Mild asthma: A fundamental change in management

The management of mild asthma underwent some considerable changes in recent years. The GINA guidelines no longer recommend short-acting β2-agonists (SABA) as needed as sole treatment.

In the last decade, it became increasingly evident that even patients with mild asthma are at risk of serious adverse events, Prof. Roland Buhl (Johannes Gutenberg University of Mainz, Germany) stated in his lecture on the changing landscape in the management of mild asthma [1]. Severe exacerbations in mild asthma represent 30-40% of asthma exacerbations requiring emergency consultation [2]. Frequent use of short-acting bronchodilators has been associated with several adverse events, such as a reduced bronchodilator response, rebound increase in bronchial hyperresponsiveness, and increase in eosinophilic airway inflammation [3,4]. This is particularly true for extremely frequent SABA use: the use of 2 or more SABA canisters in adults is associated with a heightened risk of asthma-related exacerbations [5]. Increasing β-agonist use elevates even the risk of fatal or near-fatal asthma [6]. All these studies highlighted the risk of SABA only use, especially with regard to severe exacerbations. “This is why SABA only is probably not the best choice in mild disease,” Prof. Buhl stated.

In more severe disease, a bronchodilator is already combined with an anti-inflammatory agent to control airway inflammation. “It is only a small step to go from inhaled corticosteroids (ICS)/long-acting β-agonists (LABA) to ICS plus formoterol, a long but still rapid-acting bronchodilator to be able to control smooth muscle contraction and airway inflammation with one drug,” said Prof. Buhl. If patients with mild asthma develop symptoms, they should start a fixed ICS/formoterol combination. They can stop therapy when the symptoms disappear. This approach has been tested in clinical trials, but participants in a controlled setting tend to use ICS regularly, whereas patients in real life tend to only use ICS when symptomatic. This explained the motivation for a real-life study performed last year [7].

In the Novel START trial, patients (n=668) with mild asthma were treated open-label for 52 weeks in 3 arms: one with a fixed ICS/formoterol combination as-needed, one with ICS (i.e. budesonide) plus as-needed albuterol (budesonide maintenance group), and one with as-needed albuterol only, which is the strategy recommended up to 2018 in the GINA guidelines. The results showed that the ICS/LABA combination as needed was as effective as maintenance therapy, but significantly more effective than albuterol as needed with regard to prevention of exacerbations (see Figure). Regarding severe exacerbations, the ICS/formoterol as-needed strategy was even more effective than maintenance ICS [7]. “This is pretty clear because patients will take more reliever when they suffer from severe symptoms, and in this way will also take more ICS leading to an overall better outcome; therefore, it makes sense to use the fixed combination ICS/formoterol,” Prof. Buhl said.

 

One of the secondary outcomes assessed was the fraction of exhaled nitric oxide (FeNO), which is a very sensitive parameter of airway inflammation. Regarding a reduction in the median FeNO from baseline, the maintenance therapy and as-needed therapy showed similar results [7]. “This result tells us that bronchial inflammation in patients during symptom-free periods is so mild that without treatment there is no rise in FeNO,” Prof. Buhl explained. Thus, an as-needed medication is sufficient for patients with mild asthma. Another trial showed that patients with mild asthma treated with as-needed ICS/formoterol or ICS maintenance therapy can reduce exacerbation risk by 50% [8]. These results led to a change in the GINA treatment recommendations for patients with mild asthma: ICS/formoterol as needed is now a preferred alternative in step 1 to maintenance ICS in step 2.

 

Figure: Budesonide/formoterol as-needed is equally effective as maintenance therapy and more effective than albuterol in a real-life study [7]



 

1. 
   
   1. Buhl R. Refining asthma treatment for mild asthma. Abstract 4201, ERS International Virtual Congress 2020, 7-9 Sept.
   2. Dusser D, et al. Allergy 2007;62(6):591-604.
   3. Hancox RJ, et al. Respir Med 2000;94(8):767-771.
   4. Aldridge RE, et al. Am J Respir Crit Care Med 2000;161:1459-1464.
   5. Stanford RH, et al. Ann Allergy Asthma Immunol 2012;109: 403-477.
   6. Suissa S, et al. Eur Respir J 1994;7:1602-1609.
   7. Beasley R, et al. N Engl J Med 2019;380:2020-2030.
   8. Wong GWK. N Engl J Med 2019;380:2064-2066.

 



Posted on 29 October, 20206 November, 2020