Diagnostic role of fractional exhaled nitric oxide in pediatric eosinophilic esophagitis, relationship with gastric and duodenal eosinophils

BACKGROUND Eosinophilic esophagitis(EoE)is an eosinophilic-predominant inflammation of the esophagus diagnosed by upper endoscopy and biopsies.A non-invasive and cost-effective alternative for management of EoE is being researched.Previous studies assessing utility of fractional exhaled nitric oxide(FeNO)in EoE were low powered.None investigated the contribution of eosinophilic inflammation of the stomach and duodenum to FeNO.AIM To assess the utility of FeNO as a non-invasive biomarker of esophageal eosinophilic inflammation for monitoring disease activity.METHODS Patients aged 6-21 years undergoing scheduled upper endoscopy with biopsy for suspected EoE were recruited in our observational study.Patients on steroids and with persistent asthma requiring daily controller medication were excluded.FeNO measurements were obtained in duplicate using a chemiluminescence nitric oxide analyzer(NIOX MINO,Aerocrine,Inc.;Stockholm,Sweden)prior to endoscopy.Based on the esophageal peak eosinophil count(PEC)/high power field on biopsy,patients were classified as EoE(PEC≥15)or control(PEC≤14).Mean FeNO levels were correlated with presence or absence of EoE,eosinophil counts on esophageal biopsy,and abnormal downstream eosinophilia in the stomach(PEC≥10)and duodenum(PEC≥20).Wilcoxon rank-sum test,Spearman correlation,and logistic regression were used for analysis.P value<0.05 was considered significant.RESULTS We recruited a total of 134 patients,of which 45 were diagnosed with EoE by histopathology.The median interquartile range FeNO level was 17 parts per billion(11-37,range:7-81)in the EoE group and 12 parts per billion(8-19,range:5-71)in the control group.After adjusting for atopic diseases,EoE patients had significantly higher FeNO levels as compared to patients without EoE(Z=3.33,P<0.001).A weak yet statistically significant positive association was found between the number of esophageal eosinophils and FeNO levels(r=0.30,P<0.005).On subgroup analysis within the EoE cohort,higher FeNO levels were noted in patients with abnormal gastric(n=23,18 vs 15)and duodenal eosinophilia(n=28,21 vs 14);however,the difference was not statistically significant.CONCLUSION After ruling out atopy as possible confounder,we found significantly higher FeNO levels in the EoE cohort than in the control group.

Significance of Fractional Exhaled Nitric Oxide Combined with Serum Procalcitonin and C-Reactive Protein in Evaluation of Elderly Asthma

Bronchial asthma is a common chronic airway inflammatory disease. Asthma is associated with high mortality, especially in the elderly patients. Repeated exacerbations cause disease progression. Therefore, identifying the onset of acute elderly asthma as soon as possible and giving the effective treatment is crucial to improve the prognosis. This study was to investigate the significance of fractional exhaled nitric oxide （FeNO） combined with serum procalcitonin （PCT） and C-reactive protein （CRP） in the evaluation of elderly asthma. A total of 120 elderly patients with an acute attack of asthma from July, 2010 to May, 2012 were studied. On presentation, FeNO, serum PCT and CRP concentrations were measured and sputum culture was also performed. The elderly patients were re-evaluated when they had returned to their stable clinical state. The elderly patients were classified into two groups： positive bac- terial culture group （A） and negative bacterial culture group （B）. The results showed that： （1） In patients with an acute exacerbation of asthma, 48 （40%） patients had positive sputum bacterial culture and 72 （60%） had negative sputum bacterial culture. （2） The levels of FeNO in patients with acute exacerbation of asthma were significantly higher than in those with no acute exacerbation state （63.8±24.6 vs. 19±6.5 ppb, P〈0.05）. There was no significant difference in FeNO between group A and group B （P〉0.05）. （3） The levels of PCT and CRP in group A patients with an acute exacerbation of asthma were significantly higher （P〈0.05） than in group B （for PCT： 27.46±9.32 vs. 7.85±3.52 ng/mL; for CRP： 51.25±11.46 vs. 17.11±5.87 mg/L, respectively）. When they had returned to stable clinical state, the levels of PCT and CRP in group A were decreased significantly （P〈0.05）, and those in group B had no significant change （P〉0.05） when compared with the exacerbation group. There were no significant differences in the levels of PCT and CRP between the two groups in non-acute exacerbation state （/9〉0.05）. These results suggest that the increase in FeNO indicates the acute exacerbation of asthma, and the elevation of serum PCT and CRP levels may be associated with bacterial infection.

Correlation of eosinophil counts in induced sputum and fractional concentration of exhaled nitric oxide and lung functions in patients with mild to moderate asthma

Background The airway inflammation could be assessed by some noninvasive approaches. To investigate the value of eosinophil counts in induced sputum and fractional concentration of exhaled nitric oxide （FENO） for the regimen adjustment in patients with asthma, the correlation was analyzed between the two parameters and lung function parameter （forced expiratory volume in one second （FEV1））. Methods Sixty-five outpatients with mild to moderate non-exacerbation asthma from Beijing Chao-Yang Hospital were enrolled as treatment group. Combined medications of inhaled corticosteroids plus long-acting beta-2 agonist were administered for one year. Lung function parameters, eosinophil counts in induced sputum, concentration of exhaled nitric oxide and the Asthma Control Test scores were recorded, at regular intervals in the follow-up period. Twenty-one healthy volunteers were enrolled as control group and underwent examination of eosinophil counts in induced sputum, lung function and concentration of exhaled nitric oxide. Results Sixty-three subjects from treatment group completed follow-up period for one year or longer. Mean FEV1 value of the 63 subjects was （2.75±0.54） L at baseline, （2.97±0.56） L and （3.07±0.52） L at month 3 and month 6, respectively, and maintained as （3.14±0.51） L in the following six months. Mean FENO decreased from （61±25） parts per billion （ppb） at baseline to （32±19） ppb at month 3 （P 〈0.05）, and continued to decrease to （22±12） ppb at month 6, the difference being significant when compared to both baseline and control group （（13±8） ppb）. Mean eosinophil counts decreased to （0.032±0.011） ×106/ml at month 3, which was significantly different from baseline （（0.093±_0.023） xl06/ml） and the control group （（0.005±0.003）×l06/ml （both P 〈0.05）. The eosinophil counts in induced sputum correlated positively with concentration of FENO in the first six months （all P 〈0.05）. The concentration of FENO had a significant negative correlation with FEV1 value （all P 〈0.05） in any time point in the follow-up period. The Asthma Control Test scores were 18±5, 19±7, 23±-2, 24±1 and 24±1 at months 1, 3, 6, 9 and 12, respectively, which were significantly different from the score at baseline （14±3） （P 〈0.05 ）. The most rapid clinical effect was observed at the second month after treatment. Conclusion Eosinophil counts in induced sputum and FENO are sensitive parameters to detect airway inflammation and may be useful in evaluating the efficacy of treatment and adjusting medication regimens.

Characteristics of pulmonary inflammation in combined pulmonary fibrosis and emphysema

Background The condition of concomitant upper lobe emphysema and lower lobe fibrosis as identified by computer tomography is known as combined pulmonary fibrosis and emphysema （CPFE）. CPFE has distinct clinical characteristics compared with emphysema alone （EA） and idiopathic pulmonary fibrosis （IPF） without emphysema. However, the pulmonary inflammation characteristics of CPFE are not well known, and the differences between CPFE and the other two diseases with regards to pulmonary inflammation need to be explored. The pulmonary inflammatory characteristics were investigated in CPFE patients and compared with EA and IPF. Methods Fraction exhaled nitric oxide （Fe,NO） and differential cell counts, the concentrations of monokine induced by interferon gamma （MIG/CXCL9）, interferon-inducible protein 10 （IP-10/CXCL10）, and interferon-inducible T cell alpha chemoattractant （I-TAC/CXCL11） were measured in induced sputum obtained from subjects with CPFE （n=22）, EA （n=22）, IPF （n=14）, and healthy volunteers （HV, n=12）. In addition, immunohistochemistry was used to quantify the expression of nitric oxide synthases in alveolar macrophages in 23 lung tissues from patients and control subjects. Results The CPFE group had higher alveolar NO than subjects in the EA and HV groups （P=0.009, P=-0.001, respectively） but not than the IPF group （P 〉0.05）. Numbers of sputum eosinophils were significantly elevated in CPFE and IPF groups compared with the HV group （P=-0.001, P=-0.008）. In contrast, eosinophil counts in EA group did not differ from those in the HV group. Compared with the EA and HV groups, the CPFE group had a lower concentration of I-TAC/CXCL11 in sputum supernatants （P=0.003, P=0.004）. Immunoreactivity for inducible nitric oxide synthase （iNOS） was higher in the CPFE group than in the EA group （P=-0.018, P=0.006, respectively）. Conclusions The pulmonary inflammation of CPFE group is more similar to IPF group, while the distal airway inflammation is more significant in CPFE and IPF groups than in EA group. Lung eosinophil cell infiltration and high NOS expression in alveolar macrophage might participate in this pathogenesis.

Serum macrophage migration inhibitory factor as a potential biomarker to evaluate therapeutic response in patients with allergic asthma:an exploratory study

Background:Previous studies have shown that macrophage migration inhibitory factor(MIF)is involved in the pathogenesis of asthma.This study aimed to investigate whether serum MIF reflects a therapeutic response in allergic asthma.Methods:We enrolled 30 asthmatic patients with mild-to-moderate exacerbations and 20 healthy controls,analyzing the parameter levels of serum MIF,serum total immunoglobulin E(tIgE),peripheral blood eosinophil percentage(EOS%),and fractional exhaled nitric oxide(FeNO).Lung function indices were used to identify disease severity and therapeutic response.Results:Our study showed that all measured parameters in patients were at higher levels than those of controls.After one week of treatment,most parameter levels decreased significantly except for serum tIgE.Furthermore,we found that serum MIF positively correlated with EOS%as well as FeNO,but negatively correlated with lung function indices.Receiver operator characteristic(ROC)curve analysis indicated that among the parameters,serum MIF exhibited a higher capacity to evaluate therapeutic response.The area under the curve(AUC)of MIF was 0.931,with a sensitivity of 0.967 and a specificity of 0.800.Conclusions:Our results suggested that serum MIF may serve as a potential biomarker for evaluating therapeutic response in allergic asthma with mild-to-moderate exacerbations.