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1.
BMC Pulm Med ; 24(1): 270, 2024 Jun 06.
Article En | MEDLINE | ID: mdl-38844887

INTRODUCTION: The evaluation of the asthmatic patient is usually based on clinical and functional parameters that do not necessarily evidence the degree of airway inflammation. The aim of this study was to analyze whether clinical scores (CS) correlate with spirometry (S), impulse oscillometry (IO) and FeNO, in severe asthmatic children. MATERIAL AND METHODS: A multicentric, prospective, cross-sectional study was conducted over a 12-month period. All SA patients (6-18 years old) followed-up in the Pulmonology Department were recruited. CS, FeNO measurements, IO and S were consecutively performed on the same day. Asthma control was ascertained using ACT and GINAq. A cut-off value of ≥ 25 parts per billion (ppb) was used to define airway inflammation. RESULTS: Eighty-one patients were included. ACT: 75% (n 61) were controlled; GINAq: 44.5% (n 36) were controlled; 39.5% (n 32) were partly controlled, and 16% (n 13) were uncontrolled. FeNO had a median value of 24 ppb (IQR 14-41); FeNO ≥ 25 ppb was observed in 49% of patients (n 39). ROC AUC for FeNO vs. ACT was 0.71 (95%CI 0.57-0.86), PPV 0.47, NPV 0.87, SE 0.61, SP 0.80; FeNO vs. GINAq was ROC AUC 0.69 (95%CI 0.54-0.85), PPV 0.34, NPV 0.91, SE 0.62, SP 0.77; Youden cut-off FeNO > 39 ppb for both CS. CONCLUSION: In severe asthmatic children, current symptoms control as evidenced by ACT and GINA correlates with low FeNO values. Clinical scores showed good correlation with airway inflammation.


Asthma , Nitric Oxide , Oscillometry , Severity of Illness Index , Spirometry , Humans , Asthma/diagnosis , Asthma/physiopathology , Child , Female , Male , Oscillometry/methods , Cross-Sectional Studies , Prospective Studies , Adolescent , Nitric Oxide/analysis , Nitric Oxide/metabolism , ROC Curve
2.
BMC Pulm Med ; 24(1): 272, 2024 Jun 06.
Article En | MEDLINE | ID: mdl-38844929

BACKGROUND AND AIM: There are few long-term studies of respiratory health effects of landscape fires, despite increasing frequency and intensity due to climate change. We investigated the association between exposure to coal mine fire PM2.5 and fractional exhaled nitric oxide (FeNO) concentration 7.5 years later. METHODS: Adult residents of Morwell, who were exposed to the 2014 Hazelwood mine fire over 6 weeks, and unexposed residents of Sale, participated in the Hazelwood Health Study Respiratory Stream in 2021, including measurements of FeNO concentration, a marker of eosinophilic airway inflammation. Individual exposure to coal mine fire PM2.5 was modelled and mapped to time-location diaries. The effect of exposure to PM2.5 on log-transformed FeNO in exhaled breath was investigated using multivariate linear regression models in the entire sample and stratified by potentially vulnerable subgroups. RESULTS: A total of 326 adults (mean age: 57 years) had FeNO measured. The median FeNO level (interquartile range [IQR]) was 17.5 [15.0] ppb, and individual daily exposure to coal mine fire PM2.5 was 7.2 [13.8] µg/m3. We did not identify evidence of association between coal mine fire PM2.5 exposure and FeNO in the general adult sample, nor in various potentially vulnerable subgroups. The point estimates were consistently close to zero in the total sample and subgroups. CONCLUSION: Despite previous short-term impacts on FeNO and respiratory health outcomes in the medium term, we found no evidence that PM2.5 from the Hazelwood coal mine fire was associated with any long-term impact on eosinophilic airway inflammation measured by FeNO levels.


Coal Mining , Nitric Oxide , Particulate Matter , Humans , Male , Particulate Matter/analysis , Particulate Matter/adverse effects , Female , Middle Aged , Nitric Oxide/analysis , Nitric Oxide/metabolism , Aged , Adult , Fires , Environmental Exposure/adverse effects , Breath Tests , Linear Models , Exhalation , Air Pollutants/analysis , Air Pollutants/adverse effects
3.
BMC Pulm Med ; 24(1): 214, 2024 May 02.
Article En | MEDLINE | ID: mdl-38698432

BACKGROUND: In western Yokohama, our hospital and primary care clinics manage adults with asthma via a coordinated care system. We investigated the changes in the fractional expired nitric oxide (FeNO), forced expiratory volume in 1 second (FEV1), and forced oscillation technique (FOT) parameters over 3 years in a cohort of patients in our collaborative system. METHODS: From 288 adults with well controlled asthma managed under the Yokohama Seibu Hospital coordinated care system between January 2009 and May 2018, we selected 99 subjects to undergo spirometry, FeNO and FOT testing over 3 years and analyzed the changes in these parameters. RESULTS: Of the 99 patients enrolled, 17 (17.2%) experienced at least one exacerbation (insufficiently controlled (IC)), whereas, 82 (82.8%) remained in well controlled during the 3-year study period. Of well-controlled patients, 54 patients (54.5%) met the criteria for clinical remission under treatment (CR); the remaining 28 patients did not meet the CR criteria (WC). There were no differences in FeNO, FEV1, or FOT parameters at baseline among the IC, WC, and CR groups. The levels of FEV1 decreased gradually, whereas the levels of FeNO decreased significantly over 3 years. The levels of percent predicted FEV1 (%FEV1) significantly increased. We also observed significant improvement in FOT parameters; reactance at 5 Hz (R5), resonant frequency (Fres), and integral of reactance up to the resonant frequency (AX). The CR group demonstrated significant relationships between the change in FeNO and the change in FEV1 and between the change in FEV1 and the change in FOT parameters. No significant correlations emerged in the IC or WC group. CONCLUSION: The decrease in FeNO and increase in %FEV1, we observed in all study participants suggest that the coordinated care system model benefits patients with asthma. Although it is difficult to predict at baseline which patients will experience an exacerbation, monitoring changes in FeNO and FEV1 is useful in managing patients with asthma. Furthermore, monitoring changes in R5, Fres, and AX via forced oscillation technique testing is useful for detecting airflow limitation.


Asthma , Spirometry , Humans , Male , Female , Asthma/physiopathology , Asthma/therapy , Asthma/diagnosis , Forced Expiratory Volume , Middle Aged , Adult , Nitric Oxide/analysis , Nitric Oxide/metabolism , Aged , Fractional Exhaled Nitric Oxide Testing
4.
Biosens Bioelectron ; 258: 116344, 2024 Aug 15.
Article En | MEDLINE | ID: mdl-38696967

Autophagy is an essential degradative process that governs the renewal of organelle and maintains the homeostasis of cellular microenvironment. Its dysregulation has been demonstrated to be an indicator for neuroinflammation. To elucidate the interrelationship between neuroinflammation and autophagy, optical probes are ideal tools as they offer a number of advantages such as high spatiotemporal resolution and non-invasive sensing, which help to visualize the physiological and pathological functions of interested analytes. However, single autophagy parameter-response probes may generate false-positive results since they cannot distinguish between neuroinflammation and other autophagic stimuli. In contrast, chemosensors that respond to two (or more) targets can improve selectivity by qualifying response conditions. Herein, a "dual-key-and-lock" strategy was applied to construct probe (Vis-NO) to selectively recognize autophagy under inflammation out of other stimuli. The red fluorescence of Vis-NO was lit up only in the simultaneously presence of high viscosity and nitric oxide (NO) in lysosome. Due to the characteristics of high viscosity and overexpressed NO within lysosomes, Vis-NO could be used to selectively identify autophagy during neuroinflammation, providing expanding insights into the interrelationship between autophagy, neuroinflammation and stroke in pathology, and informing about the mechanisms through which autophagy regulates inflammation.


Autophagy , Biosensing Techniques , Neuroinflammatory Diseases , Nitric Oxide , Biosensing Techniques/methods , Biosensing Techniques/instrumentation , Animals , Neuroinflammatory Diseases/pathology , Nitric Oxide/metabolism , Nitric Oxide/analysis , Humans , Lysosomes/metabolism , Mice , Inflammation , Fluorescent Dyes/chemistry
5.
Anal Chem ; 96(19): 7763-7771, 2024 May 14.
Article En | MEDLINE | ID: mdl-38699865

Given its pivotal role in modulating various pathological processes, precise measurement of nitric oxide (●NO) levels in physiological solutions is imperative. The key techniques include the ozone-based chemiluminescence (CL) reactions, amperometric ●NO sensing, and Griess assay, each with its advantages and drawbacks. In this study, a hemin/H2O2/luminol CL reaction was employed for accurately detecting ●NO in diverse solutions. We investigated how the luminescence kinetics was influenced by ●NO from two donors, nitrite and peroxynitrite, while also assessing the impact of culture medium components and reactive species quenchers. Furthermore, we experimentally and theoretically explored the mechanism of hemin oxidation responsible for the initiation of light generation. Although both hemin and ●NO enhanced the H2O2/luminol-based luminescence reactions with distinct kinetics, hemin's interference with ●NO/peroxynitrite- modulated their individual effects. Leveraging the propagated signal due to hemin, the ●NO levels in solution were estimated, observing parallel changes to those detected via amperometric detection in response to varying concentrations of the ●NO-donor. The examined reactions aid in comprehending the mechanism of ●NO/hemin/H2O2/luminol interactions and how these can be used for detecting ●NO in solution with minimal sample size demands. Moreover, the selectivity across different solutions can be improved by incorporating certain quenchers for reactive species into the reaction.


Hemin , Hydrogen Peroxide , Nitric Oxide , Hemin/chemistry , Nitric Oxide/analysis , Hydrogen Peroxide/chemistry , Hydrogen Peroxide/analysis , Molecular Probes/chemistry , Luminol/chemistry , Solutions , Luminescent Measurements , Peroxynitrous Acid/analysis , Peroxynitrous Acid/chemistry , Kinetics , Oxidation-Reduction
6.
Lung ; 202(3): 275-280, 2024 Jun.
Article En | MEDLINE | ID: mdl-38733542

This study aimed to investigate the effects of high-dose inhaled corticosteroids (ICS) on chronic cough patients with elevated fractional exhaled nitric oxide (FeNO) levels. In a prospective study, adults with chronic cough and FeNO ≥ 25 ppb, without any other apparent etiology, received fluticasone furoate (200 mcg) for three weeks. Outcomes were evaluated using FeNO levels, cough severity, and Leicester Cough Questionnaire (LCQ) before and after treatment. Of the fifty participants (average age: 58.4 years; 58% female), the treatment responder rate (≥ 1.3-point increase in LCQ) was 68%, with a significant improvement in cough and LCQ scores and FeNO levels post-treatment. However, improvements in cough did not significantly correlate with changes in FeNO levels. These findings support the guideline recommendations for a short-term ICS trial in adults with chronic cough and elevated FeNO levels, but the lack of correlations between FeNO levels and cough raises questions about their direct mechanistic link.


Cough , Nitric Oxide , Humans , Cough/drug therapy , Female , Middle Aged , Male , Prospective Studies , Administration, Inhalation , Chronic Disease , Nitric Oxide/metabolism , Nitric Oxide/analysis , Aged , Treatment Outcome , Fractional Exhaled Nitric Oxide Testing , Androstadienes/administration & dosage , Adult , Severity of Illness Index , Surveys and Questionnaires , Exhalation , Adrenal Cortex Hormones/administration & dosage , Chronic Cough
7.
Anal Chem ; 96(19): 7479-7486, 2024 May 14.
Article En | MEDLINE | ID: mdl-38689560

In the pathogenesis of microglia, brain immune cells promote nitrergic stress by overproducing nitric oxide (NO), leading to neuroinflammation. Furthermore, NO has been linked to COVID-19 progression, which has caused significant morbidity and mortality. SARS-CoV-2 infection activates inflammation by releasing excess NO and causing cell death in human microglial clone 3 (HMC3). In addition, NO regulates lysosomal functions and complex machinery to neutralize pathogens through phagocytosis. Therefore, developing lysosome-specific NO probes to monitor phagocytosis in microglia during the COVID-19 infection would be a significant study. Herein, a unique synthetic strategy was adopted to develop a NO selective fluorescent probe, PDM-NO, which can discriminate activated microglia from their resting state. The nonfluorescent PDM-NO exhibits a turn-on response toward NO only at lysosomal pH (4.5-5.5). Quantum chemical calculations (DFT/TD-DFT/PCM) and photophysical study revealed that the photoinduced electron transfer (PET) process is pivotal in tuning optical properties. PDM-NO demonstrated good biocompatibility and lysosomal specificity in activated HMC3 cells. Moreover, it can effectively map the dynamics of lysosomal NO against SARS-CoV-2 RNA-induced neuroinflammation in HMC3. Thus, PDM-NO is a potential fluorescent marker for detecting RNA virus infection and monitoring phagocytosis in HMC3.


COVID-19 , Fluorescent Dyes , Lysosomes , Microglia , Nitric Oxide , Phagocytosis , SARS-CoV-2 , Microglia/virology , Microglia/metabolism , SARS-CoV-2/isolation & purification , Humans , Lysosomes/metabolism , Nitric Oxide/metabolism , Nitric Oxide/analysis , COVID-19/virology , COVID-19/diagnosis , COVID-19/metabolism , Fluorescent Dyes/chemistry , RNA, Viral/analysis , RNA, Viral/metabolism , Neuroinflammatory Diseases , Cell Line , Phenotype
8.
Clinics (Sao Paulo) ; 79: 100384, 2024.
Article En | MEDLINE | ID: mdl-38754226

OBJECTIVE: This article focused on the correlation between the changes of serum total Immunoglobulin E (IgE) and Fractional exhaled Nitric Oxide (FeNO) and idiosyncratic reactions in children with bronchiolitis. METHODS: One hundred children with bronchiolitis and fifty healthy children were enrolled. Serum total IgE and FeNO were assessed, and the diagnostic value for bronchiolitis and the correlation with the severity of bronchiolitis were analyzed. Bronchiolitis children were divided into idiosyncratic + bronchiolitis and non-idiosyncratic + bronchiolitis groups, the relationship between serum total IgE and FeNO and idiosyncratic reaction was determined, and the diagnostic value of serum total IgE and FeNO for idiosyncratic bronchiolitis was examined. RESULTS: FeNO in bronchiolitis children was lower than that in healthy children but there was no significant difference in serum total IgE levels between the two populations. Serum total IgE increased while FeNO decreased with the aggravation of bronchiolitis in bronchiolitis children. The serum total IgE was positively correlated while FeNO was negatively correlated with the severity of bronchiolitis. Serum total IgE was higher in children with idiosyncratic bronchiolitis, but serum total IgE and FeNO were not the risk factors for idiosyncratic bronchiolitis; Area Under the Curve (AUC) of serum total IgE and FeNO for the diagnosis of idiosyncratic bronchiolitis was less than 0.7. CONCLUSION: Serum total IgE and FeNO in children with bronchiolitis are related to disease severity and idiosyncratic reaction. FeNO has a diagnostic value for bronchiolitis, but not for idiosyncratic bronchiolitis.


Bronchiolitis , Immunoglobulin E , Nitric Oxide , Severity of Illness Index , Humans , Immunoglobulin E/blood , Bronchiolitis/blood , Bronchiolitis/immunology , Female , Male , Infant , Nitric Oxide/analysis , Nitric Oxide/blood , Case-Control Studies , Child, Preschool , Fractional Exhaled Nitric Oxide Testing , Biomarkers/blood , Biomarkers/analysis , Reference Values , Statistics, Nonparametric
9.
Anal Chem ; 96(21): 8689-8695, 2024 May 28.
Article En | MEDLINE | ID: mdl-38748889

Tumor microenvironment-responsive phototheranostic agents are highly sought after for their ability to improve diagnostic accuracy and treatment specificity. Here, we introduce a novel single-molecule probe, POZ-NO, which is activated by nitric oxide (NO) and weak acidity, enabling dual-mode imaging and photothermal therapy (PTT) of tumors. In acidic environments with elevated NO levels, POZ-NO exhibits a distinctive ratiometric fluorescence signal shift from the red to near-infrared, accompanied by a 700 nm photoacoustic signal. Additionally, POZ-NO demonstrated potent photothermal effects upon NO and acidity activation, achieving an impressive conversion efficiency of 74.3% under 735 nm laser irradiation. In vivo studies confirm POZ-NO's ability to accurately image tumors through ratiometric fluorescence and photoacoustic modes while selectively treating tumors with PTT.


Nitric Oxide , Photoacoustic Techniques , Photothermal Therapy , Tumor Microenvironment , Nitric Oxide/analysis , Nitric Oxide/metabolism , Nitric Oxide/chemistry , Animals , Humans , Mice , Optical Imaging , Hydrogen-Ion Concentration , Theranostic Nanomedicine , Mice, Inbred BALB C , Female , Fluorescent Dyes/chemistry , Fluorescence
10.
Bioorg Chem ; 148: 107476, 2024 Jul.
Article En | MEDLINE | ID: mdl-38788368

Depression is a debilitating mental illness that poses a serious threat to human health. Nitric Oxide (NO), as an important gasotransmitter, is closely associated with the pathogenesis of depressive disorders. Effective monitoring of NO fluctuation is beneficial for the diagnosis of depression and therapy assessment of antidepressants. Currently, there is a lack of effective methods for rapidly and sensitively identifying NO and elucidating its relationship with depression diseases. Herein, we developed a NIR dye TJ730-based fluorescent probe TJ730-Golgi-NO incorporating benzenesulfonamide as a Golgi-targeted moiety and the thiosemicarbazide group for NO detection. The probe exhibited turn-on fluorescence ability and a large Stokes shift of 158 nm, which shows high sensitivity, selectivity, and rapid response (<1 min) for NO detection. TJ730-Golgi-NO could detect exogenous and endogenous NO in cells stimulated by Glu and LPS, and target Golgi apparatus. Moreover, we disclose a significant increase of NO in the depression model and a weak fluorescence evidenced in the fluoxetine-treated depression mice. This study provides a competent tool for studying the function of NO and helping improve the effective treatment of depression diseases.


Depression , Fluorescent Dyes , Golgi Apparatus , Nitric Oxide , Fluorescent Dyes/chemistry , Fluorescent Dyes/chemical synthesis , Fluorescent Dyes/pharmacology , Animals , Nitric Oxide/metabolism , Nitric Oxide/analysis , Mice , Golgi Apparatus/metabolism , Depression/drug therapy , Molecular Structure , Humans , Disease Models, Animal , Male , Structure-Activity Relationship , Infrared Rays , Dose-Response Relationship, Drug , Optical Imaging , RAW 264.7 Cells
11.
Environ Int ; 188: 108759, 2024 Jun.
Article En | MEDLINE | ID: mdl-38788415

Aviation has been shown to cause high particle number concentrations (PNC) in areas surrounding major airports. Particle size distribution and composition differ from motorized traffic. The objective was to study short-term effects of aviation-related UFP on respiratory health in children. In 2017-2018 a study was conducted in a school panel of 7-11 year old children (n = 161) living North and South of Schiphol Airport. Weekly supervised spirometry and exhaled nitric oxide (eNO) measurements were executed. The school panel, and an additional group of asthmatic children (n = 19), performed daily spirometry tests at home and recorded respiratory symptoms. Hourly concentrations of various size fractions of PNC and black carbon (BC) were measured at three school yards. Concentrations of aviation-related particles were estimated at the residential addresses using a dispersion model. Linear and logistic mixed models were used to investigate associations between daily air pollutant concentrations and respiratory health. PNC20, a proxy for aviation-related UFP, was virtually uncorrelated with BC and PNC50-100 (reflecting primarily motorized traffic), supporting the feasibility of separating PNC from aviation and other combustion sources. No consistent associations were found between various pollutants and supervised spirometry and eNO. Major air pollutants were significantly associated with an increase in various respiratory symptoms. Odds Ratios for previous day PNC20 per 3,598pt/cm3 were 1.13 (95%CI 1.02; 1.24) for bronchodilator use and 1.14 (95%CI 1.03; 1.26) for wheeze. Modelled aviation-related UFP at the residential addresses was also positively associated with these symptoms, corroborating the PNC20 findings. PNC20 was not associated with daily lung function, but PNC50-100 and BC were negatively associated with FEV1. PNC of different sizes indicative of aviation and other combustion sources were independently associated with an increase of respiratory symptoms and bronchodilator use in children living near a major airport. No consistent associations between aviation-related UFP with lung function was observed.


Air Pollutants , Particulate Matter , Humans , Child , Particulate Matter/analysis , Air Pollutants/analysis , Male , Female , Particle Size , Aviation , Vehicle Emissions/analysis , Spirometry , Nitric Oxide/analysis , Air Pollution/statistics & numerical data , Asthma , Environmental Exposure , Environmental Monitoring
12.
J Mol Model ; 30(6): 166, 2024 May 14.
Article En | MEDLINE | ID: mdl-38744728

CONTEXT: Coronavirus (COVID-19) is a novel respiratory viral infection, causing a relatively large number of deaths especially in people who underly lung diseases such as chronic obstructive pulmonary and asthma, and humans are still suffering from the limited testing capacity. In this article, a solution is proposed for the detection of COVID-19 viral infections through the analysis of exhaled breath gasses, i.e., nitric oxide, a prominent biomarker released by respiratory epithelial, as a non-invasive and time-saving approach. Here, we designed a novel and low-cost N and P co-doped C60 fullerene-based breathalyzer for the detection of NO gas exhaled from the respiratory epithelial cells. This breathalyzer shows a quick response to the detection of NO gas by directly converting NO to NO2 without passing any energy barrier (0 kcal/mol activation energy). The recovery time of breathalyzer is very short (0.98 × 103 s), whereas it is highly selective for NO sensing in the mixture of CO2 and H2O gasses. The study provides an idea for the synthesis of low-cost (compared to previously reported Au atom decorated nanostructure and metal-based breathalyzer), efficient, and highly selective N and P co-doped C60 fullerene-based breathalyzer for COVID-19 detection. METHODS: The geometries of N and P-doped systems and gas molecules are simulated using spin-polarized density functional theory calculations.


Biomarkers , COVID-19 , Fullerenes , Nitric Oxide , Fullerenes/chemistry , Humans , Nitric Oxide/analysis , Nitric Oxide/chemistry , COVID-19/virology , COVID-19/diagnosis , Breath Tests/methods , SARS-CoV-2
13.
BMC Pulm Med ; 24(1): 244, 2024 May 17.
Article En | MEDLINE | ID: mdl-38760654

BACKGROUND: Whether asthma patients could benefit from home monitoring for fractional exhaled nitric oxide (flow of 50 mL/s, FeNO50) is unknown. We explore the application value of home monitoring FeNO50 in daily asthma management. METHODS: Twenty-two untreated, uncontrolled asthma patients were selected. Medical history, blood and sputum samples, pulmonary function, Asthma Control Test (ACT), and other clinical data of the subjects were collected. All subjects underwent daily monitoring for four weeks using a FeNO50 monitor and mobile spirometry (mSpirometry). The diurnal differences and dynamic changes were described. Compare the effect-acting time and the relative plateau of treatment between FeNO50 and mSpirometry monitoring. RESULTS: In the first two weeks, the morning median (IQR) level of FeNO50 was 44 (35, 56) ppb, which was significantly higher than the evening median level [41 (32, 53) ppb, P = 0.028]. The median (IQR) effect-acting time assessed by FeNO50 was 4 (3, 5) days, which was significantly earlier than each measure of mSpirometry (P < 0.05). FeNO50 reached the relative plateau significantly earlier than FEV1 (15 ± 2 days vs. 21 ± 3 days, P < 0.001). After treatment, the daily and weekly variation rates of FeNO50 showed a gradually decreasing trend (P < 0.05). The ACT score, sputum eosinophils, and blood eosinophils also significantly improved (P ≤ 0.01). CONCLUSIONS: The daily home monitoring of FeNO50 in asthmatic patients showed significant circadian rhythm, and the sensitivity of FeNO50 in evaluating the response to treatment was higher than mSpirometry. The daily and weekly variation rates of FeNO50 change dynamically with time, which may be used to assess the condition of asthma.


Asthma , Nitric Oxide , Spirometry , Humans , Asthma/drug therapy , Asthma/metabolism , Asthma/diagnosis , Asthma/physiopathology , Pilot Projects , Male , Female , Adult , Middle Aged , Nitric Oxide/analysis , Nitric Oxide/metabolism , Forced Expiratory Volume , Fractional Exhaled Nitric Oxide Testing , Circadian Rhythm , Sputum/metabolism , Eosinophils/metabolism , Exhalation , Breath Tests/methods
14.
Acta Otorhinolaryngol Ital ; 44(2): 100-112, 2024 Apr.
Article En | MEDLINE | ID: mdl-38651552

The goal of this meta-analysis was to study nasal nitric oxide (nNO) measurements in allergic rhinitis (AR) and non-allergic rhinitis (non-AR). The protocol was registered with PROSPERO (no: CRD4202124828). Electronic databases from PubMed, Google Scholar, Scopus, Web of Science, and Cochrane were all thoroughly searched and studies were chosen based on the qualifying requirements. The quality of the studies was evaluated by Joanna Briggs Institute evaluation tools, and publication bias using funnel plots. The meta-analysis included 18 studies, whereas the systematic review included 20 studies, totaling 3097 participants (1581 AR, 458 non-AR, and 1058 healthy/control). Patients with AR had significantly greater nNO levels than the control group, although this did not change significantly before or after treatment. AR patients had significantly greater nNO levels than non-AR patients, but there was no significant difference between non-AR patients and healthy controls. Nineteen of the studies were of high quality and the remaining one was of moderate quality. nNO measurement has a promising role in the management of AR and non-AR patients, but more investigations are needed to document clinical benefits.


Nitric Oxide , Rhinitis, Allergic , Rhinitis , Humans , Nitric Oxide/analysis , Nitric Oxide/metabolism , Rhinitis, Allergic/diagnosis
15.
MMW Fortschr Med ; 166(Suppl 4): 3-8, 2024 04.
Article De | MEDLINE | ID: mdl-38575832

BACKGROUND: Diagnostic and therapeutic options for asthma have improved with asthma control and remission being of central importance. The RELEVANT study aimed for a nationwide snapshot of current asthma diagnosis and treatment in general practice and specialty care for identification of further aspects for optimization. METHOD: RELEVANT is a nationwide cross-sectional study using a structured questionnaire. This comprised 14 questions on asthma-related topics covering diagnostics and therapy. Participants were general practitioners/internal medicine specialists and pulmonologists. RESULTS: A total of 1,558 persons took part in the survey. Regarding relevant specific diagnostic procedures for asthma, GPs/internists almost exclusively mentioned pulse oximetry. Among the pulmonologists, fractional exhaled nitric oxide (FeNO) measurement was mentioned, among others. FeNO and blood eosinophils were only mentioned by the pulmonologists as diagnostic and treatment-relevant markers. A total of more than 60% of the GPs/internists surveyed stated that only around 25% or fewer of their patients would voluntarily report restrictions in their everyday lives. Regarding drug treatment, the majority stated that they recognized differences between various ICS/LABA combination therapies. CONCLUSIONS: The results indicate a need for optimization, particularly regarding asthma control. This involves both a better assessment by patients' everyday life restrictions and modern ways of assessing asthma control in cooperation between GPs/internal medicine specialists and pulmonologists. One fifth of respondents do not see any differences between various ICS/LABA combinations in daily practice, although there are pharmacodynamic and pharmacokinetic differences.


Asthma , Nitric Oxide , Humans , Cross-Sectional Studies , Nitric Oxide/analysis , Nitric Oxide/therapeutic use , Adrenal Cortex Hormones/therapeutic use , Asthma/diagnosis , Asthma/drug therapy , Germany , Administration, Inhalation
16.
BMC Pulm Med ; 24(1): 199, 2024 Apr 23.
Article En | MEDLINE | ID: mdl-38654208

BACKGROUND: Fractional exhaled nitric oxide (FeNO) has been extensively studied in various causes of pulmonary hypertension (PH), but its utility as a noninvasive marker remains highly debated. The objective of our study was to assess FeNO levels in patients with idiopathic pulmonary arterial hypertension (IPAH) and mixed connective tissue disease complicating pulmonary hypertension (MCTD-PH), and to correlate them with respiratory functional data, disease severity, and cardiopulmonary function. METHODS: We collected data from 54 patients diagnosed with IPAH and 78 patients diagnosed with MCTD-PH at the Shanghai Pulmonary Hospital Affiliated to Tongji University. Our data collection included measurements of brain natriuretic peptide (pro-BNP), cardiopulmonary exercise test (CPET), pulmonary function test (PFT), impulse oscillometry (IOS), and FeNO levels. Additionally, we assessed World Health Organization functional class (WHO-FC) of each patient. RESULTS: (1) The fractional exhaled concentration of nitric oxide was notably higher in patients with IPAH compared to those with MCTD-PH. Furthermore, within the IPAH group, FeNO levels were found to be lower in cases of severe IPAH compared to mild IPAH (P = 0.024); (2) In severe pulmonary hypertension as per the WHO-FC classification, FeNO levels in IPAH exhibited negative correlations with FEV1/FVC (Forced Expiratory Velocity at one second /Forced Vital Capacity), MEF50% (Maximum Expiratory Flow at 50%), MEF25%, and MMEF75/25% (Maximum Mid-expiratory Flow between 75% and 25%), while in severe MCTD-PH, FeNO levels were negatively correlated with R20% (Resistance at 20 Hz); (3) ROC (Receiving operator characteristic curve) analysis indicated that the optimal cutoff value of FeNO for diagnosing severe IPAH was 23ppb; (4) While FeNO levels tend to be negatively correlated with peakPETO2(peak end-tidal partial pressure for oxygen) in severe IPAH, in mild IPAH they had a positive correlation to peakO2/Heart rate (HR). An interesting find was observed in cases of severe MCTD-PH, where FeNO levels were negatively correlated with HR and respiratory exchange ratio (RER), while positively correlated with O2/HR throughout the cardiopulmonary exercise test. CONCLUSION: FeNO levels serve as a non-invasive measure of IPAH severity. Although FeNO levels may not assess the severity of MCTD-PH, their significant makes them a valuable tool when assessing severe MCTD-PH.


Exercise Test , Familial Primary Pulmonary Hypertension , Mixed Connective Tissue Disease , Nitric Oxide , Humans , Female , Male , Middle Aged , Adult , Mixed Connective Tissue Disease/complications , Nitric Oxide/analysis , Nitric Oxide/metabolism , Familial Primary Pulmonary Hypertension/physiopathology , Familial Primary Pulmonary Hypertension/diagnosis , Familial Primary Pulmonary Hypertension/complications , Biomarkers/analysis , Biomarkers/metabolism , Respiratory Function Tests , Fractional Exhaled Nitric Oxide Testing , Severity of Illness Index , Hypertension, Pulmonary/physiopathology , Hypertension, Pulmonary/diagnosis , Natriuretic Peptide, Brain/metabolism , China , Aged
17.
Int J Immunopathol Pharmacol ; 38: 3946320241246713, 2024.
Article En | MEDLINE | ID: mdl-38649141

Purpose: This retrospective study investigates the influence of overweight and obesity status on pulmonary function, airway inflammatory markers, and airway responsiveness in elderly asthma patients. Methods: Patients with asthma older than 65 years old who completed a bronchial provocation test (BPT) or bronchial dilation test (BDT) and a fractional exhaled nitric oxide (FeNO) test between December 2015 and June 2020 were identified retrospectively for this study. All of the patients were categorized into overweight/obesity and non-obesity groups based on their BMI. Pulmonary function test (PFT) and FeNO measurements were accomplished according to the 2014 recommendations of the Chinese National Guidelines of Pulmonary Function Test and American Thoracic Society/European Respiratory Society recommendations, respectively. Results: A total of 136 patients with an average age of 71.2 ± 5.40 years were identified. The average BMI was 23.8 ± 3.63, while the value of FeNO was 42.3 ± 38.4 parts per billion (ppb). In contrast to the non-obesity group, which had a value of 48.8 ± 43.1 ppb for FeNO, the overweight/obesity group had a significant lower value of 35.4 ± 31.4 ppb. There was no significant difference in the proportion of individuals with high airway hyperresponsiveness between the overweight/obesity and non-obesity groups (96 patients in total). Multiple linear regression analysis established an inverse correlation between FeNO and Provocation concentration causing a 20% fall in FEV1(PC20) but excluded significant relationships with age and BMI. The model's R is 0.289, and its p value is 0.045. Conclusion: The elderly Chinese Han asthmatics with overweight/obesity had lower FeNO levels than those with non-obese according to our findings. In addition, the FeNO level was inversely correlated between FeNO levels and PC20 in elderly asthmatics.


Asthma , Nitric Oxide , Obesity , Overweight , Humans , Asthma/physiopathology , Asthma/metabolism , Asthma/diagnosis , Aged , Male , Female , Retrospective Studies , Obesity/physiopathology , Obesity/metabolism , Overweight/physiopathology , Overweight/metabolism , Nitric Oxide/metabolism , Nitric Oxide/analysis , Respiratory Function Tests , Fractional Exhaled Nitric Oxide Testing , China/epidemiology , Bronchial Provocation Tests , Body Mass Index , Asian People , Respiratory Hypersensitivity/physiopathology , Respiratory Hypersensitivity/metabolism , Respiratory Hypersensitivity/diagnosis , Breath Tests
18.
ACS Sens ; 9(4): 1682-1705, 2024 Apr 26.
Article En | MEDLINE | ID: mdl-38593007

Gasotransmitters, including nitric oxide (NO), carbon monoxide (CO), and hydrogen sulfide (H2S), are a class of gaseous, endogenous signaling molecules that interact with one another in the regulation of critical cardiovascular, immune, and neurological processes. The development of analytical sensing mechanisms for gasotransmitters, especially multianalyte mechanisms, holds vast importance and constitutes a growing area of study. This review provides an overview of electrochemical sensing mechanisms with an emphasis on opportunities in multianalyte sensing. Electrochemical methods demonstrate good sensitivity, adequate selectivity, and the most well-developed potential for the multianalyte detection of gasotransmitters. Future research will likely address challenges with sensor stability and biocompatibility (i.e., sensor lifetime and cytotoxicity), sensor miniaturization, and multianalyte detection in biological settings.


Carbon Monoxide , Electrochemical Techniques , Gasotransmitters , Hydrogen Sulfide , Nitric Oxide , Gasotransmitters/analysis , Electrochemical Techniques/methods , Carbon Monoxide/analysis , Nitric Oxide/analysis , Hydrogen Sulfide/analysis , Humans , Biosensing Techniques/methods , Animals
19.
J Mater Chem B ; 12(21): 5076-5084, 2024 May 29.
Article En | MEDLINE | ID: mdl-38567488

Nitric oxide (NO) is a diatomic inorganic free radical ubiquitous in mammalian tissues and cells that plays a multifaceted role in a variety of physiological and pathophysiological processes. The strict dependence of the biological effects of NO on its concentration makes its real-time monitoring crucial. In view of the reactivity of NO with multiple bio-targets, the development of NO sensors that associate a fast response rate with selectivity and sensitivity is very challenging. Herein we report a fluorescent NO probe based on a BODIPY fluorogenic unit covalently linked to a trimethoxy aniline derivative through a flexible spacer. NO leads to effective nitrosation of the highly electron-rich amino active site of the probe through the secondary oxide N2O3, resulting in an increase of BODIPY fluorescence quantum yield from Φf = 0.06 to Φf = 0.55, accompanied by significant changes in the relative amplitude of the fluorescence lifetimes. In situ generation of NO, achieved by a tailored light-activatable NO releaser, allows the real-time detection of NO as a function of its concentration and permits demonstrating that the probe exhibits a very fast response time, being ≤0.1 s. This remarkable data combines with the high sensitivity of the probe to NO (LOD = 35 nM), responsiveness also to ONOO-, the other important secondary oxide of NO, independence from the fluorescence response within a wide pH range, good selectivity towards different analytes and small interference by typical physiological concentrations of glutathione. Validation of this probe in melanoma cell lines is also reported.


Boron Compounds , Fluorescent Dyes , Nitric Oxide , Nitric Oxide/analysis , Nitric Oxide/metabolism , Fluorescent Dyes/chemistry , Fluorescent Dyes/chemical synthesis , Humans , Boron Compounds/chemistry , Boron Compounds/pharmacology , Molecular Structure , Cell Line, Tumor
20.
BMC Pulm Med ; 24(1): 210, 2024 Apr 29.
Article En | MEDLINE | ID: mdl-38684989

BACKGROUND: Measurement of exhaled nitric oxide (FeNO) is a potentially useful diagnostic test for asthma. However, no study has explored the relationship between FeNO and respiratory symptoms of nontuberculous mycobacterial pulmonary disease (NTM-PD) complicated with asthma. The objective of this study was to assess the utility of measuring FeNO levels in patients with NTM-PD complicated by asthma. METHODS: In this single-center retrospective cohort study, 140 NTM-PD patients with FeNO measured were enrolled. We selected NTM-PD patients who complicated with asthma as the NTM+BA group, defined using the following criteria: NTM patients with symptoms consistent with asthma, and NTM patients with symptomatic improvement after diagnostic therapy with ICS ± a long-acting beta 2-agonist (LABA). We then calculated a diagnostic cutoff point to distinguish between the NTM+BA groups and the NTM groups (all others). High-resolution computed tomography (HRCT) images were evaluated using the CT scoring system and their association with FeNO was examined. RESULTS: A total of 89 patients were included in the study. (31 in the NTM+BA group and 58 in the NTM group). Compared with the NTM group, the NTM+BA group had higher rates of allergic disease (51.6% vs. 22.4%; p=0.0085) and higher FeNO values (median, 23 [interquartile range {IQR}, 15.0-43.0] ppb vs. median, 17 [IQR, 11.8-23.0] ppb; p=0.015). With diagnostic asthma care using mainly ICS/LABA with reference to the FeNO, most patients (91.0%, 20/22) in the NTM-preceding subgroup in the NTM+BA group demonstrated a prompt improvement of their symptoms and AFB culture findings did not worsen (Culture positive rate (%): Pre-treatment: 59.1% vs. Post-treatment: 40.9%, p=0.3660) at 6 months after starting diagnostic therapy. The optimal diagnostic cutoff point of FeNO to distinguish between the two groups was calculated as 21.5 ppb by the ROC curve (sensitivity 75%, specificity 71.93%, p<0.0001; area under the curve: 0.7989). No significant correlation was observed between FeNO and the severity of CT images in the patients. CONCLUSIONS: A certain number of patients with NTM-PD showed exacerbated respiratory symptoms due to asthmatic complications. Elevated FeNO levels suggest asthma complications, even in patients with NTM.


Asthma , Cough , Mycobacterium Infections, Nontuberculous , Nitric Oxide , Humans , Female , Male , Mycobacterium Infections, Nontuberculous/diagnosis , Mycobacterium Infections, Nontuberculous/complications , Middle Aged , Retrospective Studies , Asthma/complications , Asthma/diagnosis , Aged , Nitric Oxide/analysis , Nitric Oxide/metabolism , Cough/etiology , Tomography, X-Ray Computed , Fractional Exhaled Nitric Oxide Testing , Breath Tests/methods , ROC Curve
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