Analysis of cell-specific peripheral blood biomarkers in severe allergic asthma identifies innate immune dysfunction

Asthma is a disease of complex origin and multiple pathologies. There are currently very few biomarkers of proven utility in its diagnosis, management or response to treatment. Recent studies have identified multiple asthma phenotypes following biofluid analysis; however, such findings may be driven by the well-characterised alterations in immune cell populations in asthma. We present a study designed to identify cell type-specific gene signatures of severe allergic asthma in peripheral blood samples. Using transcriptomic profiling of four magnetically purified peripheral blood cell types, we identify significant gene expression changes in monocytes and NK cells but not T lymphocytes in severe asthmatics. Pathway analysis indicates dysfunction of immune cell regulation and bacterial suppression in the NK cells. These gene expression changes may be useful on their own as prognostic peripheral blood cell markers of severe asthma, but also may indicate novel cell pathways for therapeutic intervention.

Predictors of a Minimal Clinically Important Difference Following Omalizumab Treatment in Adult Patients With Severe Allergic Asthma

Several factors have been found to be predictors of a good response following omalizumab treatment in patients with severe allergic asthma (SAA). However, it remains unclear whether clinical characteristics can predict a minimal clinically important difference (MCID) following omalizumab treatment in this population. Therefore, the aim of this study was to investigate the features associated with an MCID following omalizumab treatment in adult patients with SAA. Of the 124 participants enrolled in this retrospective, cross-sectional study, 94, 103, 20 and 53 achieved the MCID following treatment with omalizumab and were considered to be responders of exacerbation reduction (no exacerbation during the 1-year follow-up period or ≧50% reduction in exacerbations from baseline), oral corticosteroid (OCS) sparing (no use of OCS to control asthma during the study period or a reduction of the monthly OCS maintenance dose to <50% of baseline), lung function (an increase of ≧230 ml in the forced expiratory volume in 1 s from baseline) and asthma control (an increase of ≧3 points in the asthma control test score from baseline), respectively. Normal weight [<25 vs. ≧30 kg/m2, odds ratio (OR) = 3.86, p = 0.024] was predictive of a responder of reduction in exacerbations following omalizumab treatment while subjects with a blood eosinophil level of <300 cells/μL (<300 vs. ≧300 cells/μL, OR = 5.81, p = 0.001) were more likely to exhibit an MCID in OCS sparing. No factor was found to be a predictor of lung function or asthma control. When choosing treatment for adult patients with SAA, our findings may help to select those who may benefit the most from omalizumab treatment.

Severe pediatric asthma with a poor response to omalizumab: a report of three cases and three-dimensional bronchial wall analysis

Omalizumab is used for the treatment of persistent severe allergic asthma in adults and children. However, some patients remain symptomatic even after omalizumab treatment. In bronchial asthma, chronic inflammation of the bronchial wall causes thickening of the airway wall, resulting from irreversible airway remodeling. Progression of airway remodeling causes airflow obstruction, leading to treatment resistance. We report three Japanese children with severe asthma who had a poor response to omalizumab treatment. They had a long period of inadequate management of asthma before initiating omalizumab. Even after omalizumab treatment, their symptoms persisted, and the parameters of spirometry tests did not improve. We hypothesized that omalizumab was less effective in these patients because airway wall remodeling had already progressed. We retrospectively evaluated the bronchial wall thickness using a three-dimensional bronchial wall analysis with chest computed tomography. The bronchial wall thickness was increased in these cases compared with six responders. Progressed airway wall thickness caused by airway remodeling may be associated with a poor response to omalizumab in children with severe asthma.

Clinical Experience with Anti-IgE Monoclonal Antibody (Omalizumab) in Pediatric Severe Allergic Asthma—A Romanian Perspective

Background: Asthma is the most common chronic disease affecting children, with a negative impact on their quality of life. Asthma is often associated with comorbid allergic diseases, and its severity may be modulated by immunoglobulin E (IgE)-mediated allergen sensitization. Omalizumab is a humanized monoclonal anti-IgE antibody, the first biological therapy approved to treat patients aged ≥6 years with severe allergic asthma. The primary objective of our study was to investigate the efficacy and safety of Omalizumab in Romanian children with severe allergic asthma. Methods: In this observational real-life study, 12 children and adolescents aged 6 to 18 years (mean 12.4 years) with severe allergic asthma received Omalizumab as an add-on treatment. Asthma control, exacerbations, lung function, and adverse events were evaluated at baseline and after the first year of treatment. Results: We observed general improvement in total asthma symptom scores and reduction in the rate of exacerbation of severe asthma. Omalizumab treatment was associated with improvement in the measures of lung function, and no serious adverse reactions were reported. FEV1 improved significantly after one year of treatment with Omalizumab [ΔFEV1 (% pred.) = 18.3], and [similarly, ΔMEF50 (%) = 25.8]. The mean severe exacerbation rate of asthma decreased from 4.1 ± 2.8 to 1.15 ± 0.78 (p < 0.0001) during the year of treatment with Omalizumab. Conclusions: This study showed that Omalizumab can be an effective and safe therapeutic option for Romanian children and adolescents with severe allergic asthma, providing clinically relevant information on asthma control and exacerbation rate in children and adolescents. The results demonstrated the positive effect of Omalizumab in young patients with asthma, starting from the first year of treatment.

Case Report: Self-Administration of Omalizumab in an Adolescent With Severe Asthma During SARS-CoV-2 Infection

Acute asthma remains one of the most frequent causes of children's access to healthcare. Asthma exacerbation is an essential defining characteristic of its severity, and respiratory infections entail increased risks of exacerbations with potential hospitalization. In the literature, contradictory findings have been reported about the risk and severity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in patients affected by asthma, with several implications for its management. Anti-IgE monoclonal antibody therapy is meant for patients affected by severe persistent allergic asthma without adequate control with other treatments. Indeed, biological therapies, such as omalizumab, are used as add-on treatments (step 5 in the Global Initiative for Asthma report) for severe asthma with several benefits, including a reduction in the frequency of exacerbations. To the best of our knowledge, we hereby report the first case in which an adolescent with severe allergic asthma treated with omalizumab has switched to self-administration at home during SARS-CoV-2 infection. Based on our peculiar experience, physicians may consider switching to self-administration of omalizumab at home, even during the coronavirus disease 2019 pandemic. However, more extensive research data from future studies are needed to confirm these first findings.

Clinical Experience with Anti-IgE Monoclonal Antibody (Omalizumab) In Paediatric Severe Allergic Asthma – A Romanian Perspective

Background: Asthma is the most common chronic disease affecting children and altering their quality of life. The severity of asthma is often modulated by immunoglobulin E (IgE)-mediated allergen sensitization and is associated with comorbid allergic dis-eases. Omalizumab is a humanized monoclonal antibody anti-IgE, the first biological therapy approved to treat patients aged &ge;6 years with severe allergic asthma. The primary objective of our study was to investigate the efficacy and safety of Omali-zumab in Romanian paediatric patients with severe allergic asthma. Methods: In this observational real-life study, 12 children aged 6 to 18 years, (mean age 12.4 years ) with severe allergic asthma received Omalizumab as an add-on treatment. The levels of asthma control, exacerbations, lung function and adverse events were evaluated at baseline and after the first year of treatment. Results: We noticed general improvements in total asthma symptom scores and the rate of exacerbation of severe asthma. Omalizumab increased the initial variables of lung function, and no serious adverse reactions were reported. FEV1 improved statistically significant after one year of treatment with Omalizumab, [&Delta;FEV1 (% pred.) =18.3, and similarly, &Delta;MEF50 (%) = 25.8]. The mean severe exacerbation rates due to asthma decreased from 4.1 (2.8 SD) to 1.15 (0.78 SD) during the treatment year (p&lt;0.0001) with Omalizumab. Conclusions: Treatment with Omalizumab can be an effective and safe therapeutic option for Romanian children with severe allergic asthma, providing clinically relevant in-formation on asthma control and exacerbation rate in children and adolescents. The results highlighted the effect of Omalizumab in young patients, starting from the first year of treatment.