Fractional Exhaled Nitric Oxide for the Diagnosis of Childhood Asthma: a Systematic Review and Meta-analysis

Tang, Suo-Qin; Xie, Yiqiang; Yuan, CongHu; Sun, Xuemei; Cui, Yubao

doi:10.1007/s12016-016-8573-4

Cited by 22 publications

(15 citation statements)

References 34 publications

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“…However, this is the first study to reveal diagnostic power of CD93for asthma diagnosis. In addition, this moderate predictive power is comparable to that of previously studied biomarkers, including serum periostin and fractional exhaled nitric oxide 26,27 . Because of small number of asthma subjects (n = 28), we could not find significant correlation of level of CD93 with lung function or level of eosinophil.…”

Section: Discussionsupporting

confidence: 72%

Soluble CD93 in allergic asthma

Park

Han

et al. 2020

Sci Rep

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Jung-Won park 2,3 & Jae-Hyun Lee 2,3* CD93 has been shown critical roles in inflammatory and immune diseases. However, in allergic asthma, the potential roles of soluble CD93 (sCD93) have not been well studied. We conducted house dust mite (HDM) stimulation with Der p 1 in BEAS-2B and U937 cells, followed by treatment with dexamethasone or small interfering RNA against CD93. A HDM-induced murine allergic asthma model was also established. We estimated the power of sCD93 to predict allergic asthma in a retrospective post-hoc analysis containing 96 human samples. HDM-stimulated BEAS-2B cells showed increased mRNA expression levels of IL-6, IL-8, IL-33, TSLP, and CD93. The CD93 level in culture supernatants steadily increased for 24 h after allergen stimulation, which was significantly suppressed by both dexamethasone and CD93 silencing. CD93 silencing increased IL-6 and TSLP, but not IL-33 levels in culture supernatants. HDM-induced asthma mice showed significant airway hyperresponsiveness and inflammation with Th2 cytokine activation, along with decreased CD93 expression in bronchial epithelial cells and lung homogenates but increased serum CD93 levels. The sCD93 level in asthma patients was significantly higher than that in healthy controls and could predict asthma diagnosis with moderate sensitivity (71.4%) and specificity (82.4%) (AUC = 0.787, P < 0.001). The level of sCD93 which has potential role to predict asthma significantly increased after HDM stimulation via IL-6 and TSLP in vitro and in vivo. Asthma is a chronic inflammatory airway disease that is typically diagnosed based on a pulmonary function test with a bronchodilator and a bronchial provocation test 1. However, these tests require the effort and cooperation of the patient, which is often impossible owing to old age, deafness, misunderstanding, severe dyspnea, paroxysmal cough, and risk of an asthma attack 2. Therefore, there is a clinical need to identify a serum biomarker that can act as a non-invasive method of diagnosis for asthma patients; although several biomarkers have been suggested, they are not widely used in clinical settings owing to limited evidence 3,4. CD93 (C1qRp) is a transmembrane glycoprotein that is expressed on various cell types, including endothelial cells, epithelial cells, stem cells, platelets, and leukocytes 5,6. CD93 can be shed in a soluble form (sCD93) in response to inflammatory mediators, can be easily measured, and is considered to be associated with various inflammatory and immune associated diseases, including asthma 7,8. In addition, CD93 has angiogenic and growth-stimulating effects 9-11. Raedler et al. 12 showed that CD93 gene expression was significantly higher in non-allergic asthma patients than healthy controls, and Sigari et al. 13 demonstrated that the serum CD93 level increased under asthma exacerbation and decreased following proper treatment. We also previously reported the potential of sCD93 as a novel biomarker for asthma using an ovalbumin-induced asthma murine model and human patients 14,15. Howev...

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Section: Discussionsupporting

confidence: 72%

Soluble CD93 in allergic asthma

Park

Han

et al. 2020

Sci Rep

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“…Recommendations for standardized methodologies and clinical use of FeNO measurement have been applied in adults and older children . However, FeNO values for atopic asthma diagnosis are not well defined and a large overlap in the distribution of FeNO levels from children with allergic asthma, non‐allergic asthma, allergy without asthma, and healthy population has been reported . Besides, several potential confounders have been highlighted, such as age , gender, infection, race, atopic eczema , obesity, smoking, diet (alcohol, coffee), steroid intake, and menarche.…”

Section: Diagnosis and Managementmentioning

confidence: 99%

Asthma and allergic rhinitis in childhood: what's new

Mastrorilli

Posa

Cipriani

et al. 2016

Pediatric Allergy Immunology

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Novel approaches are currently offered for the diagnostic workup and therapeutic management of allergic rhinitis and asthma. New predictive biomarkers of allergy and asthma are available. Primary and secondary prevention, earlier intervention, and modification of the natural history of allergic rhinitis and asthma are being intensively investigated. This review highlights advances in the understanding of the etiology, diagnosis, and management of atopic airway diseases in childhood, as well as prenatal and early-life risk factors and strategies for prevention.

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“…Although the diagnostic accuracy of exhaled NO in the identification of asthma in children is moderate, it suggests that it might be a promising tool and the confounding or effect modification of atopy is believed to be a key feature that limits the usefulness of exhaled NO in asthma diagnosis.…”

Section: Introductionmentioning

confidence: 99%

Spirometry‐adjusted fraction of exhaled nitric oxide increases accuracy for assessment of asthma control in children

Martins

Silva

Severo

et al. 2017

Pediatric Allergy Immunology

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Spirometry and exhaled nitric oxide are two important complimentary tools to identify and assess asthma control in children. We aimed to determine the ability of a new suggested spirometry-adjusted fraction of exhaled nitric oxide (NO) index in doing that. A random sample of 1602 schoolchildren were screened by a health questionnaire, skin prick tests, spirometry with bronchodilation and exhaled NO. A total of 662 children were included with median (IQR) exhaled NO 11(14) ppb. Receiver operating characteristic (ROC) curves using exhaled NO equations from Malmberg, Kovesi and Buchvald, and spirometry-adjusted fraction of exhaled NO values were applied to identify asthmatic children and uncontrolled asthma. Receiver operating characteristic (ROC) curves failed to identify asthmatic children (all AUC < 0.700). Spirometry-adjusted fraction of exhaled NO/FEV (AUC = 0.712; P = .010) and NO/FEF (AUC = 0.735 P = .004) had a fair and increased ability to identify uncontrolled disease compared with exhaled NO (AUC = 0.707; P = .011) or the Malmberg equation (AUC = 0.701; P = .014). Sensitivity and specificity identifying non-controlled asthma were 59% and 81%, respectively, for the cut-off value of 9.7 ppb/L for exhaled NO/FEV , and 40% and 100% for 15.7 ppb/L/s for exhaled NO/FEF . Exhaled NO did not allow to identify childhood asthma. Spirometry-adjusted fraction of exhaled NO performed better-assessing asthma control in children. Thus, although more validation studies are needed, we suggest its use in epidemiological studies to assess asthma control.

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Fractional Exhaled Nitric Oxide for the Diagnosis of Childhood Asthma: a Systematic Review and Meta-analysis

Cited by 22 publications

References 34 publications

Soluble CD93 in allergic asthma

Soluble CD93 in allergic asthma

Asthma and allergic rhinitis in childhood: what's new

Spirometry‐adjusted fraction of exhaled nitric oxide increases accuracy for assessment of asthma control in children

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