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Original Research: Asthma |

Fraction of Exhaled Nitric Oxide and Bronchial Responsiveness Are Associated and Continuous Traits in Young Children Independent of AsthmaExhaled Nitric Oxide and Bronchial Responsiveness

Ann-Marie Malby Schoos, MD; Bo Lund Krogsgaard Chawes, MD, PhD; Klaus Bønnelykke, MD, PhD; Hans Bisgaard, MD, DMSc
Author and Funding Information

From the Copenhagen Prospective Studies on Asthma in Childhood, Faculty of Health Sciences, University of Copenhagen, and Copenhagen University Hospital Gentofte, Copenhagen, Denmark.

Correspondence to: Hans Bisgaard, MD, DMSc, Copenhagen Prospective Studies on Asthma in Childhood, Danish Pediatric Asthma Center, Copenhagen University Hospital, Ledreborg Alle 34, 2820 Gentofte, Copenhagen, Denmark; e-mail: bisgaard@copsac.com


Drs Malby Schoos and Chawes contributed equally to this article.

Funding/Support: The Copenhagen Prospective Studies on Asthma in Childhood (COPSAC) is funded by private and public research funds, which are listed at www.copsac.com. The Lundbeck Foundation, Pharmacy Foundation of 1991, Augustinus Foundation, Danish Medical Research Council, and Danish Pediatric Asthma Centre provided core support for COPSAC.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.


Chest. 2012;142(6):1562-1568. doi:10.1378/chest.12-0658
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Background:  Elevated fraction of exhaled nitric oxide (Feno) and bronchial hyperresponsiveness are used as surrogate markers of asthma. These traits may be continuous in the population. The objective of this study was to investigate whether Feno and bronchial responsiveness are associated in both children with and children without a history of asthma symptoms.

Methods:  One hundred ninety-six 6-year-old children with no asthma symptoms, intermittent asthma symptoms, and persistent asthma were randomly included from the Copenhagen Prospective Study on Asthma in Childhood prospective clinical birth cohort of mothers with asthma. Bronchial responsiveness was assessed as the relative change in specific airway resistance after cold dry air hyperventilation. Feno measurements were performed prior to the hyperventilation test. The association between Feno and bronchial responsiveness was assessed by generalized linear models.

Results:  Bronchial responsiveness and Feno exhibited a significant and linear association in the population. A doubling of Feno corresponded to an 8.4% (95% CI, 3.7%-13.1%; P = .0006) increase in airway resistance after challenge testing and remained significant after adjustment for sex, allergic rhinitis, current asthma, inhaled corticosteroid treatment, and upper respiratory tract infections prior to testing. Stratified analyses showed similar associations in children with and without asthma.

Conclusions:  Feno and bronchial responsiveness are associated and continuous traits in young children regardless of asthma symptoms, suggesting a continuous subclinical to clinical process underlying asthma. The findings also suggest caution against the use of these surrogate markers for a dichotomized approach to asthma diagnosis.

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