Leukotriene Research Articles

Exploring the roles of prostanoids, leukotriens, and dietary fatty acids in cutaneous inflammatory diseases: Insights from pharmacological and genetic approaches.

Prostanoids and leukotrienes (LTs) are representative of ω6 fatty acid-derived metabolites that exert their actions through specific receptors on the cell surface. These lipid mediators, being unstable in vivo, act locally at their production sites; thus, their physiological functions remain unclear. However, recent pharmacological and genetic approaches using experimental murine models have provided significant insights into the roles of these lipid mediators in various pathophysiological conditions, including cutaneous inflammatory diseases. These lipid mediators act not only through signaling by themselves but also by potentiating the signaling of other chemical mediators, such as cytokines and chemokines. For instance, prostaglandin E2 -EP4 and LTB4 -BLT1 signaling on cutaneous dendritic cells substantially facilitate their chemokine-induced migration ability into the skin and play critical roles in the priming and/or activation of antigen-specific effector T cells in the skin. In addition to these ω6 fatty acid-derived metabolites, various ω3 fatty acid-derived metabolites regulate skin immune cell functions, and some exert potent anti-inflammatory functions. Lipid mediators act as modulators of cutaneous immune responses, and manipulating the signaling from lipid mediators has the potential as a novel therapeutic approach for human skin diseases.

The First Definition of Pulmonary Component of Hypereosinophilic Syndrome: Bronchial Casts.

Hypereosinophilic syndrome is a heterogeneous disease characterized by eosinophilic tissue inflammation and eosinophilia. Pulmonary involvement could be seen in up to 55% among children with hypereosinophilic syndrome. A 3-year-old boy with chronic hypereosinophilia and respiratory complaints was diagnosed with idiopathic hypereosinophilic syndrome. Atelectasis was detected in the radiological evaluation, and bronchial casts with eosinophilic structures were removed by bronchoscopy. Steroid, inhaled hypertonic saline, inhaled bronchodilator, inhaled corticosteroid, and leukotriene receptor antagonist were used for 1 year in the management of hypereosinophilic syndrome, and related eosinophilic casts and repetitive bronchoscopies were administered for removal of the casts. The patient was successfully managed with an inhaled N-acetyl cysteine treatment. In children, the long-term prognosis of hypereosinophilic syndrome is uncertain. Comprehensive diagnostic tests are required for the early diagnosis and management of pediatric hypereosinophilic syndrome. In the presented case, the rare occurrence of pulmonary involvement of hypereosinophilic syndrome in a 3 year-old-boy with recurrent hypereosinophilic casts and its management were discussed.

Effect of transfected induced pluripotent stem cells with Decorin gene on control of lung remodeling in allergic asthma.

Asthma is a complex respiratory disease, which is controlled by genetic and environmental factors. Type 2-dominant immune response is responsible for asthma. Decorin (Dcn) and stem cells have modulatory effect on immune system and may control tissue remodeling and asthma pathophysiology. In this study, immunomodulatory effect of transduced induced pluripotent stem cells (iPSCs) with expression of Dcn gene on allergic asthma pathophysiology was evaluated. After transduction of iPSCs with Dcn gene, allergic asthma mice were treated with iPSCs and transduced iPSCs via intrabronchial. Then, airway hyperresponsiveness (AHR), levels of interleukin (IL)-4, IL-5, IL-13, IL-33, total IgE, leukotrienes (LTs) B4, C4, hydroxyproline (HP) content, and transforming growth factor-beta (TGF-β) were measured. Also, lung histopathology study was done. AHR, levels of IL-4, IL-5, IL-13, IL-33, total IgE, LTs B4, C4, TGF-β, HP content, mucus secretion, goblet cell hyperplasia, and eosinophilic inflammation were controlled by iPSCs and transduced iPSCs treatment. Therapeutic effect of iPSCs could control main allergic asthma symptoms and related pathophysiologic mechanisms and the effect can be increased when applied with Dcn expression gene.

Exploring the neuroprotective effects of montelukast on brain inflammation and metabolism in a rat model of quinolinic acid-induced striatal neurotoxicity

BackgroundOne intrastriatal administration of quinolinic acid (QA) in rats induces a lesion with features resembling those observed in Huntington’s disease. Our aim is to evaluate the effects of the cysteinyl leukotriene receptor antagonist montelukast (MLK), which exhibited neuroprotection in different preclinical models of neurodegeneration, on QA-induced neuroinflammation and regional metabolic functions.MethodsThe right and left striatum of Sprague Dawley and athymic nude rats were injected with QA and vehicle (VEH), respectively. Starting from the day before QA injection, animals were treated with 1 or 10 mg/kg of MLK or VEH for 14 days. At 14 and 30 days post-lesion, animals were monitored with magnetic resonance imaging (MRI) and positron emission tomography (PET) using [18F]-VC701, a translocator protein (TSPO)-specific radiotracer. Striatal neuroinflammatory response was measured post-mortem in rats treated with 1 mg/kg of MLK by immunofluorescence. Rats treated with 10 mg/kg of MLK also underwent a [18F]-FDG PET study at baseline and 4 months after lesion. [18F]-FDG PET data were then used to assess metabolic connectivity between brain regions by applying a covariance analysis method.ResultsMLK treatment was not able to reduce the QA-induced increase in striatal TSPO PET signal and MRI lesion volume, where we only detected a trend towards reduction in animals treated with 10 mg/kg of MLK. Post-mortem immunofluorescence analysis revealed that MLK attenuated the increase in striatal markers of astrogliosis and activated microglia in the lesioned hemisphere. We also found a significant increase in a marker of anti-inflammatory activity (MannR) and a trend towards reduction in a marker of pro-inflammatory activity (iNOS) in the lesioned striatum of MLK—compared to VEH-treated rats. [18F]-FDG uptake was significantly reduced in the striatum and ipsilesional cortical regions of VEH-treated rats at 4 months after lesion. MLK administration preserved glucose metabolism in these cortical regions, but not in the striatum. Finally, MLK was able to counteract changes in metabolic connectivity and measures of network topology induced by QA, in both lesioned and non-lesioned hemispheres.ConclusionsOverall, MLK treatment produced a significant neuroprotective effect by reducing neuroinflammation assessed by immunofluorescence and preserving regional brain metabolism and metabolic connectivity from QA-induced neurotoxicity in cortical and subcortical regions.

Fluticasone Furoate/Vilanterol Use Trends and Characteristics in Patients With Obstructive Airway Disease: A Real-World Study of 10,374 Patients From India.

Introduction Obstructive Airway Diseases (OADs) are the leading cause of death among chronic respiratory diseases worldwide, and novel therapies are direly needed. Fluticasone furoate/vilanterol (FF/Vi) (100/25 µg) is the first once-daily ICS/uLABA marketed in India for COPD since 2021. Considering its limited real-world experience in OAD patients in Indian clinical settings, a large drug utilization study (DUS) was planned. Methodology We conducted a cross-sectional, observational DUS at 1900 outpatient clinics in India from October 2021 to March 2022. Prescription data and medical history of patients who were prescribed the FF/Vi combination werecollected. Results It was observed that FF/Vi was prescribed in an almost equal number of patients with COPD (44.2%) and asthma (42.9%). The majority of the patients (74%) were switched from previous ICS/LABA to this ICS/uLABA, while 26% of patients were treatment naïve.The average CAT score was 19.5±7.8 (43.2% GOLD Group C and 32.2% GOLD Group B) in COPD patients, while the average ACQ-5 score was 2.6±1.3 (33.1% GINA Step 3, 29.5% GINA Step 2) in asthmatic patients. Most of the patients (63.9%) had raised biomarkers (Blood eosinophil count >300 cells/μl). Prior history of exacerbation was present in 65% of patients with annual exacerbation rates of 1.2 in COPD, 1.1 in asthma, and 1.2 in asthma-COPD overlap syndrome (ACOS). Leukotriene inhibitors (42%) and LAMAs (30.8%) were common add-on medications. Conclusion We observed a trend towards a shift to once-daily ICS/uLABA (FF/Vi) by physicians, especially in symptomatic and exacerbating OAD patients with underlying comorbidities.

DNA Methylation and Gene Expression of the Cysteinyl Leukotriene Receptors as a Prognostic and Metastatic Factor for Colorectal Cancer Patients.

Colorectal cancer (CRC), one of the leading causes of cancer-related deaths in the western world, is the third most common cancer for both men and women. As a heterogeneous disease, colon cancer (CC) is caused by both genetic and epigenetic changes. The prognosis for CRC is affected by a variety of features, including late diagnosis, lymph node and distant metastasis. The cysteinyl leukotrienes (CysLT), as leukotriene D4 and C4 (LTD4 and LTC4), are synthesized from arachidonic acid via the 5-lipoxygenase pathway, and play an important role in several types of diseases such as inflammation and cancer. Their effects are mediated via the two main G-protein-coupled receptors, CysLT1R and CysLT2R. Multiple studies from our group observed a significant increase in CysLT1R expression in the poor prognosis group, whereas CysLT2R expression was higher in the good prognosis group of CRC patients. Here, we systematically explored and established the role of the CysLTRs, cysteinyl leukotriene receptor 1(CYSLTR1) and cysteinyl leukotriene receptor 2 (CYSLTR2) gene expression and methylation in the progression and metastasis of CRC using three unique in silico cohorts and one clinical CRC cohort. Primary tumor tissues showed significant CYSLTR1 upregulation compared with matched normal tissues, whereas it was the opposite for the CYSLTR2. Univariate Cox proportional-hazards (CoxPH) analysis yielded a high expression of CYSLTR1 and accurately predicted high-risk patients in terms of overall survival (OS; hazard ratio (HR) = 1.87, p = 0.03) and disease-free survival [DFS] Hazard ratio [HR] = 1.54, p = 0.05). Hypomethylation of the CYSLTR1 gene and hypermethylation of the CYSLTR2 gene were found in CRC patients. The M values of the CpG probes for CYSLTR1 are significantly lower in primary tumor and metastasis samples than in matched normal samples, but those for CYSLTR2 are significantly higher. The differentially upregulated genes between tumor and metastatic samples were uniformly expressed in the high-CYSLTR1 group. Two epithelial-mesenchymal transition (EMT) markers, E-cadherin (CDH1) and vimentin (VIM) were significantly downregulated and upregulated in the high-CYSLTR1 group, respectively, but the result was opposite to that of CYSLTR2 expression in CRC. CDH1 expression was high in patients with less methylated CYSLTR1 but low in those with more methylated CYSLTR2. The EMT-associated observations were also validated in CC SW620 cell-derived colonospheres, which showed decreased E-cadherin expression in the LTD4 stimulated cells, but not in the CysLT1R knockdown SW620 cells. The methylation profiles of the CpG probes for CysLTRs significantly predicted lymph node (area under the curve [AUC] = 0.76, p < 0.0001) and distant (AUC = 0.83, p < 0.0001) metastasis. Intriguingly, the CpG probes cg26848126 (HR = 1.51, p = 0.03) for CYSLTR1, and cg16299590 (HR = 2.14, p = 0.03) for CYSLTR2 significantly predicted poor prognosis in terms of OS, whereas the CpG probe cg16886259 for CYSLTR2 significantly predicts a poor prognosis group in terms of DFS (HR = 2.88, p = 0.03). The CYSLTR1 and CYSLTR2 gene expression and methylation results were successfully validated in a CC patient cohort. In this study, we have demonstrated that CysLTRs' methylation and gene expression profile are associated with the progression, prognosis, and metastasis of CRC, which might be used for the assessment of high-risk CRC patients after validating the result in a larger CRC cohort.

Associations of Microbial Diversity with Age and Other Clinical Variables among Pediatric Chronic Rhinosinusitis (CRS) Patients.

Chronic rhinosinusitis (CRS) is a heterogenous disease that causes persistent paranasal sinus inflammation in children. Microorganisms are thought to contribute to the etiology and progression of CRS. Culture-independent microbiome analysis offers deeper insights into sinonasal microbial diversity and microbe-disease associations than culture-based methods. To date, CRS-related microbiome studies have mostly focused on the adult population, and only one study has characterized the pediatric CRS microbiome. In this study, we analyzed the bacterial diversity of adenoid tissue, adenoid swab, maxillary sinus, and sinus wash samples from 45 pediatric CRS patients recruited from the Johns Hopkins All Children's Hospital (JHACH) in St. Petersburg, FL, USA. The alpha diversity in these samples was associated with baseline nasal steroid use, leukotriene receptor antagonist (LTRA) use, and total serum immunoglobulin (Ig) E (IgE) level. Streptococcus, Moraxella, and Haemophilus spp. were most frequently identified from sinus cultures and the sequenced 16S rRNA gene content. Comparative analyses combining our samples with the samples from the previous microbiome study revealed differentially abundant genera between patients with pediatric CRS and healthy controls, including Cutibacterium and Moraxella. Additionally, the abundances of Streptobacillus and Staphylococcus were consistently correlated with age in both adenoid- and sinus-derived samples. Our study uncovers new associations of alpha diversity with clinical parameters, as well as associations of specific genera with disease status and age, that can be further investigated.

Targeting interleukin-4 and interleukin-13 in the treatment of severe eosinophilic asthma

Asthma is a chronic inflammatory airway disease affecting about 300 million people and responsible for 500,000 deaths annually globally. Eosinophilic asthma is one of the most common phenotypes of asthma. It constitutes about 50% to 60% of all cases of asthma, and it is the most common phenotype in children presenting with severe acute asthma. The mechanism of eosinophilic asthma is chronic airway inflammation which leads to airway hyperresponsiveness, and remodeling due to the immunopathological effects of inflammatory cytokines. The duet cytokines interleukin-4 (IL-4) and IL-13 play the most central role in the pathophysiology of eosinophilic asthma. The two sister cytokines are slightly similar with a 25% homology, they share a common signaling IL-4Rα chain, and have identical biological effects. Their principal biological effect is the development of Th2 cells from naïve T helper type 0 (Th0) lymphocytes. Th2 cells produce several cytokines responsible for inducing airway eosinophilic inflammation. They induce the ε isotype switch and the switching of the B cell immunoglobulin (Ig) production from IgM to IgE. Furthermore, they stimulate eosinophil proliferation, and migration to the allergic airways and promote eosinophil survival by suppressing eosinophil apoptosis. Activated eosinophils secrete several cytotoxic cationic proteins which damage the airway epithelium, and amplify the inflammatory cascade and airway remodeling. Most patients with eosinophilic asthma can achieve control on a long-acting β2-agonist, inhaled corticosteroid, and a leukotriene receptor antagonist. However, about 3.6-10% do not achieve asthma control. These patients usually benefit from treatment with a biologic. Dupilumab is the only biologic targeting IL-4 and IL-13 approved for the treatment of moderate-to-severe eosinophilic asthma. Clinical trials have shown that treatment with dupilumab results in good asthma control, and significantly reduces moderate-to-severe exacerbation rates (p &lt; 0.001). Additionally, treatment with dupilumab has been shown to significantly improve lung function (p &lt; 0.001), and health-related quality of life, and allows patients to taper or discontinue corticosteroid treatment.

Comprehensive elucidation of developmental functions of arachidonic acid-derived lipid mediators in zebrafish.

Prostaglandins (PGs) and leukotrienes (LTs) are major physiologically active lipid, which are biosynthesized from arachidonic acid (AA). AA is released from membrane phospholipids by phospholipase A2 (PLA2), and thus PGs and LTs are derived from membrane phospholipids. Zebrafish is a vertebrate model organism that has been widely used in the studies on development and drug discovery for the reasons as follows: (i) embryo development occurs outside the maternal body, (ii) embryo is transparent, (iii) high conservation between human and zebrafish genes, etc. Nevertheless, the systematic identification and characterization of zebrafish PG and LT receptors have not been performed. Therefore, we identified twelve zebrafish PG receptors and characterized their pharmacological properties. Furthermore, to identify the physiological role of zebrafish PG receptors, we generated each receptor-deficient zebrafish, and analyzed developmental processes. Here, we report that PGE2 plays essential roles in the embryonic lymphatic development through the EP3 receptor, one of the PGE2 receptors. Using pharmacological and genetic approaches, we demonstrated that the COX1-derived PGE2-EP3 pathway is required for embryonic lymphatic development by upregulating the expression of critical factors for the lymphatic specification. We recently focused the zebrafish cysteinyl LT (cysLT) receptors, cloned four zebrafish cysLT receptors, and analyzed the expression profile of these receptors in developmental stages. As results, we revealed that the four zebrafish cysLT receptors show unique tissue distribution patterns. Each receptor may hence be involved in unique physiological functions. This work provides further insights into the diverse functions of arachidonate metabolites in zebrafish.

LC-MS/MS Analytical Method for Determination of Montelukast in Human Plasma and its Application to a Bioequivalence Study

Background: This study aimed to develop a sensitive, rapid method based on HPLC-MS/MS for the quantification of Montelukast in human plasma utilizing Montelukast-D6 as an internal standard. Montelukast is a leukotriene inhibitor and is used to prevent asthma attacks in adults and children. Method: Separation was achieved using Thermo Hypersil GOLD™ Cyano HPLC columns (50 × 4.6 mm; 5 μm) with a mobile phase consisting of 0.5 mM ammonium chloride: ACN (20:80%; v/v). Results: The method was found to be linear over a concentration range of 10.0 - 600.0 ng/mL with a correlation coefficient (r2) ≥ 0. 0.9989. The stabilities of Montelukast and internal standard were assessed in several conditions with recovery results &gt; 85%. The precision results were less than 4.0%, while the accuracy results were within 93.0 107.0%. The method proved to be selective with no matrix effect. Conclusion: This method was found to be highly reproducible and was utilized successfully for the analysis of plasma samples following the oral administration of Montelukast (10 mg) in 28 healthy male human volunteers.

Pediatric Urinary Mast Cell Mediator Levels

Increased urinary excretion of metabolites of the mast cell mediators prostaglandin D2, (2,3-dinor-11β prostaglandin F2α) (2,3-BPG), leukotriene (LT) C4 (LTE4) and histamine (N-methyl histamine (NMH)) support the diagnosis of various allergic disorders in the adult population. In the pediatric population, the reference range and clinical utility of mast cell mediators have not been well defined.

Mast Cell CysLT2 Receptor Signaling Desensitizes CysLT1 Receptor-induced MAP Kinase Activation through PKA Activation

The currently available type 1 cysteinyl leukotriene receptor (CysLT1R) antagonists have proven benefits for the treatment of asthma and allergic rhinitis. The type 2 cysteinyl leukotriene receptor (CysLT2R) mediates complex, cell type- or stimulus-specific functions that may either protect from or promote Type 2 immunity in allergic inflammation.

Galactolipids from Launaea capitata (Spreng.) Dandy with In Vitro Anti-Inflammatory and Neuroprotective Activities

Plant secondary metabolites have a long history of potential use in managing human diseases by inhibiting enzymes that are highly expressed due to various pathogenic conditions. Prostaglandins (PGs) and leukotrienes (LTs) are proinflammatory mediators synthesized from arachidonic acid (AA) by the action of cyclooxygenases (COXs) and lipoxygenases (LOXs), respectively. Particularly, COX-2/5-LOX enzymes play a significant role in inflammatory processes and the pain associated with them. Butyrylcholinesterase (BchE) was recently suggested as a more reliable potential target for sustaining normal cholinergic function. In an attempt to identify new potential COX-2/5-LOX and BchE inhibitors, a phytochemical investigation of Launaea capitata (Spreng.) Dandy (Asteraceae) was executed. This investigation led to the isolation of a new digalactosyldiacylglycerol isomer, namely 1,2-dilinolenoyl-3-O-(α-galactopyranosyl-(1,6)-O-α-D-galactopyranosyl)-sn-glycerol (1) in addition to 1-myristoyl-2-palmitoyl-3-O-(α-galactopyranosyl-(1,6)-O-β-D-galactopyranosyl)-sn-glycerol (2), which was isolated herein for the first time from nature. The structures of the two isolates were elucidated by using 1D-, 2D-NMR, and ESI-MS spectroscopy. Compounds 1 and 2 exhibited good in vitro inhibitory activities against 5-LOX (59.01 and 21.67 μg/mL) and BchE (13.37 and 24.32 μg/mL), respectively. However, they exhibited weak inhibition of COX-2 (110.44 and 179.63 μg/mL, respectively). These inhibitory activities were explained in silico using a computational docking study. The docking results were consistent with the in vitro enzyme inhibitory activity. The lowest binding affinity for 1 and 2 was observed against COX-2 (−7.360 and −5.723 kcal/mol), whereas they exhibited greater binding affinity to 5-LOX (−8.124 and −8.634 kcal/mol), respectively, compared to its natural substrate, AA (−5.830 kcal/mol). Additionally, 1 and 2 exhibited remarkable binding affinity to BchE (−8.313 kcal/mol and −7.502 kcal/mol, respectively), which was comparable to the co-crystallized ligand, thioflavin T (−8.107 kcal/mol). This was related to the multiple and crucial hydrogen bonding interactions of these compounds with the amino acid residues in the active sites of the investigated enzymes. This study demonstrated the role of plant galactolipids as potential leads in the development of new drugs that alleviate the neuroinflammatory conditions associated with various diseases, such as Alzheimer’s disease and Type 2 diabetes mellitus.

Commentary on 'Identification and characterization of select oxysterols as ligands for GPR17'.

Commentary on 'Identification and characterization of select oxysterols as ligands for GPR17'.

Expert consensus on the diagnosis and treatment of SARS-CoV-2-associated cough

Cough is a common symptom in the acute phase of novel coronavirus SARS-CoV-2 infection, and some patients may develop persistent cough (subacute cough or even chronic cough), which affects the quality of life. Currently, the Omicron variant of SARS-CoV-2 infection is still widespread in China. In order to guide physicians on the diagnosis and treatment of SARS-CoV-2-associated cough, the Asthma Group of the Chinese Thoracic Society and the National Centre for Respiratory Medicine organized relevant experts to develop the Expert Consensus on the Diagnosis and Treatment of SARS-CoV-2-associated Cough. This consensus includes five parts: epidemiology and pathogenesis, clinical manifestations, diagnosis and differential diagnosis, treatment and outlook.The incidence of acute cough is 44%-72.5%, and about one third is productive cough. Current data shows that the average duration of cough is proximately 2 weeks, but in some patients, cough could last longer, even up to several months. SARS-CoV-2 infection cough is associated with airway epithelial damage, immunogenic or neurogenic inflammation, airway mucus hypersecretion, and cough hypersensitivity (peripheral or central).The diagnosis of SARS-CoV-2-associated cough in acute phase relies on epidemiological history, clinical characteristics, physical examination, and SARS-CoV-2 antigen or nucleic acid tests. It is also important to distinguish it from cough following other respiratory infections. The patients in acute and subacute phases of cough are currently treated symptomatically, by using cough suppressants and expectorants according to the types of the cough. For patients with severe cough, central or peripheral cough suppressants can be used. Combined first-generation antihistamines/decongestants (A/D preparations) are recommended. Anti-viral treatment such as Paxlovid is used in severe patients or patients who are likely to develop severe conditions. Anti-bacterial treatment is not recommended except for patients with bacterial infectious traits. Inhaled corticosteroids or corticosteroids plus long acting beta agonists or leukotriene antagonists are only used for patients with wheezing, or those who have asthma or allergy history, or who have evidence of eosinophilic inflammation or who are refractory to antitussive treatment. Patients who have chronic respiratory diseases such as COPD or asthma should maintain the regular treatments. With regard to TCM treatment, effectiveness is indicated both in the acute phase or non-acute phase based on clinical practice, and collection of more evidence on this aspect is also under way.There is limited data on SARS-CoV-2-associated cough in regard of epidemiology, pathogenesis, features of cough, treatment, and prognosis. More studies are warranted to improve our understanding and management of SARS-CoV-2-associated cough in the future.

Montelukast Increased IL-25, IL-33, and TSLP via Epigenetic Regulation in Airway Epithelial Cells.

The epithelium-derived cytokines interleukin (IL)-25, IL-33, and thymic stromal lymphopoietin (TSLP) are important mediators that initiate innate type 2 immune responses in asthma. Leukotriene receptor antagonists (LTRAs) are commonly used to prevent asthma exacerbations. However, the effects of LTRAs on epithelium-derived cytokines expression in airway epithelial cells are unclear. This study aimed to investigate the effects of LTRAs on the expression of epithelium-derived cytokines in human airway epithelial cells and to explore possible underlying intracellular processes, including epigenetic regulation. A549 or HBE cells in air-liquid interface conditions were pretreated with different concentrations of LTRAs. The expression of epithelium-derived cytokines and intracellular signaling were investigated by real-time PCR, enzyme-linked immunosorbent assay, and Western blot. In addition, epigenetic regulation was investigated using chromatin immunoprecipitation analysis. The expression of IL-25, IL-33, and TSLP was increased under LTRAs treatment and suppressed by inhaled corticosteroid cotreatment. Montelukast-induced IL-25, IL-33, and TSLP expression were mediated by the mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) pathways and regulated by histone H3 acetylation and H3K36 and H3K79 trimethylation. LTRAs alone might increase inflammation and exacerbate asthma by inducing the production of IL-25, IL-33, and TSLP; therefore, LTRA monotherapy may not be an appropriate therapeutic option for asthma.

Clinical and functional characteristics of OSA in children with comorbid asthma treated by leukotriene receptor antagonist: A descriptive study.

Obstructive sleep apnea (OSA) is the most common form of respiratory disorders during sleep in children, especially those with severe asthma. However, optimal treatment of asthma might significantly improve OSA severity. It was a cohort study including children aged >5 years old and diagnosed with asthma according to GINA (Global Initiative for Asthma). The data related to age, gender, height, weight, body mass index (BMI), clinical symptoms and medical history of asthma, spirometry (FEV1: forced expiratory in 1 s), and exhaled nitric oxide (FENO) were recorded for analysis. Respiratory polygraphy (RPG) was done for each study subject to diagnose OSA and its severity. Among 139 asthmatic children, 99 patients with OSA (71.2%) were included in the present study (9.3 ± 0.2 years): 58.6% with uncontrolled asthma and 32.3% with partial controlled asthma. The mean ACT (asthma control testing) score was 19.0 ± 3.4. The most frequent night-time symptoms were restless sleep (76.8%), snoring (61.6%), sweating (52.5%), and trouble breathing during sleep (48.5%). The common daytime symptoms were irritable status (46.5%) and abnormal behavior (30.3%). The mean AHI (apnea-hypopnea index) was 3.5 ± 4.0 events/h. There was a significant correlation between BMI and snoring index (R = 0.189 and P = 0.027), bronchial and nasal FENO with AHI (R = 0.046 and P < 0.001; R = 0.037 and P < 0.001; respectively). There was no significant correlation between asthma level, FEV1 and AHI. The severity of asthma and respiratory function were improved significantly after 3 months and 6 months of asthma treatment in combination with leukotriene receptor antagonist (LRA) treatment. The symptoms related to OSA were significantly improved after treatment with LRA. The severity of OSA was decreased significantly after 3 months and 6 months of treatment. The treatment of asthmatic children with comorbid OSA by LRA in combination with standard therapy for asthma could improve the control of asthma and the symptoms and severity of OSA.

Impacts of Asthma in Patients With Bronchiectasis: Findings From the KMBARC Registry

Although the coexistence of asthma and bronchiectasis is common, the impacts of asthma on bronchiectastic patients (BE) have not been well evaluated because this issue using bronchiectasis cohorts has been investigated in only a few studies. In the present study, 598 patients who were prospectively enrolled in the Korean bronchiectasis registry were evaluated. The clinical characteristics between BE with asthma and those without asthma were compared. Asthma was found in 22.4% of BE. BE with asthma had a higher body mass index (BMI) (P = 0.020), more dyspnea (P < 0.001), larger sputum volume (P = 0.015), and lower forced expiratory volume in 1 second (FEV1) (P < 0.001) than those without asthma. BE with asthma had a higher rate of previous pneumonia (P = 0.017) or measles (P = 0.037) than those without asthma. Regarding treatment, BE with asthma used inhaled corticosteroids, long-acting muscarinic antagonists, and leukotriene receptor antagonists more frequently than those without asthma. Although intergroup differences were not observed in disease severity of bronchiectasis (P = 0.230 for Bronchiectasis Severity Index and P = 0.089 for FACED), the Bronchiectasis Health Questionnaire (BHQ) scores indicating the quality of life, were significantly lower in BE with asthma than in those without asthma (61.6 vs. 64.8, P < 0.001). In a multivariable model adjusting for age, sex, body mass index, forced expiratory volume in 1 second %predicted, sputum volume, modified Medical Research Council dyspnea scale ≥ 2, and the number of involved lobes, asthma was associated with lower BHQ scores (β-coefficient = -2.579, P = 0.014). BE with asthma have more respiratory symptoms, worse lung function, and poorer quality of life than those without asthma. A better understanding of the impacts of asthma in BE will guide appropriate management in this population.

Allergic rhinitis and its management: a review article

Allergic rhinitis (AR) is a common disease worldwide affecting nearly 10%-20% of the population, a severe form of AR could have a significant impact on the quality of life, sleep, and work performance which places a marked financial and logistical burden on healthcare systems. Regardless of these harmful outcomes, the disease has been generally overlooked, with physicians and researchers only recently starting to pay more attention to it. A complete medical history and physical examination are the cornerstone for diagnosing AR. Allergy testing is considered to be an important part to confirm the underlying cause of AR. Referral to an allergist should be considered when the diagnosis of AR is in doubt. The current treatment modalities for AR include the following: patient education, strategies to prevent irritants and allergens, medication, allergen immunotherapy, nasal irrigates, and other uncommon treatments like surgery and acupuncture. Currently, pharmacotherapy comprises short-term nasal decongestants, antihistamines, leukotriene receptor antagonists, nasal/oral corticosteroids, and mast cell stabilizers. Patients with the disease usually do not realize the impact of the disease on their quality of life and daily living activities. Therefore, health workers must pay more attention to the early development of the illness to be diagnosed correctly and treated efficiently. This study reviews AR and its management.

Efficacy and Safety of Autologous Serum Therapy in Chronic Spontaneous Urticaria in the Pediatric Population: A Prospective Pilot Study.

Chronic spontaneous urticaria (CSU) in children is mostly spontaneous in onset (57%). Treatment comprises long-term antihistaminic therapy without need for elaborate investigations. A subset of such patients don't respond to conventional treatment and novel therapies to help reduce pill burden is the need of the hour. To determine the efficacy and safety of autologous serum therapy (AST) in pediatric patients with chronic spontaneous urticaria. All pediatric patients, aged between 6-16 years, attended to our OPD from March 2019 to March 2020 were recruited. Clinico-demographic data and baseline investigations of all patients were performed. Two-weekly AST therapy was given for 8 visits with levocetrizine tablet 5mg on an on-demand basis. Urticaria activity score (UAS) sheet was provided to record and return every 2 weeks. Statistical analysis was done using the IBM SPSS 26 software package. Autologous serum skin test (ASST) was positive in 63% patients. Both the ASST positive and ASST negative group showed significant reduction in UAS7 score at week 14 compared to baseline. The reduction in mean UAS7 score was associated with a decreased pill burden and positive response in the patient and physician global assessment scale. No statistically significant difference between the two groups in terms of mean UAS7 reduction was found. This study has explored the efficacy and safety of autologous serum therapy in the pediatric CSU patients. Both ASST positive and ASST negative group respond to AST therapy.