Airway remodeling, oscillometry in asthma care take the spotlight in expert debate
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NASHVILLE, Tenn. — There are no simple solutions in asthma treatment, as evidenced by a debate that covered airway remodeling and the use of oscillometry among other topics at the CHEST Annual Meeting.
Taking their cues from the ESPN program “Pardon the Interruption,” the members of the panel discussion were collegial in their agreements but unafraid to challenge each other’s opinions when they differed.
Airway remodeling
As moderator, David Schulman, MD, MPH, president of the American College of Chest Physicians, asked the panel if airway remodeling could be measured or modified.
“Airway remodeling involves the composition of epithelial cells, the constituents of the cells and everything else changing. We just don’t know exactly how to define it, but we kind of understand when we see it,” Frances Eun-Hyung Lee, MD, associate professor of medicine at the Emory School of Medicine, said.
Lee asked her colleagues if it also involves basement membrane changes, angiogenesis or fibrosis.
“All of the above,” Monica Kraft, MD, Murray M. Rosenberg Professor of Medicine and system chair of the department of medicine at the Icahn School of Medicine at Mount Sinai, said in response.
“So how do we measure it? We don’t have good biomarkers,” Lee continued. “Some patients get better when you treat them with steroids or some of these new biologics. Have we remodeled them?”
Kraft asked if biologics would particularly target smooth muscle in the airway, which she said plays a big role in asthma. Research, she continued, would help answer this question.
“We need to do bronchoscopy studies at the time of biologic administration and then keep patients on them for a long period of time and do it again,” Kraft said.
“Does it matter?” Sumita Khatri, MD, vice chair of the Respiratory Institute and director of the Asthma Center at Cleveland Clinic, then asked. “Airway remodeling is happening, and we know it.”
Instead, Khatri suggested, there is a need to make the process easier.
“Let’s make it into phenotypes that people understand — airflow limitation, airway inflammation, lower airway infections and impaired defenses,” Khatri said.
Mario Castro, MD, MPH, L.E. Phillips and Lenora Carr Phillips Professor of Medicine and chief of the division of pulmonary, critical care and sleep medicine at the University of Kansas Medical Center, indicated that tezepelumab-ekko (Tezspire; Amgen, AstraZeneca) reduces mucus plugs, which he called easy to see on a CT scan.
“We as clinicians can look at a CT scan and tell whether or not a patient is improving in terms of their mucus plugs,” he said. “I think lung function and CT scans are what I would use to measure remodeling.”
Kraft then questioned if biologics have remodeling effects in adults, as studies have examined whether they have had disease-modifying effects in children.
“I think that’s a huge issue. But I’d love to know about the long term in adults and what’s really going on at the airway level so we can sit here and tell our clinical colleagues about that because that might help in the decision-making, long term, [regarding] what you treat your patient with,” she said.
Lee asked her colleagues if they think that airway remodeling has already happened when patients present with lots of sputum production and nighttime exacerbations during a first-time diagnosis of asthma. Kraft indicated that some subepithelial membrane thickness already is present in pediatric asthma.
“There may be a reversible piece,” Kraft said. “That’s what I want to know about. That would be really, really good.”
Lee agreed that the basement membrane is constantly changing as proteins enter the environment and get broken down.
“Those mesenchymal cells, those fibroblasts making that basement membrane, we’re probably modifying that, and that would be really important to understand,” Lee said.
The role of oscillometry
The differences in the panelists’ opinions also were clear after Schulman asked them if oscillometry had a clinical role in asthma treatment.
“I’m tired of undiagnosed asthma. I’m tired of overdiagnosed asthma too. But underdiagnosed people have been suffering for years and years,” Khatri said.
When treatment does not work, instead of just trying more steroids, she continued, different approaches are needed in diagnosing the problem.
“We have very, very poor measures of lung function in certain people. So, I think oscillometry would be amazing. Honestly, I know it’s very difficult to interpret. I know it’s difficult to have some uniformity. You have to use the same machine,” she said.
Studies are then needed to examine resistance and elastance as well as activity in smaller areas of the airways, which is currently happening with COVID-19, she continued.
“I think it’s pretty worthless,” Castro countered, adding that he was involved in a study with more than 200 children indicating that oscillometry was characterized by “huge” variability and that it had no predictive value.
Kraft quickly answered that she was first author on a recent paper with nearly a thousand subjects that indicated otherwise.
“It showed oscillometry actually can predict exacerbations and it actually negates the effect of FEV1 when you put it in a model of other predictors of exacerbations like blood [eosinophils], [Global Initiative for Asthma (GINA)] stage and an exacerbation in the last year,” Kraft said. “I think there’s a place for it.”
“So why don’t we use it?” Lee asked. “Is it resistance? We don’t understand it? We don’t know how to measure?”
Kraft responded by saying oscillometry can be easy to use.
“It’s just that we don’t really understand necessarily the physiology as well as what you are really measuring. So, we just have to get the word out,” she said. “It’s approachable. We can get there. We’re smart people. We can do it.”
References:
- ACCP Chest. Pardon the interruption 2022: Controversies in asthma. https://www.youtube.com/watch?v=CRbYX-K1m2Y. Published Oct. 17, 2022. Accessed Oct. 19, 2022.
- Kraft M, et al. Lancet Respir Med. 2022;doi:10.1916/S2213-2600(21)00536-1.