The new recommendations for asthma management published by the Global Initiative for Asthma (GINA) are considered to be the most fundamental change in managing asthma in 30 years.1 The initiatives aim at providing evidence-based treatment options in mild asthma for patients and physicians, and the recommendations follow a decade of work by GINA, tackling the risks and consequences of short-acting β2-agonists (SABAs) alone in asthma management, were presented at the European Respiratory Society (ERS) 2019 International Congress in Madrid, Spain.2,3
The need for a global initiative in asthma care
Intermittent or persistent mild asthma affects between 50% and 75% of asthmatic patients.4 The GINA recommendations provide an integrated evidence-based strategy to be translated into the management of mild asthma.1,2,5 Their main goal is to improve the symptoms and seek interventions for mild asthma to reduce the risk of asthma-related exacerbations or death.2 GINA focuses on further enhancing the current understanding of underlying disease processes and integrating recent findings into clinical practice.2
Patients with mild asthma are at risk of acute exacerbations and 30%-37% of adults with mild asthma experience more than one acute symptom per week.4 The triggers for exacerbations may vary significantly among individuals. Viruses, pollen, pollution, and poor adherence to treatment regimens are the most common triggers.5 Inhaled SABA has been the first-line treatment for asthma for 50 years. In addition to patient satisfaction, the reliance on SABA treatment is reinforced by its rapid relief of symptoms, its prominence in emergency management, and low cost.5
Short-acting β2-agonists alone are no longer recommended for the quick relief of asthma symptoms
Introducing the GINA recommendations at the press conference at ERS 2019 congress, Prof. Helen Reddel, Chair of the GINA science committee, from the Woolcock Institute of Medical Research in Sydney, Australia, commented, “The primary recommendation we made is against the use of quick relief medication SABA, which has been the first-line treatment of asthma for 50 years.”3
According to the 2019 GINA recommendations for adults and adolescents, SABA alone is no longer recommended for the quick relief of asthma symptoms (Figure 1).1,2 Although the basis of this recommendation is safety, it is a major revolutionary change in asthma management.
Prof. Reddel further justified the recommendation, stating “The paradox we need to explain is that SABA can save your life, but it can also kill you.”3
SABA has been the focus of extensive research in the last two decades, mainly due to its adverse events.6 Furthermore, a number of case control studies have shown the overuse of SABA to be linked with increased risk of asthma-related deaths.7,8 According to a number of randomized controlled trials, the efficacy of regular-use SABA was non-inferior to as-needed SABA.9 Considering these results, most guidelines published during the last decade recommended SABA for as-needed rather than for regular use. Still, the short-term regular use of SABA has demonstrated reduced bronchoprotection and bronchodilator response, increased airway hyper-responsiveness, exercise-induced bronchoconstriction and allergic responses, and increased eosinophilic inflammation and mast cell mediator release.10
ICS is a preferred controller treatment in mild asthma. It was found that patients with a lower ratio of ICS to SABA were at greater risk of asthma-related hospitalization and urgent admission.11 Concurrently, population-based strategies that increased access to ICS were able to reduce asthma-related hospitalizations and deaths.12 Therefore, current guidelines recommend low-dose ICS to be taken whenever SABA is taken. In addition, concerns about the risk of SABA has resulted a shift towards using long-acting β2-agonists (LABAs), but the management of mild asthma with LABA only is not recommended.2
GINA also recommends that all adults and adolescents with asthma to receive symptom driven or regular low-dose ICS-containing controller treatment, aiming to reduce the risk of serious exacerbations.1,2 Regular use of ICS has been demonstrated to significantly reduce the risk of asthma-related hospitalization and death.13,14 Furthermore, large randomized controlled trials on daily ICS use in mild asthma has shown a 31% reduction in hospitalization due to acute exacerbations.14 Additionally, daily low-dose ICS has controlled asthma symptoms and improved the quality of life.15 However, the acceptance of daily doses of ICS is slow, particularly due to the concerns of physicians about the serious side effects related to oral corticosteroids.6
Due to the serious side-effects of both ICS and SABA, GINA recommends a combination of as-needed low-dose ICS and low-dose formoterol – a LABA, for mild asthma.1,2 Formoterol was introduced due to its superiority over the other β2-agonists used in the treatment of mild asthma. When compared to terbutaline – a SABA, formoterol combined with budesonide demonstrated a 64% reduction of severe exacerbations.16 Also, as-needed formoterol and budesonide was non-inferior to budesonide maintenance therapy for patients with severe exacerbations.17
Although combining LABA and ICS has not caused any additional risk increase in serious asthma-related events compared to ICS alone, it has significantly reduced the events of asthma exacerbations.18 In light of these findings, Prof. Reddel concluded the session, emphasizing, “These new guidelines introduced will help circumvent some reliever overuse and preventer underuse.”3
Separate recommendations for children aged 6-11 years
The newest recommendations feature a separate treatment figure for children aged 6-11 years (Figure 2).1,2 Children with mild persistent asthma should not be treated with rescue SABA alone, and the most effective treatment to prevent acute asthma exacerbations is daily ICS. In addition, ICS as rescue medication with SABA is an effective strategy for children with well-controlled, mild asthma.19 However, the introduction of formoterol for both maintenance and as-needed symptom relief reduces the exacerbation rate compared with ICS alone in children with asthma.20 In situations where medium dose ICS-LABA may be needed, expert advice is warranted.2
As a global initiative, GINA aims to improve asthma care by presenting evidence-based treatment options. In the latest 2019 guidelines, GINA recommends against the use of quick relief medication SABA, which has been the first-line treatment of asthma for 50 years. According to the new guidelines, controller treatment for all adults and adolescents with mild asthma should consist of symptom driven or regular low-dose ICS. However, adherence to maintenance treatment with ICS in mild asthma remains a distant hope. Therefore, GINA recommends the combination of as-needed low-dose ICS and low-dose LABA for the management of mild asthma as the second step. The new recommendations will allow patients with mild asthma to experience a better quality of life by reducing the risk of acute exacerbations.
1. Reddel HK et al. GINA 2019: a fundamental change in asthma management: Treatment of asthma with short-acting bronchodilators alone is no longer recommended for adults and adolescents. Eur Respir J. 2019;53(6).
2. GINA-2019-main-Pocket-Guide-wms.pdf. https://ginasthma.org/wp-content/uploads/2019/04/GINA-2019-main-Pocket-Guide-wms.pdf. Accessed November 1, 2019.
3. Big Changes in Asthma Treatment in New Global Guidelines. Medscape. http://www.medscape.com/viewarticle/919266. Accessed November 1, 2019.
4. Dusser D et al. Mild asthma: an expert review on epidemiology, clinical characteristics and treatment recommendations. Allergy. 2007;62(6):591-604.
5. Muneswarao J et al. It is time to change the way we manage mild asthma: an update in GINA 2019. Respir Res. 2019;20(1):183.
6. Crompton G. A brief history of inhaled asthma therapy over the last fifty years. Prim Care Respir J. 2006;15(6):326-331.
7. Suissa S et al. A cohort analysis of excess mortality in asthma and the use of inhaled beta-agonists. Am J Respir Crit Care Med. 1994;149(3 Pt 1):604-610.
8. Abramson MJ et al. Are asthma medications and management related to deaths from asthma? Am J Respir Crit Care Med. 2001;163(1):12-18.
9. Drazen JM et al. Comparison of regularly scheduled with as-needed use of albuterol in mild asthma. Asthma Clinical Research Network. N Engl J Med. 1996;335(12):841-847.
10. Hancox RJ. Concluding remarks: can we explain the association of beta-agonists with asthma mortality? A hypothesis. Clin Rev Allergy Immunol. 2006;31(2-3):279-288.
11. Anis AH et al. Double trouble: impact of inappropriate use of asthma medication on the use of health care resources. CMAJ. 2001;164(5):625-631.
12. Souza-Machado C et al. Rapid reduction in hospitalisations after an intervention to manage severe asthma. Eur Respir J. 2010;35(3):515-521.
13. Suissa S et al. Low-dose inhaled corticosteroids and the prevention of death from asthma. N Engl J Med. 2000;343(5):332-336.
14. Suissa S et al. Regular use of inhaled corticosteroids and the long term prevention of hospitalisation for asthma. Thorax. 2002;57(10):880-884.
15. Yeo S-H et al. Efficacy and safety of inhaled corticosteroids relative to fluticasone propionate: a systematic review of randomized controlled trials in asthma. Expert Rev Respir Med. 2017;11(10):763-778.
16. O’Byrne PM et al. Inhaled Combined Budesonide–Formoterol as Needed in Mild Asthma. New England Journal of Medicine. 2018;378(20):1865-1876.
17. Bateman ED et al. As-Needed Budesonide–Formoterol versus Maintenance Budesonide in Mild Asthma. New England Journal of Medicine. May 2018. https://www.nejm.org/doi/10.1056/NEJMoa1715275. Accessed November 4, 2019.
18. Busse WW et al. Combined Analysis of Asthma Safety Trials of Long-Acting β2-Agonists. New England Journal of Medicine. 2018;378(26):2497-2505.
19. Martinez FD et al. Use of beclomethasone dipropionate as rescue treatment for children with mild persistent asthma (TREXA): a randomised, double-blind, placebo-controlled trial. The Lancet. 2011;377(9766):650-657.
20. Bisgaard H et al. Budesonide/formoterol maintenance plus reliever therapy: a new strategy in pediatric asthma. Chest. 2006;130(6):1733-1743.