Chest
Volume 145, Issue 3, March 2014, Pages 492-499
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Original Research: Asthma
Abnormal Small Airways Function in Children With Mild Asthma

https://doi.org/10.1378/chest.13-0784Get rights and content

Background

Small airways disease is a hallmark in adults with persistent asthma, but little is known about small airways function in children with mild asthma and normal spirometry. We assessed ventilation heterogeneity, a marker of small airways function, with an easy tidal breath single-breath washout (SBW) technique in school-aged children with mild asthma and normal FEV1 and healthy age-matched control subjects.

Methods

The primary outcome was the double-tracer gas phase III slope (SDTG), an index of ventilation heterogeneity in acinar airways derived from the tidal double-tracer gas SBW test. The second outcome was the nitrogen phase III slope (SN2), an index of global ventilation heterogeneity derived from the tidal nitrogen SBW test using pure oxygen. Triplicate SBW and spirometry tests were performed in healthy children (n = 35) and children with asthma (n = 31) at baseline and in children with asthma after bronchodilation.

Results

Acinar (SDTG) but not global (SN2) ventilation heterogeneity was significantly increased in asthma despite normal FEV1. Of the 31 children with asthma, abnormal results were found for SDTG (≤ −2 z scores) in 11; forced expiratory flow, midexpiratory phase (FEF25%-75%) in three; and FEV1 in zero. After bronchodilation, SDTG, SN2, FEF25%-75%, and FEV1 significantly changed (mean [95% CI] change from baseline, 36% [15%-56%], 38% [18%-58%], 17% [9-25%], and 6% [3%-9%], respectively).

Conclusions

Abnormal acinar ventilation heterogeneity in one-third of the children suggests that small airways disease may be present despite rare and mild asthma symptoms and normal spirometry. The easy tidal SBW technique has considerable potential as a clinical and research outcome in children with asthma.

Section snippets

Study Population

We enrolled 70 children aged 6 to 16 years from an asthma outpatient clinic and a healthy volunteer database at the Children's Hospital Bern. Children with asthma were eligible if they had a history of controlled mild asthma (daytime symptoms ≤ 2 d/wk), normal FEV1 ± 1.96 z scores, a prescription for low to moderate inhaled corticosteroid doses (≤ 200 μg/d fluticasone or equivalent), and no history of increased use of asthma medication during the previous 6 months.25 Healthy children had no

Results

Sixty-six children (31 with asthma) were studied, and 561 tidal SBW tests were achieved. Twenty-one children with asthma (67%) were atopic, and 22 (71%) received inhaled corticosteroids in the previous month. Healthy control subjects and children with asthma were comparable regarding age, height, weight, and sex (Table 1).

Children with mild asthma had significantly increased acinar ventilation heterogeneity (Figs 1–3, Table 2). SDTG was abnormal (≤ −2 z scores) in 11 children with asthma (36%)

Discussion

Ventilation heterogeneity is increased in children with mild asthma despite rare symptoms and normal FEV1. More than one-third of children with asthma had abnormal SDTG findings, suggesting impaired small airways function in the acinar lung region. Measures of global ventilation heterogeneity (SN2) and airways obstruction (FEF25%-75%) are normal in the majority of children with mild asthma. sRaw is elevated on average but is only weakly associated with ventilation heterogeneity. Administration

Acknowledgments

Author contributions: Dr Latzin had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Dr Singer: contributed to the study concept and design; data acquisition, analysis, and interpretation; and drafting, critical revision for important intellectual content, and final approval of the manuscript.

Dr Abbas: contributed to the study concept and design; data acquisition, analysis, and interpretation; and drafting,

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    Drs Singer and Abbas contributed equally to this work.

    Funding/Support: This work was funded by the Federal Department of Economic Affairs Switzerland, Commission for Technology and Innovation, Innovation Promotion Agency [unrestricted educational grant 14435.1 PFLS-LS] and the Julia Bangerter-Rhyner Foundation.

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

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