Leukotriene Research Articles

Specialized Pro-Resolving Mediator (SPM) Profile in Blood from Children with Sickle Cell Disease (SCD): Comparison with Age-, and Race- Matched Controls

Introduction: Specialized Pro-resolving Mediators (SPMs) are lipid mediators, biosynthesized from the n-3 polyunsaturated fatty acids (PUFAs) docosahexaenoic acid (DHA), docosapentaenoic acid (DPA) and eicosapentaenoic acid (EPA); and the n-6 PUFA arachidonic acid (AA). SPMs are grouped into four families of lipid mediators including resolvins, protectins, maresins and lipoxins; and these mediators play a role in the resolution of inflammation. Inflammation plays a crucial role in the pathogenesis of clinical complications in sickle cell disease (SCD). In addition, multiple studies in SCD have documented decreased levels of anti-inflammatory fatty acids DHA and EPA in blood cells and plasma. We assessed whether the decreased DHA and EPA content play a role in modulation of peripheral blood SPM levels in SCD. Methods: Using targeted liquid chromatography (LC)-tandem mass spectrometry (MS/MS), we investigated plasma SPM profile in children with SCD in steady state (n=45, subjects with confirmed SCD genotypes SS and Sβ0 thalassemia, ages 2-20 years), and compared to that from an age- and race-matched control group (n=24). Analysis also included the SPM pathway markers, prostaglandins, thromboxane and leukotriene and their metabolites. (n-3) PUFA content in total blood cells was measured in both groups using capillary gas chromatography. Results: Consistent with the published results, a significant decrease in (n-3) PUFA content (measured as percent of total fatty acids) was noted in children with SCD (2.14% ± 0.47% in SCD vs 2.39% ± 0.45% in control, mean ± SD, P=0.04). In plasma from both SCD and controls, we identified and quantitated 6 SPMs which included DHA-derived resolvin (Rv) D1, RvD3 and 17R-RvD3; EPA-derived RvE2; and DPA(n-3)-derived RvD5(n-3) and protectin D (PD)-1 (n-3). Median RvD1 level (pg/ml) in SCD plasma was significantly elevated (65 in SCD vs 36 in controls, P=0.002). Levels of other SPMs were not significantly different between the two groups. Multiple SPM pathway markers including mono-hydroxy-PUFAs (EPA-derived 5-HEPE, 12-HEPE, 15-HEPE and 18-HEPE; DHA-derived 4-HDHA, 7-HDHA and 14-HDHA; and AA-derived 5-HETE, 12-HETE and 15-HETE) were present in both control and SCD plasma. Levels (median, pg/ml) of 5-lipoxygenase-derived EPA-metabolite 5-HEPE (212 vs 122, P=0.027) and DHA-derived metabolite 7-HDHA (62 vs 39, P=0.036), and 12-lipoxygenase-derived AA-metabolite 12-HETE (16783 vs 11796, P=0.025) were increased significantly in SCD compared to those from the controls. 15-Lipoxygenase derived pathway markers (15-HEPE and 15-HETE) were not different between the two groups. The cyclo-oxygenase-derived eicosanoids identified and quantitated in both groups included PGE2, PGD2 and TxB2 with a significant increase observed in TxB2 level in SCD plasma (1213 vs 970 pg/ml, P=0.038). Leukotriene (LT) B4 (an AA-derived pro-inflammatory mediator) and lipoxins (AA-derived SPMs), and their metabolites 20-OH-LTB4 and 20-COOH-LTB4 were absent in plasma from both SCD and control. Conclusions: Our results taken together demonstrate that the decreased bioavailability of (n-3) PUFA in children with SCD does not appear to limit SPM production in steady state as documented with normal/increased plasma levels of SPMs and their pathway markers. Whether the SPM profile in circulation is different in SCD pathologies associated with inflammation including vaso-occlusive pain crisis and acute chest syndrome, compared to steady state disease, require further investigation.

Urticaria: Etiology, pathogenesis, diagnosis, and treatment

Urticaria is the most common skin disease, it may be chronic or acute. Infections, medicines, psychogenic factors, food, and respiratory allergens such factors are accused of etiology. But sometimes it may be idiopathic. H1 antihistamines and short-term systemic corticosteroids are taken for the treatment. H2 antagonists may be preferred during resistant cases. Cyclosporine, omalizumab, and leukotriene receptor antagonists are other treatment options considered during missed events.

Abstract 12174: Inflammation-Dependent Hydroxyeicosatetraenoic Acids Dysregulate Macrophage Resolution Function

Introduction and Hypothesis: Macrophage efferocytosis is a critical step in the resolution of inflammation. Dysregulated macrophage efferocytosis has been implicated in the pathogenesis of chronic inflammatory disorders including atherosclerosis and IBD. Nonetheless, the nature of possible dysregulating mechanisms remains incompletely understood. We reported that non-enzymatic lipid peroxidation and the mucosal levels of monohydroxylated PUFAs including 12- and 15-hydroxyeicosatetraenoic acid (HETE) correlated with disease in murine models of IBD. HETEs can form enzymatically and non-enzymatically and can signal through the leukotriene (LT) receptor BLT2. LTB4-BLT1/2 signaling can suppress macrophage efferocytosis capacity. We hypothesized that non-enzymatically derived mucosal HETEs correlate with disease in a murine Crohn’s disease (CD) model and in IBD patient biopsies; and that HETEs suppress murine and human macrophage efferocytosis capacity. Methods: We exploited the stereospecificity of enzymatic HETE formation to determine by chiral-LC-MS/MS the levels of non-enzymatically derived HETEs in intestine from a murine myeloid Cox2 knock-out model of Crohn’s disease (CD) and in human IBD patient biopsies. We assessed the effect of racemic HETEs on the efferocytosis capacity of murine BMDMs and human THP1 macrophages for apoptotic MPRO neutrophils. We performed proteomics using accurate mass LC-MS/MS followed by GO enrichment analysis. Results: Non-enzymatically derived mucosal 5-, 12-, and 15HETE were elevated with disease: a) by 3-4 fold in the murine CD model (p<0.01 to p<0.0001); and b) by 2-3 fold in ileal and colonic biopsies from areas of active inflammation in CD and ulcerative colitis patients compared to remission controls (p<0.05). Racemic HETEs suppressed efferocytosis of apoptotic neutrophils by murine (12- and 15-HETE: p<0.0001) and human (12-HETE: p<0.0001) macrophages. Racemic 12-HETE altered the proteome of efferocytic BMDM by inducing 200 proteins while silencing 200 more (<1% FDR), and by suppressing pathways associated with efferocytosis. Conclusion: Inflammation-dependent HETEs may suppress macrophage efferocytosis in chronic inflammatory disorders including IBD and atherosclerosis.

The Role of Montelukast Sodium in Children with Adenoid Hypertrophy - A Comparative Study.

Background Adenoid Hypertrophy (AH) results in symptoms ranging from mild nasal obstruction to the dangerous obstructive sleep apnoea. Normally for such patients Adenoidectomy with or without Tonsillectomy is carried out. However complications like haemorrhage and recurrence of adenoid tissue are common. Thus, non-surgical therapies have attracted considerable attention as an alternative strategy. The present study is aimed at evaluating the effect of oral Montelukast, a cysteinyl- leukotriene receptor antagonist, in children with AH. Materials and Methods Sixty children aged between 6 and 12 years with adenoid hypertrophy were randomly divided into two groups of thirty each. The study group was prescribed Tablet Montelukast 5mg daily for 12 weeks while the control group received matching placebo. A questionnaire based upon the severity of the symptoms as well as the Adenoid Nasopharynx ratio (A/N), as measured via X-ray Adenoids and the Nasal endoscopic scores done before and after treatment (at 3 months) in the two groups were taken into consideration . Results The Mann Whitney Test which was used found no distinction in snoring, sleep discomfort and mouth breathing between the two groups before the start of treatment. But a significant difference was indeed observed between the two groups after treatment in case of snoring (P < 0.006), sleep discomfort(P < 0.001) and mouth breathing (P < 0.001). Conclusion Oral Montelukast therapy is seen to be effective not only in the reduction of the size of adenoids but also in improvement of the overall symptoms and can thus be considered as a viable alternative .

REFRACTORY CHRONIC SPONTANEOUS URTICARIA AFTER TREATED GRAVES' DISEASE

<h3>Introduction</h3> Chronic spontaneous urticaria (CSU) has been well described in autoimmune thyroid disorders, but less associated with Graves' Disease (GD), and the mechanism of their relationship is still unknown. Thyroid-associated CSU has been shown to be more difficult to manage. <h3>Case Description</h3> We present a 10-year-old female with difficult to control CSU with associated facial angioedema that started six months after diagnosis of Graves' disease that was being treated with methimazole. Her symptoms presented multiple times each week as bodily hives, angioedema of her cheeks, tongue, and throat with difficulty breathing, which caused her to be treated multiple times with epinephrine for concern of anaphylaxis. Therapy was rapidly escalated with H1 and H2 antihistamines, leukotriene receptor antagonist, chronic steroids and omalizumab without resolution. She was positive for thyroid stimulating immunoglobulins and p-ANCA antibodies; and negative for anti-TPO and anti-FcεRI antibodies. Due to the concern of vasculitic conversion, methimazole was stopped and she underwent radioiodine ablation for her GD to eventually become euthyroid. She was subsequently started on cyclosporine, but symptoms continue intermittently. <h3>Discussion</h3> Thyroid-associated CSU remains difficult to control from standard therapies, even when the patient becomes euthyroid. Several reports show that controlling the thyroid levels would resolve the CSU and a few only after thyroidectomy. Most studies note that anti-TPO antibodies have been associated with CSU, but only a few report an association with GD. Methimazole can cause p-ANCA positivity for concern of vasculitic conversion. Further studies are needed to evaluate the mechanism of GD with CSU to better manage these complicated patients.

Treatment of Allergic Rhinitis and Asthma in Primary Care: Dispensations Do Not Align with Prescriptions.

Appropriate use of effective treatments is required for satisfactory control of allergic symptoms. Coherent medical care -regular prescribing by the same Health Care Professionals- is a preliminary need. We investigated the numbers of distinct prescribers, the regularity of medical visits, and the agreement between prescriptions and associated dispensations in individual patients with perennial allergic rhinitis (PAR) and asthma. In primary care electronic health records (EHRs), a cohort of patients with PAR and asthma was identified. Individual EHRs were linked to corresponding claims recording all dispensations. Prescribing patterns were analyzed for the major treatment classes, and the dispensations linked to individual prescriptions were retrieved to compute the proportions of days covered (PDCs) for asthma and PAR therapy. A total of 3654 patients were included, with 62% being female (mean age, 46.1 years). At inclusion, asthma control was not optimal in 51% of the patients and 48% had received oral corticosteroids. The mean interval between successive prescriptions varied between 93 (leukotriene receptor antagonists, LTRAs) and 103 (inhaled corticosteroids, ICS) days, and 97 (antihistamines, AHs) and 103 days (nasal corticosteroids, NCS). On average, individual prescriptions lead to 1.2, 1.5, 1.7 and 1.8 dispensations of ICS, ICS/Long-Acting Beta-Agonist (LABA) fixed-dose combinations, LABAs, and LTRAs, respectively, and to 1.3 and 1.6 dispensations of NCS and AHs, respectively. PDCs then varied between 37.8% for ICS and 58.6% for LTRAs, and between 39.7% for NCS and 50.4% for AHs. Care was nonetheless coherent, with >90% of all dispensations related to prescriptions issued by single General Practitioners (GPs). Despite regular healthcare visits and medication prescriptions, allergic patients only partly and selectively refilled their treatments, preferring the less effective therapy, in a context of poor control of asthma symptoms.

HEREDITARY ALPHA TRYPTASEMIA MASKED AS ASTHMA EXACERBATION

<h3>Introduction</h3> Clinical phenotypes of hereditary alpha tryptasemia (HAT) are variable and can range from asymptomatic to anaphylaxis. Due to this broad range of presentations, diagnosis can be challenging, particularly if only one organ system is involved. <h3>Case Description</h3> An 8-year-old male presented to the emergency department with hypoxemia and stridor. His exam was notable for inspiratory and expiratory stridor with increased work of breathing. He received nebulized racemic epinephrine without improvement, and then had resolution of symptoms with intramuscular epinephrine and oral corticosteroids. Spirometry was suggestive but not diagnostic of asthma. Due to symptoms localized only to the respiratory tract, asthma was initially suspected. However, mast cell disorders were also considered since he required epinephrine before symptom improvement. Serum tryptase was elevated on initial and repeat testing. Genetic testing demonstrated increased copies of <i>TPSAB1</i>, consistent with HAT. <h3>Discussion</h3> Hereditary alpha tryptasemia is an autosomal dominant disorder resulting from increased copies of <i>TPSAB1</i> which encodes alpha tryptase. Disease severity varies from asymptomatic to anaphylaxis. Higher tryptase levels and increased symptom severity parallels increased number of <i>TPSAB1</i> copies. Serum tryptase level is the initial screening test. If elevated, genetic testing for <i>TPSAB1</i> should be performed. Though presentations with single organ involvement are not normally concerning for systemic disease, severe presentations of atopic diseases, including asthma, should prompt consideration of HAT. Treatment is symptom directed and may include antihistamines, mast cell stabilizers, leukotriene inhibitors, and epinephrine.

AN UNUSUAL CASE OF CHRONIC COUGH IN A PEDIATRIC PATIENT

<h3>Introduction</h3> Common causes of chronic cough in children are postinfectious, asthma, rhinosinusitis, and gastroesophageal reflux. Sensory neuropathic cough (SNC) is a rare cause of chronic cough in children. Its diagnosis is by exclusion; therefore, treatment is often delayed. We present a difficult pediatric case of sensory neuropathic cough. <h3>Case Description</h3> A 12-year-old female with well-controlled asthma developed a new-onset dry to wet cough after a viral infection that persisted for 6 weeks. Symptoms occurred both day and night. No wheezing was reported. She was hoarse but was able to speak in full sentences between coughing. There were no apparent triggers. Initial treatment with daily inhaled corticosteroid, long and short-acting beta-2-agonists, oral leukotriene receptor antagonist, and short courses of systemic steroids failed to relieve her symptoms. The addition of oral histamine-1-and-2-receptor antagonists, intranasal topical steroids and antihistamines, and antibiotics for potential sinus infection was also unsuccessful. Impulse oscillometer and computed tomography of the chest showed no abnormalities. Laryngoscopy was negative for vocal cord dysfunction, pooling of secretions, masses, polyps, or laryngeal swelling. She was seen by a neurologist 8 weeks after the cough began where she was diagnosed with sensory neuropathic cough and started on amitriptyline, resolving her cough. <h3>Discussion</h3> Our case illustrates the challenges of diagnosing sensory neuropathic cough as there are no standardized diagnostic criteria. Peripheral and central neurological sensitization are potential pathophysiologic explanations. Neuromodulating agents such as amitriptyline and gabapentin can potentially provide relief to some. Our patient had resolution of symptoms after use of amitriptyline.

Enhanced efficacy of formoterol-montelukast salt in relieving asthma features and in preserving β2-agonists rescue therapy

Adrenergic β2-agonists represent a mainstay in asthma management. Their chronic use has been associated with decreased bronchoprotection and rebound hyperresponsiveness. Here we investigate on the possible therapeutic advantage of a pharmacological association of β2-agonists with montelukast, a highly selective leukotriene receptor antagonist, in modulating bronchial reactivity and controlling asthma features. The study has been conducted in vitro and in vivo and also takes advantage of the synthesis of a salt that gave us the possibility to simultaneously administer in vivo formoterol and montelukast (MFS). In vitro studies demonstrate that montelukast (1) preserves β2-agonist response in isolated bronchi by preventing homologous β2-adrenoceptor desensitization; (2) reduces desensitization by modulating β2-receptor translocation in bronchial epithelial cells. In vivo studies demonstrate that sensitized mice receiving formoterol or montelukast display a significant reduction in airway hyperresponsiveness, but the β2-agonist relaxing response is still impaired. Allergen challenge causes β2 heterologous desensitization that is further increased by treatment in vivo with formoterol. Conversely MFS not only inhibits airway hyperresponsiveness but it rescues the β2-agonist response. Histological analysis confirms the functional data, demonstrating an enhanced therapeutic efficiency of MSF in controlling also pulmonary metaplasia and lung inflammation. MFS is efficacious also when sensitized mice received the drug by local administration. In conclusion, the data obtained evidenced a therapeutic advantage in the association of β2-agonists with montelukast in the control of asthma-like features and a better rescue bronchodilation response to β2-agonists.

Montelukast reduces grey matter abnormalities and functional deficits in a mouse model of inflammation-induced encephalopathy of prematurity

Encephalopathy of prematurity (EoP) affects approximately 30% of infants born < 32 weeks gestation and is highly associated with inflammation in the foetus. Here we evaluated the efficacy of montelukast, a cysteinyl leukotriene receptor antagonist widely used to treat asthma in children, to ameliorate peripheral and central inflammation, and subsequent grey matter neuropathology and behaviour deficits in a mouse model of EoP. Male CD-1 mice were treated with intraperitoneal (i.p.) saline or interleukin-1beta (IL-1β, 40 μg/kg, 5 μL/g body weight) from postnatal day (P)1–5 ± concomitant montelukast (1–30 mg/kg). Saline or montelukast treatment was continued for a further 5 days post-injury. Assessment of systemic and central inflammation and short-term neuropathology was performed from 4 h following treatment through to P10. Behavioural testing, MRI and neuropathological assessments were made on a second cohort of animals from P36 to 54. Montelukast was found to attenuate both peripheral and central inflammation, reducing the expression of pro-inflammatory molecules (IL-1β, IL-6, TNF) in the brain. Inflammation induced a reduction in parvalbumin-positive interneuron density in the cortex, which was normalised with high-dose montelukast. The lowest effective dose, 3 mg/kg, was able to improve anxiety and spatial learning deficits in this model of inflammatory injury, and alterations in cortical mean diffusivity were not present in animals that received this dose of montelukast. Repurposed montelukast administered early after preterm birth may, therefore, improve grey matter development and outcome in EoP.

Use of chronic medications and risk of death due to COVID-19 in hospitalised patients

ObjectivesTo evaluate the potential association between chronic exposure to medication and death related to COVID-19.MethodsThis is a retrospective cross-sectional study that included all patients hospitalised due to COVID-19 from 11...

Increased Risk of Tourette Syndrome with Leukotriene Modifier Use in Children with Allergic Diseases and Asthma: A Nationwide Population-Based Study.

(1) Background: Cysteinyl leukotriene receptor antagonists (LTRAs), including montelukast and zafirlukast, are FDA-approved for treating pediatric asthma and allergic diseases. Tourette syndrome (TS), a common neuropsychiatric disorder in children, is associated with allergic diseases and asthma. In this study, we investigated the risk of TS following an LTRA prescription for pediatric allergic diseases. (2) Methods: Children younger than 18 years of age who were newly diagnosed with asthma, allergic rhinitis, or atopic dermatitis between 1 January 2005 and 31 December 2018 and who were registered in the Taiwan National Health Insurance Research Database, which comprises the medical records of nearly 23 million Taiwanese population, were enrolled. LTRA users were matched with randomly selected LTRA non-users by sex, age, asthma-diagnosis year, and urbanization level. In total, 26,984 participants with allergic disease and TS were enrolled and included in the Cox proportional hazards model analysis. (3) Results: Children with allergic disease and asthma treated with LTRAs had a higher risk for TS than LTRA non-users (adjusted hazard ratio 1.376 [95% CI: 1.232-1.536], p &lt; 0.001). LTRA users had a significantly higher risk for TS than LTRA non-users with allergic disease. The cumulative incidence of TS was significantly higher in LTRA users than in non-users with allergic diseases and asthma (log-rank test, p &lt; 0.0001). (4) Conclusion: A prescription of LTRAs, mainly montelukast, increased the risk of TS among children with asthma, allergic rhinitis, or atopic dermatitis. The mechanism underlying the neuropsychiatric effect of LTRAs needs further investigation.

Obstructive sleep apnea syndrome in children as a multi-disciplinary problem (a review)

Aim. To analyze the data of modern scientific literature about the etiology, risk factors, pathogenesis, diagnosis and treatment of obstructive sleep apnea (OSA) in children. Results. The prevalence of OSA in children is about 1–5 %, with a peak incidence between the ages of 2 and 6 years. The main risk factors for OSA include adenotonsillar hypertrophy, obesity, and craniofacial anomalies. Nocturnal and daytime symptoms are clinically distinguished. Nocturnal ones include snoring, mouth breathing, pauses in breathing, restless sleep, enuresis and sweating; daytime symptoms are nasal obstruction, mouth breathing, morning headache, drowsiness, violation in attention concentration and hyperactivity. Nocturnal polysomnography is the gold standard for the diagnosis of OSA, in the absence of which the use of screening systems is possible, in particular – cardiorespiratory monitoring. The apnea/hypopnea index ≥1 per hour is considered a diagnostic criterion for mild OSA in children and differs from that in adults ≥5. Among the most effective treatments for OSA are adenoidectomy, CPAP therapy, intranasal corticosteroids, leukotriene receptor antagonists, and lifestyle modification in obesity is obvious. Conclusions. The problem of OSA syndrome is underestimated, and the vigilance of physicians as well as diagnostic opportunities of treatment and prevention facilities in Ukraine are quite low. Nocturnal polysomnography or screening diagnostic methods (cardiorespiratory monitoring) should be used in case of suspected OSA. Therapeutic measures for apnea are primarily aimed at eliminating etiological and risk factors. The presence of OSA in children with adenoids is an absolute indication for their removal.

A Mysterious Case of Abdominal Pain

A Mysterious Case of Abdominal Pain

Boswellia serrata Extract, 5-Loxin®, Prevents Joint Pain and Cartilage Degeneration in a Rat Model of Osteoarthritis through Inhibition of Inflammatory Responses and Restoration of Matrix Homeostasis.

Osteoarthritis (OA) is a chronic, progressive joint disease associated with pain, functional impairment, and diminished quality of life in affected individuals. At a societal level, it also has a high economic burden. Boswellia serrata has been reported to have potent anti-inflammatory, antiarthritic, and analgesic effects. The aim of this study was to explore the therapeutic potential and possible underlying mechanism of 5-Loxin®, a standardized Boswellia serrata extract, in a rat model of OA. The OA model was established by the intra-articular injection of 50 μL of monosodium iodoacetate (MIA) (60 mg/mL). 5-Loxin® was administered orally, and efficacy was evaluated through serum analysis, real-time polymerase chain reaction (PCR), histologic staining, and micro-computed tomography (micro-CT). Results indicated that administration of 5-Loxin® can relieve OA joint pain through inhibition of both inflammatory processes and cartilage degeneration. In the group of rats treated with 5-Loxin®, the suppression of inflammatory enzymes such as cyclooxygenase (COX)-2 and 5-lipoxygenase (LOX) resulted in a significant reduction in the prostaglandin (PG) E2 and leukotriene (LT) B4 levels. Moreover, 5-Loxin® ameliorated the deterioration of the main components of the articular extracellular matrix (ECM), such as glycosaminoglycans (GAGs) and aggrecan, through the downregulation of matrix metalloproteinases (MMPs). These findings suggest that 5-Loxin® may be a potential therapeutic agent for the treatment of OA.

Leukotriene D4 accelerates antigen-mediated mast cell responses via the cysteinyl leukotriene 1 receptor

Cysteinyl leukotrienes (CysLTs), released from mast cells (MCs), are important mediators in allergy. Type 1 receptors for CysLTs (CysLT1R) are involved in accelerating IgE-mediated MC activation. In this study, we aimed to elucidate the mechanisms underlying CysLT1R-mediated MC activation. The CysLT1R agonist/antagonist was applied to two types of major MC models—RBL-2H3 cells and bone marrow-derived MCs (BMMCs). The use of CysLT1R and CysLT2R inhibitors revealed that CysLT1R plays a major role in the acceleration of MC activation. The administration of the CysLT1R agonist leukotriene D4 upregulated IgE-mediated Akt and ERK phosphorylation and subsequently enhanced TNF-α expression, suggesting that CysLT1R regulates the downstream pathway of MC activation. However, these observations were not corroborated by CysLT1R knockdown using shRNA, suggesting a differential regulatory mechanism between the temporal and constitutive inhibitions of CysLT. In conclusion, CysLT1R enhances MC activation by accelerating IgE-induced signal transduction, which enables the co-regulation of rapid degranulation and delayed synthesis of inflammatory mediators in MCs.

Evaluating the effect of montelukast tablets on respiratory complications in patients following blunt chest wall trauma: A double-blind, randomized clinical trial

PurposePatients with multiple traumas are at high risk of developing respiratory complications, including pneumonia and acute respiratory distress syndrome. Many pulmonary complications are associated with systemic inflammation and pulmonary neutrophilic infiltration. Leukotriene-receptor antagonists are anti-inflammatory and anti-oxidant drugs subsiding airway inflammation. The present study investigates the effectiveness of montelukast in reducing pulmonary complications among trauma patients. MethodsThis randomized, double-blind, placebo-control trial was conducted in patients with multiple blunt traumas and evidence of lung contusion detected via CT scan. We excluded patients if they met at least one of the following conditions: < 16 years old, history of cardiopulmonary diseases or positive history of montelukast-induced hypersensitivity reactions. Patients were allocated to the treatment (10 mg of montelukast) or placebo group using permuted block randomization method. The primary measured outcome was the volume of pulmonary contusion at the end of the trial. The secondary outcomes were intensive care unit and hospital length of stay, ventilation days, multi-organ failure, and the in-hospital mortality rate. ResultsIn total, 65 eligible patients (treatment = 31, placebo = 34) were included for the final analysis. The treatment group had more pulmonary contusion volume (mean (SD), mm3) at the right (68726.97 (93656.54) vs. 59730.27 (76551.74)) and the left side (67501.71 (91514.04) vs. 46502.21 (80604.21)), higher initial C-reactive peptide level (12.16 (10.58) vs. 10.85 (17.87)) compared to the placebo group, but the differences were not statistically significant (p > 0.05). At the end of the study, the mean (SD) of pulmonary contusion volume (mm3) (right side = 116748.74 (361705.12), left side = 64522.03 (117266.17)) of the treatment group were comparable to that of the placebo group (right side = 40051.26 (64081.56), left side = 25929.12 (47417.13), p = 0.228 and 0.082, respectively). Moreover, both groups have statistically similar hospital (mean (SD), days) (10.87 (9.83) vs. 13.05 (10.12)) and intensive care unit length of stays (mean (SD), days) (7.16 (8.15) vs. 7.82 (7.48)). Of note, the frequency of the in-hospital complications (treatment vs. control group) including acute respiratory distress syndrome (12.9% vs. 8.8%, p = 0.71), pneumonia (19.4% vs. 17.6%, p = 0.85), multi-organ failure (12.9% vs. 17.6%, p = 0.58) and the mortality rate (22.6% vs. 14.7%, p = 0.41) were comparable between the groups. ConclusionAdministrating montelukast has no preventive or therapeutic effects on lung contusion or its complications.

Multicenter Prospective Observational Study to Evaluate the Therapeutic Effect and Safety of a Combination of Montelukast and Levocetirizine for Allergic Rhinitis when Administered to Patients with Allergic Rhinitis and Asthma

Introduction: Allergic rhinitis and asthma share a common inflammatory mechanism and are closely related, recognized as “one airway disease.” Thus, the guidelines recommend allergic rhinitis and asthma be treated together, and leukotriene antagonists and antihistamines have been administered simultaneously; however, there are few reports of the use of combination drugs so far. Methods: The aim of the study was to evaluate the treatment effects and adverse events of Monterizine® (a combination of montelukast and levocetirizine); a total of 2,254 patients with perennial allergic rhinitis and asthma were prospectively enrolled from 60 hospitals nationwide in Korea. They were followed up for 3 (Period 1) or 6 months (Period 2). Total nasal symptom score (TNSS), satisfaction, and safety data were collected and compared to baseline. Results: TNSS scores were analyzed for 2,254 subjects. At Period 1 (n = 2,024) and 2 (n = 1,861), the scores decreased significantly from baseline (−1.20 ± 2.49 and −1.63 ± 2.78, p < 0.001). The mean quality of life (QoL) was significantly improved at Period 1 and 2 relative to baseline (−3.75 ± 6.58, −4.83 ± 7.11, both p < 0.0001). There were no serious adverse drug reactions, but there were some minor reactions including nasopharyngitis (2.92%), rhinitis (0.37%), and somnolence (0.34%). Conclusions: TNSS score and QoL were significantly improved by 3–6 months’ treatment with Monterizine without significant adverse reactions. These results indicate that Monterizine, as a combination drug, is effective and safe for improving nasal symptoms and quality of life in patients with allergic rhinitis who also have asthma.

Asma bronquial

Asthma is a chronic inflammatory disease of the respiratory tract with multiple risk factors involved in its pathogenesis. It is clinically characterized by dyspnea, cough, and wheezing.Symptoms and respiratory function are the key tools for diagnosing it (spirometry with obstruction, reversibility, variability, fractional exhaled nitric oxide —FENO—, bronchial provocation). The goals of asthma treatment are disease control and maintaining symptoms and exacerbations stable. In order to implement a suitable treatment, asthma is classified according to its severity and based on that, the six-step treatment algorithm indicated in the Spanish GEMA guidelines is followed. The fundamental pillar of therapy is inhaled corticosteroids, which is present in each of the steps, and other drugs are associated for disease control (beta2-agonists, muscarinic receptor antagonists, leukotriene receptor antagonists). In recent years, the incorporation of monoclonal antibodies into the treatment arsenal for severe allergic and eosinophilic asthma is noteworthy.

S3495 What Do These Eosinophils Mean? Treatment Naive Systemic Lupus Erythematosus Presenting With Eosinophilic Ascites, Eosinophilic Pleural Fluid, and Enteritis of Unclear Etiology

Introduction: Eosinophilic ascites (EA), lupus enteritis (LE), and eosinophilic enteritis (EE) are rare systemic lupus erythematosus (SLE) complications. When they do occur, overlapping diagnostic criteria causes problems in distinguishing between a SLE-related etiology or EE. For example, intestinal eosinophil infiltration associated with EE is also consistently found in disseminated SLE autopsy case reports. Although both conditions are treated with steroids, therapies after treatment failure are different. We present a rare case of a SLE patient with this diagnostic dilemma with suboptimal response to SLE therapies, questioning whether an EE treatment algorithm may be more appropriate. Case Description/Methods: An afebrile 55 year old female with untreated SLE presented with constipation and a mildly tender distended abdomen. Imaging described moderate ascites, continuous small bowel thickening, ileus, and bilateral pulmonary infiltrates with pleural effusions. Significant results included a white blood cell count of 3.8 without eosinophils, erythrocyte sedimentation rate 5, C-reactive protein < 1, positive ANA (1:160), positive double stranded DNA, and low C3/C4 complement. Paracentesis yielded an exudative eosinophilic (71%) ascitic fluid with a low serum-ascites albumin gradient of 0.9 g/dL, high protein of 3.9 g/dL, and no evidence of malignancy or infection. She also had exudative eosinophilic pleural fluid. Endoscopy revealed mild cecal ischemia, mild gastritis, and a normal terminal ileum without eosinophils. Rheumatology diagnosed her with SLE serositis with peritoneal and pleural involvement complicated by LE, but they were unable to rule out EE. She responded to intravenous steroids but deteriorated when she was switched to oral prednisone. She then failed a regimen of hydroxychloroquine and oral prednisone. During her most recent hospitalization, the patient was transitioned to a regimen of hydroxychloroquine, mycophenolate mofetil, and oral prednisone. Discussion: It is unclear whether our patient’s sub-optimal therapy response is due to SLE or EE, with our case illustrating the difficulties in determining a diagnosis. Determining a diagnosis influences treatment and the patient's clinical course. In EE, treatment includes dietary therapy, antihistamines, leukotriene antagonists, and mast-cell stabilizers. However, our patient’s symptoms are attributed to serositis, leading to a focus on escalating her SLE immunosuppressive therapy rather than re-examine the diagnosis.