Antipruritic effect of ursolic acid through MRGPRX2/MrgprB2-dependent inhibition of mast cell degranulation and reduced TSLP production.

Ursolic acid (UA), a pentacyclic triterpene, exhibits diverse pharmacological effects, including potential treatment for allergic diseases. It downregulates thymic stromal lymphopoietin (TSLP) and disrupts mast cell signaling pathways. However, the exact molecular mechanism by which UA interferes with mast cell action remains unclear. Therefore, the current study aimed to uncover molecular entities underlying the effect of UA on mast cells and its potential antipruritic effect, specifically investigating its modulation of key molecules such as TRPV4, PAR2, and MRGPRX2, which are involved in TSLP regulation and sensation. Calcium imaging experiments revealed that UA pretreatment significantly suppressed MRGPRX2 activation (and its mouse orthologue MrgprB2), a G protein-coupled receptor predominantly expressed in mast cells. Molecular docking predictions suggested potential interactions between UA and MRGPRX2/MrgprB2. UA pretreatment also reduced mast cell degranulation through MRGPRX2 and MrgprB2-dependent mechanisms. In a dry skin mouse model, UA administration decreased tryptase and TSLP production in the skin, and diminished TSLP response in the sensory neurons. While PAR2 and TRPV4 activation enhances TSLP production, UA did not inhibit their activity. Notably, UA attenuated compound 48/80-induced scratching behaviors in mice and suppressed spontaneous scratching in a dry skin model. The present study confirms the effective inhibition of UA on MRGPRX2/MrgprB2, leading to reduced mast cell degranulation and suppressed scratching behaviors. These findings highlight the potential of UA as an antipruritic agent for managing various allergy- or itch-related conditions.

Phase 1 Safety and Pharmacokinetics Study of TAVO101, an Anti-Human Thymic Stromal Lymphopoietin Antibody for the Treatment of Allergic Inflammatory Conditions.

TAVO101 is a humanized anti-human thymic stromal lymphopoietin (TSLP) monoclonal antibody under clinical development for the treatment of atopic dermatitis (AD) and other allergic inflammatory conditions. The crystallizable fragment region of the antibody was engineered for half-life extension and attenuated effector functions. This Phase 1, double-blinded, randomized, placebo-controlled study assessed the safety, tolerability, pharmacokinetics, and immunogenicity of TAVO101 in healthy adult subjects in seven ascending dose cohorts. Subjects received a single intravenous administration of TAVO101 or placebo with a 195-day follow-up. TAVO101 was safe and well tolerated. The incidences and severities of treatment-emergent adverse events were mostly mild and comparable between the active and placebo groups, with no trends of dose relationship. There were no severe adverse events, deaths, or treatment-related withdrawals. TAVO101 exhibited a linear pharmacokinetic profile, low clearance, and a median elimination half-life of 67 days in healthy subjects. All TAVO101-treated subjects tested negative for anti-drug antibodies. To support development in AD, TAVO101 was studied in an oxazolone-induced AD model in hTSLP transgenic mice and demonstrated efficacy. This long-acting anti-TSLP antibody has the potential for stronger and sustained allergic inflammatory disease control. The results from this study warranted further clinical development of TAVO101 in patients.

Anakinra-Loaded Sphingomyelin Nanosystems Modulate In Vitro IL-1-Dependent Pro-Tumor Inflammation in Pancreatic Cancer.

Pancreatic cancer is a very aggressive disease with a dismal prognosis. The tumor microenvironment exerts immunosuppressive activities through the secretion of several cytokines, including interleukin (IL)-1. The IL-1/IL-1 receptor (IL-1R) axis is a key regulator in tumor-promoting T helper (Th)2- and Th17-type inflammation. Th2 cells are differentiated by dendritic cells endowed with Th2-polarizing capability by the thymic stromal lymphopoietin (TSLP) that is secreted by IL-1-activated cancer-associated fibroblasts (CAFs). Th17 cells are differentiated in the presence of IL-1 and other IL-1-regulated cytokines. In pancreatic cancer, the use of a recombinant IL-1R antagonist (IL1RA, anakinra, ANK) in in vitro and in vivo models has shown efficacy in targeting the IL-1/IL-1R pathway. In this study, we have developed sphingomyelin nanosystems (SNs) loaded with ANK (ANK-SNs) to compare their ability to inhibit Th2- and Th17-type inflammation with that of the free drug in vitro. We found that ANK-SNs inhibited TSLP and other pro-tumor cytokines released by CAFs at levels similar to ANK. Importantly, inhibition of IL-17 secretion by Th17 cells, but not of interferon-γ, was significantly higher, and at lower concentrations, with ANK-SNs compared to ANK. Collectively, the use of ANK-SNs might be beneficial in reducing the effective dose of the drug and its toxic effects.

Association between bronchial asthma and TSLP gene polymorphism: a systematic review and meta-analysis.

Aims: This study entails an association between bronchial asthma and common single nucleotide polymorphisms (SNPs) in thymic stromal lymphopoietin (TSLP) gene; rs2289278, rs3806933, rs2289276, and rs1837253. Methods: The databases of PubMed, Embase, Web of Science, and Google Scholar were searched for studies reporting TSLP polymorphisms and asthma from inception to January 2022. Hardy-Weinberg equilibriums (HWE) for each polymorphism of the control group were checked using the χ 2 test. The association was estimated by means of odds ratio (OR) with 95% CI in both dominant and recessive modes of inheritance, respectively. Results: Altogether, 11 studies with 3121 asthma cases and 3041 healthy controls were added. Results from six studies showed that the SNP rs2289278 had a protective role in asthma development (OR=0.65, 95% CI: 0.44-0.97, P=0.04). Pooling of four studies showed that the SNP rs3806933 had higher odds of developing asthma (OR=1.32, 95% CI:1.14-1.54, P<0.01). However, the SNP rs2289276 and rs1837253 showed no significant association. From the subgroup analysis, SNPs rs2289278 and rs1837253 were protective against the development of asthma in Asia. However, SNP rs2289276 showed a risk association in Asia and in adults. Conclusion: This meta-analysis shows that the SNP rs2289278 has a protective effect on the development of asthma; whereas rs3806933 has a risk of asthma. Additionally, this study adds genomic-based support to the recent FDA approval of tezepelumab, an anti-TSLP agent.

Type 2 severe asthma: pathophysiology and treatment with biologics.

INTRODUCTION: The hallmark of most patients with severe asthma is type 2 inflammation, driven by innate and adaptive immune responses leading to either allergic or non-allergic eosinophilic infiltration of airways. The cellular and molecular pathways underlying severe type 2 asthma can be successfully targeted by specific monoclonal antibodies. AREAS COVERED: This review article provides a concise overview of the pathophysiology of type 2 asthma, followed by an updated appraisal of the mechanisms of action and therapeutic efficacy of currently available biologic treatments used for management of severe type 2 asthma. Therefore, all reported information arises from a wide literature search performed on PubMed. EXPERT OPINION: The main result of the recent advances in the field of anti-asthma biologic therapies is the implementation of a personalized medicine approach, aimed to achieve clinical remission of severe asthma. Today this accomplishment is made possible by the right choice of the most beneficial biologic drug for the pathologic traits characterizing each patient, including type 2 severe asthma and its comorbidities.

Tezepelumab for refractory eosinophilic granulomatosis with polyangiitis-related asthma.

Conventional immunosuppressants are ineffective for the management of EGPA-related asthma. Tezepelumab is a human monoclonal antibody that inhibits thymic stromal lymphopoietin (TLSP) that has proven efficacy in several phase 3 studies for the treatment of asthma. We treated with off-label tezepelumab the first two patients with severe refractory EPGA-related asthma. These preliminary findings suggest that targeting upstream signaling of the T2 inflammatory pathway can improve symptoms, reduce BVAS and increase Asthma Control Test scores, even in patients with refractory asthma who have failed several previous lines of treatment. Nevertheless, by analogy with dupilumab-induced IL-4/13 blockade, the persistence of sputum eosinophilia (reported in both patients) raises questions as to whether TSLP inhibition could lead to a rebound of eosinophilia and potentially to eosinophil-related symptoms in patients with EGPA.

Thymic stromal lymphopoietin and digital microvascular damage in systemic sclerosis patients: A pilot study.

BACKGROUND: Systemic sclerosis (SSc) is a complex autoimmune connective-tissue disease, characterised by vasculopathy and fibrosis of the skin and internal organs. Activation of microvascular endothelial cells (ECs) causes the intimal hyperplasia that characterises the vascular remodelling in SSc. The most frequent complication of SSc is the development of digital ulcers (DUs). Thymic stromal lymphopoietin (TSLP) may trigger fibrosis and sustain vascular damage. Aim of this study was to evaluate the correlation between serum level of TSLP and DUs. METHODS: 75 consecutive SSc patients were enrolled and serum TSLP levels were measured. The presence of history of DUs (HDU) was evaluated. Recurrent new DUs were defined as the presence of at least 3 episodes of DUs in a 12-months follow up period. The risk of developing new DUs was calculated by applying the capillaroscopic skin ulcer risk index (CSURI). RESULTS: The median value of TSLP was higher in patients with HDU than patients without HDU [181.67 pg/ml (IQR 144.67; 265.66) vs 154.67 pg/ml (IQR 110.67; 171.33), p < 0.01]. The median value of TSLP was higher in patients with an increased CSURI index than patients without an increased CSURI [188 pg/ml (IQR 171.33; 246.33) vs 159.33 pg/ml (IQR 128.67; 218), p < 0.01]. Kaplan-Meier curves demonstrated that free survival from new DUs was significantly (p < 0.01) lower in SSc patients with increased TSLP serum levels. CONCLUSION: TSLP might have a key role in digital microvascular damage of SSc patients.

Role of Thymic Stromal Lymphopoietin in the Pathophysiology of Asthma and Clinical and Biological Effects of Blockade With Tezepelumab.

BACKGROUND: The airway epithelium is the first line of defense of the respiratory system against the external environment. It plays an active role in the initiation of immune and allergic responses against potential hazards. Among the various specialized cells and cytokines that participate in epithelium-induced responses, alarmins are particularly interesting, given their ample role in mediating T2 and non-T2 inflammatory mechanisms involved in the pathogenesis of asthma. Thymic stromal lymphopoietin (TSLP) is an alarmin with broad effects in asthma that result from its widespread action on multiple cell types, including eosinophils, mast cells, dendritic cells, and group-2 innate lymphoid cells. Its role in allergy-mediated responses, eosinophilic inflammation, airway hyperresponsiveness, mucus hyperproduction, viral tolerance, and airway remodeling is of the utmost importance, as more comprehensive asthma assessments have been developed to explore these pathogenic features. Therefore, blockade with targeting molecules, such as monoclonal antibodies, has emerged as a promising therapeutic option, particularly in patients with multiple pathogenic pathways. In this review, we examine the roles of alarmins (mainly TSLP) in the pathogenesis of asthma and clinical expression and discuss the effects of inhibiting TSLP on several inflammatory and clinical outcomes. We also review the literature supporting treatment with anti-TSLP biologics and the unanswered questions and unmet needs associated with targeting alarmins in asthma.

Potential New Inflammatory Markers in Bronchiectasis: A Literature Review.

Specific molecular and inflammatory endotypes have been identified for chronic respiratory disorders, including asthma and COPD (chronic obstructive pulmonary disease). These endotypes correspond with clinical aspects of disease, enabling targeted medicines to address certain pathophysiologic pathways, often referred to as "precision medicine". With respect to bronchiectasis, many comorbidities and underlying causes have been identified. Inflammatory endotypes have also been widely studied and reported. Additionally, several genes have been shown to affect disease progression. However, the lack of a clear classification has also hampered our understanding of the disease's natural course. The aim of this review is, thus, to summarize the current knowledge on biomarkers and actionable targets of this complex pathologic condition and to point out unmet needs, which are required in the design of effective diagnostic and therapeutic trials.

Upper Airway Alarmin Cytokine Expression in Asthma of Different Severities.

Background: The secretion of alarmin cytokines by epithelial cells, including thymic stromal lymphopoietin (TSLP), interleukin (IL)-25, and IL-33, initiates inflammatory cascades in asthma. However, alarmin cytokine expression in the upper airways in asthma remains largely unknown. Methods: We recruited 40 participants with asthma into four groups as per the Global Initiative for Asthma (GINA) steps (10 in each group of GINA 1/2, 3, 4, and 5). Cells were derived from nasal, buccal, and throat brushings. Intracellular cytokine expression (TSLP, IL-25, and IL-33) was assessed by flow cytometry in cytokeratin 8+ (Ck8+) epithelial cells immediately following collection. Results: TSLP was significantly increased (p < 0.001) in GINA 5 patients across nasal, buccal, and throat Ck8+ epithelial cells, while IL-25 was elevated in nasal and throat samples (p < 0.003), and IL-33 levels were variable, compared with GINA 1-4 patients. Individual GINA subgroup comparison showed that TSLP levels in nasal samples from GINA 5 patients were significantly (p = 0.03) elevated but did not differ between patients with and without nasal comorbidities. IL-25 and IL-33 (obtained from nasal, buccal, and throat samples) were not significantly different in individual groups. Conclusions: Our study demonstrates for the first time that Ck8+ nasal epithelial cells from GINA 5 asthma patients express elevated levels of TSLP.

Exploring the therapeutic potential of monoclonal antibodies targeting TSLP and IgE in asthma management.

BACKGROUND: In recent years, there has been a growing interest in the utilization of biologic therapies for the management of asthma. Both TSLP and IgE are important immune molecules in the development of asthma, and they are involved in the occurrence and regulation of inflammatory response. METHODS: A comprehensive search of PubMed and Web of Science was conducted to gather information on anti-TSLP antibody and anti-IgE antibody. RESULTS: This investigation elucidates the distinct mechanistic roles of Thymic Stromal Lymphopoietin (TSLP) and Immunoglobulin E (IgE) in the pathogenesis of asthma, with a particular emphasis on delineating the therapeutic mechanisms and pharmacological properties of monoclonal antibodies targeting IgE and TSLP. Through a meticulous examination of clinical trials involving paradigmatic agents such as omalizumab and tezepelumab, we offer valuable insights into the potential treatment modalities for diseases with shared immunopathogenic pathways involving IgE and TSLP. CONCLUSION: The overarching objective of this comprehensive study is to delve into the latest advancements in asthma therapeutics and to provide guidance for future investigations in this domain.

Thymic Stromal Lymphopoietin and Tezepelumab in Airway Diseases: From Physiological Role to Target Therapy.

Thymic stromal lymphopoietin (TSLP), is a protein belonging to a class of epithelial cytokines commonly called alarmins, which also includes IL-25 and IL-33. Functionally, TSLP is a key player in the immune response to environmental insults, initiating a number of downstream inflammatory pathways. TSLP performs its role by binding to a high-affinity heteromeric complex composed of the thymic stromal lymphopoietin receptor (TSLPR) chain and IL-7Rα. In recent years, the important role of proinflammatory cytokines in the etiopathogenesis of various chronic diseases such as asthma, chronic rhinosinusitis with nasal polyposis (CRSwNP), chronic obstructive pulmonary diseases (COPDs), and chronic spontaneous urticaria has been studied. Although alarmins have been found to be mainly implicated in the mechanisms of type 2 inflammation, studies on monoclonal antibodies against TSLP demonstrate partial efficacy even in patients whose inflammation is not definable as T2 and the so-called low T2. Tezepelumab is a human anti-TSLP antibody that prevents TSLP-TSLPR interactions. Several clinical trials are evaluating the safety and efficacy of Tezepelumab in various inflammatory disorders. In this review, we will highlight major recent advances in understanding the functional role of TSLP, its involvement in Th2-related diseases, and its suitability as a target for biological therapies.

Disrupting TSLP-TSLP receptor interactions via putative small molecule inhibitors yields a novel and efficient treatment option for atopic diseases.

Thymic stromal lymphopoietin (TSLP) is a key player in atopic diseases, which has sparked great interest in therapeutically targeting TSLP. Yet, no small-molecule TSLP inhibitors exist due to the challenges of disrupting the protein-protein interaction between TSLP and its receptor. Here, we report the development of small-molecule TSLP receptor inhibitors using virtual screening and docking of >1,000,000 compounds followed by iterative chemical synthesis. BP79 emerged as our lead compound that effectively abrogates TSLP-triggered cytokines at low micromolar concentrations. For in-depth analysis, we developed a human atopic disease drug discovery platform using multi-organ chips. Here, topical application of BP79 onto atopic skin models that were co-cultivated with lung models and Th2 cells effectively suppressed immune cell infiltration and IL-13, IL-4, TSLP, and periostin secretion, while upregulating skin barrier proteins. RNA-Seq analysis corroborate these findings and indicate protective downstream effects on the lungs. To the best of our knowledge, this represents the first report of a potent putative small molecule TSLPR inhibitor which has the potential to expand the therapeutic and preventive options in atopic diseases.

A Comparative Study on Serum Levels of "Thymic Stromal Lymphopoietin" Between Patients with Psoriasis Vulgaris and Healthy Individuals: A Case-Control Study.

Background: Thymic stromal lymphopoietin (TSLP) is a cytokine initially implicated to be associated with allergic disorders inducing Th2 response. Emerging studies have shown that TSLP is also involved in autoimmune diseases. In psoriasis, TSLP acts in synergy with T cell-derived CD40L to promote the release of IL-23 from dendritic cells. IL-23 is responsible for the inappropriate immune reaction and keratinocyte proliferation in psoriasis. Targeting TSLP could be a novel therapeutic approach in the treatment of psoriasis. Objective: To compare the serum levels of TSLP between patients with psoriasis and healthy individuals. Materials and Methods: A prospective hospital-based case-control study was carried out on 38 patients with psoriasis. The severity of psoriasis was graded into mild, moderate, and severe according to PASI. A total of 30 healthy individuals with matched age and sex were taken as controls. 5 ml of venous blood was collected, centrifuged, and the collected serum was stored at -80°C until quantitative assessment by sandwich enzyme-linked immunosorbent assay (ELISA) technique. Results: TSLP has been found to be significantly elevated in the sera of cases (0.1380178 pg/ml) than in controls (0.1125974 pg/ml). There was also a significant proportionate increase in the mean TSLP with the mean PASI score. Limitations: The sample size was small and we could not follow-up the cases to study the changes in TSLP levels with remission of the lesions. Conclusion: We found that serum TSLP was elevated in psoriasis patients and correlated with disease severity, indicating a possible pathogenetic role.

Tezepelumab improved chronic rhinosinusitis with nasal polyps in a Patient with aspirin exacerbated respiratory disease.

Introduction: Patients with chronic rhinosinusitis with nasal polyps (CRSwNP) and aspirin-exacerbated respiratory disease (AERD) have more severe sinus disease than those without AERD. CRSwNP associated with type 2 inflammation and AERD can be difficult to control with standard medical therapy and sinus surgery. Case study: 74-year-old Japanese woman with chronic sinusitis since age 50 and asthma since age 60. At age 64, she began to experience asthma exacerbations and was started on short-term corticosteroid therapy with prednisolone. At age 70, she experienced urticaria, nasal congestion, and wheezing after taking an NSAID; based on an NSAID provocation test, we diagnosed the patient with AERD and CRSwNP. A diagnosis of severe eosinophilic chronic rhinosinusitis was also made based on the scoring system and algorithm used in the Japanese Epidemiological Survey of Refractory Eosinophilic Chronic Rhinosinusitis. Results: Treatment with benralizumab (30 mg), formoterol-fluticasone combination via pressurized metered inhaler (1000 µg), and leukotriene receptor antagonist improved the asthma symptoms and exacerbations so the short-term prednisolone was stopped; however, nasal congestion and olfactory dysfunction (hyposmia) persisted, and peripheral blood eosinophil count (peak, 1500 cells/µL) and fractional exhaled nitric oxide (peak, 42 ppb) became elevated. Swapping the benralizumab for monthly tezepelumab (210 mg) improved not only the asthma symptoms but also the nasal congestion, olfactory dysfunction, eosinophil count (<300 cells/µL), and fractional exhaled nitric oxide level [8ppb]. Conclusion: Changing from benralizumab to tezepelumab improved asthma symptoms, nasal obstruction, and olfactory dysfunction in elderly, female, Japanese patient with AERD and CRSwNP.

Targeting dendritic cell activation: the therapeutic impact of paeoniflorin in cortosteroid-dependent dermatitis management.

This study investigates the mechanism through which paeoniflorin inhibits TSLP expression to regulate dendritic cell activation in corticosteroid-dependent dermatitis treatment. Utilizing databases like TCMSP, we identified paeoniflorin's components, targets, and constructed networks. Molecular docking and gene enrichment analysis helped pinpoint key targets and pathways affected by paeoniflorin. In vitro and in vivo models were used to study CD80, CD86, cytokines, T-cell activation, skin lesions, histopathological changes, TSLP, CD80, and CD86 expression. Our study revealed paeoniflorin's active constituent targeting IL-6 in corticosteroid-dependent dermatitis. In vitro experiments demonstrated reduced TSLP expression, CD80, CD86, and cytokine secretion post-paeoniflorin treatment. In vivo, paeoniflorin significantly decreased skin lesion severity, cytokine levels, TSLP, CD80, and CD86 expression. The study highlights paeoniflorin's efficacy in inhibiting TSLP expression and suppressing dendritic cell activation in corticosteroid-dependent dermatitis, suggesting its potential as a therapeutic intervention. Additionally, it offers insights into the complex molecular mechanisms underlying paeoniflorin's anti-inflammatory properties in treating corticosteroid-dependent dermatitis.

Towards precision medicine in COPD: Targeting type 2 cytokines and alarmins.

Chronic obstructive pulmonary disease (COPD) is a main global epidemic increasing as population age and affecting approximately 10% of subjects over 45 years. COPD is a heterogeneous inflammatory disease with several endo-phenotypes and clinical presentations. Although neutrophilic inflammation is canonically considered a hallmark of COPD, eosinophilic inflammation can also be present in a subgroup of patients. Several other immune cells and cytokines play a key role in orchestrating and perpetuating the inflammatory pathways in COPD, making them attractive targets for treating this disorder. Recent studies have started to evaluate the possible role of type 2 (T2) inflammation and epithelial-derived alarmins (TSLP and IL-33) in COPD. Two phase III randomized clinical trials (RCTs) showed a modest reduction in exacerbations in COPD patients with eosinophilic phenotype treated with mepolizumab (anti-IL-5) or benralizumab (anti-IL-5Rα). A phase III RCT showed a 30% reduction in exacerbations in COPD patients with ≥ 300 eosinophils/µL treated with dupilumab (anti-IL-4Rα). These results suggest that blocking a single cytokine (e.g., IL-5) or its main target (i.e., IL-5Rα) is less promising than blocking a wider spectrum of cytokines (i.e., IL-4 and IL-13) in COPD. TSLP and IL-33 are upstream regulators of T2-high and T2-low immune responses in airway inflammation. Several ongoing RCTs are evaluating the efficacy and safety of anti-TSLP (tezepelumab), anti-IL-33 (itepekimab, tozorakimab), and anti-ST2 (astegolimab) in patients with COPD, who experience exacerbations. In conclusion, targeting T2 inflammation or epithelial-derived alarmins might represent a step forward in precision medicine for the treatment of a subset of COPD.

Exploring TSLP and IL-33 Serum Levels and Genetic Variants: Unveiling Their Limited Potential as Biomarkers for Mild Asthma in Children.

As the burden of mild asthma is not well understood, the significance of expanding research in the group of patients with mild asthma is emphasized. Thymic stromal lymphopoietin (TSLP) and interleukin 33 (IL-33) are involved in the pathogenesis of atopy and the immune response to inhaled environmental insults, such as allergens, in asthmatic patients. Objectives: The objective of this study was to explore the correlation between specific polymorphisms within the genes encoding TSLP and IL-33, as well as the concentrations of TSLP and IL-33 in the serum, and the occurrence of pediatric mild asthma. Methods: The analysis encompassed 52 pediatric patients diagnosed with mild bronchial asthma, including both atopic and non-atopic cases, and a control group of 26 non-asthmatic children. Recruitment was conducted through a comprehensive questionnaire. Parameters such as allergic sensitization, serum levels of circulating TSLP and IL-33, and the identification of single-nucleotide polymorphisms in TSLP (rs11466750 and rs2289277) and IL-33 (rs992969 and rs1888909) were assessed for all participants. Results: Significantly lower mean serum TSLP concentrations were observed in asthmatic subjects compared to the control group, with atopic asthma patients showing even lower TSLP levels than non-atopic counterparts. No significant differences were found in mean serum IL-33 concentrations between the two groups. Considering the allele model, for both tested SNPs of IL-33, we observed that patients with asthma, atopic asthma, and atopy statistically less frequently possess the risk allele. Conclusions: Our study findings suggest that IL-33 and TSLP do not serve as ideal biomarkers for mild asthma in children. Their effectiveness as biomarkers might be more relevant for assessing disease severity rather than identifying asthma in pediatric patients. Further research focusing on the association between TSLP and IL-33 gene polymorphisms and asthma is expected to significantly advance disease management.

Advancements in biologic therapy in eosinophilic asthma.

INTRODUCTION: Asthma encompasses a spectrum of phenotypes often categorized into two groups- type 2 high (T2 high) and type 2 low (T2 low). T2 high includes atopic and eosinophilic presentations whereas T2 low is non-atopic, non-eosinophilic, and oft associated with neutrophilic inflammation. Eosinophilic asthma is often driven by IgE, IL-4, IL-5, and IL-13 and TSLP. This can lead to eosinophilic inflammatory response in the airways which in turn can be used as target for treatment. AREAS COVERED: The article will focus on biologic therapy that is currently being used in eosinophilic asthma management in mainly the adult population including clinical trials and co-morbidities that can be treated using the same biologics. A review on asthma biologics for pediatric population has been reviewed elsewhere. EXPERT OPINION: Biological therapy for asthma targeting the IgE, IL-4, IL-5, IL-13, and TSLP pathways are shown to have benefit for the treatment of eosinophilic asthma, as exemplified in real-world studies. When choosing the right biological agent factors such as phenotype, comorbidities, and cost-effectiveness of the biologic agent must be taken into consideration.