Asthma-related mortality decreased substantially after inhaled corticosteroids (ICSs) became a mainstay of treatment. Between 1985 and 2005, international mortality rates decreased 63%; however, such progress has since slowed, and it is estimated that 50% of remaining asthma-related deaths could be prevented with improvements in treatment. In addition to better adherence to clinical guidelines, novel treatment strategies are also needed, according to a paper published in March 2019 in the Journal of Asthma.1

The treat-to-target (TTT) approach that is increasingly used in the management of rheumatoid arthritis (RA), diabetes, and other chronic conditions could be effectively used in asthma treatment, the authors suggested. The TTT approach involves aggressive treatment aimed at reaching and maintaining specific goals. For a primary target of clinical remission in RA, for example, the primary goal is to “maximize long-term health-related quality of life through control of symptoms, prevention of structural damage, and normalization of function and social participation,” they explained. “Applying the TTT approach to asthma, the primary target could also be clinical remission and the primary goals eliminating symptoms and exacerbation risk, preventing airway remodeling, and normalizing lung function.”

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Although the role of chronic inflammation is well established in asthma, clinical guidelines have long recommended symptom-driven treatment with short-acting β2 agonists (SABA) alone in patients at the step 1 treatment level, without addressing the underlying inflammatory process.1 Because symptoms in these patients may be infrequent or mild, they tend to opt for SABA alone even when ICSs are also recommended. Emerging evidence shows that regular SABA use “can lead to increased bronchial hyper-responsiveness, loss of asthma control, worsening lung function, and delays in seeking help,” and ultimately an “increased risk of life-threatening exacerbations and respiratory arrest,” as stated in the review.1 Excessive use of β2 agonists is one factor that has been linked with asthma mortality.

The author advocated for a shift away from the traditional approach, with the use of a simple TTT algorithm that primarily changes the first 2 treatment steps.1 This includes removal of the SABA-only option altogether in favor of “anti-inflammatory reliever therapy” comprised of ICS/SABA or ICS/formoterol for step 1 treatment; and daily ICS (as a disease-modifying anti-asthmatic drug, in the way that disease-modifying antirheumatic drugs are used in RA), as well as ICS/formoterol as “anti-inflammatory reliever therapy,” for step 2 treatment.

Similar to these suggestions, the 2019 Global Initiative for Asthma (GINA) treatment recommendations contain the following revisions: SABA-only therapy is no longer supported, and off-label recommendations have been added.2 Step 1 recommendations now include as-needed low-dose ICS-formoterol as the preferred option and low-dose ICS to be taken whenever SABA is taken. These recommendations have also been added to step 2 treatment strategies, which still include daily low-dose ICS as a preferred option.3

Pulmonology Advisor spoke with Emily Pennington, MD, a pulmonologist in the Asthma Center at Cleveland Clinic, Cleveland, Ohio, to further discuss this new direction in asthma treatment.

Pulmonology Advisor: What are some of the limitations of the current approach to asthma management? 

Dr Pennington: Patients have always been instructed to use albuterol for their rescue medication and a separate medication for their controller inhaler. This has led to confusion with patients and suboptimal management of asthma, with the long-term risk for airway remodeling. Rather than use their controller inhaler — which, from a patient’s perspective, doesn’t provide any immediate benefit — patients often just use albuterol more often because that inhaler gives them relief from their symptoms immediately; however, of course, it is the inhaled steroid that is necessary to control airway inflammation and prevent airway remodeling. 

On the other end of the spectrum, although we do have a number of new treatments for patients with severe asthma over the last few years, they are all targeted for allergic and eosinophilic asthma. There are still a number of patients with severe asthma who do not fall into these categories and who are not as responsive to inhaled steroids. We need more treatment options for this group of patients.  

Pulmonology Advisor: What are your thoughts about a TTT approach for asthma like the one proposed by Luis J. Nannini, MD, author of the Journal of Asthma paper

Dr Pennington: I agree that we need to rethink our approach to asthma management. The most recent guidelines from GINA also include this approach in recommending an as-needed low-dose ICS/formoterol for all patients as rescue therapy. This still provides patients with the quick relief that they are used to receiving with albuterol but also includes the ICS to help control the underlying airway inflammation. Multiple studies have shown now that this approach leads to better asthma control in patients [with mild asthma].3 

Pulmonology Advisor: What are the relevant treatment implications for physicians? 

Dr Pennington: I think this approach will change asthma management in the future. We will likely no longer prescribe just SABAs for patients with asthma. We will need to be cautious, though, in overinterpreting the currently available studies. This approach has only been demonstrated to be effective in patients with mild intermittent and mild persistent asthma. For patients with more severe disease, we do not know the implications of prescribing ICSs/formoterol for their anti-inflammatory reliever therapy and then prescribing different ICSs/LABAs as their controller therapy. For this reason, the better approach may be to use ICS/SABA inhalers in the future. This will all need to be studied in asthma populations at all severities.   

Pulmonology Advisor: What further research is needed to move this area forward?

Dr Pennington: Anti-inflammatory reliever therapy will need to be studied in more [populations with more] severe asthma — including patients already receiving ICSs/LABAs on a daily basis — to see if they experience the same benefit from this approach.

References

1. Nannini LJ. Treat to target approach for asthma. J Asthma. 2019:1-4.

2. Global Initiative for Asthma. https://ginasthma.org/wp-content/uploads/2019/06/GINA-2019-main-report-June-2019-wms.pdf Updated 2019. Accessed September 12, 2019.

3. Muneswarao J, Hassali MA, Ibrahim B, Saini B, Ali IAH, Verma AK. It is time to change the way we manage mild asthma: an update in GINA 2019. Respir Res. 2019;20(1):183.