Comparison of salbutamol efficacy in children- via the metered-dose inhaler (MDI) with Volumatic® spacer and via the dry powder inhaler, Easyhaler®, with the nebulizer - in mild to moderate asthma exacerbation: a multicenter, randomized study.

Background: β2 agonist administered via a nebulizer is the standard treatment for acute asthma exacerbation. There are some limitations for the use of nebulization. We conducted a study to determine the efficacy of salbutamol administered via the pMDI with Volumatic® spacer and the Easyhaler®(DPI) compared to nebulization in mild to moderate asthma exacerbations in children. Methods: A multicenter, randomized, controlled study was conducted in children between 5 and 18 years of age who presented at an emergency or outpatient department. They were randomized to receive either 6 puffs of salbutamol via the pMDI with Volumatic® spacer, or via the Easyhaler®, or 0.15 mg/kg of salbutamol nebulized via oxygen (or compressed air). The primary outcome was the clinical response which was assessed using the modified Wood’s asthma score. The secondary outcomes were: hospitalization, asthma re-visit within 3 days, systemic corticosteroid use and adverse events. The clinical score, oxygen saturation, PR, RR, BP and adverse events were recorded at time 0 (before treatment) and 20, 40 and 60 minutes after drug administration. Results: There were no statistically significant differences in the clinical response between the three groups at the 1st, 2nd or 3rd dose or for the SpO2 or the respiratory rate while the children in the Easyhaler® group had significantly less tachycardia after the 2nd dose. No significant adverse events were noted among the three groups. Conclusions: Salbutamol administered via pMDI with Volumatic® spacer or DPI (Easyhaler®) are as effective as salbutamol given via a nebulizer in providing effective relief of mild to moderate severity acute asthma exacerbation in children between 5 and 18 years of age.

Prevention of recurrent wheezing in young children by loratadine compared with ketotifen.

BACKGROUND: Various trials showed benefit of the prophylactic agent ketotifen in prevention of recurrent wheezing in young children, but no such clinical trial with loratadine or comparison trial is available. OBJECTIVE: To study the efficacy and safety of loratadine syrup compared with ketotifen and placebo in prevention of recurrent wheezing in young children. MATERIAL AND METHOD: Randomized double-blind placebo controlled trial on 90 recurrent wheezing children aged less than 6 years old was done. Children were randomized to receive loratadine, ketotifen syrup, or placebo with dose of 0.25 cc/kg once a day for four months. Blood biochemistry (CBC, LFT) and EKG were performed pre and post treatment period. Assessment of symptoms--wheezing and night cough including use of bronchodilators was done daily via patient diary card. Subjects were asked to do monthly visits to the clinic for physical examination. At those visits, the doctors questioned the patients about adverse event. RESULT: Of the 90 children enrolled, 12 dropped out. Thus, 27 children remained in the loratadine, 26 in the placebo, and 25 in the ketotifen group. The demographic data were comparable among the three treatment groups. It was noted that wheezing decreased significantly at 2 months in the ketotifen (p = 0.008) and at 3 months in the loratadine (p = 0.029) but not in the placebo group. Coughing at night decreased significantly at 3 months in both the loratadine (p = 0.005) and the ketotifen (p = 0.036) group. The use of bronchodilator drug was significantly decreased at 2 months in the ketotifen (p = 0.028) and placebo (p = 0.025) group, and at 3 months in the loratadine (p = 0.009) group. Only a few patients had mild adverse events in all groups. CONCLUSION: Loratadine and ketotifen are safe and effective significantly in prevention of recurrent wheezing in young children.

Cow's milk allergy in Thai children.

Cow's milk allergy (CMA) is nowadays a common problem in Thai children. We reviewed medical records of patients with CMA from the Department of Pediatrics at King Chulalongkom Memorial Hospital of the past 10 years, from 1998 to 2007. The criteria for the diagnosis of CMA included: elimination of cow's milk formula resulting in improvement of symptoms, and: recurrence of symptoms after reintroduction of cow's milk by oral challenge or by accidental ingestion. Of the 382 children with a diagnosis of CMA, 168 were girls and 214 were boys. The average age at the time of diagnosis was 14.8 months (7 days-13 years). The average duration of symptoms before diagnosis was 9.2 months. A family history of atopic diseases was found in 64.2% of the patients. All of the mothers reported an increased consumption of cow's milk during their pregnancy. The most common symptoms were respiratory (43.2%) followed by gastrointestinal (GI) (22.5%) and skin manifestations (20.1%). Less common symptoms included failure to thrive (10.9%), anemia (2.8%), delayed speech due to chronic serous otitis media (0.2%) and anaphylactic shock (0.2%). A prick skin test with cow milk extract was positive in 61.4%. Exclusively breast-fed was found in 13.2% of the patients. Successful treatment included elimination of cow's milk and milk products and substitution with soy formula in 42.5%, partial hydrolysate formula (pHF) in 35.7%, extensive hydrolysate formula (eHF) in 14.2%, and amino acid formula in 1.7%. Continued breast feeding was successful in 5.9% (with maternal restriction of cow's milk and milk products). Our study demonstrates the variety of clinical manifestations of CMA in Thai children especially respiratory symptoms which are usually overlooked.

Nonsense mutations of the CYBB gene in two Thai families with X-linked chronic granulomatous disease.

X-linked chronic granulomatous disease (X-CGD) is an immunodeficiency disorder characterized by defective intracellular killing of microorganisms due to the neutrophils' inability to generate superoxide ions. Although it is always caused by mutations in the CYBB gene, clinical and molecular characteristics vary in different ethnic backgrounds. Two unrelated Thai boys presented with severe persistent pulmonary infections at the age of two months. Their abnormal dihydrorhodamine (DHR) flow cytometry assays supported the diagnosis of X-CGD. Mutation analysis was performed by polymerase chain reaction (PCR) amplification and sequencing of the entire coding regions of CYBB. Mutations identified were confirmed by restriction enzyme analyses. PCR-sequencing of the entire coding regions of CYBB identified nonsense mutations, 271C>T (R91X) in exon 4 and 456T>A (Y152X) in exon 5, in probands of each family. Both of the patients' mothers were found to be carriers. This observation supports that CYBB is the gene responsible for X-CGD across different populations and nonsense mutations are associated with severe phenotypes.

Montelukast in general pediatric practices.

Allergic diseases, e.g., allergic rhinitis, atopic dermatitis and asthma, are common problems in children. Researches on the pathogenesis of allergic diseases have led to the development of new specific antiinflammatory medications, including Montelukast, which blocks the interaction of cysteinyl leukotrienes to their receptors and resulting downstream events. Several studies have demonstrated the effect of regular Montelukast therapy on asthma, allergic rhinitis, viral-induced wheezing in bronchiolitis and chronic rhinitis symptoms. Evidence base medicine now shows that Montelukast can be used as a monotherapy in mild persistent asthma and can be an add-on drug to inhaled corticosteroid (ICS) in moderate to severe persistent asthma. Even in allergic rhinitis, Montelukast has a role in controlling rhinitis symptoms. Montelukast demonstrated a safety profile similar to placebo and more safety than ICS. Moreover Montelukast can improve quality of life in patients with asthma and comorbid allergic rhinitis.

Peak inspiratory flow rate and the ability to use the Turbuhaler in Thai children aged 3-7 years.

A Turbuhaler is a dry powder inhaler device commonly used by asthmatic patients. Its superiority over a metered-dose inhaler device includes easy technique, convenience in handling and absence of chloro fluoro carbon (CFC). However, the use of this device has some limitations in young children who may not be able to generate the inspiratory flow rate high enough to assure adequate medication delivery. Even though the Turbuhaler has been used in Thailand for many years, the study of inspiratory flow rate and the ability to use this device in Thai preschool children is lacking. In the present study, the authors aimed to evaluate the ability to use the Turbuhaler in Thai preschool children by measuring the peak inspiratory flow rate, peak inspiratory flow rate through the Turbuhaler as well as positive test of the Turbutester. Subjects included 468 Thai preschool children, aged 3-7 years old. They were assigned to perform the test with In-Check Dial, Mini-Wright Peak Flow Meter and Turbutester. The authors found that the ability to use the device correlated directly with age and children with age of 5 years or more could perform significantly better. Children weight of 20 kilograms or more, or a height of 113 centimeters or more were also able to generate adequate inspiratory flow rate for medication delivery. The authors concluded that children from the age of five years, or with a weight from 20 kilograms or a height from 113 centimeters were able to generate adequate inspiratory flow rate for effective medication delivery by the Turbuhaler.