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 - © 2023 The Authors. Pediatric Allergy and Immunology published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.
PY - 2023/11
Y1 - 2023/11
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 - Humans
KW - Child
KW - Child, Preschool
KW - Adolescent
KW - Nitric Oxide
KW - Immunoglobulin E
KW - Asthma/diagnosis
KW - Allergens
KW - Exhalation
KW - Biomarkers
KW - Breath Tests
UR - http://www.scopus.com/inward/record.url?scp=85176000374&partnerID=8YFLogxK
U2 - 10.1111/pai.14044
DO - 10.1111/pai.14044
M3 - Journal article
C2 - 38010005
SN - 0905-6157
VL - 34
SP - e14044
JO - Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology
JF - Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology
IS - 11
M1 - e14044
ER -