$31 million study to test use of inhaled corticosteroids, azithromycin in asthma treatment

With $31 million in funding from the Patient-Centered Outcomes Research Institute, researchers will investigate the effectiveness of inhaled corticosteroids and azithromycin, used either alone or together, in treating asthma.

The American Academy of Family Physicians (AAFP) and Penn State College of Medicine will collaborate on the Individualizing Treatment for Asthma in Primary Care (iTREAT-PC) study, which will test these interventions.

For 16 months, the researchers will follow more than 3,000 patients aged 12 to 75 years with persistent asthma requiring inhaled steroids for management at 10 health care systems and research networks across the country.

According to the researchers, iTREAT-PC will be the first study to compare the use of the antibiotic azithromycin to treat a broad spectrum of individuals with asthma and the use of inhaled corticosteroids as part of rescue therapy.

This study follows the results of the Person Empowered Asthma Relief Trial, which found that a strategy of using patient-activated reliever-triggered inhaled glucocorticoids with usual care and medication reduced asthma symptoms and improved quality of life among Black and “Latinx” adults with moderate to severe asthma.

Healio spoke with Wilson Pace, MD, principal investigator and clinical lead for iTREAT-PC, and Christina Hester, PhD, MPH, director of practice-based research, innovation and evaluation at the AAFP and iTREAT-PC co-investigator, to find out more about the new study.

Healio: Could you explain the pros and cons of using inhaled steroids for asthma?

Pace: Inhaled steroids are the first line of therapy for patients with asthma. They are used for long-term control of asthma symptoms and effectively reduce inflammation in the lungs that causes the symptoms of asthma. Inhaled steroids are considered safe and effective for management of asthma. However, their use can lead to side effects such as thrush, weakened bones, increased risk for diabetes and disrupted growth in children.

Healio: Which patients have the best outcomes with inhaled steroids? And which ones have the worst?

Wilson Pace

Pace: Inhaled steroids are appropriate for asthma management for most patients. In some cases, particularly among patients with severe asthma symptoms, inhaled steroids do not effectively reduce asthma symptoms and improve quality of life, so alternative treatments are then evaluated.

Overall, patients who smoke are less responsive to inhaled corticosteroids. Patients with high eosinophil counts are considered likely to be more responsive to inhaled corticosteroids but, in clinical studies, any differences are small. Even if someone is more or less likely to respond to inhaled steroids, if they have persistent asthma symptoms, they should be on one of these medications.

Healio: Could you explain the pros and cons of using specific antibiotics for asthma?

Pace: Antibiotics are not generally used for asthma management and treatment, except in cases where bacterial infection is suspected. In some patients, specific types of antibiotics called macrolides have been shown to help reduce the severity of asthma. However, we do not yet know how to readily identify the patients for whom macrolides may be most effective.

Macrolides have intrinsic anti-inflammatory properties, which may help improve asthma symptoms. In addition, in animal models, various chronic lung infections create an asthma-like picture that can be responsive to macrolide antibiotics. Whether either of the mechanisms is the primary reason many people with asthma get improvement from long-term macrolide therapy is not known.

Healio: Which patients have the best outcomes with specific antibiotics? And which ones have the worst?

Pace: We do not yet know at a population level which patients have the best outcomes with antibiotics. Patients whose asthma symptoms are not well controlled with standard medications have shown benefit from antibiotics, specifically long-term use of macrolide antibiotics.

Antibiotics are not currently used broadly to treat asthma, but some patients have seen significant improvement in their symptoms with macrolide treatment. This study will help us understand which patients are most likely to benefit from antibiotics as asthma therapy.

Healio: Could you summarize the goals of this study?

Christina Hester

Hester: The primary goals of the study are to compare the effectiveness of different asthma treatments, separately and together, on asthma control and exacerbations. In this study, we will examine whether inhaled steroids as part of rescue therapy, long-term macrolide treatment, or a combination of both inhaled steroids and macrolide treatment best reduces asthma exacerbations. We will also evaluate how the treatments impact asthma control, quality of life, and missed days of school or work.

Healio: Why is it important to look at patient-reported outcomes?

Hester: It is important to look at the outcomes that are most important to patients when considering the effectiveness of a particular treatment because sometimes the outcomes that are considered by physicians — for example, reduction of a lab value — do not translate to patients feeling better every day. Here, we will collect data from patients about whether their quality of life improves in addition to examining clinically relevant outcomes.

Healio: How do you expect the findings of this study to impact patient quality of life?

Pace: Understanding which treatments are most effective for which patients will enable physicians to select individualized treatment plans for the most effective asthma management, in terms of both clinical and patient-reported outcomes.

In our previous study looking at as-needed inhaled corticosteroids on top of usual controller medications, quality of life did improve for patients using the combined treatment. This approach will be used by two of the four arms of this trial and, thus, we do expect improvement in quality of life for some participants. We do not know if the antibiotic arms will experience this improvement as well.

Healio: How do you expect the findings of this study to impact approaches to treatment?

Hester: This study will provide the data needed to help physicians identify which patients may most benefit from a specific treatment approach based on their own individual characteristics.

Healio: Do you have anything else you would like to add?

Hester: The iTREAT-PC project perfectly fits in the mission of AAFP research. It’s research that has the potential to improve the health of patients, families and communities. The strength of our AAFP research is that we engage our family physician members in defining the problem and collecting the data. This allows us to ensure that we’re exploring the topics that will have the most impact on how family physicians deliver patient-centered care.

Reference:

• AAFP approved for $31 million for large study on asthma treatments. https://www.aafp.org/news/media-center/releases/aafp-approved-for-31-million-for-large-study-on-asthma-treatment.html. Published July 26, 2022. Accessed Aug. 5, 2022.