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Clinical & Experimental Allergy

Exhaled nitric oxide predicts persistence of wheezing, exacerbations, and decline in lung function in wheezy infants and toddlers

Authors

  • M. Elliott,

    1. Division of Pulmonary Medicine, Department of Pediatrics, Seattle Children's Hospital, University of Washington, Seattle, WA, USA
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  • S. L. Heltshe,

    1. Division of Pulmonary Medicine, Department of Pediatrics, Seattle Children's Hospital, University of Washington, Seattle, WA, USA
    2. Center for Clinical and Translational Research, Seattle Children's Research Institute, Seattle, WA, USA
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  • D. C. Stamey,

    1. Division of Pulmonary Medicine, Department of Pediatrics, Seattle Children's Hospital, University of Washington, Seattle, WA, USA
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  • E. S. Cochrane,

    1. Division of Pulmonary Medicine, Department of Pediatrics, Seattle Children's Hospital, University of Washington, Seattle, WA, USA
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  • G. J. Redding,

    1. Division of Pulmonary Medicine, Department of Pediatrics, Seattle Children's Hospital, University of Washington, Seattle, WA, USA
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  • J. S. Debley

    Corresponding author
    1. Division of Pulmonary Medicine, Department of Pediatrics, Seattle Children's Hospital, University of Washington, Seattle, WA, USA
    • Correspondence:

      Jason S. Debley, Pulmonary Division (A-5937), Seattle Children's Hospital, 4800 Sand Point Way NE, Seattle 98105, WA, USA.

      E-mail:jason.debley@seattlechildrens.org

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Summary

Background

There are limited data assessing the predictive value of fraction of exhaled nitric oxide (FENO) for persistence of wheezing, exacerbations, or lung function change over time in infants/toddlers with recurrent wheezing.

Objectives

In an ongoing longitudinal cohort of infants and toddlers with recurrent wheezing, we compared predictive values of single-breath FENO (SB-FENO), tidal-breathing mixed expired FENO (tidal-FENO), bronchodilator responsiveness (BDR) and the Castro-Rodriquez Asthma Predictive Index (API) for persistence of wheezing, exacerbations and lung function change through age 3 years.

Methods

Enrolment forced expiratory flows and volumes infant pulmonary function tests (iPFTs) were measured in 44 infants/toddlers using the raised volume rapid thoracoabdominal compression method. SB-FENO was measured at 50 mL/s, and tidal-FENO was measured during awake tidal breathing. Clinical outcomes were assessed at age 3 years in 42 infants. Follow-up iPFTs were completed between ages 2.5–3 years in 32 subjects.

Results

An enrolment SB-FENO concentration ≥ 30 p.p.b. predicted persistence of wheezing at age 3 years with a sensitivity of 77%, a specificity of 94%, and an area under the curve (AUC) of 0.86 (95% CI: 0.74–0.98). The sensitivity, specificity, positive predictive, and negative predictive values of SB-FENO for persistence of wheezing and exacerbations were superior to tidal-FENO, BDR, and the API. SB-FENO ≥ 30 p.p.b. and tidal-FENO ≥ 7 p.p.b. measured at enrolment was associated with a decline in both FEV0.5 and FEF25–75 between enrolment and age 3 years.

Conclusions

In wheezy infants/toddlers, SB-FENO was superior to tidal-FENO, BDR, and the API in predicting future exacerbations and persistence of wheezing at age 3 years. Both SB-FENO and tidal-FENO were associated with lung function decline over time.

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