A review of the therapeutic potential of the cysteinyl leukotriene antagonist Montelukast in the treatment of bronchiolitis obliterans syndrome following lung and hematopoietic-stem cell transplantation and its possible mechanisms.

Lung and hematopoietic stem cell transplantation are therapeutic modalities in chronic pulmonary and hematological diseases, respectively. One of the complications in these patients is the development of bronchiolitis obliterans syndrome (BOS). The efficacy and safety of available treatment strategies in BOS remain a challenge. A few mechanisms have been recognized for BOS in lung transplant and graft-versus-host disease (GVHD) patients involving the TH-1 and TH-2 cells, NF-kappa B, TGF-b, several cytokines and chemokines, and cysteinyl leukotrienes (CysLT). Montelukast is a highly selective CysLT receptor antagonist that has been demonstrated to exert anti-inflammatory and anti-fibrotic effects in abundant experiments. One area of interest for the use of montelukast is lung transplants or GVHD-associated BOS. Herein, we briefly review data regarding the mechanisms involved in BOS development and montelukast administration as a treatment modality for BOS, and finally, the possible relationship between CysLTs antagonism and BOS improvement will be discussed.

A review of the therapeutic potential and possible mechanism of Montelukast in the treatment of bronchiolitis obliterans syndrome following lung and hematopoietic stem cell transplantationLung and bone marrow transplantation are therapeutic modalities in chronic diseases of the lungs and the blood, respectively. One of the complications in these patients is the development of Bronchiolitis obliterans syndrome (BOS). The efficacy and safety of available treatment strategies in BOS remain a challenge. A few mechanisms for BOS in lung transplant and graft-versus-host disease (GVHD) patients involving many immune components have been recognized. Cysteinyl leukotrienes are products of plasma membrane phospholipids that increase smooth muscle contraction, microvascular permeability, and airway mucus secretion. Montelukast is a highly selective cysteinyl leukotriene receptor blocker demonstrated to exert anti-inflammatory and anti-fibrotic effects. One area of interest for the use of montelukast is in lung transplant- or GVHD-associated BOS. In this article, we briefly review data regarding the mechanisms involved in BOS development and montelukast administration as a treatment modality for BOS. Finally, the possible relationship between cysteinyl leukotriene inhibition and BOS improvement will be discussed.

The role of oxylipins in NSAID-exacerbated respiratory disease (N-ERD).

Nonsteroidal anti-inflammatory drug (NSAID)-exacerbated respiratory disease (N-ERD) is characterized by nasal polyp formation, adult-onset asthma, and hypersensitivity to all cyclooxygenase-1 (COX-1) inhibitors. Oxygenated lipids are collectively known as oxylipins and are polyunsaturated fatty acids (PUFA) oxidation products. The most extensively researched oxylipins being the eicosanoids formed from arachidonic acid (AA). There are four major classes of eicosanoids including leukotrienes, prostaglandins, thromboxanes, and lipoxins. In N-ERD, the underlying inflammatory process of the upper and lower respiratory systems begins and occurs independently of NSAID consumption and is due to the overproduction of cysteinyl leukotrienes. Leukotriene mediators all induce edema, bronchoconstriction, and airway mucous secretion. Thromboxane A2 is a potent bronchoconstrictor and induces endothelial adhesion molecule expression. Elevated Prostaglandin D2 metabolites lead to vasoconstriction, additionally impaired up-regulation of prostaglandin E2 leads to symptoms seen in N-ERD as it is essential for maintaining homeostasis of inflammatory responses in the airway and has bronchoprotective and anti-inflammatory effects. A characteristic feature of N-ERD is diminished lipoxin levels, this decreased capacity to form endogenous mediators with anti-inflammatory properties could facilitate local inflammatory response and expose bronchial smooth muscle to relatively unopposed actions of broncho-constricting substances. Treatment options, such as leukotriene modifying agents, aspirin desensitization, biologic agents and ESS, appear to influence eicosanoid pathways, however more studies need to be done to further understand the role of oxylipins. Besides AA-derived eicosanoids, other oxylipins may also pay a role but have not been sufficiently studied. Identifying pathogenic N-ERD mechanism is likely to define more effective treatment targets.

Montelukast, an Antagonist of Cysteinyl Leukotriene Signaling, Impairs Burn Wound Healing.

BACKGROUND: Burns are severe injuries often associated with impaired wound healing. Impaired healing is caused by multiple factors, including dysregulated inflammatory responses at the wound site. Interestingly, montelukast, an antagonist for cysteinyl leukotrienes and U.S. Food and Drug Administration approved for treatment of asthma and allergy, was previously shown to enhance healing in excision wounds and to modulate local inflammation. METHODS: In this study, the authors examined the effect of montelukast on wound healing in a mouse model of scald burn injury. Burn wound tissues isolated from montelukast- and vehicle-treated mice at various times after burn injury were analyzed for wound areas ( n = 34 to 36), reepithelialization ( n = 14), inflammation ( n = 8 to 9), and immune cell infiltration ( n = 3 to 6) and proliferation ( n = 7 to 8). RESULTS: In contrast to previously described beneficial effects in excision wounds, this study shows that montelukast delays burn wound healing by impairing the proliferation of keratinocytes and endothelial cells. This occurs largely independently of inflammatory responses at the wound site, suggesting that montelukast impairs specifically the proliferative phase of wound healing in burns. Wound healing rates in mice in which leukotrienes are not produced were not affected by montelukast. CONCLUSION: Montelukast delays wound healing mainly by reducing the proliferation of local cells after burn injury. CLINICAL RELEVANCE STATEMENT: Although additional and clinical studies are necessary, our study suggests that burn patients who are on montelukast may exhibit delayed healing, necessitating extra observation.

The comparative effect of Leukotriene receptor antagonist add on therapy and step up inhaled Corticosteroid in partially controlled asthma: An open-labeled randomized controlled trial.

BACKGROUND: No studies are comparing the impact of the add-on leukotriene-receptor antagonist (LTRA) with a step-up dose of inhaled corticosteroids (ICS) in partly controlled asthma patients with asthma control test (ACT) score ˂ 23. OBJECTIVE: To study the effect of LTRA add-on therapy in comparison to a step-up to medium dose of ICS in partially controlled asthma. METHODS: An open-labeled randomized controlled trial was conducted in asthma subjects with partly controlled asthma who had been in regular receipt of low dose ICS. All subjects were assessed for asthma using ACT, daytime and nighttime symptoms, rate of relievers used, spirometry, and impulse oscillometry (IOS) at 3 and 6 months. Subjects were randomized to receive daily oral LTRA 10 mg or step-up medium dose of ICS. RESULTS: Between June 2020 and January 2021, 50 participants were enrolled, all patients completing the study. After treatment, mean ACT scores were increased to more than 23 indicating well-controlled asthma in both groups, control being sustained throughout the whole 6-month study period (P ˂ 0.001). Within each group, ACT scores were improved by a minimal clinical important difference (MCID) ≥ 3 points at 6 months, compared to baseline values. There were significant decreases in nighttime and daytime symptoms, and the numbers of rescue relievers used in 4 weeks in both groups compared to baseline (P ˂ 0.001). CONCLUSIONS: LTRA add-on therapy in partially controlled asthma patients is comparable with step-up to medium dose of ICS/LABA as regards asthma control.

Targeted Delivery of Montelukast for the Treatment of Alzheimer's Disease.

Alzheimer's Disease (AD) is one of the most common neurodegenerative diseases, which affects millions of people worldwide. Accumulation of amyloid-ß plaques and hyperphosphorylated neurofibrillary tangles are the key mechanisms involved in the etiopathogenesis of AD, characterized by memory loss and behavioural changes. Effective therapies targeting AD pathogenesis are limited, making it the largest unmet clinical need. Unfortunately, the available drugs provide symptomatic relief and primary care, with no substantial impact on the disease pathology. However, in recent years researchers are working hard on several potential therapeutic targets to combat disease pathogenesis, and few drugs have also reached clinical trials. In addition, drugs are being repurposed both in the preclinical and clinical studies for the treatment of AD. For instance, montelukast is the most commonly used leukotriene receptor antagonist for treating asthma and seasonal allergy. Its leukotriene antagonistic action can also be beneficial for the reduction of detrimental effects of leukotriene against neuro-inflammation, a hallmark feature of AD. The available marketed formulations of montelukast present challenges such as poor bioavailability and reduced uptake, reflecting the lack of effectiveness of its desired action in the CNS. While on the other side, targeted drug delivery is a satisfactory approach to surpass the challenges associated with the therapeutic agents. This review will discuss the enhancement of montelukast treatment efficacy and its access to CNS by using new approaches like nano-formulation, nasal gel, solid lipid formulation, nano-structure lipid carrier (NSLC), highlighting lessons learned to target AD pathologies and hurdles that persist.

The comparative effect of Leukotriene receptor antagonist add on therapy and step up inhaled Corticosteroid in partially controlled asthma: an open-labeled randomized controlled trial

Background No studies are comparing the impact of the add-on leukotriene-receptor antagonist (LTRA) with a step-up dose of inhaled corticosteroids (ICS) in partly controlled asthma patients with asthma control test (ACT) score ˂ 23.Objective To study the effect of LTRA add-on therapy in comparison to a step-up to medium dose of ICS in partially controlled asthma.Methods An open-labeled randomized controlled trial was conducted in asthma subjects with partly controlled asthma who had been in regular receipt of low dose ICS. All subjects were assessed for asthma using ACT, daytime and nighttime symptoms, rate of relievers used, spirometry, and impulse oscillometry (IOS) at 3 and 6 months. Subjects were randomized to receive daily oral LTRA 10 mg or step-up medium dose of ICS.Results Between June 2020 and January 2021, 50 participants were enrolled, all patients completing the study. After treatment, mean ACT scores were increased to more than 23 indicating well-controlled asthma in both groups, control being sustained throughout the whole 6-month study period (P ˂ 0.001). Within each group, ACT scores were improved by a minimal clinical important difference (MCID) ≥ 3 points at 6 months, compared to baseline values. There were significant decreases in nighttime and daytime symptoms, and the numbers of rescue relievers used in 4 weeks in both groups compared to baseline (P ˂ 0.001).Conclusions LTRA add-on therapy in partially controlled asthma patients is comparable with step-up to medium dose of ICS/LABA as regards asthma control (AU)

Peroxiredoxin III Protects Tumor Suppressor PTEN from Oxidation by 15-Hydroperoxy-eicosatetraenoic Acid.

Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is a lipid and protein phosphatase that coordinates various cellular processes. Its activity is regulated by the reversible oxidation of an active-site cysteine residue by H2O2 and thioredoxin. However, the potential role of lipid peroxides in the redox regulation of PTEN remains obscure. To evaluate this, 15-hydroperoxy-eicosatetraenoic acid (15s-HpETE), a lipid peroxide, was employed to investigate its effect on PTEN using molecular and cellular-based assays. Exposure to 15s-HpETE resulted in the oxidation of recombinant PTEN. Reversible oxidation of PTEN was also observed in mouse embryonic fibroblast (MEF) cells treated with a 15s-HpETE and Lipofectamine mixture. The oxidative dimerization of thioredoxin was found simultaneously. In addition, the absence of peroxiredoxin III aggravated 15s-HpETE-induced PTEN oxidation in MEF cells. Our study provides novel insight into the mechanism linking lipid peroxidation to the etiology of tumorigenesis.

Asthma pharmacotherapy: an update on leukotriene treatments.

Introduction: Asthma is a chronic inflammatory disease of the airways with a large heterogeneity of clinical phenotypes. There has been increasing interest regarding the role of cysteinyl leukotriene (LT) and leukotriene receptor antagonists (LTRA) in asthma treatment.Areas covered: This review summarized the data (published in PubMed during 1984-2019) regarding LTRA treatment in asthma and LTs-related airway inflammation mechanisms. Involvement of LTs C4/D4/E4 has been demonstrated in the several aspects of airway inflammation and remodeling. Novel pathways related to LTE4, the most potent mediator, and its respective receptors have recently been studied. Antagonists against cysteinyl leukotriene receptor (CysLTR) type 1, including montelukast, pranlukast and zafirlukast, have been widely prescribed in clinical practices; however, some clinical trials have shown insignificant responses to LTRAs in adult asthmatics, while some phenotypes of adult asthma showed more favorable responses to LTRAs including aspirin-exacerbated respiratory disease, elderly asthma, asthma associated with smoking, obesity and allergic rhinitis.Expert opinion: Further investigations are needed to understand the role of LTs in airway inflammation and remodeling of the asthmatic airways. There is a lack of biomarkers to predict responsiveness to LTRA, especially in adult asthmatics. Besides CysLTR1 antagonists, targets aiming other LT pathways should be considered.

Montelukast en pacientes con rinitis alérgica crónica sin asma / Montelukast in patients with chronic allergic rhinitis without asthma

CONTEXTO CLÍNICO: La rinitis alérgica (RA) consiste en la inflamación de la membrana mucosa de la nariz y, en algunos casos, de las mucosas de los ojos, trompas de Eustaquio, oído medio, senos paranasales y faringe. Se caracteriza por presentar una serie de síntomas como estornudos, congestión nasal, picazón nasal y rinorrea. Se desencadena ante la exposición de un alérgeno (proteína extrínseca), la cual genera una respuesta inmune mediada por inmunoglobulina E (IgE) con liberación de mediadores inflamatorios (histamina, triptasa, quininas, heparina, leucotrienos y prostaglandina D2). La RA puede clasificarse de tres maneras, sobre la base del patrón temporal de la exposición alergénica: estacional (por ejemplo, alergia a pólenes), perenne (alergia a los ácaros del polvo doméstico) o episódica (exposición a alérgenos a los cuales el enfermo no está expuesto de manera regular); de acuerdo con la frecuencia de los síntomas: intermitente (menos de cuatro días por semana o menos de cuatro semanas por año) o persistente (más de cuatro días por semana y más de cuatro semanas por año); o de acuerdo a la gravedad de los síntomas: leve (cuando las manifestaciones clínicas no comprometen la calidad de vida) o moderada/grave (cuando los síntomas interfieren con la calidad de vida). La Administración de Alimentos y Medicamentos (FDA, su sigla del inglés Food and Drug Administration) suele definir la RA como estacional o perenne para la aprobación de nuevos fármacos. TECNOLOGÍA: Los leucotrienos cisteinílicos (LTC4, LTD4, LTE4) son potentes eicosanoides inflamatorios liberados por diversas células, incluidos los mastocitos y eosinófilos. Estos mediadores plasmáticos se unen a los receptores de los leucotrienos cisteinílicos (CysLT) que se encuentran en las vías respiratorias y producen varios efectos sobre ellas, incluidos broncoespasmo, secreción mucosa, permeabilidad vascular y acumulación de eosinófilos. Montelukast es un antagonista de los receptores de leucotrienos que bloquea el efecto de los leucotrienos en las vías aéreas. OBJETIVO: El objetivo del presente informe es evaluar la evidencia disponible acerca de la eficacia, seguridad y aspectos relacionados a las políticas de cobertura del uso de montelukast para rinitis crónica alérgica en pacientes sin asma. MÉTODOS: Se realizó una búsqueda en las principales bases de datos bibliográficas, en buscadores genéricos de internet, y financiadores de salud. Se priorizó la inclusión de revisiones sistemáticas (RS), ensayos clínicos controlados aleatorizados (ECAs), evaluaciones de tecnologías sanitarias (ETS), evaluaciones económicas, guías de práctica clínica (GPC) y políticas de cobertura de diferentes sistemas de salud. RESULTADOS: Se incluyeron cuatro RS, cinco GPC, una evaluación económica y 10 informes de políticas de cobertura de montelukast en pacientes con rinitis alérgica sin asma. CONCLUSIONES: Evidencia de moderada calidad muestra que la eficacia de montelukast monoterapia en rinitis alérgica crónica sin asma es inferior a aquella de los corticosteroides tópicos y similar o inferior a la de los antihistamínicos en monoterapia. Montelukast en combinación con antihistamínicos, comparado a los antihistamínicos administrados en monoterapia, demostró una leve mejoría clínica en reducir la intensidad de los síntomas nasales diarios, y no hubo diferencias significativas en el control de síntomas nasales nocturnos, oculares y en la calidad de vida entre ambos grupos terapéuticos. La combinación de montelukast con antihistamínicos en pacientes con rinitis alérgica crónica sin asma demostró ser inferior a corticoesteroides tópicos nasales respecto al control de síntomas nasales y calidad de vida. Existe consenso entre las diferentes guías de práctica clínica identificadas en que los inhibidores de leucotrienos no deben utilizarse como tratamiento de primera línea para la rinitis alérgica crónica. Su uso se reserva como terapia complementaria en pacientes con rinitis alérgica que no responden al tratamiento inicial con corticoides y antihistamínicos. Si bien no se encontraron estudios de costo-efectividad realizados en Argentina, el elevado costo de la tecnología en comparación a sus comparadores, junto al escaso beneficio clínico sugeriría que no es una intervención costo-efectiva.

[Study on the situation of drug use in patients with chronic obstructive pulmonary diseases in the Chinese communities of large cities].

Objectives: To understand the medication being used among patients with chronic obstructive pulmonary diseases (COPD) in Chinese communities of large cities. Methods: A cross-sectional survey was carried out in Beijing, Shanghai, Chengdu and Guangzhou with the total number as 678 COPD cases who were continuously recruited. Subjects were face-to-face interviewed using a structured questionnaire and with medical records checked at the same time. All data were double entered into a database under EpiData 3.1, and analyzed by SAS 9.2. Results: One quarter of all the subjects did not receive any clinical treatment. The top three drugs for COPD were expectorant (50.74%), phosphodiesterase inhibitors (49.56%), and leukotriene (49.12%). Totally, there were 36 different types combination of drugs used for COPD and the proportions of drugs being used as one, two, and three or more at the same time were 29.5%(200 cases), 39.7%(269 cases) and 30.8%(209 cases) respectively. In addition 36.6% (248 cases) of them used oxygen. There were statistical correlations between drug-use patterns and the severity of COPD. Conclusion: The patterns of medication varied over COPD cases in communities from Chinese large cities and appeared differently under the recommendations in the clinical guidelines set for COPD. Guidance and surveillance programs on drugs use for COPD should be improved on patients with COPD in the Chinese communities.

[Research advances in gene polymorphisms in biological pathways of drugs for asthma].

The studies on gene polymorphisms in biological pathways of the drugs for the treatment of asthma refer to the studies in which pharmacogenetic methods, such as genome-wide association studies, candidate gene studies, genome sequencing, admixture mapping analysis, and linkage disequilibrium, are used to identify, determine, and repeatedly validate the effect of one or more single nucleotide polymorphisms on the efficacy of drugs. This can provide therapeutic strategies with optimal benefits, least side effects, and lowest costs to patients with asthma, and thus realize individualized medicine. The common drugs for asthma are ß2 receptor agonists, glucocorticoids, and leukotriene modifiers. This article reviews the research achievements in polymorphisms in biological pathways of the common drugs for asthma, hoping to provide guidance for pharmacogenetic studies on asthma in future and realize individualized medicine for patients with asthma soon.

Termoplastía bronquial para el manejo del asma severo: experiencia inicial en Chile / Bronchial thermoplasty for severe asthma: Initial experience in Chile

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The treatment of allergic respiratory disease during pregnancy

Pregnancy may be complicated by new-onset or preexisting asthma and allergic rhinitis. This article reviews the recognition and management f asthma and allergic rhinitis during pregnancy, paying close attention to the general principles of allergy and use of asthma medication during pregnancy. Both allergic rhinitis and asthma can adversely affect both maternal quality of life and, in the case of maternal asthma, perinatal outcomes. Optimal management is thus important for both mother and baby. This article reviews the safety of asthma and allergy medications commonly used during pregnancy (AU)

El embarazo puede complicarse por una nueva presentación de un asma y rinitis alérgica preexistentes. En este artículo se revisa el reconocimiento y manejo del asma y la rinitis alérgica durante el embarazo, con atención especial a los principios generales del tratamiento de la alergia y el asma durante esta situación. Ambas patologías pueden afectar de forma adversa a la calidad de vida de la madre y al periodo perinatal. El manejo óptimo de esta situación es muy importante tanto para la madre como para el hijo. Este artículo revisa la seguridad del tratamiento habitualmente utilizado durante el embarazo del asma bronquial (AU)

Role of interactions in pharmacogenetic studies: leukotrienes in asthma.

Researchers have identified thousands of loci involved in complex traits and drug response. However, in most cases they only explain a small proportion of the heritability of the trait. Among different strategies conducted to identify this 'missing heritability', here we illustrate the importance of complex gene-environment interactions using findings regarding the role of leukotrienes on the bronchodilator response to albuterol in Latino asthmatics. Patients managing their asthma with leukotriene-modifying medication presented higher increases in the bronchodilator response to albuterol. Moreover, interactions between genes responsible for leukotriene production were associated with a decreased risk of asthma. Combining genetic and pharmacologic effects, leukotriene-modifying users carrying certain combinations of alleles presented higher improvements in lung function after bronchodilator administration. Genes and drugs act at different orders of interaction (from individual effects to gene-gene-drug-drug interactions) and population-specific effects have to be considered. These results may be extrapolated to other complex phenotypes.

Utilización de montelukast en población pediátrica: estudio en tres farmacias comunitarias / Using montelukast in pediatric population: a study in three community pharmacies

Objetivo: El objetivo de este trabajo es analizar, desde tres farmacias comunitarias, el uso que se está haciendo de montelukast en la población pediátrica. Método: Estudio observacional de prescripción de montelukast realizado en tres oficinas de farmacia en niños (≤15 años) a los que se dispensó el fármaco; la recopilación de datos de los pacientes (edad, patologías, régimen de dosificación, duración del tratamiento, medicación asociada) se hizo a través de encuesta. Se remitió al médico cuando se detectó un tratamiento inadecuado, para su revisión. Resultados: Se recogieron un total de 75 prescripciones médicas. Sólo el 36% de los niños eran asmáticos; de ellos, al 70% se les pautó montelukast como terapia inicial, y el 45% no seguían las recomendaciones de la Guía Española para el Manejo del Asma. El 64% de los niños no eran asmáticos y estaban recibiendo montelukast fuera de indicación (off-label) (44% rinitis alérgica, 56% bronquiolitis), el 21% de ellos en monoterapia y el resto en combinación con otros fármacos. Conclusiones: Se está haciendo un uso fuera de indicación de montelukast en niños no asmáticos con rinitis alérgica o bronquiolitis, y en este último caso no existe evidencia de efectividad. El uso inadecuado podría acarrear problemas de seguridad para los pacientes. Se evidencia la necesidad de proporcionar información independiente a los profesionales sanitarios sobre el papel de montelukast en la terapéutica (AU)

Objective: The objective of this paper is to analyze, from 3 community pharmacies, the use that is being made of montelukast in pediatric population. Method: Observational study of montelukast prescriptions in children (≤15 years). A survey was done in 3 community pharmacies when dispensing this drug to collects patients' data (age, dosing regimen, pathologies, duration of treatment, associated medication). Referral to doctor was done, when inappropriate treatment was detected, for review of drug treatment. Results: There were a total of 75 medical prescriptions. Children diagnosis of asthma was in only 36% and of those, 70% were receiving montelukast as initial therapy; 45% of them were not following the recommendations of the Spanish Guidelines for Asthma Management. 64% of children were not asthmatic and are receiving «off-label» montelukast (44% allergic rhinitis, 56% bronchiolitis): 21% of them were in a monotherapy regimen, and the rest, in combination with other drugs. Conclusions: A use of «off-label» montelukast is being made in children with allergic rhinitis or bronchiolitis, without asthma diagnosis, with no evidence of effectiveness in bronchiolitis. Inappropriate use could result in security issues for the patients. This study shows the need to provide independent information on the role of montelukast in therapeutic practice to health professionals (AU)

Telangiectasia macularis eruptive perstans (TMEP) in childhood: A case report and literature review

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Anti-inflammatory properties of montelukast, a leukotriene receptor antagonist in patients with asthma and nasal polyposis.

BACKGROUND: Leukotrienes, especially LTC4, are important inflammatory mediators in allergic and nonallergic inflammation of the entire airways. Of particular interest are numerous theories regarding the pathogenesis of aspirin intolerance with subsequent hyperproduction of leukotrienes and inhibition of cyclooxygenase. OBJECTIVE: To examine the influence of the cysteinyl-leukotriene receptor antagonist montelukast on clinical symptoms and inflammatory markers in nasal lavage fluid in patients with bronchial asthma and nasal polyps, and determine its dependency on aspirin sensitization. METHODS: Twenty-four patients (7 women, 17 men; median age, 55.5 years) with nasal polyps and controlled asthma (n=12 with aspirin intolerance) were treated with 10 mg montelukast once daily for 6 weeks in a blinded, placebo-controlled fashion. The placebo phase was randomly assigned 4 weeks before (n=12) or after treatment (n=12). Symptom score, rhinoendoscopy, rhinomanometry, smears for eosinophils, and nasal lavages for the determination of different mediators were performed. RESULTS: Compared to placebo, there were significant improvements in the nasal symptom score and airflow limitation as well as a reduction in the inflammatory mediators in nasal lavage fluid after treatment. Furthermore, reduced eosinophils in nasal smears and peripheral blood were observed 2 and 6 weeks after treatment. CONCLUSION: Leukotriene 1 receptor blockade led to a significant decrease in eosinophil inflammation accompanied by a reduction in other mediators such as neurokinin A and substance P in the nasal lavage fluid of patients with nasal polyps and asthma, with or without aspirin intolerance.

Which anti-inflammatory drug should we use in asthma?

Asthma is a chronic and heterogeneous inflammatory disorder of the airways defined by its clinical, physiological and pathological characteristics. Accordingly to currently available guidelines inhaled glucocorticosteroids (ICS) represent the most effective anti-inflammatory medication for the treatment of persistent asthma, and this class of drugs is recommended as the first-line controller therapy both in children and adults. Leukotriene modifiers (LTRAs) are usually used as a second line of add-on therapy, although they may be regarded as the first-line therapy in exercise induced bronchoconstriction, in patients with comorbid allergic rhinitis and in children with asthma and frequent viral infections. A recently published pragmatic (real-life) study showed that LTRAs provide an alternative treatment for asthma, which, at least for the evaluated endpoints, may be as effective as ICS in our every-day practice. To assess how the recent data may affect our every-day practice and current guidelines for clinical management of asthma, it needs to be clearly understood what pragmatic trials add to our knowledge. In our opinion, it is premature to change current guidelines. However, pragmatic and observational studies are clearly needed as they provide additional information to randomized controlled trials. The main goal of all those efforts is to improve asthma control and decrease the burden of the disease for patients and societies. It may be that the future approach will introduce several new strategies based on system biology studies for the treatment of asthma guided in a personalized medicine approach.