Hugo Van Bever

The role of inflammation in the development of chronic lung disease in neonates

Abstract Chronic lung disease (CLD) has been associated with chorioamnionitis and upper respiratory tract colonisation with Ureaplasma urealyticum. The aim of this review is to describe the increasing evidence that inflammation plays a critical role in the early stages of CLD of the neonate. Ongoing lung damage in the premature infant may be caused by failure to downregulate and control this inflammatory response. Tumour necrosis factor alpha (TNF-α), interleukin-6 (IL-6) and IL-8 are important pro-inflammatory cytokines of which IL-8 is an important chemotactic factor in the lung. Data suggest that preterm newborns with lung inflammation may be unable to activate the anti-inflammatory cytokine IL-10. Therefore, early post-natal anti-inflammatory therapy could help in preventing development of CLD. Prophylactic dexamethasone therapy cannot yet be recommended. There are a number of potential interactions between surfactant and cytokine effects on the preterm lung which have not been evaluated. Surfactant protein A may be an important modulator of the immune response to lung injury. The role of high-frequency ventilation in the prevention of CLD still remains unclear. Conclusion Many aspects of the pathogenesis of the inflammatory response in the development of chronic lung disease remain to be elucidated. Further research to identify preterm infants at highest risk for the development of this multifactorial and complex disease is needed.

Does treatment of asthmatic children with inhaled corticosteroids affect their adult height

In this retrospective study, adult height was assessed in young adult asthmatics who were treated with inhaled corticosteroids (ICs) during childhood (n = 42; 26 boys) and compared to those obtained in asthmatic patients who were never treated with ICs during childhood (n = 43; 23 boys). Standing height of all subjects and their parents was measured. Height data were analyzed using actual length and target height in centimeters, standard deviation scores (SDS), and difference between adult height of the patients and their target height (adult height minus target height).

Prevalence of anxiety and depressive symptoms in adolescents with asthma: A meta-analysis and meta-regression

To cite this article: Lu Y, Mak K‐K, van Bever HPS, Ng TP, Mak A, Ho RC‐M. Prevalence of anxiety and depressive symptoms in adolescents with asthma: A meta‐analysis and meta‐regression. Pediatr Allergy Immunol 2012: 23: 707–715.

Parvalbumin : the major tropical fish allergen

Fish allergy is common in countries where consumption is high. Asian nations are amongst the world’s largest consumers of fish but the allergen profiles of tropical fish are unknown. This study sought to evaluate the allergenicity of four commonly consumed tropical fish, the threadfin (Polynemus indicus), Indian anchovy (Stolephorus indicus), pomfret (Pampus chinensis) and tengirri (Scomberomorus guttatus). Immunoglobulin E (IgE) cross‐reactivity with parvalbumin of cod fish (Gad c 1), the major fish allergen, was also studied. Detection of tropical fish and cod specific‐IgE was performed by UniCap assay, and skin prick tests were also carried out. The IgE‐binding components of tropical fish were identified using IgE immunoblot techniques, and cross‐reactivity with Gad c 1 was assessed by ELISA inhibition and IgE immunoblot inhibition. Clinically, nine of 10 patients studied were allergic to multiple fish. All patients exhibited detectable specific‐IgE to cod fish (10 of 10 skin prick test positive, eight of 10 UniCap assay positive) despite lack of previous exposure. The major allergen of the four tropical fish was the 12‐kDa parvalbumin. IgE cross‐reactivity of these allergens to Gad c 1 was observed to be moderate to high in the tropical fish studied. Parvalbumins are the major allergens in commonly consumed tropical fish. They are cross‐reactive with each other as well as with Gad c 1. Commercial tests for cod fish appear to be sufficient for the detection of tropical fish specific‐IgE.

Evolution of the late asthmatic reaction during immunotherapy and after stopping immunotherapy

In previous studies it was demonstrated that the frequency and the severity of the late asthmatic reaction (LAR) can be attenuated by immunotherapy (IT). The present study was set up to observe the evolution of the LAR under IT and after having stopped IT. Nineteen children with bronchial asthma and an LAR to house dust mite (Dermatophagoides pteronyssinus) (HDM) were selected for this study. All subjects received IT with HDM extract during 1 year. Thereafter, the children were divided randomly into two groups to receive, double-blind, during a second year, IT with HDM (N = 9) or placebo injections (N = 10). Bronchial challenges were performed after the first and second year. After the first year, a significant decrease in the severity of the LAR was noted in all but one subject (mean decrease of FEV1 before, 40.53% versus after 1 year, 22.95%; p less than 0.0001). After the second year, the severity of the LAR remained the same in the group that received HDM injections during the second year (20.78% versus 23.00%), but in the group that received placebo injections during 1 year, a significant worsening of the LAR was observed after the second year (24.90% versus 31.20%; p = 0.038). From this study it can be concluded that the severity of the LAR decreases after the first year of IT but that the severity of the LAR remains the same after the second year of IT. In children who stop receiving IT after 1 year, we observed a recurrence of the LAR after 1 year to the same level as before IT was started.

Pediatric sublingual immunotherapy efficacy: evidence analysis, 2009-2012

OBJECTIVE To perform a structured analysis of the latest scientific evidence obtained for the clinical efficacy of sublingual immunotherapy (SLIT) in children. DATA SOURCES PubMed, Embase, reference lists from reviews, and personal databases were reviewed for original articles on clinical trials with SLIT in patients younger than 18 years published from January 1, 2009, through December 31, 2012, using broad search and medical subject heading terms. STUDY SELECTIONS Clinical trials, irrespective of their design, of SLIT in the treatment of respiratory and food allergy in patients 18 years or younger were selected. Clinical outcomes (symptom scores, medication use, provocation tests, pulmonary function tests, skin prick tests, and adverse events) and immunologic changes were tabulated. Quality of each trial and total quality of compounded evidence was analyzed with the Grading of Recommendations Assessment, Development and Evaluation system. RESULTS Of 56 articles, 29 met the inclusion criteria. New evidence is robust for the precoseasonal tablet and drop grass pollen SLIT efficacy in allergic rhinitis and scarce for seasonal asthma. Some evidence for Alternaria SLIT efficacy is appearing. For house dust mite (HDM) SLIT in asthma, there is high-quality evidence for medication reduction while maintaining symptom control; evidence for HDM SLIT efficacy in allergic rhinitis is of moderate-low quality. There is moderate evidence for efficacy of dual grass pollen-HDM SLIT after 12 months of treatment and 1 year after discontinuation. Specific provocation test results (nasal, skin) improve with grass pollen and HDM SLIT but nonspecific bronchial provocation testing does not. Food oral immunotherapy is more promising than food SLIT. Possible new surrogate markers have been reported. No anaphylaxis was found among 2469 treated children. CONCLUSION Evidence for efficacy of SLIT in children with respiratory or food allergy is growing.

A matched patient-sibling study on the usage of paracetamol and the subsequent development of allergy and asthma

A number of studies have suggested that intake of paracetamol during pregnancy and during the first months of life is associated with an increased risk of childhood asthma. We aimed to determine the association between paracetamol usage during pregnancy and the first 6 months of life, and childhood allergy (i.e. positive skin prick tests), allergic asthma, and asthma, using a matched patient‐sibling study comparing patients with allergic asthma with their healthy siblings without any symptoms of allergic diseases. Allergy in patients and their siblings was determined by skin prick tests. Children having at least one positive skin prick test were considered to be allergic. Intake of paracetamol was assessed by standardized, interviewer‐administered, questionnaire. Nineteen pairs of allergic asthma patients vs. non‐allergic siblings were compared to determine the risk factors for allergic asthma, while 15 pairs of allergic asthma patients vs. allergic siblings were compared to determine the risk factors for asthma. Moreover, 33 pairs of allergic asthma patients vs. non‐asthmatic siblings (with and without allergy) were compared to determine the risk factors for asthma. In addition, 17 allergic siblings (without asthma) were compared with 19 non‐allergic siblings (without asthma) to determine the risk factors for allergy. Usage of paracetamol during pregnancy was associated with allergic asthma (p = 0.03). Furthermore, usage of paracetamol between birth and 6 months of age, and between 4 and 6 months of age, was also found to be associated with non‐allergic asthma (p = 0.008 and p = 0.03 respectively). Usage of paracetamol during pregnancy and during the early months of life may play a role in the development of allergic and non‐allergic asthma in children. However, due to obvious ethical reasons, direct evidence for this association (i.e. a double‐blind, prospective study) is not available.

The influence of childhood atopic dermatitis on health of mothers, and its impact on Asian families

Ho RCM, Giam YC, Ng TP, Mak A, Goh D, Zhang MWB, Cheak A, Van Bever HP. The influence of childhood atopic dermatitis on health of mothers, and its impact on Asian families.
Pediatr Allergy Immunol 2010: 21: 501–507.
© 2010 John Wiley & Sons A/S

The methodology of the GUSTO cohort study: a novel approach in studying pediatric allergy

Growing Up in Singapore Towards healthy Outcomes (GUSTO) is Singapores largest birth cohort study to date. The main aim of GUSTO is to evaluate the role of developmental factors in the early pathways to metabolic compromise. Detailed data is collected for a range of environmental exposures in the parents and offspring, and allergic disorders are among a number of outcomes assessed in infancy and childhood. Under the Allergy domain of GUSTO, this integrated study will describe the epidemiology of allergic manifestations and different phenotypes in the Asian context and help shed light on the association of metabolic disease to allergy. Epigenetic mechanisms and associations with other childhood disorders will also be explored. The aim of this report is to focus on methodology of GUSTO, and to suggest similar approaches (i.e., integrated cohort studies on pediatric allergy) worldwide. Recruitment commenced in 2009 with a cohort of 1,163 pregnant mothers in their first trimester. The mothers and children were followed throughout pregnancy and follow-up will continue until the child reaches 3 years of age. Preliminary results showed that 39.8% of the mothers had a personal history of having at least one allergic disease, which included asthma, eczema and allergic rhinitis. Further data collection and analyses are still ongoing. Allergy is a complex spectrum of disorders with numerous poorly-understood aspects. The ongoing GUSTO cohort study, with its longitudinal design and multi-disciplinary nature, may provide new insights into developmental influences on allergy. As a Singapore-based study, it will be the first integrated allergy cohort in Southeast Asia, of which recruitment started during pregnancy.

Determination of T-cell subpopulations and intracellular cytokine production (interleukin-2, interleukin-4, and interferon-γ) by cord blood T-lymphocytes of neonates from atopic and non-atopic parents

This report describes the results of a prospective study on immunological markers in cord blood for the prediction of allergic diseases in children. First we evaluated methodological aspects of the flow cytometric technique on cord blood cytokine measurements. Subsequently, the T‐cell subsets and percentage of cytokine‐producing cord blood T‐helper (Th) and T‐suppressor/cytotoxic lymphocytes of neonates from atopic and non‐atopic parents were compared. A group of 33 healthy, full‐term newborn infants of whom 23/33 were at risk for atopy (i.e. having at least one parent with one or more atopic symptoms and positive specific immunoglobulin E [IgE] to at least one common inhalant allergen) was studied. A flow cytometric technique was used to analyze cord blood T‐cell subsets and to determine the percentage of interleukin (IL)‐2‐, IL‐4‐, and interferon‐γ (IFN‐γ)‐producing cord blood Th and T‐suppressor/cytotoxic lymphocytes following stimulation with phorbol 12‐myristate 13‐acetate (PMA) and ionomycin. The percentage of CD3 (T lymphocytes), CD3+ CD4+ (Th lymphocytes), CD3+ CD8+ (T‐suppressor/cytotoxic lymphocytes), CD19+ (B lymphocytes), CD3+ CD4+ CD45RO+ (memory Th lymphocytes), and CD3+ CD4+ CD45RA+ (naive Th lymphocytes) cells was unrelated to parental atopic status. PMA stimulation augmented the percentage of IL‐2‐ and IFN‐γ‐producing Th and T‐suppressor/cytotoxic lymphocytes, whereas the number of IL‐4‐producing T lymphocytes remained very low or undetectable. No differences in the percentage of IL‐2‐, IL‐4‐ and IFN‐γ‐producing Th and T‐suppressor/cytotoxic lymphocytes were found between neonates from atopic and non‐atopic parents. These results will be re‐evaluated when the atopic status of the children at the age of 1 and 2 years can be assessed.