Research Article: Association between fractional exhaled nitric oxide, sputum induction and peripheral blood eosinophil in uncontrolled asthma

Date Published: May 23, 2018

Publisher: BioMed Central

Author(s): Jie Gao, Feng Wu.


The fractional exhaled nitric oxide (FeNO) and blood eosinophils are biomarkers of eosinophilic airway inflammation used in the diagnosis and management of asthma, although induced sputum is the gold standard test for phenotypic asthma. Nevertheless, the clinical application of the correlation between sputum eosinophils, FeNO and blood eosinophils is controversial.

To investigate the clinical application of the correlation between sputum eosinophils, FeNO and blood eosinophils with uncontrolled asthmatic patients. It also examined the relationships between these biomarkers in bronchial reversibility and bronchial hyper-responsiveness (BHR).

This study evaluated 75 uncontrolled asthmatic patients (symptom control and future risk of adverse outcomes). All patients underwent the following on the same day: FeNO, spirometry, BHR or bronchodilator reversibility, sputum induction and blood collection. Eosinophilic airway inflammation was defined as sputum eosinophils ≥ 2.5% or FeNO levels ≥ 32 parts per billion (ppb).

A significant positive relationship was between percentage of sputum eosinophils and FeNO (r = 0.4556; p < 0.0001) and percentage of blood eosinophils (r = 0.3647; p = 0.0013), and a significant negative correlation was between percentage of sputum neutrophils and FeNO (r = − 0.3653; p = 0.0013). No relationship between FeNO and percentage of blood eosinophils (p = 0.5801). ROC curve analysis identified FeNO was predictive of sputum eosinophilia [area under the curve (AUC) 0.707, p = 0.004] at a cutoff point of 35.5 ppb (sensitivity = 67.3%, specificity = 73.9%). Percentage of blood eosinophils was also highly predictive with an AUC of 0.73 (p = 0.002) at a cut-off point of 1.5%, sensitivity and specificity were 61.5 and 78.3%, respectively. Although the sputum neutrophil percentage was correlated with FeNO, ROC curve of these parameters did not show useful values (AUC = 0.297, p = 0.003; AUC = 0.295, p = 0.021). Blood eosinophils and FeNO can accurately predict eosinophilic airway inflammation in uncontrolled asthmatic patients. FeNO is poor surrogates for sputum neutrophils and blood eosinophils. The FeNO level and blood eosinophils, which determine an optimal cutoff for sputum eosinophilia, need more studies.

Partial Text

Asthma is a heterogeneous disease, characterized by the history of variable respiratory symptoms such as wheeze, shortness of breath, chest tightness and cough, usually together with variable expiratory airflow limitation. This was reached by consensus, recommended by the 2017 Global Initiative for Asthma (GINA) [1]. It has been recognized that among asthmatic patients there are clusters of demographic, clinical and/or pathophysiological characteristics, which has been called “asthma phenotypes” [1, 2]. However, to date, no strong relationship has been found between specific pathological features and particular clinical or treatment responses [3]. When examining the airway inflammation using sputum analysis, patients with asthma can be classified in four different inflammatory phenotypes. Based on the percentage of eosinophils and neutrophils in sputum, it was to define four airway inflammatory subgroups: eosinophilic asthma, neutrophilic asthma, mixed granulocytic asthma and paucigranulocytic asthma [4]. There is recent evidence from prospective clinical studies that airway inflammatory phenotype can help to optimise therapy and disease outcome. Eosinophilic asthma responds well to anti-inflammatory treatment with steroids, non-eosinophilic asthma shows little or no response [5]. This suggests that biomarkers of inflammation could be considered in identifying and monitoring of asthmatic patients in clinical practice, such as the titration of steroid treatment.

This study assessed the correlation of FeNO level, sputum eosinophils and blood eosinophils in initial diagnosis and uncontrolled asthma. All the people in the study were Chinese. FeNO level and percentage of blood eosinophils can accurately predict sputum eosinophilia. Percentage of sputum neutrophils was correlated with FeNO level and percentage of blood eosinophils, but not enough to be clinically useful. We also identified some additional findings, namely PD20/∆FEV1 association with FeNO level and percentage of sputum/blood eosinophils, which may reflect nothing.

This study provides that inflammatory biomarkers, including sputum eosinophils, FeNO level and blood eosinophils, can accurately predict sputum eosinophilia in patients with uncontrolled asthma. It suggests that peripheral blood eosinophil is a useful tool better than FeNO level for monitoring sputum eosinophilia in uncontrolled asthma. FeNO level is poor surrogates for sputum neutrophils and blood eosinophils. These data may be useful for identifying patients with eosinophilic airway inflammation who will have a beneficial response to treatment with an ICS, and it is important to help guide treatment and management of asthmatic patients.




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