Improved Asthma Outcomes for Black and Latinx Adults
In this video, Elliot Israel, MD, speaks about his team's research titled "A Randomized, Open-Label, Pragmatic Study to Assess Reliever-Triggered Inhaled Corticosteroid in African American/Black and Hispanic/Latinx Adults With Asthma." He speaks about the disproportionate morbidity of asthma in African American/Black and Hispanic/Latinx patients and his work demonstrating that adding patient-activated reliever-triggered inhaled corticosteroids to existing therapy can reduce the excess morbidity and improve quality of life.
- Israel E, Cardet JC, Carroll JK, et al. A randomized, open-label, pragmatic study to assess reliever-triggered inhaled corticosteroid in African American/Black and Hispanic/Latinx adults with asthma: Design and methods of the PREPARE trial. Contemp Clin Trials. 2021;101:106246. doi:10.1016/j.cct.2020.106246
Elliot Israel, MD, is a professor of medicine at Harvard Medical School, the Gloria M. and Anthony C. Simboli Distinguished Chair in Asthma Research, and the Director of Clinical Research in the Pulmonary, Critical Care Divisions at Brigham and Women's Hospital (Boston, MA).
Dr Elliot Israel: Hi, I'm Elliot Israel, I'm professor of medicine at Harvard Medical School, the Gloria and Anthony Simboli Chair in Asthma Research, and a member of the Pulmonary Critical Care Division at the Brigham and Women’s Hospital, and member of the Allergy and Immunology Division at Brigham and Women’s Hospital. Thanks for asking me to speak about our study related to improving the outcomes in African-American, Black, and Hispanic, Latinx patients with asthma.
We're excited about this study. This was a study that was motivated by the fact that there really seems to be, and we know there is, a disproportionate morbidity of asthma in black, African-American patients and Hispanic, Latinx patients. That excess morbidity, the excess deaths, the excess hospitalizations, the excess exacerbations really have been very hard to reduce. The studies that have been most successful in reducing that excess morbidity generally have been studies where there's had to be a lot of resource utilization, nurses, and calling patients frequently.
The logistics of that and the ability to carry that out in a constrained healthcare system really are limited. We identify this as a continued unmet need. We conferred with patients, African-American, black patients, and Hispanic, Latinx patients in terms of different options that we might be able to do in terms of trying to intervene. One of the options that we had identified as a potential way to decrease asthma's effects was a patient empowered strategy.
We had shown in the past that rather than using inhaled corticosteroids on a regular basis, that one could try to use inhaled corticosteroids on an as-needed basis and that could improve asthma outcome. We approached patients and we also believed that if we could do that on top of patients' asthma regimen, that we could actually improve morbidity as well.
We worked with African-American, black and Hispanic, Latinx patients who are patient partners in a patient-centered outcome research study that was supported by PCORI, the Patient-Centered Outcome Research Institute, where we actually looked at the possibility of doing this.
What we did was, based on the advice we got, we proposed to patients that on top of their usual asthma medications, whatever medications they were on, we would give them an inhaler, an inhaled corticosteroid inhaler, and we would tell them that each time they use their reliever inhaler, they should use this inhaled corticosteroid inhaler. Each time they use their nebulizer inhaler, they should use five puffs of this inhaled corticosteroid inhaler. We gave them a beclomethasone dipropionate inhaler to use.
The reason we used five puffs of the inhaled corticosteroid inhaler when they used the nebulizer was that the data has shown that five puffs of metered-dose inhaler is about the equivalent of a nebulizer in terms of producing effects.
Now, one could ask, why is this important to do? Don't we know that there's been now a proposal that people use SMART therapy, which is Simultaneous Maintenance and Reliever Therapy, which involves formoterol inhaled corticosteroid? The reason that this is important is that SMART therapy, there are several actual impediments to SMART therapy.
First of all, SMART therapy is a intervention that requires one to change the underlying medications. That's not easy to do. In addition, SMART therapy, when it's been studied, has been studied in patients who do not use nebulizers. We found that 60% of the population that we're studying and actually a large part of the moderate, severe asthma population actually uses nebulizers, and that 45% of our population is using their nebulizers more than once a week. On average, our population is using their nebulizers two and a half times a week. SMART therapy doesn't work well when patients use nebulizers as relievers. That's another reason that we thought that this intervention is important.
In addition, the FDA, the Food and Drug Administration, does not approve the use of formoterol inhaled corticosteroid as an intermittent therapy, even though this has been recommended by the NAPP. We saw this as an easy to implement strategy, which patients felt would empower them in terms of using and possibly reduce asthma morbidity.
The other thing that we felt was, based on the feedback from the patients, was that this would be an easy to learn strategy, easy for patients to learn, but also easy for providers to provide, so it would be a low resource intervention as well. What we did is we identified patients, the patients who had to come into the studies, opposed to studies with SMART, either could have had a exacerbation in the past year or were on any dose of inhaled corticosteroid plus any other medications and were still symptomatic. As opposed to the SMART studies, everyone in the SMART studies, everyone had to have had an exacerbation in the past year and they had to bronchodilate.
We did not do any PFTs. These were patients with an asthma diagnosis. Patients, this were not done in pediatrics, it was adults, patients 18 to 75. You just had to have an asthma diagnosis from your physician and either be symptomatic on an inhaled corticosteroid plus, or have had an exacerbation. We met with them one time and they were given the inhaled corticosteroid inhaler and told to do what I said, which is to either use the inhaled corticosteroid every time they used their metered dose inhaler reliever, and five times when they use their nebulizer.
We randomized patients to either receive that intervention or to continue with their regular therapy. All the patients watched a video on how to control their asthma, and all the patients were given a pouch to hold their inhalers in. That was it. We did not actually do any further instruction. Patients were surveyed once a month to find out what their asthma control was and whether they'd had an exacerbation. The primary outcome of the study was asthma exacerbations.
We also looked at the Asthma Control Test, which is an instrument that measures the asthma control. We also looked at something known as the Asthma Symptom Utility Index, which measures the change in the quality of life for patients with asthma. We also had patients report to us on days that they lost from school or work as a result of the impact of asthma, because our patient partners had told us that the reason they thought exacerbations was a major point and major outcome was that they felt that had a major impact on their lives. Asthma exacerbations caused them to have to go to be involved with the medical system.
It would cause them to lose days from work. It would cause them to lose days from school. It would prevent them from taking care of their children. Many patients thought about how they lost their jobs because asthma exacerbations would continuously cause them to have absences from work. What we found was... And we followed these patients for 15 months. There's only one instructional visit, and then we followed these patients for 15 months.
What we found was that we were able to reduce asthma exacerbations. The amount of asthma exacerbation reduction that we achieved, which was .12, I'm sorry, .13 exacerbations per patient per year, actually it was the same as was reported with SMART studies. If you looked at the SMART studies that were done in patients who had moderate, severe asthma, which is what our patient population was, the mean change in the SMART studies was .12 exacerbations per patient per year.
Those studies were enough to cause the NAEP, the National Asthma Education Program, to change its recommendations to say that moderate to severe asthmatics should go onto SMART. We achieved an effect that was similar to SMART. The thing was that we had not chosen patients who'd had an exacerbation beforehand. Remember I mentioned that all the SMART studies in moderate, severe asthmatics were done in patients who had both an exacerbation and who bronchodilated. We didn't know whether our patients bronchodilated, but we had asked our patients if they'd had an exacerbation in the past year.
When we looked at that, if we looked at only the population that reported that they had an exacerbation, which was about 67% of our population, then the degree of reduction of exacerbations in that group was .23 exacerbations per patient per year. We actually had a large reduction in patient exacerbations.
In addition to the exacerbations, the Asthma Control Test showed us that we had about a three and a half-point improvement in the Asthma Control Test, which was significant. For an individual patient, a three-point change in the Asthma Control Test is significant. In the Asthma Symptom Utility Index, as I recall, I think we had a .09 difference in the Asthma Symptom Utility Index with exceeding the minimum important difference for patients where an individual patient was seeing a difference.
In addition, we reduced the days lost from work and school significantly as well. We had outcomes that were really important for patients. I think this is very important for clinical practice, because what we've shown is that you can take a simple intervention which is low resource in terms of teaching patients, so low resource in terms of the providers and also low impact for the patients, but that this intervention without having to change the underlying therapy, which can be very confusing for patients and which is not... There's not [inaudible 00:10:39] insurance coverage, which there is for SMART, that we can reduce asthma exacerbations in a population where it's been very difficult to reduce asthma exacerbations.
The other thing is when we looked at the amount of extra inhaled corticosteroid that was used in these patients, what we found was that, on average, the patients use 1.1 extra canisters of their controller medication per year. That compares to, in SMART therapy, more than four canisters a year. Not only were we producing effects that were equal or greater than SMART, we were doing that with less of an increase in the inhaled corticosteroid dose.
What we also found, which was really important as well, was that there was a reduction in the metered-dose inhaler use as well by one and a half to two canisters a year and that, also, there was a reduction in nebulizer use as well. We know that both metered dose inhaler and nebulizer use are associated with increased asthma mortality. Again, I think we were seeing a positive outcome here as well.
The overall take-home message from this research really is that there's an easy method to improve outcomes in patients who are poorly controlled. While this worked in African-American, black and Hispanic, Latinx patients, I don't think there's any reason to believe that this wouldn't be as successful in the general population.
I think we have an intervention which is easy to implement, which actually in most cases, would be covered by insurance, and which reduces outcomes that patients say are important to them and works as effectively as we see or more effectively than what's currently being recommended in the current guidelines. I think we're excited about this. I think we've come up with something the patients like to do, feels empowers them, and is also good for them and has a low burden on the medical system.