Comparison of treatment efficacy of omega-3 fish oil and montelukast in ovalbumin-protease-induced allergic rhinitis model in rats.

OBJECTIVES: Montelukast is a well-known leukotriene receptor antagonist commonly used in treating allergic rhinitis and asthma. Omega-3 fatty acid is also known as an antiallergic and immunomodulator molecule. This study aimed to elucidate the efficacy of systemic montelukast and omega-3 fatty acid treatment in allergic rhinitis models in Wistar Hannover rats. METHODS: This research was conducted on 28 healthy Wistar Hannover rats weighing 250-350 g. After establishing the allergic rhinitis model, nasal symptoms were observed and scored, and the nasal mucosa of all rats was investigated histologically. Light microscopy was utilized to evaluate the degree of ciliary loss, goblet cell hyperplasia, vascular congestion, vascular proliferation, inflammatory cell infiltration, eosinophil infiltration, and hypertrophy in chondrocytes. RESULTS: As a result of the analysis of the data obtained from the study, it was determined that typical allergic rhinitis symptoms such as nasal scratching and sneezing were significantly reduced in the rats in the montelukast and omega-3 treated group, and these symptoms did not increase after repeated intranasal OVA-protease applications. Histological examinations after fish oil treatment did not reveal typical inflammatory changes in allergic rhinitis. None of the rats in the montelukast and omega-3 groups had any increase in goblet cells, whereas 14.3% of the rats in the control group and 28.6% of the rats in the allergic rhinitis group had mild increase. Last but not least, 71.4% of rats in the allergic rhinitis group had a moderate increase. The difference between the groups was statistically significant (p < 0.001). CONCLUSION: Regarding the outcomes of this research, it was observed that w-3 fatty acids had antiallergic effects, both histopathological and clinical, in the allergic rhinitis model. We believe that further randomized controlled trials incorporating larger cohorts are warranted to verify the use of omega-3 fatty acids in treating allergic rhinitis. The level of evidence of this article is Level 2.

The Risk of Neuropsychiatric Adverse Events With Use of Leukotriene Receptor Antagonists in Patients With Asthma: Analysis of Korea's National Health Insurance Sharing Service Database.

BACKGROUND: Montelukast, a selective leukotriene receptor antagonist, is a commonly prescribed allergy medication but its potential association with neuropsychiatric adverse events is concerning. OBJECTIVE: To analyze Korea's National Health Insurance System claims records to identify the risk of neuropsychiatric adverse events in patients with asthma treated with montelukast. METHODS: This retrospective population-based study analyzed the National Health Insurance claims records of the entire Korean population between 2008 and 2015. We compared the risk of neuropsychiatric adverse events among patients with asthma using inhaled corticosteroids and/or long-acting ß2-agonists with montelukast or pranlukast and those not using leukotriene receptor antagonists (control group). RESULTS: There was no increased risk of the composite outcome of all measured neuropsychiatric adverse events in patients with asthma who were prescribed montelukast or pranlukast compared with those who were not. However, montelukast use was associated with an increased risk of hallucinations (inverse probability treatment weighting hazard ratio, 1.45; 95% CI, 1.07-1.96) and attention problems (inverse probability treatment weighting hazard ratio, 1.24; 95% CI, 1.01-1.52). Significant negative hazards for disorientation, anxiety, stress reactions, and somatic symptoms were observed in the montelukast group. When grouped by sex, the risk of hallucinations and attention problems was higher in men prescribed montelukast compared with the controls. CONCLUSIONS: We did not observe an increase in all neuropsychiatric adverse events in the leukotriene receptor antagonist-treated group; however, an increased risk of hallucinations and attention problems was observed in those taking montelukast, regardless of the medication administration period.

Effects of treatment with montelukast alone, budesonide/formoterol alone and a combination of both in cough variant asthma.

BACKGROUND: Whether cysteinyl-leukotriene receptor antagonists (LTRAs) have a similar antitussive effect to inhaled corticosteroids and long-acting ß2-agonist (ICS/LABA), and that LTRA plus ICS/LABA is superior to LTRAs alone or ICS/LABA alone in treating cough variant asthma (CVA) remain unclear. This study aimed to investigate and compare the efficacy of montelukast alone, budesonide/formoterol alone and the combination of both in the treatment of CVA. METHODS: Ninety-nine CVA patients were assigned randomly in a 1:1:1 ratio to receive montelukast (M group: 10 mg, once daily), budesonide/formoterol (BF group: 160/4.5 µg, one puff, twice daily), or montelukast plus budesonide/formoterol (MBF group) for 8 weeks. The primary outcomes were changes in the cough visual analogue scale (VAS) score, daytime cough symptom score (CSS) and night-time CSS, and the secondary outcomes comprised changes in cough reflex sensitivity (CRS), the percentage of sputum eosinophils (sputum Eos%) and fractional exhaled nitric oxide (FeNO). CRS was presented with the lowest concentration of capsaicin that induced at least 5 coughs (C5). The repeated measure was used in data analysis. RESULTS: The median cough VAS score (median from 6.0 to 2.0 in the M group, 5.0 to 1.0 in the BF group and 6.0 to 1.0 in the MBF group, all p < 0.001), daytime CSS (all p < 0.01) and night-time CSS (all p < 0.001) decreased significantly in all three groups after treatment for 8 weeks. Meanwhile, the LogC5 and sputum Eos% improved significantly in all three groups after 8 weeks treatment (all p < 0.05). No significant differences were found in the changes of the VAS score, daytime and night-time CSSs, LogC5 and sputum Eos% among the three groups from baseline to week 8 (all p > 0.05). The BF and MBF groups also showed significant decreases in FeNO after 8 weeks treatment (p = 0.001 and p = 0.008, respectively), while no significant change was found in the M group (p = 0.457). Treatment with MBF for 8 weeks significantly improved the FEV1/FVC as well as the MMEF% pred and decreased the blood Eos% (all p < 0.05). CONCLUSIONS: Montelukast alone, budesonide/formoterol alone and a combination of both were effective in improving cough symptom, decreasing cough reflex sensitivity and alleviating eosinophilic airway inflammation in patients with CVA, and the antitussive effect and anti-eosinophilic airway inflammation were similar. Trial registration ClinicalTrials.gov, number NCT01404013.

Natural Anti-inflammatory and Anti-allergy Agents: Herbs and Botanical Ingredients.

Allergies have been known to be an abnormally vigorous immune response in which the immune system fights off an allergen or antigen, initiating mast cells to release histamine into the blood. Substances that prevent mast cells from releasing histamine are considered antiallergic agents. The drugs utilized to treat allergy are mast cell stabilizers, steroids, anti-histamine, leukotriene receptor antagonists, and decongestants. Anti-histamine drugs have side effects such as drowsiness, confusion, constipation, difficulty urinating, blurred vision, etc. The use of medicinal plants for the effective and safe management of diseases has recently received much attention. Various herbs are utilized for their antiallergic and anti-histaminic properties. Some of the herbs useful in the management of allergic diseases of the respiratory tract, like Piper longum, Ocimum tenuiflorum, Solanum xanthocarpum have been discussed. Ample scientific evidence is available for the anti-histaminic and antiallergic activity of Azadirachta indica, Aloe vera, Tinospora cordifolia, and many other such herbs are safer to use as antiallergic agents have been reported. The review summarizes a wide variety of herbs and botanical ingredients with their common scientific names and distribution for easy identification and usage as safe antiallergic agents and discusses their molecular mechanisms involved in combating allergic reactions.

Involvement of GPR17 in Neuronal Fibre Outgrowth.

Characterization of new pharmacological targets is a promising approach in research of neurorepair mechanisms. The G protein-coupled receptor 17 (GPR17) has recently been proposed as an interesting pharmacological target, e.g., in neuroregenerative processes. Using the well-established ex vivo model of organotypic slice co-cultures of the mesocortical dopaminergic system (prefrontal cortex (PFC) and substantia nigra/ventral tegmental area (SN/VTA) complex), the influence of GPR17 ligands on neurite outgrowth from SN/VTA to the PFC was investigated. The growth-promoting effects of Montelukast (MTK; GPR17- and cysteinyl-leukotriene receptor antagonist), the glial cell line-derived neurotrophic factor (GDNF) and of two potent, selective GPR17 agonists (PSB-16484 and PSB-16282) were characterized. Treatment with MTK resulted in a significant increase in mean neurite density, comparable with the effects of GDNF. The combination of MTK and GPR17 agonist PSB-16484 significantly inhibited neuronal growth. qPCR studies revealed an MTK-induced elevated mRNA-expression of genes relevant for neuronal growth. Immunofluorescence labelling showed a marked expression of GPR17 on NG2-positive glia. Western blot and RT-qPCR analysis of untreated cultures suggest a time-dependent, injury-induced stimulation of GPR17. In conclusion, MTK was identified as a stimulator of neurite fibre outgrowth, mediating its effects through GPR17, highlighting GPR17 as an interesting therapeutic target in neuronal regeneration.

Biliary excretion of arsenic by human HepaRG cells is stimulated by selenide and mediated by the multidrug resistance protein 2 (MRP2/ABCC2).

Millions of people worldwide are exposed to unacceptable levels of arsenic, a proven human carcinogen, in drinking water. In animal models, arsenic and selenium are mutually protective through formation and biliary excretion of seleno-bis (S-glutathionyl) arsinium ion [(GS)2AsSe]-. Selenium-deficient humans living in arsenic-endemic regions are at increased risk of arsenic-induced diseases, and may benefit from selenium supplementation. The influence of selenium on human arsenic hepatobiliary transport has not been studied using optimal human models. HepaRG cells, a surrogate for primary human hepatocytes, were used to investigate selenium (selenite, selenide, selenomethionine, and methylselenocysteine) effects on arsenic hepatobiliary transport. Arsenite + selenite and arsenite + selenide at different molar ratios revealed mutual toxicity antagonism, with the latter being higher. Significant levels of arsenic biliary excretion were detected with a biliary excretion index (BEI) of 14 ± 8%, which was stimulated to 32 ± 7% by selenide. Consistent with the formation and biliary efflux of [(GS)2AsSe]-, arsenite increased the BEI of selenide from 0% to 24 ± 5%. Arsenic biliary excretion was lost in the presence of selenite, selenomethionine, and methylselenocysteine. Sinusoidal export of arsenic was stimulated ∼1.6-fold by methylselenocysteine, but unchanged by other selenium forms. Arsenic canalicular and sinusoidal transport (±selenide) was temperature- and GSH-dependent and inhibited by MK571. Knockdown experiments revealed that multidrug resistance protein 2 (MRP2/ABCC2) accounted for all detectable biliary efflux of arsenic (±selenide). Overall, the chemical form of selenium and human MRP2 strongly influenced arsenic hepatobiliary transport, information critical for human selenium supplementation in arsenic-endemic regions.

LTA4H rs2660845 association with montelukast response in early and late-onset asthma.

Leukotrienes play a central pathophysiological role in both paediatric and adult asthma. However, 35% to 78% of asthmatics do not respond to leukotriene inhibitors. In this study we tested the role of the LTA4H regulatory variant rs2660845 and age of asthma onset in response to montelukast in ethnically diverse populations. We identified and genotyped 3,594 asthma patients treated with montelukast (2,514 late-onset and 1,080 early-onset) from seven cohorts (UKBiobank, GoSHARE, BREATHE, Tayside RCT, PAGES, GALA II and SAGE). Individuals under montelukast treatment experiencing at least one exacerbation in a 12-month period were compared against individuals with no exacerbation, using logistic regression for each cohort and meta-analysis. While no significant association was found with European late-onset subjects, a meta-analysis of 523 early-onset individuals from European ancestry demonstrated the odds of experiencing asthma exacerbations by carriers of at least one G allele, despite montelukast treatment, were increased (odds-ratio = 2.92, 95%confidence interval (CI): 1.04-8.18, I2 = 62%, p = 0.0412) compared to those in the AA group. When meta-analysing with other ethnic groups, no significant increased risk of asthma exacerbations was found (OR = 1.60, 95% CI: 0.61-4.19, I2 = 85%, p = 0.342). Our study demonstrates that genetic variation in LTA4H, together with timing of asthma onset, may contribute to variability in montelukast response. European individuals with early-onset (≤18y) carrying at least one copy of rs2660845 have increased odd of exacerbation under montelukast treatment, presumably due to the up-regulation of LTA4H activity. These findings support a precision medicine approach for the treatment of asthma with montelukast.

Tratamento da UCE refratária aos anti-histamínicos e na impossibilidade do omalizumabe, nos adultos / Treatment of CSU refractory to antihistamines and in the impossibility of omalizumab therapy in adults

Há o empenho contínuo de especialistas no desenvolvimento de tratamentos resolutivos ou eficazes nos controles das doenças, no entanto, a entidade urticária crônica espontânea (UCE), quando refratária à primeira linha de tratamento, os anti-histamínicos, apresenta um prognóstico desfavorável. Existe um arsenal de medicamentos biológicos disponíveis já consolidados como eficazes e seguros, porém eventualmente nos defrontamos com a inacessibilidade a estes medicamentos, devido aos custos dos mesmos e aos trâmites necessários para dar início ao tratamento. Tais fatos fundamentam a discussão sobre terapias alternativas com outros fármacos, visando manter o manejo adequado da doença e a qualidade de vida dos pacientes.

Specialists have made a continuous effort for the development of effective treatments for disease control; however, chronic spontaneous urticaria (CSU), when refractory to the first line of treatment, ie, antihistamines, has an unfavorable prognosis. There are biological medicines available, which have been consolidated as effective and safe, but we are occasionally faced with a lack of access to these medicines due to their costs and the necessary procedures to start treatment. Such facts support the discussion about alternative therapies with other drugs, aiming at maintaining the adequate management of the disease and the quality of life of patients.

Extract matrix composition does not affect in vitro leukotriene inhibitory effects of the Petasites hybridus extract Ze 339.

It has been shown that a lipophilic CO2-extract prepared from the leaves of Petasites hybridus (Ze 339) inhibited leukotriene synthesis in vitro and ex vivo. The inhibition of the leukotriene synthesis was solely attributed to the sum of the petasins, namely petasin and its isomers isopetasin and neopetasin. To further investigate the influence of the extract matrix on leukotriene synthesis inhibition, we compared twelve selected batches of Ze 339 that differed significantly in the composition of the extract matrix. Quantitative analysis of the twelve extract batches revealed high contents of petasins [28.8-41.9%], fatty acids [17.1-27.2%] and crude oil and fat [17.7-44.2%]. The amount of sterols ranged between 3.0 and 4.9% and that of essential oils between 1.3 and 10.5%. Based on the quantitative analysis, 97-100% of the extract mass could be attributed to the above mentioned groups of ingredients. Despite significant differences in extract matrix composition, only the content of petasins was critical for the dose-dependent inhibition of leukotriene synthesis. However, at equal concentrations of petasins, no significant differences in 5-LOX, LTC4 synthase and LTA4 hydrolase inhibition were detected between the selected extract batches, despite differences in the composition of the petasin isomers. Our data suggest that the extract matrix of Ze 339 has no effect on leukotriene inhibitory effects of the petasins.

Therapeutic Potential of Antileukotriene Drug-Camellia sinensis Extract Co-Formulation on Histamine Induced Asthma in Guinea Pigs.

BACKGROUND/OBJECTIVE: To study the therapeutic potential of Antileukotriene drug- Camellia sinensis extract co-formulation on histamine induced asthma in guinea pigs. METHODS: SRSD of Montelukast sodium was prepared by the solvent evaporation method. Lyophilized aqueous extract of Camellia sinensis leaves and SRSD mixture was filled in capsule and the capsule shell was coated to achieve initial release lag time. In vitro and pharmacokinetic study of capsules was performed and compared with commercial tablets. A further role of green tea, as an antioxidant adjunct for asthma management, has been analyzed by lung histology, mast cell count and oxidative stress assay in the serum of control and experimental animals. RESULTS: The drug release from the commercial tablet was immediate and rapid, but capsule has shown an initial 3.5 hr lag time followed by sustained action up to 8 hr. Pharmacokinetic results show that studied formulations are bioequivalent with respect to Cmax and AUC, while rest parameters showed asignificant difference. Mast cells count in lung tissue were increased (p<0.001) in the experimental group along with glycoprotein deposition in asthmatic bronchioles. Levels of SOD and GPX were decreased (p<0.05) while CAT was increased (p<0.04) in the asthma group in comparison to control. CONCLUSION: In the experimental animal model, co-formulation was effective in modulating allergic inflammation and contributing to better control of the inflammatory response. Our findings suggest that Camellia sinensis leaves extract may be used as an adjunct for future improvements in asthma treatment and prevention.

Comparing LAMA with LABA and LTRA as add-on therapies in primary care asthma management.

The Global Initiative for Asthma recommends a stepwise approach to adjust asthma treatment to the needs of individual patients; inhaled corticosteroids (ICS) remain the core pharmacological treatment. However, many patients remain poorly controlled, and evidence-based algorithms to decide on the best order and rationale for add-on therapies are lacking. We explore the challenges of asthma management in primary care and review outcomes from randomised controlled trials and meta-analyses comparing the long-acting muscarinic antagonist (LAMA) tiotropium with long-acting ß2-agonists (LABAs) or leukotriene receptor antagonists (LTRAs) as add-on to ICS in patients with asthma. In adults, LAMAs and LABAs provide a greater improvement in lung function than LTRAs as add-on to ICS. In children, results were positive and comparable between therapies, but data are scarce. This information could aid decision-making in primary care, supporting the use of add-on therapy to ICS to help improve lung function, control asthma symptoms and prevent exacerbations.

Efficacy of Montelukast in Allergic Rhinitis Treatment: A Systematic Review and Meta-Analysis.

BACKGROUND: In treating allergic rhinitis, montelukast has the potential to be used as an alternative or addition to an oral antihistamine or intranasal corticosteroid. OBJECTIVE: The objective of this systematic review was to assess the effectiveness of montelukast in treating allergic rhinitis. METHODS: An electronic literature search was performed using the Cochrane Central Register of Controlled Trials, EMBASE, and MEDLINE from 1966 to 21 January 2019. The eligibility criteria were randomized controlled trials comparing montelukast with placebo or other standard treatments. The primary outcomes assessed were daytime nasal symptom score (DNS) and night-time nasal symptom score (NNS). The secondary outcomes assessed were composite nasal symptom score (CSS), daytime eyes symptom score (DES), and rhinoconjunctivitis quality-of-life questionnaires (RQLQ). The meta-analysis was conducted using Review Manager 5.3 software based on the random-effects model. RESULTS: Fifteen studies of 10387 participants met the inclusion criteria. Montelukast was more effective than placebo in improving DNS (mean difference [MD] - 0.12, 95% confidence interval [CI] - 0.15 to - 0.08; p < 0.001), NNS (MD - 0.09, 95% CI - 0.13 to - 0.05; p < 0.001), CSS (MD - 0.08, 95% CI - 0.11 to - 0.06; p < 0.001), DES (MD - 0.17, 95% CI - 0.33 to - 0.02; p < 0.030), and RQLQ (MD - 0.34, 95% CI - 0.49 to - 0.20; p < 0.001). Oral antihistamine was superior to montelukast in improving DNS (MD 0.08, 95% CI 0.03-0.13; p = 0.002), CSS (MD 0.03, 95% CI - 0.02 to 0.07; p = 0.27), DES (MD 0.06, 95% CI 0-0.12; p = 0.040), and RQLQ (MD 0.03, 95% CI - 0.05 to 0.12; p = 0.430). Montelukast was superior to oral antihistamine in improving NNS (MD -0.03, 95% CI - 0.08 to 0.03; p = 0.330). Intranasal fluticasone spray was superior to montelukast in improving DNS (MD 0.71, 95% CI 0.44-0.99; p < 0.001) and NNS (MD 0.63, 95% CI 0.29-0.97; p < 0.001). Combined montelukast and oral antihistamine was superior to oral antihistamine in improving DNS (MD - 0.15, 95% CI - 0.27 to - 0.03; p = 0.010), NNS (MD - 0.16, 95% CI - 0.28 to - 0.05; p = 0.006), CSS (MD - 0.12, 95% CI - 0.25 to - 0.01; p = 0.070), DES (MD - 0.12, 95% CI - 0.30 to 0.06; p = 0.180), and RQLQ (MD - 0.10, 95% CI - 0.28 to 0.08; p = 0.290). Combined montelukast and OAH was superior to montelukast in improving DNS (MD 0.15, 95% CI 0.08-0.21; p < 0.001), NNS (MD 0.05, 95% CI - 0.09 to 0.19; p = 0.510), CSS (MD 0.1, 95% CI 0.03-0.17; p = 0.007), DES (MD 0.18, 95% CI 0-0.36; p = 0.050), and RQLQ (MD 0.07 95% CI - 0.15 to 0.29; p = 0.530). CONCLUSIONS: Montelukast is more effective than placebo in treating the overall symptoms of allergic rhinitis while the combined therapy of montelukast and an oral antihistamine is superior to either montelukast or an oral antihistamine alone.

Pharmacotherapeutic management of asthma in the elderly patient.

INTRODUCTION: Asthma is a heterogeneous syndrome with variable phenotypes. Reversible airway obstruction and airway hyper-responsiveness often with an atopic or eosinophilic component is common in the elderly asthmatic. Asthma chronic obstructive pulmonary disease overlap syndrome (ACOS), a combination of atopy-mediated airway hyper-responsiveness and a history of smoking or other environmental noxious exposures, can lead to some fixed airway obstruction and is also common in elderly patients. Little specific data exist for the treating the elderly asthmatic, thus requiring the clinician to extrapolate from general adult data and asthma treatment guidelines. AREAS COVERED: A stepwise approach to pharmacotherapy of the elderly patient with asthma and ACOS is offered and the literature supporting the use of each class of drugs reviewed. EXPERT OPINION: Inhaled, long-acting bronchodilators in combination with inhaled corticosteroids represent the backbone of treatment for the elderly patient with asthma or ACOS . Beyond these medications used as direct bronchodilators and topical anti-inflammatory agents, a stepwise approach to escalation of therapy includes multiple options such as oral leukotriene receptor antagonist or 5-lipoxygense inhibitor therapy, oral phosphodiesterase inhibitors, systemic corticosteroids, oral macrolide antibiotics and if evidence of eosinophilic/atopic component disease exists then modifying monoclonal antibody therapies.

The Role of Leukotrienes Inhibitors in the Management of Chronic Inflammatory Diseases.

BACKGROUND: Leukotrienes are powerful mediators of inflammation and interact with specific receptors in target cell membrane to initiate an inflammatory response. Thus, Leukotrienes (LTs) are considered to be potent mediators of inflammatory diseases including allergic rhinitis, inflammatory bowel disease and asthma. Leukotriene B4 and the series of cysteinyl leukotrienes (C4, D4, and E4) are metabolites of arachidonic acid metabolism that cause inflammation. The cysteinyl LTs are known to increase vascular permeability, bronco-constriction and mucus secretion. OBJECTIVES: To review the published data for leukotriene inhibitors of plant origin and the recent patents for leukotriene inhibitors, as well as their role in the management of inflammatory diseases. METHODS: Published data for leukotrienes antagonists of plant origin were searched from 1938 to 2019, without language restrictions using relevant keywords in both free text and Medical Subject Headings (MeSH terms) format. Literature and patent searches in the field of leukotriene inhibitors were carried out by using numerous scientific databases including Science Direct, PubMed, MEDLINE, Google Patents, US Patents, US Patent Applications, Abstract of Japan, German Patents, European Patents, WIPO and NAPRALERT. Finally, data from these information resources were analyzed and reported in the present study. RESULTS: Currently, numerous anti-histaminic medicines are available including chloropheneremine, brompheniramine, cetirizine, and clementine. Furthermore, specific leukotriene antagonists from allopathic medicines are also available including zileuton, montelukast, pranlukast and zafirlukast and are considered effective and safe medicines as compared to the first generation medicines. The present study reports leukotrienes antagonistic agents of natural products and certain recent patents that could be an alternative medicine in the management of inflammation in respiratory diseases. CONCLUSION: The present study highlights recent updates on the pharmacology and patents on leukotriene antagonists in the management of inflammation respiratory diseases.

Treatment strategies for the yellow zone.

OBJECTIVE: To evaluate relevant studies and documents that address treatment strategies for acute loss of asthma control (yellow zone). DATA SOURCES: Publications available on various treatment strategies for the yellow zone, Global Initiative for Asthma, and FDA Drug Safety Communication. STUDY SELECTIONS: Studies that assessed the effectiveness of specific therapies as yellow zone strategies were included in this review. RESULTS: Multiple yellow zone strategies exist, but only a few have been shown consistently effective. No specific evidence suggests that scheduled SABA can prevent exacerbation. Results for intermittent leukotriene receptor antagonist use have been mixed. Strong evidence supports intermittent inhaled corticosteroid (ICS) dosing for preschool-aged children with intermittent viral-induced wheeze, but data regarding this strategy for older children and adults are limited. As for short-term increase in scheduled ICS controller, doubling the dose seems to be ineffective, whereas results for a more substantial increase in ICS dose (quadrupling and quintupling) have been mixed. Dynamic dosing appears most promising, because symptom-driven ICS in tandem with rescue beta agonist use (whether short- or long-acting) is the strategy with the most robust data demonstrating reduction in exacerbations while minimizing ICS exposure. CONCLUSION: Varying study designs and the heterogeneity of asthma itself likely account for the difference in outcomes seen with the various yellow zone intervention strategies studied. More studies are needed to determine the right yellow zone therapies for the right patients, but this is likely to be most effective through a personalized approach.

Healthcare utilization in infants and toddlers with asthma-like symptoms.

BACKGROUND: Recurrent asthma-like symptoms are common in infants, but few population studies describe diagnostic and treatment practice. METHODS: Using the electronic data repository of Clalit Health Services, the largest integrated health care provider in Israel, we evaluated children born 2005-2012, who before 3 years of age had >3 episodes of asthma-like symptoms and/or >2 bronchodilator purchases within a year. We described health care utilization and the odds ratio for subsequent utilization after 3 and 12 months' controller therapy. The primary outcome measure was respiratory-related doctor visits. Linear and categorical regression analysis measured overall effectiveness of therapy. RESULTS: Among 689 171 infants, 262 900 (38.1%) had > 3 asthma-like episodes/year during at least 1 year. Of those, 26 108 (10%) purchased controller therapy: 20 316 (77.8%) inhaled corticosteroids (ICS) with or without leukotriene receptor antagonists (LTRA), and 5792 (22.2%) LTRA alone. For these 26 108 over 3 months there were 93 845 respiratory-related doctor visits, 3110 hospital admissions, 5568 diagnoses of pneumonia, 9960 chest X-rays, 37 127 purchases for oral steroids, and 45 142 for antibiotics courses. Healthcare utilization decreased following ICS ± LTRA and LTRA alone, respectively, as follows: doctor visits 7% and 3%, chest X-rays 16% and 17%, bronchodilators 20% and 11%, systemic steroids 17% and 12%, and antibiotics by 35% and 22%, (P < .001 for all). Twelve months' therapy remained effective. CONCLUSIONS: Asthma-like symptoms are common in infants. Health care utilization is very high and physician practices should be reassessed. Following controller therapy, health care utilization decreased. Yet controllers were prescribed in only a minority of eligible children.

Systematic reviews of pharmacological and nonpharmacological treatments for patients with chronic urticaria: An umbrella systematic review.

A wide range of pharmacological and nonpharmacological interventions for chronic urticaria (CU) have been evaluated in systematic reviews (SRs). We conducted an umbrella review of SRs of the effectiveness and safety of pharmacological and nonpharmacological interventions for CU, which allow the findings of separate reviews to be compared and contrasted and thereby provide decision makers in healthcare with the evidence they need.We included SRs evaluating pharmacological and nonpharmacological interventions for CU. Comprehensive searches were conducted in 7 bibliographic databases, relevant journals up to July 2018. Two reviewers independently assessed the studies' relevance and quality. The assessment of multiple systematic reviews tool and grading of recommendations assessment, development and evaluation method was used to assess the methodological quality of the SRs and classify the quality of the outcomes.In total, 41 SRs were included. Thirty-seven reviews performed quantitative research syntheses, and 4 reviews performed qualitative research syntheses. The majority of SRs evaluated interventions based on combination therapies, antihistamines, traditional Chinese medicines, autohemotherapy, omalizumab, acupuncture, cyclosporine, and leukotriene receptor antagonist. Positive intervention outcomes were reported in the majority (75.32%) of the reviews. However, the methodological quality and evidence quality of the reviews were generally poor.There is some evidence to support a variety of interventions for CU. However, there was much heterogeneity in evidence quality among SRs. Many of the SRs had methodological weaknesses that make them vulnerable to bias. Moreover, there remained little information on the relative effectiveness of one intervention compared with another. Therefore, further SRs that adherence to strict scientific methods are necessary, and primary studies make comparisons between the different treatment options directly.

Real-life experience in the treatment of solar urticaria: retrospective cohort study.

BACKGROUND: Solar urticaria (SU) is a rare photodermatosis causing a significant impact on patients' quality of life (QoL), and treatment is often challenging. AIM: To analyse clinical experience with a tailored stepwise therapeutic approach. METHODS: A retrospective cohort design was used. Patients with suspected SU underwent laboratory investigations and photoprovocation. Those with a high minimal urticaria dose (MUD) were treated with a single antihistamine (protocol 1), and those with a lower MUD received three types of antihistamines (protocol 2); both protocols included a leucotriene receptor antagonist (LRA). In cases of failure, treatment was switched to omalizumab at doses of < 300 mg/month with incremental dosage increases as necessary (monthly dose range, 150-600 mg/month). Symptom relief and photoprovocation under treatment were evaluated. RESULTS: In total, 30 patients (10 men, 20 women) were enrolled. Most (87%) were sensitive to visible light (1-70 J/cm2 ) with or without extension to ultraviolet A. Of the 30 patients, 23 opted for our stepwise approach: 22 achieved complete remission on protocols 1 or 2 (n = 17) or after switching to omalizumab (n = 5), and another patient achieved partial remission under omalizumab. There were no treatment-related severe adverse effects. CONCLUSIONS: Symptoms of SU can be well controlled by treatment with antihistamines and an LRA tailored to the degree of photosensitivity, followed by omalizumab in refractory cases. This has important implications for patient QoL.