OBJECTIVETo investigate the effects of inhaled short-acting bronchodilators on diaphragm function and neural respiratory drive in patients with chronic obstructive pulmonary disease (COPD) during maximal isocapnic ventilation (MIV).

METHODSForty-seven patient with moderate to severe COPD were randomized into 4 groups: placebo group (n=12), salbutamol group (n=13), ipratropium group (n=10), and combined group (salbutamol and ipratropium, n=12). Each subject received an initial MIV for 3 min at baseline and inhaled placebo (400 µg), salbutamol (400 µg), ipratropium (80 µg), or both salbutamol and ipratropium, followed 30 min later by another 3 min of MIV. The parameters of diaphragm function and neural respiratory drive were monitored continuously and calculated during MIV.

RESULTSDuring the initial MIV, all the patients experienced a linear increase in root mean square (RMS) of diaphragm electromyogram with a gradual decrease in transdiaphragmatic pressure (Pdi), minute ventilation (VE), and VE/RMS, and these parameters all improved significantly after inhalation of the bronchodilators. Compared with the placebo group at the same time point, the 3 bronchodilator-treated groups showed significantly decreased RMS and Borg score and increased Pdi, VE and VE/RMS; VE/RMS was the highest in the combined treatment group (P<0.05). The Delta Borg was significantly correlated with Delta Pdi, Delta VE, Delta RMS, and Delta VE/RMS (P<0.05).

CONCLUSIONSIn COPD patients, inhaled short-acting bronchodilators can alleviate diaphragm fatigue during MIV, increase lung ventilation, reduce neural respiratory drive, and improve neuro-ventilatory coupling to relieve dyspnoea, and the combination of β-2 agonists and anti-muscarinic antagonists produces a stronger efficacy.

Administration, Inhalation ; Albuterol ; therapeutic use ; Bronchodilator Agents ; therapeutic use ; Diaphragm ; drug effects ; Humans ; Ipratropium ; therapeutic use ; Pulmonary Disease, Chronic Obstructive ; drug therapy ; Respiration

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

Adolescent ; Adult ; Aged ; Albuterol ; pharmacology ; therapeutic use ; Asthma ; drug therapy ; Child ; Female ; Heart Rate ; drug effects ; Humans ; Male ; Middle Aged ; Terbutaline ; pharmacology ; therapeutic use

Adolescent ; Adrenergic beta-Agonists ; therapeutic use ; Albuterol ; analogs & derivatives ; therapeutic use ; Asthma ; drug therapy ; physiopathology ; Child ; Child, Preschool ; Female ; Forced Expiratory Volume ; drug effects ; Humans ; Male ; Salmeterol Xinafoate

OBJECTIVETo evaluate the efficacy of 3 commonly used protocols for management of acute exacerbation of asthma in children.

METHODSTotally 113 asthmatic children were randomized into 3 groups. In group A (53 cases), the children were treated with inhalation of nebulized budesonide suspension plus salbutamol and ipratropium bromide twice daily for 5 days; in group B (41 cases), budesonide plus salbutamol and ipratropium aerosol was administered, and in group C (29 cases), dexathmisone plus aminophylline injection was given once daily for 5 days. All the children received basic treatment with fluid infusion, antibiotics or/and anti-virus medications.

RESULTSThe children in both groups A and C showed effectively controlled asthma attack, with significant differences in the therapeutic effects (P>0.05). In contrast, only a few children showed improvement in group B, suggesting the ineffectiveness of the treatment.

CONCLUSIONNebulized medicine is one of the best means for management of acute asthma exacerbation in children, and inhalation of budesonide suspension plus salbutamol and ipratropium bromide can effectively relieve the asthmatic symptoms in these children with good compliance and convenient administration.

Acute Disease ; Adolescent ; Aerosols ; Albuterol ; administration & dosage ; therapeutic use ; Asthma ; drug therapy ; Bronchodilator Agents ; administration & dosage ; therapeutic use ; Budesonide ; administration & dosage ; therapeutic use ; Child ; Child, Preschool ; Drug Therapy, Combination ; Female ; Humans ; Infant ; Ipratropium ; administration & dosage ; therapeutic use ; Male ; Treatment Outcome

BACKGROUNDAcute exacerbation of chronic obstructive pulmonary disease (AECOPD) is a common condition, which affects not only the quality of life of patients but also their prognosis. The purpose of this study was to explore the effects of an inhaled salbutamol sulfate solution and an inhalation suspension of the glucocorticoid budesonide that were atomized with heliox to treat patients with AECOPD.

METHODSTwenty-three patients with AECOPD were divided into a treatment group (He/O2 = 70%/30%) and a control group (N2/O2 = 70%/30%). The salbutamol sulfate and budesonide were administered by inhalation twice a day for 7 days. Vital signs, arterial blood gas levels, pulmonary function and the levels of serum myostatin (sMSTN) were measured and lung vibration imaging was performed.

RESULTSWe found that the PaO2 and PaCO2 values were not significantly different between the two groups at the various time points (P > 0.05). There were also no significant differences in any of the parameters of pulmonary function between the two groups. However, after baseline correction, the increase rate of the forced expiratory volume in one second (FEV1), the forced vital capacity (FVC), and the maximum minute ventilation (MVV) appeared to be significantly increased at some time points compared with the baseline (before treatment) in both groups (P < 0.05). Although the values of quantitative lung distribution (QLD) for different regions and the levels of sMSTN were slightly different between the two groups, the repeated measures analysis of variance (ANOVA) revealed that there were no significant differences between the two groups or within any group (P > 0.05).

CONCLUSIONAlthough the use of heliox as a driving gas can improve symptoms and benefit patients with AECOPD, the heliox treatment group did not have significant differences in arterial blood gases, lung function, lung vibration response imaging or the levels of sMSTN compared with the control group. (Chinese Clinical Trial Register Center ChiCTRTRC-00000273).

Administration, Inhalation ; Aged ; Albuterol ; administration & dosage ; therapeutic use ; Budesonide ; administration & dosage ; therapeutic use ; Drug Interactions ; Female ; Helium ; administration & dosage ; therapeutic use ; Humans ; Male ; Middle Aged ; Oxygen ; administration & dosage ; therapeutic use ; Prospective Studies ; Pulmonary Disease, Chronic Obstructive ; drug therapy

OBJECTIVETo compare tulobuterol patch and oral salbutamol sulfate in terms of efficacy and safety in children with mild or moderate acute attack of bronchial asthma.

METHODSA total of 92 children with mild and moderate acute asthmatic attack were randomly divided into salbutamol group (n=46) and tulobuterol group (n=46). Both groups received routine treatment with antihistamine, selective leukotriene receptor antagonist and glucocorticoid. In addition, the salbutamol group was given slow-release capsules of salbutamol sulfate, and the tulobuterol group was treated with tulobuterol patch. The two groups were compared with respect to symptom scores of cough, wheeze, respiratory rate, wheezing sound, three depression sign and peak expiratory flow, as well as adverse events.

RESULTSAs the treatment proceeded, symptom scores decreased in both groups; on the third day of treatment, all symptom scores except cough score showed a significant decrease in both groups (P<0.05), but the tulobuterol group had significantly lower symptom scores than the salbutamol group (P<0.05). On the fourteenth day of treatment, both groups had a significant decrease in cough score (P<0.05), but the tulobuterol group had a significantly lower cough score than the salbutamol group (P<0.05). One child developed hand trembling in the salbutamol group, while no adverse event occurred in the tulobuterol group.

CONCLUSIONSCompared with oral salbutamol sulfate, tulobuterol patch has a better therapeutic efficacy and a higher safety in children with mild or moderate acute asthmatic attack.

Acute Disease ; Administration, Oral ; Adrenergic beta-2 Receptor Agonists ; therapeutic use ; Albuterol ; administration & dosage ; adverse effects ; therapeutic use ; Asthma ; drug therapy ; Female ; Humans ; Terbutaline ; administration & dosage ; adverse effects ; analogs & derivatives ; therapeutic use

Adrenergic beta-Agonists ; therapeutic use ; Aged ; Albuterol ; analogs & derivatives ; therapeutic use ; Bronchi ; drug effects ; physiopathology ; Bronchodilator Agents ; therapeutic use ; Coal Mining ; Humans ; Male ; Middle Aged ; Pneumoconiosis ; drug therapy ; physiopathology ; Respiratory Function Tests ; Salmeterol Xinafoate ; Treatment Outcome

BACKGROUNDThe interleukin (IL)-32/tumor necrosis factor (TNF) a pathway is supposed to play a key role in the amplification of the immune response in chronic obstructive pulmonary disease (COPD) inflammation. Inhaled corticosteroids (ICS) in combination with long-acting β2-agonists (LABA) have shown airway anti-inflammatory effects in recent studies, but the mechanism is still uncertain.

METHODSPatients were treated in a randomized, open-labeled, parallel group clinical trial with either a combination of salmeterol xinafoate/fluticasone propionate (SF; Seretide, GlaxoSmithKline) Diskus (50/500 µg twice daily) or ipratropium bromide/salbutamol (IS; Combivent, Boehringer Ingelheim) MDI (42 µg/240 µg quartic daily) for 12 weeks. At the start and the end of treatment, induced sputum was collected and the concentration of IL-32 and TNF-α, the number of neutrophils and eosinophils were measured.

RESULTSFollowing 12 weeks of treatment, a statistically significant fall from baseline in the concentration of TNF-α in sputum (P = 0.004) was seen after treatment with SF but not with IS. However, neither treatment had significant effects on the concentration of IL-32 in sputum. There was a decrease from baseline in the number of sputum neutrophils with SF that approached statistical significance (P = 0.028) but not with IS, while the number of sputum eosinophils did not change significantly from baseline in either treatment group. There was a statistically significant decline from baseline in the quality of life as assessed by the St George's respiratory questionnaire in both the SF (P = 0.004) and IS (P = 0.030) treatment groups, but no evidence of improvement in lung function was observed in either group.

CONCLUSIONThe sputum TNF-α and neutrophils, but not IL-32 and macrophages, could be reduced by ICS/LABA treatment, suggesting that IL-32 could be involved in the corticosteroid resistance of COPD inflammation.

Adult ; Aged ; Aged, 80 and over ; Albuterol ; analogs & derivatives ; therapeutic use ; Androstadienes ; therapeutic use ; Anti-Inflammatory Agents ; therapeutic use ; Drug Combinations ; Female ; Fluticasone-Salmeterol Drug Combination ; Humans ; Interleukins ; metabolism ; Male ; Middle Aged ; Pulmonary Disease, Chronic Obstructive ; drug therapy ; metabolism

OBJECTIVES: To investigate the clinical efficacy and safety of salbutamol in the treatment of children with later-onset spinal muscular atrophy (SMA). METHODS: This study is a prospective single-arm phase Ⅲ clinical study. Pediatric patients with SMA type Ⅱ and Ⅲ who visited Department of Neurology, Children's Hospital, Zhejiang University School of Medicine from December 2020 to June 2022 were enrolled. All patients were evaluated with motor function scales, pulmonary function test and drug safety before study. Patients were treated with salbutamol tablets orally, with an initial dose of 1 mg (tid). If tolerable, the dose was increased to 1.5 mg (tid) in the second week, then increased to 2 mg (tid) from the third week and maintained for 6 months. Patients were followed up at 1, 3 and 6 months of treatment. RESULTS: Twenty-six patients were enrolled, including 10 boys and 16 girls. There were 16 cases of SMA type Ⅱ and 10 cases of type Ⅲ with age at treatment initiation of 5.67 (3.13, 7.02) years and disease duration of 2.54 (1.31, 4.71) years. The Hammersmith Functional Motor Scale-Expanded (HFMSE) scores were increased from 14.0 (6.5, 43.0) before treatment to 26.0 (15.0, 46.5) after treatment (Z=－4.144, P<0.01) in 25 cases. The Revised Upper Limb Module Scale scores were increased from 33.0 (25.5, 36.0) before treatment to 35.0 (31.0, 36.5) after treatment (Z=－2.214, P<0.05) in 9 cases. In 7 ambulant children with SMA type Ⅲ, the six minutes walking distance was increased by 30 (15, 52) m after a 6-month treatment (Z=－2.366, P<0.05). Compared with the baseline pulmonary functions the patients showed a significant increase in forced vital capacity (FVC), forced expiratory volume in one second (FEV₁), and peak expiratory flow (PEF) in 15 cases after treatment (all P<0.05). According to patients and caregivers subjective reporting, there were various degrees of improvement in coughing, sputum production ability and exercise endurance. No serious adverse events were observed during the study. CONCLUSIONS Short-term oral administration of salbutamol may improve motor and pulmonary functions in later-onset SMA children with good safety.
Male ; Female ; Humans ; Child ; Albuterol/therapeutic use* ; Prospective Studies ; Muscular Atrophy, Spinal/drug therapy* ; Spinal Muscular Atrophies of Childhood/drug therapy* ; Treatment Outcome