Practical recommendations for home-nebulized corticosteroid use in children aged ≤ 5 years with asthma: A review and advisory group consensus.

BACKGROUND: Despite nebulized budesonide being identified by the Global Initiative for Asthma report as a viable alternative to inhaled corticosteroids (ICS) delivered by pressurized metered-dose inhalers (pMDIs) with spacers, practical guidance on nebulized corticosteroid use in the pediatric population remains scarce. OBJECTIVE: To review the current literature and provide practical recommendations for nebulized budesonide use in children aged ≤ 5 years with a diagnosis of asthma. METHODS: A group of 15 expert pediatricians in the respiratory and allergy fields in Thailand developed Delphi consensus recommendations on nebulized budesonide use based on their clinical expertise and a review of the published literature. Studies that evaluated the efficacy (effectiveness) and/or safety of nebulized budesonide in children aged ≤ 5 years with asthma were assessed. AR patients. RESULTS: Overall, 24 clinical studies published between 1993 and 2020 met the inclusion criteria for review. Overall, results demonstrated that nebulized budesonide significantly improved symptom control and reduced exacerbations, asthma-related hospitalizations, and the requirement for oral corticosteroids compared with placebo or active controls. Nebulized budesonide was well tolerated, with no severe or drug-related adverse events reported. Following a review of the published evidence and group consensus, a treatment algorithm as per the Thai Pediatric Asthma 2020 Guidelines was proposed, based on the availability of medications in Thailand, to include nebulized budesonide as the initial treatment option alongside ICS delivered by pMDIs with spacers in children aged ≤ 5 years. CONCLUSIONS: ThNebulized budesonide is an effective and well-tolerated treatment option in children aged ≤ 5 years with asthma.

Practical considerations of nebulized corticosteroid in children with acute asthmatic exacerbation: A consensus.

BACKGROUND: Acute asthmatic exacerbation in children causes economic burdens both directly and indirectly. The GINA guideline does mention the use of inhaled or oral corticosteroids in the treatment of asthmatic exacerbation, it provides little practical guidance on the use of nebulized corticosteroid. OBJECTIVE: To review and recommend the practical considerations in the use of nebulized corticosteroid in children with acute asthmatic exacerbation. METHODS: This consensus was developed by a group of expert pediatricians in respiratory and allergy fields in Thailand. The recommendations were made based on a review of published studies and clinical opinions. The eligible studies were confined to those published in English, and randomized controlled trials and meta-analyses involving nebulized corticosteroids in asthmatic exacerbation in children aged between 1-18 years. RESULTS: There were 13 randomized controlled-trial studies published from 1998 to 2017. Nine of the 13 studies compared nebulized with systemic corticosteroid conducted in moderate to severe exacerbation, while the remaining four compared nebulized corticosteroid with placebo conducted in mild to severe exacerbation. The admission rate was significantly lower in severe exacerbation (one study) and pooled four mild to severe exacerbation studies comparing with placebo (p 0.022). Other clinical parameters were significantly improved with nebulized corticosteroid such as clinical scores, systemic corticosteroid/bronchodilator use, or shorter ER stays. Only one study used fluticasone, while the other 12 studies conducted by budesonide (92.31%). CONCLUSIONS: Nebulized corticosteroid may offer an effective therapeutic option for the management of acute exacerbation of asthma in all severities. Nebulized budesonide is the preferred corticosteroid.

Accuracy of childhood asthma control test among Thai childhood asthma patients.

BACKGROUND: The Childhood Asthma Control Test (C-ACT) was developed to assess asthma control in children worldwide. A self-administered questionnaire for children translated into Thai language was used. OBJECTIVE: To validate the C-ACT cut-points for evaluating the level of asthma control among Thai children, using the Global Initiative for Asthma (GINA) guideline as a gold standard. METHODS: C-ACT score, FEV1 and assessment of level of asthma control were recorded at baseline, 3-month, 6-month, and 1-year visits among children with asthma. Receiver operating characteristic (ROC) curves was used to determine the area under the curve (AUC) of C-ACT score for determining the level of asthma control. Validity indicators were calculated at different C-ACT cut-points to determine those most appropriate for predicting controlled and uncontrolled asthma. RESULTS: We enrolled 279 children, 64% males, with mean age 6.87±2.4 years. C-ACT score was significantly correlated with FEV1 at 3-month, 6-month, and 1-year visits (p<0.001). The AUC of C-ACT score compared with GINA score were above 80% at all visits. The suggested C-ACT score cut-point of controlled asthma was ≥ 23 (sensitivity 69.5%, specificity 73.3%, positive predictive value (PPV) 81.2%, negative predictive value (NPV) 63.8%); that of uncontrolled asthma was ≤ 18 (sensitivity 54.2%, specificity 96.9%, PPV 61.9%, NPV 95.7%). CONCLUSIONS: The Thai version of the C-ACT is an accurate, simple, and useful tool for assessing asthma control among Thai children. The high AUC suggests that the Thai C-ACT is as good as the GINA guideline in predicting asthma control level.

Cytokine responses during exacerbation compared with stable phase in asthmatic children.

Bronchial asthma is a chronic inflammatory disorder of the airways. Balancing in Th1 and Th2 response is a target in the treatment. Recent studies show that interleukin-10 (IL-10) has an important role in the regulation of Th2 and allergic responses and its amount was found to decrease in asthmatic patients. This study was to focus on cytokine responses, including interferon-gamma (IFN- gamma), IL-4 and IL-10 in asthmatic children during acute exacerbation compared to stable period. Peripheral blood mononuclear cells (PBMCs) from fourteen asthmatic children during exacerbation and stable phase were stimulated with phytohemagglutinin (PHA) and mite allergen (Der p) for 72 hours. Levels of IFN-gamma, IL-4 and IL-10 in cell culture supernatants were measured using enzyme-linked immunosorbent assay. The median level of IL-10 in PBMCs stimulated with PHA was significantly lower in acute asthma exacerbation compared with stable phase (464 vs. 859.5 pg/ml, p = 0.03). However, there was no difference in the level of IL-10 in PBMCs stimulated with Der p. The level of IFN- and IL-4 were not different between exacerbation and stable phase both in PHA and Der p-stimulated PBMCs. The decrease of IL-10 production in asthmatic children during acute exacerbation may emphasize the role of IL-10 in immune regulation in allergic disease.

Sensitivity of Turbutester and Accuhaler tester in asthmatic children and adolescents.

BACKGROUND: Dry powder inhalers (DPI) are alternative devices for delivering medication for treatment of asthma. The amount of drug delivery to the lungs is directly influenced by peak inspiratory flow rate (PIFR). A minimum PIFR of -30 L/min is needed for the Turbuhaler and Accuhaler. METHODS: In order to evaluate the sensitivity of the Turbutester and Accuhaler tester in detecting the minimum and optimum PIFR for the Turbuhaler and Accuhaler in asthmatic children, PIFR was measured using the In-Check Dial through the internal resistance of the Turbuhaler and Accuhaler and compared according to the child's ability to make a whistle sound via both testers. RESULTS: A total of 259 asthmatic children were studied: 20 pre-school children, aged 5-6 years; 174 school-age children, aged 7-12 years; and 65 adolescents, aged 13-18 years. The sensitivity of the Turbutester and Accuhaler tester to detect optimum PIFR were 98.40% and 97.2%, respectively. In the comparison among age groups, the sensitivity of the Accuhaler tester to detect optimum or minimum PIFR for the Accuhaler was 95%, 97.7% and 95.4%, respectively. The sensitivity of the Turbutester to detect optimum PIFR for the Turbuhaler was 94.4%, 98.8% and 98.5%, respectively. The sensitivity of the Turbutester to detect minimum PIFR for the Turbuhaler was 94.7%, 100% and 100%, respectively. There were no significant differences in percentage of having optimum or minimum PIFR among asthma severity and current device usage in all age groups. CONCLUSIONS: Most children aged at least 5 years could generate enough PIFR to use dry powder inhaler devices. Both the Turbutester and Accuhaler tester were found to have high sensitivity in detecting optimum and minimum required PIFR.

Serum TGF-beta1 in atopic asthma.

Asthma is a chronic inflammatory disease of the airway. Pathological repair of chronic inflammation leads to airway remodeling. Transforming growth factor-beta (TGF-beta), a profibrotic cytokine, plays an important role in promoting the structural changes of airway remodeling. TGF-beta effects on the proliferation, differentiation and extracellular matrix (ECM) metabolism of airway structural cells. This study assessed serum TGF-beta1 in different severity of atopic asthma compared to non-atopic controls. Thirty-one atopic asthmatic patients and 34 non-atopic controls, aged 7-18 years, were recruited as to the asthma severity: steroid naïve mild asthma, moderate asthma, and asthma in remission. Serum TGF-beta1 was measured by enzyme-linked immunosorbent assay. There was a significant difference between serum TGF-beta1 in asthmatic patients and that in control patients (39.59 ng/ml vs. 0.26 ng/ml, p < 0.001). Serum TGF-beta1 was highest in steroid naïve mild asthma group when compared to the moderate asthma and asthma in remission groups (47.44 ng/ml vs. 38.64 ng/ml and 47.44 ng/ml vs. 35.94 ng/ml, p = 0.013 and 0.001, respectively). There were no correlations among serum TGF-beta1 and pulmonary function test parameters, duration of asthma, and duration of inhaled corticosteroid treatment. These data support the role of TGF-beta1 in airway remodeling in asthma.

Impact of particulate air pollutants on allergic diseases, allergic skin reactivity and lung function.

Elevated levels of particulate matter can exacerbate existing asthma and atopy, while evidence that it can promote the induction of atopy and asthma is limited. A cross sectional study was taken to compare the prevalence of eye, nose, ear and airway allergic symptoms, allergic skin sensitivity and lung function in 290 high school students with a history of high 24 hour average exposure to particulate matter less than 10 microm in diameter (PM10) = 170 microg/m3 versus low PM10 of 36 microg/m3 in central Bangkok. Multivariate analysis revealed an increased risk of eye and airway symptoms in groups exposed to higher PM10 levels (p = 0.003, and 0.05, respectively). Positive skin prick tests and a history of having a lawn at home were associated with nasal symptoms (p = 0.008 and 0.04, respectively). Mean FEF(25-75%) (forced expiratory flow that occurs during the middle 50% of the forced expiratory effort) was significantly lower in those who were exposed to higher PM10 levels (3.89 +/- 1 vs 4.42 +/- 0.9 l/sec, p < 0.001). A significant increase in days of school absence and medical expenses was associated with high PM10 exposure. It is concluded that chronic exposure to high PM 10 levels was significantly associated with increased prevalence of eye and airway symptoms and a decrement of FEF(25-75%) resulting in increase of school absence and medical expense.