scholarly journals Small RNA Species and microRNA Profiles are Altered in Severe Asthma Nanovesicles from Broncho Alveolar Lavage and Associate with Impaired Lung Function and Inflammation

2019 ◽  
Vol 5 (4) ◽  
pp. 51 ◽  
Author(s):  
Ana S. Francisco-Garcia ◽  
Eva M. Garrido-Martín ◽  
Hitasha Rupani ◽  
Laurie C. K. Lau ◽  
Rocio T. Martinez-Nunez ◽  
...  
Keyword(s):  
Severe Asthma ◽  
Small Rna ◽  
Small Rna Sequencing ◽  
Filtration Method ◽  
Asthmatic Patients ◽  
Expression Of Genes ◽  
Severe Asthmatic ◽  
Asthma Patients ◽  
Impaired Lung Function ◽  
The Impact

MicroRNAs are known to regulate important pathways in asthma pathology including the IL-6 and IFN pathways. MicroRNAs have been found not only within cells but also within extracellular vesicles such as exosomes. In this study, we particularly focused on microRNA cargo of nanovesicles in bronchoalveolar lavage of severe asthmatic patients. We extracted nanovesicle RNA using a serial filtration method. RNA content was analyzed with small RNA sequencing and mapped to pathways affected using WebGestalt 2017 Software. We report that severe asthma patients have deficient loading of microRNAs into their airway luminal nanovesicles and an altered profile of small RNA nanovesicle content (i.e., ribosomal RNA and broken transcripts, etc.). This decrease in microRNA cargo is predicted to increase the expression of genes by promoting inflammation and remodeling. Consistently, a network of microRNAs was associated with decreased FEV1 and increased eosinophilic and neutrophilic inflammation in severe asthma. MicroRNAs in airway nanovesicles may, thus, be valid biomarkers to define abnormal biological disease processes in severe asthma and monitor the impact of interventional therapies.

scholarly journals Risk factors for the development of bronchiectasis in patients with asthma

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Donghai Ma ◽  
María-Jesús Cruz ◽  
Iñigo Ojanguren ◽  
Christian Romero-Mesones ◽  
Diego Varona-Porres ◽  
...  
Keyword(s):  
Risk Factors ◽  
Logistic Regression ◽  
Asthma Control ◽  
Severe Asthma ◽  
Factors Associated ◽  
Asthmatic Patients ◽  
Asthma Exacerbations ◽  
Severe Asthmatic ◽  
Asthma Patients ◽  
High Age

AbstractThough asthma and bronchiectasis are two different diseases, their coexistence has been demonstrated in many patients. The aim of the present study is to compare the characteristics of asthmatic patients with and without bronchiectasis and to assess risk factors for the development of this condition. Two hundred and twenty-four moderate-severe asthmatic patients were included. The severity of bronchiectasis was assessed by Reiff and FACED parameters. Logistic regression was used to identify independent factors associated with bronchiectasis. Bronchiectasis was identified in 78 asthma patients. In severe asthma patients, its prevalence was 56.9%. Bronchiectasis was defined as mild in81% of patients using modified Reiff criteria and in 74% using FACED criteria. Asthmatic patients with bronchiectasis had decreasing FEV1, FVC and FEV1/FVC (p = 0.002, 0.005 and 0.014 respectively), presented more frequent asthma exacerbations (p < 0.001) and worse asthma control (ACT 21 vs 16pts, p < 0.001). Factors independently associated with bronchiectasis were older age (42–65 years: OR, 3.99; 95% CI 1.60 to 9.95, P = 0.003; ≥ 65 years: OR, 2.91; 95% CI 1.06 to 8.04, P = 0.039), severe asthma grade (OR, 8.91; 95% CI 3.69 to 21.49; P < 0.001) and frequency of asthma exacerbations (OR, 4.43; 95% CI 1.78 to 11.05; P < 0.001). In patients with severe asthma, age of asthma onset (OR, 1.02; 95% CI 1.01 to 1.04; P = 0.015) and asthma exacerbations (OR, 4.88; 95% CI 1.98 to 12.03; P = 0.001) were independently associated with the development of bronchiectasis. The prevalence of bronchiectasis in severe asthmatic patients is high. Age of asthma onset and exacerbations were independent factors associated with the occurrence of bronchiectasis.

scholarly journals The 14q32 maternally imprinted locus is a major source of longitudinally stable circulating microRNAs as measured by small RNA sequencing

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Gabriel N. Valbuena ◽  
Sophia Apostolidou ◽  
Rhiannon Roberts ◽  
Julie Barnes ◽  
Wendy Alderton ◽  
...  
Keyword(s):  
Chronic Disease ◽  
Rna Sequencing ◽  
Small Rna ◽  
Intraclass Correlation ◽  
Correlation Coefficients ◽  
Critical Factor ◽  
Alternative Methods ◽  
Small Rna Sequencing ◽  
Diagnosis And Prognosis ◽  
The Impact

Abstract Understanding the normal temporal variation of serum molecules is a critical factor for identifying useful candidate biomarkers for the diagnosis and prognosis of chronic disease. Using small RNA sequencing in a longitudinal study of 66 women with no history of cancer, we determined the distribution and dynamics (via intraclass correlation coefficients, ICCs) of the miRNA profile over 3 time points sampled across 2–5 years in the course of the screening trial, UKCTOCS. We were able to define a subset of longitudinally stable miRNAs (ICC >0.75) that were individually discriminating of women who had no cancer over the study period. These miRNAs were dominated by those originating from the C14MC cluster that is subject to maternal imprinting. This assessment was not significantly affected by common confounders such as age, BMI or time to centrifugation nor alternative methods to data normalisation. Our analysis provides important benchmark data supporting the development of miRNA biomarkers for the impact of life-course exposure as well as diagnosis and prognostication of chronic disease.

scholarly journals Elevation of serum soluble E-selectin and VCAM-1 in severe asthma

2001 ◽  
Vol 10 (6) ◽  
pp. 339-342 ◽  
Author(s):  
Agnes Hamzaoui ◽  
Jamel Ammar ◽  
Fethi El Mekki ◽  
Olfa Borgi ◽  
Hédia Ghrairi ◽  
...  
Keyword(s):  
Severe Asthma ◽  
Serum Levels ◽  
Assay Method ◽  
Moderate Asthma ◽  
Asthmatic Patients ◽  
Immunological Markers ◽  
Healthy Donors ◽  
Severe Asthmatic ◽  
Enzymelinked Immunosorbent Assay ◽  
Cell Adhesion Molecule 1

Objective:To investigate the significance of circulating adhesion molecules associated with leucocyteendothelial cell interactions in asthma, serum levels of soluble E (sE)-selectin, soluble P (sP)-selectin, soluble L (sL)-selectin, and soluble vascular cell adhesion molecule-1 (sVCAM-1) were measured in mild, moderate and severe asthma.Method:Serum levels of sE-selectin, sP-selectin, sLselectin, and sVCAM-1 were measured in 32 women with asthma and 30 healthy donors using an enzymelinked immunosorbent assay method. Twenty patients were suffering from severe asthma, and 12 from mild/moderate asthma.Results:Serum sE-selectin and sVCAM-1 levels from patients with asthma were significantly higher than those observed in healthy donors(p<0.01). The levels of sP-selectin were the same as those of controls. The level of sE-selectin exhibited an important increase in the severe asthmatic patients compared with mild/moderate asthma(p<0.01). The sVCAM-1 level was increased in severe asthma when compared with healthy controls. There was no correlation between the levels of soluble selectins and the age of the patients. A significant correlation was found between sE-selectin and sVCAM-1 levels.Conclusion:These data indicate that circulating soluble forms of the selectins may have different kinetics during the clinical course of asthma, suggesting that they may reflect different inflammatory pathways in severe asthma. Both sVCAM-1 and sE-selectin may be useful immunological markers for monitoring disease activity in asthma.

scholarly journals The Levels of Serum Biomarkers in Stable Asthma Patients with Comorbidities

2019 ◽  
Author(s):  
Emel Ceylan ◽  
Sertan Bulut ◽  
Mustafa Yılmaz ◽  
Hüseyin Örün ◽  
Fisun Karadağ ◽  
...  
Keyword(s):  
Systemic Inflammation ◽  
Venous Blood ◽  
Clinical Manifestations ◽  
High Sensitivity ◽  
Control Group ◽  
Inflammation Markers ◽  
Cationic Protein ◽  
Asthmatic Patients ◽  
Asthma Patients ◽  
The Impact

The effects of comorbidities on systemic inflammation markers in stable asthmatics and the consequences of such effects have not been well evaluated. We aimed to evaluate the effect of comorbidities on clinical manifestations and systemic inflammation in asthmatic patients under control. The study group consisted of asthmatic patients who applied to our pulmonology outpatient clinic and volunteered to participate. 120 clinically stable asthma patients (71 females and 49 males) and 35 healthy controls (19 females and 16 males) with similar age, gender, and body mass index distributions were admitted to the study. The levels of osteopontin, interleukin 6 (IL-6), interleukin 8 (IL-8), interleukin 13 (IL-13), eosinophilic cationic protein, adiponectin, and high-sensitivity C-reactive protein of the individuals were evaluated using commercial ELISA kits by taking venous blood samples. Of 120 asthmatic subjects, 47 (39,2%) had comorbidities and allergic rhinitis (15%) coexisted most frequently. Other comorbidities associated with asthma were gastroesophageal reflux, sinusitis, hypertension, diabetes, gastritis, and peptic ulcus respectively. There was no physician-diagnosed comorbidity in the control group. The levels of IL-6 and IL-8 were found higher in asthma group with comorbidities when compared to those with no comorbidities (p values were 0.032 and 0.046, respectively). Comorbidities interfere with the diagnosis and treatment of asthma, besides affecting the disease control. Our findings suggest the possibility of the impact of comorbidities on systemic inflammation markers, especially IL-6 and IL-8. To evaluate the impact of comorbidities on asthma control and systemic markers, further studies are needed.

scholarly journals FACTORS ASSOCIATED WITH A SEVERE ASTHMA IN ASTHMATIC ADOLESCENT PATIENTS

2020 ◽  
Vol 4 (12) ◽  
Author(s):  
Khaled Hassan
Keyword(s):  
Severe Asthma ◽  
Well Being ◽  
Asthma Patient ◽  
Cross Sectional ◽  
Significance Level ◽  
Factors Associated ◽  
Individual Interviews ◽  
Asthmatic Patients ◽  
Asthma Patients ◽  
History Of

Introduction: The present study aims to determine the frequency of severe asthma in asthma patients followed at the National Hospital of Pneumo-Phtisiology (CNHPP) of Cotonou and to identify the risk factors associated with it Methods: The cross-sectional, descriptive and analytical study focused on 213 asthmatic patients in the 2013 active file of the CNHPP. The data were collected through the use of files and individual interviews with patients. They were processed and analyzed using EPIINFO7 and STATA11 software. Pearson's Chi 2 test, unvaried and multivariate logistic regression were used at the significance level of 0.05 Results: A total of 154 asthmatic patients, ie 72.7%, answered the questionnaire. Among them 20.8% (95% CI: (14.67; 28.05)) suffered from severe asthma. Patient ages ranged from 10 to 76 years with a median of 41 years; 51.3% were female, 79.9% had a history of allergy, 61.7% started their asthma after the age of 12, and only 11% had used or consumed tobacco. The factors associated with the onset of severe asthma were: age 46 to 55 years (p = 0.04); the third and fourth quintiles of economic well-being (p = 0.01) and the onset of asthma after the age of 12 (p <0.001) Conclusion: The study showed a high frequency of severe asthma in Benin and will improve its management at the CNHPP. Keywords: Severe asthma, patients, associated factors, Benin

Evaluation of bronchial wall thickness in asthma using magnetic resonance imaging

2021 ◽  
pp. 2100329
Author(s):  
Ilyes Benlala ◽  
Gaël Dournes ◽  
Pierre-Olivier Girodet ◽  
Thomas Benkert ◽  
François Laurent ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Magnetic Resonance ◽  
Severe Asthma ◽  
Altman Analysis ◽  
Resonance Imaging ◽  
Bronchial Wall ◽  
Bland Altman Analysis ◽  
Wall Area ◽  
Asthmatic Patients ◽  
Severe Asthmatic

BackgroundBronchial thickening is a pathological feature of asthma that has been evaluated using computed tomography (CT), an ionised radiation technique. Magnetic Resonance Imaging (MRI) with Ultrashort Echo Time (UTE) pulse sequences could be an alternative to CT.ObjectivesTo measure bronchial dimensions using MRI-UTE in asthmatic patients, by evaluating the accuracy and agreement with CT, by comparing severe and non-severe asthma and by correlating with pulmonary function tests.MethodsWe assessed bronchial dimensions (wall area (WA), lumen area (LA), normalised wall area (WA%), and wall thickness (WT)) by MRI-UTE and CT in 15 non-severe and 15 age- and sex-matched severe asthmatic patients (NCT03089346). Accuracy and agreement between MRI and CT was evaluated by paired t-tests and Bland-Altman analysis. Reproducibility was assessed by intra-class correlation coefficient and Bland-Altman analysis. Comparison between non-severe and severe asthmatic parameters was performed by Student-t, Mann-Whitney or Fisher's Exact tests. Correlations were assessed by Pearson or Spearman coefficients.ResultsLA, WA%, and WT were not significantly different between MRI-UTE and CT, with good correlations and concordance. Inter- and intra-observer reproducibility was moderate to good. WA% and WT were both higher in severe than in non-severe asthmatic patients. WA, WA% and WT were all negatively correlated with FEV1.ConclusionWe demonstrated that MRI-UTE is an accurate and reliable radiation-free method to assess bronchial wall dimensions in asthma, with enough spatial resolution to differentiate severe from non-severe asthma.

scholarly journals Oral Corticosteroids Dependence and Biologic Drugs in Severe Asthma: Myths or Facts? A Systematic Review of Real-World Evidence

2021 ◽  
Vol 22 (13) ◽  
pp. 7132
Author(s):  
Luigino Calzetta ◽  
Marina Aiello ◽  
Annalisa Frizzelli ◽  
Giuseppina Bertorelli ◽  
Paola Rogliani ◽  
...  
Keyword(s):  
Systematic Review ◽  
Severe Asthma ◽  
Real World ◽  
Symptom Control ◽  
Airflow Limitation ◽  
Biologic Drugs ◽  
Asthmatic Patients ◽  
Severe Asthmatic ◽  
Oral Corticosteroids ◽  
Sparing Effect

Airway inflammation represents an important characteristic in asthma, modulating airflow limitation and symptom control, and triggering the risk of asthma exacerbation. Thus, although corticosteroids represent the cornerstone for the treatment of asthma, severe patients may be dependent on oral corticosteroids (OCSs). Fortunately, the current humanised monoclonal antibodies (mAbs) benralizumab, dupilumab, mepolizumab, omalizumab, and reslizumab have been proven to induce an OCS-sparing effect in randomized controlled trials (RCTs), thus overcoming the problem of OCS dependence in severe asthma. Nevertheless, a large discrepancy has been recognized between selected patients enrolled in RCTs and non-selected asthmatic populations in real-world settings. It is not possible to exclude that the OCS-sparing effect of mAbs resulting from the RCTs could be different than the real effect resulting in clinical practice. Therefore, we performed a systematic review and correlation analysis to assess whether mAbs are effective in eliciting an OCS-sparing effect and overcoming the OCS dependence in severe asthmatic patients in real-world settings. Overall, real-world studies support the evidence that OCS dependence is a real condition that, however, can be found only in a small number of really severe asthmatic patients. In most patients, the dependence on OCS can be related to modifying factors that, when adequately modulated, may lead to a significant reduction or suspension of OCS maintenance. Conversely, in severe asthmatics in whom OCS resistance is proved by a high daily dose intake, mAbs allow reversion of the OCS dependence, leading to the suspension of OCS therapy in most patients or >50% reduction in the daily OCS dose.

scholarly journals Small-RNA sequencing reveals altered skeletal muscle microRNAs and snoRNAs signatures in weanling male offspring from mouse dams fed a low protein diet during lactation

2021 ◽  
Author(s):  
Ioannis Kanakis ◽  
Moussira Alameddine ◽  
Leighton Folkes ◽  
Simon Moxon ◽  
Ioanna Myrtziou ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Small Rna ◽  
Molecular Mechanisms ◽  
Male Offspring ◽  
Protein Diet ◽  
Low Protein Diet ◽  
Histological Evaluation ◽  
Small Rna Sequencing ◽  
Low Protein ◽  
The Impact

ABSTRACTNutrition plays a key role in pre- and postnatal growth of the musculoskeletal system. Maternal diet during gestation and lactation affects the development of skeletal muscles in the offspring and determines muscle health in later life, however, the molecular mechanisms that govern these effects are largely unknown. In this study, we aim to describe the association between maternal low protein diet-induced changes in offspring skeletal muscle and the differential expression (DE) of small non-coding RNAs (sncRNAs). We used a mouse model of maternal protein restriction to characterise the impact of early-life undernutrition on skeletal muscle morphology in male offspring at weaning. Mouse dams were fed either a normal (N, 20%) or a low protein (L, 8%) diet during gestation and newborn pups were cross-fostered to N or L lactating dams, resulting in the generation of NN, NL and LN offspring groups. Total body and tibialis anterior (TA) weights were decreased in NL males but not different in the LN group, as compared to NN, although neonates from low protein fed dams were smaller at birth than those born to dams fed a normal protein. However, histological evaluation of TA muscle revealed reduced muscle fibre size in both groups at the end of lactation. Small RNA-seq analysis demonstrated DE of multiple classes of sncRNAs, including miRs, snoRNAs and snRNAs. Bioinformatic analyses of miRs-15a, −34a, −122 and −199a, in combination with known myomiRs, confirmed their implication in key muscle-specific biological processes and cellular functions and suggest a promising set of miRs in muscle physiology studies. To our knowledge, this is the first comprehensive report for the DE of sncRNAs in nutrition-associated programming of skeletal muscle development, highlighting the need for further research.

scholarly journals Defining type 2 asthma and patients eligible for dupilumab in Italy: a biomarker-based analysis

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Giorgio Walter Canonica ◽  
Francesco Blasi ◽  
Nunzio Crimi ◽  
Pierluigi Paggiaro ◽  
Alberto Papi ◽  
...  
Keyword(s):  
Severe Asthma ◽  
Immunoglobulin E ◽  
Cost Effective ◽  
Mucus Production ◽  
Clinical Indicators ◽  
Asthmatic Patients ◽  
Eligible Population ◽  
Asthma Patients ◽  
Severe Type

Abstract Background Asthma is a chronic disease characterized by airway hyperresponsiveness, inflammation and mucus production. In Type 2 asthma, two phenotypic components are often co-expressed (eosinophilic and allergic). Elevated biomarker levels, such as eosinophils (EOS), fraction of exhaled nitric oxide (FeNO) and immunoglobulin E (IgE), are key clinical indicators of Type 2 inflammation. Dupilumab has been recently approved for the treatment of uncontrolled severe Type 2 asthma. Type 2 asthma includes allergic and/or eosinophilic phenotypes. The aim of this analysis was to estimate the dupilumab-eligible population in Italy and characterize it by expected biomarker status. Methods A 4-step approach was carried out to calculate dupilumab-eligible population. The approach consisted in: (1) estimating the total number of asthma patients in Italy (using 2016–2017 Italian-adapted Global Initiative for Asthma -GINA- guidelines); (2) estimating the number of severe asthma patients with poorly controlled or uncontrolled disease (using the findings of two recent administrative claim analyses conducted in Italy); (3) stratifying the severe uncontrolled population by biomarker levels (EOS, FeNO and IgE) according to the outcomes of the QUEST trial (a clinical study assessing the efficacy of dupilumab in patients with uncontrolled moderate-to-severe asthma; NCT02414854); (4) identifying the sub-populations of severe uncontrolled asthma patients characterised by raised blood EOS and/or FeNO level (thus indicated to receive dupilumab). Results According to these estimates, about 3.3 million asthmatic patients live in Italy (6.10% of the population). Of them, almost 20 thousand (N = 19,960) have uncontrolled severe asthma. Dupilumab-eligible patients would be N = 15,988, corresponding to 80.1% of the total uncontrolled severe population. Most of these patients (89.3%; N = 14,271) have at least an increase of EOS level, while slightly more than half (51.9%; N = 8,303) have raised levels of both biomarkers. Increased FeNO levels without increased EOS are observed less frequently (N = 1,717; 10.7% of the eligible population). Conclusions There is a strong rationale for testing all asthma biomarkers during diagnosis and disease follow-up. Given the large availability and the limited costs, these tests are cost-effective tools to detect severe Type 2 asthma, stratify patients by phenotype, and drive appropriate treatment decisions.

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