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Longitudinal Assessment of High Versus Low Levels of Fractional Exhaled Nitric Oxide Among Children with Asthma and Atopy

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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 understand 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 randomly 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 (standard 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.

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Acknowledgments

This study was supported in part by the Johns Hopkins Center for Global Health. Mary Elmasri and Karina Romero were Fogarty International Center Research Fellows during the conduct of this work (R25TW009340). Colin Robinson was a Fogarty International Clinical Research Scholar during the time of this work and was further supported by Tufts University School of Medicine. Lauren Baumann was supported by a pre-doctoral NIH T35 Training Grant (T35AI065385). Nadia Hansel and William Checkley were supported by a R01 grant from the National Institutes of Environmental Health Sciences (R01ES018845). William Checkley was further supported by a Pathway to Independence Award (R00HL096955) from the National Heart, Lung and Blood Institute, National Institutes of Health and by a contract (HHSN268200900033C) with the National Heart, Lung and Blood Institute, National Institutes of Health. Study sponsors played no role in the study design, data collection, data analysis, data interpretation or the decision to submit the article for publication.

Conflicts of interest

The authors have no conflicts of interest to disclose.

Author information

Authors and Affiliations

  1. Division of Pulmonary and Critical Care, School of Medicine, Johns Hopkins University, 1800 Orleans Ave Suite 9121, Baltimore, MD, 21205, USA

    Mary Elmasri, Nadia N. Hansel, Colin L. Robinson, Lauren M. Baumann & William Checkley

  2. Asociacion Benefica PRISMA, Lima, Peru

    Karina M. Romero, Robert H. Gilman & Lilia Cabrera

  3. CRONICAS Center in Chronic Diseases, Universidad Peruana Cayetano Heredia, Lima, Peru

    Karina M. Romero & William Checkley

  4. Program in Global Disease Epidemiology and Control, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA

    Robert H. Gilman & William Checkley

  5. Department of Environmental Health Sciences, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA

    Nadia N. Hansel

  6. Division of Allergy and Clinical Immunology, School of Medicine, Johns Hopkins University, Baltimore, MD, USA

    Robert G. Hamilton

Authors
  1. Mary Elmasri
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  2. Karina M. Romero
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  3. Robert H. Gilman
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  4. Nadia N. Hansel
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  5. Colin L. Robinson
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  6. Lauren M. Baumann
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  7. Lilia Cabrera
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  8. Robert G. Hamilton
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  9. William Checkley
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Consortia

PURA Study Investigators

Corresponding author

Correspondence to William Checkley.

Additional information

Other PURA Study Investigators Include

Juan Combe (A.B. PRISMA, Lima, Peru), Alfonso Gomez (A.B. PRISMA, Lima, Peru), Guillermo Gonzalvez (PAHO Lima, Peru), Lilia Cabrera (A.B. PRISMA, Lima, Peru), Kathleen Barnes (Johns Hopkins University, Baltimore, MD), Robert Wise (Johns Hopkins University, Baltimore, MD), Patrick Breysse (Johns Hopkins University, Baltimore, MD), D’Ann Williams (Johns Hopkins University, Baltimore, MD).

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Elmasri, M., Romero, K.M., Gilman, R.H. et al. Longitudinal Assessment of High Versus Low Levels of Fractional Exhaled Nitric Oxide Among Children with Asthma and Atopy. Lung 192, 305–312 (2014). https://doi.org/10.1007/s00408-013-9551-8

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  • DOI: https://doi.org/10.1007/s00408-013-9551-8

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