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

OBJECTIVE: To explore the clinical symptoms, lung function and airway inflammation phenotype characteristics of asthmatic patients who are sensitive to cold stimulation. METHODS: Eighty patients with newly diagnosed bronchial asthma or with mild to moderate acute exacerbation of previously diagnosed bronchial asthma but without regular treatment were selected. According to whether cold air stimulation could induce respiratory symptoms such as cough and wheeze, the patients were divided into cold-insensitive group (45 cases) and cold-sensitive group (35 cases). All the patients were treated with inhaled corticosteroid (ICS), long-acting β2 receptor agonist (LABA; salmeterol xinafoate and fluticasone propionate powder for inhalation, 50 μg/250 μg, twice daily) and montelukast sodium tablets (10 mg, once daily); short-acting β2 receptor agonist (SABA) and/or systemic glucocorticoid (prednisone acetate tablets, 10 mg, once daily; or injection of methylprednisolone sodium succinate, 40 mg) were given if necessary. Asthma Control Test (ACT) score before treatment and at 3 months of treatment was used to assess the clinical symptoms such as cough and wheeze; spirometry was performed to determine lung function impairment and recovery. Blood and induced sputum cell counts were examined to determine the characteristics of airway inflammation. RESULTS: The two groups were comparable for age, gender, BMI, proportion of smokers and allergic rhinitis before treatment. The cold-sensitive patients experienced significantly more frequent acute exacerbations than the cold-insensitive patient within 1 year before the visit ( < 0.05), but the use of SABA and glucocorticoid for symptom control during the treatment did not differ significantly between the two groups ( > 0.05). The ACT scores of the cold-sensitive group were significantly lower than those of the cold-insensitive group both before and after the treatment ( < 0.01). Compared with the cold-insensitive patients, the cold-sensitive patients had more obvious impairment of FEV1/FVC% and FEV1%pred before treatment ( < 0.01), and also showed poorer recovery after treatment ( < 0.05). The percentages of eosinophils in blood and induced sputum samples did not differ significantly between the two groups either before and after the treatment, but the percentage of neutrophils was significantly higher in the cold-sensitive group ( < 0.01). In the induced sputum samples collected before treatment, the cell populations consisted mainly of eosinophilic subtype (60%) and neutrophilic subtype (20%) in the cold-insensitive group; in the cold-sensitive patients, the sputum neutrophilic subtype cells increased significantly to 42.86% (=0.03) and the eosinophilic subtype cells were lowered to 31.43% (=0.01). CONCLUSIONS The cold-sensitive asthmatic patients experience frequent recurrent and/or aggravated symptoms and have obvious lung function impairment. Different from that in patients with classic asthma, the airway inflammatory phenotype in these patients is characterized by the domination by neutrophilic subtype.
Administration, Inhalation ; Adrenal Cortex Hormones ; therapeutic use ; Anti-Asthmatic Agents ; therapeutic use ; Asthma ; drug therapy ; physiopathology ; Cold Temperature ; adverse effects ; Cryopyrin-Associated Periodic Syndromes ; physiopathology ; Disease Progression ; Eosinophils ; Humans ; Phenotype ; Recurrence ; Sputum ; cytology

OBJECTIVE: To explore the intervention measures to maintain clinical control in children with asthma in the remission stage when concomitant with acute upper respiratory infection (AURI). METHODS: A total of 100 asthmatic children who had achieved clinical control were randomly divided into observation group and control group. The two groups were both treated with a combination of inhaled corticosteroids and long-acting β2 receptor agonist (ICS/LABA) at the lowest dose every night. Conventional therapies were used for the two groups when suffering from AURI. In addition to conventional therapies, the observation group was given early short-term upgrade therapy, i.e., on the basis of maintenance therapy, the same amount of ICS/LABA complex preparation was inhaled every morning, which lasted for 7-10 days. Both groups were treated following asthma guidelines according to the severity of the disease at the time of acute attacks. The control rate of asthma, severity of acute attacks, changes in pulmonary function indices, and occurrence of adverse events were evaluated after 3, 6, 9, and 12 months of treatment. RESULTS: At each time point of follow-up, the rate of asthma control in the observation group was significantly higher than that in the control group (90% vs 80%; P<0.05). The severity of acute attacks in the observation group was significantly lower than that in the control group at all follow-up time points (P<0.05). Compared with the control group, the observation group had significantly improved pulmonary function indices of large and small airways (P<0.05) and significantly reduced mean amount of inhaled glucocorticoids and impact on family life (P<0.01). CONCLUSIONS Early short-term upgrade therapy for children with asthma in the remission stage when concomitant with AURI can prevent acute attacks of asthma, raise the rate of asthma control and improve pulmonary function.
Administration, Inhalation ; Adrenal Cortex Hormones ; Adrenergic beta-Agonists ; Anti-Asthmatic Agents ; Asthma ; Child ; Drug Therapy, Combination ; Humans

OBJECTIVE: To study the incidence of acute attacks of asthma and dynamic changes in laboratory markers in children with well-controlled asthma after the withdrawal of low-dose inhaled corticosteroids (ICS), and to provide a basis for optimal long-term control regimens for children with asthma. METHODS: A total of 63 children with well-controlled asthma were enrolled as subjects. According to their parents' wishes, they were continuously administered with ICS (ICS treatment group; n=35) and without ICS (ICS withdrawal group; n=28). They were followed up for 18 months. The incidence of acute attacks of asthma was evaluated, dynamic monitoring was performed for pulmonary function and fractional exhaled nitric oxide (FeNO), and childhood asthma control test (C-ACT) was performed every three months. RESULTS: At 3, 6, 9, and 12 months of follow-up, there was no significant difference in FeNO between the ICS treatment and withdrawal groups (P>0.05). However, at 15 and 18 months of follow-up, the withdrawal group had a significantly higher level of FeNO than the ICS treatment group (P<0.05). There was no significant difference in the C-ACT score between the two groups at all time points of follow-up (P>0.05). At 3, 6, 9, and 12 months of follow-up, there were no significant differences between the two groups in the percentage of forced expiratory volume in 1 second, the ratio of forced expiratory volume in 1 second to forced vital capacity, percentage of predicted maximum mid-expiratory flow (MMEF%), and maximal expiratory flow at 50% of vital capacity (MEF50) (P>0.05), while at 15 and 18 months of follow-up, the ICS treatment group had significantly higher MMEF% and MEF50 than the withdrawal group (P<0.05). During follow-up, 3 children (9%) in the ICS treatment group and 8 (29%) in the withdrawal group experienced acute attacks of asthma (P=0.0495). CONCLUSIONS Continuous inhalation of low-dose ICS can maintain the stability of pulmonary function and reduce acute attacks of asthma in children with well-controlled asthma.
Administration, Inhalation ; Adrenal Cortex Hormones ; Anti-Asthmatic Agents ; Asthma ; Child ; Follow-Up Studies ; Forced Expiratory Volume ; Humans ; Nitric Oxide

Benralizumab is a monoclonal antibody that targets interleukin-5 receptor α to deplete blood eosinophils and improve the clinical outcomes of allergic asthma. We conducted a meta-analysis to evaluate the safety and efficacy of different doses of benralizumab in patients with eosinophilic asthma. All randomized controlled trials involving benralizumab treatment for patients with eosinophilic asthma, which were searched in PubMed, Embase, and the Cochrane Library published until January 2017, as well as the rate of asthmatic exacerbation, pulmonary functionality, asthma control, quality of life scores, and adverse events were included. Randomized-effect models were used in the meta-analysis to calculate the pooled mean difference, relative risks, and 95% confidence intervals. Five studies involving 1951 patients were identified. Compared with the placebo, benralizumab treatment demonstrated significant improvements in the forced expiratory volume in 1 s (FEV1), Asthma Quality of Life Questionnaire scores, decreased asthmatic exacerbation and Asthma Control Questionnaire-6 (ACQ-6) scores. Benralizumab treatment was also not associated with increased adverse events. These findings indicated that benralizumab can be safely used to improve FEV1, enhance patient symptom control and quality of life, and reduce the risk of exacerbations and ACQ-6 scores in patients with eosinophilic asthma. Furthermore, our meta-analysis showed that benralizumab with 30 mg (every eight weeks) dosage can improve the health-related quality of life and appear to be more effective than 30 mg (every four weeks) dosage. Overall, data indicated that the optimal dosing regimen for benralizumab was possibly 30 mg (every eight weeks).
Adult ; Anti-Asthmatic Agents ; administration & dosage ; therapeutic use ; Antibodies, Monoclonal, Humanized ; administration & dosage ; therapeutic use ; Asthma ; drug therapy ; Disease Progression ; Dose-Response Relationship, Drug ; Eosinophils ; Forced Expiratory Volume ; Humans ; Leukocyte Count ; Quality of Life ; Randomized Controlled Trials as Topic

BACKGROUND/AIMS: Asthma is characterized by airway hyperresponsiveness, inflammation, and remodeling. Peroxisome proliferator-activated receptors have been reported to regulate inflammatory responses in many cells. In this study, we examined the effects of intranasal rosiglitazone on airway remodeling in a chronic asthma model. METHODS: We developed a mouse model of airway remodeling, including smooth muscle thickening, in which ovalbumin (OVA)-sensitized mice were repeatedly exposed to intranasal OVA administration twice per week for 3 months. Mice were treated intranasally with rosiglitazone with or without an antagonist during OVA challenge. We determined airway inflammation and the degree of airway remodeling by smooth muscle actin area and collagen deposition. RESULTS: Mice chronically exposed to OVA developed sustained eosinophilic airway inflammation, compared with control mice. Additionally, the mice developed features of airway remodeling, including thickening of the peribronchial smooth muscle layer. Administration of rosiglitazone intranasally inhibited the eosinophilic inflammation significantly, and, importantly, airway smooth muscle remodeling in mice chronically exposed to OVA. Expression of Toll-like receptor (TLR)-4 and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappaB) was increased in the OVA group and decreased in the rosiglitazone group. Co-treatment with GW9660 (a rosiglitazone antagonist) and rosiglitazone increased the expression of TLR-4 and NF-kappaB. CONCLUSIONS: These results suggest that intranasal administration of rosiglitazone can prevent not only air way inf lammation but also air way remodeling associated with chronic allergen challenge. This beneficial effect is mediated by inhibition of TLR-4 and NF-kappaB pathways.
Actins/metabolism ; Administration, Inhalation ; Airway Remodeling/*drug effects ; Animals ; Anti-Asthmatic Agents/*administration & dosage ; Asthma/chemically induced/*drug therapy/metabolism/physiopathology ; Chronic Disease ; Collagen/metabolism ; Disease Models, Animal ; Female ; Lung/*drug effects/metabolism/physiopathology ; Mice, Inbred BALB C ; NF-kappa B/metabolism ; Ovalbumin ; PPAR gamma/agonists/metabolism ; Pneumonia/chemically induced/physiopathology ; Pulmonary Eosinophilia/chemically induced/prevention & control ; Signal Transduction/drug effects ; Thiazolidinediones/*administration & dosage ; Toll-Like Receptor 4/metabolism

OBJECTIVETo evaluate the therapeutic effect and safety of montelukast sodium combined with budesonide in children with cough variant asthma.

METHODSThe databases CNKI, Wanfang Data, VIP, PubMed, EMbase, and BioMed Central were searched for randomized controlled trials (RCTs) of montelukast sodium combined with budesonide in the treatment of children with cough variant asthma. Data extraction and quality assessment were performed for RCTs which met the inclusion criteria, and RevMan 5.3 software was used to perform quality assessment of the articles included and Meta analysis.

RESULTSA total of 11 RCTs involving 1 097 patients were included. The results of the Meta analysis showed that compared with the control group (inhalation of budesonide alone), the observation group (inhalation of montelukast sodium combined with budesonide) had significantly higher overall response rate and more improved pulmonary function parameters including forced expiratory volume in the first second, percentage of forced expiratory volume in the first second, and peak expiratory flow, as well as significantly lower recurrence rate (P<0.01). The incidence of adverse events showed no significant difference between the two groups.

CONCLUSIONSInhalation of montelukast sodium combined with budesonide has a significant effect in children with cough variant asthma and does not increase the incidence of adverse events.

Acetates ; administration & dosage ; adverse effects ; Anti-Asthmatic Agents ; administration & dosage ; adverse effects ; Asthma ; drug therapy ; Bronchodilator Agents ; administration & dosage ; adverse effects ; Budesonide ; administration & dosage ; adverse effects ; Child ; Cough ; drug therapy ; Drug Therapy, Combination ; Humans ; Quinolines ; administration & dosage ; adverse effects

Administration, Inhalation ; Adrenal Cortex Hormones ; therapeutic use ; Adrenergic beta-Agonists ; therapeutic use ; Anti-Asthmatic Agents ; therapeutic use ; Antibodies, Monoclonal, Humanized ; therapeutic use ; Asthma ; prevention & control ; therapy ; Guideline Adherence ; Humans ; Molecular Targeted Therapy ; Muscarinic Antagonists ; therapeutic use ; Omalizumab ; therapeutic use ; Practice Guidelines as Topic ; Primary Prevention ; Quality Improvement ; Sublingual Immunotherapy

The geriatric population is increasing, and asthma severity increases with age. We determined the predictors of asthma control, exacerbation, and the factors that affect asthma-specific quality of life (A-QOL) in elderly asthmatic patients. This was a prospective, multicenter, real-life study for 6 months with stepwise pharmacologic treatment based on the Global Initiative for Asthma (GINA) guideline. A total of 296 asthmatic patients aged > or = 60 yr were recruited from 5 university centers in Korea. The improved-asthma control group was defined as the group of patients who maintained well-controlled or improved disease and the not-improved asthma control group was defined as the remaining patients. Fewer number of medications for comorbidities (2.8 +/- 3.3 in the improved vs. 4.5 +/- 4.4 in the control) and higher physical functioning (PF) scale (89.8 +/- 14.2 in the improved vs. 82.0 +/- 16.4 in the control) were significant predictors in the improved-asthma control group (OR = 0.863, P = 0.004 and OR = 1.028, P = 0.018, respectively). An asthma control test (ACT) score of < or = 19 at baseline was a significant predictor of asthma exacerbation (OR = 3.938, P = 0.048). Asthma duration (F = 5.656, P = 0.018), ACT score (F = 12.237, P = 0.001) at baseline, and the presence of asthma exacerbation (F = 5.565, P = 0.019) were significant determinants of changes in A-QOL. The number of medications for comorbidities and performance status determined by the PF scale may be important parameters for assessing asthma control in elderly asthmatic patients.
Aged ; Aged, 80 and over ; Anti-Asthmatic Agents/*administration & dosage ; Asthma/*diagnosis/epidemiology/*therapy ; Critical Pathways/statistics & numerical data ; Dose-Response Relationship, Drug ; Female ; Geriatric Assessment/*methods/statistics & numerical data ; Humans ; Male ; Middle Aged ; Outcome Assessment (Health Care)/*methods ; *Quality of Life ; Reproducibility of Results ; Republic of Korea/epidemiology ; Sensitivity and Specificity ; Treatment Outcome

OBJECTIVETo observe the efficacy and safety of Danlong Oral Liquid (DOL) combined Western medicine (WM) in treating mild-to-moderate bronchial asthma patients (heat wheezing syndrome) at acute onset.

METHODSTotally 480 mild-to-moderate bronchial asthma patients (heat wheezing syndrome) at acute onset were randomly assigned to two groups in the ratio 3:1, the treatment group (360 cases) and the control group (120 cases). All patients received basic WM treatment. Patients in the treatment group took DOL, 10 mL each time, 3 times per day for 7 days in total, while those in the control group took Kechuanning Oral Liquid (KOL) , 10 mL each time, 3 times per day for 7 days in total. Efficacy for asthma symptoms, lung functions and scores of TCM syndrome and/or main symptoms were evaluated.

RESULTSThe percentage of clinical control and significant effectiveness of asthma symptoms in the treatment group was significantly higher than that of the control group (77.36% vs 56.07%, P < 0.01). The percentage of clinical control and significant effectiveness of lung functions in the treatment group was significantly higher than that of the control group (74.28% vs 50.00%, P < 0.01). The anterior-posterior difference in scores of TCM syndrome was significantly superior in the treatment group than in the control group (-11.26 ± 4.70 vs -9.21 ± 5.09, P < 0.01). The anterior-posterior difference in scores of main symptoms was significantly better in the treatment group than in the control group (-6.58 ± 3.08 vs -5.16 ± 3.45, P < 0.01). The incidence of adverse reactions was significantly lower in the treatment group than in the control group [1.73% (6/346 cases) vs 10.17% (12/118 cases) , P < 0.05].

CONCLUSIONDOL combined WM was superior to KOL in treating mild-to-moderate bronchial asthma patients (heat wheezing syndrome) at acute onset.

Anti-Asthmatic Agents ; administration & dosage ; therapeutic use ; Asthma ; drug therapy ; Biomedical Research ; Drug Therapy, Combination ; methods ; Drugs, Chinese Herbal ; administration & dosage ; therapeutic use ; Hot Temperature ; Humans ; Lung ; Medicine, Chinese Traditional ; Phytotherapy ; Respiratory Sounds ; Syndrome