Hyunwook Lim; Eunji Kim; Chang Hoon Lim; Sang Hee Park; Ji Tae Choung; Young Yoo

doi:10.4168/aard.2016.4.1.14

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Lim, Kim, Lim, Park, Choung, and Yoo: Relationships between fractional exhaled nitric oxide levels and FEF25%–75% in children with asthma

Original Article

Allergy, Asthma & Respiratory Disease 2016; 4(1): 14-21.

Published online: 29 January 2016

DOI: https://doi.org/10.4168/aard.2016.4.1.14

Relationships between fractional exhaled nitric oxide levels and FEF_25%–75% in children with asthma

Hyunwook Lim¹, Eunji Kim¹, Chang Hoon Lim¹, Sang Hee Park¹, Ji Tae Choung^1,², Young Yoo^1,^2,³

¹Department of Pediatrics, Korea University College of Medicine, Seoul, Korea.

²Environmental Health Center, Korea University Anam Hospital, Seoul, Korea.

³Allergy Immunology Center, Korea University, Seoul, Korea.

Correspondence to: Young Yoo. Department of Pediatrics, Korea University Anam Hospital, 73 Inchon-ro, Seongbuk-gu, Seoul 02841, Korea. Tel: +82-2-920-5090, Fax: +82-2-922-7476, yoolina@korea.ac.kr

Received 22 June 2015 Revised 24 August 2015 Accepted 2 September 2015

(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/4.0/).

Abstract

Purpose

Fractional exhaled nitric oxide (FeNO) is considered an indirect marker of airway inflammation, and forced expiratory flow between 25% and 75% of vital capacity (FEF_25%–75%) is widely used as a sensitive indicator of small airway obstruction in asthma. The aim of this study was to investigate relationships between FeNO and FEF_25%–75% in children with asthma.

Methods

A total of 118 children with asthma underwent spirometry and measurement of eosinophil markers. FeNO levels were measured, and skin prick tests to 13 common allergens were done. Study subjects were divided into 2 groups according to FEF_25%–75% values (group 1, normal FEF_25%–75%≥65%pred, n=90; group 2, impaired FEF_25%–75%<65%pred, n=28).

Results

The mean (±standard deviation, SD) age was not significantly different between groups 1 and 2 (10.3±2.8 years vs. 11.1±3.4 years), and the sex ratio was also not significantly different between 2 groups. The geometric mean (range of 1 SD) concentration of FeNO was significantly higher in group 2 than in group 1 (25.8 ppb [14.2–46.9 ppb] vs. 37.2 ppb [24.2–57.2 ppb], P=0.008). A significant inverse correlation between FeNO and FEF_25%–75% was observed in group 2 (r=–0.493, P=0.038), but not in group 1 (r=–0.037, P=0.749) after adjustment for confounders, such as atopy, age, sex, weight, and height.

Conclusion

FeNO levels were higher in group of asthmatic children with impaired FEF_25%–75% level. FeNO levels were inversely correlated with FEF_{_25%–75%}only in impaired small-airway obstruction group after adjustment for atopy. These results suggest that small-airway obstruction may relate more closely to airway inflammation in asthmatic children with impaired small-airway function.

Keywords: Asthma, Child, Spirometry, FeNO

Figures and Tables

Fig. 1

FeNO values do not correlate with FEV₁ %pred (r=–0.144, P=0.154; A), FVC %pred (r=–0.049, P=0.627; B) and FEV₁/FVC (r=–0.195, P=0.053; C), but show significantly inverse correlation with FEF_25%–75% %pred (r=–0.211, P=0.035; D) in total asthmatic children. FeNO, fractional exhaled nitric oxide; FEV₁, forced expiratory volume in 1 second; FVC, forced vital capacity; FEF_25%–75%, forced expiratory flow between 25% and 75% of vital capacity.

Fig. 2

FeNO values show significant correlation with neither FEV₁ %pred (r=–0.018, P=0.878; A), FVC %pred (r=–0.072, P=0.534; B), FEV₁/FVC (r=–0.104, P=0.367; C) nor FEF_25%–75% %pred (r=–0.037, P=0.749; D) in children with group 1 (normal FEF_25%–75%, ≥65%pred). FeNO, fractional exhaled nitric oxide; FEV₁, forced expiratory volume in 1 second; FVC, forced vital capacity; FEF_25%–75%, forced expiratory flow between 25% and 75% of vital capacity.

Fig. 3

FeNO values do not correlate with inversely correlate with with FEV₁ %pred (r=–0.066, P=0.795; A) or FVC %pred (r=0.179, P=0.477; B), but show significant FEV₁/FVC (r=–0.566, P=0.014; C), and FEF_25%–75% %pred (r=–0.493, P=0.038; D) in children with group 2 (impaired FEF_25%–75%, <65%pred). FeNO, fractional exhaled nitric oxide; FEV₁, forced expiratory volume in 1 second; FVC, forced vital capacity; FEF_25%–75%, forced expiratory flow between 25% and 75% of vital capacity.

Table 1

Clinical characteristics in children with asthma

Characteristic	Group 1 (n = 90)	Group 2 (n = 28)	Total (n = 118)	P-value
Age (yr)	10.3 ± 2.8	11.1 ± 3.4	10.5 ± 2.9	0.229
Boys	58 (64.4)	19 (67.9)	77 (65.3)	0.823
Atopy	65 (79.3)	20 (86.9)	85 (80.9)	0.553
Body mass index (kg/m²)	19.4 ± 3.9	20.8 ± 3.9	19.7 ± 3.9	0.108
FEV₁ %pred	93.6 ± 10.6	71.2 ± 15.9	88.3 ± 15.3	<0.001
FVC %pred	97.7 ± 12.1	88.2 ± 18.9	95.5 ± 14.5	0.017
FEV₁/FVC	88.2 ± 4.9	74.5 ± 8.2	84.9 ± 14.5	<0.001
FEF_25%-75% %pred	97.5 ± 17.7	47.8 ± 13.4	85.7 ± 27.0	<0.001
Eosinophil (%)	3.6 (1.3–9.8)	4.2 (2.5–7.3)	3.7 (1.5–9.3)	0.783
ECP (µg/L)	17.6 (5.9–52.0)	17.2 (7.6–39.4)	17.5 (6.3–48.8)	0.320
FeNO (ppb)	25.8 (14.2–46.9)	37.2 (24.2–57.2)	28.2 (15.7–50.4)	0.006

Valus are presented as mean±standard deviation, number (%), or geometric mean (range).

Group 1, normal FEF_25%–75% group (FEF_25%–75%≥65%pred); group 2, impaired FEF_25%–75% group (FEF_25%–75%<65%pred); FEV₁, forced expiratory volume in 1 second; FVC, forced vital capacity; FEF_25%–75%, forced expiratory flow between 25% and 75% of vital capacity; ECP, eosinophil cationic protein; FeNO, fractional exhaled nitric oxide.

Table 2

Comparison of clinical characteristics between atopy and nonatopy group

Characteristic	Atopy group (n = 85)	Nonatopy group (n = 20)	P-value
Age (yr)	10.7 ± 2.8	10.0 ± 2.9	0.338
Boys	55 (67.0)	10 (50.0)	0.154
Body mass index (kg/m²)	19.8 ± 3.7	19.6 ± 4.8	0.843
FEV₁ %pred	88.0 ± 14.8	90.9 ± 12.8	0.432
FVC %pred	95.5 ± 14.5	98.0 ± 13.3	0.500
FEV₁/FVC	94.8 ± 7.7	85.3 ± 8.6	0.821
FEF_25%-75% %pred	85.1 ± 27.1	88.8 ± 22.3	0.575
Eosinophil (%)	2.4 (2.25–2.47)	1.5 (1.36–1.57)	0.001
ECP (µg/L)	20.6 (8.3–51.1)	7.9 (2.7–23.5)	<0.001
FeNO (ppb)	31.7 (20.1–49.9)	17.8 (8.7–36.4)	0.003

Valus are presented as mean±standard deviation, number (%), or geometric mean (range).

FEV₁, forced expiratory volume in 1 second; FVC, forced vital capacity; FEF_25%–75%, forced expiratory flow between 25% and 75% of vital capacity; ECP, eosinophil cationic protein; FeNO, fractional exhaled nitric oxide.

Notes

This study was supported in part by grants from the Environmental Health Center for Childhood Asthma (2014) and the Allergy Immunology Center, Korea University, Korea.

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ORCID iDs: Young Yoo
https://orcid.org/http://orcid.org/0000-0003-3354-6969
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