BACKGROUND: Despite the recommendation of inhaled corticosteroids (ICSs) plus long-acting beta 2-agonist (LABA) and leukotriene receptor antagonist (LTRA) or ICS/LTRA as stepwise approaches in asthmatic children, there is a lack of published systematic review comparing the efficacy and safety of the two therapies in children and adolescents aged 4 to 18 years. This study aimed to compare the safety and efficacy of salmeterol/fluticasone (SFC) vs. montelukast (MON), or combination of montelukast and fluticasone (MFC) in children and adolescents aged 4 to 18 years with bronchial asthma. METHODS: A systematic search was conducted in MEDLINE, EMBASE, the Cochrane Library, China BioMedical Literature Database, Chinese National Knowledge Infrastructure, VIP Database for Chinese Technical Periodical, and Wanfang for randomized controlled trials (RCTs) published from inception to May 24, 2021. Interventions are as follows: SFC vs. MON, or combination of MFC, with no limitation of dosage or duration. Primary and secondary outcome measures were as follows: the primary outcome of interest was the risk of asthma exacerbation. Secondary outcomes included risk of hospitalization, pulmonary function, asthma control level, quality of life, and adverse events (AEs). A random-effects (I2 ≥ 50%) or fixed-effects model (I2 < 50%) was used to calculate pooled effect estimates, comparing the outcomes between the intervention and control groups where feasible. RESULTS: Of the 1006 articles identified, 21 studies met the inclusion criteria with 2643 individuals; two were at low risk of bias. As no primary outcomes were similar after an identical treatment duration in the included studies, meta-analysis could not be performed. However, more studies favored SFC, instead of MON, owing to a lower risk of asthma exacerbation in the SFC group. As for secondary outcome, SFC showed a significant improvement of peak expiratory flow (PEF)%pred after 4 weeks compared with MFC (mean difference [MD]: 5.45; 95% confidence interval [CI]: 1.57-9.34; I2 = 95%; P = 0.006). As for asthma control level, SFC also showed a higher full-controlled level (risk ratio [RR]: 1.51; 95% CI: 1.24-1.85; I2 = 0; P < 0.001) and higher childhood asthma control test score after 4 weeks of treatment (MD: 2.30; 95% CI: 1.39-3.21; I2 = 72%; P < 0.001) compared with MFC. CONCLUSIONS: SFC may be more effective than MFC for the treatment of asthma in children and adolescents, especially in improving asthma control level. However, there is insufficient evidence to make firm conclusive statements on the use of SFC or MON in children and adolescents aged 4 to 18 years with asthma. Further research is needed, particularly a combination of good-quality long-term prospective studies and well-designed RCTs. PROSPERO REGISTRATION NUMBER CRD42019133156.
Acetates ; Administration, Inhalation ; Adolescent ; Adrenal Cortex Hormones/therapeutic use* ; Albuterol/therapeutic use* ; Anti-Asthmatic Agents/therapeutic use* ; Asthma/drug therapy* ; Child ; Cyclopropanes ; Drug Therapy, Combination ; Fluticasone/therapeutic use* ; Humans ; Quinolines ; Salmeterol Xinafoate/therapeutic use* ; Sulfides

BACKGROUNDThe efficacy of montelukast (MONT), a cysteinyl leukotriene receptor antagonist, in nonasthmatic eosinophilic bronchitis (NAEB), especially its influence on cough associated life quality is still indefinite. We evaluated the efficacy of MONT combined with budesonide (BUD) as compared to BUD monotherapy in improving life quality, suppressing airway eosinophilia and cough remission in NAEB.

METHODSA prospective, open-labeled, multicenter, randomized controlled trial was conducted. Patients with NAEB (aged 18-75 years) were randomized to inhaled BUD (200 μg, bid) or BUD plus oral MONT (10 μg, qn) for 4 weeks. Leicester cough questionnaire (LCQ) life quality scores, cough visual analog scale (CVAS) scores, eosinophil differential ratio (Eos), and eosinophil cationic protein (ECP) in induced sputum were monitored and compared.

RESULTSThe control and MONT groups contained 33 and 32 patients, respectively, with similar baseline characteristics. Significant with-in group improvement in CVAS, LCQ scores, Eos, and ECP was observed in both groups during treatment. After 2-week treatment, add-on treatment of MONT was significantly more effective than BUD monotherapy for CVAS decrease and LCQ scores improvement (both P < 0.05). Similar results were seen at 4-week assessment (both P < 0.05). 4-week add-on therapy of MONT also resulted in a higher percentage of patients with normal sputum Eos (<2.5%) and greater decrease of ECP (both P < 0.05).

CONCLUSIONSMONT combined with BUD was demonstrated cooperative effects in improvement of life quality, suppression of eosinophilic inflammation, and cough remission in patients with NAEB.

Acetates ; therapeutic use ; Adolescent ; Adult ; Aged ; Aged, 80 and over ; Bronchitis ; drug therapy ; immunology ; Budesonide ; therapeutic use ; Cough ; drug therapy ; Female ; Humans ; Inflammation ; drug therapy ; Male ; Middle Aged ; Quality of Life ; Quinolines ; therapeutic use ; Young Adult

OBJECTIVETo observe the effect of montelukast treatment on levels of serum leukotriene B4 and urinary leukotriene E4 in infants with bronchiolitis.

METHODSSeventy-five children who were diagnosed with bronchiolitis between June 2014 and December 2014 were randomly assigned into two groups, one with thirty-eight cases as the montelukast treatment group and another thirty-seven cases as the control group. All of the children were given routine medical treatment. The children in the montelukast treatment group were additionally given montelukast daily (4 mg once a day, for 7 days). The serum leukotriene B4 and urinary leukotriene E4 levels were measured using ELISA before and after treatment. The relationship between serum leukotriene B4 and urinary leukotriene E4 levels was analyzed by Peason correlation analysis.

RESULTSAfter 7 days of treatment, the serum leukotriene B4 and urinary leukotriene E4 levels in the montelukast treatment and control groups were significantly reduced compared with before treatment (P<0.05). The montelukast treatment group showed significantly lower serum leukotriene B4 and urinary leukotriene E4 levels than the control group (P<0.05). The remission time of cough, wheezing and lung wheezes and the length of hospital stay in the montelukast treatment group were significantly shortened compared with the control group (P<0.05). There was a positive correlation between serum leukotriene B4 and urinary leukotriene E4 levels (r=0.723, P<0.05).

CONCLUSIONSMontelukast has a reliable clinical curative efficacy for bronchiolitis in infants, possibly by decreasing serum leukotriene D4 and urinary leukotriene E4 levels.

Acetates ; therapeutic use ; Bronchiolitis ; drug therapy ; metabolism ; Humans ; Infant ; Leukotriene B4 ; blood ; Leukotriene E4 ; urine ; Quinolines ; therapeutic use

OBJECTIVE: To investigate the clinical efficacy of montelukast plus budesonide nasal spray and desloratadine citrate disodium tablets on moderate and severe persistent allergic rhinitis. METHOD: Senenty patients with moderate and severe persistent allergic rhinitis were devided randomly study group (n = 35) and control group (n = 35). The study group were treated with montelukast sodium tablets combined with budesonide nasal spray and desloratadine citrate disodium tablets for 4 weeks, the control group received budesonide nasal spray and desloratadine citrate disodium tablets for 4 weeks. Comparing visual analogue scale (VAS) scores of nasal symptoms, rhino conjunctivitis quality of life questionnaire (RQLQ) scores and total effective rate in two groups at baseline and after treatment. RESULT: (1) VAS scores of nasal symptoms: the difference of total nasal symptoms VAS scores or single nasal symptom VAS scores from both groups at 2 weeks and 4 weeks after treatment were statistically significant (P < 0.05); (2) RQLQ scores: the difference of RQLQ scores of 2 group's at baseline and 4 weeks after treatment were statistically significant, the difference of RQLQ scores about nasal symptoms in two groups at 4 weeks after treatment were statistically significant (P < 0.05); (3) The total effective rate was 94.29% in study group but 80.00% in control group, the differences were statistically significant (P < 0.05). CONCLUSION Montelukast plus budesonide nasal spray and desloratadine citrate disodium tablets can work together better on relieving clinical syptoms quickly and promoting the life quality of patients with moderate and severe persistent allergic rhinitis.
Acetates ; administration & dosage ; therapeutic use ; Budesonide ; administration & dosage ; therapeutic use ; Humans ; Loratadine ; administration & dosage ; analogs & derivatives ; therapeutic use ; Nasal Sprays ; Quinolines ; administration & dosage ; therapeutic use ; Rhinitis, Allergic, Perennial ; drug therapy ; Surveys and Questionnaires

Allergic rhinitis (AR) clinically expressed by sneezing, rhinorrhea, nasal itching and congestion is an allergen-driven mucosal inflammatory disease which is modulated by immunoglobulin E. Epidemiological studies have indicated that prevalence of AR continues to increase, and it has been a worldwide health problem that places a significant healthcare burden on individuals and society. Given the evolving understanding of the process by which an allergen is recognized and the roles of mediators which account for AR progress, the pathogenesis of AR has become clearer. Current studies have demonstrated local allergic rhinitis (LAR) that patients with both sug- gestive symptoms of AR and a negative diagnostic test for atopy may have local allergic inflammation is a prevalent entity in patients evaluated with rhinitis, but further research remains needed. Management of AR includes aller- gen avoidance, pharmacological treatment and allergen-specific immunotherapy. Recently montelukast has exhibited previously undocumented anti-inflammatory properties, leukotriene receptor antagonists therefore may serve a more important role in the treatment of AR. Not only has immunotherapy proved its efficacy, but also been able to alter disease course and thereby mitigate progression to asthma. Thus immunotherapy can be initiated while receiving pharmacotherapy, especially in children with AR. As clinical guidelines, the ARIA (Allergic Rhinitis and its Impact on Asthma) provides basic principles of effective treatment of AR. Besides, choosing an appropriate treatment strategy should be based on the severity and chronicity of patient's symptom. The aim of this review was to provide an update mainly on the pathophysiology, epidemiology, and management of AR.
Acetates ; therapeutic use ; Allergens ; Anti-Inflammatory Agents ; therapeutic use ; Asthma ; prevention & control ; Child ; Humans ; Hypersensitivity, Immediate ; diagnosis ; physiopathology ; Immunoglobulin E ; immunology ; Immunotherapy ; Inflammation ; physiopathology ; Leukotriene Antagonists ; therapeutic use ; Prevalence ; Quinolines ; therapeutic use ; Rhinitis, Allergic ; diagnosis ; immunology ; physiopathology

Acetates ; therapeutic use ; Diagnosis, Differential ; Female ; Follow-Up Studies ; Humans ; Hyperplasia ; Infant ; Lung ; diagnostic imaging ; pathology ; physiopathology ; Lung Diseases, Interstitial ; diagnosis ; drug therapy ; physiopathology ; Methylprednisolone ; therapeutic use ; Neuroendocrine Cells ; pathology ; Quinolines ; therapeutic use ; Tomography, X-Ray Computed

Acetates ; administration & dosage ; therapeutic use ; Asthma ; drug therapy ; etiology ; metabolism ; Bronchiolitis, Viral ; drug therapy ; Cysteine ; metabolism ; Humans ; Infant ; Infant, Newborn ; Leukotriene Antagonists ; administration & dosage ; therapeutic use ; Leukotrienes ; biosynthesis ; Nasopharynx ; secretion ; Quinolines ; administration & dosage ; therapeutic use ; Respiratory Syncytial Virus Infections ; drug therapy ; metabolism ; virology ; Risk Factors

BACKGROUNDEvidence has demonstrated that the distal lung, which includes airways of < 2 mm in diameter and lung parenchyma, constitutes an important component of asthma pathology. Cysteinyl leukotrienes (CysLTs) are potent proinflammatory mediators and bronchoconstrictors involved in the asthmatic process. Guidelines recommend the leukotriene-modifying agents for asthma treatment. We hypothesized that a leukotriene receptor antagonist with an inhaled corticosteroid (ICS) and long-acting β2 agonist (LABA) combination would improve small airways function in moderate-to- severe asthmatics evaluated by physiological tests and high-resolution computed tomography (HRCT) analysis. This study was performed at a tertiary university hospital in Beijing.

METHODSThis was a randomized, double-blind, parallel study performed in 38 patients with moderate-to-severe asthma treated with salmeterol/futicasone (SFC) plus montelukast (SFC+M) or SFC plus placebo over 24 weeks. Small airway function was assessed by physiological studies and HRCT image analysis.

RESULTSMontelukast significantly improved air trapping as expressed by the residual volume (RV)/total lung capacity (TLC). Over 24 weeks of treatment, RV/TLC was improved by (15.41 ± 6.67)% in patients receiving SFC+M while RV/TLC was decreased by (8.57 ± 10.26)% in patients receiving SFC alone, the difference between the two groups was significant (P = 0.02). There was a trend towards a significant difference in forced expiratory volume in the first second (FEV1)/forced vital capacity (FVC) in the SFC+M group compared to that in the SFC group ((17.87 ± 8.17)% vs. (12.28 ± 9.20)%, P = 0.056). There was no significant change in percentage wall area (WA%) after 24 weeks of add-on treatment with montelukast. Patients receiving SFC+M showed significant improvement in the ratio of CT-determined values at full expiration to those at full inspiration (E/I ratio) (0.894 ± 0.005 vs. 0.871 ± 0.003, P = 0.002).

CONCLUSIONWe have shown, using lung function tests and HRCT image technique, that add-on therapy with montelukast improves distal lung function reflected by air trapping, but not airway wall thickness in moderate-to-severe asthma.

Acetates ; therapeutic use ; Adult ; Airway Remodeling ; drug effects ; Anti-Asthmatic Agents ; therapeutic use ; Asthma ; drug therapy ; physiopathology ; Double-Blind Method ; Female ; Forced Expiratory Volume ; drug effects ; Humans ; Leukotriene Antagonists ; therapeutic use ; Male ; Middle Aged ; Pilot Projects ; Quinolines ; therapeutic use ; Total Lung Capacity ; drug effects

OBJECTIVETo investigate the role of transforming growth factor beta(1) (TGF-beta(1)) in the pathogenesis of bronchial asthma in children and assess the effect of montelukast sodium (leukotriene receptor antagonist) on TGF-beta(1) levels.

METHODA 12 weeks single-blind, placebo-controlled trail was conducted in 60 children with mild persistent asthma [aged 5 - 14 years, mean (7.10 ± 0.27) years]. Patients were randomly assigned to receive 5 mg montelukast sodium or placebo for 12 weeks. And 30 healthy control children [aged 5 - 14 years, mean (7.60 ± 0.25) years] were also recruited in this study from Sep. 2009 to Sep. 2010. Clinical effects and pulmonary function were evaluated before and 12 weeks after treatment. The mRNA expression of TGF-beta(1) in the peripheral blood mononuclear cells was detected by using RT-PCR with beta-actin as internal control. The percentage of the different subpopulations of Foxp(3)(+)CD4(+) T cells was assayed by 4-color flow cytometric analysis system and the levels of TGF-beta(1) in plasma by ELISA.

RESULT(1) The basic characteristics between asthma group and healthy group had no significant difference. (2) Following treatment, there was significant increase in pulmonary function in asthmatic children. The effect in the group of montelukast sodium was superior to that of placebo group (P < 0.05). (3) The serum expression of TGF-beta(1) in asthmatic children was lower than that in control group (q = 20.01, P < 0.01); after 12 weeks of treatment, the mean expression of TGF-beta(1) was (20.03 ± 1.14) ng/L for montelukast sodium group and (12.10 ± 3.91) ng/L for placebo group (P < 0.05). (4) The mRNA expression of TGF-beta(1) in asthma children was lower than that in control group (0.31 ± 0.07 vs 0.61 ± 0.2, q = 8.97, P < 0.05); after 12 weeks of treatment, the mean expression of TGF-beta(1) was (0.46 ± 0.13) for montelukast sodium group and (0.32 ± 0.04) for placebo group (q = 8.25, P < 0.05). (5) It was shown that the total Foxp(3)(+)CD(4)(+) cell percentage was higher in asthmatic children than those of control group (8.30% ± 1.30% vs 6.05% ± 1.80%); the proportion of the three subpopulation was different between groups: CD(45) RA(+)Foxp(3)(lo) was higher in asthmatic group (4.60% ± 1.04% vs 3.27% ± 1.03%) and CD(45) RA(-)Foxp(3)(hi) was lower (0.75% ± 0.13% vs 0.93% ± 0.26%); while CD(45) RA(-)Foxp(3)(lo) had no significant difference among groups (2.40% ± 0.83%, 1.61% ± 1.10%). After 12 weeks of treatment, the percentage of CD(45) RA(-)Foxp(3)(hi) was increased in montelukast sodium group compared with placebo group (1.16% ± 0.24% vs 0.89% ± 0.22%). (6) Spearman correlation analysis revealed that TGF-beta(1) levels had no correlation with the levels of pulmonary function.

CONCLUSIONThe protein and mRNA expression level of TGF-beta(1) was low in those asthmatic children. Insufficient secretion of TGF-beta(1) and the defective ability of activated regulatory T cells (CD(45) RA(-)Foxp(3)(hi)) in Foxp(3)(+)CD(4)(+) Treg cells might play an important role in pathogenesis of asthma. Up-regulation of the expression of TGF-beta(1) and induction of the expression of CD(45) RA(-)Foxp(3)(hi) in Foxp(3)(+)CD(4)(+)Treg cells by montelukast sodium may be one of the immunomodulatory mechanisms in asthma.

Acetates ; therapeutic use ; Adolescent ; Anti-Asthmatic Agents ; therapeutic use ; Asthma ; blood ; drug therapy ; immunology ; Child ; Child, Preschool ; Female ; Humans ; Male ; Quinolines ; therapeutic use ; Single-Blind Method ; T-Lymphocytes, Regulatory ; immunology ; Transforming Growth Factor beta1 ; blood

Acetates ; therapeutic use ; Acute Disease ; Anti-Asthmatic Agents ; therapeutic use ; Asthma ; prevention & control ; Child ; Child, Preschool ; Female ; Humans ; Leukotriene Antagonists ; therapeutic use ; Male ; Quinolines ; therapeutic use