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Published on: December 17, 2017
Exhaled nitric oxide is only an asthma-relevant biomarker among children with allergic sensitization
Rikke Bjersand Sunde1,2, Jonathan Thorsen1, Frederikke Skov1,2
1COPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark.
Insights
Fraction of exhaled nitric oxide (FeNO) is elevated in children with asthma. FeNO is a valid asthma biomarker only in children with allergic sensitization, impacting clinical guidelines.
Area of Science:
- Pediatric Allergy and Immunology
- Respiratory Medicine
- Biomarker Research
Background:
- Fraction of exhaled nitric oxide (FeNO) is a diagnostic tool for childhood asthma.
- The impact of allergic sensitization on FeNO levels in children remains unclear.
- This study investigates the interplay between asthma, allergic sensitization, and FeNO in childhood.
Purpose of the Study:
- To determine how asthma and allergic sensitization influence FeNO levels throughout childhood.
- To assess the validity of FeNO as an asthma biomarker in relation to allergic sensitization.
- To provide insights for clinical guidelines on FeNO usage in pediatric asthma management.
Main Methods:
- Analysis of FeNO levels from ages 5-18 years in the COPSAC₂₀₀₀ birth cohort (n=411).
- Repeated measurement mixed models adjusted for confounders like gestational age, sex, infections, and environmental exposures.
- Replication of findings in the COPSAC₂₀₁₀ birth cohort (n=700).
Main Results:
- Both asthma and aeroallergen sensitization were independently associated with higher FeNO levels.
- Asthma increased FeNO in sensitized children but decreased it in non-sensitized children (p-interaction <.0001).
- Asthma-associated traits (eosinophils, IgE, bronchodilator response, bronchial hyperreactivity) correlated with FeNO only in sensitized children.
Conclusions:
- FeNO levels in children are influenced by asthma and allergic sensitization.
- FeNO is a reliable asthma biomarker in children only when concurrent aeroallergen sensitization is present.
- Findings necessitate re-evaluation of FeNO's clinical utility in pediatric asthma guidelines.
Background:
Fraction of exhaled nitric oxide (FeNO) is used for diagnosing and monitoring asthma in children, but the influence of allergic sensitization is still poorly understood. Here, we investigate how asthma and allergic sensitization influence FeNO levels during childhood.
Methods:
We investigated the associations between asthma, aeroallergen sensitization, and FeNO measured from age 5-18 years in the COPSAC2000 birth cohort of 411 children using repeated measurement mixed models adjusted for gestational age, sex, concurrent airway infection, inhaled corticosteroids, and tobacco exposure. Replication was sought in the similarly designed COPSAC2010 cohort of 700 children.
Results:
In the COPSAC2000 cohort, 133 had asthma between age 5 and 18 years, and in the COPSAC2010 cohort, 112 had asthma between age 5 and 10 years. In the COPSAC2000 cohort, asthma and aeroallergen sensitization were both associated with higher FeNO from age 5 to 18 years: adjusted geometric mean ratio (aGMR), 1.22 (1.08-1.35), p < .01, and 1.41 (1.21-1.65), p < 0.001, respectively. However, asthma was associated with increased FeNO among children with aeroallergen sensitization: 1.44 (1.23-1.69), p < .0001, whereas asthma was associated with decreased FeNO among nonsensitized children: 0.80 (0.65-0.99), p = .05 (p-interaction<.0001 for asthma x sensitization). Replication in the COPSAC2010 cohort showed similar results (p-interaction <.01). Further, blood eosinophil count, total-IgE, bronchodilator response, and bronchial hyperreactivity were all associated with increased FeNO among children sensitized to aeroallergens, but not among nonsensitized children.
Conclusion:
Fraction of exhaled nitric oxide is elevated through childhood in children with asthma and is correlated with asthma-associated traits depending on the presence of aeroallergen sensitization. These findings indicate that FeNO is only a valid asthma biomarker in children with concurrent aeroallergen sensitization, which is important for guideline recommendations on the clinical use of FeNO.
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