Leading expert Jerry Krishnan, MD clears up confusion about differing GINA and EPR-4 asthma guidelines at CHEST

By Lisa Marie Basile | Fact-checked by MDLinx staff
Published October 14, 2024

Key Takeaways

  • The session highlighted variations between the National Asthma Education and Prevention Program (NAEPP) and GINA guidelines for step-up asthma treatment in patients over 12.

  • There's a need for need for clinicians to distinguish between various ICS-formoterol formulations due to the complexity of asthma pharmacotherapy.

This article is part of our CHEST 2024 coverage. Explore more.

A Tuesday morning session examined how the National Asthma Education and Prevention Program Coordinating Committee (NAEPP) Expert Panel 4 (EPR-4) and the Global Initiative for Asthma (GINA)  approached guidelines for step-up asthma treatment in both adults and the pediatrics population. 

Here were some key takeaways from the session: 

Reviewing the use of ICS-Formoterol and the terms “SMART” versus “MART”

Jerry Krishnan, MD, kicked off the session by defining some relevant terminology—focusing especially on Single Maintenance and Reliever Therapy (SMART)—preferred by the NAEPP, and Maintenance and Reliever Therapy (MART)—preferred by GINA. Clinicians may see these terms everywhere but not realize they’re interchangeable. 

Both SMART and MART refer to the use of ICS-formoterol inhalers. “A lot of us use [ICS-formoterol] off-label, he says, but you should be aware it’s not approved in the United States,” Dr. Krishnan says. 

ICS–formoterol inhalers

But the medicine is recommended: “The Global Initiative for Asthma 2023 update preferentially recommends use of ICS–formoterol inhalers at all steps of asthma management for ages 12 and up,” says the Journal of Allergy and Clinical Immunology. 

Formoterol is a hybrid, or dual agent,” he says. “It functions with a short-acting and long-acting beta 2 agonist (LABA) functions—although it’s not the same as an  ultra long-acting beta 2 agonist, which lasts a full day.” For this reason, he says clinicians need to make sure that their prescriptions are clear, as there are many formulations. Be sure you know the difference, say, between “ICS-formoterol” not “ICS-LABA.”

“Pharmacotherapy in this space is getting a little more complex,” Dr. Krishnan says.

Step approaches to managing asthma in patients 12 and older Dr. Krishnan then showed the room the step-approach for the management of asthma via both GINA and NAEPP. The steps differ a bit for moderate to severe asthma (steps 3-5):

  • Step 1: NAEPP not reviewed.

  • Step 1: GINA suggests as-needed low-dose ICS-formoterol. Step 2: NAEPP suggests daily low-dose ICS and PRN SABA or PRN concomitant ICS and SABA.

  • Step 2: GINA suggests as-needed low-dose ICS-formoterol.

  • Step 3: NAEPP suggests daily and PRN combination low-dose ICS-formoterol.

  • Step 3: GINA suggests low-dose maintenance ICS-formoterol.

  • Step 4: NAEPP suggests daily and PRN combination medium-dose.

  • Step 4: GINA suggests medium-dose maintenance ICS-formoterol.

  • Step 5: NAEPP suggests medium-high dose ICS-LABA + LAMA and PRN. SABA. Note that NAEPP did not review biologics.

  • Step 5: Add-on LAMA, refer for assessment of phenotype. Consider high-dose maintenance ICS-formoterol + recommendations for biologics, like anti-IgE, anti-IL5R, anti-IL4R, and anti-TSLP. 

Asthma treatment in the pediatric population

Michelle Cloutier, MD then discussed asthma in pediatrics, saying it’s hard to define and predict asthma in children. She then asked how many people in the room treated children. Less than 10 hands went up in total in a full room. 

Voices from the floor

She explains further: “Half of all children experience one or more episodes of wheezing by six years of age, and 80% of children hospitalized for wheezing are never hospitalized again,” she says. This is what makes prediction especially tricky.

Treatment recommendations, she says, are essentially extrapolated from studies in older patients and are generated mostly by expert opinion, Dr. Cloutier adds. When it comes to escalating treatment she says, “There is a paucity of data—and I mean that politely.”

There are key differences in treatment for the 0-4 age group for inadequate control with low daily dose ICS + SABA between NAEPP and GINA, specifically in the use of LTRA and LABA therapy:

  • NAEPP recommends a preferred medium daily dose of ICS+ PRN SABA at step 3

  • GINA recommends a preferred double dose of ICS + PRN SABA at step 3

  • GINA notes that an alternative could be daily low-dose ICS + leukotriene receptor antagonists  (LTRA) at step 3.

  • NAEPP does not recommend LTRA, and notes a black box warning at step 3. 

  • NAEPP recommends daily medium-dose ICS-LABA + PRN SABA with no alternative at step 4.

  • GINA recommends ICS + PRN SABA and “referring to specialist” with an alternative ICS + LTRA + PRN SABA treatment at step 4. 

In kids 4-11, there are more similarities than differences starting at step 3:

  • NAEPP recommends daily and PRN low-dose ICS-formoterol (SMART) at step 3

  • GINA recommends daily medium-dose ICS and PRN SABA OR daily low-dose ICS-LABA and PRN OR daily and OPRN very low-dose ICS-formoterol at step 3

  • NAEPP recommends daily and PRN combination medium dose ICS-formoterol while GINA recommends medium-dose ICS-LABA OR daily and PRN low-dose ICS-formoterol 

Cloutier says there are 3 biologics approved for kids: Omalizumab, Mepolizumab, and Dupilumab. Dr. Cloutier says the biologics are roughly, “the same in terms of exacerbation rate, and may allow you to decrease steroid use.” This is important, too: “I think we are just uncovering some of the long-term effects of exposure to corticosteroids,” she says. 

The paucity of data she mentioned earlier? It’s the same with biologics. “Recommendations on exactly how to use them are seriously lacking. There's a major need for that,” Dr. Cloutier says. 

Reframing how clinicians approach escalation of treatment 

Dr. Krishnan also talked about how clinicians think about escalating treatment. “It’s easy to keep treatment escalating…. [but] you need to make sure they actually have asthma. Maybe it’s heart failure or lymphoma, for example. So, be aware before treatment escalation that the diagnosis is right.”

He suggests that clinicians ensure that patients know precisely how to use the medication as prescribed. “Engage them in how they’re using their medication,” Dr. Krishnasn says. 

“Asthma is by and large a condition that reflects the environment, so make sure the patient is also doing what they can to mitigate risks in their environment. The idea is that as you engage up and down these steps, you may need to do evaluation as well,” he adds.

“The other component is step-down,” he continues. “Don’t always think you should step-up. In general, look for opportunities to step-down therapy. Three months is a reasonable time to ask, is it time to step down, or not?”

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