Predictive Markers of Bronchial Hyperreactivity in a Large Cohort of Young Adults With Cough Variant Asthma

Cough variant asthma (CVA), a common asthma phenotype characterized by nonproductive cough and bronchial hyperreactivity (BHR), is usually detected by bronchial provocation tests (BPTs) which are timeconsuming, expensive, and unsafe. The primary study objective was to provide proof of concept for the use of fractional exhaled nitric oxide (FNO), eosinophil count percentage in induced sputum (sEOS%), forced expiratory flow between 25 and 75% of forced vital capacity (FEF) % predicted value, and FEF z-scores as surrogate markers predicting BHR in young adults with suspected CVA; the secondary objective was to compare the diagnostic performance of the various techniques. Three hundred and ten subjects (median age 24 years) were included in a cross-sectional study. Subjects were characterized as BHR positive (POS) ( = 147) or BHR negative (NEG) (n = 163) according to methacholine BPT. Classification accuracies were expressed as areas under the receiver operator characteristic curves (AUC). Compared with BHR NEG, FEF % predicted value and FEF z-scores were lower in the BHR POS group ( < 0.001), whereas FNO ( < 0.001) and sEOS% were higher ( < 0.001). AUC values for detecting BHR were as follows: FNO, 0.98 (SD = 0.02); sEOS%, 0.98 (SD = 0.02); FEF % pred, 0.93 (SD = 0.05); FEF z scores, 0.92 (SD = 0.05). Optimal cutoff values (OCV) for BHR prediction were as follows: FNO, 32.7 ppb (sensitivity = 0.93, specificity = 0.96), sEOS%, 3.80% (sensitivity = 0.94, specificity = 0.94), FEF % predicted value, 80.0% (sensitivity = 0.90, specificity = 0.87), and FEF z-score, -0.87 (sensitivity = 0.89, specificity = 0.87). Non-invasive/semi-invasive airway inflammatory or small airway functional measures might be used as surrogate markers predicting BHR in young adults with suspected CVA.