The efficacy and safety of fluticasone/salmeterol compared to fluticasone in children younger than four years of age.

BACKGROUND: Fluticasone propionate 50 µg/salmeterol xinafoate 25 µg (FP/SAL) is widely used in adults and children with asthma, but there is sparse information on its use in very young children. METHODS: This was a randomized, double-blind, multicentre, controlled trial conducted in children aged 8 months to 4 years. During a 2-week run-in period, they all received FP twice daily. At randomization, they commenced FP/SAL or FP twice daily for 8 weeks. All were then given FP/SAL only, in a 16-week open-label study continuation. Medications were inhaled through an AeroChamber Plus with attached face mask. The primary end-point was mean change in total asthma symptom scores from baseline to the last 7 days of the double-blind period. Analyses were undertaken in all children randomized to treatment and who received at least one dose of study medication. RESULTS: Three hundred children were randomized 1:1 to receive FP/SAL or FP. Mean change from baseline in total asthma symptom scores was -3.97 for FP/SAL and -3.01 with FP. The between-group difference was not statistically significant (P = 0.21; 95% confidence interval: -2.47, 0.54). No new safety signals were seen with FP/SAL. CONCLUSION: This is the first randomized, double-blind study of this size to evaluate FP/SAL in very young children with asthma. FP/SAL did not show superior efficacy to FP; no clear add-on effect of SAL was demonstrated. No clinically significant differences in safety were noted with FP/SAL usage.

Pranlukast reduces asthma exacerbations during autumn especially in 1- to 5-year-old boys.

BACKGROUND: Leukotriene receptor antagonists have been used to prevent virus-induced asthma exacerbations in autumn. Its efficacy, however, might differ with age and sex. OBJECTIVE: This study aimed to investigate whether pranlukast added to usual asthma therapy in Japanese children during autumn, season associated with the peak of asthma, reduces asthma exacerbations. It was also evaluated the effect of age and sex on pranlukast's efficacy. METHODS: A total of 121 asthmatic children aged 1 to 14 years were randomly assigned to receive regular pranlukast or not according to sex, and were divided in 2 age groups, 1-5 years and 6-14 years. The primary outcome was total asthma score calculated during 8 weeks by using a sticker calendar related to the days in which a child experienced a worsening of asthma symptoms. This open study lasted 60 days from September 15 to November 14, 2007. RESULTS: Significant differences in pranlukast efficacy were observed between sex and age groups. Boys aged 1 to 5 years had the lower total asthma score at 8 weeks (p = 0.002), and experienced fewer cold episodes (p = 0.007). There were no significant differences between pranlukast and control group in total asthma score at 8 weeks (p = 0.35), and in the days in which a child experienced a worsening of asthma symptoms (p = 0.67). CONCLUSION: There was a substantial benefit of adding pranlukast to usual therapy in asthmatic children, especially in boys aged 1 to 5 years, during autumn season.

Bacterial colonization in respiratory secretions from acute and recurrent wheezing infants and children.

Lower respiratory tract infection in childhood often results in airway obstruction, characterized by wheezing. However, contribution of bacterial colonization to the wheezy state in children remains unclear. Wheezing and non-wheezing children requiring hospitalization were classified into three groups: (i) wheezing children having a past history of recurrent wheezing; (ii) wheezing children without such history; and (iii) non-wheezing children as control subjects. Respiratory secretions as sputum were analyzed microscopically, and cultured. Cultured pathogenic bacterial species in sputum were categorized into two subgroups according to their amounts, i.e., dominant and non-dominant amounts of colonies. Incidence of bacterial colonization and wheezing were assessed. Hospitalized children were mainly 1- to 2-yr old, and rapidly decreased in number for older ages. Children in the three groups belonged to different clinical entities. Children in the recurrent wheezing group were highly sensitized to mite allergens, and still required hospitalization after 2 yr of age. Incidence of bacterial colonization was similar between the three groups. Dominant and non-dominant amounts of bacterial colonization were 170/997 (17.1%) and 170/997 (17.1%), respectively, in the recurrent wheezing group; 28/146 (19.2%) and 35/146 (24.0%), respectively, in the acute wheezing group; and 15/56 (26.8%) and 7/56 (12.5%), respectively, in the non-wheezing group. Regardless of the presence of wheezing, bacterial colonization commonly occurred at a young age in the three groups. In recurrent wheezing children, boys (122/611, 20.0%) carried non-dominant amounts of bacteria more frequently than girls (48/386, 12.4%) (p < 0.01). Boys showed predominant wheezing and susceptibility to bacterial colonization. Assessment of bacterial colonization allowed us to characterize asthma onset and outgrowth in childhood.

Age and sex as factors of response to RSV infections among those with previous history of wheezing.

Although enhanced immune reaction caused by the respiratory syncytial virus (RSV) in allergen-sensitized animal model has been reported, RSV illnesses in children already sensitized or having recurrent wheezing episodes have not been completely studied. In addition, the reason for male dominances in RSV infection at young ages was also inconclusive. Therefore, gender analysis in recurrent wheezing children with RSV infection can shed light on asthma pathogenesis. We studied the clinical features and the laboratory data of RSV infections in children who had recurrent wheezing histories. The subjects with RSV infection consisted of 98 boys and 58 girls. The children under 4 yr of age were 123 (78.8%) in number. Children with pneumonia were 78 and those with febrile episode were 119. Children above 1 yr of age were highly sensitized with mite antigen (75/96, 78.1%). The clinical symptoms and signs differed according to their ages. Children in each age group behaved differently in their immune reaction to RSV. Above all, 3-yr-old children deteriorated clinically during acute RSV infection, accompanied by transient elevated C-reactive protein (CRP) and suppressed blood eosinophil counts. Clinical features differed in several points between boys and girls. In general, the white blood cell count and the CRP levels were higher in girls in every age group. Blood eosinophil counts at the acute illness were significantly higher in boys than girls aged 2 and 3< yr. Age and gender comparison in already sensitized children might suggest a clue to asthma pathogenesis.

Gender analysis in acute bronchiolitis due to respiratory syncytial virus.

It is reasonable to compare immune reactions between boys and girls because many infections in the early stages are predominant in males. A relationship between immunomodulatory effects of sex hormone surge in boys at early months and infectious diseases is still unclear. We compared clinical features between boys and girls who suffered from wheezing that was initially triggered by acute respiratory syncytial virus (RSV) bronchiolitis. For systemic immune response evaluation, white blood cell (WBC) count, blood eosinophil count, and serum C-reactive protein (CRP) were measured. For local inflammation evaluation, scores for eosinophils and neutrophils in sputum were evaluated microscopically. Patients consisted of 90 boys and 51 girls. Most children were under 6 months of age. WBC counts and serum CRP levels were significantly increased in girls compared with boys. Blood eosinophilia at the acute stage was rarely observed in children after 6 months of age. For local response evaluation, sputum specimens obtained from 42 boys and 29 girls were microscopically examined. Sputum eosinophil score of 2+ and more was observed in boys (6/42) exclusively. In contrast, sputum neutrophilia was commonly observed in boys and girls. From a follow-up study, we confirmed that 28 children with RSV bronchiolitis showed wheezing episodes afterwards. However, their blood and sputum eosinophilia during RSV bronchiolitis did not reflect their subsequent wheezing. We speculated that gender-specific responses to RSV infection might account for male susceptibility. Differences in RSV pathogenicity between boys and girls should be further investigated in terms of asthma progression.

Changes in Histamine/Tryptase Levels in Skin Chambers: Application for Clinical Evaluation of Atopic Dermatitis.

We measured changes in histamine and tryptase levels in fluid of children with atopic dermatitis using skin chamber methods and evaluated the correlation with clinical symptoms. Skin chambers were applied to forearm skin which had been scratched with a needle, and an extract of Dermatophagoides farinae (mite antigen) at 50 µg/ml in saline was added through 0.3-µm filters as a challenge. We measured the concentrations of tryptase and histamine 2, 6, 12, and 24 h after challenge. The skin chamber test was done before and after hospitalization therapy or beach camp therapy. We also tested patients with atopic dermatitis of varying severity, asthmatic patients without dermatitis, and normal volunteers. The histamine levels dramatically increased 24 h after challenge with mite antigen in patients with severe atopic dermatitis, whereas this was not observed in patients with mild atopic dermatitis or asthma and in normal volunteers. The levels of histamine in the chambers 24 h after challenge decreased along with improvement of skin condition after various kinds of treatment and beach camp therapy. These results indicate that the skin chamber test will be a useful objective tool to evaluate the skin conditions of patients with atopic dermatitis. The increase of histamine level was not accompanied by an increase in tryptase level, suggesting the importance of basophil activation in this disease.