A new role for exhaled nitric oxide as a functional marker of peripheral airway caliber changes: a theoretical study

Though considered as an inflammation marker, exhaled nitric oxide (FENO) was shown to be sensitive to airway caliber changes to such an extent that it might be considered as a marker of them. It is thus important to understand how these changes and their localization mechanically affect the total NO flux penetrating the airway lumen (JawNO), hence FENO, independently from any inflammatory status change. A new model was used which simulates NO production, consumption and diffusion inside the airway epithelium wall, then, NO excretion through the epithelial wall into the airway lumen and, finally, its axial transport by diffusion and convection in the airway lumen. This model may also consider the presence of a mucus layer coating the epithelial wall. Simulations were performed that showed the great sensitivity of JawNO to peripheral airways caliber changes. Moreover, FENO showed distinct behaviors depending on the location of the caliber change. Considering a bronchodilation, absence of FENO change was associated with dilation of central airways, FENO increase with dilation up to pre-acinar small airways, and FENO decrease with intra-acinar dilation due to amplification of the back-diffusion flux. The presence of a mucus layer was also shown to play a significant role in FENO changes. Altogether, the present work provides theoretical evidences that specific FENO changes in acute situations are linked to specifically located airway caliber changes in the lung periphery. This opens the way for a new role for FENO as a functional marker of peripheral airway caliber change

Exposure to Household Air Pollution from Biomass Cookstoves and Levels of Fractional Exhaled Nitric Oxide (FeNO) among Honduran Women

Household air pollution is estimated to be responsible for nearly three million premature deaths annually. Measuring fractional exhaled nitric oxide (FeNO) may improve the limited understanding of the association of household air pollution and airway inflammation. We evaluated the cross-sectional association of FeNO with exposure to household air pollution (24-h average kitchen and personal fine particulate matter and black carbon; stove type) among 139 women in rural Honduras using traditional stoves or cleaner-burning Justastoves. We additionally evaluated interaction by age. Results were generally consistent with a null association; we did not observe a consistent pattern for interaction by age. Evidence from ambient and household air pollution regarding FeNO is inconsistent, and may be attributable to differing study populations, exposures, and FeNO measurement procedures (e.g., the flow rate used to measure FeNO)

FAKTOR PENYEBAB TERJADINYA TINDAK PIDANA ANAK DAN UPAYA PENYELESAIANNYA

Today, the problems of children in Indonesia are quite diverse and the mostfrightening thing is that children are in conflict with the law. Because based on data fromthe Indonesian Child Protection Commission during 2011-2017 there were 9,266 (ninethousand two hundred and sixty-six) cases. Juvenile delinquency is in the spotlight.The research method used in this study is empirical juridical, the types of datainclude primary data and secondary data. The data collection is done by interview orinterview and documentation. The data analysis was carried out in a qualitativedescriptive manner.In conclusion (1) the factors that cause criminal acts committed by children, namelythe influence of education, talent factors and environmental influences. The types ofcrimes committed include drug abuse, sexual harassment and sexual intercourse. (2) Inthe process of carrying out an investigation into criminal acts by children at the SampangPolice, this is done by making reports, summoning, arresting, detaining, searching,confiscation, examination, post-mortem , settlement and submission of case files. Inaccordance with Law Number 11 of 2012 concerning Juvenile Criminal Justice SystemArticles 26 to 40. (3) Barriers or obstacles experienced by police investigators incarrying out the investigation process of criminal acts committed by children at theSampang Police have limited time in processing files from criminal act. In criminal actsthat require a visa, the relatively expensive visa fee is considered too burdensome for thevictim. Children are also less proficient in speaking and difficult to cooperate, whencalling, children are sometimes unable to attend and sometimes parents cannotaccompany them

Exhaled Nitric Oxide is Not a Biomarker for Pulmonary Tuberculosis.

To reduce transmission of tuberculosis (TB) in resource-limited countries where TB remains a major cause of mortality, novel diagnostic tools are urgently needed. We evaluated the fractional concentration of exhaled nitric oxide (FeNO) as an easily measured, noninvasive potential biomarker for diagnosis and monitoring of treatment response in participants with pulmonary TB including multidrug resistant-TB in Lima, Peru. In a longitudinal study however, we found no differences in baseline median FeNO levels between 38 TB participants and 93 age-matched controls (13 parts per billion [ppb] [interquartile range (IQR) = 8-26] versus 15 ppb [IQR = 12-24]), and there was no change over 60 days of treatment (15 ppb [IQR = 10-19] at day 60). Taking this and previous evidence together, we conclude FeNO is not of value in either the diagnosis of pulmonary TB or as a marker of treatment response

Tailored interventions based on exhaled nitric oxide versus clinical symptoms for asthma in children and adults

BackgroundThe measurement of severity and control of asthma in both children and adults can be based on subjective or objective measures. It has been advocated that fractional exhaled nitric oxide (FeNO) can be used to monitor airway inflammation as it correlates with some markers of asthma. Interventions for asthma therapies have been traditionally based on symptoms and/or spirometry.ObjectivesTo evaluate the efficacy of tailoring asthma interventions based on exhaled nitric oxide in comparison to clinical symptoms (with or without spirometry/peak flow) for asthma related outcomes in children and adults.Search strategyWe searched the Cochrane Airways Group Specialised Register of Trials, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and reference lists of articles. The last search was completed in February 2009.Selection criteriaAll randomised controlled comparisons of adjustment of asthma therapy based on exhaled nitric oxide compared to traditional methods (primarily clinical symptoms and spirometry/peak flow).Data collection and analysisResults of searches were reviewed against pre-determined criteria for inclusion. Relevant studies were independently selected in duplicate. Two authors independently assessed trial quality and extracted data. Authors were contacted for further information with response from one.Main resultsTwo studies have been added for this update, which now includes six (2 adults and 4 children/adolescent) studies; these studies differed in a variety of ways including definition of asthma exacerbations, FeNO cut off levels, the way in which FeNO was used to adjust therapy and duration of study. Of 1053 participants randomised, 1010 completed the trials. In the meta-analysis, there was no significant difference between groups for the primary outcome of asthma exacerbations or for other outcomes (clinical symptoms, FeNO level and spirometry). In post-hoc analysis, a significant reduction in mean final daily dose inhaled corticosteroid per adult was found in the group where treatment was based on FeNO in comparison to clinical symptoms, (mean difference -450 mcg; 95% CI -677 to 223 mcg budesonide equivalent/day). However, the total amount of inhaled corticosteroid used in one of the adult studies was 11% greater in the FeNO arm. In contrast, in the paediatric studies, there was a significant increase in inhaled corticosteroid dose in the FeNO strategy arm (mean difference of 140 mcg; 95% CI 29 to 251, mcg budesonide equivalent/day).Authors' conclusionsTailoring the dose of inhaled corticosteroids based on exhaled nitric oxide in comparison to clinical symptoms was carried out in different ways in the six studies and found only modest benefit at best and potentially higher doses of inhaled corticosteroids in children. The role of utilising exhaled nitric oxide to tailor the dose of inhaled corticosteroids cannot be routinely recommended for clinical practice at this stage and remains uncertain

Safety and Efficacy of Long-Term Co-Administration of Fenofibrate and Ezetimibe in Patients With Mixed Hyperlipidemia

ObjectivesThis study sought to determine the long-term safety and efficacy of co-administered fenofibrate (FENO) and ezetimibe (EZE) in patients with mixed hyperlipidemia.BackgroundBoth EZE and FENO offer complementary benefits to the lipid profile of patients with mixed hyperlipidemia.MethodsAfter completing the 12-week randomized, double-blind base study that compared EZE 10 mg, FENO 160 mg, FENO 160 mg plus EZE 10 mg, and placebo in patients with mixed hyperlipidemia, patients continued into a double-blind, 48-week extension phase. Those patients in the FENO plus EZE and FENO groups continued on their respective base study treatment, and patients in the EZE and placebo groups were switched to FENO plus EZE and FENO, respectively.ResultsOf the 587 patients who completed the base study, 576 continued into the extension study (n = 340 in FENO plus EZE and n = 236 in FENO). The FENO plus EZE produced significantly greater reductions in low-density lipoprotein-cholesterol compared with FENO (−22% vs. −9%, respectively; p < 0.001). There were also significantly greater improvements in triglycerides, high-density lipoprotein cholesterol (HDL-C), total cholesterol, non–HDL-C, and apolipoprotein B with FENO plus EZE compared with FENO. Changes in apolipoprotein A-I and high-sensitivity C-reactive protein were similar between groups. Overall, FENO plus EZE was well tolerated during the extension study. The proportion of patients with consecutive elevations of alanine aminotransferase/aspartate aminotransferase ≥3 times upper limit of normal were similar between the FENO plus EZE (1.2%) and FENO (1.7%) groups. No cases of creatine phosphokinase elevations ≥10 times upper limit of normal or myopathy were observed in either group.ConclusionsLong-term, 48-week co-administration of FENO plus EZE was well tolerated and more efficacious than FENO in patients with mixed hyperlipidemia

Could Fractional Exhaled Nitric Oxide Test be Useful in Predicting Inhaled Corticosteroid Responsiveness in Chronic Cough? A Systematic Review

© 2016 Background Fractional exhaled nitric oxide (FENO) is a safe and convenient test for assessing T H 2 airway inflammation, which is potentially useful in the management of patients with chronic cough. Objective To summarize the current evidence on the diagnostic usefulness of FENO for predicting inhaled corticosteroid (ICS) responsiveness in patients with chronic cough. Methods A systematic literature review was conducted to identify articles published in peer-reviewed journals up to February 2015, without language restriction. We included studies that reported the usefulness of FENO (index test) for predicting ICS responsiveness (reference standard) in patients with chronic cough (target condition). The data were extracted to construct a 2 × 2 accuracy table. Study quality was assessed with Quality Assessment of Diagnostic Accuracy Studies 2. Results We identified 5 original studies (2 prospective and 3 retrospective studies). We identified considerable heterogeneities in study design and outcome definitions, and thus were unable to perform a meta-analysis. The proportion of ICS responders ranged from 44% to 59%. Sensitivity and specificity ranged from 53% to 90%, and from 63% to 97%, respectively. The reported area under the curve ranged from abou t 0.60 to 0.87; however, studies with a prospective design and a lower prevalence of asthma had lower area under the curve values. None measured placebo effects or objective cough frequency. Conclusions We did not find strong evidence to support the use of FENO tests for predicting ICS responsiveness in chronic cough. Further studies need to have a randomized, placebo-controlled design, and should use validated measurement tools for cough. Standardization would facilitate the development of clinical evidence

Daily ambulatory exhaled nitric oxide measurements in asthma

Exhaled NO (FENO) is a non-invasive, validated marker for asthmatic airway inflammation. Recently, a new hand-held NO-analyzer has been developed which makes it possible to monitor FENO at home. We assessed feasibility and analyzed variability of daily FENO home measurements. Twenty-one asthmatics (mean age 14.5 yr; range 8-25 yr) participated. Nineteen used a stable dose of inhaled corticosteroids and all of them were in a stable clinical condition. FENO was measured twice daily for 14 consecutive days. Measurements and symptom scores were recorded on a smart card in the analyzer. Symptom score items included well-being, wheeze, activity, and nocturnal symptoms. Measurements showed a success rate of 93%. We found a significant diurnal variation in FENO with geometric mean morning levels 14% higher than evening levels (95% CI: 4%-25%; p = 0.013). Individual subjects showed marked fluctuation of FENO. The mean intrasubject coefficient of variation of FENO was 40% for morning and 36% for evening values. FENO and cumulative symptom scores did not correlate. Home FENO measurements are feasible, and offer the possibility to asses airway inflammation on a daily basis. Further study is needed to interpret and evaluate possible benefits of FENO home monitoring

Exhaled nitric oxide in a population-based study of Southern California Schoolchildren

<p>Abstract</p> <p>Background</p> <p>Determinants of exhaled nitric oxide (FeNO) need to be understood better to maximize the value of FeNO measurement in clinical practice and research. Our aim was to identify significant predictors of FeNO in an initial cross-sectional survey of southern California schoolchildren, part of a larger longitudinal study of asthma incidence.</p> <p>Methods</p> <p>During one school year, we measured FeNO at 100 ml/sec flow, using a validated offline technique, in 2568 children of age 7–10 yr. We estimated online (50 ml/sec flow) FeNO using a prediction equation from a separate smaller study with adjustment for offline measurement artifacts, and analyzed its relationship to clinical and demographic characteristics.</p> <p>Results</p> <p>FeNO was lognormally distributed with geometric means ranging from 11 ppb in children without atopy or asthma to 16 ppb in children with allergic asthma. Although effects of atopy and asthma were highly significant, ranges of FeNO for children with and without those conditions overlapped substantially. FeNO was significantly higher in subjects aged > 9, compared to younger subjects. Asian-American boys showed significantly higher FeNO than children of all other sex/ethnic groups; Hispanics and African-Americans of both sexes averaged slightly higher than non-Hispanic whites. Increasing height-for-age had no significant effect, but increasing weight-for-height was associated with decreasing FeNO.</p> <p>Conclusion</p> <p>FeNO measured offline is a useful biomarker for airway inflammation in large population-based studies. Further investigation of age, ethnicity, body-size, and genetic influences is needed, since they may contribute to substantial variation in FeNO.</p