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Park, Lee, Kim, and Hahn: Relationships of bronchodilator response with asthma control and fractional exhaled nitric oxide in children with atopic asthma
Original Article

Allergy, Asthma & Respiratory Disease 2015; 3(1): 40-46.

Published online: 31 January 2015

DOI: https://doi.org/10.4168/aard.2015.3.1.40

Relationships of bronchodilator response with asthma control and fractional exhaled nitric oxide in children with atopic asthma

Joohyun Park1, Youn Kyung Lee1, Heon Kim2, Youn-Soo Hahn1

1Department of Pediatrics, Chungbuk National University College of Medicine, Cheongju, Korea.

2Department of Preventive Medicine, Chungbuk National University College of Medicine, Cheongju, Korea.

Correspondence to: Youn-Soo Hahn. Department of Pediatrics, Chungbuk National University College of Medicine, 410 Sunbong-ro, Heungdeok-gu, Cheongju 361-763, Korea. Tel: +82-43-269-6042, Fax: +82-43-264-6620, yshahn@chungbuk.ac.kr

Received 25 August 2014       Revised 29 October 2014       Accepted 24 November 2014

© 2015 The Korean Academy of Pediatric Allergy and Respiratory Disease; The Korean Academy of Asthma, Allergy and Clinical Immunology

(open-access):

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/).

Abstract

Purpose

Because bronchodilator response (BDR) is variable among asthmatic patients, there are practical limitations in using BDR to assess asthma control. We investigated the relationships of BDR with asthma control status and fractional exhaled nitric oxide (FeNO) in children with atopic asthma.

Methods

One hundred ninety-one patients aged 8 to 16 years with atopic asthma were enrolled. Pulmonary function tests including BDR and FeNO were serially measured 10 times or more over 2 years when subjects were not receiving controller medications. During the last year of follow-up, the loss of asthma control was assessed in all participants.

Results

We identified 114 children (60%) with at least 1 positive BDR (≥12%) over the 2-year observation period. Higher levels of BDRs and higher rates of positive BDRs were associated with lower lung function and lower methacholine PC20 (provocative concentration of methacholine causing a 20% fall in forced expiratory volume in one second). The loss of asthma control occurred in 106 of individuals (93%) who had positive BDRs, as compared to 52 of 77 (68%) with negative BDRs (P<0.001). There was no difference in FeNO levels between individuals with positive and negative BDRs. However, among children with negative BDRs, those developing the loss of asthma control had higher maximal FeNO levels and higher rates of FeNO>21 parts per billion than those who maintained asthma control (all P<0.001).

Conclusion

Positive BDRs are linked to a higher probability of asthma control loss in children with atopic asthma. In addition, high FeNO is associated with asthma control loss in asthmatic children with negative BDRs.

Keywords: Asthma, Child, Lung function, FeNO

Figures and Tables

Fig. 1

Study schedule. BDR, bronchodilator response; FeNO, fractional exhaled nitric oxide; PC20, provocative concentration of methacholine causing a 20% fall in forced expiratory volume in one second.

aard-3-40-g001
Fig. 2

Comparison of number of individuals developing loss of asthma control (A) and number of asthma control loss per year (B) between groups with positive and negative bronchodilator responses (BDRs).

aard-3-40-g002
Table 1

Demographic data of the study population (n=191)

aard-3-40-i001
Variable Value
Age (yr) 10.86 ± 2.96
Sex (female:male) 54:137
Height (m) 1.42 ± 0.16
Weight (kg) 39.85 ± 13.80
Body mass index (kg/m2) 19.15 ± 3.39
Exposure to smoke, n (%) 76 (39.8)
Total serum IgE (IU/mL), geometric mean (95% CI) 431.0 (218.1-849.1)
Methacholine PC20 (mg/mL), geometric mean (95% CI) 1.44 (1.15-1.74)
M-BDR (%) 15.58 ± 9.43
R12BDR (%) 21.72 ± 14.65

Values are presented as mean±standard deviation unless otherwise indicated.

CI, confidence interval; PC20, provocative concentration of methacholine causing a 20% fall in forced expiratory volume in one second (FEV1); BDR, bronchodilator response; M-BDR, maximal value of BDR; R12BDR, rate of BDR higher than 12% increase in FEV1.

Table 2

Association of BDR with other spirometric values

aard-3-40-i002
Variable BDR
r P-value
%FVC 0.05 0.718
%FEV1 -0.19 0.011
FEV1/FVC -0.40 <0.001
%FEF25%-75% -0.36 <0.001
lnPC20 -0.39 <0.001

BDR, bronchodilator response; %FVC, percent predicted functional vital capacity; %FEV1, percent predicted forced expiratory volume in one second; %FEF25%-75%, percent predicted forced expiratory flow 25%-75%; lnPC20, natural log-transformed provocative concentration of methacholine causing a 20% fall in FEV1.

Table 3

Characteristics of individuals with positive and negative BDRs

aard-3-40-i003
Variable BDR+ (n=114) BDR- (n=77) P-value
Age (yr) 10.31±3.00 11.68±2.72 0.562
Sex (female:male) 34:80 25:52 0.700
Height (m) 1.38±0.16 1.47±0.16 0.479
Weight (kg) 39.32±12.72 41.59±14.55 0.341
Body mass index (kg/m2) 18.92±3.31 19.50±3.38 0.242
Exposure to smoke, n (%) 49 (43.0) 27 (35.1) 0.314
Total serum IgE (IU/mL) 457.72±744.91 391.02±741.94 0.385
Methacholine PC20 (mg/mL), geometric mean (95% CI) 1.25 (1.31-1.54) 1.95 (1.55-2.44) 0.007
M-BDR (%) 20.7 8.0 <0.001
ICS use (day/yr) 74±39 78±43 0.839

Values are presented as mean±standard deviation unless otherwise indicated.

BDR, bronchodilator response; PC20, provocative concentration of methacholine causing a 20% fall in forced expiratory volume in one second; CI, confidence interval; M-BDR, maximal value of BDR; ICS, inhaled corticosteroid.

Table 4

Comparison of M-FeNO and R21FeNO between individuals with positive and negative BDRs

aard-3-40-i004
BDR P-value
Positive (n=114) Negative (n=77)
M-FeNO 50.96 (47.01-55.38) 52.06 (46.93-57.87) 0.784
R21FeNO 40.77 (33.97-48.74) 46.83 (37.55-57.31) 0.170

Values are presented as geometric mean (95% confidence interval).

M-FeNO, maximal value of fractional exhaled nitric oxide (FeNO); R21FeNO, rate of FeNO higher than 21 ppb; BDR, bronchodilator response.

Table 5

Comparison of M-FeNO and R21FeNO between individuals with and without LOC among patients with positive and negative BDRs

aard-3-40-i005
BDR+ (n = 114) BDR- (n = 77)
LOC+ (n = 106) LOC- (n = 8) P-value LOC+ (n = 52) LOC- (n = 25) P-value
M-FeNO 57.89 (52.94-62.98) 35.63 (27.75-44.13) < 0.019 65.21 (58.9-72.4) 32.46 (28.7-36.9) < 0.001
R21FeNO 57.25 (51.32-63.21) 26.88 (11.88-43.11) < 0.007 72.91 (64.5-80.1) 18.64 (11.9-28.2) < 0.001

Values are presented as geometric mean (95% confidence interval).

M-FeNO, maximal value of fractional exhaled nitric oxide (FeNO); R21FeNO, rate of FeNO higher than 21 ppb; BDR, bronchodilator response; LOC, loss of asthma control.

Notes

This work was supported by the research grant of Chungbuk National University in 2013.

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