Tiotropium as an add-on treatment to inhaled corticosteroids in children with severe and mild symptomatic asthma: Multi-center observational study for efficacy and safety analysis.

Children aged 6-11 years with uncontrolled asthma are treated with low-dose inhaled corticosteroid (ICS) with stepwise increase in ICS dosage and/or add-on maintenance treatment, as necessary. The objective of the present study was to evaluate the efficacy and safety of tiotropium add-on treatment in children with severe and mild symptomatic asthma. The present prospective cohort study included 144 children with severe and mild asthma (age, 6-11 years) who received ICS (budesonide) with ≥1 controller treatment combination therapies for ≥1 month and score ≥1.5 based on Asthma Control Questionnaire-Interviewer-Administered. In addition to ICS with ≥1 controller treatment, children received 5 µg once-daily tiotropium (treatment group; n=72) or did not receive tiotropium (control group; n=72). The peak forced expiratory volume in 1-sec change from the baseline 3 h post-administration of tiotropium was significantly improved in the treatment group compared with the control group (384±31 vs. 248±28 ml; P<0.0001). The trough forced expiratory volume in 1-sec (224±28 vs. 140±31 ml; P<0.0001) and forced expiratory flow at 25-75% of forced vital capacity (389±36 vs. 116±27 ml/sec; P<0.0001) showed significant improvement following treatment with tiotropium. Significant differences were noted for trough forced vital capacity (153±29 vs. 139±30 ml/sec; P<0.0001), mean weekly rescue treatment usage (0.29±0.08 vs. 0.36±0.09; P<0.0001), mean weekly peak expiratory flow measurement (4.12±3.56 vs. 7.46±3.29 l/min; P<0.0001) and mean weekly symptom-free time (0.19±0.04 vs. 0.16±0.04 days; P<0.0001) between both cohorts. Children of both groups tolerated any adverse effects. Tiotropium 5 µg administered once/day as an add-on treatment to ICS with ≥1 controller treatments in children (6-11 years of age) with severe and mild symptomatic asthma was found to be efficacious and safe (level of evidence 2; technical efficacy stage 4).

Correlation between asthmatic infants with rickets and vitamin D, inflammatory factors and immunoglobulin E.

Correlation between asthmatic infants with rickets and vitamin D, inflammatory factors and immunoglobulin was investigated. A total of 60 child patients with asthma who met the inclusion criteria and received treatment from January 2016 to October 2017 were collected. Among them, 17 asthmatic infants with rickets were set as observation group, while 43 child patients with simple asthma were regarded as the control group. Venous blood was drawn from the two groups of subjects after admission. The levels of interleukin-1 (IL-1), IL-6 and IL-17 in serum were determined by ELISA, vitamin D and immunoglobulin E levels in serum were detected using a fully-automatic biochemical analyzer, and wheezing duration during asthma attack was recorded. IL-1, IL-6, IL-17 and immunoglobulin E levels in serum of observation group were significantly higher than those of the control group (P<0.05). The vitamin D level in the observation group was remarkably lower than that in the control group (P<0.05). Wheezing duration in observation group was evidently longer than that in control group (P<0.05). Moreover, IL-1, IL-6, IL-17 and immunoglobulin E levels in serum were positively related to wheezing duration, but the vitamin D level was negatively associated with wheezing duration. Infantile asthma with rickets is closely correlated with vitamin D, inflammatory factors and immunoglobulin E, which are major risk factors in infantile asthma with rickets.

Bacterial respiratory tract inflammation in neonatal rat model is attenuated by benzofuran through inhibition of GATA3.

The current study was aimed to investigate the effect of benzofuran on asthma neonatal rat model. Twenty-five neonatal rats were assigned into five groups; Normal control, untreated, 1 mg/kg, 8 mg/kg and 10 mg/kg treatment groups. Methacholine was administered orally to the rats of untreated and treatment groups. Animals in the normal control group were given PBS as a vehicle. FlexiVent system employing a computer-controlled mouse ventilator along with respiratory mechanics was used for the analysis of airway resistance in the rats. Cytokine level and IFN-γ in the rat serum samples was performed by ELISA in accordance with the instructions of manufacturer. Methacholine administration into the rats caused a marked increase in lung airway resistance. However, treatment with 8 and 10 mg/kg doses of benzofuran led to marked decrease in the airway resistance. Benzofuran treatment prevented accumulation of macrophages and inflammatory cells in the lung airways. Inhibition of inflammation in methacholine administered rats by benzofuran was also confirmed by hematoxylin & eosin-staining. Examination of the rat serum showed significantly higher level of Th2 cytokines (IL-4, -5 and -13) in the untreated rats. However, treatment of methacholine administered rats with benzofuran significantly inhibited Th2 cytokine expression. The level of IFN-γ was increased by benzofuran treatment in methacholine administered rats. In methacholine administered rats the level of IgE was markedly higher however treatment of asthma rats with benzofuran inhibited up-regulation of IgE significantly. The expression of T-bet is decreased and that of GATA-3 is increased by methacholine administration in the rat lungs. Benzofuran treatment of methacholine administered rats prevented reduction in T-bet and up-regulation of GATA-3 expression in the rat lungs. The effect of benzofuran was significant at the doses of 8 and 10 mg/kg and non-significant at 1 mg/kg. These finding suggest that benzofuran inhibits expression of dominant T-helper 2 cytokines through targeting GATA-binding protein 3 transcription factor. Thus benzofuran can be of therapeutic importance for the treatment of asthma.