Fractional Exhaled Nitric Oxide (FeNO) Combined with Pulmonary Function Parameters Shows Increased Sensitivity and Specificity for the Diagnosis of Cough Variant Asthma in Children

Abstract

Background Cough variant asthma in children presents with a dry nonproductive cough. This study aimed to investigate the diagnostic value of fractional exhaled nitric oxide (FeNO) combined with small airway functional parameters in cough variant asthma. Material/Methods Children with asthma (n=136) were divided into a cough variant asthma (CVA) group (n=57; mean age, 8.03±2.1 years) and a non-cough variant asthma (nCVA) group (n=79; mean age, 8.61±1.7 years). In both groups, FeNO and other pulmonary function parameters were measured including forced expiratory volume in one second (FEV1), forced vital capacity (FVC), peak expiratory flow (PEF), maximum mid-expiratory flow (MMEF), forced expiratory flow (FEF), and maximum expiratory flow at 25%, 50%, and 75% expired volume (MEF25, MEF50, and MEF75). Receiver-operating characteristic (ROC) curve analysis compared the sensitivity and specificity between the diagnostic parameters. Results The FeNO values were significantly increased in the CVA group compared with the nCVA group (Z=6.890, p<0.001). The MMEF, MEF25, MEF50, and MEF75 values were significantly lower in the CVA group compared with the nCVA group (p=0.000, p=0.014, p=0.000, and p=0.000, respectively). The FeNO values were negatively correlated with MEF25, MEF50, and MMEF (r=−0.334, r=−0.257 and r=−0.276, respectively). FeNO was significantly more efficient diagnosing cough variant asthma comparing with pulmonary parameters (p<0.05), and was most sensitive and specific when combined with MMEF/MEF50 compared with single diagnostic parameters (p<0.05). Conclusions FeNO combined with pulmonary function parameters of MMEF/MEF50 showed increased sensitivity and specificity for the diagnosis of cough variant asthma.

The value of small airway function parameters and fractional exhaled nitric oxide for predicting positive methacholine challenge test in asthmatics of different ages with FEV1 ≥ 80% predicted

“…This is consistent with previous results that normal aging contributed to SAD in different subgroups of patients with asthma 9,22,23 ; moreover, it indicates that SAD might be more severe and common in older patients than in younger patients. Consistent with this finding, in our study, the cut‐off value of FEF 25%–75% and FEF 50% for a positive MCT prediction for asthma diagnosis in patients aged ≥55 years (65.0% for FEF 25%–75% and 62.9% for FEF 50% ) was much lower than that in patients aged <55 years (74.2% for FEF 25%–75% and 74.9% for FEF 50% ), which is consistent with previous findings that the optimal cut‐off value of FEF 25%–75% was lower in Chinese adults with CVA (78.5%) 11 than in Chinese children with CVA (80.5%) 24 . Moreover, the cut‐off values of FEF 25%–75% and FEF 50% in older patients with a positive MCT (65.0% for FEF 25%–75% and 62.9% for FEF 50% ) decreased significantly compared with those in patients not stratified by age (75.2% for FEF 25%–75% and 73.7% for FEF 50% ).…”

“…There were no significant between‐age‐group differences in the FEF 25% and PEF (all p > 0.05) in patients with a positive MCT. Furthermore, we found that the predictive value of FEF 25%–75% was lower in elder patients (Table 2), which was consistent with previous findings (0.800 for children and 0.702 for adults with CVA, respectively) 11,24 . Notably, regardless of age stratification, the FEF 25%–75% and FEF 50% alone could not predict AHR in patients with suspected asthma since the AUC was <0.8.…”

“…The FeNO value has been reported to be affected by age 13,14 . Specifically, FeNO >25.5 ppb had a high predictive value (AUC = 0.905) with a sensitivity and specificity of 82.2% and 90.0%, respectively, for CVA diagnosis in Chinese children with an average age of 8 years, 24 which differed from that in the aforementioned Chinese adults with CVA 11 . Consistent with this trend, our study showed that the FeNO value was higher in patients with positive AHR aged <55 years than in those aged ≥55 years ( p < 0.05), which indicated that airway eosinophilic inflammation might be more severe in younger patients with asthma who may be more sensitive to corticosteroids.…”

Elevated Serum Levels of Herpes Virus Entry Mediator and IL-5 in Cough Variant Asthma Versus Classic Asthma Patients

“…It may suggest that the decline of pulmonary function is relatively milder in CVA patients. However, previous studies found that the values of MEF50% and MEF25% in CVA patients were lower compared with CA patients, and suggested that CVA is mainly characterized by dysfunctions of small airways [15,16] . The discrepancy in results may be explained by the different enrolled subjects.…”

Fractional Exhaled Nitric Oxide (FeNO) Integrating Airway Hyperresponsiveness (AHR) Examination Promotes Etiologic Diagnosis and Treatment for Children with Chronic Cough

“…Pulmonary function is commonly used to reflect diagnosis and treatment for children’s chronic cough, and the airway reversibility test is of diagnostic value for etiologic diagnosis [ 8 ]. There is an appropriate correlation between level of fractional exhaled nitric oxide (FeNO) and eosinophilic inflammation of the airway in bronchial asthma patients [ 9 , 10 ]. The Global Initiative for Asthma Guidelines [ 11 ] and China’s Guidelines for the Prevention and Treatment of Children’s Bronchial Asthma [ 8 ] also list FeNO as a noninvasive biomarker for inflammation of the asthmatic airway together with sputum inflammatory cell detection.…”