The KAAACI Standardization Committee Report on the procedure and application of fractional exhaled nitric oxide measurement

Jae-Woo Kwon; Woo-Jung Song; Min-Hye Kim; Kyung-Hwan Lim; Min-Suk Yang; Jae-Woo Jung; Jeongmin Lee; Dong In Suh; Yoo Seob Shin; Sae-Hoon Kim; Sang-Heon Kim; Byung-Jae Lee; Sang-Heon Cho

doi:10.4168/aard.2017.5.4.185

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Kwon, Song, Kim, Lim, Yang, Jung, Lee, Suh, Shin, Kim, Kim, Lee, Cho, and The Korean Academy of Asthma, Allergy and Clinical Immunology Standardization Committee: The KAAACI Standardization Committee Report on the procedure and application of fractional exhaled nitric oxide measurement

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Allergy Asthma Respir Dis 2017;5(4):185-192.

Published online: 5 July 2017

DOI: https://doi.org/10.4168/aard.2017.5.4.185

The KAAACI Standardization Committee Report on the procedure and application of fractional exhaled nitric oxide measurement

Jae-Woo Kwon¹, Woo-Jung Song², Min-Hye Kim³, Kyung-Hwan Lim⁴, Min-Suk Yang^2,⁵, Jae-Woo Jung⁶, Jeongmin Lee⁷, Dong In Suh⁸, Yoo Seob Shin⁹, Sae-Hoon Kim^2,¹⁰, Sang-Heon Kim¹¹, Byung-Jae Lee¹², Sang-Heon Cho²; The Korean Academy of Asthma, Allergy and Clinical Immunology Standardization Committee

¹Department of Internal Medicine, Kangwon National University School of Medicine, Chuncheon, Korea

²Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea

³Department of Internal Medicine, Ewha Womans University School of Medicine, Seoul, Korea

⁴Department of Internal Medicine, Armed Forces Capital Hospital, Seongnam, Korea

⁵Department of Internal Medicine, Seoul Metropolitan Government - Seoul National University Boramae Medical Center, Seoul, Korea

⁶Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Korea

⁷Department of Pediatrics, Yonsei University Wonju College of Medicine, Wonju, Korea

⁸Department of Pediatrics, Seoul National University College of Medicine, Seoul, Korea

⁹Department of Allergy and Clinical Immunology, Ajou University School of Medicine, Suwon, Korea

¹⁰Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea

¹¹Department of Internal Medicine, Hanyang University College of Medicine, Seoul, Korea

¹²Division of Allergy, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea

Correspondence to: Woo-Jung Song https://orcid.org/0000-0002-4630-9922 Division of Allergy and Clinical Immunology, Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul 03080, Korea Tel: +82-2-2072-3241, Fax: +82-2-742-3291, E-mail: swj0126@gmail.com

• This research was supported by a fund (A092076) by Research of Korea Centers for Disease Control and Prevention.

Received 5 April 20178 June 2017 Accepted 23 June 2017

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/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Fractional exhaled nitric oxide (FeNO) is a biomarker for type 2 inflammation in the airways, and its measurement has the distinct strengths of being simple, rapid, convenient, and reproducible. Since the discovery of FeNO in the 1990s, its measurement tools have been extensively developed and validated by several researchers. In particular, FeNO showed the potential to support the diagnosis of asthma and eosinophilic bronchitis. Since it has begun to be widely utilized in clinical research areas as well as daily practice, we summarized the standardized diagnostic procedures and suggested the clinical application of FeNO measurement in Korean population.

Keywords: Nitric oxide, Diagnostic techniques and procedures, Asthma, Reference standards

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Fig. 1.

Distribution of fractional exhaled nitric oxide (FeNO) levels in community based adult population and its comparison with asthma patients in Korea. Males (A) and females (B). ppb, parts per billion. Reprinted from Allergy Asthma Immunol Res 2014;6:504-10.³⁹

Table 1.

Factors affecting fractional exhaled nitric oxide levels

Factor
Increased
Bronchodilator
Respiratory tract infection
Nitrate-rich diet
Decreased
Bronchoconstriction
Spirometric maneuver
Corticosteroid, antileukotrienes
Water, coffee intake
Cigarette smoke
Exercise

Table 2.

Summary of diagnostic accuracy meta-analyses on fractional exhaled nitric oxide tests to predict asthma

Study	Population	Summary AUC (95% CI)	Sensitivity (95% CI)	Specificity (95% CI)
Karrasch et al. (2017⁾⁴²	Patients with symptoms suggestive of asthma	0.80 (0.77–0.85)	65% (58–72)	82% (76–86)
Song et al. (2017)⁴¹	Patients with chronic cough	0.87 (0.83–0.89)	72% (61–81)	85% (81–88)

AUC, area under the curve; CI, confidence interval.

Table 3.

Summary of diagnostic accuracy studies on fractional exhaled nitric oxide tests to predict asthma in Korean populations

Study	Population	Demographic	Cutoff value	Sensitivity	Specificity
Park et al. (2012)⁴⁵	Patients with recurrent cough, dyspnea or wheeze (n=161)	Adults (mean, 43 yr)	25.5 ppb	57.1%	75.7%
Jo et al. (2014)³⁹	Community-based general adult population (n=570) vs. patients with asthma (n=74)	Adults (mean, 59 yr)	Male, 30.5 ppb; female, 20.5 ppb	Male, 70%; female, 79.5%	Male, 90%; female, 86.9%
Woo et al. (2014)⁴⁴	Patients with recurrent cough, dyspnea, or wheeze (n=245)	Children (8–16 yr)	22 ppb	56.9%	87.2%

ppb, parts per billion.

Table 4.

Summary of diagnostic accuracy meta-analyses on fractional exhaled nitric oxide to predict eosinophilic airway inflammation

Study	Population	Summary AUC (95% CI)	Sensitivity (95% CI)	Specificity (95% CI)
Korevaar et al. (2015)⁴⁹	Patients with asthma	Adults, 0.75 (0.72–0.78); Children, 0.81 (0.72–0.89)	Adults, 66% (57–75); Children, 72% (24–95)	Adults, 76% (65–85); Children, 77% (20–98)
Song et al. (2017)⁴¹	Patients with nonasthmatic chronic cough	0.81 (0.77–0.84)	72% (62–80)	83% (73–90)

AUC, area under the curve; CI, confidence interval.

Table 5.

Summary of diagnostic accuracy studies on fractional exhaled nitric oxide tests to predict eosinophilic airway inflammation in Korean populations

Study	Population	Demographics	Cutoff values	Sensitivity	Specificity
Oh et al. (2008)⁵³	Patients with cough >3 wk (n=211)	Adults (mean, 46 yr)	31.7 ppb	86%	76%
Yune et al. (2015)¹⁹	Patients with symptoms suggestive of asthma (n=40)	Adults (mean, 53 yr)	37.5 ppb	90%	81%

ppb, parts per billion.

Table 6.

Clinical application of fractional exhaled nitric oxide tests in asthma patients with current respiratory symptoms

Fractional exhaled nitric oxide values	Allergic airway inflammation	Consideration
>50 ppb (in adults)>35 ppb (in children)	Likely	Increase inhaled corticosteroids Check inhaler errors Check adherence Control allergen exposure (if patients have allergic asthma) Consider corticosteroid-resistant eosinophilic asthma
25–50 ppb (in adults) 20–35 ppb (in children)	Possible; cautious interpretation is recommended.	Increase inhaled corticosteroids Check inhaler errors Check adherence Control allergen exposure (if patients have allergic asthma)
<25 ppb (in adults) <20 ppb (in children)	Less likely	Review asthma diagnosis Consider noneosinophilic asthma Consider comorbid diseases like rhinosinusitis, gastroesophageal reflux diseases, or cardiac diseases

ppb, parts per billion.

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