H. Van Bever

International consensus on (ICON) pediatric asthma

Asthma is the most common chronic lower respiratory disease in childhood throughout the world. Several guidelines and/or consensus documents are available to support medical decisions on pediatric asthma. Although there is no doubt that the use of common systematic approaches for management can considerably improve outcomes, dissemination and implementation of these are still major challenges. Consequently, the International Collaboration in Asthma, Allergy and Immunology (iCAALL), recently formed by the EAACI, AAAAI, ACAAI, and WAO, has decided to propose an International Consensus on (ICON) Pediatric Asthma. The purpose of this document is to highlight the key messages that are common to many of the existing guidelines, while critically reviewing and commenting on any differences, thus providing a concise reference. The principles of pediatric asthma management are generally accepted. Overall, the treatment goal is disease control. To achieve this, patients and their parents should be educated to optimally manage the disease, in collaboration with healthcare professionals. Identification and avoidance of triggers is also of significant importance. Assessment and monitoring should be performed regularly to re‐evaluate and fine‐tune treatment. Pharmacotherapy is the cornerstone of treatment. The optimal use of medication can, in most cases, help patients control symptoms and reduce the risk for future morbidity. The management of exacerbations is a major consideration, independent of chronic treatment. There is a trend toward considering phenotype‐specific treatment choices; however, this goal has not yet been achieved.

Distinct pattern of commensal gut microbiota in toddlers with eczema.

Background: Recent studies have demonstrated differences in the composition of gut microbiota in infants with and without allergic diseases, particularly eczema. Methods: A case-control study involving 21 toddlers (age 3.0 ± 0.5 years) with and 28 age-matched toddlers without eczema was conducted. Four groups of aerobic gut microbiota were identified and quantitated in stool samples grown on selective media. Three groups of anaerobes were enumerated by fluorescent in situ hybridization followed by quantitative flow cytometry. We also performed molecular typing of lactic-acid-producing bacteria (LAB) and enterococcal isolates to facilitate detailed analysis at species level by bacterial 16S rDNA sequencing. Results: Toddlers with eczema harbored significantly lower counts of Bifidobacterium [(median 0.14 (25th and 75th percentile: 0.04 and 0.47) vs. 0.71% (0.16, 1.79) of cells acquired, p = 0.003)] and Clostridium [(0.28 (0.09, 0.78) vs. 0.83% (0.35, 1.82) of cells acquired, p = 0.012)] but significantly higher counts of total LAB [7.3 (6.1, 8.5) vs. 5.7 (4.4, 7.3) log CFU/g, p = 0.006] in particular enterococci [6.3 (4.8, 7.4) vs. 5.0 (3.4, 6.4) log CFU/g, p = 0.018]. There was no significant correlation between eczema severity score and bifidobacterial counts. Conclusion: The results further confirm previous reports that the gut microecosystem differs between children with and without eczema and extend them beyond infancy.

Anaphylaxis after hamster bites – identification of a novel allergen

Background Hamsters are popular household pets and anaphylaxis after their bites have described. However, the putative allergen has not been identified.

Clinical and immunochemical profiles of food challenge proven or anaphylactic shrimp allergy in tropical Singapore

Shellfish allergy in Singapore is highly prevalent, and shrimp allergy is the most common.

Endotoxin Levels in Rural Thai and Urban Singaporean Homes

Background: Exposure to dust endotoxin and allergens in early childhood may influence the development of allergic diseases. Aims: This study aimed to evaluate dust endotoxin and dust mite allergens in urban Singapore and rural Thai homes of young children and study potential environmental influences. Methods: Mattress dust endotoxin and Der p 1, Der f 1, group 2 (Der f 2 and Der p 2) and Blo t 5 allergen levels were quantified in 101 infant mattress dust samples, 51 from urban Singapore and 50 from rural Thailand. Comprehensive questionnaires on the home environment and cleaning practices were completed. Results: Endotoxin levels in rural Thailand were significantly higher than in urban Singapore (geometric mean 26,334.12 ± 4.60 and 18,377.85 ± 2.52 endotoxin units/g, respectively; p = 0.032). In contrast, higher levels of Der f 1 (p = 0.02), group 2 (p < 0.01) and Blo t 5 (p < 0.01) allergens were found in Singapore homes compared with rural Thai homes. Multiple logistic regression analysis showed that the use of detergents (p = 0.001) and disinfectants (p = 0.024) to clean floors and mattress protectors (p = 0.021) were independently associated with lower endotoxin levels. Conclusion: Endotoxin levels are higher in rural compared with urban homes in South East Asia. The reverse was true for dust mite allergen levels. Certain identifiable home environmental conditions and practices accounted for the differences in endotoxin levels.

Tobacco smoke exposure and respiratory morbidity in young children

Objective Secondhand smoke exposure is a potentially preventable cause of significant respiratory morbidity in young children. Our study aimed to quantify respiratory morbidity in young children exposed to secondhand smoke to identify potentially modifiable factors. Materials and methods This study was embedded in a prospective birth cohort study of pregnant women and their children from fetal life onwards in Singapore (Growing Up in Singapore Towards healthy Outcomes, or GUSTO). Data on prenatal, antenatal and postnatal active and secondhand tobacco smoke exposure were obtained by an investigator-administered questionnaire for the periods before pregnancy, at 26–28 weeks’ gestation and 24 months after delivery. Data on respiratory morbidity (wheezing episodes, croupy cough, nebuliser use, snoring) and other morbidity (fever, hospitalisation, ear infection) of the child was collected at week 3 and at months 3, 6, 9, 12, 15, 18 and 24 after delivery. Information on parental atopy and potential confounders such as socioeconomic status and maternal educational level were also obtained. Statistical analysis of the data was performed to quantify any significant differences in incidence of respiratory morbidity in children exposed to tobacco smoke in utero and postdelivery, compared with those in smoke-free environments. Results Women who smoked regularly prior to pregnancy comprised 12.5% (n=155) of the study population; this number fell to 2.3% (n=29) during pregnancy. Mothers exposed to secondhand smoke in the household before pregnancy comprised 35.7% of the study population (n=441) and 31.5% (n=389) were exposed during pregnancy. Postnatally, the prevalence of secondhand tobacco smoke exposure from birth to 2 years of age was 29% (n=359). Participants of Malay ethnicity (p<0.001), mothers with no or primary level education (p<0.001) and mothers with low socioeconomic status (p<0.001) had the highest exposure to tobacco smoke. Offspring secondhand smoke exposure at home by 12 months and by 24 months of age was associated with an increase in hospital admissions due to respiratory disease (RR 1.89, 95% CI 1.02 to 3.50, p=0.04 by 12 months and RR 1.64, 95% CI 1.05 to 2.55, p=0.03 by 24 months) as well as all-cause hospitalisation (RR 1.57, 95% CI 1.14 to 2.17, p=0.01 by 12 months and RR 1.49, 95% CI 1.17 to 1.90, p=0.001 by 24 months), adjusting for parental atopy and child atopic dermatitis. Participants exposed to secondhand smoke by 12 months postdelivery had a significantly increased risk of having at least one wheezing episode (RR 1.71, 95% CI 1.38 to 2.11, p<0.001). Conclusions Secondhand smoke exposure during the prenatal and postnatal periods is associated with increased respiratory morbidity in children. Opportunistic screening and targeted smoking cessation counselling for parents at child hospital admissions and well-child outpatient visits, as well as preconception smoking cessation counselling for future pregnancies, may be beneficial to protect the child from negative health impacts.

Novel strategies in immunotherapy for allergic diseases

Conventional immunotherapy (IT) for optimal control of respiratory and food allergies has been fraught with concerns of efficacy, safety, and tolerability. The development of adjuvants to conventional IT has potentially increased the effectiveness and safety of allergen IT, which may translate into improved clinical outcomes and sustained unresponsiveness even after cessation of therapy. Novel strategies incorporating the successful use of adjuvants such as allergoids, immunostimulatory DNA sequences, monoclonal antibodies, carriers, recombinant proteins, and probiotics have now been described in clinical and murine studies. Future approaches may include fungal compounds, parasitic molecules, vitamin D, and traditional Chinese herbs. More robust comparative clinical trials are needed to evaluate the safety, clinical efficacy, and cost effectiveness of various adjuvants in order to determine ideal candidates in disease-specific and allergen-specific models. Other suggested approaches to further optimize outcomes of IT include early introduction of IT during an optimal window period. Alternative routes of administration of IT to optimize delivery and yet minimize potential side effects require further evaluation for safety and efficacy before they can be recommended.

Economic value of using partially hydrolysed infant formula for risk reduction of atopic dermatitis in high-risk, not exclusively breastfed infants in Singapore

INTRODUCTION Previous trials have demonstrated reductions in atopic dermatitis (AD) incidence when healthy, high-risk, non-exclusively breastfed infants were fed until four months of age with 100% whey-based partially hydrolysed formula (PHF-W) versus standard cows milk formula (CMF). We assessed the cost-effectiveness of this intervention in Singapore. METHODS Modelling techniques were used to simulate, from birth to Month 30, the incidence and clinical/economic burden of AD in high-risk, non-exclusively breastfed infants fed with PHF-W or CMF for up to four months. Epidemiologic and clinical data were from a local comparative trial. Expert opinion informed AD treatment patterns and outcomes. Outcomes included reduction in AD risk, time spent with AD, days without AD flare, quality-adjusted life years (QALYs) and direct/indirect costs. Multivariate probabilistic sensitivity analysis was used to assess model parameter uncertainty. RESULTS Over 30 months, with the use of PHF-W instead of CMF, the proportion of children who developed AD and the time spent with AD decreased by 16.0% (28.3% vs. 44.3%) and 6.4 months, respectively, while time without AD flare and QALYs increased by 14.9 days and 0.021 QALYs per patient, respectively. Estimated AD-related discounted costs per child for PHF-W and CMF were SGD 771 and SGD 1,309, respectively (net savings: SGD 538). PHF-W was less expensive and more effective than CMF for 73%, and cost less than SGD 50,000 per QALY for 87% of all multivariate simulations. CONCLUSION Early short-term nutritional intervention with PHF-W instead of CMF may reduce AD incidence and costs for healthy, high-risk, non-exclusively breastfed infants in Singapore.

Anaphylaxis after hamster bites—Identification of a novel allergen

BACKGROUND Hamsters are popular household pets and anaphylaxis after their bites have described. However, the putative allergen has not been identified. OBJECTIVE This study was conducted to identify the allergen causing dwarf hamster (Phodopus sungoris) bite-induced anaphylaxis. METHODS Two children with hamster bite-induced anaphylaxis were enrolled. They both had negative results to skin testing and specific IgE to hamster epithelium. However, they were both allergic to Dermatophagoides pteronyssinus (Der p). Identification of the putative IgE-binding allergens from the hamster saliva was performed using immunoblot analysis. RESULTS A specific IgE-binding component at 21 kD in the hamster saliva was identified. ELISA inhibition tests showed partial inhibition with Der p. CONCLUSIONS The putative allergen from the hamster saliva causing dwarf hamster-induced anaphylaxis was identified. Possible cross-reactivity with Der p was demonstrated. Further studies will be needed to identify the exact nature and function of this allergen.