TY - JOUR

T1 - Exhaled nitric oxide is only an asthma-relevant biomarker among children with allergic sensitization

AU - Sunde, Rikke Bjersand

AU - Thorsen, Jonathan

AU - Skov, Frederikke

AU - Hesselberg, Laura

AU - Kyvsgaard, Julie

AU - Følsgaard, Nilofar V.

AU - Schoos, Ann Marie Malby

AU - Stokholm, Jakob

AU - Bønnelykke, Klaus

AU - Chawes, Bo

N1 - Publisher Copyright: © 2023 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

PY - 2023

Y1 - 2023

N2 - 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.

AB - 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.

KW - asthma

KW - blood eosinophil count

KW - FeNO

KW - sensitization

KW - total IgE

U2 - 10.1111/pai.14044

DO - 10.1111/pai.14044

M3 - Journal article

C2 - 38010005

AN - SCOPUS:85176000374

VL - 34

JO - Pediatric Allergy and Immunology, Supplement

JF - Pediatric Allergy and Immunology, Supplement

SN - 0906-5784

IS - 11

M1 - e14044

ER -