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.

BackgroundFluticasone 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.MethodsThis 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.ResultsThree 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.ConclusionThis 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.

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.

Children who are destined to develop asthma are considered to be susceptible to a variety of respiratory pathogens. To elucidate respiratory inflammation among these children, we measured the levels of eosinophil cationic protein (ECP) and tryptase in sputum taken from three different groups of wheezy infants and young children: those with a first wheeze (n = 15); those with recurrent wheeze (n = 27); and those with recurrent wheeze with respiratory distress, namely asthma (n = 56). The numbers of eosinophils or metachromatic cells determined by microscopic analysis of sputum samples were also evaluated in combination with the ECP and tryptase levels. Although neither sputum ECP nor tryptase was a clear discriminative marker that differentiated the three different types of wheezy disease, ECP levels in sputum from the asthma group were significantly higher (2,269.2 +/- 6,216.8 ng/g) than those in the recurrent wheezy group (440.3 +/- 1,199.8 ng/g) or in the first-wheeze group (209.0 +/- 172.9 ng/g). A similar trend was observed with tryptase levels in sputum, but there were no significant differences among the three groups. Sputum taken from asthmatic children showed a marked accumulation of eosinophils. However, an accumulation of eosinophils in sputum (even in the presence of an elevated level of sputum ECP) was not identified in the asthmatic infants < 1 year of age. An accumlation of eosinophils in sputum was not evident until children became > 1 year old and thereafter the eosinophils rapidly increased in number until the children reached 5 years of age. It was noteworthy that sputa positive for pathogenic bacteria, taken from the 1- and 2-year-old asthmatic infants, had a tendency to show high levels of ECP but a reduced number of eosinophils. Along with the wheezy episodes induced by viral infection, primarily and occasionally in combination with secondary bacterial infection, eosinophil activation and infiltration may develop. These predestined immune reactions to various pathogens might be associated with triggering the onset of asthma.

Serum glutamic-oxaloacetic transaminase (GOT) levels were determined in 214 infants (133 males and 81 females) with atopic dermatitis during their first visit to the Department of Allergy, National Children’s Hospital, Tokyo, Japan. Compared with the normal hospital range, their levels were found to be significantly higher, a tendancy which was more conspicuous in lower age groups. We carried out a ¹³C-methacetin breath test (MBT), administering the stable-isotope-labeled compound to 11 children with higher serum GOT values and 5 within the normal range to investigate hepatic metablism of methacetin in infants with atopic dermatitis. ¹³C-methacetin was given orally, and the ¹³CO₂ level in the breath was determined immediately before and after administration, by mass spectrometry. Compared to the normal controls, the atopic infants demonstrated significantly lower ¹³CO₂ peak excretion and delayed peak time. The clearance rate of ¹³CO₂ was also decreased. These results suggest some relationship between atopic dermatitis and liver function in infants.