Managing Severe Asthma: What to Know About Latest Advances

Graphs and charts don’t always tell the whole story. Sometimes numbers can deceive. However, anyone can look at U.S. trends for asthma mortality and see that they are in the right direction.

An analysis of 2019 in the American Journal of Respiratory and Critical Care MedicineFrom 1999 to 2015 asthma mortality decreased by 43%. “The decrease in asthma-related mortality was consistent in both sexes and in all race groups, with the largest decrease in patients older than 65 years,” the authors concluded. The positive trend is evident in the U.S. Centers for Disease Control and Prevention figures, and similar data from Europe and the U.K. show that it has continued into 2019.

“What I see in the clinic today is completely different than it was 10 years ago,” says Dr. Christopher Brightling, a clinical professor in respiratory medicine at the University of Leicester and a senior investigator at the National Institute for Health and Care Research in the U.K. “The treatment space is looking really positive, and with the newest drugs I would anticipate responses to be even better.”

According to him and others, biologics have been a major breakthrough in fighting severe asthma. Many patients have found these drugs to be life-saving. They work by altering the activity of cells or genes. Inhaler-based medicines, as well as connected technologies, are another bright spot. Many health systems are shifting their care team out of clinics to make it more accessible to underserved communities.

These and other recent advancements have led to real improvements in the patient’s access and outcome. “It is really a very exciting time in asthma research right now,” says Dr. Derek Chu, an assistant professor of medicine and a researcher in allergy and clinical immunology at McMaster University in Canada. “There’s a lot in development for both mild and moderate-severe asthma.”

Chu is joined by other specialists to discuss the latest developments in this groundbreaking treatment and strategy.

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What’s new in biologics?

The first FDA-approved biologic to treat severe asthma was approved by the U.S. Food and Drug Administration in 2003. Omalizumab is a monoclonal anti-inflammatory drug that reduces blood IgE levels. This antibody contributes to severe asthmatic airway inflammation.

Omalizumab’s breakthrough was not the only thing that happened, however experts claim the recent years have seen newer biologics emerge. They have almost eliminated the severe asthma burden for the majority of patients. “These have been totally transformational,” says David Jackson, a respiratory medicine specialist at King’s College London. “Since 2017, a new biologic has been added to our armory on almost an annual basis, and the number of patients with uncontrolled asthma has gotten smaller and smaller.”

Whereas the first biologics blocked IgE, the latest drugs in this category target—with greater and greater precision—the specific immune pathways and cells that drive asthma-related inflammation and symptoms. “Cells called eosinophils are a hallmark of severe asthma, and these newer biologic therapies can dampen down their production and related pathways in a much more targeted way,” Jackson says. Jackson uses an analogy from the military to illustrate the efficacy of new biologics. “These are like precision-guided laser bombs, as opposed to the old B52s dropping bombs from 50,000 ft. and just hoping for best.”

Two immune system proteins are targeted by some of the newest biologics: interleukin33 and thymic stromal lipopoietin. “These two activate cells in the airways, which leads to a release of all these [inflammation] players,” Brightling explains. Because these two are farther “upstream” than some of the pathways targeted by older biologics, mellowing their activity may produce broader benefits, he says.

There are downsides to biologics. For one thing, they’re expensive. Jackson estimates that they can cost as high as $30,000 per year in the United States. Insurance does not cover them all. Their administration used to require regular visits to the clinic and office. Biologics can be administered by injection from as often as once every two months up to twice every two weeks. The coronavirus epidemic has seen the drug’s use shift away from clinics to the homes. “There’s been a big push to self-administration,” Jackson says. “What we normally do now is to start in the clinic—so give the first one to three administrations here—then go to home administration when it’s clear the patient is doing well.”

Biologics offer many benefits, even if there are still logistical or financial obstacles. The latest and greatest biologics work so well that many patients are effectively relieved of the burden of severe asthma attacks or symptoms—something that would have seemed unbelievable just a decade ago.

Not everyone is eligible for these medications. “Awareness of this medicine is not what it should be,” Jackson says. “A lot of patients continue to have asthma attacks and their doctor hasn’t picked up on the fact that there are newer therapies.” If every clinician who treats severe asthma was up to speed on these drugs—and if everyone who truly needs them had access to these medicines—it’s possible that virtually every person with severe asthma could avoid the worst symptoms, he says.

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Phenotyping advances

Asthma was used to be considered a single condition that could affect anyone. But that’s changed. “The model of asthma as a single entity is now obsolete due to an increased understanding of its underlying heterogeneity,” wrote the authors of a 2019 study in Clinical Reviews in Allergy & Immunology.

At this point, “asthma” is an umbrella term for a number of related but distinct diseases that are differentiated in part by the activation of various immune pathways. These pathways can now be mapped more accurately than ever. By identifying the ones driving pathology in an individual patient—a process often called “phenotyping”—clinicians can better predict how that person will fare on a drug. “The phenotyping piece has been one of the big shifts,” Brightling says. “It can help us understand which patients will respond best to a treatment.”

Phenotyping often starts with an assessment of a patient’s demographic or symptom characteristics. Are they young or old? Are they suffering from early-onset, or late-onset asthma Are they overweight? Are they overweight? In the near future—and this is where some of the latest advancements have occurred—phenotyping may involve blood and breath tests. Brightling says blood tests can provide helpful information on eosinophils and other immune system players that give rise to a person’s asthma symptoms. Exhaled nitric dioxide can be detected in the lungs by performing breath tests.

Effective treatments need to be discovered and adapted to patients in order to make them effective. The key to successful matchmaking is Phenotyping.

‘Smart’ inhalers are getting smarter

It can be hard for patients with asthma to remember their medications. Asthma experts know this. Adherence is often low, especially among severe asthma patients who are young. The 2018 Study in the European Respiratory JournalIt was found that 63% of severe asthma patients did not follow their treatment plans, even though they had received special education courses on inhaler usage and disease management.

“I think one of the biggest challenges, especially with severe asthma, is that patients feel fine a lot of the time, and it’s difficult to remember to take a medication every single day if you’re feeling good,” says Dr. Ruchi Gupta, a professor of pediatrics, preventive medicine, and medicine (allergy and immunology) at Northwestern University’s Feinberg School of Medicine and Lurie Children’s Hospital. Experts also believe that expensive biologics may not be necessary if patients suffering from severe asthma take their inhaled corticosteroids more often.

There’s a new solution to this problem: smart inhalers that can notify patients or their care team when doses are missed. You can find a study on 2021 here Pediatrics,Gupta and her team examined whether inhalers that are Bluetooth connected could be useful for children suffering from asthma. The inhalers notified a child’s care team if they missed their daily doses several days in a row, or if they took too many rescue doses in a single day. Study results showed that after 12 months, asthma sufferers had increased their treatment compliance by 17%, and had also seen a decrease in the burden of symptoms. “Patients felt like someone was looking out for them and taking care of them,” Gupta says.

These smart-inhaler technology are available, though they may not be covered by insurance. Patients can purchase inhaler sensors to remind them when they have to take their medication. Some healthcare systems use office notifications in a similar way to what Gupta (and her team) studied. These new technologies have not been widely adopted. “My dream is that every time a patient uses their inhaler, this information would go straight into their electronic medical chart,” she says. “I know some groups are working on that.”

Accessible innovations

Modern medicine faces many challenges, including ensuring equitable access to quality healthcare. Gupta mentions the obstacles that prevent patients from receiving the care they require, such as drug prices, Medicare coverage and Medicaid access.

As an attempt to deliver quality healthcare to those who are least fortunate, asthma experts have started to travel to the community to see patients. “Doctors here in Chicago are going out into the community and setting up tents where people know they’ll be, or going to schools and giving checkups in parking lots,” Gupta says.

She also mentions the “asthma vans” that are now operating in Chicago. The clinics are staffed by allergist professionals and drive into underserved neighborhoods to offer treatment. “These have been very effective resources,” she says. We need more options like these to increase access to the best asthma care.

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Road ahead

There’s a lot more going on in the field of severe asthma care. A 2021 study is available here. JAMA, Chu found that triple-drug therapy—adding a third medication to the common two-drug combination of corticosteroids and bronchodilators—led to a lower incidence of severe attacks among patients who use inhalers.

He believes that the future is bright but there are still many challenges. “The main issues are the critical need for head-to-head studies of active drugs or management approaches, rather than purely placebo-controlled studies,” he says. The best treatments could be clarified by this research.

Many people suffering from severe asthma have never had a better life. “Many patients almost feel like they don’t have the disease anymore,” says Jackson. “They stop having attacks, stop showing up in hospitals, and can function without asthma interfering in their life.” That’s worth celebrating.

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