Challenges and evidence gaps in management of mild asthma

Mild cases are estimated to comprise over half of the overall asthma population. Unlike in most other chronic conditions, patients with mild asthma are still at risk of serious outcomes, including death, according to Professor Helen Reddel of the Woolcock Institute of Medical Research, University of Sydney, who spoke at the Advances in Medicine 2020 virtual conference. [Eur Respir J 2007;30:403-406; Can Respir J 2010;17:74-80; Royal College of Physicians. Why asthma still kills: National Review of Asthma Deaths Confidential Enquiry Report. London, 2014]

In the past, mild asthma was mostly managed with as-needed short-acting β₂-agonists (SABA) with an occasional course of oral corticosteroids (OCS), but there is increasing concern about the risks of SABA overuse and the cumulative long-term adverse effects of even occasional OCS use. [J Asthma Allergy 2018;11:193-204]

“Low-dose inhaled corticosteroids [ICS] reduce the risk of asthma hospitalization by 31 percent and asthma deaths by >50 percent. In mild asthma, low-dose ICS almost halve the risk of serious exacerbations – even in patients who experience symptoms once a week or less,” said Reddel. [N Engl J Med 2000;343:332-336; Lancet 2003;361:1071-1076; Lancet 2017;389:157-166] “However, very few patients take ICS-containing medication regularly. Many rely on their SABA reliever instead. This poor adherence is associated with an increased risk of exacerbations and death.” [Respir Care 2015;60:455-468]

Based on evidence about as-needed budesonide-formoterol from the SYGMA 1, SYGMA 2, Novel START and PRACTICAL studies in almost 10,000 patients, as-needed ICS-formoterol was included in global recommendations for mild asthma as a safer treatment than SABA alone, and as an efficacious alternative to maintenance low-dose ICS. [Eur Respir J 2019;53:1901046]

Some exacerbations and asthma deaths are associated with eosinophilic inflammation, while others are mainly associated with intense bronchoconstriction without eosinophils. [Eur Respir J 2002;19:68-75; Eur Respir J 2005;26:429-434] “As-needed budesonide-formoterol reduces the risk of severe exacerbations compared with regular ICS, and compared with as-needed SABA, regardless of ‘type 2’ inflammation caused by blood eosinophils or baseline fractional exhaled nitric oxide level,” explained Reddel. [N Engl J Med 2019;380:2020-2030; Lancet 2019;394:919-928; Eur Respir J Open Res 2020;6:00068-2020]

“From the patient’s perspective, SABA, which offers rapid symptom relief, in combination with an occasional course of OCS represents a satisfactory treatment option. As a result, it is difficult to change behaviours regarding SABA use among patients, clinicians and policy makers,” said Reddel. A patient survey at the end of the PRACTICAL study found that 90 percent of patients randomized to receive as-needed budesonide-formoterol would prefer this option. At the same time, 60 percent of patients who received maintenance ICS and as-needed SABA indicated they would prefer this treatment. [Eur Respir J 2020;55:1902073]

“The absolute risk of severe exacerbations in mild asthma is low, but can be reduced further,” stated Reddel. “A population-level risk reduction strategy, such as one implemented with statins and antihypertensives, would be required to minimize severe exacerbations in mild asthma, but patients themselves may not know if they have benefitted.”

“While a wealth of data supports recent guideline changes, evidence gaps still exist in the paediatric population, pregnant women, and patients with symptoms <2 times a month or seasonal asthma. It is also unclear which patients would benefit from regular daily treatment instead of the as-needed approach and when stepping up treatment would be necessary,” highlighted Reddel.