Tom Castles

Our mobile devices are slowly and steadily weaving themselves into the fabric of our society. Healthcare — while a bit slower to adapt to this sea change – is no exception. In fact, cell phones have recently become the cornerstone of an entire branch of healthcare called mobile health, or mHealth for short, whose fundamental aim is to increase patient engagement with the healthcare system.  

While excitement (and hype) surrounding mHealth’s potential to build stronger patient-provider relationships and improve outcomes abounds, early results around its efficacy are murky. Published studies of cell phone-based healthcare interventions are generally of low quality, leaving anyone looking to draw conclusions about the subject’s efficacy forced to do so with a grain of salt.

But now, investigators at Boston Children’s Hospital are seeing some promising mHealth results in a small sample of children with asthma. After placing 26 of these patients between the ages of 6 and 17 on an mHealth tracking system for asthma management, the study met its primary endpoint of positive changes in Asthma Control Test (ACT) scores, as well as its secondary endpoint of a positive change in adherence rates and self-reported satisfaction from the device.

The study group was made of 26 patients between the ages of 6 and 17 with a diagnosis of asthma, who were enrolled in the study for a period of 12 weeks. Participants each received an electronic monitoring device paired with a mobile app to support adherence to a controller inhaler. There were 2 phone call follow-ups at 4 and 8 weeks, and a final visit at 12 weeks. Outcomes measured were changes in ACT score, caregiver satisfaction, and medication adherence.

According to the study authors led by Leili Behrooz, MD, MPH, participants were 62% male and 38% female with a mean age of 9.1 years. Based on ACT scores, 28% of participants with uncontrolled asthma at baseline became controlled at final visit. “This improvement was observed at 4 weeks follow up and remained improved until the end of the study,” the authors wrote.

Non-adherence score increased from 1.1 at baseline to 1.9 at final visit (

=.10). 57% of participants reported no use of rescue medication at final visit, versus 36% at baseline. Moreover, 87% of caregivers reported that they would recommend the device and app to friends, and 78% found the device to be an effective tool for the management of asthma.

In a systematic review of mHealth interventions published in early 2018 in the Journal of Medical Internet Research, researchers found that mHealth interventions are generally effective for asthma maintenance. Positive impact has been demonstrated with moderate-quality evidence that text messaging interventions showed greater improvements in the pooled symptom score (mean difference 0.36, 95% CI) compared with a control group.

The review also found that mHealth interventions can increase adherence to treatment among patients with many conditions, including diabetes, hepatitis A and C, and asthma.

The study provided a “thorough review of available evidence on effectiveness of mHealth interventions in different health conditions, and in the processes of health care service delivery, so it is useful to guide clinical and health policy decisions,” wrote review author David Novillo-Ortiz, MLIS, MSc, PhD. Still, he acknowledged several limitations, including lack of assessment of risks, consumer satisfaction, and acceptability of the intervention.

“More attention to cost implications seems warranted,” he wrote. “Additionally, future studies should compare effects in different contexts.”

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Asthma is the most common chronic disease of childhood. Cellphones might help improve its management.
 

mHealth Intervention for Pediatric Asthma Boosts Adherence, ATC Scores

Recommended storage for epinephrine auto-injectors (EAIs) is near room temperature — between 20-25°C (68-77°F) with permitted excursions between 15-30°C (59-86°F). But for many of the millions of people in the US who carry EAIs for their severe allergies, and especially those in colder climates, ensuring their EAI stays within that small range of temperatures is a big challenge.

But it might not have to be that way. New research presented at the annual meeting of the American College of Asthma, Allergy and Immunology in Seattle, Washington found that even after leaving EAIs in freezing temperatures for a full 24 hours, they still maintain a low risk for malfunction.

“Many people who use EAIs have been concerned about the current shortage of EpiPens,” said allergist Anne Ellis, MD, chair of the ACAAI Anaphylaxis Committee. “It’s important for those who have severe, life threatening reactions to their allergies to have confidence in the EAIs they carry and know they’ll work in an emergency. This study showed that even when an EAI has been unintentionally frozen, the risk is low that it will malfunction.”

To arrive at their results, investigators paired 104 same-lot post-consumer single-common-brand expired EAIs (50 0.3 mg and 50 0.15 mg devices). One of each pair was frozen at -25°C (-13°F) for 24 hours, while the other was kept at recommended temperatures as a control.

After thawing the frozen device, both devices were fired into meat. The increase in meat mass and decrease in device mass were measured to estimate the mass of solution fired.

There was sufficient power (>95%) to conclude equivalence for both outcomes, defined as equivalent if the average difference in mass for frozen devices was within 10% of the difference for unfrozen devices. Two one-sided t-tests showed equivalence for both outcomes (

 < .0001), indicating frozen and thawed devices fired a similar mass of epinephrine solution compared with unfrozen devices. Testing continued to show equivalence after controlling for device epinephrine dose (0.3 mg vs 0.15 mg) and expiration date, using two one-sided tests in a general linear model.

“Since many people who live in cold climates use an EAI, we wanted to explore the effects of freezing on how an EAI functions,” said Julie Brown, MD, co-author of the study. “The change in meat weight and device weight was similar between frozen-thawed devices and their controls, indicating that freezing did not affect how the EAIs functioned once they were thawed.”

If a patient has an EAI that was unintentionally frozen and they experience an anaphylactic reaction, it’s better to use a frozen and thawed device than nothing at all, the authors wrote. While the study corroborates evidence from previous reports indicating that frozen EAIs still fire effectively, patients should continue to talk to their allergists to receive a prescription for a newer, never-frozen device if theirs becomes frozen.

Results may ease concerns for many physicians and patients who live in colder climates.
 

Despite Storage Rules, Frozen Epinephrine Auto-Injectors Still Work After Thawing

There are few physicians better poised to offer insights into the right situations and methods for oral food challenges than Dave Stukus, MD. At his busy academic center in Columbus, Ohio, Stukus and colleagues conduct between 20-25 oral food challenges per week. In his own more than 10-year career as an allergist, Stukus has conducted no less than a thousand oral food challenges.

A lot of allergists are interested in oral food challenges. So why are some so wary of the practice and what are their big concerns?

Shortly after hosting a presentation on the topic in front of a standing-room only crowd at the 

 of the American College of Asthma, Allergy and Immunology in Seattle, Washington, we caught up with Stukus to learn more about when and how to conduct oral food challenges.

I think the overarching thing we hear is that it's a difficult thing to do oral food challenges in a busy clinical practice. You need to have dedicated exam rooms where you can stay for several hours, and you need to have support staff that's available in case an allergic reaction occurs so you can drop everything and treat them immediately if that happens. Working that out in an outpatient center that may be miles away from a medical facility or an emergency room is understandably logistically challenging for a lot of folks.

What evidence supports oral food challenges? If I was a physician on the fence about it, how would you help me arrive at a decision?

Also, with the specialty of allergy and immunology, there are a lot of folks who don't have a comfort level in treating young infants and children. Therefore, they may be more reluctant to do oral food challenges in that subset of the population.

It's widely believed that oral food challenges are the gold standard and absolute best test to diagnose food allergy. They can be used at the time of initial diagnosis when the clinical history and/or IgE testing is indeterminate, or to determine if somebody with known food allergies develops tolerance over time. So, that's really the best way to figure this out.

We know that with food challenges, if you select the patient properly, prepare the patient and/or family ahead of time regarding what to expect and the potential for a reaction to occur, and we proceed slowly, it's very safe to do.

There's a misconception that if somebody has a reaction during a food challenge that it's going to be all or nothing and they're going to immediately have a life-threatening allergic reaction, but that's not what we see generally. So when patients pass the test and they're able to eat a couple of servings of food without having any reaction and they're no longer considered allergic, that's a life-changing moment for them. They may not have to avoid their allergen and sometimes they won’t have to carry epinephrine anymore. It can change everything about how they navigate the world.

Can you point to a particular case of an oral food challenge that you want to highlight as an example for other physicians to follow?

Even when people have symptoms during a challenge, they also have improved quality of life because 1) it proves that they're allergic, so it removes any question; 2) It reinforces the need to follow food allergy management strategies; 3) It teaches them exactly what an allergic reaction would look like, and most importantly; 4) They see how quickly symptoms subside when you give them the proper treatment. So it's a real life example that occurs in a very safe clinical setting under supervision, that demonstrates to people that this is what it would look like if you're out to a restaurant or in school and you start to have an allergic reaction, and this is how it should be treated.

Some of the more dramatic examples are people who take an allergy avoidance strategy because they have a incomplete understanding of true risks. For example, I met a family that felt because of their child's peanut allergy that they couldn't send their child to school. They didn't go to church anymore, they were too afraid to go to a restaurant, or even to walk inside a grocery store. They never went trick-or-treating. It’s extreme stuff, because they thought that if you accidentally touch a peanut you could die. Well, lo and behold, his allergy tests were very mild but nobody was willing to do the oral food challenge because they were worried that a peanut challenge in the young child could cause a severe reaction.

I was willing to do that, so they drove 10 hours to come see me. He passed the challenge just fine. It turned out he was never allergic in the first place! I still get updates from them almost 2 years later about his first time trick-or-treating, a field trip for kindergarten and first grade, and simple things like enjoying Thanksgiving like everybody else. It was a dramatic, emotional, life-changing experience for this family.

What sort of questions do you get about oral food challenges?

I have other examples where it's adolescents that have been avoiding a food for their whole lives. Now they're heading off to college or just scared of the unknown. They have no idea what would happen if they were to accidentally eat something, so they'll do a challenge sometimes even knowing that they might potentially react. But we do it in a safe way, and then whenever they do have symptoms, we treat them immediately. They're usually mild with some itching or hives or maybe upset stomach, but they get better. These folks say that it was a really helpful exercise to go through, because they were thinking that if they accidentally took a bite of something or have even a trace amount that they would die immediately.

There are two themes  to the questions. One is that a lot of people are making the diagnosis of food allergy based on testing alone. We spend a lot of time talking about why the clinical history is the most important part in making a diagnosis and how the tests that we have available are not the end-all-be-all and should not be interpreted as positive or negative. There's a scale that determines the likelihood that somebody is allergic and I think there's a lot of questions in regards to that.

So how about that second question? What sort of advice do you give on incorporating oral food challenges into practice?

What's the key takeaway for those interested in oral food challenges?

And then the second part is about how do I make oral food challenges work in my busy office setting? I want to do the right thing. I want to help my patients, but I'm stuck with my current office setup. What can I do to change that?

It's really about getting comfortable, and kind of reinforcing that we all receive the specialized training during fellowship as allergists. Really, we’re the experts when it comes to this. Other physicians don't receive the proper training in regards to oral food challenges, or in the recognition of anaphylaxis. So if our patients can’t rely on us, who can they rely on? It's really all about that positive messaging and trying to build some confidence through that. It’s also important to begin thinking about the logistics of how their flow goes inside the clinic setting. How many rooms do they have? What's the support staff like? What kind of experience do they have with food challenges already? What are some limitations that they're having now? Everybody has a little bit of a different case.

It's the most important part of establishing a diagnosis -- either establishing a diagnosis of food allergy and food allergy management to determine if someone's no longer allergic. There's just no getting away from it. It can be anxiety-provoking for patients and families, and rightfully so, but if we've approached it in a reassuring way and we follow safe, standardized ways of doing it, they can be a huge benefit.

Demystifying the oral food challenge starts with understanding its risks and benefits. 

When and How To Conduct Oral Food Challenges

Describe the Phase 3 Liberty Asthma Quest study of dupilumab.

For physicians treating patients with asthma, why is it important to have dupilumab as an additional treatment option?

 of the American College of Asthma, Allergy and Immunology in Seattle, Washington, investigators found that add-on dupilumab (Dupixent, Sanofi/Regeneron) reduced severe asthma exacerbations and improved lung function in patients with allergic and non-allergic uncontrolled, moderate-to-severe asthma and was generally well tolerated. In an interview with 

, study co-author Nicola Alexander Hanania, MD, a pulmonologist at the Baylor College of Medicine in Houston, Texas, explained what the study means for practicing pulmonologists and allergists.

This was an analysis of the large Quest Liberty study, which was the large 1900-patient study looking at patients with severe asthma and the effect of the aisle 4 receptor antagonist dupilumab in these patients. This abstract looks at the allergic subpopulation in the large study population. the main study was published in the New England Journal of Medicine, so this is a subgroup analysis. We looked at patients who had allergic asthma, defined by the presence of allergy specific IgE in the blood (one or more positive), and high serum ige -- that’s how we defined the population. We found in this population that about 56% of the patients had allergic phenotypes, which was shown in the large study. Looking at dupilumab, even though it's approved for eosinophilic asthma in the United States, it actually works very well in patients with allergic phenotypes, so that's really the take home message

When it comes to severe asthma, we have overlapping phenotypes. Some severe asthmatics have eosinophilic asthma and they don't have allergic symptoms and they're not sensitized. For those, we have several drugs currently approved, including the anti-aisle 5 therapies. Dupilumab will work with that as well.

What we also have is another phenotype that doesn't have very high eosinophils, but they have allergic asthma, which is characterized by sensitization to allergens and high IgE. Right now we have a treatment which is an anti-IgE, which is omalizumab, which has been approved for a long time for that population. What dupilumab does is it actually can target those populations, the eosinophilic and also allergic. It is an aisle 4 receptor antagonist that can block the IgE synthesis, and therefore it does work nicely in allergic asthma by reducing the production of IgE.

What are the best practices for prescribing dupilumab?

Coming back to clinicians, I think there's obviously overlap between all the biologics available, but knowing where each drug will work will help them identify the best treatment for the patient. So it’s mainly about improving the personalized approach to therapy, keeping in mind that there's going to be overlap between eosinophilic and allergic asthma in real life. Some patients with allergic asthma also have eosinophilic asthma, but knowing that the drug works in both populations is reassuring.

This is true for all biologics, not just to dupilumab -- before we jump into describing a biologic one has to determine whether the patient that we are dealing with has severe disease. By definition, severe disease is in patients with asthma who require a high dose of inhaled corticosteroids, plus another controller like a long-acting beta2-agonist to maintain control, without which the pt is uncontrolled. So severe disease is all those patients who continue to be uncontrolled despite that therapy. Another very important group is those who are still dependent -- more than 50% that group with severe asthma.

This should be underlined: We have to rule out good adherence, comorbidities management, and chiggers. Because you may get patients who need all these medications because they're not taking their inhaler correctly or they're not taking their medication, or they’re continuously exposed to chiggers, or they have comorbidities. But if all these are dealt with and the patient is still needing inhaled steroids at a high dose to keep the asthma under control, then that’s severe asthma. That's when you need to biologic.

Study co-author Nicola Alexander Hanania, MD, explains what the new data means for practicing pulmonologists and allergists. 