Diagnostic value of fractional exhaled nitric oxide in predicting cough variant asthma in children with chronic cough: a systematic review and meta-analysis

doi:10.3969/j.issn.1674-8115.2023.06.004

Abstract

Abstract:

Objective ·To evaluate the values of fractional exhaled nitric oxide (FeNO) for the diagnosis of cough variant asthma (CVA) in children with chronic cough by systematic review and meta-analysis. Methods ·PubMed, Embase, Cochrane Library, Web of Science, China Biology Medicine Database (SinoMed), China National Knowledge Infrastructure (CNKI), and Wanfang Database were systematically searched for cohort studies and case-control studies to March 1, 2022. Two researchers independently screened the studies according to the inclusion and exclusion criteria, and the number of true positive, false positive, true negative, and false negative patients and the cut-off value of FeNO were extracted from the studies. Diagnostic accuracy studies tool version 2 (QUADAS-2) was used to evaluate the quality of the included literature in terms of risk bias and clinical applicability. Revman 5.4 was used to draw the quality evaluation chart. A meta-analysis was performed by the midas and spearman commands of Stata 17.0. Spearman correlation coefficients of sensitivity logarithm and (1-specificity) logarithm were used to test the threshold effect. The substantial heterogeneity caused by non-threshold effect was tested by bivariate box plot and I² statistic. The effect size was pooled by bivariate random effect model. Publication bias was evaluated by Deek′s Funnel plot. Results ·One thousand and ninety-nine studies were retrieved in total and 9 were finally included. The diagnostic criteria of the included study were all from expert consensus or guidelines. The QUADAS-2 showed that the quality of the included study was low. The Spearman correlation coefficient of sensitivity and (1-specificity) was 0.05 (P=0.90), indicating that there was no heterogeneity caused by threshold effect. The results ofbivariate box plot and I²=0 showed that there was no heterogeneity caused by non-threshold effect. Combined effect showed that the sensitivity was 0.82 (95%CI 0.78－0.85), the specificity was 0.93 (95%CI 0.89?0.95), the positive likelihood ratio was 11.30 (95%CI 7.40?17.10), the negative likelihood ratio was 0.19 (95%CI 0.16?0.24), the diagnostic odds ratio was 58 (95%CI 34?101), and the area under the summary receiver operating characteristic (SROC) curve was 0.89 (95%CI 0.86?0.92). The result of Deek′s Funnel plot showed that there was no publication bias. Conclusion ·FeNO test has a moderate diagnostic value in prediciting CVA in children with chronic cough. However, the results of the study need to be interpreted with caution due to the low quality of the original evidence.

Key words: fractional exhaled nitric oxide (FeNO), cough variant asthma (CVA), child, diagnosis

CLC Number:

R725.6

DANG Xiangyang, TANG Yuyi, LI Weiguo, LIU Enmei. Diagnostic value of fractional exhaled nitric oxide in predicting cough variant asthma in children with chronic cough: a systematic review and meta-analysis[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2023, 43(6): 680-688.

Figures/Tables 7

TrendMD

References 38

1	MARCHANT J M, NEWCOMBE P A, JUNIPER E F, et al. What is the burden of chronic cough for families?[J]. Chest, 2008, 134(2): 303-309.
2	CHANG A B, OPPENHEIMER J J, WEINBERGER M, et al. Etiologies of chronic cough in pediatric cohorts: chest guideline and expert panel report[J]. Chest, 2017, 152(3): 607-617.
3	中华医学会儿科学分会临床药理学组, 国家儿童健康与疾病临床医学研究中心, 中华医学会儿科学分会呼吸学组, 等. 中国儿童咳嗽诊断与治疗临床实践指南(2021版)[J]. 中华儿科杂志, 2021, 59(9): 720-729.
	The Subspecialty Group of Pharmacology, the Society of Pediatrics, Chinese Medical Association, National Clinical Research Center for Child Health and Disorders, the Subspecialty Group of Respiratory Diseases, the Society of Pediatrics, Chinese Medical Association, et al. Clinical practice guidelines for the diagnosis and management of children with cough in China (version 2021)[J]. Chinese Journal of Pediatrics, 2021, 59(9): 720-729.
4	CHANG A B, OPPENHEIMER J J, IRWIN R S, et al. Managing chronic cough as a symptom in children and management algorithms: chest guideline and expert panel report[J]. Chest, 2020, 158(1): 303-329.
5	SONG D J, SONG W J, KWON J W, et al. KAAACI evidence-based clinical practice guidelines for chronic cough in adults and children in Korea[J]. Allergy Asthma Immunol Res, 2018, 10(6): 591-613.
6	MORICE A H, MILLQVIST E, BIEKSIENE K, et al. ERS guidelines on the diagnosis and treatment of chronic cough in adults and children[J]. Eur Respir J, 2020, 55(1): 1901136.
7	中国儿童慢性咳嗽病因构成比研究协作组. 中国儿童慢性咳嗽病因构成比多中心研究[J]. 中华儿科杂志, 2012, 50(2): 83-92.
	Clinical Research Coordination Group of the Causes Constituents Ratio of Chronic Cough in Chinese Children. Prospective multicenter clinical study on the causes constituents ratio of chronic cough in Chinese children[J]. Chinese Journal of Pediatrics, 2012, 50(2): 83-92.
8	CHEN X, PENG W S, WANG L. Etiology analysis of nonspecific chronic cough in children of 5 years and younger[J]. Medicine (Baltimore), 2019, 98(3): e13910.
9	LAI K F, CHEN R C, LIN J T, et al. A prospective, multicenter survey on causes of chronic cough in China[J]. Chest, 2013, 143(3): 613-620.
10	ZHOU X L, ZHANG Y, LIU L, et al. Therapeutic effect of acupuncture combined montelukast sodium on cough variant asthma in children: a protocol for systematic review and meta-analysis[J]. Medicine (Baltimore), 2021, 100(51): e28048.
11	FUJIMURA M, OGAWA H, NISHIZAWA Y, et al. Comparison of atopic cough with cough variant asthma: is atopic cough a precursor of asthma?[J]. Thorax, 2003, 58(1): 14-18.
12	MANISCALCO M, FUSCHILLO S, GAUDIOSI C, et al. Exhaled and nasal nitric oxide measurement in the evaluation of chronic cough[J]. Nitric Oxide, 2019, 83: 19-23.
13	中华医学会儿科学分会呼吸学组哮喘协作组. 儿童呼出气一氧化氮检测及临床应用专家共识(2021版)[J]. 中华实用儿科临床杂志, 2021, 36(6): 417-423.
	Collaboration Group of Asthma, the Subspecialty Group of Respiratory Diseases, the Society of Pediatrics, Chinese Medical Association. Expert consensus on detection and clinical application of exhaled nitric oxide in children (2021 edition)[J]. Chinese Journal of Applied Clinical Pediatrics, 2021, 36(6): 417-423.
14	王芷婧, 王淼, 王圣元, 等. FeNO检测对中国人群激素敏感性咳嗽诊断价值的meta分析[J]. 国际呼吸杂志, 2020, 40(5): 359-367.
	WANG Z J, WANG M, WANG S Y, et al. Diagnostic value of fractional exhaled nitric oxide test in corticosteroid responsive cough patients in China: a meta-analysis[J]. International Journal of Respiration, 2020, 40(5): 359-367.
15	SONG W J, KIM H J, SHIM J S, et al. Diagnostic accuracy of fractional exhaled nitric oxide measurement in predicting cough-variant asthma and eosinophilic bronchitis in adults with chronic cough: a systematic review and meta-analysis[J]. J Allergy Clin Immunol, 2017, 140(3): 701-709.
16	郭治, 王鑫, 邢国宏, 等. 呼出气一氧化氮检测对咳嗽变异型哮喘诊断价值的meta分析[J]. 国际呼吸杂志, 2015, 35(20): 1535-1540.
	GUO Z, WANG X, XING G H, et al. Fractional exhaled nitric oxide in cough variant asthma: a meta-analysis[J]. International Journal of Respiration, 2015, 35(20): 1535-1540.
17	张瑞, 陈如冲, 贾留群, 等. 呼出气一氧化氮对慢性咳嗽人群中咳嗽变异型哮喘的诊断价值: meta分析[J]. 国际呼吸杂志, 2017, 37(16): 1201-1206.
	ZHANG R, CHEN R H, JIA L Q, et al. Diagnostic accuracy of fractional exhaled nitric oxide for cough variant asthma in chronic cough patients: a meta-analysis[J]. International Journal of Respiration, 2017, 37(16): 1201-1206.
18	中华医学会儿科学分会呼吸学组, 《中华儿科杂志》编辑委员会. 儿童慢性咳嗽诊断与治疗指南(试行)[J]. 中华儿科杂志, 2008, 46(2): 104-107.
	The Subspecialty Group of Respiratory Diseases, the Society of Pediatrics, Chinese Medical Association, Editorial Board of Chinese Journal of Pediatrics. Guideline for diagnosis and treatment of chronic cough in pediatrics[J]. Chinese Journal of Pediatrics, 2008, 46(2): 104-107.
19	中华医学会儿科学分会呼吸学组慢性咳嗽协作组, 《中华儿科杂志》编辑委员会. 中国儿童慢性咳嗽诊断与治疗指南(2013年修订)[J]. 中华儿科杂志, 2014, 52(3): 184-188.
	Collaboration Group of Chronic Cough, the Subspecialty Group of Respiratory Diseases, the Society of Pediatrics, Chinese Medical Association, Editorial Board of Chinese Journal of Pediatrics. Guideline for diagnosis and treatment of chronic cough in Chinese pediatrics (2013 version)[J]. Chinese Journal of Pediatrics, 2014, 52(3): 184-188.
20	IRWIN R S, BAUMANN M H, BOLSER D C, et al. Diagnosis and management of cough executive summary: ACCP evidence-based clinical practice guidelines[J]. Chest, 2006, 129(1 Suppl): 1S-23S.
21	WHITING P F, RUTJES A W, WESTWOOD M E, et al. QUADAS-2: a revised tool for the quality assessment of diagnostic accuracy studies[J]. Ann Intern Med, 2011, 155(8): 529-536.
22	REITSMA J B, GLAS A S, RUTJES A W, et al. Bivariate analysis of sensitivity and specificity produces informative summary measures in diagnostic reviews[J]. J Clin Epidemiol, 2005, 58(10): 982-990.
23	RUTTER C M, GATSONIS C A. A hierarchical regression approach to meta-analysis of diagnostic test accuracy evaluations[J]. Stat Med, 2001, 20(19): 2865-2884.
24	张天嵩, 李博, 钟文昭. 实用循证医学方法学[M]. 3版. 长沙: 中南大学出版社, 2021.
	ZHANG T S, LI B, ZHONG W Z. Applied Methodology for Evidence-based Medicine[M]. 3rd ed. Changsha: Central South University Press, 2021.
25	季秀梅, 王凯旋, 陈菊萍, 等. 慢性咳嗽儿童呼出气一氧化氮检测的临床意义[J]. 中国现代医生, 2013, 51(15): 39-41.
	JI X M, WANG K X, CHEN J P, et al. Clinical significance of fractional exhaled nitric oxide in children with chronic cough[J]. China Modern Doctor, 2013, 51(15): 39-41.
26	曹兴丽, 武怡. 呼出气一氧化氮在儿童咳嗽变异性哮喘诊断中的价值[J]. 徐州医学院学报, 2015, 35(5): 328-330.
	CAO X L, WU Y. Measurement of fractional nitric oxide concentration in exhaled breath to assess cough variant asthma in child patients[J]. Journal of Xuzhou Medical University, 2015, 35(5): 328-330.
27	朱海艳, 于兴梅, 郝创利, 等. 呼出气一氧化氮测定对儿童咳嗽变异性哮喘的诊断价值[J]. 中华结核和呼吸杂志, 2015, 38(5): 352-355.
	ZHU H Y, YU X M, HAO C L, et al. The diagnostic value of the fractional exhaled nitric oxide for cough variant asthma in children[J]. Chinese Journal of Tuberculosis and Respiratory Diseases, 2015, 38(5): 352-355.
28	牛文泽, 杜许芳, 孟柳明, 等. 呼出气一氧化氮检测在儿童咳嗽变异性哮喘中的诊疗价值[J]. 中国中西医结合儿科学, 2016, 8(3): 269-272.
	NIU W Z, DU X F, MENG L M, et al. Value of fractional exhaled nitric oxide in the diagnosis and treatment of children with cough variant asthma[J]. Chinese Pediatrics of Integrated Traditional and Western Medicine, 2016, 8(3): 269-272.
29	ZHOU J, ZHAO X H, ZHANG X, et al. Values of fractional exhaled nitric oxide for cough-variant asthma in children with chronic cough[J]. J Thorac Dis, 2018, 10(12): 6616-6623.
30	YILDIZ Y, IGDE M. Evaluation of fractioned nitric oxide in chronic cough patients[J]. Niger J Clin Pract, 2018, 21(1): 1-6.
31	周晓娜, 谭淑英. FeNO、FEV₁/FVC%、BPT在小儿CVA诊断中的价值分析[J]. 临床肺科杂志, 2018, 23(6): 1048-1051.
	ZHOU X N, TAN S Y. Value of FeNO, FEV₁/FVC% and BPT in diagnosis of children with CVA[J]. Journal of Clinical Pulmonary Medicine, 2018, 23(6): 1048-1051.
32	李卫兵. 呼出气一氧化氮检测对儿童咳嗽变异性哮喘的诊断价值[J]. 江苏医药, 2018, 44(2): 213-215.
	LI W B. Value of fractional exhaled nitric oxide in the diagnosis of children with cough variant asthma[J]. Jiangsu Medical Journal, 2018, 44(2): 213-215.
33	ZHU H Y, ZHANG R R, HAO C L, et al. Fractional exhaled nitric oxide (FeNO) combined with pulmonary function parameters shows increased sensitivity and specificity for the diagnosis of cough variant asthma in children[J]. Med Sci Monit, 2019, 25: 3832-3838.
34	MUNAKATA M. Exhaled nitric oxide (FeNO) as a non-invasive marker of airway inflammation[J]. Allergol Int, 2012, 61(3): 365-372.
35	YI F, CHEN R C, LUO W, et al. Validity of fractional exhaled nitric oxide in diagnosis of corticosteroid-responsive cough[J]. Chest, 2016, 149(4): 1042-1051.
36	SONG W J, KWON J W, KIM E J, et al. Clinical application of exhaled nitric oxide measurements in a Korean population[J]. Allergy Asthma Immunol Res, 2015, 7(1): 3-13.
37	中华医学会儿科学分会呼吸学组肺功能协作组, 《中华实用儿科临床杂志》编辑委员会. 儿童肺功能及气道非创伤性炎症指标系列指南(七): 呼出气体一氧化氮监测[J]. 中华实用儿科临床杂志, 2017, 32(21): 1622-1627.
	Collaboration Group of Pulmonary Function, the Subspecialty Group of Respiratory Diseases, the Society of Pediatrics, Chinese Medical Association, Editorial Board of Chinese Journal of Applied Clinical Pediatrics. Series guidelines for pediatric pulmonary function and non-invasive airway inflammation marker (part Ⅶ): fractional exhaled nitric oxide monitoring[J]. Chinese Journal of Applied Clinical Pediatrics, 2017, 32(21): 1622-1627.
38	王天玥, 尚云晓, 张晗. 呼出气一氧化氮浓度测定在儿童支气管哮喘和咳嗽变异性哮喘中的诊断价值[J]. 中国当代儿科杂志, 2015, 17(8): 800-805.
	WANG T Y, SHANG Y X, ZHANG H. Diagnostic values of fractional exhaled nitric oxide for typical bronchial asthma and cough variant asthma in children[J]. Chinese Journal of Contemporary Pediatrics, 2015, 17(8): 800-805.

Study	Country	Design	Sample size (CVA/nCVA)	Age/year	Cut-off value/ppb	FeNO measurement	Diagnostic criterion for CVA	FeNO test
Study	Country	Design	Sample size (CVA/nCVA)	Age/year	Cut-off value/ppb	FeNO measurement	Diagnostic criterion for CVA	TP/n	FP/n	FN/n	TN/n
JI et al, 2013^[25]	China	Retrospective	42/44	5‒14	22.5	NIOX MINO (Aerocrine, Sweden)	Chinese guideline for diagnosis and treatment of chronic cough in pediatrics (2008 version)^[18]	37	4	7	38
CAO et al, 2015^[26]	China	Prospective	81/127	0‒12	36	Nano Coulomb Nitric Oxide Analyzer (Sunvou Medical Electronics Co., Ltd., China)	Chinese guideline for diagnosis and treatment of chronic cough in pediatrics (2008 version)^[18]	68	4	13	123
ZHU et al, 2015^[27]	China	Prospective	38/46	6‒12	25.5	NIOX MINO (Aerocrine, Sweden)	Chinese guideline for diagnosis and treatment of chronic cough in pediatrics (2008 version)^[18]	47	8	10	71
NIU et al, 2016^[28]	China	Prospective	106/68	6‒14	20.5	Nano Coulomb Nitric Oxide Analyzer (Sunvou Medical Electronics Co., Ltd., China)	Guideline for diagnosis and treatment of chronic cough in Chinese pediatrics (2013 version)^[19]	79	9	27	59
ZHOU et al, 2018^[29]	China	Prospective	53/62	6‒14	25	NIOX MINO (Aerocrine, Sweden)	ACCP evidence-based clinical practice guideline (2006 version)^[20]	45	2	8	60
YILDIZ et al, 2018^[30]	Turkey	Retrospective	27/63	6‒17	24	NIOX MINO (Aerocrine, Sweden)	ACCP evidence-based clinical practice guideline (2006 version)^[20]	21	5	6	58
ZHOU et al, 2018^[31]	China	Retrospective	41/65	6‒13	27.64	NIOX MINO (Aerocrine, Sweden)	Guideline for diagnosis and treatment of chronic cough in Chinese pediatrics (2013 version)^[19]	36	10	5	55
LI et al, 2018^[32]	China	Retrospective	43/65	0‒12	35	NIOX MINO (Aerocrine, Sweden)	Chinese guideline for diagnosis and treatment of chronic cough in pediatrics (2008 version)^[18]	36	2	7	63
ZHU et al, 2019^[33]	China	Prospective	57/79	6‒12	25.5	NIOX MINO (Aerocrine, Sweden)	Guideline for diagnosis and treatment of chronic cough in Chinese pediatrics (2013 version)^[19]	47	8	10	71

Study	Country	Design	Sample size (CVA/nCVA)	Age/year	Cut-off value/ppb	FeNO measurement	Diagnostic criterion for CVA	FeNO test
Study	Country	Design	Sample size (CVA/nCVA)	Age/year	Cut-off value/ppb	FeNO measurement	Diagnostic criterion for CVA	TP/n	FP/n	FN/n	TN/n
JI et al, 2013^[25]	China	Retrospective	42/44	5‒14	22.5	NIOX MINO (Aerocrine, Sweden)	Chinese guideline for diagnosis and treatment of chronic cough in pediatrics (2008 version)^[18]	37	4	7	38
CAO et al, 2015^[26]	China	Prospective	81/127	0‒12	36	Nano Coulomb Nitric Oxide Analyzer (Sunvou Medical Electronics Co., Ltd., China)	Chinese guideline for diagnosis and treatment of chronic cough in pediatrics (2008 version)^[18]	68	4	13	123
ZHU et al, 2015^[27]	China	Prospective	38/46	6‒12	25.5	NIOX MINO (Aerocrine, Sweden)	Chinese guideline for diagnosis and treatment of chronic cough in pediatrics (2008 version)^[18]	47	8	10	71
NIU et al, 2016^[28]	China	Prospective	106/68	6‒14	20.5	Nano Coulomb Nitric Oxide Analyzer (Sunvou Medical Electronics Co., Ltd., China)	Guideline for diagnosis and treatment of chronic cough in Chinese pediatrics (2013 version)^[19]	79	9	27	59
ZHOU et al, 2018^[29]	China	Prospective	53/62	6‒14	25	NIOX MINO (Aerocrine, Sweden)	ACCP evidence-based clinical practice guideline (2006 version)^[20]	45	2	8	60
YILDIZ et al, 2018^[30]	Turkey	Retrospective	27/63	6‒17	24	NIOX MINO (Aerocrine, Sweden)	ACCP evidence-based clinical practice guideline (2006 version)^[20]	21	5	6	58
ZHOU et al, 2018^[31]	China	Retrospective	41/65	6‒13	27.64	NIOX MINO (Aerocrine, Sweden)	Guideline for diagnosis and treatment of chronic cough in Chinese pediatrics (2013 version)^[19]	36	10	5	55
LI et al, 2018^[32]	China	Retrospective	43/65	0‒12	35	NIOX MINO (Aerocrine, Sweden)	Chinese guideline for diagnosis and treatment of chronic cough in pediatrics (2008 version)^[18]	36	2	7	63
ZHU et al, 2019^[33]	China	Prospective	57/79	6‒12	25.5	NIOX MINO (Aerocrine, Sweden)	Guideline for diagnosis and treatment of chronic cough in Chinese pediatrics (2013 version)^[19]	47	8	10	71

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