Early control treatment with montelukast in preschool children with asthma: A randomized controlled trial.

BACKGROUND: While Japanese guideline recommends initial control treatment for preschool children with asthma symptoms more than once a month, Western guidelines do not. To determine whether control treatment with montelukast was more effective than as-needed ß2-agonists in this population, we conducted a randomized controlled trial. METHODS: Eligible patients were children aged 1-5 years who had asthma symptoms more than once a month but less than once a week. Patients were randomly assigned in a 1:1 ratio to receive montelukast 4 mg daily for 48 weeks or as-needed ß2-agonists. The primary endpoint was the number of acute asthma exacerbations before starting step-up treatment with inhaled corticosteroids. This study is registered with the University Hospital Medical Information Network clinical trials registry, number UMIN000002219. RESULTS: From September 2009 to November 2012, 93 patients (47 in the montelukast group and 46 in the no-controller group) were enrolled into the study. All patients were included in the analysis. During the study, 13 patients (28%) in the montelukast group and 23 patients (50%) in the no-controller group had acute exacerbations with the mean numbers of 0.9 and 1.9/year, respectively (P = 0.027). In addition, 10 (21%) and 19 (41%) patients received step-up treatment, respectively. Cumulative incidence of step-up treatment was significantly lower in the montelukast group (hazard ratio 0.45, 95% confidence interval 0.21 to 0.92; P = 0.033). CONCLUSIONS: Montelukast is an effective control treatment for preschool children who had asthma symptoms more than once a month but less than once a week.

Prophylactic effectiveness of suplatast tosilate in children with asthma symptoms in the autumn: a pilot study.

BACKGROUND: Exacerbations of bronchial asthma usually occur in the autumn. To our knowledge, however, the effectiveness of drugs for preventing exacerbations of asthma in the autumn has not been studied previously, except for leukotriene receptor antagonists and Omalizmab. METHODS: This study compared the prophylactic effectiveness of suplatast tosilate with that of mequitazine in children with asthma symptoms, which is usually exacerbated in the autumn. The study group comprised 27 children aged 2 to 15 years who required treatment for asthmatic attacks during the past year and tested positive at least for mite allergen in the preceding autumn. The subjects were randomly assigned to receive either suplatast or mequitazine. The primary endpoint of this study was the number of days without symptoms during the 8 weeks of treatment. In addition, the Japanese Pediatric Asthma Control Program (JPAC) scores were also recorded every 2 weeks in each group. RESULTS: Overall, 14 patients received suplatast, and 13 received mequitazine for 8 weeks from September through early October. During follow-up, the number of days without symptoms and the total JPAC scores did not differ significantly between the groups. However, as compared with weeks 1 to 2 of treatment, the mean number of days without symptoms during weeks 7 to 8 increased significantly in only the suplatast group (8.6 vs. 11.5 days; p = 0.004). CONCLUSIONS: Our results suggest that short-term additional treatment with suplatast is useful for preventing asthma symptoms in children with asthma, which is usually exacerbated in the autumn.

Salivary cortisol monitoring: determination of reference values in healthy children and application in asthmatic children.

Venipuncture testing of adrenocortical function in asthmatic infants and young children receiving inhaled corticosteroids can raise cortisol levels and mask physiological responses. This study aimed to establish reference ranges for salivary cortisol levels and evaluate the safety and effects of jet-nebulized budesonide inhalation suspension (BIS) on salivary cortisol levels and patient outcomes in infants and young children with mild or persistent asthma. Reference salivary cortisol levels were determined in healthy children aged 6 months to 4 years old. A 12-week multicenter, randomized, parallel-group, open-label study was performed involving 53 age-matched asthmatic children who received either 0.5 mg/day of BIS or 40-60 mg/day of cromolyn sodium inhalation suspension (CIS) via compressor nebulizer. The effective measuring range of salivary cortisol concentration in asthmatic children was 0.12-3.00 micrograms/dL. The upper and lower limits of the reference range were 0.827 and 0.076 micrograms/dL, respectively. No significant difference was seen from baseline through week 12 in the CIS and BIS groups. BIS was safe in these patients, with no inhibitory effects on adrenocortical function. Salivary cortisol measurement offers a useful and accurate tool for testing adrenocortical function in infants and young children. Longer-term studies that incorporate testing of the hypothalamic-pituitary-adrenal axis are warranted to confirm our findings.

Development and validation of a nighttime sleep diary in asthmatic children.

The aim of this study was to derive a shorter version of the asthma diary, 'a nighttime sleep diary' from the traditional asthma diary (original version). The nighttime sleep diary mainly consisted of nighttime awakening that met the criteria of validity and practicality necessary for monitoring clinical control in infants and young children with asthma symptoms. Validation of the diary was performed in a 6-week prospective study of 40 children aged 6 months to 6 years treated with nebulized budesonide inhalation suspension or cromolyn sodium nebulized solution. The nighttime awakening score was significantly and positively associated with the nighttime asthma symptom score and daytime asthma symptom score along with the number of days with a cough. Therefore, the nighttime sleep diary is a simple and useful instrument to monitor day-to-day fluctuations in young children with asthma.

Functional identification of the alveolar edema reabsorption activity of murine tumor necrosis factor-alpha.

Tumor necrosis factor-alpha (TNF-alpha) activates sodium channels in Type II alveolar epithelial cells, an important mechanism for the reported fluid resorption capacity of the cytokine. Both TNF-alpha receptor-dependent and -independent effects were proposed for this activity in vitro, the latter mechanism mediated by the lectin-like domain of the molecule. In this study, the relative contribution of the receptor-dependent versus receptor-independent activities was investigated in an in situ mouse lung model and an ex vivo rat lung model. Fluid resorption due to murine TNF-alpha (mTNF-alpha) was functional in mice that were genetically deficient in both types of mTNF-alpha receptor, establishing the importance of mTNF-alpha receptor-independent effects in this species. In addition, we assessed the capacity of an mTNF-alpha-derived peptide (mLtip), which activates sodium transport by a receptor-independent mechanism, to reduce lung water content in an isolated, ventilated, autologous blood-perfused rat lung model. The results show that in this model, mLtip, in contrast to mTNF-alpha, produced a progressive recovery of dynamic lung compliance and airway resistance after alveolar flooding. There was also a significant reduction in lung water. These results indicate that the receptor-independent lectin-like domain of mTNF-alpha has a potential physiological role in the resolution of alveolar edema in rats and mice.