Changes in fractional exhaled nitric oxide, forced expiratory volume in one second, and forced oscillation technique parameters over three years in adults with bronchial asthma managed under Yokohama Seibu Hospital's coordinated care system.

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.

Efficient detection of nitric oxide a biomarker associated with COVID19 via N, P co-doped C60 fullerene: a computational study.

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.

Unique Synthetic Strategy for Probing in Situ Lysosomal NO for Screening Neuroinflammatory Phenotypes against SARS-CoV-2 RNA in Phagocytotic Microglia.

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.

Hemin as a Molecular Probe for Nitric Oxide Detection in Physiological Solutions: Experimental and Theoretical Assessment.

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.

Nasal nitric oxide measurement in allergic rhinitis and non-allergic rhinitis: a meta-analysis.

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.

A Mitochondria-Targeted Nitric Oxide Probe for Multimodality Imaging of Macrophage Immune Responses.

Nitric oxide (NO) is a crucial signal molecule closely linked to the biological immune response, especially in macrophage polarization. When activated, macrophages enter a pro-inflammatory state and produce NO, a marker for the M1 phenotype. In contrast, the anti-inflammatory M2 phenotype does not produce NO. We developed a mitochondria-targeted two-photon iridium-based complex (Ir-ImNO) probe that can detect endogenous NO and monitor macrophages' different immune response states using various imaging techniques, such as one- and two-photon phosphorescence imaging and phosphorescence lifetime imaging. Ir-ImNO was used to monitor the immune activation of macrophages in mice. This technology aims to provide a clear and comprehensive visualization of macrophage immune responses.

Effect of overweight/obesity on relationship between fractional exhaled nitric oxide and airway hyperresponsiveness in Chinese elderly patients with asthma.

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.

Fractional exhaled nitric oxide in idiopathic pulmonary arterial hypertension and mixed connective tissue disease complicating pulmonary hypertension.

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.

[Diagnosis and therapy of patients with asthma in Germany. Results of the care study RELEVANT]. / Diagnostik und Therapie von Patienten mit Asthma in Deutschland : Ergebnisse der Versorgungsstudie RELEVANT.

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.

Electrochemical Detection of Gasotransmitters: Status and Roadmap.

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.

The diagnostic impact of fractional exhaled nitric oxide for asthmatic cough in nontuberculous mycobacterial pulmonary disease.

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.

A NIR-II Photoacoustic Probe for High Spatial Quantitative Imaging of Tumor Nitric Oxide in Vivo.

Nitric oxide (NO) exhibits both pro- and anti-tumor effects. Therefore, real-time in vivo imaging and quantification of tumor NO dynamics are essential for understanding the conflicting roles of NO played in pathophysiology. The current molecular probes, however, cannot provide high-resolution imaging in deep tissues, making them unsuitable for these purposes. Herein, we designed a photoacoustic probe with an absorption maximum beyond 1000 nm for high spatial quantitative imaging of in vivo tumor NO dynamics. The probe exhibits remarkable sensitivity, selective ratiometric response behavior, and good tumor-targeting abilities, facilitating ratiometric imaging of tumor NO throughout tumor progression in a micron-resolution level. Using the probe as the imaging agent, we successfully quantified NO dynamics in tumor, liver and kidney. We have pinpointed an essential concentration threshold of around 80 nmol/cm3 for NO, which plays a crucial role in the "double-edged-sword" function of NO in tumors. Furthermore, we revealed a reciprocal relationship between the NO concentration in tumors and that in the liver, providing initial insights into the possible NO-mediated communication between tumor and the liver. We believe that the probe will help resolve conflicting aspects of NO biology and guide the design of imaging agents for tumor diagnosis and anti-cancer drug screening.

Potential Anti-Inflammatory Constituents from Aesculus wilsonii Seeds.

A chemical study of Aesculus wilsonii Rehd. (also called Suo Luo Zi) and the in vitro anti-inflammatory effects of the obtained compounds was conducted. Retrieving results through SciFinder showed that there were four unreported compounds, aeswilosides I-IV (1-4), along with fourteen known isolates (5-18). Their structures were elucidated by extensive spectroscopic methods such as UV, IR, NMR, [α]D, and MS spectra, as well as acid hydrolysis. Among the known ones, compounds 5, 6, 8-10, and 12-16 were obtained from the Aesculus genus for the first time; compounds 7, 11, 17, and 18 were first identified from this plant. The NMR data of 5 and 18 were reported first. The effects of 1-18 on the release of nitric oxide (NO) from lipopolysaccharide (LPS)-induced RAW264.7 cells were determined. The results showed that at concentrations of 10, 25, and 50 µM, the novel compounds, aeswilosides I (1) and IV (4), along with the known ones, 1-(2-methylbutyryl)phloroglucinyl-glucopyranoside (10) and pisuminic acid (15), displayed significant inhibitory effects on NO production in a concentration-dependent manner. It is worth mentioning that compound 10 showed the best NO inhibitory effect with a relative NO production of 88.1%, which was close to that of the positive drug dexamethasone. The Elisa experiment suggested that compounds 1, 4, 10, and 15 suppressed the release of TNF-α and IL-1ß as well. In conclusion, this study enriches the spectra of compounds with potential anti-inflammatory effects in A. wilsonii and provides new references for the discovery of anti-inflammatory lead compounds, but further mechanistic research is still needed.

Association between endotoxemia and blood no in the portal circulation of cirrhotic patients: results of a pilot study.

Pathophysiology of portal vein thrombosis (PVT) in cirrhosis is still not entirely understood. Elevated levels of lipopolysaccharides (LPS) in portal circulation are significantly associated with hypercoagulation, increased platelet activation and endothelial dysfunction. The aim of the study was to investigate if LPS was associated with reduced portal venous flow, the third component of Virchow's triad, and the underlying mechanism. Serum nitrite/nitrate, as a marker of nitric oxide (NO) generation, and LPS were measured in the portal and systemic circulation of 20 patients with cirrhosis undergoing transjugular intrahepatic portosystemic shunt (TIPS) procedure; portal venous flow velocity (PVV) was also measured in each patient and correlated with NO and LPS levels. Serum nitrite/nitrate and LPS were significantly higher in the portal compared to systemic circulation; a significant correlation was found between LPS and serum nitrite/nitrate (R = 0.421; p < 0.01). Median PVV before and after TIPS was 15 cm/s (6-40) and 31 cm/s (14-79), respectively. Correlation analysis of PVV with NO and LPS showed a statistically significant negative correlation of PVV with portal venous NO concentration (R = - 0.576; p = 0.020), but not with LPS. In vitro study with endothelial cells showed that LPS enhanced endothelial NO biosynthesis, which was inhibited by L-NAME, an inhibitor of NO synthase, or TAK-242, an inhibitor of TLR4, the LPS receptor; this effect was accomplished by up-regulation of eNOS and iNOS. The study shows that in cirrhosis, endotoxemia may be responsible for reduced portal venous flow via overgeneration of NO and, therefore, contribute to the development of PVT.

Ultrasensitive Online NO Sensor Based on a Distributed Parallel Self-Regulating Neural Network and Ultraviolet Differential Optical Absorption Spectroscopy for Exhaled Breath Diagnosis.

The concentration of fractional exhaled nitric oxide (FeNO) is closely related to human respiratory inflammation, and the detection of its concentration plays a key role in aiding diagnosing inflammatory airway diseases. In this paper, we report a gas sensor system based on a distributed parallel self-regulating neural network (DPSRNN) model combined with ultraviolet differential optical absorption spectroscopy for detecting ppb-level FeNO concentrations. The noise signals in the spectrum are eliminated by discrete wavelet transform. The DPSRNN model is then built based on the separated multipeak characteristic absorption structure of the UV absorption spectrum of NO. Furthermore, a distributed parallel network structure is built based on each absorption feature region, which is given self-regulating weights and finally trained by a unified model structure. The final self-regulating weights obtained by the model indicate that each absorption feature region contributes a different weight to the concentration prediction. Compared with the regular convolutional neural network model structure, the proposed model has better performance by considering the effect of separated characteristic absorptions in the spectrum on the concentration and breaking the habit of bringing the spectrum as a whole into the model training in previous related studies. Lab-based results show that the sensor system can stably achieve high-precision detection of NO (2.59-750.66 ppb) with a mean absolute error of 0.17 ppb and a measurement accuracy of 0.84%, which is the best result to date. More interestingly, the proposed sensor system is capable of achieving high-precision online detection of FeNO, as confirmed by the exhaled breath analysis.

Association between individual sensor behavior of an electronic nose and airways inflammation in children with asthma: a pilot study at alpine altitude climate.

BACKGROUND: Markers of airway inflammation can be helpful in the management of childhood asthma. Residential activities, such as intensive asthma camps at alpine altitude climate (AAC), can help reduce bronchial inflammation in patients who fail to achieve optimal control of the disease. Analysis of volatile organic compounds (VOCs) can be obtained using electronic devices such as e-Noses. We aimed to identify alterations in urinary e-Nose sensors among children with asthma participating in an intensive camp at AAC and to investigate associations between urinary e-Nose analysis and airway inflammation. METHODS: We analyzed data collected in children with asthma recruited between July and September 2020. All children were born and resided at altitudes below 600 m asl. Urinary VOCs (measured using the Cyranose 320® VOC analyzer), Fractional exhaled Nitric Oxide (FeNO) and spirometry were evaluated upon children's arrival at the Istituto Pio XII, Misurina (BL), Italy, at 1756 m asl (T0), and after 7 (T1) and 15 days (T2) of stay. RESULTS: Twenty-two patients (68.2% males; median age: 14.5 years) were enrolled. From T0 to T1 and T2, the negative trend for FeNO was significant (p < .001). Significant associations were observed between e-Nose sensors S7 (p = .002), S12 (p = .013), S16 (p = .027), S17 (p = .017), S22 (p = .029), S29 (p = .021), S31 (p = .009) and ΔFeNO at T0-T1. ΔFeNO at T0-T2 was significantly associated with S17 (p = .015), S19 (p = .004), S21 (p = .020), S24 (p = .012), S25 (p = .018), S26 (p = .008), S27 (p = .002), S29 (p = .007), S30 (p = .013). CONCLUSIONS: We showed that a decrease in FeNO levels after a short sojourn at AAC is associated with behaviors of individual urinary e-Nose sensors in children with asthma.

The utility of nasal nitric oxide in the diagnostic evaluation of primary ciliary dyskinesia.

BACKGROUND: There is no gold-standard test for primary ciliary dyskinesia (PCD), rather American Thoracic Society guidelines recommend starting with nasal nitric oxide (nNO) in children ≥5 years old and confirming the diagnosis with genetic testing or ciliary biopsy with transmission electron microscopy (TEM). These guidelines have not been studied in a clinical setting. We present a case series describing the PCD diagnostic process at our pediatric PCD center. METHODS: Diagnostic data from 131 patients undergoing PCD consultation were reviewed. RESULTS: In all participants ≥ 5 years old and who completed nNO using resistor methodology, the first diagnostic test performed was nNO in 77% (73/95), genetic testing in 14% (13/95), and TEM in <1% (9/95). nNO was the only diagnostic test performed in 75% (55/73) of participants who completed nNO first. Seventy-five percent (55/73) had a single above the cutoff nNO value and PCD was determined to be unlikely in 91% (50/55) without performing additional confirmatory testing. Eleven percent (8/73) had multiple below the cutoff nNO values, with 38% (3/8) being diagnosed with PCD by confirmatory testing and 50% (4/8) with negative confirmatory testing, but being managed as PCD. The genetic testing positivity rate was 50% in participants who completed nNO first and 8% when genetic testing was completed first. CONCLUSION: nNO is useful in three situations: an initial above the cutoff nNO value makes PCD unlikely and prevents additional confirmatory testing, repetitively below the cutoff nNO values without positive confirmatory testing suggests a probable PCD diagnosis and the yield of genetic testing is higher when nNO is performed first.

fMRI BOLD responses to film stimuli and their association with exhaled nitric oxide in asthma and health.

Little is known about central nervous system (CNS) responses to emotional stimuli in asthma. Nitric oxide in exhaled breath (FENO) is elevated in asthma due to allergic immune processes, but endogenous nitric oxide is also known to modulate CNS activity. We measured fMRI blood oxygen-dependent (BOLD) brain activation to negative (blood-injection-injury themes) and neutral films in 31 participants (15 with asthma). Regions-of-interest analysis was performed on key areas relevant to central adaptive control, threat processing, or salience networks, with dorsolateral prefrontal cortex (PFC), anterior insula, dorsal anterior cingulate cortex (dACC), amygdala, ventral striatum, ventral tegmentum, and periaqueductal gray, as well as top-down modulation of emotion, with ventrolateral and ventromedial PFC. Both groups showed less BOLD deactivation from fixation cross-baseline in the left anterior insula and bilateral ventromedial PFC for negative than neutral films, and for an additional number of areas, including the fusiform gyrus, for film versus recovery phases. Less deactivation during films followed by less recovery from deactivation was found in asthma compared to healthy controls. Changes in PCO2 did not explain these findings. FENO was positively related to BOLD activation in general, but more pronounced in healthy controls and more likely in neutral film processing. Thus, asthma is associated with altered processing of film stimuli across brain regions not limited to central adaptive control, threat processing, or salience networks. Higher levels of NO appear to facilitate CNS activity, but only in healthy controls, possibly due to allergy's masking effects on FENO.

The Association Between Personal Air Pollution Exposures and Fractional Exhaled Nitric Oxide (FeNO): A Systematic Review.

PURPOSE OF REVIEW: Airway inflammation is a common biological response to many types of environmental exposures and can lead to increased nitric oxide (NO) concentrations in exhaled breath. In recent years, several studies have evaluated airway inflammation using fractional exhaled nitric oxide (FeNO) as a biomarker of exposures to a range of air pollutants. This systematic review aims to summarize the studies that collected personal-level air pollution data to assess the air pollution-induced FeNO responses and to determine if utilizing personal-level data resulted in an improved characterization of the relationship between air pollution exposures and FeNO compared to using only ambient air pollution exposure data. RECENT FINDINGS: Thirty-six eligible studies were identified. Overall, the studies included in this review establish that an increase in personal exposure to particulate and gaseous air pollutants can significantly increase FeNO. Nine out of the 12 studies reported statistically significant FeNO increases with increasing personal PM2.5 exposures, and up to 11.5% increase in FeNO per IQR increase in exposure has also been reported between FeNO and exposure to gas-phase pollutants, such as ozone, NO2, and benzene. Furthermore, factors such as chronic respiratory diseases, allergies, and medication use were found to be effect modifiers for air pollution-induced FeNO responses. About half of the studies that compared the effect estimates using both personal and ambient air pollution exposure methods reported that only personal exposure yielded significant associations with FeNO response. The evidence from the reviewed studies confirms that FeNO is a sensitive biomarker for air pollutant-induced airway inflammation. Personal air pollution exposure assessment is recommended to accurately assess the air pollution-induced FeNO responses. Furthermore, comprehensive adjustments for the potential confounding factors including the personal exposures of the co-pollutants, respiratory disease status, allergy status, and usage of medications for asthma and allergies are recommended while assessing the air pollution-induced FeNO responses.

Acute exposure to pollen and airway inflammation in adolescents.

INTRODUCTION: Pollen exposure is known to exacerbate allergic asthma and allergic rhinitis symptoms, yet few studies have investigated if exposure to pollen affects lung function or airway inflammation in healthy children. METHODS: We evaluated the extent to which higher pollen exposure was associated with differences in airway inflammation and lung function among 490 early adolescent participants (mean age of 12.9 years) in Project Viva, a prebirth cohort based in Massachusetts. We obtained regional daily total pollen counts, including tree, grass, and weed pollen, from a Rotorod pollen counter. We evaluated associations of 3- and 7-day moving averages of pollen with fractional exhaled nitric oxide (FeNO) and lung function using linear regression models and evaluated the linearity of associations with penalized splines. We tested if associations of pollen with FeNO and lung function were modified by current asthma diagnosis, history of allergic rhinitis, aeroallergen sensitivity, temperature, precipitation, and air pollution. RESULTS: Three- and 7-day median pollen concentrations were 19.0 grains/m3 (IQR: 73.4) and 20.9 grains/m3 (IQR: 89.7). In main models, higher concentrations of total pollen over the preceding 3 and 7 days were associated with a 4.6% (95% CI: 0.1,9.2) and 7.4% (95% CI: 0.9,14.3) higher FeNO per IQR of pollen, respectively. We did not find associations of pollen with lung function in main models. Asthma, allergic rhinitis, precipitation, and air pollution (nitrogen dioxide and ozone) modified associations of pollen with lung function (Pinteraction < 0.1), while temperature, sex, and aeroallergen sensitization did not. CONCLUSION: Short-term exposure to pollen was associated with higher FeNO in early adolescents, even in the absence of allergic sensitization and asthma.