scholarly journals Precision Medicine in Targeted Therapies for Severe Asthma: Is There Any Place for “Omics” Technology?

2018 ◽  
Vol 2018 ◽  
pp. 1-15 ◽  
Author(s):  
Carla Galeone ◽  
Chiara Scelfo ◽  
Francesca Bertolini ◽  
Marco Caminati ◽  
Patrizia Ruggiero ◽  
...  
Keyword(s):  
Severe Asthma ◽  
Current Knowledge ◽  
Asthma Management ◽  
Biological Therapies ◽  
Omics Technologies ◽  
Asthma Phenotypes ◽  
Asthmatic Patients ◽  
Severe Asthmatic ◽  
Appropriate Therapy ◽  
Personalized Approach

According to the current guidelines, severe asthma still represents a controversial topic in terms of definition and management. The introduction of novel biological therapies as a treatment option for severe asthmatic patients paved the way to a personalized approach, which aims at matching the appropriate therapy with the different asthma phenotypes. Traditional asthma phenotypes have been decomposing by an increasing number of asthma subclasses based on functional and physiopathological mechanisms. This is possible thanks to the development and application of different omics technologies. The new asthma classification patterns, particularly concerning severe asthma, include an increasing number of endotypes that have been identified using new omics technologies. The identification of endotypes provides new opportunities for the management of asthma symptoms, but this implies that biological therapies which target inflammatory mediators in the frame of specific patterns of inflammation should be developed. However, the pathway leading to a precision approach in asthma treatment is still at its beginning. The aim of this review is providing a synthetic overview of the current asthma management, with a particular focus on severe asthma, in the light of phenotype and endotype approach, and summarizing the current knowledge about “omics” science and their therapeutic relevance in the field of bronchial asthma.

A study on symptom improvement and efϑicacy of formoterol plus budesonide in the asthma management in northern parts of Tamil Nadu

2021 ◽  
Vol 12 (1) ◽  
pp. 742-748
Author(s):  
Mani Dhandayuthapani ◽  
Murugesh Shivashankar ◽  
Uma K
Keyword(s):  
Tamil Nadu ◽  
Asthma Management ◽  
Symptom Improvement ◽  
Asthmatic Patients ◽  
Severe Asthmatic ◽  
Number Of Patients ◽  
One Year ◽  
Experienced Symptom

The purpose is to study the asthma symptom improvement and efficacy of formoterol (LABA) and Budesonide (ICS) combination in the asthma management in northern districts of Tamilnadu. It is a multicentric, non-comparative, questionnaire and random sampling study was conducted in 145 mild to severe asthmatic patients. They were in Formoterol plus budesonide combination inhalation drugs available in DPI and pMDI. Among the 145 asthmatic patients, 45 patients, 6 patients and 94 patients were in DPI, nebuliser and pMDI devices respectively. During drug initiation, The Asthmatics were in mild (27%), Moderate (57%) and Severe (16%) stages. After one year of follow-up, the number of patients in the mild is 84%, moderate 14% and severe 2%. Among 45 DPI Asthmatic patients, 29 patients, 15 patients and 1 patient have reported the handling the devices as easy, medium and hard respectively. On the other hand, 94 pMDI asthmatic patients, 38 patients, 48 patients and 8 patients have reported the handling of devices as easy, medium and hard respectively. The treatment resulted in 77 patients as good, 65 as satisfactory and 3 as same. After one year, all the 145 asthmatic patients adhered with the treatment and experienced symptom improvement with 53% patients as good, 45% patients as satisfactory and 2% patients as same. The treatment of formoterol and budesonide combination in the northern districts of Tamilnadu have effectively controlled the asthmatic symptoms and improved the quality of life in asthmatics. Moreover, the patient's adherence to the treatment is good in the northern parts of Tamilnadu.

scholarly journals Asthma Control during COVID-19 Lockdown in Patients with Severe Asthma under Biological Drug Treatment

2021 ◽  
Vol 11 (24) ◽  
pp. 12089
Author(s):  
Corrado Pelaia ◽  
Alessandro Casarella ◽  
Gianmarco Marcianò ◽  
Lucia Muraca ◽  
Vincenzo Rania ◽  
...  
Keyword(s):  
Asthma Control ◽  
Severe Asthma ◽  
Health Facilities ◽  
Biological Therapies ◽  
Biological Drugs ◽  
Exacerbation Rate ◽  
Severe Asthmatic ◽  
Access To Health ◽  
The Mean ◽  
Act Score

Introduction: Coronavirus disease 2019 (COVID-19) has deeply affected the management of patients with severe asthma, treated with add-on biological therapies. Objective: In this study, severe asthmatic patients on treatment with one of three different biologics (omalizumab, mepolizumab, benralizumab) underwent a survey to evaluate the effects of COVID-19 on the management of their clinical condition, with regard to the changes caused by the limited access to health facilities during the pandemic period. Methods: In this prospective observational study, 28 severe asthmatic outpatients referring to the Respiratory Unit of Magna Graecia University Hospital, Catanzaro (Italy), were asked to answer a telephone survey from May to July 2021. This survey included the evaluation of demographic and clinical data, as well as the number of lung function tests performed, exacerbations, biologic doses administered at hospital, or at general practitioner office, or through self-administration. Adherence to biological therapies before and during the pandemic period was also assessed. Moreover, the most recent asthma control test (ACT) score and the last forced expiratory volume in the first second (FEV1) measurement, recorded during the pandemic phase, were compared to the pre-pandemic (baseline) period. Results: When comparing the pre-pandemic data with the pandemic observations, the mean ACT score and the exacerbation rate did not significantly change [ACT, 21.5 ± 2.8 to 23.0 ± 3.9 (p = 0.1); exacerbation rate, 0.3 ± 0.6 and 0.5 ± 1.5 (p = 0.3)]. When considering some variables related to disease management in the same periods, a statistically significant difference was detected with regard to the mean number of outpatient visits (5.2 ± 3.8 vs. 0.9 ± 2.5, p < 0.0001), as well as to the mean number of accesses to health facilities for the administration of biological drugs (from 7.0 ± 3.4 to 2.5 ± 3.9, p < 0.0001). None of the patients reported to have been infected with the SARS-CoV-2 virus and no adverse drug reactions (ADR) occurred during the study. Conclusions: The above results suggest that COVID-19 pandemic did not induce any significant change related to severe asthma control. Indeed, add-on treatment with biological drugs was regularly continued, despite the obvious limited access to health facilities.

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 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.

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 Molecular Targets for Biological Therapies of Severe Asthma

2020 ◽  
Vol 11 ◽  
Author(s):  
Corrado Pelaia ◽  
Claudia Crimi ◽  
Alessandro Vatrella ◽  
Caterina Tinello ◽  
Rosa Terracciano ◽  
...  
Keyword(s):  
Severe Asthma ◽  
Inflammatory Responses ◽  
Immunoglobulin E ◽  
Asthma Management ◽  
Bronchial Obstruction ◽  
Biological Therapies ◽  
Interleukin 5 ◽  
Individual Traits ◽  
The Individual

Asthma is a heterogeneous respiratory disease characterized by usually reversible bronchial obstruction, which is clinically expressed by different phenotypes driven by complex pathobiological mechanisms (endotypes). Within this context, during the last years several molecular effectors and signalling pathways have emerged as suitable targets for biological therapies of severe asthma, refractory to standard treatments. Indeed, various therapeutic antibodies currently allow to intercept at different levels the chain of pathogenic events leading to type 2 (T2) airway inflammation. In addition to pro-allergic immunoglobulin E (IgE), that chronologically represents the first molecule against which an anti-asthma monoclonal antibody (omalizumab) was developed, today other targets are successfully exploited by biological treatments of severe asthma. In particular, pro-eosinophilic interleukin 5 (IL-5) can be targeted by mepolizumab or reslizumab, whereas benralizumab is a selective blocker of IL-5 receptor. Moreover, dupilumab behaves as a dual receptor antagonist of pleiotropic interleukins 4 (IL-4) and 13 (IL-13). Besides these drugs that are already available in medical practice, other biologics are under clinical development such as those targeting innate cytokines, also including the alarmin thymic stromal lymphopoietin (TSLP), which plays a key role in the pathogenesis of type 2 asthma. Therefore, ongoing and future biological therapies are significantly changing the global scenario of severe asthma management. These new therapeutic options make it possible to implement phenotype/endotype-specific treatments, that are delineating personalized approaches precisely addressing the individual traits of asthma pathobiology. Such tailored strategies are thus allowing to successfully target the immune-inflammatory responses underlying uncontrolled T2-high asthma.

Asthma: An Important Disease to Otolaryngologists — Part III: Anti-Inflammatory Therapy

1996 ◽  
Vol 75 (4) ◽  
pp. 216-224 ◽  
Author(s):  
Bruce R. Gordon
Keyword(s):  
Lower Respiratory Tract ◽  
Current Knowledge ◽  
Asthma Management ◽  
Chronic Inflammatory Disease ◽  
Beta Agonist ◽  
Asthmatic Patients ◽  
Environmental Controls ◽  
Anti Inflammatory ◽  
Pharmacologic Treatments ◽  
Important Disease

Asthma is a chronic inflammatory disease of the lower respiratory tract which is triggered by exposure to allergens or other airway irritants, and is commonly encountered in otolaryngologic practice. This three-part review is designed to assist otolaryngologists in recognizing and managing asthmatic patients. Part one summarized current knowledge of the pathophysiology and increasing prevalence of asthma, and its assessment and diagnosis. Part two discussed asthma management by environmental controls, anti-inflammatory therapies, and patient education, and compared pharmacologic treatments which are not primarily anti-inflammatory. These include mucolytic, anticholinergic, antihistamine, theophylline and beta agonist drugs. In this final part, anti-inflammatory treatments for asthma control are critically reviewed, including a balanced discussion of cromolyn, nedocromil, glucocorticoids, allergy immunotherapy, and the appropriate indications, possible toxicities and reasonable precautions for their use.

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 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.

New oxazolidines inhibit the secretion of IFN-γ and IL-17 by PBMCS from moderate to severe asthmatic patients

2020 ◽  
Vol 16 ◽  
Author(s):  
Renata Virgínia Cavalcanti Santos ◽  
Eudes Gustavo Constantino Cunha ◽  
Gabriela Souto Vieira de Mello ◽  
José Ângelo Rizzo ◽  
Jamerson Ferreira de Oliveira ◽  
...  
Keyword(s):  
Severe Asthma ◽  
Treatment Resistance ◽  
In Silico Analysis ◽  
Asthmatic Patients ◽  
Novel Approach ◽  
Severe Asthmatic ◽  
Cytokine Levels ◽  
Ifn Γ ◽  
Neurokinin 1 ◽  
Common Target

Background: Moderate to severe asthma could be induced by diverse proinflammatory cytokines, as IL-17 and IFN-γ, which are also related to treatment resistance and airway hyperresponsiveness. Oxazolidines emerged as a novel approach for asthma treatment, since some chemical peculiarities were suggested by previous studies. Objective: The present study aimed to evaluate the IL-17A and IFN-γ modulatory effect of two new oxazolidine derivatives (LPSF/NB-12 and -13) on mononucleated cells of patients with moderate and severe asthma. Methods: The study first looked at potential targets for oxazolidine derivatives using SWISS-ADME. After the synthesis of the compounds, cytotoxicity and cytokine levels were analyzed. Results: We demonstrated that LPSF/NB-12 and -13 reduced IFN-γ and IL-17 production in peripheral blood mononucleated cells from asthmatic patients in a concentrated manner. Our in silico analysis showed the neurokinin-1 receptor as a common target for both compounds, which is responsible for diverse proinflammatory effects of moderate and severe asthma. Conclusion: The work demonstrated a novel approach against asthma, which deserves further studies of its mechanisms of action.

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