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

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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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