Dataset Information

The Role of FeNO in Predicting Asthma.

ABSTRACT: Asthma-like symptoms like wheezing and dyspnea affect 1 in every 3 preschool children. An easily available biomarker that predicts later asthma or unfavorable lung growth in these children may be helpful in targeting the right child with the right drugs and avoiding exposure to potentially harmful drugs in others. The fraction of exhaled nitric oxide (FeNO) has been suggested as a marker of eosinophilic inflammation. FeNO can be measured in a standardized way from the age of 4 but several methods have been developed to measure FeNO also in younger children. Several studies have assessed the predictive value of FeNO in preschool wheezing children for asthma later in life. These studies have shown that FeNO may be helpful in defining different preschool wheezing phenotypes, and in assessing the risk of later asthma or impaired lung growth. However, data are conflicting on the added value over clinical parameters. In two studies in school children, high FeNO was predictive for asthma development during follow up and also predicted lower lung function growth. In school children with respiratory symptoms suggestive of asthma, particularly in atopic children, FeNO has diagnostic value for an asthma diagnosis, mostly for ruling in asthma. There are not enough data to assess if FeNO has a predictive value for lung development in school children.

SUBMITTER: Pijnenburg MW

PROVIDER: S-EPMC6393362 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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The Role of FeNO in Predicting Asthma.

Pijnenburg Mariëlle W MW

Frontiers in pediatrics 20190221

Asthma-like symptoms like wheezing and dyspnea affect 1 in every 3 preschool children. An easily available biomarker that predicts later asthma or unfavorable lung growth in these children may be helpful in targeting the right child with the right drugs and avoiding exposure to potentially harmful drugs in others. The fraction of exhaled nitric oxide (FeNO) has been suggested as a marker of eosinophilic inflammation. FeNO can be measured in a standardized way from the age of 4 but several method ...[more]

PMID: 30847334

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Project description:BackgroundFractional exhaled nitric oxide (FeNO) is promising for diagnosing asthma and could replace bronchial provocation (BP). To date, cut-off values have been derived by post hoc analysis only. The aim was to validate the diagnostic accuracy for predefined FeNO cut-off values and the predictive value for responsiveness to inhaled corticosteroids (ICS).MethodsWe conducted a prospective, diagnostic, multicentre study with patients attending three private practices of pneumologists in Upper Bavaria, Germany, from July 3, 2020 to Jan 21, 2022. Index test was FENO measurement. Reference standard was Tiffeneau ratio (FEV1/VC) or airway resistance as assessed by whole body plethysmography, with additional BP or bronchodilation test. Follow-up was performed after 12 weeks. Analyses of Receiver Operating Characteristics curves were conducted to determine the diagnostic accuracy and predictive value of FeNO.Findings308 patients with complete follow-up were recruited, 186 (60·4%) were female, average age was 44·7 years, 161 (52·3%) had asthma. Regarding diagnostic accuracy, the area under the curve (AUC) was 0·718 (95% CI 0·661-0·775; p < 0·001). Sensitivity at FeNO >50 ppb was 0·24 (95% CI 0·18-0·32), specificity 0·99 (0·95-1·0), positive predictive value (PPV) 0·95 (0·84-0·99), negative predictive value (NPV) 0·54 (0·48-0·60). In 66 patients with ´wheezing´ and ´allergic rhinitis´, the sensitivity at FeNO >33 ppb was 0·49 (0·34-0·64), specificity 0·88 (0·64-0·99), PPV 0·92 (0·75-0·99), NPV 0·38 (0·23-0·54). In 68 patients with ICS medication, responsiveness was predicted at the cut-off >43 ppb, with a sensitivity of 0·55 (95%CI 0·36-0·74), specificity 0·82 (0·66-0·92), PPV 0·70 (0·47-0·87), NPV 0·71 (0·56-0·84).InterpretationFeNO measurement allows a valid ruling-in of an asthma diagnosis, whereas ruling-out of asthma is not possible. Enhanced probability of ICS responsiveness is also given with increased FeNO values.FundingCircassia Germany gave 25% discount on the purchase of three NIOX VERO devices.

Project description:THREE DIISOCYANATES CAN CAUSE OCCUPATIONAL ASTHMA (OA): toluene diisocyanate (TDI), 4,4 diphenylmethane diisocyanate (MDI), and 1,6-hexamethylene diisocyanate (HDI). We analyzed potential biomarkers of isocyanate-induced OA, based on investigated immunologic, genetic, neurogenic, and protein markers, because there is no serological testing method. The prevalence of serum IgG to cytokeratin (CK)18 and CK19 in TDI-OA was significantly higher than in controls, although the prevalence of these antibodies was too low for them to be used as biomarkers. Another candidate biomarker was serum IgG to tissue transglutaminase (tTG), because the prevalence of serum specific IgG to tTG was significantly higher in patients with TDI-OA than in controls. The human leukocyte antigen (HLA) DRB1*1501-DQB1*0602-DPB1*0501 haplotype may be used as a genetic marker for TDI-OA in Koreans via enhanced specific IgE sensitization in exposed subjects. The genetic polymorphisms of catenin alpha 3, alpha-T catenin (CTNNA3) were significantly associated with TDI-OA. Additionally, examining the neurokinin 2 receptor (NK2R) 7853G>A and 11424 G>A polymorphisms, the NK2R 7853GG genotype had higher serum vascular endothelial growth factor (VEGF) levels than the GA or AA genotypes among Korean workers exposed to TDI. To identify new serologic markers using a proteomic approach, differentially expressed proteins between subjects with MDI-OA and asymptomatic exposed controls in a Korean population showed that the optimal serum cutoff levels were 69.8 ng/mL for ferritin and 2.5 µg/mL for transferrin. When these two parameters were combined, the sensitivity was 71.4% and the specificity was 85.7%. The serum cytokine matrix metalloproteinase-9 (MMP-9) level is a useful biomarker for identifying cases of TDI-OA among exposed workers. Despite these possible biomarkers, more effort should be focused on developing early diagnostic biomarkers using a comprehensive approach based on the pathogenic mechanisms of isocyanate-induced OA.

Project description:Background:FeNO has been used as a marker for Th2-mediated airway inflammation in asthma. There is evidence which recommends the use of this biomarker in asthma management. Little is known about whether the FeNO test alone or in combination with the ACT score can reflect asthma control in Vietnamese patients. Materials and Methods:A cross-sectional study was conducted in asthmatic patients (?18 years old) recruited at the University Medical Center, Ho Chi Minh City, Vietnam from March 2016 to March 2017. Asthma control levels were assessed following the GINA 2017 guidelines, and FeNO was measured by a Niox Mino device. FeNO cut-offs predicting asthma control status were determined using the ROC curve analysis. The combination of FeNO and ACT was investigated in detecting well-controlled and uncontrolled asthma. The results of the study are as follows: 278 patients with 68% females, mean age of 44 years, and mean asthma duration of 10 years were analyzed. All patients were treated following step 2 to 4 of GINA guidelines. Mean (SD) FeNO was 30.6 (24) ppb. Patients with uncontrolled (16%), partly controlled (29%), and well-controlled asthma (55%) had a median (IQR) FeNO of 50.0 (74), 25.0 (23), and 21.0 (22.3) ppb, respectively, and the mean of FeNO in the uncontrolled group was significantly higher than that in other groups (p < 0.001). The area under the ROC curve (AUC) for FeNO detecting uncontrolled asthma was 0.730 with an optimal cut-off point of FeNO?>?50?ppb, and this AUC increased to 0.89 when combining FeNO and ACT. The AUC for FeNO detecting well-controlled asthma was 0.601 with an optimal cut-off point of FeNO <25?ppb and this AUC increased to 0.78 if combining FeNO and ACT. Conclusions:FeNO can predict asthma control status with an estimated cut-off point of <25?ppb for well-controlled and >50?ppb for uncontrolled asthma. The combination of FeNO and ACT provides better information regarding asthma control than FeNO alone, and this combination is useful to predict asthma control statuses in asthmatic patients in Viet Nam.

Project description:BackgroundWhile a connection has been established between serum interleukin-6 (IL-6) levels and the IL-6 gene (- 174G/C) polymorphism in allergic diseases such as asthma, its specific association with severe asthma remains unexplored. This study examined the relationship between the IL-6 (- 174G/C) gene polymorphism and mild and severe asthma, focusing on its influence on type 2 inflammation.MethodsOur study comprised 98 patients with mild asthma and 116 with severe asthma. Additionally, we recruited 121 healthy participants to serve as controls for comparative analyses. The IL-6 gene (- 174G/C) polymorphism was assessed utilizing the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method.ResultsIn our study, the risk of mild asthma exhibited a significant fourfold increase in individuals with the GG genotype pattern compared to healthy controls, yielding an odds ratio (OR) of 4.4 (p < 0.001). Conversely, we found no significant correlation between the IL-6 - 174G/C gene polymorphism and severe asthma when compared to the healthy control group. However, a noteworthy pattern emerged when we compared subgroups of mild and severe asthma. The risk of severe asthma increased fivefold in individuals with the GC polymorphism pattern, with an OR of 4.99 (p < 0.001), while the likelihood of mild asthma showed a similar fourfold increase with the GG polymorphism pattern, OR = 4.4 (p < 0.001). Consequently, we observed a significantly higher frequency of the C allele in patients with severe asthma, whereas the G allele was more prevalent in individuals with mild asthma (p = 0.05). Additionally, the correlation between markers of type 2 inflammation and the dominant model of the IL-6 gene -174G/C polymorphism (CC + CG vs GG) revealed a significant increase in total serum immunoglobulin E (IgE), Blood Eosinophil Counts (BEC), and Fractional Exhaled Nitric Oxide (FeNO) levels in asthmatic patients with the CC + CG gene pattern compared to those with GG, with p-values of 0.04, 0.03, and 0.04, respectively. Furthermore, after adjusting for other risk factors, the likelihood of developing severe asthma increased from fourfold to eightfold, with an OR of 8.12 (p = 0.01) with (CC + CG) gene pattern. Other predictors for severe asthma included older age and childhood-onset disease (OR = 1.13 and 19.19, p < 0.001). Allergic rhinitis (AR) and nasal polyps (NP) also demonstrated a substantial association with an increased risk of severe asthma, with odds ratios of 5 and 32.29 (p = 0.01 and < 0.001), respectively. Additionally, elevated Body Mass Index (BMI), BEC, and FeNO were linked to severe asthma, with ORs of 1.11, 1.00, and 1.04, respectively (p = 0.04, 0.05, and 0.001).ConclusionThis study illuminated the intricate relationship between the IL-6 gene polymorphism, type 2 inflammation markers, and diverse risk factors in shaping asthma severity. As a significant association between the GG polymorphism of the IL-6 gene (- 174G/C) and mild asthma was found, while possessing at least one C allele, whether in a homozygous (CC) or heterozygous (CG) combination, independently predicts the likelihood of severe asthma.

Dataset Information

The Role of FeNO in Predicting Asthma.

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The Role of FeNO in Predicting Asthma.

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