Exhaled nitric oxide rather than lung function distinguishes preschool children with probable asthma Longitudinal Assessment of High Versus Low Levels of Fractional Exhaled Nitric Oxide Among Children with Asthma and Atopy Predictive value of fractional nitric oxide in asthma diagnosis-subgroup analyses. The performance of tests of publication bias and other sample size effects in systematic reviews of diagnostic test accuracy was assessed. Corticosteroids decrease exhaled nitric oxide in children with acute asthma. Diagnostic value of exhaled nitric oxide in childhood asthma and allergy.
Background : Respiratory function and airway inflammation can be evaluated in preschool children with special techniques , but their relative power in identifying young children with asthma has not been studied . This study was undertaken to compare the value of exhaled nitric oxide ( FENO ) , baseline lung function , and bronchodilator responsiveness in identifying children with newly detected probable asthma . Methods : Ninety six preschool children ( age 3.8–7.5 years ) with asthmatic symptoms or history and 62 age matched healthy non-atopic controls were studied .  FENO was measured with the st and ard online single exhalation technique , and  baseline lung function and bronchodilator responsiveness were measured using impulse oscillometry ( IOS ) . Results : Children with probable asthma ( n=21 ) , characterised by recent recurrent wheeze , had a significantly higher mean ( SE ) concentration of FENO than controls ( 22.1 ( 3.4 ) ppb v 5.3 ( 0.4 ) ppb ; mean difference 16.8 ppb , 95 % CI 12.0 to 21.5 ) and also had higher baseline respiratory resistance , lower reactance , and larger bronchodilator responses expressed as the change in resistance after inhalation of salbutamol . Children with chronic cough only ( n=46 ) also had significantly raised mean FENO ( 9.2 ( 1.5 ) ppb ; mean difference 3.9 ppb , 95 % CI 0.8 to 7.0 ) but their lung function was not significantly reduced . Children on inhaled steroids due to previously diagnosed asthma ( n=29 ) differed from the controls only in their baseline lung function . The analysis of receiver operating characteristics ( ROC ) showed that FENO provided the best power for discriminating between children with probable asthma and healthy controls , with a sensitivity of 86 % and specificity of 92 % at the cut off level of 1.5 SD above predicted . Conclusions : FENO is superior to baseline respiratory function and bronchodilator responsiveness in identifying preschool children with probable asthma . The results emphasise the presence of airway inflammation in the early stages of asthma , even in young children Abstract Purpose Fractional exhaled nitric oxide ( FeNO ) has emerged as an important biomarker in asthma . Increasing evidence points to atopy as a confounding factor in the interpretation of elevated FeNO . We conducted a longitudinal study to underst and the clinical significance of FeNO as an inflammatory biomarker . Methods We identified 19 children aged 13–15 years at baseline with a significant elevation in FeNO ≥ 80 parts per billion ( ppb ) and r and omly selected a group of children of similar age with a moderate elevation ( 40–79 ppb ) and normal-to-low FeNO ( < 40 ppb ) . Between November 2010 and July 2011 , three additional study visits were conducted . Results Ninety-three children participated in the study . There were 16 , 24 , and 53 participants in the high , mid , and low FeNO groups . During 1.5 years of follow-up , mean FeNO levels were 82.6 ppb ( st and ard deviation [ SD ] = 65.9 ) for atopic asthmatics , 50.6 ppb ( SD = 42.6 ) for nonasthmatic atopics , 17.0 ppb ( SD = 10.8 ) for nonatopic asthmatics , and 17.8 ppb ( SD = 13.9 ) for nonatopic nonasthmatics ( p < 0.001 ) . FeNO levels remained stable : 63 % of the high FeNO group had a FeNO ≥ 80 across all 4 measurements and 87 % of the normal-to-low FeNO group had a FeNO of < 40 across all 4 measurements . The high FeNO group also was found to have an elevation in IL-5 ( p = 0.04 ) , IL-6 ( p = 0.003 ) , IL-10 ( p = 0.002 ) , and total serum IgE ( p < 0.001 ) , after adjustment by age , sex , height , body mass index , and atopy and asthma status . Conclusions An elevation of FeNO appears to indicate an atopic phenotype regardless of an asthma diagnosis , clinical symptoms , or corticosteroid use . An elevation of FeNO also is associated with a systemic elevation in inflammatory cytokines BACKGROUND There are no studies investigating the benefit of using FeNO measurements in correlation with sensitization to perennial and seasonal allergens in children with asthma . OBJECTIVE To define the group of children with respiratory symptoms in whose FeNO measurement has predictive value for asthma . We assessed the effect of age , allergy profile , atopy , lung function and the presence of allergic rhinitis on interpretation of FeNO levels for clinical applications . METHODS It was a retrospective , cross-sectional study . We evaluated data from medical documentation of 1767 children with symptoms of allergic diseases such as asthma and /or allergic rhinitis . We included in the analyses subjects who had the following tests done during diagnostic procedures ( single measurement ) : FeNO , spirometry , specific IgE results . All subjects had undergone a minimum 3-years prospect i ve clinical observation after the first FeNO measurement until the later assignment ( or not ) of an asthma/allergic rhinitis diagnosis . RESULTS We included 1767 children into the analysis ; asthma diagnosis was confirm in 1054 ( 59.6 % ) children . We showed that only atopy ( OR : 1.9 ; 95%CI : 1.5 - 2.4 ) and presence of allergic rhinitis ( OR : 1.6 ; 95%CI : 1.4 - 1.9 ) were independently associated with increased FeNO level . Only among patients with atopy and allergic rhinitis FeNO level ( above 23 ppb ) was associated with asthma diagnosis . Sensitivity , specificity , positive predictive value and negative predictive value of FeNO > 23 ppb for asthma diagnosis were as follows : 0.9(95%CI : 0.68 - 0.98 ) , 0.52(95%CI : 0.42 - 0.61 ) , 0.25(95%CI : 0.16 - 0.37 ) , 0.97(95%CI : 0.88 - 0.99 ) . CONCLUSION We showed that in children with atopy and with allergic rhinitis a negative predictive value for asthma diagnosis was very high with the optimal cut-off point of FeNO 23 ppb . Therefore we showed the utility of FeNO measurements to exclude asthma in the subgroup of patients with atopy and allergic rhinitis BACKGROUND AND OBJECTIVE Publication bias and other sample size effects are issues for meta-analyses of test accuracy , as for r and omized trials . We investigate limitations of st and ard funnel plots and tests when applied to meta-analyses of test accuracy and look for improved methods . METHODS Type I and type II error rates for existing and alternative tests of sample size effects were estimated and compared in simulated meta-analyses of test accuracy . RESULTS Type I error rates for the Begg , Egger , and Macaskill tests are inflated for typical diagnostic odds ratios ( DOR ) , when disease prevalence differs from 50 % and when thresholds favor sensitivity over specificity or vice versa . Regression and correlation tests based on functions of effective sample size are valid , if occasionally conservative , tests for sample size effects . Empirical evidence suggests that they have adequate power to be useful tests . When DORs are heterogeneous , however , all tests of funnel plot asymmetry have low power . CONCLUSION Existing tests that use st and ard errors of odds ratios are likely to be seriously misleading if applied to meta-analyses of test accuracy . The effective sample size funnel plot and associated regression test of asymmetry should be used to detect publication bias and other sample size related effects OBJECTIVES Nitric oxide ( NO ) produced in human airways seems to have both homeostatic and proinflammatory actions in the respiratory system . NO production has been shown to be higher in the exhaled air of asthmatic adults than in normal subjects . The aim of this study was to evaluate exhaled NO production during asthma exacerbation in children and the effect of a rescue course of oral steroid therapy . STUDY DESIGN We measured NO in the exhaled air of 16 children ( 8 girls and 8 boys , aged 6 to 13 years ) with an acute asthmatic episode before and after 5 days of therapy with prednisone , and in 16 healthy children . To measure NO , children inhaled NO-free air and , breathing at tidal volume , exhaled in a circuit from which a chemiluminescence analyzer sample d continuously . To assess the effect of acute changes in bronchial caliber on exhaled NO levels , we measured NO before and after a positive bronchodilation test result with albuterol in seven children with asthma whose disease was stable . RESULTS In the group with acute asthma ( forced expiratory volume in 1 second 62 % + /- 4.4 % predicted , mean + /- SEM ) , NO levels were significantly higher ( 31.3 + /- 4.2 parts per billion [ ppb ] ) than in healthy children ( 5.4 + /- 0.4 ppb , p < 0.001 ) . Administration of prednisone ( 1 mg/kg per day orally ) for 5 days result ed in a mean decrease of 46 % + /- 4 % in exhaled NO concentrations ( 16.5 + /- 2.3 ppb , p < 0.001 ) compared with baseline , accompanied by a significant improvement in lung function ( forced expiratory volume in 1 second 90.7 % + /- 4.3 % predicted ) . However , in patients with asthma  exhaled NO levels remained significantly higher than in control children ( p < 0.001 ) after steroid treatment . When exhaled NO was measured before and after a positive result after bronchodilator reversibility testing , we found no difference in exhaled NO levels ( 24 + /- 3.8 ppb vs 23.8 + /- 3 ppb ; difference not significant ) . This demonstrates that inhaled albuterol and acute changes in bronchial caliber do not affect exhaled NO measurement . CONCLUSIONS These data show that children with asthma exacerbation have high levels of exhaled NO that rapidly decrease with oral steroid therapy . We suggest that measurement of exhaled NO may represent a noninvasive method of monitoring airway inflammation in children with asthma Fractional exhaled nitric oxide ( FE(NO ) ) has been proposed as a diagnostic test of asthma . We aim ed to investigate in a population based birth cohort of children the usefulness of FE(NO ) as a diagnostic tool . The 10-yr follow up of the Environment and Childhood Asthma Study in Oslo included 616 children representative of the prospect i ve birth cohort . Both  FE(NO ) ( single breath technique ) and skin prick test ( SPT )  were measured in 331 , limited at the time by equipment availability . Structural parental interview , spirometry , methacholine challenge and exercise test were performed .  FE(NO )  was significantly elevated in children with current asthma ( geometric mean 9.6 ( 95 % confidence interval ( CI ) ( 6.9 , 13.4 ) p.p.b . ) compared with healthy children ( 5.8 ( 5.4 , 6.3 ) p.p.b . ; p < 0.001 ) .  FE(NO )  was highest among children with current allergic asthma ( asthma and positive SPT ) ( 14.0 ( 8.9 , 22.1 ) p.p.b . ) , whereas children with non-allergic asthma ( 6.1 ( 4.0 , 9.2 ) p.p.b . ) had comparable FE(NO ) levels to healthy children ( p = 0.99 ) . Allergic sensitization was most closely associated with FE(NO ) . A FE(NO ) cut-off value of 20.4 p.p.b . had a high specificity ( 0.97 ) , but a low sensitivity ( 0.41 ) and a Positive Likelihood Ratio of 16.1 for current allergic asthma . In the present childhood population -based study , high FE(NO ) levels were closely associated with current allergic asthma and not with current asthma without allergic sensitization . Estimating the individual predictive probability of having asthma by use of FE(NO , ) improves the diagnostic utility of the test
The gold st and ard for diagnosing asthma in children is based on clinical history of respiratory symptoms , physical examination , and respiratory function testing .
Recent advances indicate that a non-invasive measure of airway inflammation , fractional exhaled nitric oxide ( FeNO ) , provides objective data for use in asthma diagnosis .
However , the diagnostic performance of FeNO in children with asthma has not been clearly defined .
This systematic review and meta- analysis aim ed to evaluate the diagnostic accuracy of FeNO in the clinical determination of asthma in children .