Airway contribution to alveolar nitric oxide in healthy subjects and stable asthma patients

2008 ◽  
Vol 104 (4) ◽  
pp. 918-924 ◽  
Author(s):  
Yannick Kerckx ◽  
Alain Michils ◽  
Alain Van Muylem
Keyword(s):  
Nitric Oxide ◽  
Asthma Control ◽  
Healthy Subjects ◽  
Molecular Diffusion ◽  
Forced Expiratory Volume ◽  
No Production ◽  
Asthma Control Questionnaire ◽  
Asthma Patients ◽  
The Impact

Alveolar nitric oxide (NO) concentration (FaNO), increasingly considered in asthma, is currently interpreted as a reflection of NO production in the alveoli. Recent modeling studies showed that axial molecular diffusion brings NO molecules from the airways back into the alveolar compartment during exhalation (backdiffusion) and contributes to FaNO. Our objectives in this study were 1) to simulate the impact of backdiffusion on FaNO and to estimate the alveolar concentration actually due to in situ production (FaNO,prod); and 2) to determine actual alveolar production in stable asthma patients with a broad range of NO bronchial productions. A model incorporating convection and diffusion transport and NO sources was used to simulate FaNO and exhaled NO concentration at 50 ml/s expired flow (FeNO) for a range of alveolar and bronchial NO productions. FaNO and FeNO were measured in 10 healthy subjects (8 men; age 38 ± 14 yr) and in 21 asthma patients with stable asthma [16 men; age 33 ± 13 yr; forced expiratory volume during 1 s (FEV1) = 98.0 ± 11.9%predicted]. The Asthma Control Questionnaire (Juniper EF, Buist AS, Cox FM, Ferrie PJ, King DR. Chest 115: 1265–1270, 1999) assessed asthma control. Simulations predict that, because of backdiffusion, FaNO and FeNO are linearly related. Experimental results confirm this relationship. FaNO,prod may be derived by FaNO,prod = (FaNO − 0.08·FeNO)/0.92 ( Eq. 1 ). Based on Eq. 1 , FaNO,prod is similar in asthma patients and in healthy subjects. In conclusion, the backdiffusion mechanism is an important determinant of NO alveolar concentration. In stable and unobstructed asthma patients, even with increased bronchial NO production, alveolar production is normal when appropriately corrected for backdiffusion.

scholarly journals Is ventilation heterogeneity related to asthma control?

2016 ◽  
Vol 48 (2) ◽  
pp. 370-379 ◽  
Author(s):  
Sarah Svenningsen ◽  
Parameswaran Nair ◽  
Fumin Guo ◽  
David G. McCormack ◽  
Grace Parraga
Keyword(s):  
Quality Of Life ◽  
Asthma Control ◽  
Forced Expiratory Volume ◽  
Life Questionnaire ◽  
Strongly Correlated ◽  
Asthma Control Questionnaire ◽  
Asthma Patients ◽  
Ventilation Heterogeneity ◽  
Magnetic Resonance Imaging Mri

In asthma patients, magnetic resonance imaging (MRI) and the lung clearance index (LCI) have revealed persistent ventilation heterogeneity, although its relationship to asthma control is not well understood. Therefore, our goal was to explore the relationship of MRI ventilation defects and the LCI with asthma control and quality of life in patients with severe, poorly controlled asthma.18 patients with severe, poorly controlled asthma (mean±sd 46±12 years, six males/12 females) provided written informed consent to an ethics board approved protocol, and underwent spirometry, LCI and 3He MRI during a single 2-h visit. Asthma control and quality of life were evaluated using the Asthma Control Questionnaire (ACQ) and Asthma Quality of Life Questionnaire (AQLQ). Ventilation heterogeneity was quantified using the LCI and 3He MRI ventilation defect percent (VDP).All participants reported poorly controlled disease (mean±sd ACQ score=2.3±0.9) and highly heterogeneous ventilation (mean±sd VDP=12±11% and LCI=10.5±3.0). While VDP and LCI were strongly correlated (r=0.86, p<0.0001), in a multivariate model that included forced expiratory volume in 1 s, VDP and LCI, VDP was the only independent predictor of asthma control (R2=0.38, p=0.01). There was also a significantly worse VDP, but not LCI in asthma patients with an ACQ score >2 (p=0.04) and AQLQ score <5 (p=0.04), and a trend towards worse VDP (p=0.053), but not LCI in asthma patients reporting ≥1 exacerbation in the past 6 months.In patients with poorly controlled, severe asthma MRI ventilation, but not LCI was significantly worse in those with worse ACQ and AQLQ.

Endothelial microparticles increase in mitral valve disease and impair mitral valve endothelial function

2013 ◽  
Vol 304 (7) ◽  
pp. E695-E702 ◽  
Author(s):  
Hong-Bo Ci ◽  
Zhi-Jun Ou ◽  
Feng-Jun Chang ◽  
Dong-Hong Liu ◽  
Guo-Wei He ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Endothelial Cells ◽  
Mitral Valve ◽  
Mitral Regurgitation ◽  
Mitral Valve Disease ◽  
Healthy Subjects ◽  
Heat Shock Protein 90 ◽  
Valve Disease ◽  
No Production ◽  
Endothelial Microparticles

Mitral valve endothelial cells are important for maintaining lifelong mitral valve integrity and function. Plasma endothelial microparticles (EMPs) increased in various pathological conditions related to activation of endothelial cells. However, whether EMPs will increase in mitral valve disease and their relationship remains unclear. Here, 81 patients with mitral valve disease and 45 healthy subjects were analyzed for the generation of EMPs by flow cytometry. Human mitral valve endothelial cells (HMVECs) were treated with EMPs. The phosphorylation of Akt and endothelial nitric oxide synthase (eNOS), the association of eNOS and heat shock protein 90 (HSP90), and the generation of nitric oxide (NO) and superoxide anion (O2˙−) were measured. EMPs were increased significantly in patients with mitral valve disease compared with those in healthy subjects. EMPs were negatively correlated with mitral valve area in patients with isolated mitral stenosis. EMPs were significantly higher in the group with severe mitral regurgitation than those in the group with mild and moderate mitral regurgitation. Furthermore, EMPs were decreased dramatically in both Akt and eNOS phosphorylation and the association of HSP90 with eNOS in HMVECs. EMPs decreased NO production but increased O2˙− generation in HMVECs. Our data demonstrated that EMPs were significantly increased in patients with mitral valve disease. The increase of EMPs can in turn impair HMVEC function by inhibiting the Akt/eNOS-HSP90 signaling pathway. These findings suggest that EMPs may be a therapeutic target for mitral valve disease.

scholarly journals NIR Bioluminescence Probe Enables Discovery of Diet-Induced Modulation of the Tumor Microenvironment via Nitric Oxide

2021 ◽  
Author(s):  
Anuj K Yadav ◽  
Michael C. Lee ◽  
Melissa Lucero ◽  
Christopher J. Reinhardt ◽  
ShengZhang Su ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Tumor Microenvironment ◽  
Tumor Progression ◽  
Critical Role ◽  
Cellular Systems ◽  
Tissue Imaging ◽  
Molecular Evidence ◽  
No Production ◽  
The Impact

<p>Nitric oxide (NO) plays a critical role in acute and chronic inflammation. NO’s contributions to cancer are of particular interest due to its context-dependent bioactivities. For example, immune cells initially produce cytotoxic quantities of NO in response to the nascent tumor. However, it is believed that this fades over time and reaches a concentration that supports the tumor microenvironment (TME). These complex dynamics are further complicated by other factors, such as diet and oxygenation, making it challenging to establish a complete picture of NO’s impact on tumor progression. Although many activity-based sensing (ABS) probes for NO have been developed, only a small fraction have been employed <i>in vivo </i>and fewer yet are practical in cancer models where the NO concentration is < 200 nM. To overcome this outstanding challenge, we have developed BL<sub>660</sub>-NO, the first ABS probe for NIR bioluminescence imaging of NO in cancer. Owing to the low intrinsic background, high sensitivity, and deep tissue imaging capabilities of our design, BL<sub>660</sub>-NO was successfully employed to visualize endogenous NO in cellular systems, a human liver metastasis model, and a murine breast cancer model. Importantly, its exceptional performance facilitated the design of a dietary study to examine the impact of NO on the TME by varying the intake of fat. BL<sub>660</sub>-NO provides the first direct molecular evidence that intratumoral NO becomes elevated in mice fed a high-fat diet who became obese with larger tumors compared to control animals on a low-fat diet. These results indicate that an inflammatory diet can increase NO production via recruitment of macrophages and overexpression of iNOS which in turn can drive tumor progression.<br></p>

scholarly journals Assessing the Impact of Denitrifier-Produced Nitric Oxide on Other Bacteria

2006 ◽  
Vol 72 (3) ◽  
pp. 2200-2205 ◽  
Author(s):  
Peter S. Choi ◽  
Zeki Naal ◽  
Charles Moore ◽  
Emerilis Casado-Rivera ◽  
Hector D. Abruña ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Paracoccus Denitrificans ◽  
Nitrate Respiration ◽  
No Production ◽  
Response Gene ◽  
Surrounding Environment ◽  
Zones Of Inhibition ◽  
Series Of Experiments ◽  
The Impact ◽  
Stress Response Gene

ABSTRACT A series of experiments was undertaken to learn more about the impact on other bacteria of nitric oxide (NO) produced during denitrification. The denitrifier Rhodobacter sphaeroides 2.4.3 was chosen as a denitrifier for these experiments. To learn more about NO production by this bacterium, NO levels during denitrification were measured by using differential mass spectrometry. This revealed that NO levels produced during nitrate respiration by this bacterium were in the low μM range. This concentration of NO is higher than that previously measured in denitrifiers, including Achromobacter cycloclastes and Paracoccus denitrificans. Therefore, both 2.4.3 and A. cycloclastes were used in this work to compare the effects of various NO levels on nondenitrifying bacteria. By use of bacterial overlays, it was found that the NO generated by A. cycloclastes and 2.4.3 cells during denitrification inhibited the growth of both Bacillus subtilis and R. sphaeroides 2.4.1 but that R. sphaeroides 2.4.3 caused larger zones of inhibition in the overlays than A. cycloclastes. Both R. sphaeroides 2.4.3 and A. cycloclastes induced the expression of the NO stress response gene hmp in B. subtilis. Taken together, these results indicate that there is variability in the NO concentrations produced by denitrifiers, but, irrespective of the NO levels produced, microbes in the surrounding environment were responsive to the NO produced during denitrification.

Angiotensin II receptor subtypes determine induced NO production in rat glomerular mesangial cells

2000 ◽  
Vol 279 (6) ◽  
pp. F1092-F1100 ◽  
Author(s):  
Jörg Schwöbel ◽  
Tina Fischer ◽  
Bettina Lanz ◽  
Markus Mohaupt
Keyword(s):  
Nitric Oxide ◽  
Angiotensin Ii ◽  
Mesangial Cells ◽  
Receptor Expression ◽  
Receptor Subtypes ◽  
No Production ◽  
Ang Ii ◽  
Glomerular Mesangial Cells ◽  
Nitrite Production ◽  
The Impact

Angiotensin II (ANG II) and nitric oxide (NO) have contrasting vascular effects, yet both sustain inflammatory responses. We investigated the impact of ANG II on lipopolysaccharide (LPS)/interferon-γ (IFN)-induced NO production in cultured rat mesangial cells (MCs). LPS/IFN-induced nitrite production, the inducible form of nitric oxide synthase (NOS-2) mRNA, and protein expression were dose dependently inhibited by ANG II on coincubation, which was abolished on ANG II type 2 (AT2) receptor blockade by PD-123319. Homology-based RT-PCR verified the presence of AT1A, AT1B, and AT2 receptors. To shift the AT receptor expression toward the type 1 receptor, two sets of experiments were performed: LPS/IFN preincubation for 24 h was followed by 8-h coincubation with ANG II; or during 24-h coincubation of LPS/IFN and ANG II, dexamethasone was added for the last 6-h period. Both led to an amplified overall expression of NOS-2 protein and NO production that was inhibitable by actinomycin D in the first setup. Induced NO production was enhanced via the AT1 receptor; however, it was diminished via the AT2 receptor. In conclusion, induced NO production is negatively controlled by the AT2, whereas AT1 receptor stimulation enhanced NO synthesis in MCs. The overall NO availability depended on the onset of the inflammatory stimuli with respect to ANG II exposure and the available AT receptors.

Factors affecting asthma psychomorbidity, control and illness-related quality of life: what is the interaction?

2011 ◽  
Vol 26 (S2) ◽  
pp. 1745-1745
Author(s):  
N. Pilipenko ◽  
M. Karekla
Keyword(s):  
Quality Of Life ◽  
Asthma Control ◽  
Research Literature ◽  
Smoking History ◽  
Inflammatory Disorder ◽  
Chronic Inflammatory Disorder ◽  
Asthma Patients ◽  
Related Quality ◽  
The Impact

Asthma is a chronic inflammatory disorder of the airways, ounknown etiology and growing prevalence (GINA, 2009). Appropriate asthma management can control the disorder and enable patients to enjoy a good quality of life (WHO, 2007).Yet, many asthma patients are unable to maintain asthma control (Rabe et al., 2003) for various reasons, including psychological ones (Feldman et al., 2005).This study examined the prevalence of psychomorbidity, and its interaction with asthma control difficulties and asthma-related quality of life in a sample of 200 asthma patients in Cyprus. Asthma diagnoses and severity were established by medical chart review.Psychomorbidity was evaluated using the Patient Health Questionnaire (Spitzer, 1999). Additionally, the impact of asthma-specific (e.g. asthma knowledge), health-specific (e.g. smoking history) and socio-demographic (e.g. perceived poverty) factors was examined as prior research literature suggests these may significantly impact asthma control and asthma-related quality of life.Currently, the present study is in its final stages of data collection (to conclude 2010). The results will offer valuable insights into the mechanisms and factors which affect asthma control, quality of life, and psychomorbidity. In doing so, the present study will contribute to the improved understanding of asthma patients’ experiences, essential to guide medical and psychological interventions.

scholarly journals Long-term adherence to inhaled corticosteroids and asthma control in adult-onset asthma

2021 ◽  
Vol 7 (1) ◽  
pp. 00715-2020
Author(s):  
Iida Vähätalo ◽  
Hannu Kankaanranta ◽  
Leena E. Tuomisto ◽  
Onni Niemelä ◽  
Lauri Lehtimäki ◽  
...  
Keyword(s):  
Asthma Control ◽  
Inhaled Corticosteroids ◽  
Early Recognition ◽  
Forced Expiratory Volume ◽  
Rapid Decline ◽  
Adult Onset ◽  
Lung Function Decline ◽  
Adult Asthma ◽  
Asthma Patients

BackgroundIn short-term studies, poor adherence to inhaled corticosteroids (ICS) has been associated with worse asthma control, but the association of long-term adherence and disease control remains unclear.ObjectiveTo assess the relationship between 12-year adherence to ICS and asthma control in patients with adult-onset asthma.MethodsAs part of the Seinäjoki Adult Asthma Study, 181 patients with clinically confirmed new-onset adult asthma and regular ICS medication were followed-up for 12 years. Adherence (%) to ICS was assessed individually ((µg dispensed/µg prescribed)×100) during the follow-up. Asthma control was evaluated after 12 years of treatment according to the Global Initiative for Asthma 2010 guideline.ResultsAsthma was controlled in 31% and not controlled (partly controlled or uncontrolled) in 69% of the patients. Patients with not-controlled asthma were more often male, older, nonatopic and used higher doses of ICS than those with controlled disease. The mean±sd 12-year adherence to ICS was 63±38% in patients with controlled asthma and 76±40% in patients with not-controlled disease (p=0.042). Among patients with not-controlled asthma, those with lower 12-year adherence (<80%) had more rapid decline in forced expiratory volume in 1 s (−47 mL·year−1) compared to patients with better adherence (≥80%) (−40 mL·year−1) (p=0.024). In contrast, this relationship was not seen in patients with controlled asthma.ConclusionsIn adult-onset asthma, patients with not-controlled disease showed better 12-year adherence to ICS treatment than those with controlled asthma. In not-controlled disease, adherence <80% was associated with more rapid lung function decline, underscoring the importance of early recognition of such patients in routine clinical practice.

scholarly journals The impact of using a mobile application to improve asthma patients’ adherence to medication in Jordan

2021 ◽  
Vol 27 (3) ◽  
pp. 146045822110429
Author(s):  
Mohammad K Al-Nawayseh ◽  
Montaha AL-Iede ◽  
Eman Elayeh ◽  
Rima Hijazeen ◽  
Khaled Al Oweidat ◽  
...  
Keyword(s):  
Medication Adherence ◽  
Asthma Control ◽  
Mobile Application ◽  
Intervention Group ◽  
P Value ◽  
Asthma Control Test ◽  
Adherence To Medication ◽  
Asthma Patients ◽  
Act Score ◽  
The Impact

The main aim of this study is to assess the effectiveness of using a developed asthma mobile application to enhance medication adherence in Jordan. Asthma patients visiting outpatient respiratory clinics and using inhalers were recruited. Patients were assigned into two groups: intervention and control. The intervention group was instructed to download and use the application. Asthma control was assessed using Asthma Control Test (ACT) at baseline and at follow-up of 3 months for both groups. A total of 171 patients (control, n = 83, and intervention, n = 88) participated in the study. After 3 months of usage, patients in the intervention group achieved a significant improvement in ACT score compared to control ( p-value <0.05), and reported a significant satisfaction of the application use. Therefore, the asthma mobile application is found as an effective tool to enhance medication adherence in asthma patients.

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