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

Allergic rhinitis (AR) can significantly reduce the quality of life of patients leading to increased fatigue, mood changes, cognitive impairment, and depression. In clinical practice, insufficient effectiveness of initial AR monotherapy is often noted, and a significant proportion of patients referring for medical care have moderate-severe AR. In this regard, the issues of optimization of combined pharmacological treatment of AR are becoming more and more urgent. This paper provides analysis of the opportunities of combined pharmacotherapy within the framework of current management strategy of AR. Based on the results of some studies and known pharmacological properties of medications it is being discussed the advantages of combined use of intranasal corticosteroids and leukotriene receptor antagonists, in particular mometasone furoate and montelukast, in the therapy of AR, including such comorbidities as bronchial asthma, chronic polyposis rhinosinusitis and pharyngeal tonsil hyperplasia. Some aspects of combination therapy with montelukast and second-generation systemic antihistamines as an alternative approach in case of inability to take intranasal corticosteroids, including the reasonability of using a fixed combination of montelukast and levocetirizine, are analyzed from the perspective of rational pharmacotherapy. The problem of interchangeability of brand-name and generic drugs for the treatment of AR is discussed, considering the almost complete absence of studies of their therapeutic equivalence.
Аллергический ринит (АР) может существенно снижать качество жизни пациентов, приводя к повышенной утомляемости, изменениям настроения, нарушениям когнитивной функции, депрессии. При этом в клинической практике часто отмечается недостаточная эффективность начальной монотерапии АР, а значительное число больных, обращающихся за медицинской помощью, имеют среднетяжелое и тяжелое течение заболевания. В связи с этим все более актуальными становятся вопросы оптимизации комбинированного медикаментозного лечения АР. В статье представлен анализ возможностей комбинированной фармакотерапии в рамках современной стратегии ведения пациентов с АР. На основе результатов ряда исследований и известных фармакологических свойств препаратов обсуждены преимущества совместного применения интраназальных глюкокортикостероидов и антагонистов лейкотриеновых рецепторов, в частности мометазона фуроата и монтелукаста, в терапии АР, в том числе при сочетании с бронхиальной астмой, хроническим полипозным риносинуситом и гиперплазией глоточной миндалины. Проанализированы некоторые аспекты комбинированной терапии монтелукастом и системными антигистаминными препаратами последнего поколения в качестве альтернативного подхода в случае невозможности приема интраназальных кортикостероидов, включая целесообразность применения фиксированной комбинации монтелукаста и левоцетиризина, с позиций рациональной фармакотерапии. Обсуждена проблема взаимозаменяемости оригинальных и воспроизведенных препаратов для лечения АР с учетом практически полного отсутствия исследований их терапевтической эквивалентности.

BACKGROUND: The benefits and harms of adding antileukotrienes to H1 antihistamines (AHs) for the management of urticaria (hives, itch, and/or angioedema) remain unclear.
OBJECTIVE: We sought to systematically synthesize the treatment outcomes of antileukotrienes in combination with AHs versus AHs alone for acute and chronic urticaria.
METHODS: As part of updating American Academy of Allergy, Asthma & Immunology and American College of Allergy, Asthma, and Immunology Joint Task Force on Practice Parameters urticaria guidelines, we searched Medline, Embase, Central, LILACS, WPRIM, IBECS, ICTRP, CBM, CNKI, VIP, Wanfang, US Food and Drug Administration, and European Medicines Agency databases from inception to December 18, 2023, for randomized controlled trials (RCTs) evaluating antileukotrienes and AHs versus AHs alone in patients with urticaria. Paired reviewers independently screened citations, extracted data, and assessed risk of bias. Random effects models pooled effect estimates for urticaria activity, itch, wheal, sleep, quality of life, and harms. The GRADE approach informed certainty of evidence ratings. The study was registered at the Open Science Framework (osf.io/h2bfx/).
RESULTS: Thirty-four RCTs enrolled 3324 children and adults. Compared to AHs alone, the combination of a leukotriene receptor antagonist with AHs probably modestly reduces urticaria activity (mean difference, -5.04; 95% confidence interval, -6.36 to -3.71; 7-day urticaria activity score) with moderate certainty. We made similar findings for itch and wheal severity as well as quality of life. Adverse events were probably not different between groups (moderate certainty); however, no RCT reported on neuropsychiatric adverse events.
CONCLUSIONS: Among patients with urticaria, adding leukotriene receptor antagonists to AHs probably modestly improves urticaria activity with little to no increase in overall adverse events. The added risk of neuropsychiatric adverse events in this population with leukotriene receptor antagonists is small and uncertain.

Certain guidelines recommend a second-generation H1-antihistamine (AH) as first-line treatment for patients with chronic urticaria (CU). However, some patients show insufficient response to a standard dose of this therapy and might benefit from adding leukotriene receptor antagonists (LTA). Therefore, we aimed to perform a systematic review and meta-analysis comparing LTA plus antihistamines with antihistamines alone. We performed a systematic review and meta-analysis, searching PubMed, EMBASE, and Cochrane Central for randomized clinical trial (RCT) data comparing LTA plus AH treatment to AH alone in patients with CU. Statistical analysis was performed using R Studio 4.3.2. Heterogeneity was assessed with I2 statistics. Three studies comprising 234 patients with urticaria were included. The mean age was 37.23 years in the leukotriene antagonist + antihistamines (LTA + AH) group and 39.14 years in the antihistamines (AH) group. Follow-up ranged from 2 to 18 months between studies. There was no statistically significant difference between groups in terms of TSS level (SMD: -74.82; 95% CI: -222.66 to 73.02; P = 0.32; I2 = 98%), neither in terms of pruritus (MD: -0.07; 95% CI: -0.42 to 0.28; P = 0.70; I2 = 74%). After sensitivity analysis, with the systematic exclusion of each study from the grouped estimates, the result for TSS level did not change. These findings suggest that leukotriene receptor antagonists with antihistamines do not have better outcomes than antihistamines alone regarding TSS and pruritus in patients with CU.

暂无摘要。

Obstructive sleep apnea syndrome (OSA) is the main manifestation of sleep-disordered breathing in children. Untreated OSA can lead to a variety of complications and adverse consequences mainly due to intermittent hypoxemia. The pathogenesis of OSA is multifactorial. In children aged 2 years or older, adenoid and/or tonsil hypertrophy are the most common causes of upper airway lumen reduction; obesity becomes a major risk factor in older children and adolescents since the presence of fat in the pharyngeal soft tissue reduces the caliber of the lumen. Treatment includes surgical and non-surgical options. This narrative review summarizes the evidence available on the first-line approach in children with OSA, including clinical indications for medical therapy, its effectiveness, and possible adverse effects. Literature analysis showed that AT is the first-line treatment in most patients with adenotonsillar hypertrophy associated with OSA but medical therapy in children over 2 years old with mild OSA is a valid option. In mild OSA, a 1- to 6-month trial with intranasal steroids (INS) alone or in combination with montelukast with an appropriate follow-up can be considered. Further studies are needed to develop an algorithm that permits the selection of children with OSA who would benefit from alternatives to surgery, to define the optimal bridge therapy before surgery, to evaluate the long-term effects of INS +/- montelukast, and to compare the impact of standardized approaches for weight loss.

New asthma guidelines (GINA, 2022; NAEPP EPR-4, 2020) include considerable changes in treatment recommendations, specifically regarding anti-inflammatory rescue and Single MAintenance and Reliever Therapy (SMART).
To explore American College of Allergy, Asthma and Immunology members\' preferred treatment and perceived hurdles.
A survey (SurveyMonkey) regarding steps 1 to 3 asthma therapy was e-mailed to American College of Allergy, Asthma and Immunology members.
The allergists completed 147 surveys (46% with >20 years of experience; 98% from United States; 29% academic, 75% [also] private practice). In addition, 69% follow the National Asthma Education and Prevention Program and 81% the Global Initiative for Asthma recommendations. Of 147 allergists, 117 (80%) indicated correctly what SMART strategy is; 21%/36%/50%/39% would use SMART in step 3 treatment of a below 5-year-old/5- to 11-year-old/12- to 65-year-old/above 65-year-old patient, respectively. In this group, 11% to 14% incorrectly chose inhaled corticosteroid (ICS) plus salmeterol and 9% ICS plus vilanterol for SMART. In a 4-year-old needing step 1 therapy (N = 129), 55% of the respondents would add anti-inflammatory therapy; for step 2 treatment, most would prescribe ICS 100 to 200 µg budesonide equivalent daily; in step 3, 49% would prescribe ICS plus long-acting beta-agonist (LABA). In a 7-year-old needing step 1 treatment (N = 134), 40% would prescribe only short-acting beta-agonist; in step 3, 45% would institute SMART strategy, but only 8 of 135 (6%) chose very-low dose ICS plus formoterol (as recommended in Global Initiative for Asthma); most (39%) use low-dose ICS plus formoterol. As for rescue therapy, 59% is now instituting some form of anti-inflammatory rescue. Finally, in a 25-year-old patient (N = 144): in step 1, 39% would prescribe exclusively short-acting beta-agonist; in step 2, 4% only anti-inflammatory rescue and the rest prescribes ICS maintenance; one-third begins SMART strategy at step 2 and 50% in step 3. Major hurdles for prescribing one\'s preferred strategy included incomplete insurance coverage, insurance not approving more than one canister of ICS-formoterol per month, and cost.
Asthma therapy varies among physicians, with respondents suggesting underutilization of the recommended anti-inflammatory rescue and SMART therapy. A major hurdle is lack of insurance coverage of medication in line with the guidelines.

BACKGROUND: Asthma is the most common chronic lung disease among children. International guidelines recommend inhaled corticosteroids (ICS) as the first-line daily controller therapy for children with asthma and leukotriene receptor antagonists (LTRA) as the second alternative therapy. Adherence to treatment is the most significant component to optimize the benefits of therapy in asthma.
OBJECTIVE: This study aims to investigate the frequency of drug discontinuation due to adverse drug reactions (ADRs) that affect adherence to treatment in children with asthma or asthma and allergic rhinitis using LTRA or ICS as monotherapy.
METHODS: The subjects aged 4-18 years with asthma or asthma and allergic rhinitis and using montelukast or ICS as monotherapy were included in the study. They were evaluated in terms of ADRs affecting adherence to treatment in the first and third months of treatment.
RESULTS: A total of 468 cases, 356 of whom received montelukast monotherapy and 112 of whom received ICS treatment, with a mean age of 9.10 ± 3.08 (4-17) years, were included in the study. Males constituted 65.6% of the total cases (n = 307). In the first month of follow-up of the cases, it was observed that 4.8% (n = 17) of the patients in the montelukast group could not continue the treatment due to ADR. It was determined that the drug discontinuation rate in the montelukast group in the first month was significantly higher than in the ICS group (P = 0.016), and the risk of drug discontinuation due to ADR in the montelukast group was 1.333 (95% CI, 1.26-1.40) times higher.
CONCLUSIONS: As a result, it was observed that the drug was discontinued due to ADR at a higher rate in children with asthma who received montelukast monotherapy compared to those who received ICS monotherapy.

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

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