A minimally invasive tool to study immune response and skin barrier in children with atopic dermatitis.

BACKGROUND: Atopic dermatitis (AD) affects children of all skin types. Most research has focused on light skin types. Studies investigating biomarkers in people with AD with dark skin types are lacking. OBJECTIVES: To explore skin barrier and immune response biomarkers in stratum corneum (SC) tape strips from children with AD with different skin types. METHODS: Tape strips were collected from lesional and nonlesional forearm skin of 53 children with AD and 50 controls. We analysed 28 immunomodulatory mediators, and natural moisturizing factors (NMF) and corneocyte morphology. RESULTS: Interleukin (IL)-1ß, IL-18, C-X-C motif chemokine (CXCL) 8 (CXCL8), C-C motif chemokine ligand (CCL) 22 (CCL22), CCL17, CXCL10 and CCL2 were significantly higher (P < 0·05) in lesional AD skin compared with nonlesional AD skin; the opposite trend was seen for IL-1α. CXCL8, CCL2 and CCL17 showed an association with objective SCORing Atopic Dermatitis score. NMF levels showed a gradual decrease from healthy skin to nonlesional and lesional AD skin. This gradual decreasing pattern was observed in skin type II but not in skin type VI. Skin type VI showed higher NMF levels in both nonlesional and lesional AD skin than skin type II. Corneocyte morphology was significantly different in lesional AD skin compared with nonlesional AD and healthy skin. CONCLUSIONS: Minimally invasive tape-stripping is suitable for the determination of many inflammatory mediators and skin barrier biomarkers in children with AD. This study shows differences between children with AD with skin type II and skin type VI in NMF levels, suggesting that some aspects of pathophysiological mechanisms may differ in AD children with light versus dark skin types.

Stability and predictiveness of multiple trigger and episodic viral wheeze in preschoolers.

BACKGROUND: In 2008, the European Respiratory Society Task Force proposed the terms multiple-trigger wheeze (MTW) and episodic (viral) wheeze (EVW) for children with wheezing episodes. We determined MTW and EVW prevalence, their 24-month stability and predictiveness for asthma. METHODS: In total, 565 preschoolers (1-, 2- and 3-year-olds) in primary care with respiratory symptoms were followed until the age of 6 years when asthma was diagnosed. MTW status and EVW status were determined using questionnaire data collected at baseline and after one and 2 years. We distinguished 3 phenotypes and determined their 24-month stability, also accounting for treatment with inhaled corticosteroids (ICS). Logistic regression was used to analyse the phenotypes' associations with asthma. RESULTS: Two hundred and eighty-one children had complete information. MTW and EVW were stable in 10 of 281 (3.6%) and 24 of 281 (8.5%), respectively. The odds of developing asthma for children with stable MTW and stable EVW were 14.4 (1.7-119) and 3.6 (1.2-11.3) times greater than those for children free of wheeze (for at least 1 year). ICS was associated with increased stability of MTW and EVW. CONCLUSIONS: Stable multiple-trigger and stable episodic viral wheeze are relatively uncommon. However, 1- to 3-year-olds with stable MTW are at much increased risk of asthma.

Exclusively breastfed infants at risk for false negative double blind placebo controlled milk challenge.

The double blind placebo controlled food challenge (DBPCFC) is the gold standard for diagnosing cow's milk allergy (CMA). However, false-negative DBPCFC have been reported. We present 2 cases with a false negative DBPCFC in exclusively breastfed infants suspected of CMA. These cases highlight the occurrence of severe allergic reactions of infants who were exclusively breastfed. Several reported causes of a false negative DBPCFC will be discussed. However, there is currently no clear understanding of the cause of a false negative DBPCFC. This paper highlights that a negative outcome of a DBFCFC must be interpreted with caution, because a severe allergic reaction might occur upon re-introduction of cow's milk. Therefore, an additional open food challenge under medical supervision is recommended in exclusively breastfed infants with a negative DBPCFC.

No detectable beneficial systemic immunomodulatory effects of a specific synbiotic mixture in infants with atopic dermatitis.

BACKGROUND: In a murine model of allergic inflammation, Bifidobacterium breve M-16V has been shown to reduce IL-4 and IgE by inducing IL-10 and IFN-γ. However, it remains unknown whether this strain has the same effect in humans with allergic disease. OBJECTIVE: To determine the effects of Bifidobacterium breve M-16V combined with a prebiotic oligosaccharide mixture (synbiotic) on atopic markers, ex vivo cytokine production by peripheral blood mononuclear cells (PBMCs) and circulating regulatory T cell percentage in infants with atopic dermatitis. METHODS: In a double-blind, placebo-controlled multi-centre trial, 90 infants with atopic dermatitis, age <7 months, were randomized to receive an infant formula with Bifidobacterium breve M-16V and a mixture of short chain galactooligosaccharides and long chain fructooligosaccharides (Immunofortis(®) ), or the same formula without synbiotics during 12 weeks. At week 0 and 12, plasma levels of IL-5, IgG1, IgG4, CTACK and TARC, ex vivo cytokine responses by PBMCs and percentage of regulatory T cells, were determined. RESULTS: There were no significant differences between the synbiotic and the placebo group in IL-5, IgG1, IgG4, CTACK and TARC levels and ex vivo cytokine production by anti-CD3/anti-CD28-stimulated PBMCs. With allergen-specific stimuli, we found a decreased IL-12p40/70 and IL-12p70 production in response to egg allergen (P = 0.04 and P = 0.01, respectively) and decreased IL-12p70 production in response to peanut allergen (P = 0.003) in the synbiotic compared with the placebo group. Circulating regulatory T cell percentage did not significantly differ between the groups. CONCLUSIONS AND CLINICAL RELEVANCE: This synbiotic mixture has no detectable effect on plasma levels of the analysed atopic disease markers, ex vivo cytokine production and circulating regulatory T cell percentage in infants with atopic dermatitis, besides down-regulation of IL-12 production in egg- and peanut-stimulated PBMCs. These results do not support the use of this synbiotic in clinical practice.

Assessing quality of care in pediatric asthma: applicability of a revised version of the QUOTE-CNSLD questionnaire.

AIM: To establish the validity and applicability of a revised version of the QUality Of care Through the patient's Eyes-Chronic Non Specific Lung Disease (QUOTE-CNSLD) instrument in a population of children with controlled and partly controlled asthma. METHODS: Randomized controlled trial evaluating quality of care in three follow-up settings: follow-up by the general practitioner, the pediatrician, and the specialized asthma nurse, for a period of 2 years. RESULTS: One hundred and seven children were recruited, 45 from general practice and 62 from hospital practice. The revised QUOTE-CNSLD instrument completed by parents at baseline (T0), after 1 year (T1) and after 2 years (T2) showed that a process-, a structure-, and an asthma-specific domain could be deduced (Cronbach's α of 0.81, 0.82, and 0.62). A separate five-item "child-specific" questionnaire about their caregiver, completed by children, has a Cronbach's α of 0.88. The revised instrument could discriminate between quality of care in different follow-up settings for children with stable asthma, and the asthma-specific domain showed particularly discriminative properties. Quality aspects with potential for improvement could be derived from the scores in all three study groups. CONCLUSION: The revised QUOTE-CNSLD instrument is applicable in a pediatric population with stable asthma and it has discriminative value between different follow-up settings.

Synbiotics prevent asthma-like symptoms in infants with atopic dermatitis.

BACKGROUND: Infants with atopic dermatitis (AD) have a high risk of developing asthma. We investigated the effect of early intervention with synbiotics, a combination of probiotics and prebiotics, on the prevalence of asthma-like symptoms in infants with AD. METHODS: In a double-blind, placebo-controlled multicentre trial, ninety infants with AD, age <7\ months, were randomized to receive an extensively hydrolyzed formula with Bifidobacterium breve M-16V and a galacto/fructooligosaccharide mixture (Immunofortis(®) ), or the same formula without synbiotics during 12 weeks. After 1 year, the prevalence of respiratory symptoms and asthma medication use was evaluated, using a validated questionnaire. Also, total serum IgE and specific IgE against aeroallergens were determined. FINDINGS: Seventy-five children (70.7% male, mean age 17.3 months) completed the 1-year follow-up evaluation. The prevalence of 'frequent wheezing' and 'wheezing and/or noisy breathing apart from colds' was significantly lower in the synbiotic than in the placebo group (13.9%vs 34.2%, absolute risk reduction (ARR) -20.3%, 95% CI -39.2% to -1.5%, and 2.8%vs 30.8%, ARR -28.0%, 95% CI -43.3% to -12.5%, respectively). Significantly less children in the synbiotic than in the placebo group had started to use asthma medication after baseline (5.6%vs 25.6%, ARR -20.1%, 95% CI -35.7% to -4.5%). Total IgE levels did not differ between the two groups. No children in the synbiotic and five children (15.2%) in the placebo group developed elevated IgE levels against cat (ARR -15.2%, 95% CI -27.4% to -2.9%). CONCLUSION: These results suggest that this synbiotic mixture prevents asthma-like symptoms in infants with AD.

Different definitions in childhood asthma: how dependable is the dependent variable?

There is abundant literature on how to select and statistically deal with predictors in prediction models. Less attention has been paid to the choice of the outcome. We assessed the impact of different asthma definitions on prevalence estimates and on the prediction model's performances. We searched PubMed and extracted data of definitions used to diagnose childhood asthma (between 6 and 18 yrs) in cohort studies. Next, using data from an ongoing cohort study (n = 186), we constructed and compared four prediction models which all predict asthma at age 6 yrs, using a fixed set of predictors and four different definitions in turn. We defined an area of clinical indecision (posterior probability between 25% and 60%) and calculated the number of children who remained inside this area. 122 papers yielded 60 different definitions. Prevalence estimates varied between 15.1% and 51.1% depending on the asthma definition used. The percentage of children whose posterior asthma probability was in the area of clinical indecision varied from 14.9% to 65.3%. Variation in definitions and its effect on the performance of prediction models may be another source of otherwise inexplicable variation in daily clinical decision making. More uniformity of operational asthma definitions seems needed.

Effect of a new synbiotic mixture on atopic dermatitis in infants: a randomized-controlled trial.

BACKGROUND: Clinical trials investigating the therapeutic effect of probiotics on atopic dermatitis (AD) show inconsistent results. Better results can possibly be achieved by combining probiotics with prebiotics, i.e. synbiotics. OBJECTIVE: To investigate the therapeutic effect of a synbiotic mixture on the severity of AD in infants. METHODS: In a double-blind, placebo-controlled multi-centre trial, 90 infants with AD [SCORing Atopic Dermatitis (SCORAD) score > or =15], aged < 7 months and exclusively formula fed, were randomly assigned to receive either an extensively hydrolysed formula with Bifidobacterium breve M-16V and a galacto-/fructooligosaccharide mixture (Immunofortis), or the same formula without synbiotics for 12 weeks. The primary outcome was severity of AD, assessed using the SCORAD index. A secondary outcome measure was intestinal microbiota composition. RESULTS: There was no difference in SCORAD score improvement between the synbiotic and the placebo group. The synbiotic group did have a significantly higher percentage of bifidobacteria (54.7% vs. 30.1%, P<0.001) and significantly lower percentages of Clostridium lituseburense/Clostridium histolyticum (0.5 vs. 1.8, P=0.02) and Eubacterium rectale/Clostridium coccoides (7.5 vs. 38.1, P<0.001) after intervention than the placebo group. In the subgroup of infants with IgE-associated AD (n=48), SCORAD score improvement was significantly greater in the synbiotic than in the placebo group at week 12 (-18.1 vs. -13.5 points, P=0.04). CONCLUSIONS: This synbiotic mixture does not have a beneficial effect on AD severity in infants, although it does successfully modulate their intestinal microbiota. Further randomized-controlled trials should explore a possible beneficial effect in IgE-associated AD.

Definition, assessment and treatment of wheezing disorders in preschool children: an evidence-based approach.

There is poor agreement on definitions of different phenotypes of preschool wheezing disorders. The present Task Force proposes to use the terms episodic (viral) wheeze to describe children who wheeze intermittently and are well between episodes, and multiple-trigger wheeze for children who wheeze both during and outside discrete episodes. Investigations are only needed when in doubt about the diagnosis. Based on the limited evidence available, inhaled short-acting beta(2)-agonists by metered-dose inhaler/spacer combination are recommended for symptomatic relief. Educating parents regarding causative factors and treatment is useful. Exposure to tobacco smoke should be avoided; allergen avoidance may be considered when sensitisation has been established. Maintenance treatment with inhaled corticosteroids is recommended for multiple-trigger wheeze; benefits are often small. Montelukast is recommended for the treatment of episodic (viral) wheeze and can be started when symptoms of a viral cold develop. Given the large overlap in phenotypes, and the fact that patients can move from one phenotype to another, inhaled corticosteroids and montelukast may be considered on a trial basis in almost any preschool child with recurrent wheeze, but should be discontinued if there is no clear clinical benefit. Large well-designed randomised controlled trials with clear descriptions of patients are needed to improve the present recommendations on the treatment of these common syndromes.

Bacille-Calmette-Guerin vaccination and the development of allergic disease in children: a randomized, prospective, single-blind study.

BACKGROUND: The increase in the prevalence of allergic diseases in countries with a so-called western lifestyle may be due to a decrease in exposure to infectious agents in early life. OBJECTIVE: To establish the effect of Bacille-Calmette-Guerin (BCG) vaccination in 6-week-old high-risk infants in a prospective single-blind, randomized, placebo-controlled trial on the prevalence of allergic disease at the age of 4 and 18 months. METHODS: Subjects were 121 predominantly Caucasian high-risk newborns, having either a mother, or both a father and at least one sibling with past or present allergic disease. BCG or placebo was administered at the age of 6 weeks, and repeated once when both a post-vaccination scar and a positive TB skin test were absent at the age of 4 months. RESULTS: At the age of 18 months, the prevalence of allergic disease was not significantly different between the two groups. A trend towards less eczema (P=0.07) and significantly less use of medication for eczema was shown in the BCG group compared with the placebo group (P=0.04). CONCLUSION: A single (or once repeated) BCG vaccination in 6-week-old high-risk Caucasian infants was not associated with a 50% reduction in the prevalence of allergic disease. However, there could be a smaller beneficial effect of BCG, especially because a trend towards less eczema and significantly less use of medication for eczema was shown. For definite proof, a larger study should be carried out.

Adherence to inhaled corticosteroids in children with asthma and their parents.

Poor adherence to inhaled corticosteroids (ICSs) may contribute to the recent rise in asthma morbidity. In general, appropriate adherence to ICSs is a complex process that is influenced by various determinants. The purpose of this study was to identify factors that were associated with adherence to ICSs in children with asthma and their parents in a multi-ethnic population in Amsterdam, the Netherlands. Two hundred and thirty-two children, aged 7-17 years, with paediatrician diagnosed asthma and their parents completed questionnaires examining socio-demographics, asthma control, knowledge of asthma and other determinants of adherence. Adherence to ICSs was assessed by self-report and pharmacy record data. We used logistic regression analyses to identify factors associated with adherence to ICSs in children and parents separately. We found no differences in adherence between the different ethnic groups. In the multivariate analysis for children, well-controlled asthma (OR: 4.12; CI: 1.50-11.3) was associated with poorer adherence, whereas positive subjective view of parents (OR: 0.45; CI:0.25-0.81) and self-efficacy (OR:0.51; CI: 0.35-0.75) were inversely associated with poorer adherence. A consistent result with the multivariate models for parents was the inversely significant association between poorer adherence and positive subjective view of parents to use ICSs (OR: 0.39; CI:0.19-0.77). Regardless of ethnic background, children positively stimulated by their parents to use ICSs showed a better adherence than children who experienced less positive influences. These results emphasise the importance of involving parents in the treatment of their child's asthma in order to enhance adherence to ICSs.

Asthma beliefs among mothers and children from different ethnic origins living in Amsterdam, the Netherlands.

BACKGROUND: Doctors and patients hold varying beliefs concerning illness and treatment. Patients' and families' explanatory models (EMs) vary according to personality and sociocultural factors. In a multi-ethnic society, it is becoming increasingly significant that doctors understand the different beliefs of their patients in order to improve patient/doctor communication as well as patient adherence to treatment. METHODS: Twelve focus groups were formed, consisting of 40 children diagnosed with asthma, as well as 28 mothers of these children. These groups included mothers and children of different ethnicities who were living in Amsterdam, the Netherlands. In order to understand the beliefs that both mothers and children hold regarding asthma and its treatment, the explanatory models were analysed and compared. RESULTS: Study findings show that mothers and children, regardless of ethnicity and age, have their own EMs. Overall, there is a great deal of uncertainty related to the causes, consequences, problems, and symptoms of asthma and its treatment. It also seems that many concerns and feelings of discomfort are the result of lack of knowledge. For instance, the fact that asthma is not seen as a chronic disease requiring daily intake of an inhaled corticosteroid, but rather as an acute phenomenon triggered by various factors, may be very relevant for clinical practice. This particular belief might suggest an explanation for non-adherent behaviour. CONCLUSION: A thorough understanding of the mothers' and children's beliefs regarding the illness and its treatment is an important aspect in the management of asthma. Gaining an understanding of these beliefs will provide a foundation for a solid clinician-patient/family partnership in asthma care. Although ethnic differences were observed, the similarities between the mothers' and children's beliefs in this multi-ethnic population were striking. In particular, a common belief is that asthma is considered an acute rather than a chronic condition. In addition, there is a lack of knowledge about the course and the self-management of asthma. Health care providers should be aware of these commonly held beliefs, and this information could be shared in educational programs.

Assessment of current serum levels of PCDD/Fs, dl-PCBs and PBDEs in a Dutch cohort with known perinatal PCDD/F exposure.

As part of a longitudinal cohort study, now in its second decade, we determined PCDDs/Fs dl-PCBs and PBDEs in serum of adolescents with known perinatal PCDD/F exposure. Of the original cohort, 33 adolescents aged 14-19 years, who had been studied previously during their neonatal (n=60), toddler and pre-pubertal period (n=41) agreed to participate in the current follow-up. PCDD/F-, dl-PCB- and PBDE congeners were measured using GC/MS. Current serum levels of PCDD/Fs determined in our cohort were relatively low (mean of 2.2 pg/g) compared to the perinatal exposure. No correlation between perinatal exposure and current serum PCDD/F was found. Planar PCB TEQ levels were 2.2 pg/g. Current summation operatorPBDE levels were 8.7 ng/g lipid. There was one outlier with a summation operatorPBDE of 74 ng/g lipid. The presence of this high value indicates that the exposure pathway is different from PCDD/F and PCB, most likely by dust and food contaminated with dust. Concluding we can say that current PCDD/F levels are quite low compared to the perinatal PCDD/F exposure of the cohort. PBDE levels however are relatively high compared to other European countries, more research on possible health effects of these levels, especially for subjects with outlier concentrations, should be performed.

Residential exposure to mould and dampness is associated with adverse respiratory health.

BACKGROUND: Indoor exposure to mould and dampness is frequently associated with asthma symptoms with and without lung function changes. However, the mechanisms contributing to this threat to respiratory health are only partly understood. OBJECTIVE: To investigate the contribution of recent exposure to mould and dampness in the living room or bedroom to respiratory health in a general practice-based cohort of 526 asthmatic children. METHODS: Parents were questioned about home characteristics, including moulds and dampness. The level of asthma control was evaluated in their participating children by means of asthma symptoms, peak expiratory flow (PEF) variability, severity of airway hyperresponsiveness (AHR), and medication usage. RESULTS: Children exposed to indoor moulds and dampness more often had severe AHR compared with non-exposed (42% vs. 16%; P< or =0.001). They also showed an increased PEF variability (11.3% vs. 8.4%; P=0.03) and, however, not significant, more frequent asthma symptoms. The use of controller medication was not significantly different between exposed and non-exposed children. After adjustment for gender, age, smoking, exposure to parental smoking, parental education, pet ownership, presence of inhalant allergy, use of controller medication, health care center, and season of study assessment, the odds ratio for severe AHR in exposed children was 3.95 [95% confidence interval (CI): 1.82-8.57]. CONCLUSION: We found a consistent association between reported moulds and dampness in the living room or the child's bedroom and an increased risk for severe AHR in a general practice-based cohort of asthmatic children, even after adjustment for gender, presence of inhalant allergy, and use of controller medication.

Severe airway hyperresponsiveness was not predictable with the use of current tools in asthmatic children in general practice.

OBJECTIVE: To evaluate whether moderate to severe airway hyperresponsiveness (AHR) could be suspected with the use of routinely available clinical and environmental information. STUDY DESIGN AND SETTING: Cross-sectional study of asthma in 526 asthmatics aged 7-17 years and treated in general practice. RESULTS: Moderate to severe AHR was present in 48% (n=253) of the participants. The presence of inhalation allergy, nocturnal symptoms, and usage of beta2-mimetics were significantly associated with moderate to severe AHR. If all three factors were present, the probability of the presence of moderate to severe and severe AHR was 76% and 36%, respectively. If all three were absent, the probability decreased to 11% and 5%, respectively. In 319 subjects (64%) AHR could not be adequately predicted with routinely available information. CONCLUSION: Moderate and severe AHR could not be suspected with the use of routinely available clinical and environmental information in the majority of children. Except for a subgroup of children, our models were not helpful in deciding in which child an inhaled corticosteroid should be started or whether the dose should be increased or decreased. We recommend measuring the severity of AHR in these children by means of an inhalation challenge test.

Beclometasone dipropionate extrafine aerosol versus fluticasone propionate in children with asthma.

Beclometasone dipropionate (BDP) extrafine is a hydrofluoroalkane-based, chlorofluorocarbon (CFC)-free inhalation aerosol. This study was conducted to determine whether BDP extrafine and CFC-fluticasone proprionate (FP) aerosols were equivalent in terms of efficacy and tolerability in children with symptomatic mild-to-moderate asthma. Male and female patients (aged 5-12 yr) with an asthma diagnosis for > or =3 months, peak expiratory flow (PEF) > or =60% of predicted normal and suboptimal asthma control were randomised to double-blind treatment with BDP extrafine 200 microg day(-1) (n=139) or CFC-FP 200 microg day(-1) (n=141) for up to 18 weeks. After 6 and 12 weeks, study medication was 'stepped down' to 100 and 50 microg day(-1), respectively, if patients had achieved good asthma control. Patients with poor asthma control discontinued from the study and those with intermediate control continued in the study but did not undergo a dose reduction. The estimated treatment difference in morning PEF% predicted at 6 weeks was -1.9% (90% CI -4.9, 1.0). There was a trend towards a greater increase in forced vital capacity (% predicted) in the BDP extrafine group (5.3 versus 0.4%; p=0.084). A 'step-down' in therapy to 100 microg day(-1) was possible in 36% and 42% of patients in the BDP extrafine and CFC-FP groups, respectively, at 6 weeks. Both drugs were well tolerated. BDP extrafine and CFC-FP aerosols were equally effective at improving asthma control in children with mild-to-moderate asthma at the same daily dose.

Predictors of asthma control in children from different ethnic origins living in Amsterdam.

To identify factors associated with asthma control in a multi-ethnic paediatric population. We interviewed 278 children with paediatrician diagnosed asthma (aged 7-17 years) and one of their parents. Asthma control was assessed with the Asthma Control Questionnaire (ACQ). Detailed information about sociodemographic variables, asthma medication, knowledge of asthma, inhalation technique and environmental factors were collected. Turkish and Moroccan parents were interviewed in their language of choice. Logistic regression analyses were used to identify correlates of asthma control. Of the 278 children, 85 (30.6%) were Dutch, 84 (30.2%) were Moroccan, 58 (20.9%) were Turkish and 51 (18.3%) were Surinamese. Overall, almost 60% had a status of well-controlled asthma, as indicated by the ACQ. Only 51 of the 142 (35.9%) Moroccan and Turkish parents had a good comprehension of the Dutch language. In logistic regression analyses the risk of having uncontrolled asthma was significantly higher among Surinamese children (OR 2.3; 95% CI 1.06-4.83), respondents with insufficient comprehension of the Dutch language (OR 2.3; 95% CI 1.08-4.78), children using woollen blankets (OR 9.8; 95% CI 1.52-63.42), and significantly lower among male (OR 0.5; 95% CI 0.31-0.91) and non-daily users of inhaled corticosteroids (OR 0.6; 95% CI 0.38-1.07). In conclusion, ethnicity as well as insufficient comprehension of the Dutch language appeared to be independent risk factors for uncontrolled asthma. Special attention should be given to children from immigrants groups for example by calling in an interpreter by physicians when comprehension is insufficient.

Inhaled corticosteroids during acute bronchiolitis in the prevention of post-bronchiolitic wheezing.

BACKGROUND: Acute bronchiolitis in infants and young children is associated with long-term airway disease also known as post-bronchiolitic wheezing. Two major hypotheses have been proposed to explain the association between bronchiolitis and PBW. The first hypothesis considers bronchiolitis to be the first manifestation of recurrent wheezing in infants and children who are susceptible to obstructive airway disease. The second hypothesis suggests that the infection and concomitant inflammatory reaction in the acute phase leads to airway epithelium injury resulting in long-term obstructive airway disease. In line with the latter hypothesis, corticosteroids may have a beneficial effect on the prevention of post-bronchiolitic wheezing. OBJECTIVES: The objective of this review was to evaluate the effect of inhaled corticosteroids, started during the acute phase of bronchiolitis, on the prevention of post-bronchiolitic wheezing. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 3, 2006) which contains the Cochrane Acute Respiratory Infections Group's trials register, MEDLINE (1966 to September 2006), EMBASE (1980 to September 2006) and Current Contents (September 2006). Abstracts and reports of congresses (ERS 1999 to September 2005, ATS 1999 to September 2005) were obtained. We contacted experts in the field and pharmaceutical companies for ongoing or unpublished studies. SELECTION CRITERIA: Randomised placebo-controlled trials studying the effect of inhaled corticosteroids in children younger than two years of age with the clinical diagnosis of acute bronchiolitis were included. DATA COLLECTION AND ANALYSIS: Two authors independently extracted data and assessed trial quality using the Jadad 5-point scale. MAIN RESULTS: Five studies matched the inclusion criteria, with a median Jadad score of 4 (Inter Quartile Range 3 to 4), involving 374 infants. Pooling of the data was limited, due to the clinical diversity of the studies. However, no effect of inhaled corticosteroids in the prevention of wheezing (diary records or GP diagnosed), hospital re-admissions or use of corticosteroids or bronchodilators could be demonstrated. Duration of therapy, length of follow up or causative agent (respiratory syncytial virus or not) did not influence the pooled effect. In the three studies that also evaluated the adverse events, none were reported. AUTHORS' CONCLUSIONS: This review does not demonstrate an effect of inhaled corticosteroids given during the acute phase of bronchiolitis in the prevention of post-bronchiolitic wheezing. The small number of included participants and the inability to pool all clinical outcomes precludes us from making strong recommendations.