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BOSTON -- Is measuring fractional exhaled nitric oxide (FeNo), a way to measure airway inflammation, a useful biomarker that should be used in all asthma patients? Or is that nothing more than "magical thinking?" Two experts offered their thoughts in a debate at the American College of Allergy, Asthma and Immunology annual meeting.

In taking the pro side, Neal Jain, MD, of San Tan Allergy & Asthma in Phoenix, argued that FeNo should be used in all patients whether type 2 (T2) inflammation was present or not. He said that not only does routine monitoring of exhaled nitric oxide have the potential to reduce exacerbation, but it can identify non-adherence to treatment in patients with T2 high disease and can help characterize subtypes of T2 asthma.

"We have been operating blindly with very few tools, but the art of probability is improving for us because of knowledge and biomarkers like FeNo," he said.

Jain added that he had been using FeNo since 2003 when it was a research tool, and argued the importance of needing to know if asthma patients have T2 disease or not. But he cited a prior study that found FeNo was better at identifying patients with eosinophilic asthma, an asthma phenotype that may be linked to increased asthma severity, compared with a methacholine challenge, a bronchial challenge test that may aid in asthma diagnosis, and other parameters.

Jain also cited research that concluded that FeNo was also better at excluding a diagnosis of asthma than these other measurements, with a negative predictive value of 96%. He cited another study that found FeNo predicted inhaled corticosteroid response better than forced expiratory volume in 1 second (FEV1).

"There's no single tool to diagnose asthma -- it's a complex condition with a lot of different subtypes," Jain said. "But FeNo measurements are point-of-care, easy to perform and low cost."

Taking the con side, Stephen Peters, MD, of Wake Forest University in Winston-Salem, North Carolina, argued that exhaled nitric oxide should not be used as a measurement in all asthma patients because there are many types of type 2 inflammation. He added that nitric oxide is an important regulatory molecule, but called it a "poor or incomplete surrogate" for T2 inflammation.

"There are many types of type 2 inflammation and one biomarker is not sufficient," Peters said.

Peters pointed to the 2011 American Thoracic Society (ATS) about the use of FeNo, where it was recommended for in the diagnosis of eosinophilic airway inflammation, in determining the likelihood of steroid responsiveness, and for accounting for patients with high allergy exposure. He added that despite these recommendations, the quality of evidence was only "moderate" in two cases, and low quality most of the time.

"Where are the convincing data and references?" Peters said. "Maybe there's a little bit of magical thinking here -- I want it to be true, so it must be true. But it adds little to a good clinician managing asthma, even though it's easy and fun to play with."

Jain acknowledged in a rebuttal that it was not a "perfect tool" for diagnosing asthma, but that FeNo had the potential to be one of many biomarkers to aid in diagnosis of the disease.

"When we see someone we're not sure about, we don't just stop at FeNo or lung function, but we gather other information," he said.

Jain also offered a rebuttal to the ATS statement from 2011, citing a that suggested there were decreased asthma exacerbations using FeNo.

In his rebuttal, Peters talked about the importance of individualized patient care, saying that the research showed "group mean responses," and certain biomarkers may work differently for certain patients. He emphasized the importance of the clinician determining a patient's diagnosis as opposed to a biomarker.

"It can be useful, but when we're talking about T2 [inflammation] in general, it's an incomplete surrogate," he said. "Somewhere, FeNo will be useful, but not for everyone and certainly not in routine practice."

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