FeNO Can Distinguish Exacerbation Events in Mepolizumab-Treated Asthma

Asthma exacerbations that occur in patients while receiving mepolizumab can be classified as 2 distinct entities, which can be differentiated using fractional exhaled nitric oxide (FeNO): noneosinophilic (driven by infection with low FeNO and high C-reactive protein [CRP] concentration) vs esinophilic (high FeNO). This is according to the results of the multicenter, prospective, observational MEX cohort study (ClinicalTrials.gov Identifier: NCT03324230) conducted at 4 UK specialist severe asthma centers among mepolizumab-eligible patients. Results of the analysis were published in The Lancet Respiratory Medicine.

The investigators sought to explore the inflammatory phenotype and physiologic features of exacerbation events in a cohort of individuals with severe eosinophilic asthma who were treated with the humanized monoclonal antibody mepolizumab. All study participants were between 18 and 80 years of age, had a diagnosis of severe eosinophilic asthma (Global Initiative for Asthma [GINA] treatment steps 4 and 5), and were eligible for mepolizumab therapy, which included having an oral corticosteroid requirement of either maintenance oral corticosteroids or ≥4 exacerbation events that had required treatment with oral corticosteroids in the prior year.

All study participants received mepolizumab 100 mg, which was administered by subcutaneous injection every 4 weeks, as well as an electronic peak expiratory flow recorder and a daily symptoms diary for the duration of the study. Characteristics of participants who experienced exacerbations on mepolizumab therapy were compared with those who did not experience exacerbations. Peak flow and symptom diaries were also compared among those in whom exacerbation events were evaluated vs those who missed assessments. Exacerbation phenotypes, which were defined by sputum eosinophil cell counts, were compared.

A total of 145 participants were enrolled and treated with mepolizumab between November 20, 2017, and May 29, 2019, with 5 of them excluded from the analysis. Overall, 62% (87 of 140) of the participants experienced a total of 172 exacerbation events. Participants who experienced exacerbation events had higher rates of exacerbations and more emergency department visits in the year prior to initiating mepolizumab treatment compared with those who did not experience exacerbation events. The change in peak expiratory flow at nadir was mean -40.5 L/min in the assessed exacerbation group vs mean -37.0 L/min in the missed exacerbation group, which was not statistically significant (P =.84); no difference in symptom burden was reported.

When exacerbations with a high sputum eosinophil count (≥2%; SEHIGH) were compared with exacerbations with a low sputum eosinophil count (<2%; SELOW), the SEHIGH group had a higher FeNO (P =.0004), with a significantly lower forced expiratory volume in 1 second (FEV1) percent predicted (P =.0075), significantly lower FEV1 to forced vital capacity (FVC) ratio (P =.0043), and significantly higher blood eosinophil counts (P =.0009). The SELOW group, on the other hand, had significantly higher CRP concentrations (P <.0001), significantly higher sputum neutrophil counts (P <.0001), and were significantly more likely to receive antibiotic treatment (P =.031). At exacerbation, FeNO was the most useful discriminator of inflammatory phenotype.

The investigators concluded that the findings warrant corroboration to verify that differentiating inflammatory phenotypes at evaluation of exacerbation will help guide better asthma management. Further studies are also needed to establish whether the absence of airway eosinophils predisposes individuals with asthma to airway infection.

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures. 


McDowell PJ, Diver S, Yang F, et al; on behalf of the Medical Research Council: Refractory Asthma Stratification Programme (RASP-UK Consortium). The inflammatory profile of exacerbations in patients with severe refractory eosinophilic asthma receiving mepolizumab (the MEX study): a prospective observational study. Lancet Respir Med. Published online May 7, 2021. doi:10.1016/S2213-2600(21)00004-7