Non-invasive Predictors Of Nonasthmatic Eosinophilic Bronchitis Remain Elusive

By Jeff Craven, MD /alert Contributor

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Non-invasive markers such as peripheral blood eosinophil (PBE) count and fractional exhaled nitric oxide (FeNO) are not reliable predictors of nonasthmatic eosinophilic bronchitis (NAEB), according to recent research published in the Journal of Investigational Allergology and Clinical Immunology.

“Though uncommon, NAEB is neither entirely benign nor self-limiting, since half of the patients experience numerous relapses,” Victoria Villalobos-Violan, of the Hospital Universitario Fundación Jiménez Díaz, Universidad Autónoma de Madrid and Instituto de Investigación Sanitaria (IIS) Fundación Jiménez Díaz in Madrid, Spain, and colleagues wrote in their study.

The researchers performed a retrospective study evaluating 41 patients with NAEB over mean 5.8 years at a single hospital between 2003 and 2019 for predictive markers of asthma and NAEB progression. Patients included in the study had experienced coughing for more than 3 weeks unrelated to allergen exposure, a chest radiograph that was normal, negative methacholine test (> 16 mg/mL), and a sputum eosinophil count of 3%. The researchers performed an adenosine challenge in some patients, while all patients received medium or high doses of inhaled steroids. 

Patients’ demographic data were collected, and they were assessed for atopy, allergic rhinitis, disease course, disease relapse, asthma development. Outcomes of testing were also recorded at first and last visit, and included PBE count, FeNO, pulmonary function tests, sputum eosinophil, and bronchial hyperreactivity to methacholine. An analysis of qualitative and quantitative variables was performed, and inter-group comparisons were made to identify variables potentially associated with asthma. The patients were divided into three groups based on relapsing disease, non-relapsing, and development of asthma. 

Researchers found 41.46% of patients experienced a relapse in disease in the form of a recurrent cough, and had a mean of two relapses. Patients were retreated with inhaled corticosteroid, which controlled the cough, they said.

Of 16 patients who had sputum tests repeated in a follow-up visit, researchers found a significant decrease in the percentage of sputum eosinophilia at the last visit compared to the first visit (2.42% vs. 8.0%; P < .05). Regarding FeNO, there were no significant differences between the last visit and first visit (34.56 ppb vs. 46.59 ppb; P = .95). The researchers found no significant correlation between sputum eosinophils and PBE (r = -0.17; P = .65), and no significant correlations between PBE (r = -0.37), FeNO (r = -0.14), or sputum eosinophils (r = 0.55) at first visit or disease relapse (P > .05).

For patients who developed asthma, the median time to development was 2.0 years, and those patients had significantly higher FeNO levels at baseline compared with patients in the rest of the study (95.2 ppb vs. 46.9 ppb; P < .05). All patients who developed asthma had atopy and allergic rhinitis compared with patients who didn’t develop asthma. 

In a univariate regression analysis accounting for age, gender and FeNO, the researchers found FeNO was significantly associated with development of asthma (odds ratio, 1.016; 95% confidence interval, 1.002-1.041; P = .028). Using the Fisher exact test to compare asthma development with age, atopy, and rhinitis, they found, atopy (P = .023) and rhinitis (P = .009) were significant 

However, when applying FeNO < 31.7 ppb as a cutoff marker, the researchers missed 40% of patients with NAEB, the researchers noted.

“The non-invasive markers PBE and FeNO were not sufficiently good to substitute induced sputum analysis for diagnosis and follow-up. Further studies are necessary to confirm these results,” the researchers concluded.


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