• Clinical and Experimental Pediatrics
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• v.56 no.10
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• pp.424-430
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• 2013

Exhaled nitric oxide (NO) has been extensively investigated as a noninvasive marker of airway inflammation in asthma. The increased NO expression induced by inflammatory mediators in airways can be monitored easily in exhaled air from asthmatic children. Based on the relationship between the increased NO expression and eosinophilic airway inflammation, fractional exhaled nitric oxide (FeNO) measurements become an important adjunct for the evaluation of asthma. In addition, the availability of portable devices makes it possible to measure FeNO more easily and frequently in the routine pediatric practice. Despite various confounding factors affecting its levels, FeNO can be applicable in diagnosing asthma, monitoring treatment response, evaluating asthma control, and predicting asthma exacerbations. Thus, although pulmonary function tests are the standard tools for objective measurements of asthmatic control, FeNO can broaden the way of asthma monitoring and supplement standard clinical asthma care guidelines.

• Journal of Environmental Health Sciences
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• v.29 no.3
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• pp.35-42
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• 2003

Nitric Oxide(NO) is produced in many organs of the body, including the lung and airways, and it is detectable in the exhaled air. The measurement of exhaled NO(eNO) provides a simple non-invasive means for measuring airway inflammation, such as asthma. We measured eNO among adult male workers to examine the distribution of eNO in healthy people and to find factors affecting eNO. We measured eNO in a sample of 921 adult workers who also performed lung function test and skin prick test. Exhaled NO was measured in a sitting posture without using a nose clip and NO free gas. NO was measured at three expiratory rates(l8; 42; 71 $m\ell$/sec) and the flow rate of 71 $m\ell$/sec was used in analysis. The average eNO concentration was 5.29 $\pm$ 2.98 ppb. The level increased with age but not significantly(P=0.0529). Exhaled NO showed positive relations to the height(P=0.0001), pollen 1 (P=0.0124), asthma history(P=0.0212), allergic rhinitis symptom(P=0.0302). Exhaled NO Concentration of smokers( 4.62 ppb) was significantly lower than that of nonsmokers(5.99 ppb; P<0.0001).

• Toxicological Research
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• v.26 no.4
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• pp.329-337
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• 2010

Inhaled inorganic dusts, such as coal, can cause inflammation and fibrosis in the lungs, known as pneumoconiosis. Diagnosis of pneumoconiosis depends on morphological changes by radiological findings and functional change by pulmonary function test (PFT). Unfortunately, current diagnostic findings are limited only to lung fibrosis, which is usually irreversibly progressive. Therefore, it is important that research on potential and prospective biomarkers for pneumoconiosis should be conducted prior to initiation of irreversible radiological or functional changes in the lungs. Analytical techniques using exhaled breath condensate (EBC) or exhaled gas are non-invasive methods for detection of various respiratory diseases. The objective of this study is to investigate the relationship between inflammatory biomarkers, such as EBC pH or fractional exhaled nitric oxide ($FE_{NO}$), and pneumoconiosis among 120 retired coal miners (41 controls and 79 pneumoconiosis patients). Levels of EBC pH and FENO did not show a statistically significant difference between the pneumoconiosis patient group and pneumoconiosis patients with small opacity classified by International Labor Organization (ILO) classification. The mean concentration of $FE_{NO}$ in the low percentage $FEV_1$ (< 80%) was lower than that in the high percentage (80% $\leq$) (p = 0.023). The mean concentration of $FE_{NO}$ in current smokers was lower than that in non smokers (never or past smokers) (p = 0.027). Although there was no statistical significance, the levels of $FE_{NO}$ in smokers tended to decrease, compared with non smokers, regardless of pneumoconiosis. In conclusion, there was no significant relationship between the level of EBC pH or $FE_{NO}$ and radiological findings or PFT. The effects between exhaled biomarkers and pneumoconiosis progression, such as decreasing PFT and exacerbation of radiological findings, should be monitored.

• Clinical and Experimental Pediatrics
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• v.57 no.5
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• pp.211-216
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• 2014

Asthma comprises a heterogeneous group of disorders characterized by airway inflammation, airway obstruction, and airway hyperresponsiveness (AHR). Airway inflammation, which induces AHR and recurrence of asthma, is the main pathophysiology of asthma. The fractional exhaled nitric oxide (FeNO) level is a noninvasive, reproducible measurement of eosinophilic airway inflammation that is easy to perform in young children. As airway inflammation precedes asthma attacks and airway obstruction, elevated FeNO levels may be useful as predictive markers for risk of recurrence of asthma. This review discusses FeNO measurements among early-childhood wheezing phenotypes that have been identified in large-scale longitudinal studies. These wheezing phenotypes are classified into three to six categories based on the onset and persistence of wheezing from birth to later childhood. Each phenotype has characteristic findings for atopic sensitization, lung function, AHR, or FeNO. For example, in one birth cohort study, children with asthma and persistent wheezing at 7 years had higher FeNO levels at 4 years compared to children without wheezing, which suggested that FeNO could be a predictive marker for later development of asthma. Preschool-aged children with recurrent wheezing and stringent asthma predictive indices also had higher FeNO levels in the first 4 years of life compared to children with wheezing and loose indices or children with no wheeze, suggesting that FeNO measurements may provide an additional parameter for predicting persistent wheezing in preschool children. Additional large-scale longitudinal studies are required to establish cutoff levels for FeNO as a risk factor for persistent asthma.

• Tuberculosis and Respiratory Diseases
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• v.85 no.4
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• pp.283-288
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• 2022

Asthma is a chronic inflammatory disease of the airways characterized by varying and recurrent symptoms, reversible airway obstruction, and bronchospasm. In this paper, clinical important studies on asthma published between March 2021 and February 2022 were reviewed. A study on the relationship between asthma and chronic rhinosinusitis, bronchiectasis, and hormone replacement therapy was published. A journal on the usefulness of fractional exhaled nitric oxide for the prediction of severe acute exacerbation was also introduced. Studies on the effect of inhaler, one of the most important treatments for asthma, were published. Studies on the control of severe asthma continued. Phase 2 and 3 studies of new biologics were also published. As the coronavirus disease 2019 (COVID-19) pandemic has been prolonged, many studies have explored the prevalence and mortality of COVID-19 infection in asthma patients.

• Clinical and Experimental Pediatrics
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• v.60 no.9
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• pp.290-295
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• 2017

Purpose: Airway pathology in children with atopic asthma can be reflected by the concave shape of the maximal expiratory flow-volume (MEFV) curve and high fractional exhaled nitric oxide (FeNO) values. We evaluated the capacity of the curvilinearity of the MEFV curve, FeNO, and their combination to distinguish subjects with atopic asthma from healthy individuals. Methods: FeNO and angle ${\beta}$, which characterizes the general configuration of the MEFV curve, were determined in 119 steroid-naïve individuals with atopic asthma aged 8 to 16 years, and in 92 age-matched healthy controls. Receiver operating characteristic (ROC) curve analyses were performed to determine the cutoff points of FeNO and angle ${\beta}$ that provided the best combination of sensitivity and specificity for asthma detection. Results: Asthmatic patients had a significantly smaller angle ${\beta}$ and higher FeNO compared with healthy controls (both, P<0.001). For asthma detection, the best cutoff values of angle ${\beta}$ and FeNO were observed at $189.3^{\circ}$ and 22 parts per billion, respectively. The area under the ROC curve for the combination of angle ${\beta}$ and FeNO improved to 0.91 (95% confidence interval [CI], 0.87-0.95) from 0.80 (95% CI, 0.75-0.86; P<0.001) for angle ${\beta}$ alone and 0.86 (95% CI, 0.82-0.91; P=0.002) for FeNO alone. In addition, the combination enhanced sensitivity with no significant decrease in specificity. Conclusion: These data suggest that the combined use of the curvilinearity of the MEFV curve and FeNO is a useful tool to differentiate between children with and without atopic asthma.

• Clinical and Experimental Pediatrics
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• v.55 no.9
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• pp.330-336
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• 2012

Purpose: Fractional exhaled nitric oxide (FeNO) and forced expiratory flow between 25% and 75% of vital capacity ($FEF_{25-75}$) are not included in routine monitoring of asthma control. We observed changes in FeNO level and $FEF_{25-75}$ after FeNO-based treatment with inhaled corticosteroid (ICS) in children with controlled asthma (CA). Methods: We recruited 148 children with asthma (age, 8 to 16 years) who had maintained asthma control and normal forced expiratory volume in the first second ($FEV_1$) without control medication for ${\geq}3$ months. Patients with FeNO levels >25 ppb were allocated to the ICS-treated (FeNO-based management) or untreated group (guideline-based management). Changes in spirometric values and FeNO levels from baseline were evaluated after 6 weeks. Results: Ninety-three patients had FeNO levels >25 ppb. These patients had lower $FEF_{25-75}$ % predicted values than those with FeNO levels ${\leq}25$ ppb (P<0.01). After 6 weeks, the geometric mean (GM) FeNO level in the ICS-treated group was 45% lower than the baseline value, and the mean percent increase in $FEF_{25-75}$ was 18.7% which was greater than that in other spirometric values. There was a negative correlation between percent changes in $FEF_{25-75}$ and FeNO (r=-0.368, P=0.001). In contrast, the GM FeNO and spirometric values were not significantly different from the baseline values in the untreated group. Conclusion: The anti-inflammatory treatment simultaneously improved the FeNO levels and $FEF_{25-75}$ in CA patients when their FeNO levels were >25 ppb.

• Clinical and Experimental Pediatrics
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• v.58 no.3
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• pp.89-95
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• 2015

Purpose: House dust mite (HDM) has been suggested to be the most important aeroallergen responsible for atopic asthma in Korea. We aimed to investigate that specific IgE antibodies to HDM and other common indoor aeroallergens contribute differently to total serum IgE and show different relationships with longitudinal fractional exhaled nitric oxide (FeNO) measurements in Korean atopic asthmatic patients. Methods: A total of 193 children aged 8 to 16 years with intermittent or mild persistent atopic asthma were recruited. Sera were assayed for total IgE and specific IgE antibodies to HDM and other common indoor allergens. FeNO was serially measured 10 times or more over 2 years when subjects were not receiving controller medications. Results: In 152 children who completed the study, IgE antibodies to specific HDM were more prevalent than those to other common indoor aeroallergens. In addition, IgE antibody titers to HDM were the strongest contributor to total IgE increases. Furthermore, only HDM-specific IgE antibody titer significantly correlated with maximum FeNO (r=0.21, P=0.029) and the rate of FeNO higher than 21 parts per billion (ppb) (r=0.30, P=0.002). Eight patients (5%) were found to have maximum FeNO of 21 ppb or less, suggesting the presence of a low FeNO phenotype among atopic asthmatic patients. Conclusion: The quantity of HDM-specific IgE antibody provides a possible explanation for increases of total IgE and significantly correlates with the amount and frequency of FeNO increases in Korean atopic asthmatic patients.

• Tuberculosis and Respiratory Diseases
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• v.42 no.4
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• pp.447-454
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• 1995

Cytokine release from alveolar macrophages and subsequent interaction of these cytokines with the bronchial epithelium can induce epithelial cells to release inflammatory mediators. Nitric oxide(NO), a highly reactive gas formed from arginine by nitric oxide synthase(NOS), is known to be involved in inflammation and edema formation, and the inducible form of NOS(iNOS) can be increased by cytokines. In this context, we hypothesized that lung epithelial cells could be stimulated by cytokines released by alveolar macrophages to express iNOS. To test this hypothesis, the murine lung epithelial cell line, LA-4, or the human lung epithelial cell line, A549, were stimulated with culture supernatant fluids from alveolar macrophages. NO production was assessed by evaluating the culture supernatant fluids for nitrite and nitrate, the stable end products of NO. Both murine and human cell culture supernatant fluids demonstrated an increase in nitrite and nitrate which were time- and dose-dependent and attenuated by $TNF{\alpha}$ and IL-$1{\beta}$ antibodies(p<0.05, all comparisons). Consistent with these observations, cytomix a combination of $TNF{\alpha}$, IL-$1{\beta}$, and $\gamma$-interferon, stimulated the lung epithelial cell lines as well as primary cultures of human bronchial epithelial cells to increase their NO production as evidenced by an increase in nitrite and nitrate in their culture supernatant fluids, an increase in the iNOS staining by immunocytochemistry, and an increase in iNOS mRNA by Northern blottin(p<0.05, all comparisons). The cytokine effects on iNOS were all attenuated by dexamethasone. To determine if these in vitro observations are reflected in vivo, exhaled NO was measured and found to be increased in asthmatics not receiving corticosteroids. These data demonstrate that alveolar macrophage derived cytokines increase iNOS expression in lung epithelial cells and that these in vitro observations are mirrored by increased exhaled NO levels in asthmatics. Increased NO in the lung may contribute to edema formation and airway narrowing.

• Tuberculosis and Respiratory Diseases
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• v.84 no.3
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• pp.182-187
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• 2021

Background: Fractional exhaled nitric oxide (FeNO) is a non-invasive marker for eosinophilic airway inflammation and a good predictor of response to corticosteroids. There is a need for a reliable and accurate measurement method, as FeNO measurements have been widely used in clinical practice. Our study aimed to compare two FeNO analyzers and derive a conversion equation for FeNO measurements in adults. Methods: We included 99 participants who had chief complaints of chronic cough and difficulty in breathing. The participants underwent concurrent FeNO measurement using NIOX VERO (Circassia AB) and NObreath (Bedfont). We compared the values of the two devices and analyzed their correlation and agreement. We then formulated an equation to convert FeNO values measured by NObreath into those obtained by NIOX VERO. Results: The mean age of the participants was 51.2±17.1 years, with a female predominance (58.6%). Approximately 60% of the participants had asthma. The FeNO level measured by NIOX VERO (median, 27; interquartile range [IQR], 15-45) was significantly lower than that measured by NObreath (median, 38; IQR, 22-58; p<0.001). There was a strong positive correlation between the two devices (r=0.779, p<0.001). Additionally, Bland-Altman plots and intraclass correlation coefficient demonstrated a good agreement. Using linear regression, we derived the following conversion equation: natural log (Ln) (NObreath)=0.728×Ln (NIOX VERO)+1.244. Conclusion: The FeNO values of NIOX VERO and NObreath were in good agreement and had positive correlations. Our proposed conversion equation could help assess the accuracy of the two analyzers.