Biomarkers related to respiratory symptoms and lung function in adults with asthma
Lucia CalcianoLaura PortasAngelo Guido CorsicoMario OlivieriPaolo DeganMarcello FerrariAlessandro G. FoisAnna Maria Fratta PasiniAndrea PasiniMaria Elisabetta ZanolinRoberto de MarcoSimone Accordini
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Abstract:
There is a need for easily measurable biomarkers that are able to identify different levels of asthma severity.To assess the association between peripheral blood cell counts, fractional nitric oxide in exhaled air (FeNO), urinary biomarkers of oxidative stress (8-hydroxy-2'-deoxyguanosine and 8-isoprostane), and asthma severity in adult patients from the general population.In the Gene Environment Interactions in Respiratory Diseases study, 287 subjects with asthma (aged 20-64) were identified from the general population in Verona (Italy) (2008-2010). Self-reported asthma attacks, asthma-like symptoms and the use of hospital services in the past year were synthesized in a score of respiratory symptoms (SRS). The association of biomarkers with SRS and lung function measures (pre-bronchodilator FEV1% predicted and FEV1/FVC) was assessed using quasi-Poisson and Gaussian regression models, respectively.Eosinophils (ratio of expected scores: RES[95%CI] = 1.19[1.09,1.30]), basophils (RES[95%CI] = 1.24[1.10,1.40]), lymphocytes (RES[95%CI] = 1.27[1.12,1.45]) and FeNO (RES[95%CI] = 1.18[1.02,1.37]) were positively associated with SRS. However, only eosinophils (RES[95%CI] = 1.15[1.02,1.30]) and lymphocytes (RES[95%CI] = 1.25[1.06,1.47]) showed an independent association. Furthermore, eosinophils (change in the expected outcome for 1-SD increase: CEO[95%CI] = -1.18[-2.09, -0.27]%), basophils (CEO[95%CI] = -1.24[-2.16, -0.33]%) and lymphocytes (CEO[95%CI] = -1.07[-1.99, -0.14]%) were individually, but not independently, associated with FEV1/FVC. Finally, neutrophils were negatively associated with FEV1% predicted (CEO[95%CI] = -2.22[-4.00, -0.44]%).We identified a pattern of association between a set of biomarkers and asthma endotypes in adult patients from the general population, which could improve understanding of the heterogeneity and severity of the disease and could be useful in defining targeted therapeutic approaches.Keywords:
Bronchial hyperresponsiveness
Summary Background Previous studies on association between level of asthma control, markers of airway inflammation and the degree of bronchial hyperresponsiveness (BHR) have yielded conflicting results. Our aim was to determine the presence and severity of BHR and the concordance between BHR, asthma control, and fractional exhaled nitric oxide (FeNO) in children with asthma on therapy. Methods In this cross‐sectional observational study, children (aged 6–18 years) with asthma on British Thoracic Society (BTS) treatment steps 2 or 3, underwent comprehensive assessment of their asthma control (clinical assessment, spirometry, asthma control test [ACT], Pediatric Asthma Quality of Life Questionnaire [PAQLQ]), measurement of FeNO and BHR (using mannitol dry powder bronchial challenge test [MCT], Aridol™, Pharmaxis, Australia). Results Fifty‐seven children (63% male) were studied. Twenty‐seven children were on BTS treatment step 2 and 30 were on step 3. Overall, 25 out of 57 (43.8%) children had positive MCT. Of note, 9 out of 27 (33.3%) children with clinically controlled asthma had positive MCT. Analyses of pair‐wise agreement between MCT (positive or negative), FeNO (>25 or ≤25 ppb) and clinical assessment of asthma control (controlled or partially controlled/uncontrolled) showed poor agreement between these measures. Conclusions A substantial proportion of children with asthma have persistent BHR despite good clinical control. The concordance between clinical assessment of asthma control, BHR and FeNO was observed to be poor. Our findings raise concerns in the context of emerging evidence for the role of bronchoconstriction in inducing epithelial stress that may drive airway remodeling in asthma. Pediatr Pulmonol. 2016;51:1004–1009. © 2016 Wiley Periodicals, Inc.
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Recent studies suggest that there is a relationship between different measures of airway inflammation in asthmatic patients. Aim and Methods: We studied the relationship between exhaled nitric oxide (eNO) and the level of bronchial responsiveness in 59 adult patients (15 M: 44 F) with a diagnosis of bronchial asthma. eNO was measured prior to bronchial hyperresponsiveness (BHR) testing; in 37 subjects at the same day, and in 22 subjects on average 13 days before the BHR testing. BHR was assessed with a standardized methacholine challenge test (MCh). Results: In the total group of asthmatics, there was no significant correlation between eNO and log(PC20). However, in the subgroup of asthmatics (n= 37) on which eNO measurement and BHR testing took place at the same day, a weak (r2= 0.138) but significant correlation (p
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The relationship between gastroesophageal reflux (GER) and asthma has been widely studied in the last years. GER may interfere with airway reactivity and aggravate or even induce asthma.To assess the prevalence of bronchial hyperresponsiveness (BHR) in patients with GER disease with a view to judging the potential influence of GER on BHR.30 patients with GER disease and no clinical evidence of asthma and 30 normal subjects underwent a methacholine bronchial challenge. The methacholine concentration that caused a 20% fall in the FEV(1) (PC20) was used to assess bronchial responsiveness.In the GER group 11 subjects of the 30 studied showed a PC20 methacholine equal to or less than 8 mg/ml while in the control group only 2 subjects had a PC20 methacholine equal to or less than 8 mg/ml (p < 0.01; ANOVA test).Subjects with GER had a greater increase in airway reactivity when inhaling methacholine compared to disease-free normal subjects.
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Objective
To evaluate the clinical value of fractional exhaled nitric oxide (FeNO) level in asthmatic children to predict bronchial hyperresponsiveness by analyzing the correlation between fraction of exhaled nitric oxide and bronchial provocation test.
Methods
One hundred and fourteen asthma outpatients of Shengjing Hospital were enrolled, FeNO levels, spirometry and bronchial provocation test were measured.
Results
In the bronchial provocation test, there were 33 positive and 81 negative cases.The positive group had a significantly higher FeNO levels than the negative ones(19.0×10-9 vs.16.0×10-9, P=0.000). By the ROC curve, the best FeNO cut-off value to predict bronchial hyperresponsiveness was 38.5×10-9 with high specificity(92.6%) but relatively low sensitivity(36.4%). There was no relationship between methacholine provocative dose causing a 20% fall in FEV1(PD20-FEV1) and the level of FeNO.
Conclusion
FeNO level has important predicting value for bronchial hyperreactivity in children with asthma.The level of FeNO >38.5×10-9 has high predictive value in asthmatic children with bronchial hyperreactivity.
Key words:
Exhaled nitric oxide; Methacholine bronchial provocation test; Asthma; Children
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Introduction: Questionnaires used to assess control of asthma are simple and pratical instruments to use in clinical practice, however its relation with airway inflammation remains unclear.
Objective: To evaluate the relation between asthma control, spirometry results and measurement of exhaled nitric oxide (FeNO) in patients with asthma and bronchial hyperresponsiveness to methacholine.
Methods: Cross-sectional study of patients with suspicion of asthma that, in a 1 year period, went to a pulmonary function test laboratory perform methacholine challenge. Selection of patients with positive methacholine challenge and application of the questionnaires CARAT (Control of Allergic Rhinitis and Asthma Test) and ACT (Asthma Control Test), measurement of FeNO and spirometric parameters.
Results: Of the 123 patients who underwent methacholine challenge, 41 (33,3%) were positive. Of these, 68,3% were female, with a mean age of 31,5 years, 73,2% non smokers, 53,7% with atopy, 63,4% with rhinitis, 31,7% in regular treatment with inhaled corticosteroids. The average score of CARAT was 19,3 and ACT 20,5. The average value of FeNO was 43,9 ppb. There was no significant association between scores of total CARAT and ACT with FeNO value or FEV1. The score between total CARAT and ACT had a significant relation (p <0,001, r=0,789). Patients with atopy had higher mean values of FeNO (56,9 vs 26,4, p=0,023).
Conclusion: In this sample, there was no significant association between asthma control and FeNO in patients with bronchial hyperresponsiveness to methacholine. There was good relation between the two questionnaires. The presence of atopy was associated with higher FeNO values.
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Reduced attention span and motor skills in children limit the practicability of bronchial provocation tests. To assess exhaled nitric oxide (FeNO) as a surrogate for bronchial hyperresponsiveness (BHR) in children with possible reactive airway disease, FeNO was measured using the single-breath method in 169 successive outpatients 11 ± 5 years of age before lung function testing and subsequent bronchial provocation by exercise (n = 165) and methacholine (n = 134). Baseline forced expiratory volume in 1 second (FEV1) less than 80% of predicted and/or BHR were seen in 59%. FeNO correlated weakly with PD20 to methacholine (r = −0.24, p < 0.05), but not with the change in FEV1 due to exercise-induced bronchoconstriction (EIB) (r = 0.1, p > 0.05). The negative predictive value of FeNO less than 10 ppb for EIB was 94%, but overall accuracy for predicting BHR was low. Measurement of FeNO is not a substitute for bronchial provocation in children.
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