Detection of exhaled nitric oxide for predicting the effect of inhaled corticosteroid on chronic obstructive pulmonary disease
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Objective To explore the value of exhaled nitric oxide detection to predicting the effect of inhaled corticosteroid on chronic obstructive pulmonary disease.Methods After eluting without inhaled corticosteroid before the test,31 ex-smokers with severe chronic obstructive pulmonary disease(mean FEV150% of predicted) were administrated fluticasone propionate 500 μg twice a day for 4 weeks,and were measured fraction of exhaled nitric oxide before the test,and pulmonary function before and after the test.Results The baseline fraction of exhaled nitric oxide was not correlated with FEV1 responses after inhaled corticosteroid.Inhaled corticosteroid responders(increased FEV1≥200 mL had significantly higher baseline fraction of exhaled nitric oxide levels compared with non-responders(P=0.028).The AUC for fraction of exhaled nitric oxide to discriminate responders from non-responders had an area under curve of 0.767.Conclusion In ex-smokers with severe chronic obstructive pulmonary disease,fraction of exhaled nitric oxide is a good indicator to predict the effect of inhaled corticosteroid.Keywords:
Fluticasone propionate
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We measured exhaled nitric oxide (NO) with a chemiluminescence method to elucidate the clinical significance of the increased concentration of exhaled NO in patients with bronchial asthma. Exhaled NO was measured in 25 patients with bronchial asthma and in 10 healthy control subjects. The concentration of exhaled NO in asthmatics was significantly higher than in the controls (250.4 +/- 30.4,59.9 +/- 9.6 ppb, respectively, p < 0.01). Symptomatic patients (unstable asthmatics) had a higher exhaled NO concentration than did the asymptomatic patients (stable asthmatics) (384.2 +/- 32.5,143.6 +/- 18.8 ppb, respectively, p < 0.01). The exhaled NO concentration was significantly correlated with the peak expiratory flow rate (r = 0.671, p < 0.01) and eosinophil ratio in induced sputum (r = 0.772, p < 0.05), but it was not correlated with the parameters of bronchial hyperactivity (Dmin and PD35 Grs). We conclude that the increased concentration of exhaled NO in patients with bronchial asthma reflects the state of airway inflammation, and we suggest that the measurement of exhaled NO is a useful, non-invasive and simple method for the management of bronchial asthma.
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Exhaled nitric oxide has been used as a marker of airway inflammation. The NO concentration in the central and peripheral airway/alveolar can be measured by a slow and fast exhalation flow rate to evaluate inflammation in different divisions within the respiratory tract. We hypothesized that FeNO200 (exhaled NO at a flow rate of 200mL/s) could be used as an evaluation tool for peripheral airway/alveolar inflammation and corticosteroid therapy in chronic obstructive pulmonary disease (COPD) patients. We recruited 171 subjects into the study: 73 healthy controls, 59 stable COPD patients, and 39 acute exacerbations of COPD (AECOPD) patients. Exhaled nitric oxide (FeNO50 (exhaled NO at a flow rate of 50mL/s)), FeNO200 and CaNO (peripheral concentration of NO/alveolar NO) and clinical variables including pulmonary function, COPD Assessment Test (CAT), C-reactive protein concentration (CRP) and circulating eosinophil count were measured among the recruited participants. FeNO50, FeNO200 and CaNO were repeatedly evaluated in 39 AECOPD patients after corticosteroid treatment. FeNO200 was significantly higher in stable COPD and AECOPD patients than in healthy controls. Nevertheless, CaNO could not differentiate COPD from healthy controls. No correlation was found between circulating eosinophil counts or FEV1 and exhaled nitric oxide (FeNO50, FeNO200, CaNO) in COPD patients. For AECOPD patients, 64% of patients had eosinophil counts >100 cells/µL; 59% of patients had FeNO200 >10 ppb; only 31% of patients had FeNO50 > 25 ppb. Among AECOPD patients, the high FeNO50 and FeNO200 groups' levels were significantly lower than their baseline levels, and significant improvements in CAT were seen in the two groups after corticosteroid treatment. These implied a good corticosteroid response in AECOPD patients with FeNO200>10ppb. FeNO200 is a straightforward and feasible method to evaluate the peripheral NO concentration in COPD. FeNO200 can be a type 2 inflammation biomarker and a useful tool for predicting corticosteroid therapy in COPD.
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Exhalation
Asthma Exacerbations
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Nitric oxide (NO) may have a role in the pathophysiology of tissue injury in response to inhaled ozone in animals.A double blind, randomised, placebo controlled, crossover study was undertaken to investigate the effects of inhaled ozone in 10 normal and 10 atopic asthmatic volunteers. Subjects were exposed to 200 ppb ozone or clean air for four hours with intermittent exercise, followed by hourly measurement of spirometric parameters and exhaled NO for four hours. Nasal NO and methacholine reactivity were measured and exhaled breath condensate and induced sputum samples were collected four and 24 hours after exposure.Exposure to ozone caused a fall in forced expiratory volume in one second (FEV(1)) of 7% in normal subjects (p<0.05) and 9% in asthmatic subjects (p<0.005). There was a 39% increase in sputum neutrophils at four hours in normal subjects (p<0.05) and a 35% increase at four hours in asthmatic subjects, remaining high at 24 hours (p<0.005 and p<0.05, respectively). There were no differences between normal and asthmatic subjects. There were no changes in methacholine reactivity, exhaled or nasal NO, nitrite levels in exhaled breath condensate, or sputum supernatant concentrations of interleukin 8, tumour necrosis factor alpha, or granulocyte-macrophage colony stimulating factor in either group.Exposure to 200 ppb ozone leads to a neutrophil inflammatory response in normal and asthmatic subjects but no changes in exhaled NO or nitrite levels.
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This study explored the relationship between the fractional exhaled nitric oxide (FeNO) level and the efficacy of inhaled corticosteroid (ICS) in asthma-chronic obstructive pulmonary disease (COPD) overlap syndrome (ACOS) patients with different disease severity. A total of 127 ACOS patients with ACOS (case group) and 131 healthy people (control group) were enrolled in this study. Based on the severity of COPD, the ACOS patients were divided into: mild ACOS; moderate ACOS; severe ACOS; and extremely severe ACOS groups. We compared FeNO levels, pulmonary function parameters including percentage of forced expiratory volume in 1 second (FEV1) to predicted value (FEV1%pred), ratio of FEV1 to forced vital capacity (FEV1/FVC), inspiratory capacity to total lung capacity (IC/TLC) and residual volume to total lung capacity (RV/TLC), arterial blood gas parameters, including PH, arterial partial pressure of oxygen (PaO₂) and arterial partial pressure of carbon dioxide (PaCO₂), total serum immunoglobulin E (IgE), induced sputum eosinophil (EOS), plasma surfactant protein A (SP-A), plasma soluble receptor for advanced glycation end products (sRAGE), sputum myeloperoxidase (MPO), sputum neutrophil gelatinase-associated lipocalin (NGAL) and Asthma Control Test (ACT) scores, and COPD Assessment Test (CAT) scores. Compared with pre-treatment parameters, the FeNO levels, RV/TLC, PaCO₂, total serum IgE, induced sputum EOS, plasma SP-A, sputum MPO, sputum NGAL, and CAT scores were significantly decreased after 6 months of ICS treatment, while FEV1%pred, FEV1/FVC, IC/TLC, PH, PaO2, plasma sRAGE, and ACT scores were significantly increased in ACOS patients with different disease severity after 6 months of ICS treatment. This finding suggests that the FeNO level may accurately predict the efficacy of ICS in the treatment of ACOS patients.
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A subset of patients with chronic obstructive pulmonary disease (COPD) may respond more favorably to inhaled corticosteroids (ICS), but no simple method is currently utilized to predict the presence or absence of ICS responses in patients with COPD.We evaluated the ability of exhaled nitric oxide (FENO) and serum inflammatory markers (C-reactive protein [CRP], interleukin-6 [IL-6], and interleukin-8 [IL-8]) to independently predict spirometric responses to ICS in patients with COPD.Among 60 ex-smokers with severe COPD (mean FEV1 1.07 L, 36% of predicted), we conducted a single-arm, open-label study. Participants spent four weeks free of any ICS, followed by four weeks of ICS use (fluticasone propionate 500 mcg twice daily). FENO, CRP, IL-6, IL-8, and pre-bronchodilator spirometry were measured immediately before and after the four weeks of ICS use.Baseline FENO, CRP, IL-6, and IL-8 showed no correlations to FEV1 responses to ICS. ICS responders (increase in FEV1 > or = 200 mL after four weeks of ICS) did have significantly higher baseline FENO levels compared with non-responders (46.5 parts per billion [ppb] vs. 25 ppb, p = 0.028). The receiver operating characteristic curve for FENO to discriminate responders from non-responders had an area under curve of 0.72. Baseline serum inflammatory markers did not differ between responders and non-responders.In ex-smokers with severe COPD, a measure of local pulmonary inflammation, FENO, may be more closely associated with FEV1 responses to four weeks of ICS than are standard markers of systemic inflammation, serum CRP, IL-6, and IL-8.
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気管支喘息の新しい早期診断法を確立するために, 気管支喘息の患者 (未治療群30名, 吸入ステロイド治療群30名) および健常人 (非喫煙群30名, 喫煙群20名) を対象として, single-deep-breath 法によって, 呼気中の一酸化炭素 (CO) 濃度を測定した. その結果, 未治療の気管支喘息患者では, 5.6 (平均) ±0.6 (標準誤差) ppmと健常人の1.5±0.1ppmに比して有意な上昇を認めた (p<0.001, n=30). また, 気管支喘息患者の呼気中CO濃度は吸入ステロイド剤のベクロメサゾン (800μg/day) の4週間の治療により正常化することが確認され, 疾患の活動性の指標となり得ることが明らかにされた. また, 呼気中のCO濃度は, 喘息患者の喀痰中の好酸球数と正の相関を示すこと, さらに一秒率と逆相関することが明らかにされた. 本法は, 高齢者や比較的重症患者においても, ベットサイドで非侵襲的に施行でき, 今後日常の診療に十分に活用されるものと考えられる.
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Theoretical non-linear modeling of exhaled nitric oxide has revealed extended flow-independent parameters that could explain where or how nitric oxide is produced in the lung and transferred to the airway gas stream. We aimed to evaluate the associations of bronchial hyperresponsiveness and bronchodilator response with extended flow-independent nitric oxide parameters. Nitric oxide (30, 50, 100, 200 ml s-1) was measured in 432 children with asthma on the same day with either a methacholine challenge test (n = 156) or spirometry with bronchodilator (n = 276; 96 previously diagnosed with asthma and treated with inhaled corticosteroid, 37 with acute exacerbation treated with systemic corticosteroid). We additionally included 107 healthy controls for evaluation of the suitability of the non-linear model of exhaled nitric oxide. In asthmatic children, the response-dose ratio of the methacholine challenge test was correlated positively with bronchial nitric oxide (JawNO) and airway tissue nitric oxide (CawNO) (r = 0.367 and r = 0.299, respectively; both p < 0.001), while the change in forced expiratory volume in 1 s, representing bronchodilator response, was associated positively with only JawNO (r = 0. 216, p < 0.001). On multiple regression, JawNO, CawNO, and the diffusing capacity of NO (DawNO) were significantly associated with the response-dose ratio. JawNO was significantly associated with change in forced expiratory volume in children with stable asthma but not those with acute exacerbation. Our findings suggest that bronchial hyperresponsiveness is associated with CawNO while factors other than airway tissue inflammation could affect bronchodilator response in children with mild asthma. Systemic corticosteroid use during asthma exacerbation could affect the association of bronchodilator response with extended nitric oxide parameters.
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Objective To investigate the correlation between exhaled nitric oxide and lung function (FEV1)in asthmatic children.Methods Fifty three stable asthmatic children aged 5 to 14 years old were recruited from ShengJing Hospital of China Medical University.According to whether the patients were treated with inhaled corticosteroid(ICS)therapy regularly,they were divided into two groups:steroid group and non-steroid group,then fraction of exhaled nitric oxide(FeNO)and lung function were measured.Results In non-steroid group,the levels of FeNO(mean 40.450±25.428 part by billion)were significantly higher than those in the steroid group(mean 19.879±13.845 part by billion),and they were statistically significant.(P = 0.003).The mean FEVI in non-steroid group was(95.152±8.993)%,and the mean FEVI in non-steroid group was(91.350±11.690)%,and there were no significant differences between two groups (P =0.189).Significantly negative correlation was found between FeNO and FEV1 in steroid group(r =-0.465,P = 0.039),but there was no significant correlation between them in steroid group(r = 0.058,P =0.747).Conclusion The levels of FeNO were higher in non-steroid group than those of the steroid group in the stable asthmatic children.FeNO is a good biomarker to evaluate the airway inflammation of asthmatic children.
Key words:
Bronchial asthma ; Exhaled nitric oxide ; Lung function ;
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