M, Benson M, Gibson P. Anticholinergic agents for chronic asthma in adults. Cochrane Database Syst Rev. 2004; Issue 3: CD003269. Available from: http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD003269.pub2/full