Severe Allergic Asthma Research Articles

Stability of severe asthma phenotypes

Introduction. Severe asthma (SA) is a heterogeneous disease with several phenotypes. There are lack of data about its stability.Aim. To assess stability of SA phenotypes in adult patients during 5 years follow-up.Materials and methods. Prospective study included 117 adult outpatients with allergic SA, 51 severe asthmatics with aspirin-induced disease, 59 patient with persistent airflow limitation (PAL) and 35 patients with SA and concomitant COPD, 65 steroid-dependent severe asthmatics and 89 patients with SA and frequent (≥2 per year) exacerbations. Spirometry and bronchodilator reversibility testing were carried out; fractional exhaled nitric oxide (FeNO) was measured; hypersensitivity to common inhalant allergens (skin prick and blood specific IgE testing) and peripheral blood eosinophil counts were estimated. Asthma control and asthma-related quality of life were assessed by using ACQ-5 and SGRQ questionnaire.Results. During 5-year prospective study stability of aspirin-induced SA and SA with COPD was 100%. Allergic phenotype was stable in 81% of SA cases and in patients with changed atopic status we revealed worsening of symptoms and accelerated lung function decline. Stability of SA phenotype with PAL without COPD was 86% and steroid-dependent SA was stable in 55% of cases. After 5 years of treatment frequent exacerbations remained in 28% of severe asthmatics.Conclusion. The most stable phenotypes of SA were aspirin-induced and asthma with concomitant COPD. Less stable were allergic SA, steroid-dependent SA and phenotype with persistent airflow limitation. The least stable was SA phenotype with frequent exacerbations.

Efficacy and safety of omalizumab combined with allergen immunotherapy in children with moderate to severe allergic asthma.

Omalizumab enables children who are intolerant to AIT to initiate AIT successfully. Combination therapy better improves asthma and rhinitis symptoms, FeNO, and lung function compared to single SCIT or omalizumab treatment. Combination therapy reduces the incidence of adverse reactions during the initial phase of SCIT and enhances its safety.

Specific microRNA Profile Associated with Inflammation and Lipid Metabolism for Stratifying Allergic Asthma Severity.

The mechanisms underlying severe allergic asthma are complex and unknown, meaning it is a challenge to provide the most appropriate treatment. This study aimed to identify novel biomarkers for stratifying allergic asthmatic patients according to severity, and to uncover the biological mechanisms that lead to the development of the severe uncontrolled phenotype. By using miRNA PCR panels, we analyzed the expression of 752 miRNAs in serum samples from control subjects (n = 15) and mild (n = 11) and severe uncontrolled (n = 10) allergic asthmatic patients. We identified 40 differentially expressed miRNAs between severe uncontrolled and mild allergic asthmatic patients. Functional enrichment analysis revealed signatures related to inflammation, angiogenesis, lipid metabolism and mRNA regulation. A random forest classifier trained with DE miRNAs achieved a high accuracy of 97% for severe uncontrolled patient stratification. Validation of the identified biomarkers was performed on a subset of allergic asthmatic patients from the CAMP cohort at Brigham and Women's Hospital, Harvard Medical School. Four of these miRNAs (hsa-miR-99b-5p, hsa-miR-451a, hsa-miR-326 and hsa-miR-505-3p) were validated, pointing towards their potential as biomarkers for stratifying allergic asthmatic patients by severity and providing insights into severe uncontrolled asthma molecular pathways.

The Impact of High-Fructose Diet and Co-Sensitization to House Dust Mites and Ragweed Pollen on the Modulation of Airway Reactivity and Serum Biomarkers in Rats.

The topic of ragweed pollen (RW) versus house dust mites (HDMs) has often been deliberated, but the increasing incidence of co-sensitization between them has been scarcely addressed. Utilizing Sprague Dawley rats, we explored the effects of co-sensitization with the combination of HDMs and RW pollen extracts in correlation with high-fructose diet (HFrD) by in vitro tracheal reactivity analysis in isolated organ bath and biological explorations. Our findings unveiled interrelated connections between allergic asthma, dyslipidemia, and HFrD-induced obesity, shedding light on their compounding role through inflammation. The increased CRP values and airway hyperresponsiveness to the methacholine challenge suggest a synergistic effect of obesity on amplifying the existing inflammation induced by asthma. One of the major outcomes is that the co-sensitization to HDMs and RW pollen led to the development of a severe allergic asthma phenotype in rats, especially in those with HFrD. Therefore, the co-sensitization to these allergens as well as the HFrD may play a crucial role in the modulation of systemic inflammation, obesity, and airway reactivity.

Basophil FceRI expression-A management tool in anti-IgE treatment of allergic asthma.

Immune-based therapy targeting immunoglobulin E (IgE), anti-IgE treatment, has emerged as an adjunct treatment for children with severe allergic asthma. After start of anti-IgE treatment, an effect of the treatment cannot be monitored by Total-IgE, because current methods measure both bound and free IgE molecules. Basophil activation test may be very useful for monitoring anti-IgE treatment efficacy. The objective of this paper is to evaluate if basophil activation test is applicable in regulating the anti-IgE treatment. A case series of 20 children with IgE-mediated severe allergic asthma were treated according to guidelines with anti-IgE (Omalizumab). Blood samples were drawn for total IgE, specific IgE, number of IgE receptors (FcεRI) and basophil sensitivity were measured at baseline before anti-IgE treatment and 4 months after initiation of anti-IgE treatment. A total of 19 out of 20 children had statistically significant and clinically relevant effects of anti-IgE treatment on symptom score, lung function and medication. All 20 children had a significant reduction in basophil allergen sensitivity and the number of IgE receptors (FcεRI) on blood basophils. Anti-IgE treatment was found to be well controlled by measuring basophil allergen sensitivity and FceRI density on blood basophils. This cohort study demonstrates a promising method, measuring basophil allergen sensitivity and in particular blood basophil FceRI density, concerning the monitoring of anti-IgE treatment in different clinical situations. There are no randomized controlled trials evaluating this method in clinical settings.

A Comparison of Natural and Therapeutic Anti-IgE Antibodies.

Immunoglobulin E (IgE) plays a critical role for the immune system, fighting against parasites, toxins, and cancer. However, when it reacts to allergens without proper regulation, it can cause allergic reactions, including anaphylaxis, through a process initiated by effector cells such as basophils and mast cells. These cells display IgE on their surface, bound to the high-affinity IgE receptor FcεRI. A cross-linking antigen then triggers degranulation and the release of inflammatory mediators from the cells. Therapeutic monoclonal anti-IgE antibodies such as omalizumab, disrupt this process and are used to manage IgE-related conditions such as severe allergic asthma and chronic spontaneous urticaria. Interestingly, naturally occurring anti-IgE autoantibodies circulate at surprisingly high levels in healthy humans and mice and may thus be instrumental in regulating IgE activity. Although many open questions remain, recent studies have shed new light on their role as IgE regulators and their mechanism of action. Here, we summarize the latest insights on natural anti-IgE autoantibodies, and we compare their functional features to therapeutic monoclonal anti-IgE autoantibodies.

From exposure to control: the application of allergen component-resolved diagnosis in the clinical management of cockroach allergies

Cockroaches are one of the most common indoor allergens worldwide, and exposure to cockroach allergens (such as the insect body, debris, and secretions) can trigger severe allergic rhinitis and(or) asthma. Currently, the World Health Organization (WHO)/International Union of Immunological Societies (IUIS) has identified 32 allergenic components in cockroaches, but none of these allergens have shown a clear immunodominance. The sensitization rate to cockroach allergens shows significant variability across different regions and populations and exhibits cross-reactivity with various invertebrates, increasing the complexity of clinical diagnosis and treatment. This article delves into the "Molecular Allergology User's Guide 2.0"(MAUG 2.0) published by the European Academy of Allergy and Clinical Immunology (EAACI) and the research progress on cockroach allergies both domestically and internationally. It elucidates the crucial role of allergen component diagnostic technology in enhancing the diagnosis and treatment of cockroach-induced allergic diseases, efficiently assisting clinicians in identifying common sensitizations and cross-reactivities, thereby offering patients more accurate diagnoses and personalized treatment plans.

Long-term use of omalizumab in patients with allergic bronchopulmonary aspergillosis: a tertiary-level care center experience

Introduction Allergic bronchopulmonary aspergillosis (ABPA) is a lung disease caused by a hypersensitivity reaction to antigens of Aspergillus fumigatus. Objective The aim of this study was to evaluate the long-term clinical outcomes of omalizumab use in patients with ABPA. Methods In this retrospective study, 12 patients diagnosed with ABPA and receiving omalizumab for at least 2 years, and 32 patients diagnosed with severe allergic asthma and receiving omalizumab for at least 2 years (control group) were evaluated. Results Evaluation was made of a total of 44 participants, comprising 11 (25%) males and 33 (75%) females, who received omalizumab for at least 2 years with the diagnosis of the control group (n = 32) and ABPA (n = 12). The increase in asthma control test (ACT) score after omalizumab was significant at 12 months and at 24 months in patients with ABPA. After omalizumab, the use of oral corticosteroid (OCS), the annual number of asthma attacks and hospitalizations were significantly decreased at 12 months and at 24 months in patients with ABPA. The increase in forced expiratory volume in 1 s (FEV1) (%) and ACT score after omalizumab were significant at 12 months and at 24 months in the control group. After omalizumab, the use of OCS, annual number of asthma attacks and hospitalizations were significantly decreased at 12 months and at 24 months in the control group. Conclusion Long-term omalizumab use in patients with ABPA seems to be an effective treatment for improving pulmonary function and reducing asthma exacerbations and hospitalizations.

Favorable clinical course after discontinuation of omalizumab treatment in patients with allergic severe asthma: A real-world clinical practice

The success rate of omalizumab discontinuation is 50–75.5%. However, such data are scarce in Japan. We retrospectively investigated the clinical progression following the cessation of long-term omalizumab treatment (>5 years) in severe allergic asthma patients who have achieved super-responder status, defined as being off any oral maintenance corticosteroids without experiencing exacerbations requiring systemic corticosteroids for >1 year. Six (28.6%) among 21 patients recommenced after a median period of 5.5 (4.3–12.5) months later due to exacerbated asthma control, resulting in improved asthma management for all patients. The rates of patients who successfully remained off omalizumab treatment for 1 and 2 years were 72.4% and 65.8%, respectively. Specific IgE levels after discontinuing omalizumab treatment significantly decreased compared to those at initiating this treatment in 10 patients who successfully remained off this treatment. Therefore, discontinuing omalizumab treatment may be considered for patients continuing treatment beyond 5 years and achieving super-responder status.

Frequency of Severe Asthma and Its Clinical Phenotypes at the Asthma Clinic in One of the Largest Sudanese Tertiary Pediatric Hospitals: A Cross-Sectional Hospital-Outpatient-Based Study.

Asthma is one of the most common non-communicable diseases. Childhood asthma has been increasing in Sudan, with a 13-16% prevalence among Khartoum school children. To achieve and maintain good asthma control, proper diagnosis, assessment of severity, and appropriate medication administration are crucial, with phenotyping being a key factor in determining patients' specific treatment. To study the frequency of severe asthma and the distribution of its different phenotypes and to investigate associations between age and gender and different phenotypes of asthma. This descriptive cross-sectional hospital-based study was conducted in the Asthma Clinic of Mohamed Al-Amin Hamid Pediatrics Hospital. It included 229 patients who were presented to the clinic from September 2021 to April 2022. Data were collected from the patients and/or their caregivers using a modified validated standard questionnaire and were analyzed using SPSS version 26.0. A p-value of 0.05 or less was considered statistically significant. In this study of 229 participants, 14.4% had severe asthma, with 44.5% and 41% exhibiting mild and moderate asthma, respectively. Most were effectively managed in steps 2 or 3. The cohort, primarily aged 5 or younger (40.2%) with a male majority (62%), showed a mean diagnosis age of 2.9 ± 2.8 years. Impressively, 90% maintained well-controlled asthma. Within severe asthma cases (87% atopic), 39.4% represented a severe allergic asthma phenotype. Elevated eosinophil counts were noted in 45.5% (serum) and 78.8% (sputum cytology), while 57.6% had normal serum IgE levels. The predominant symptom pattern in severe asthma was episodic multi-trigger wheezing (48.5%). Age and gender displayed no significant association with severe asthma phenotype. This study reveals a concerning rise in childhood asthma prevalence in Sudan, emphasizing the importance of tailored treatment strategies. Severe asthma, characterized by atopic eosinophilic involvement, necessitates targeted interventions in pediatric asthma care for specific phenotypes.

Direct comparative study of anti-IgE and anti-IL4Rα therapy effectiveness in patients with severe allergic and mixed bronchial asthma

Introduction. There is insufficiency of direct comparative studies of genetically engineered biological drugs (GEBD) for severe bronchial asthma (SA) treatment in scientific databases.Aim. To compare omalizumab and dupilumab effectiveness in patients with allergic and mixed SA in real clinical practice.Materials and methods. The direct comparative study included SA patients with an allergic component from regional registry of Sverdlovsk region. The data of patients with allergic (n = 68) and mixed (n = 27) SA treated with omalizumab (n = 62) and dupilumab (n = 33) were analyzed. Therapy effectiveness was determined for 12 months in general group No. 1, allergic asthma group No. 2 and mixed asthma group No. 3 according to the following indicators: asthma control level (ACT), proportion of patients with uncontrolled asthma, need for systemic glucocorticosteroids (SGCS) and short‐acting beta agonists (SABA), basic therapy volume, asthma exacerbations number, emergency calls and hospitalizations, forced expiratory volume in the first second (FEV ), assessment of life quality (AQLQ and SNOT-22). Control evaluation visits were conducted before therapy start, after 4 and 12 months of biologics taking.Results. In general, during the 12 months of targeted therapy in patients receiving omalizumab statistically significant positive dynamics was observed in 12 of the 13 evaluated indicators; in patients receiving dupilumab – in 9 indicators. When analyzing such indicators as, ACT, taking SGCS, exacerbations of SA, FEV , statistically significant positive dynamics was revealed for all 4 indicators in patients receiving omalizumab in group No. 2 and in patients receiving dupilumab in group No. 3.Conclusions. Patients with allergic component of SA respond equally well to therapy with omalizumab and dupilumab. At the same time, a tendency towards the advantage of omalizumab in patients with allergic asthma, and dupilumab in patients with a mixed phenotype of the disease was revealed.

Clinical and allergological characteristics of patients with severe bronchial asthma in the regional registry and phenotyping principles for the targeted therapy choice

Introduction. Severe asthma targeted therapy effectiveness depends on precise targeting of the selected drug to the key link in pathogenesis. Therefore, severe asthma phenotyping in real clinical practice is relevant.Aim. To determine main clinical and allergological characteristics of patients with severe asthma and to establish important phenotyping signs determined choice of a targeted drug for severe asthma treatment.Materials and methods. The prospective and retrospective study involved patients (n = 198) of the Sverdlovsk region registry receiving targeted therapy of severe asthma. Considering clinical and allergological picture, allergic, non-allergic eosinophilic and mixed severe asthma phenotypes were identified. Clinical and laboratory characteristics of phenotypes were described. A phenotyping algorithm was developed.Results. In the register of patients (n = 198) with severe asthma, non-allergic eosinophilic asthma was 46.5%, allergic – 34.8%, mixed – 18.7%. Significant signs for phenotyping were identified: age of asthma onset, proven allergy, Phadiatop ImmunoCAP level and blood eosinophils on baseline, concomitant allergic rhinitis, chronic rhinosinusitis with nasal polyps and hyper-sensitivity to NSAIDs. The main signs of allergic severe asthma determined: early onset, proven allergy and a positive result of Phadiatop ImmunoCAP (the probability of allergic phenotype increases with Phadiatop ≥ 1.53 PAU/l). Signs of non-allergic eosinophilic asthma were eosinophilia ≥ 150 cells/µl, absence of allergy, concomitant chronic rhinosinusitis with nasal polyps and hypersensitivity to NSAIDs, late onset (after 30 years). Signs were identified for mixed asthma: presence of proven allergy or latent sensitization in combination with high level of Phadiatop ImmunoCAP, late onset, eosinophilia ≥ 300 cells/µl, chronic rhinosinusitis with nasal polyps, hypersensitivity NSAIDs.Conclusions. The algorithm for severe asthma phenotyping based on the isolation of eosinophilia of allergic and non-allergic origin is proposed. Severe asthma phenotyping, which can be carried out in real clinical practice, should facilitate the selection of an initial targeted drug.

The Efficacy of Omalizumab in Patients with Chronic Rhinosinusitis with Nasal Polyps and Comorbid Severe Allergic Asthma.

Chronic rhinosinusitis whit nasal polyps (CRSwNP) is the most common comorbid disease accompanying asthma. Omalizumab is a recombinant anti-immunoglobulin (Ig) E antibody, and studies suggest that omalizumab may also affect CRSwNP regardless of asthma. We aimed to assess the effect of omalizumab treatment on CRSwNP accompanying severe allergic asthma (SAA) patients. Clinical data including spirometry measurements, serum/nasal secretion biomarker levels were collected. NP scores and CRS scores (Lund-Mancay [LM] scores) were also recorded before omalizumab treatment, as well as at the 4th and 12th months of omalizumab treatment. Twenty-one patients with both CRSwNP and SAA who underwent omalizumab therapy were assessed. There was a significant difference among forced expiratory volume (FEV1), ACT scores, NP scores, LM scores, serum IgE, and blood eosinophil levels of the patients before omalizumab therapy at the 4th and 12th months of omalizumab treatment. A significant negative correlation was observed between ∆FEV1 and ∆NP scores (r=-0.485), between ∆ACT and ∆NP scores (r=-0.469), and ∆ACT and ∆LM scores (r=-0.436). When we grouped the patients who benefited from 1 year of omalizumab therapy and those who did not in terms of NP, there was no difference between the two groups related to local eosinophil and local IgE levels in the nasal polyp biopsy. Omalizumab treatment is effective for asthma and CRSwNP in patients with CRSwNP accompanied by SAA. Improvement in asthma is associated with improvement in CRSwNP. The efficacy of omalizumab on NP in patients with CRSwNP accompanied by SAA is independent of local IgE and eosinophil counts.

Selective production of IL-33-neutralizing autoantibody ameliorates asthma responses and severity

BackgroundNatural anti-cytokine autoantibodies can regulate homeostasis of infectious and inflammatory diseases. The anti-cytokine autoantibody profile and relevance to the pathogenesis of asthma are unknown. We aim to identify key anti-cytokine autoantibodies in asthma patients, and reveal their immunological function and clinical significance. MethodsA Luciferase Immunoprecipitation System was used to screen serum autoantibodies against 11 key cytokines in patients with allergic asthma and healthy donors. The antigen-specificity, immunomodulatory functions and clinical significance of anti-cytokine autoantibodies were determined by ELISA, qPCR, neutralization assays and statistical analysis, respectively. Potential conditions for autoantibody induction were revealed by in vitro immunization. ResultsOf 11 cytokines tested, only anti-IL-33 autoantibody was significantly increased in asthma, compare to healthy controls, and the proportion positive was higher in patients with mild-to-moderate than severe allergic asthma. In allergic asthma patients, the anti-IL-33 autoantibody level correlated negatively with serum concentration of pathogenic cytokines (e.g., IL-4, IL-13, IL-25 and IL-33), IgE, and blood eosinophil count, but positively with mid-expiratory flow FEF25–75%. The autoantibodies were predominantly IgG isotype, polyclonal and could neutralize IL-33-induced pathogenic responses in vitro and in vivo. The induction of the anti-IL-33 autoantibody in blood B-cells in vitro required peptide IL-33 antigen along with a stimulation cocktail of TLR9 agonist and cytokines IL-2, IL-4 or IL-21. ConclusionsSerum natural anti-IL-33 autoantibodies are selectively induced in some asthma patients. They ameliorate key asthma inflammatory responses, and may improve lung function of allergic asthma.

Tezepelumab for Severe Asthma: One Drug Targeting Multiple Disease Pathways and Patient Types.

Asthma is a heterogeneous inflammatory disease of the airways, affecting many children, adolescents, and adults worldwide. Up to 10% of people with asthma have severe disease, associated with a higher risk of hospitalizations, greater healthcare costs, and poorer outcomes. Patients with severe asthma generally require high-dose inhaled corticosteroids and additional controller medications to achieve disease control; however, many patients remain uncontrolled despite this intensive treatment. The treatment of severe uncontrolled asthma has improved with greater understanding of asthma pathways and phenotypes as well as the advent of targeted biologic therapies. Tezepelumab, a monoclonal antibody, blocks thymic stromal lymphopoietin, an epithelial cytokine that has multifaceted effects on the initiation and persistence of asthma inflammation and pathophysiology. Unlike other biologic treatments, tezepelumab has demonstrated efficacy across severe asthma phenotypes, with the magnitude of effects varying by phenotype. Here we describe the anti-inflammatory effects and efficacy of tezepelumab across the most relevant phenotypes of severe asthma. Across clinical studies, tezepelumab reduced annualized asthma exacerbation rates versus placebo by 63-71% in eosinophilic severe asthma, by 58-68% in allergic severe asthma, by 67-71% in allergic and eosinophilic severe asthma, by 34-49% in type 2-low asthma, and by 31-41% in oral corticosteroid-dependent asthma. Furthermore, in all these asthma phenotypes, tezepelumab demonstrated higher efficacy in reducing exacerbations requiring hospitalizations or emergency department visits versus placebo. In patients with severe uncontrolled asthma, who commonly have multiple drivers of inflammation and disease, tezepelumab may modulate airway inflammation more extensively, as other available biologics block only specific downstream components of the inflammatory cascade.

Transcriptomic evaluation of skin tape-strips in children with allergic asthma uncovers epidermal barrier dysfunction and asthma-associated biomarkers abnormalities.

Tape-strips, a minimally invasive method validated for the evaluation of several skin diseases, may help identify asthma-specific biomarkers in the skin of children with allergic asthma. Skin tape-strips were obtained and analyzed with RNA-Seq from children with moderate allergic asthma (MAA) (n = 11, mean age 7.00; SD = 1.67), severe allergic asthma (SAA) (n = 9, mean age 9.11; SD = 2.37), and healthy controls (HCs) (n = 12, mean age 7.36; SD = 2.03). Differentially expressed genes (DEGs) were identified by fold change ≥2 with a false discovery rate <0.05. Transcriptomic biomarkers were analyzed for their accuracy in distinguishing asthma from HCs, their relationships with asthma-related outcomes (exacerbation rate, lung function-FEV1, IOS-R5-20, and lung inflammation-FeNO), and their links to skin (barrier and immune response) and lung (remodeling, metabolism, aging) pathogenetic pathways. RNA-Seq captured 1113 in MAA and 2117 DEGs in SAA. Epidermal transcriptomic biomarkers for terminal differentiation (FLG/filaggrin), cell adhesion (CDH19, JAM2), lipid biosynthesis/metabolism (ACOT2, LOXL2) were significantly downregulated. Gene set variation analysis revealed enrichment of Th1/IFNγ pathways (p < .01). MAA and SAA shared downregulation of G-protein-coupled receptor (OR4A16, TAS1R3), upregulation of TGF-β/ErbB signaling-related (ACVR1B, EGFR, ID1/2), and upregulation of mitochondrial-related (HIGD2A, VDAC3, NDUFB9) genes. Skin transcriptomic biomarkers correlated with the annualized exacerbation rate and with lung function parameters. A two-gene classifier (TSSC4-FAM212B) was able to differentiate asthma from HCs with 100% accuracy. Tape-strips detected epithelial barrier and asthma-associated signatures in normal-appearing skin from children with allergic asthma and may serve as an alternative to invasive approaches for evaluating asthma endotypes.

Health-related quality of life in severe hypersensitivity reactions: focus on severe allergic asthma and hymenoptera venom anaphylaxis-a cross-sectional study.

Growing evidence reveals the important role of clinical psychological factors in chronic-immune diseases. The aim of this study was to investigate Health-Related Quality of Life (HR-QoL), depression, anxiety, and alexithymia in patients with severe hypersensitivity reactions such as Severe Allergic Asthma (SAA) and Hymenoptera Venom Anaphylaxis (HVA). The Short-Form Health Survey-36 (SF-36), the Beck Depression Inventory Questionnaire (BDI-II), the Hamilton Anxiety Rating Scale (HAM-A) and the Toronto Alexithymia Scale (TAS-20) were used to assess HR-QoL and clinical psychological features of patients with SAA and HVA. Overall, 78 patients were recruited. Patients with SAA (n = 35) reported lower scores for physical functioning [65 (58-75) vs. 90 (85-95); p = <0.001], role limitations due to physical health [25 (0-50) vs. 62 (50-75); p = 0.004], bodily pain [47.5 (41.1-61.3) vs. 55.5 (55-96); p = 0.001], general health [40 (30-60) vs. 70 (50-80); p = 0.0003] and social functioning [50 (37.5-62.5) vs. 62.5 (54.9-75); p = 0.007] while higher scores for depressive symptoms [14 (11-15.4) vs. (9.5 (6-15.4); p = 0.05)] compared to HVA patients (n = 43). All the dimensions of SF-36 were negatively correlated with anxiety (r from -0.26 to -0.66; p all < 0.01) and depressive symptoms (r from -0.44 to -0.73; p all < 0.001). Alexithymia was negatively correlated with vitality (r = -0.28; p = 0.02) and mental health (r = -027; p = 0.03). Additionally, patients with alexithymia (38% of participants) showed higher levels of depressive symptoms [9.5 (10-19) vs. 14 (6-13.9); p = 0.005] and anxiety levels [31 (27.9-35) vs. 24 (16-33.9); p = 0.02]; they also showed less vitality [40 (39.9-50) vs. 55 (50-60) p = 0.01], social functioning [50 (37.5-62.5) vs. 62.5 (50 vs. 75); p = 0.01] and mental health [48 (44-60) vs. 68 (56-76); p = 0.004]. Clinical psychological features due to severe hypersensitive reactions may contribute to the patient's perceived HR-QoL. Focused clinical psychological interventions should be promoted to improve the clinical management of such conditions.

Efficacy of Tezepelumab in Patients With Evidence of Severe Allergic Asthma: Results From the Phase 3 NAVIGATOR Study.

Efficacy of Tezepelumab in Patients With Evidence of Severe Allergic Asthma: Results From the Phase 3 NAVIGATOR Study.

AIM2 participates in house dust mite (HDM)-induced epithelial dysfunctions and ovalbumin (OVA)-induced allergic asthma in infant mice

Objective: Allergen sensitization and high rates of concomitant allergic diseases are characteristic of severe pediatric asthma. The present study was aimed to explore the mechanism of allergic asthma via bioinformatics and experiment investigation. Methods: The GSE27011 dataset contained the expression profiles of normal and pediatric asthma white blood cells was downloaded for analyzing the different expression genes and function enrichment. The allergic asthma model in infant mice was established by ovalbumin (OVA) stimulation. The cellular model was established by house dust mite (HDM)-stimulation in human bronchial epithelial cells. The absent in melanoma 2 (AIM2) knockdown was achieved by intranasal lentivirus injection or cell infection. The bronchoalveolar lavage fluid (BALF) was collected for cell counting and ELISA assessment of cytokines. Lung tissues were collected for HE staining and immunohistochemical (IHC) staining. Real-time PCR and immunoblotting were used for the determination of key gene expressions in mouse and cell models. Results: upregulation of AIM2 gene expression was observed in pediatric asthma patients based on GSE27011 and OVA-induced infant mouse allergic asthma model. AIM2 knockdown ameliorated OVA caused elevation in airway hyper-responsiveness (AHR), elevation in cell quantities (eosinophils, neutrophils, lymphocytes), and levels of cytokines (IL-4, IL-13, TNF-α, and OVA-specific IgE) in BALF. Moreover, AIM2 knockdown relieved OVA-caused histopathological alterations in mouse lungs, up-regulation of AIM2 levels, and NOD1 and receptor-interacting protein 2 (RIP2) protein levels, as well as p65 phosphorylation. In the cell model, AIM2 knockdown partially ameliorated HDM-induced epithelial dysfunctions by promoting cell viability, down-regulating inflammatory cytokines levels, and decreasing the protein levels of AIM2, NOD1, RIP2, and phosphorylated p65. Conclusion: AIM2 participates in HDM-induced epithelial dysfunctions and OVA-induced allergic asthma progression. AIM2 could be a promising target for pediatric allergic asthma treatment regimens, which warrants further in vivo investigations.

Application of Omalizumab Combined with Enteral Nutrition in Treating Severe Allergic Asthma

To investigate the influence of omalizumab combined with enteral nutrition in treating severe allergic asthma, 102 patients in our hospital from May 2020 to May 2023 were retrospectively included, followed by dividing into a control group and a study group. The control group received only budesonide formoterol, and the study group accepted budesonide formoterol, omazumab, and an oral enteral hypernutrient polymer. After therapy, the asthma control test score, mini-asthma quality of life questionnaire score, hemoglobin level, serum total protein level, serum total immunoglobulin E level, forced expiratory volume in one second, forced expiratory volume in one second predicted, CD3+, CD4+, and CD4+/CD8+ in the study group presented higher than the control group, while CD8+, fractional concentration of exhaled nitric oxide level, and percentage of eosinophils in blood were lower. No difference was observed in the incidence of adverse reactions between the two groups (P = 0.34). To sum up, enteral nutrition combined with omalizumab can effectively inhibit airway inflammation, improve lung function, and promote the quality of life of severe allergic asthma patients with high safety, which opens a new way of biologically targeting therapy for asthma.