Leukotriene Receptor Research Articles

Role of leukotriene receptor antagonist in improvement of symptoms after functional endoscopic sinus surgery for chronic rhinosinusitis with or without sinonasal polyposis

Background: Chronic rhinosinusitis is one of the common ENT diseases encountered daily. Due to its chronicity, it leads to patient morbidity and decreased quality-of-life of the patient. Although various medical and surgical management options are available, none can manage the condition effectively. So, the aim of the study is to evaluate the efficacy of the montelukast in the subjective and objective improvement after the FESS for patients with chronic rhino sinusitis. Methods: This randomized controlled trial was conducted among 50 patients diagnosed with chronic rhino sinusitis. All the patients underwent FESS, and after that, they were divided into two groups; one group received the Montelukast tablet in addition to the standard post-operative regimen, and the other group received the standard post-operative medications only. The subjective and objective measurements were made using SNOT-22 and Lund-Kennedy endoscopic scores during the pre- and post-operative periods. Results: The study showed a significant reduction in the various parameters of SNOT-22, viz runny nose (p=0.013), cough (p=0.003), post-nasal discharge (p=0.037), thick nasal discharge (p=0.013), ear fullness (p=0.021), difficulty in falling asleep (p=0.018), walking up at night (p<0.001), reduced concentration (p=0.001) in Group-A than in Group-B. The study also showed a significant reduction in the overall SNOT-22 score in the Group-A. The Lund-Kennedy endoscopic score (p=0.006) also showed a significant reduction during the postoperative period in Group-A. Conclusion: The Montelukast positively affects the reduction of the various domains in the SNOT-22 and the Lund-Kennedy endoscopic score. It can be used as adjuvant therapy during the post-operative period in patients operated with FESS for CRS.

A RELATION BETWEEN CHRONIC RHINOSINUSITIS WITH NASAL POLYPS (CRSwNP) AND COVID-19 COURSE

Abstract The data on impact of chronic rhinosinusitis (CRS) on SARS-CoV-2 virus susceptibility and COVID-19 course were reviewed. CRS heterogeneity is determined by different types of inflammatory response. A heterogeneous CRS is divided into CRS without polyps and with nasal polyps (CRSwNP) is accounted for by diverse underlying immune responses. Hypersecretion of interleukins (IL)-4, IL-5, IL-13 in eosinophilic CRSwNP downmodulates angiotensin-converting enzyme (ACE)-2 receptor expression that should reduce SARS-CoV-2 infection risk because ACE2 is a main cellular tropism factor for SARS-CoV-2. In neutrophilic CRS type 1 immune response predominates, with activation of Th-1 cells, hypersecretion of interferon (IFN)-γ and tumor necrosis factor (TNF)-α to increase ACE2 expression. However, another data also show that hypoxemia level and pulmonary system damage did not differ between patients with CRS and CRS without polyps. Literature contradictions may be related to differences in availability of medical care, treatment of bronchial asthma (BA) as well as coverage of PCR testing. Regarding use of local or systemic glucocorticosteroids (GCS) effect on SARS-CoV-2 infection risk, some authors believe that GCS may increase COVID-19 severity and mortality, probably by downmodulating local innate immune response factors. According to other data, GCS may reduce ACE2 expression, or there is no relationship between previous GCS use, the incidence of COVID-19 and the frequency of treatment in the intensive care unit. Biological therapy of CRSwNP and BA with monoclonal antibodies did not aggravate COVID-19 severity and mortality risk. Although such data are currently limited, authors recommend not to interrupt such treatment during the epidemic, as well as continue taking leukotriene receptor blockers that can further inhibit major protease (Mpro) of the SARS-CoV-2 virus. However, according to international guidelines on COVID-19 treatment, using CRSwNP and asthma biological therapy should be discontinued until the patients recover completely. Allergen-specific immunotherapy (ASIT) should be interrupted in the case of confirmed COVID-19 due to a probability of developing severe COVID-19. After COVID-19, disturbances in the immune system may persist and possibly change the course of CRS, therefore requiring to modify therapeutic approaches for such patients. At the same time, the worldwide literature has been gradually accumulating information on pathogenesis underlying alterations in such patients including those with CRS, which requires development of new therapeutic approaches.

Role of SIRPG gene in type 1 diabetes and lichen planus.

Type 1 diabetes (T1D) is a form of diabetes caused by pancreatic β-cell destruction and absolute insulin deficiency. Lichen planus (LP) is an idiopathic inflammatory skin disease of unclear etiology. The role of SIRPG gene dysregulation in T1D and LP remains unclear. Mendelian randomization (MR) using matched samples was employed to study causal relationship between T1D and increased risk of LP. T1D-related single nucleotide polymorphism identification was conducted. Datasets GSE156035 for T1D and GSE52130 for LP were obtained from gene expression omnibus. Differentially expressed genes were identified, analyses included weighted gene co-expression network analysis, functional enrichment, gene set enrichment analysis, and protein-protein interaction network construction and analysis. Heatmaps of gene expression levels were generated. Comparative toxicogenomics database was used to identify diseases most relevant to core genes. Inverse variance weighted, MR-Egger, weighted median methods estimated genetic predisposition between T1D and LP, showing consistent positive correlations using both weighted median and inverse variance weighted methods. Horizontal pleiotropy analysis with MR-Egger intercept indicated no evidence of significant directional pleiotropy (P = .70645) for LP. There was no evidence of directional pleiotropy effects between T1D and LP. One hundred eighteen differentially expressed genes were identified. In biological processes, they were mainly enriched in apoptosis, inflammatory response, insulin receptor signaling pathway, glucose metabolism. In cellular components, enrichment was observed in mediator complex and replication fork. In molecular function, they were concentrated in leukotriene receptor activity and helicase activity. Kyoto Encyclopedia of Genes and Genomes analysis revealed enrichment in metabolic pathways, PI3K-Akt signaling pathway, cell cycle, p53 signaling pathway, AGE-RAGE signaling pathway in diabetic complications. Weighted gene co-expression network analysis with a soft threshold power of 4. SIRPG showing high expression in both T1D and LP samples. There is a positive causal relationship between T1D and LP. Comparative toxicogenomics database analysis revealed associations of core genes with metabolic syndrome, lipid metabolism disorders, cardiovascular diseases, immune system diseases, peripheral neuropathic pain, and inflammation. SIRPG is highly expressed in both T1D and LP, providing a new insight into the pathogenesis of T1D and LP.

Cysteine Leukotriene Receptor Antagonist-Montelukast Effects on Diabetic Retinal Microvascular Endothelial Cells Curtail Autophagy.

Diabetic macular edema (DME) is the primary cause of vision impairment in diabetic retinopathy (DR) patients. A previous study has shown the efficacy of montelukast, a cysteinyl leukotriene receptor (CysLTR)1 antagonist, in a diabetic mouse model. This study aims to understand the CysLTR1 signaling in retinal endothelial cells and the impact of montelukast. Primary human retinal microvascular endothelial cells (HRECs) challenged with 20 ng/mL TNF-α and 30mM D-glucose (D-glu) for six to 24 hours served as a model of endothelial activation. HRECs were incubated with L-glucose (L-glu) as an osmotic control. CysLTR1 knockdown and montelukast pretreatment assessed CysLTR1 antagonism. Gene expression, protein expression, and cell-permeable dyes were utilized to measure autophagy and inflammation. Transendothelial electrical resistance (TER) and transendothelial migration of mononuclear leukocytes across HRECs monolayer were measured as a functional assessment of vascular permeability. Endothelial activation induced by hyperglycemia and inflammation increased CysLTR1 expression, triggering autophagy within two to six hours, IL-1β production, loss of junction integrity, decreased TER, and increased leukocyte migration within six to 24 hours. Pretreatment with montelukast effectively alleviated these effects, demonstrating its dependence on CysLTR1. Dysfunctional retinal endothelium initiates a self-reinforcing loop of inflammation, autophagy, and compromised integrity associated with heightened CysLTR1 levels. The antagonistic effect of montelukast against CysLTR1 effectively mitigates these detrimental changes. This study reveals CysLTR1 as a potential therapeutic target in treating DME and offers a novel strategy to mitigate detrimental changes in DR.

Efficacy and Safety of Montelukast+Levocetirizine Combination Therapy Compared to Montelukast Monotherapy for Allergic Rhinitis in Children.

The combination therapy of leukotriene receptor antagonists and antihistamines may alleviate allergic rhinitis (AR) symptoms better than monotherapy. This study aimed to investigate the safety and efficacy of Monterizine®, a fixed-dose combination of montelukast and levocetirizine, compared to montelukast monotherapy in pediatric patients with AR. One hundred seventy-six children aged 6 to 14 years with perennial AR symptoms were recruited. One hundred forty-seven subjects were randomized into 1 of 2 groups: the mont+levo group (fixed-dose combination of montelukast [5 mg] + levocetirizine [5 mg]) or the mont group (montelukast single agent [5 mg]). Study subjects took the treatment every evening for 4 weeks and recorded their daytime nasal symptom score (DNSS) and nighttime nasal symptom score (NNSS) in a diary every day. Adverse events (AEs) were also recorded, and patients were surveyed as to their overall satisfaction with the therapeutic product they received. When DNSS and NNSS were assessed individually, daytime nasal congestion symptom scores decreased more in the mont+levo group during the 4-week treatment period than in the mont group (P = 0.0341). The daytime rhinorrhea symptom scores also decreased more in the mont+levo group (P = 0.0469). The nighttime nasal congestion score (severity when awake) decreased more in the mont+levo group than in the mont group (P = 0.0381). Study subjects in the mont+levo group experienced a greater improvement in quality of life than subjects in the mont group (P < 0.0001). The combination therapy of montelukast and levocetirizine was more effective in reducing both daytime nasal symptoms (nasal congestion and rhinorrhea) and nighttime nasal symptoms (severity of nasal congestion when awake). With fewer AEs and higher overall satisfaction, combination therapy is recommended for pediatric patients with perennial AR.

Comparative Study of Inhaled Corticosteroids and Leukotriene Receptor Antagonists As Controller Options for Mildly to Moderately Persistent, Stable Asthma.

Asthma is a chronic inflammatory disease of the airways characterized by bronchoconstriction, airway hyperresponsiveness, and variable airflow limitation. This results in symptoms such as wheezing, difficulty breathing, chest tightness, chest pain, and coughing. The primary objective of the study is to compare the efficacy of inhaled corticosteroids (ICS) versus leukotriene receptor antagonists (LTRA) in improving asthma control, lung function, and quality of life in patients with mild to moderate persistent asthma. This prospective comparative study was conducted at Khyber Teaching Hospital and Dow University Hospital from January 2018 to July 2021. 210 patients suffering from asthma were included in the study. Patients aged 18 years and older, diagnosed with mild to moderate persistent asthma as per Global Initiative for Asthma (GINA) guidelines, and requiring pharmacological intervention were included in the study. Participants were randomly allocated into two groups.Treatment efficacy was compared based on asthma control (Asthma Control Test (ACT) score), lung function (forced expiratory volume in one second (FEV1),peak expiratory flow rate (PEFR)), and quality of life using validated questionnaires. In this study involving 210 patients with asthma, Group A (ICS) had a mean age of 36.23 ± 7.09 years, while Group B (LTRA) had a mean age of 35.23 ± 8.01 years. Both groups exhibited similar baseline asthma control, as indicated by ACT scores of 17.2 ± 3.5 for Group A and 16.8 ± 3.2 for Group B. Significant improvements were observed in both groups at the end of the study, with ACT scores rising to 21.8 ± 2.1 (p < 0.001) for Group A and 20.5 ± 2.5 (p < 0.001) for Group B. Additionally, lung function, measured by FEV1 and PEFR, showed similar enhancements; Group A improved from a baseline FEV1 of 2.5 ± 0.8 L to 3.2 ± 0.6 L (p < 0.01), while Group B improved from 2.4 ± 0.7 L to 3.0 ± 0.5 L. The PEFR values also increased significantly from 300 ± 50 L/min to 380 ± 40 L/min (p < 0.001) for Group A and from 290 ± 45 L/min to 360 ± 30 L/min (p < 0.001) for Group B. Both treatments were well-tolerated, with adverse events being low and comparable between the groups. This study reveals that both ICSand LTRAsignificantly improve asthma control, lung function, and quality of life in patients with mild to moderate persistent asthma, with ICS showing superior efficacy. ICS led to greater improvements in ACT scores and lung function parameters, supporting its use as a more effective treatment option in this patient population.

Nonasthmatic Eosinophilic Bronchitis: A Systematic Review of Current Treatment Options.

Nonasthmatic eosinophilic bronchitis is characterized by persistent dry or barely productive cough and bronchial eosinophilia without airway obstruction or bronchial hyperreactivity. It is primarily a chronic disease, in which some patients have clinical and pathophysiological relapses, while others progress to asthma or chronic obstructive pulmonary disease. It accounts for 5% to 30% of cases referred for chronic cough. Exposure to common inhalants and occupational sensitizers has been proposed as a possible cause of the disease, although the etiology and underlying mechanisms are uncertain. Some features are similar to those of asthma, such as airway eosinophilia, inflammatory mediator levels, and airway remodeling. Differences in airway pathophysiology, such as the location of airway inflammation and levels of IL-13 and PGE-2, have been reported. Sputum cell count is the gold standard test for diagnosis, and other biomarkers, such as exhaled nitric oxide, could support the diagnosis. A systematic review of treatments for the disease shows that while inhaled corticosteroids are the primary option, the appropriate dose, the type of corticosteroid, and the duration of treatment remain unknown. Treatment duration is inversely correlated with the relapse rate. Increased doses of inhaled corticosteroids, oral corticosteroids, and leukotriene receptor antagonists are recommended in persistent disease. Anti-IL-5 biologics could be promising in this disease. Studies that investigate biomarkers for diagnosis and prognosis are necessary, as are randomized controlled studies for second-line treatments.

In silico Prediction of Pranlukast as a Stabilizer of PD-L1 Homodimers.

Tumors can be targeted by modulating the immune response of the patient. Programmed cell death protein 1 (PD-1) and programmed cell death ligand 1 (PD-L1) are critical immune checkpoints in cancer biology. The efficacy of certain cancer immunotherapies has been achieved by targeting these molecules using monoclonal antibodies. Small-molecule drugs have also been developed as inhibitors of the PD-1/PD-L1 axis, with a mechanism of action that is distinct from that of antibodies: they induce the formation of PD-L1 homodimers, causing their stabilization, internalization, and subsequent degradation. Drug repurposing is a strategy in which new uses are sought after for approved drugs, expediting their clinical translation based on updated findings. In this study, we generated a pharmacophore model that was based on reported small molecules that targeted PD-L1 and used it to identify potential PD-L1 inhibitors among FDA-approved drugs. We identified 12 pharmacophore-matching compounds, but only 4 reproduced the binding mode of the reference inhibitors in docking experiments. Further characterization by molecular dynamics showed that pranlukast, an antagonist of leukotriene receptors that is used to treat asthma, generated stable and energyfavorable interactions with PD-L1 homodimers and induced homodimerization of recombinant PD-L1. Our results suggest that pranlukast inhibits the PD-1/PD-L1 axis, meriting its repurposing as an antitumor drug.

CYSLTR1 antagonism displays potent anti-tumor effects in uveal melanoma

Uveal Melanoma (UM) is the most common primary intraocular malignancy in adults. Although rare, it is a deadly tumor, with a long-term prognosis of death occurring in more than 50% of the cases. It is characterized by frequent (∼80%) driver mutations in GNAQ and GNA11 genes, both of which are activated by cysteinyl leukotriene receptors (CYSLTRs). CYSLTR1 is upregulated and participated in the progression of several cancers. In the present study, we sought to determine the expression levels of CYSLTR1 in 31 human UM specimens and cell lines (3 primary and 1 metastatic), and its role in the proliferation and viability of these cells by analyzing cell metabolic activity, cell confluence and apoptosis levels. We show that all analyzed UM specimens and cells expressed CYSLTR1 at high levels. Notably, the pharmacological blockage of this receptor, using the inverse agonist MK571, reduced the growth and metabolic activity, and increased the apoptotic cell death of all analyzed UM cell lines. We provide evidence that CYSLTR1 is expressed in human UM and plays a significant role in UM progression behavior. Our data highlight the potential beneficial effects of targeting CYSLTR1 in the control of UM progression.

Cysteinyl Leukotriene Receptor Antagonism by Montelukast to Treat Visual Deficits.

Montelukast, a Food and Drug Administration-approved drug for asthma and allergic rhinitis modulates leukotriene (LT) receptors and serves as a critical anti-inflammatory agent. Recent research suggests that the LT signaling pathway targeted by montelukast has broader implications for diseases such as fibrosis, cardiovascular diseases, cancer, cerebrovascular disease, and immune defense. This expanded understanding highlights montelukast's potential for repurposing in conditions involving aberrant stress mechanisms, including ocular diseases marked by inflammation, oxidative stress, ER stress, and apoptosis, among several others. This review delves into montelukast's therapeutic mechanisms across various diseases, draws parallels to ocular conditions, and examines clinical trials and associated adverse effects to underscore the unmet need for cysteinyl LT receptor antagonism by montelukast as an effective therapy for visual deficits.

Effects of oral montelukast on pulmonary function and clinical symptoms in acute asthma exacerbations: a randomized, double-blind, placebo-controlled trial

Introduction: Montelukast is a leukotriene receptor antagonist that helps treat chronic asthma and allergic rhinitis by reducing inflammation and bronchoconstriction. However, oral montelukast’s effectiveness in managing acute asthma attacks has yet to be completely identified. Methods: This randomized, double-blind, placebo-controlled trial investigated the efficacy of oral montelukast in acute exacerbations of asthma. Seventy patients between 18 and 65 years of age with a primary diagnosis of asthma attack were included in the study and were randomly assigned to receive 10 mg of montelukast orally daily or placebo. Symptoms, signs, forced expiratory volume in 1 second (FEV1), and peak expiratory flow rate (PEFR) were evaluated. Results: Our findings showed a statistically significant difference between montelukast and placebo regarding FEV1 (78.05 ± 7.84 vs. 72.05 ± 12.00, P = 0.016), PEFR (322.86 ± 28.95 vs. 290.86 ± 44.21, P = 0.003), and wheezing (P = 0.022) on the fifth day of treatment. Additionally, FEV1 and PEFR values were compared in two subgroups of patients, ICS users (ICSU) and non-ICS users (NICSU), in both the montelukast and placebo groups. In the montelukast group, while PEFR improved significantly for day 5 in both the ICSU (P = 0.007) and NICSU (P = 0.027) subgroups, FEV1 only improved in the ICSU (P = 0.009) subgroup compared to placebo. Conclusion: The present study demonstrated that oral montelukast administered in acute asthma exacerbation could lead to better values of PEFR and FEV1 on pulmonary function and improvement of wheezing in terms of symptoms.

The role of signaling pathways mediated by the GPCRs CysLTR1/2 in melanocyte proliferation and senescence.

In contrast with sun exposure-induced melanoma, rarer melanocytic tumors and neoplasms with low mutational burden present opportunities to study isolated signaling mechanisms. These include uveal melanoma and blue nevi, which are often driven by mutations within the G protein-coupled signaling cascade downstream of cysteinyl leukotriene receptor 2. Here, we review how the same mutations within this pathway drive the growth of melanocytes in one tissue but can inhibit the growth of those in another, exemplifying the role of the tissue environment in the delicate balance between uncontrolled cell growth and senescence.

Zafirlukast ameliorates lipopolysaccharide and bleomycin-induced lung inflammation in mice

Acute lung injury (ALI) is the result of damage to the capillary endothelia and the alveolar epithelial cell caused by various direct and indirect factors, leading to significant pulmonary interstitial and alveolar edema and acute hypoxic respiratory insufficiency. A subset of ALI cases progresses to irreversible pulmonary fibrosis, a condition with fatal implications. Zafirlukast is a leukotriene receptor antagonist licensed for asthma prevention and long-term treatment. This study demonstrated a significant improvement in lung tissue pathology and a reduction in inflammatory cell infiltration in models of lipopolysaccharide (LPS)-induced ALI and bleomycin (BLM)-induced lung inflammation following zafirlukast administration, both in vivo and in vitro. Moreover, zafirlukast was found to suppress the inflammatory response of alveolar epithelial cells in vitro and lung inflammation in vivo by reducing the activation of the TLR4/NF-κB/NLRP3 inflammasome pathway. In conclusion, zafirlukast relieved lung injury and the infiltration of inflammatory cells in the lung by regulating the TLR4/NF-κB/NLRP3 pathway.

Breathing for Two: Asthma Management, Treatment, and Safety of Pharmacological Therapy during Pregnancy.

The primary objectives of asthma management during pregnancy are to achieve adequate symptom control, reduce the risk of acute exacerbations, and maintain normal pulmonary function, all of which contribute to ensuring the health and well-being of both the mother and the baby. The Global Initiative for Asthma (GINA) recommends that pregnant women with asthma continue using asthma medications throughout pregnancy, as the benefits of well-controlled asthma for both the mother and fetus outweigh the potential risks of medication side effects, poorly controlled asthma, and exacerbations. The classification of asthma medications by the US Food and Drug Administration (FDA) into categories A, B, C, D, and X is no longer applied. Instead, the potential benefits and risks of each medication during pregnancy and lactation are considered individually. The use of medications to achieve good asthma control and prevent exacerbations during pregnancy is justified, encompassing inhaled corticosteroids (ICS), some leukotriene receptor antagonists (LTRA), short-acting beta-2 agonists (SABA), long-acting beta-2 agonists (LABA), short-acting muscarinic antagonists (SAMA), long-acting muscarinic antagonists (LAMA), and, recently, biological therapies, even in the absence of definitive safety data during pregnancy.

Neuropsychiatric Events Related to Montelukast and Pranlukast in Adults With Asthma and Rhinitis: A 10-Year Nationwide Population-Based Study

Epidemiological studies of neuropsychiatric events (NPEs) associated with leukotriene receptor antagonists (LTRAs) have yielded inconsistent results. Recent studies have demonstrated strong temporal relationships between LTRA prescription and NPE occurrence, indicating a need for further investigation. To investigate potential LTRA-related NPEs and associated risk factors. Adults with asthma or rhinitis were enrolled from the Korean claims database. The temporal relationship between the first NPE diagnosis and the last LTRA prescription before NPE was evaluated. Nested case-control studies for NPEs and suicide were conducted. Cases (those with NPEs) were matched to controls for age and sex to compare the frequency of LTRA prescription in the lag time before NPE diagnosis. The risk factors for LTRA-related NPEs (developed within 6 months of LTRA prescription) were assessed in people on LTRAs by comparing those with LTRA-related NPEs to those on LTRAs who did not have NPEs. Montelukast and pranlukast were more frequently prescribed within 6 months before NPEs (odds ratio, 1.31, 95% CI, 1.21-1.41, and odds ratio, 1.25, 95% CI, 1.15-1.35). Older adults, low income, high comorbidity burden, and asthma exhibited stronger associations with LTRA-related NPEs than with general NPEs. Sleep disturbances appeared more prevalent in LTRA-related NPEs than in other NPEs. An LTRA prescription within 6 months was associated with suicide in univariate but not in multivariate analysis. Increased neuropsychiatric risk was observed within 6 months after LTRA prescription. LTRA may lower the threshold for NPEs in those at risk for NPEs, irrespective of sex.

Intranasal Versus Oral Treatments for Allergic Rhinitis: A Systematic Review With Meta-Analysis

BackgroundTreatments for allergic rhinitis include intranasal or oral medications. ObjectiveTo perform a systematic review with meta-analysis comparing the effectiveness of intranasal corticosteroids or antihistamines versus oral antihistamines or leukotriene receptor antagonists in improving allergic rhinitis symptoms and quality of life. MethodsWe searched four bibliographic databases and three clinical trial datasets for randomised controlled trials (i) assessing patients ≥12 years old with seasonal or perennial allergic rhinitis, and (ii) comparing intranasal corticosteroids or antihistamines versus oral antihistamines or leukotriene receptor antagonists. We performed a meta-analysis of the Total Nasal Symptom Score (TNSS), Total Ocular Symptom Score (TOSS), Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ), development of adverse events, and withdrawals due to adverse events. Certainty of evidence was assessed using GRADE. ResultsWe included 35 studies, most of which assessed patients with seasonal allergic rhinitis and displayed an unclear risk of bias. Superiority of intranasal treatments was found for all assessed outcomes. Intranasal corticosteroids were more effective than oral antihistamines at improving the TNSS (MD=-0.86; 95%CI=-1.21;-0.51; I2=70%), TOSS (MD=-0.36; 95%CI=-0.56;-0.17; I2=0%) and RQLQ (MD=-0.88; 95%CI=-1.15;-0.61; I2=0%), being mostly associated with clinically meaningful improvements. Superiority of intranasal corticosteroids at improving the TNSS was also found against oral leukotriene receptor antagonists (MD=-1.05; 95%CI=-1.33;-0.77). Intranasal antihistamines were more effective than oral antihistamines at improving the TNSS (MD=-0.47; 95%CI=-0.81;-0.14; I2=0%) and RQLQ (MD=-0.31; 95%CI=-0.56;-0.06; I2=0%). ConclusionsRandomized controlled trials suggest that intranasal treatments are more effective than oral treatments at improving symptoms and quality of life in seasonal allergic rhinitis.

Effectiveness of Intranasal Steroid Spray (Fluticasone Furoate) on Allergic Rhinitis: A Cross-sectional Study

Background: Treatment for allergic rhinitis in addition to avoidance of allergens, involves various medications, including antihistamines, leukotriene receptor antagonists, and both topical and systemic corticosteroids. Fluticasone furoate is commonly used as a topical steroid, with intranasal steroid sprays are considered as the most effective option. However, there is a lack of established evidence regarding the effectiveness and safety of intranasal steroids. Objectives: The primary aim of the present study is to assess the efficacy of intranasal steroid spray (specifically, fluticasone furoate) in treating allergic rhinitis. Methods: In our study, we conducted a prospective cross-sectional investigation involving 155 patients with allergic rhinitis who visited the outpatient department of City Medical College Hospital. The selected patients were provided with a questionnaire to gather information concerning their symptoms, usage of intranasal steroids, and any related concerns. Results: All 155 patients completed the questionnaire. Among them, every patient utilized of intranasal steroid spray for the last one year. Our study reported that 82.58% patients are benefited by using intranasal steroid spray, 78.71% report better airway, and 76.77% observe a decrease in nasal discharge with multiple responses simultaneously. A total of 17.42% report no benefit at all, while 13.55% note a rebound effect, with 1.29% experiencing epistaxis. Conclusion: The practical effectiveness and occurrence of adverse events associated with intranasal steroid sprays closely mirror the findings observed in clinical trials. J Com Med Col Teachers Asso Jan 2024; 28(1): 24-26

Endogenous PGD2 acting on DP2 receptor counter regulates Schistosoma mansoni infection-driven hepatic granulomatous fibrosis.

Identifying new molecular therapies targeted at the severe hepatic fibrosis associated with the granulomatous immune response to Schistosoma mansoni infection is essential to reduce fibrosis-related morbidity/mortality in schistosomiasis. In vitro cell activation studies suggested the lipid molecule prostaglandin D2 (PGD2) as a potential pro-fibrotic candidate in schistosomal context, although corroboratory in vivo evidence is still lacking. Here, to investigate the role of PGD2 and its cognate receptor DP2 in vivo, impairment of PGD2 synthesis by HQL-79 (an inhibitor of the H-PGD synthase) or DP2 receptor inhibition by CAY10471 (a selective DP2 antagonist) were used against the fibrotic response of hepatic eosinophilic granulomas of S. mansoni infection in mice. Although studies have postulated PGD2 as a fibrogenic molecule, HQL-79 and CAY10471 amplified, rather than attenuated, the fibrotic response within schistosome hepatic granulomas. Both pharmacological strategies increased hepatic deposition of collagen fibers - an unexpected outcome accompanied by further elevation of hepatic levels of the pro-fibrotic cytokines TGF-β and IL-13 in infected animals. In contrast, infection-induced enhanced LTC4 synthesis in the schistosomal liver was reduced after HQL-79 and CAY10471 treatments, and therefore, inversely correlated with collagen production in granulomatous livers. Like PGD2-directed maneuvers, antagonism of cysteinyl leukotriene receptors CysLT1 by MK571 also promoted enhancement of TGF-β and IL-13, indicating a key down-regulatory role for endogenous LTC4 in schistosomiasis-induced liver fibrosis. An ample body of data supports the role of S. mansoni-driven DP2-mediated activation of eosinophils as the source of LTC4 during infection, including: (i) HQL-79 and CAY10471 impaired systemic eosinophilia, drastically decreasing eosinophils within peritoneum and hepatic granulomas of infected animals in parallel to a reduction in cysteinyl leukotrienes levels; (ii) peritoneal eosinophils were identified as the only cells producing LTC4 in PGD2-mediated S. mansoni-induced infection; (iii) the magnitude of hepatic granulomatous eosinophilia positively correlates with S. mansoni-elicited hepatic content of cysteinyl leukotrienes, and (iv) isolated eosinophils from S. mansoni-induced hepatic granuloma synthesize LTC4 in vitro in a PGD2/DP2 dependent manner. So, our findings uncover that granulomatous stellate cells-derived PGD2 by activating DP2 receptors on eosinophils does stimulate production of anti-fibrogenic cysLTs, which endogenously down-regulates the hepatic fibrogenic process of S. mansoni granulomatous reaction - an in vivo protective function which demands caution in the future therapeutic attempts in targeting PGD2/DP2 in schistosomiasis.

Focused allergic rhinitis practice parameter for Canada.

Allergic rhinitis (AR) is a prevalent disease in Canada that affects both children and adults. Several guidelines for the management of AR have been published by professional allergy societies worldwide. However, there are regional differences in the clinical management of AR, and regulatory approval of some AR pharmacotherapies varies among countries. Thus, six research questions specific to the treatment of AR in Canada were identified for this focused practice parameter. Reviews of the literature published since 2016 were conducted to obtain evidence-based support for the responses of the Work Group to each research question. In response to research question 1 "In patients with symptoms indicative of AR, is serum-specific IgE sufficient to identify candidates for immunotherapy or is a skin prick test mandatory?" the Work Group concluded that either sIgE testing or skin prick test are acceptable for diagnosing AR and guiding immunotherapy. In response to research question 2 "When taking into account the preferences of the patient and the prescriber (stakeholder engagement) should second-generation oral antihistamine (OAH) or intranasal corticosteroid (INCS) be first line?" the Work Group concluded that existing guidelines generally agree on the use of INCS as a first-line therapy used for AR, however, patient and provider preferences and considerations can easily shift the first choice to a second-generation OAH. In response to research question 3 "Is a combination intranasal antihistamine (INAH)/INCS formulation superior to INCS plus OAH? Do they become equivalent after prolonged use?" the Work Group concluded that that the combination INAH/INCS is superior to an INCS plus OAH. However, there was insufficient evidence to answer the second question. In response to research question 4 "Do leukotriene receptor antagonists (LTRA) have a greater benefit than OAH in AR for some symptoms to justify a therapeutic trial in those who cannot tolerate INCS?" the Work Group concluded that LTRAs have inferior, or at best equivalent, daytime or overall symptom control compared with OAH, but LTRAs may improve nighttime symptom control and provide benefits in patients with AR and concomitant asthma. In response to research question 5 "Should sublingual immunotherapy (SLIT) tablets be considered first-line immunotherapeutic options over subcutaneous immunotherapy (SCIT) based on the evidence of efficacy?" the Work Group concluded that the choice of SLIT or SCIT cannot be made on efficacy alone, and differences in other factors outweigh any differences in efficacy. In response to research question 6 "Based on efficacy data, should ALL patients seen by an allergist be offered SLIT or SCIT as a treatment option?" the Work Group concluded that the efficacy data suggests that SLIT or SCIT should be used broadly in patients with AR, but other clinical concerns also need to be taken into consideration.

Drug fever-an immune-mediated delayed type hypersensitivity reaction to Vinca alkaloids in pediatric oncology patients, possibly mediated by cysteinyl leukotrienes.

Drug hypersensitivity reactions are common in pediatric hemato-oncology patients due to multiple factors including immune compromise and pharmacological complexities. Fever can signify severe delayed-type hypersensitivity reactions such as drug reaction with eosinophilia and systemic symptoms (DRESS) or drug-induced hypersensitivity syndrome (DIHS). The etiology of fever as an isolated hypersensitivity reaction to chemotherapeutic agents not fully understood. Here, we report three children with intracranial neoplasms experiencing recurrent febrile reactions following Vinca alkaloid-based chemotherapy, mitigated by cysteinyl leukotriene receptor antagonist therapy. We present a series of pediatric patients with diverse intracranial neoplasms who developed recurrent fever episodes after multiple courses of Vinca alkaloid-based chemotherapy. Treatment involved prophylactic and post-chemotherapy administration of a cysteinyl leukotriene receptor antagonist to prevent fever episodes and enable completion of chemotherapy regimens without protocol modifications or desensitization. All three patients experienced fever consistent with delayed-type hypersensitivity reactions to Vinca alkaloids. Prophylactic use of the leukotriene antagonist Montelukast successfully prevented fever recurrence, allowing uninterrupted completion of chemotherapy courses. Our findings suggest that Montelukast, a leukotriene antagonist, may be beneficial in managing fever as a delayed-type hypersensitivity reaction to Vinca alkaloids in pediatric patients. Further research is warranted to elucidate the underlying mechanisms and leukotriene pathways involved in drug-induced fever reactions.