Asthma Management: An Update on New and Upcoming Guidelines

Pharmacists can play a substantial role in the education and management of therapies for asthma. In a virtual session during the American Society of Health-System Pharmacists 2020 Midyear Clinical Meeting and Exhibition on December 6, 2020, experts discussed updates in asthma management, including new data and upcoming guideline changes that will impact pharmacy practice.¹

Guideline Updates

Nathan A. Pinner, PharmD, BCPS, associate clinical professor at Auburn University Harrison School of Pharmacy, and Brooke L. Gildon, PharmD, professor at Southwestern Oklahoma State University College of Pharmacy, provided an overview of recent updates to recommendations for the management of asthma with inhaled corticosteroids (ICS) and long-acting beta-agonists (LABAs), as well as impending guideline changes. 

ICS/LABA Therapy

Major changes were added to the Global Initiative for Asthma (GINA) 2020 recommendations, particularly regarding mild asthma.

According to the updated guidelines, GINA no longer recommends treatment with short-acting beta2-agonists (SABA) without ICS. Instead, GINA now recommends that all adults and adolescents with asthma should receive an ICS-containing controller for either symptom-driven (in mild asthma, GINA Steps 1-2) or daily (GINA Steps 2-5) treatment to reduce the risk of serious exacerbation and to control symptoms.²

According to Pinner, the most notable change is the addition of as-needed ICS-formoterol in Step 2 and as-needed ICS-formoterol as a controller option in Step 1. He noted that in Step 1, there had previously been no controller option. 

This change was based on evidence that the use of as-needed ICS-formoterol provided benefit compared with as-needed SABA or maintenance ICS and evidence that overuse of SABA is associated with an increased risk of severe exacerbations. The updated guidelines also provide more consistent messaging for patients with mild asthma, Pinner explained.

He noted that Step 1 for the GINA guidelines is very similar to the Expert Panel Report (EPR)-3 for intermittent asthma; however, Step 1 in the GINA guidelines is advised for patients who experience symptoms less than twice monthly. As-needed low dose ICS-formoterol is the preferred approach for such patients, which is supported by indirect evidence, Pinner said.

In Step 2 for mild asthma, 2 preferred controller options were recommended: daily ICS or as-needed budesonide-formoterol.

“If you have patients who are on [ICS] daily for therapy, there’s no reason to change if they’re doing well,” Pinner said. “But if there [are] some people who could benefit from using an as-needed ICS-LABA, that’s also an acceptable therapy here.”

Short-Term ICS Dose Increases

Gildon discussed the concept of short-term increases in ICS dose for worsening asthma symptoms.

According to her, GINA 2020 recommends early increases in controller therapy, specifically with early or mild asthma symptoms. These increases are based on the patient’s usual medication regimen. 

However, EPR-4 draft guidelines conditionally recommend against short-course increases for increased symptoms or decrease peak flow in patients 4 years and older with mild-to-moderate persistent asthma who are likely to adhere to daily ICS treatment. Specifically, they classify this increase as either doubling, quadrupling, or quintupling ICS.³

“The rationale for this recommendation is due to a lack of consistent efficacy data and then possibly some concerns regarding safety…with grow suppression as an example,” Gildon said. However, she noted that it’s important to keep in mind that the EPR-4 draft says there is a potential role for ICS increase in patients with poor adherence.

Gildon pointed to several studies looking at ICS increases. In 1 study, which looked at ICS increases in adults and adolescents, the results demonstrated that a temporary quadrupling of ICS with deteriorating asthma symptom control resulted in fewer severe exacerbations.⁴ On the other side, a different study that examined 7-day quintupling of ICS with asthma control in the yellow zone in children showed that the rate of severe asthma exacerbations did not differ significantly between high-dose and low-dose groups. However, the findings did suggest that increasing ICS may affect linear growth in children.⁵

“Something that was not found to be statistically significant, but something that we do want to follow is this decrease in linear growth between the high-dose and low-dose group,” Gildon said. “And that’s something I think we need to continue following when it comes to evaluating this option if we were to use it in pediatric patients.”

Furthermore, a systematic review and meta-analysis published in 2019 of 8 trials indicated that temporary increased ICS was associated with reduced risk of treatment failure. The analysis looked at increased doses compared with stable doses in adults and children. According to Gildon, the analysis demonstrated a benefit observed in adults compared with children and also identified that quadrupling the dose had a greater impact than doubling.⁶

“This review did have moderate, quality evidence that supports the increase of ICS dose in certain patient populations and a self-initiated action plan to reduce risk of exposure to systemic corticosteroids,” she explained.

According to Gildon, pharmacists should consider how these data might affect the care of patients with asthma.

Short-Course ICS/SABA in Young Children

Gildon also discussed current data around short-course ICS plus as-needed SABA at the onset of a respiratory illness in pediatric patients aged 0 to 4 years old with recurrent wheezing.

According to the EPR-4 draft recommendations, a short-course (7-10 days) of ICS and SABA for quick-relief therapy starting at the onset of a respiratory illness is recommended in such patients. Recurrent wheezing was defined as 3 or more wheezing episodes triggered by respiratory tract infection in their lifetime or 2 in the past year and are symptomatic between episodes. However, Gildon noted there are still conflicting data on the impact on height and weight gains in the literature.

Gildon emphasized the importance of caregiver education if this draft recommendation is put into place in the pediatric population.

“There is a potential for overuse in this situation, so we want to make sure parents know exactly when this short-course ICS would be recommended,” Gildon said. Intermittent ICS can be initiated at home based on a written action plan. Importantly, the plan must be initiated at the first sign of respiratory tract infection-associated symptoms.

FDA Boxed Warning for Montelukast

Gildon touched on the more recent addition of the boxed warning to montelukast.

In March 2020, the FDA officially added a boxed warning to montelukast for serious mental health adverse effects (AEs), including agitation, attention problems, vivid dreams, depression, anxiety, irritability, memory problems, suicidal actions, and tremors.

“I’ve seen this in my practice a number of times in our pediatric patients,” Gildon said. According to her, parents whose children are affected typically present with concerns about their child’s irritability and agitation, or indicate that the child is behaving differently.

“This not something new,” Gildon said. “We’ve heard about this for a while.” Back in 2008 and 2009, there was earlier communication about the risk with montelukast regarding mental health AEs, but there was no boxed warning placed at that time.

However, she noted that the boxed warning does help increase the awareness for risk and can help pharmacists discuss the risks and benefits of this medication with patients.

Other Asthma Education Opportunities

Gildon highlighted other opportunities where pharmacists can play a role in asthma education for their patients.

To improve adherence, for instance, pharmacists caring for patients can make a difference by helping them set up schedules or advising them to use reminders in their smartphones. Additionally, patients often need assistance with inhaler technique. “Patients need to be seen over and over and have consistent inhaler device technique training,” Gildon said.

Considerations of comorbid conditions and changes regarding environmental factors/allergen control can be an important educational opportunity for pharmacists as well to help patients identify factors that might be making their asthma worse. Pharmacists can also help guide self-management education, which can include self-monitoring of symptoms and/or peak expiratory flow/lung function, a written asthma action plan, and consistent follow-up with either a primary care physician or pulmonologist.

“We can [play] a huge role here when it comes to education and management of asthma,” Gildon said.

References

1. Pinner N, Gildon BL. Take a deep breath: Updates in asthma and COPD management. Presented at: ASHP Midyear 2020 Clinical Meeting & Exhibition; December 6-10, 2020; virtual.

2. Global strategy for asthma management and prevention. Global Initiative for Asthma. Updated 2020. Accessed December 6, 2020. https://ginasthma.org/wp-content/uploads/2020/06/GINA-2020-report_20_06_04-1-wms.pdf

3. Update on selected topics in asthma management: A report from the National Asthma Education and Prevention Program Coordinating Committee Expert Panel Working Group. National Heart, Lung, and Blood Institute, National Asthma Education and Prevention Program. Draft for public comment. December 2019. Accessed December 6, 2020. https://www.epr4workgroup.org/Asthma2020Guidelines/Shared%20Documents/Asthma-Guidelines-Report.pdf

4. McKeever T, Mortimer K, Wilson A, et al. Quadrupling inhaled glucocorticoid dose to abort asthma exacerbations. N Engl J Med. 2018;378(10):902-910. doi:10.1056/NEJMoa1714257

5. Jackson DJ, Bacharier LB, Mauger DT, et al. Quintupling inhaled glucocorticoids to prevent childhood asthma exacerbations. N Engl J Med. 2018;378(10):891-901. doi:10.1056/NEJMoa1710988

6. Zhang Y, He J, Yuan Y, Faramand A, Fang F, Ji H. Increased versus stable dose of inhaled corticosteroids for asthma exacerbations: A systematic review and meta-analysis. Clin Exp Allergy. 2019;49(10):1223-1290. doi:10.1111/cea.1345