Differentiation between infected and non-infected wounds using an electronic nose.

OBJECTIVES: The aim of this study was to explore whether an electronic nose, Aetholab, is able to discriminate between infected versus non-infected wounds, based on headspace analyses from wound swabs. METHODS: A total of 77 patients participated in this pilot study. Each wound was assessed for infection based on clinical judgment. Additionally, two wound swabs were taken, one for microbiological culture and one for measurement with Aetholab. Diagnostic properties with 95% confidence intervals (95%CIs) of Aetholab were calculated with clinical judgment and microbiological culture results as reference standards. RESULTS: With clinical judgment as reference standard, Aetholab had a sensitivity of 91% (95%CI 76-98) and a specificity of 71% (95%CI 55-84). Diagnostic properties were somewhat lower when microbiological culture results were used as reference standard: sensitivity 81% (95%CI 64-91), specificity 63% (95%CI 46-77). CONCLUSIONS: Aetholab seems a promising diagnostic tool for wound infection given the diagnostic properties presented in this pilot study. A larger study is needed to confirm our results.

An ultra-compact low temperature scanning probe microscope for magnetic fields above 30 T.

We present the design of a highly compact high field scanning probe microscope (HF-SPM) for operation at cryogenic temperatures in an extremely high magnetic field, provided by a water-cooled Bitter magnet able to reach 38 T. The HF-SPM is 14 mm in diameter: an Attocube nano-positioner controls the coarse approach of a piezoresistive atomic force microscopy cantilever to a scanned sample. The Bitter magnet constitutes an extreme environment for scanning probe microscopy (SPM) due to the high level of vibrational noise; the Bitter magnet noise at frequencies up to 300 kHz is characterized, and noise mitigation methods are described. The performance of the HF-SPM is demonstrated by topographic imaging and noise measurements at up to 30 T. Additionally, the use of the SPM as a three-dimensional dilatometer for magnetostriction measurements is demonstrated via measurements on a magnetically frustrated spinel sample.

Multi-centre prospective study on diagnosing subtypes of lung cancer by exhaled-breath analysis.

OBJECTIVES: Lung cancer is a leading cause of mortality. Exhaled-breath analysis of volatile organic compounds (VOC's) might detect lung cancer early in the course of the disease, which may improve outcomes. Subtyping lung cancers could be helpful in further clinical decisions. MATERIALS AND METHODS: In a prospective, multi-centre study, using 10 electronic nose devices, 144 subjects diagnosed with NSCLC and 146 healthy subjects, including subjects considered negative for NSCLC after investigation, breathed into the Aeonose™ (The eNose Company, Zutphen, Netherlands). Also, analyses into subtypes of NSCLC, such as adenocarcinoma (AC) and squamous cell carcinoma (SCC), and analyses of patients with small cell lung cancer (SCLC) were performed. RESULTS: Choosing a cut-off point to predominantly rule out cancer resulted for NSCLC in a sensitivity of 94.4%, a specificity of 32.9%, a positive predictive value of 58.1%, a negative predictive value (NPV) of 85.7%, and an area under the curve (AUC) of 0.76. For AC sensitivity, PPV, NPV, and AUC were 81.5%, 56.4%, 79.5%, and 0.74, respectively, while for SCC these numbers were 80.8%, 45.7%, 93.0%, and 0.77, respectively. SCLC could be ruled out with a sensitivity of 88.9% and an NPV of 96.8% with an AUC of 0.86. CONCLUSION: Electronic nose technology with the Aeonose™ can play an important role in rapidly excluding lung cancer due to the high negative predictive value for various, but not all types of lung cancer. Patients showing positive breath tests should still be subjected to further diagnostic testing.

A low-temperature scanning tunneling microscope capable of microscopy and spectroscopy in a Bitter magnet at up to 34 T.

We present the design and performance of a cryogenic scanning tunneling microscope (STM) which operates inside a water-cooled Bitter magnet, which can attain a magnetic field of up to 38 T. Due to the high vibration environment generated by the magnet cooling water, a uniquely designed STM and a vibration damping system are required. The STM scan head is designed to be as compact and rigid as possible, to minimize the effect of vibrational noise as well as fit the size constraints of the Bitter magnet. The STM uses a differential screw mechanism for coarse tip-sample approach, and operates in helium exchange gas at cryogenic temperatures. The reliability and performance of the STM are demonstrated through topographic imaging and scanning tunneling spectroscopy on highly oriented pyrolytic graphite at T = 4.2 K and in magnetic fields up to 34 T.

Effects of Supplementation of the Synbiotic Ecologic® 825/FOS P6 on Intestinal Barrier Function in Healthy Humans: A Randomized Controlled Trial.

BACKGROUND AND AIMS: Probiotics, prebiotics and synbiotics have been suggested as dietary strategies to improve intestinal barrier function. This study aimed to assess the effect of two weeks synbiotic supplementation on intestinal permeability under basal and stressed conditions. Secondary aims were the assessment of two weeks synbiotic supplementation on systemic immune function and gastrointestinal symptoms including defecation pattern. DESIGN: Twenty healthy adults completed a double-blind, controlled, randomized, parallel design study. INTERVENTION: Groups either received synbiotic (1.5 × 1010 CFU Ecologic® 825 + 10 g fructo-oligosaccharides (FOS P6) per day) or control supplements for two weeks. OUTCOMES: Intestinal segment specific permeability was assessed non-invasively by oral administration of multiple sugar probes and, subsequently, assessing the excretion of these probes in urine. This test was conducted at baseline and at the end of intervention, in the absence and in the presence of an indomethacin challenge. Indomethacin was applied to induce a compromised gut state. Plasma zonulin, cytokines and chemokines were measured at baseline and at the end of intervention. Gastrointestinal symptoms and stool frequency were recorded at baseline and daily during intervention. RESULTS: Significantly more male subjects were in the synbiotic group compared to the control group (P = 0.025). Indomethacin significantly increased urinary lactulose/rhamnose ratio versus without indomethacin, both in the control group (P = 0.005) and in the synbiotic group (P = 0.017). Urinary sugar recoveries and ratios, plasma levels of zonulin, cytokines and chemokines, and gastrointestinal symptom scores were not significantly different after control or synbiotic intervention. Stool frequency within the synbiotic group was significantly increased during synbiotic intervention compared to baseline (P = 0.039) and higher compared to control intervention (P = 0.045). CONCLUSION: Two weeks Ecologic® 825/FOS P6 supplementation increased stool frequency, but did not affect intestinal permeability neither under basal nor under indomethacin-induced stressed conditions, immune function or gastrointestinal symptoms in healthy adults.

Prospective multicentre cohort study of patient-reported outcomes after cholecystectomy for uncomplicated symptomatic cholecystolithiasis.

BACKGROUND: Up to 33 per cent of patients with uncomplicated symptomatic cholecystolithiasis report persistent pain after cholecystectomy. The aim of this study was to determine characteristics associated with patient-reported absence of abdominal pain after cholecystectomy, improved abdominal symptoms, and patient-reported positive cholecystectomy results in a prospective cohort multicentre study. METHODS: Patients aged 18 years or more with symptomatic cholecystolithiasis who had a cholecystectomy between June 2012 and June 2014 in one of three hospitals were included. Before surgery all patients were sent the Gastrointestinal Quality of Life Index (GIQLI) questionnaire and the McGill Pain Questionnaire (MPQ). At 12 weeks after surgery, patients were invited to complete the GIQLI and Patients' Experience of Surgery Questionnaire (PESQ). Logistic regression analyses were performed to determine associations. RESULTS: Questionnaires were sent to 552 patients and returned by 342 before and after surgery. Postoperative absence of abdominal pain was reported by 60·5 per cent of patients. A high preoperative GIQLI score, episodic pain, and duration of pain of 1 year or less were associated with postoperative absence of pain. These factors showed no association with improved abdominal symptoms (reported by 91·5 per cent of patients) or a positive surgery result (reported by 92·4 per cent). CONCLUSION: Preoperative characteristics determine the odds for relief of abdominal pain after cholecystectomy. However, these factors were not associated with patient-reported improvement of abdominal symptoms or patient-reported positive cholecystectomy results, highlighting the variation of internal standards and expectations of patients before cholecystectomy.

The effects of probiotics on barrier function and mucosal pouch microbiota during maintenance treatment for severe pouchitis in patients with ulcerative colitis.

BACKGROUND: A total of 10-15% of patients with an ileoanal pouch develop severe pouchitis necessitating long-term use of antibiotics or pouch excision. Probiotics reduce the risk of recurrence of pouchitis, but mechanisms behind these effects are not fully understood. AIM: To examine mucosal barrier function in pouchitis, before and after probiotic supplementation and to assess composition of mucosal pouch microbiota. METHODS: Sixteen patients with severe pouchitis underwent endoscopy with biopsies of the pouch on three occasions: during active pouchitis; clinical remission by 4 weeks of antibiotics; after 8 weeks of subsequent probiotic supplementation (Ecologic 825, Winclove, Amsterdam, the Netherlands). Thirteen individuals with a healthy ileoanal pouch were sampled once as controls. Ussing chambers were used to assess transmucosal passage of Escherichia coli K12, permeability to horseradish peroxidase (HRP) and 5¹Cr-EDTA. Composition and diversity of the microbiota was analysed using Human Intestinal Tract Chip. RESULTS: Pouchitis Disease Activity Index (PDAI) was significantly improved after antibiotic and probiotic supplementation. Escherichia coli K12 passage during active pouchitis [3.7 (3.4-8.5); median (IQR)] was significantly higher than in controls [1.7 (1.0-2.4); P < 0.01], did not change after antibiotic treatment [5.0 (3.3-7.1); P = ns], but was significantly reduced after subsequent probiotic supplementation [2.2 (1.7-3.3); P < 0.05]. No significant effects of antibiotics or probiotics were observed on composition of mucosal pouch microbiota; however, E. coli passage correlated with bacterial diversity (r = -0.40; P = 0.018). Microbial groups belonging to Bacteroidetes and Clostridium clusters IX, XI and XIVa were associated with healthy pouches. CONCLUSIONS: Probiotics restored the mucosal barrier to E. coli and HRP in patients with pouchitis, a feasible factor in prevention of recurrence during maintenance treatment. Restored barrier function did not translate into significant changes in mucosal microbiota composition, but bacterial diversity correlated with barrier function.

The 8-year follow-up of the PIAMA intervention study assessing the effect of mite-impermeable mattress covers.

BACKGROUND: Exposure to high levels of house dust mite (HDM) allergens is associated with the development of allergic sensitization to HDM, a risk factor for the development of asthma, rhinitis, and allergic dermatitis. We studied the effect of an early intervention with mite-impermeable mattress covers on HDM allergen levels and the development of asthma and mite allergy throughout the first 8 years of life. METHODS: High-risk children (allergic mother) were prenatally recruited and randomly allocated to two groups receiving mite allergen-impermeable (n = 416) and placebo mattress covers (n = 394) or no intervention (n = 472). Asthma and allergies were assessed yearly by questionnaire. Specific immunoglobulin E and bronchial hyper-responsiveness were measured at the age of 8 years. Mattress dust samples collected at different time points were analyzed for HDM allergens. RESULTS: At the age of 8 years, levels of HDM allergen Der f1 but not Der p1 were lower in the active than the placebo mattress cover group. In repeated measures analyses, we found a temporary decreased risk of asthma symptoms at the age of 2 years in the intervention group compared to the placebo group and a temporary association between higher HDM allergen exposure at the age of 3 months and more asthma symptoms. CONCLUSION: Early intervention with mite-impermeable mattress covers is successful in reducing exposure to Der f1; it only temporarily reduces the risk of asthma symptoms and does not reduce the risk of hay fever, eczema, and allergic sensitization.

E-cadherin gene polymorphisms in asthma patients using inhaled corticosteroids.

E-cadherins form intercellular junctions that maintain epithelial integrity. Epithelial integrity is impaired in asthma and can be restored by inhaled corticosteroids (ICSs). Our aim was to investigate the association of CDH1 gene polymorphisms (single-nucleotide polymorphisms (SNPs)) with airway remodelling, inflammation and forced expiratory volume in 1 s (FEV1) decline in asthma patients and assess whether ICSs modulate these effects. Bronchial biopsies of 138 asthmatics were available (population 1). Associations of 17 haplotype-tagging SNPs with epithelial E-cadherin expression, biopsy parameters and FEV1/vital capacity (VC) ratio were tested. FEV1 and VC data were collected in 281 asthmatics with 30-yr follow-up (population 2). Linear mixed-effect models were used to assess associations of SNPs with FEV1 decline. Seven out of the 17 SNPs were associated with airway remodelling, three with CD8+ T-cell counts, two with eosinophil counts and seven with FEV1 decline. All associations occurred only in patients using ICS. In general, alleles associated with less remodelling correlated with less FEV1 decline and higher FEV1/VC. Decreased epithelial E-cadherin expression was associated with five SNPs in non-ICS users. In conclusion, our data show that CDH1 polymorphisms are associated with epithelial E-cadherin expression and suggest that epithelial adhesion is an important contributor to airway remodelling and lung function in asthma. These effects are modified by the use of inhaled corticosteroids.

Toll-like receptors and microbial exposure: gene-gene and gene-environment interaction in the development of atopy.

Environmental and genetic factors contribute to atopy development. High microbial exposure may confer a protective effect on atopy. Toll-like receptors (TLRs) bind microbial products and are important in activating the immune system. To assess whether interactions between microbial exposures and genes encoding TLRs (and related genes) result in atopy, genes, environmental factors and gene-environment interactions of 66 single-nucleotide polymorphisms (SNPs) of 12 genes (TLR 1-6, 9 and 10, CD14, MD2, lipopolysaccharide-binding protein (LBP) and Dectin-1), and six proxy parameters of microbial exposure (sibship size, pets (three different parameters), day-care and intrauterine and childhood tobacco smoke exposure) were analysed for association with atopic phenotypes in 3,062 Dutch children (the Allergenic study). The presence of two or more older siblings increased the risk of developing high total immunoglobulin (Ig)E levels at different ages. This risk increased further in children aged 1-2 yrs carrying the minor allele of TLR6 SNP rs1039559. Furthermore, novel two- and three-factor gene-gene and gene-environment interactions were found (e.g. between sibship size, day-care and LBP SNP rs2232596). Larger sibship size is associated with increased total IgE levels. Furthermore, complex two- and three-factor interactions exist between genes and the environment. The TLRs and related genes interact with proxy parameters of high microbial exposure in atopy development.

Projections of the effects of climate change on allergic asthma: the contribution of aerobiology.

Climate change is unequivocal and represents a possible threat for patients affected by allergic conditions. It has already had an impact on living organisms, including plants and fungi with current scenarios projecting further effects by the end of the century. Over the last three decades, studies have shown changes in production, dispersion and allergen content of pollen and spores, which may be region- and species-specific. In addition, these changes may have been influenced by urban air pollutants interacting directly with pollen. Data suggest an increasing effect of aeroallergens on allergic patients over this period, which may also imply a greater likelihood of the development of an allergic respiratory disease in sensitized subjects and exacerbation of symptomatic patients. There are a number of limitations that make predictions uncertain, and further and specifically designed studies are needed to clarify current effects and future scenarios. We recommend: More stress on pollen/spore exposure in the diagnosis and treatment guidelines of respiratory and allergic diseases; collection of aerobiological data in a structured way at the European level; creation, promotion and support of multidisciplinary research teams in this area; lobbying the European Union and other funders to finance this research.

Cannabis with high δ9-THC contents affects perception and visual selective attention acutely: an event-related potential study.

OBJECTIVE: Cannabis intake has been reported to affect cognitive functions such as selective attention. This study addressed the effects of exposure to cannabis with up to 69.4mg Delta(9)-tetrahydrocannabinol (THC) on Event-Related Potentials (ERPs) recorded during a visual selective attention task. METHODS: Twenty-four participants smoked cannabis cigarettes with four doses of THC on four test days in a randomized, double blind, placebo-controlled, crossover study. Two hours after THC exposure the participants performed a visual selective attention task and concomitant ERPs were recorded. RESULTS: Accuracy decreased linearly and reaction times increased linearly with THC dose. However, performance measures and most of the ERP components related specifically to selective attention did not show significant dose effects. Only in relatively light cannabis users the Occipital Selection Negativity decreased linearly with dose. Furthermore, ERP components reflecting perceptual processing, as well as the P300 component, decreased in amplitude after THC exposure. Only the former effect showed a linear dose-response relation. CONCLUSIONS: The decrements in performance and ERP amplitudes induced by exposure to cannabis with high THC content resulted from a non-selective decrease in attentional or processing resources. SIGNIFICANCE: Performance requiring attentional resources, such as vehicle control, may be compromised several hours after smoking cannabis cigarettes containing high doses of THC, as presently available in Europe and Northern America.

TLR-related pathway analysis: novel gene-gene interactions in the development of asthma and atopy.

BACKGROUND: The toll-like receptor (TLR)-related pathway is important in host defence and may be crucial in the development of asthma and atopy. Numerous studies have shown associations of TLR-related pathway genes with asthma and atopy phenotypes. So far it has not been investigated whether gene-gene interactions in this pathway contribute to atopy and asthma development. METHODS: One hundred and sixty-nine haplotype tagging single nucleotide polymorphisms (SNPs) of 29 genes (i.e. membrane and intracellular receptors, TLR4 or lipopolysaccharide-binding/facilitating proteins, adaptors, interleukin-1 receptor associated kinases, kinases, chaperone molecules, transcription factors and inhibitors) were analysed for single- and multilocus associations with atopy [total and specific immunglobulin E (IgE) at 1-2 and 6-8 years] and asthma (6-8 years). A total of 3062 Dutch children from the birth cohorts PIAMA, PREVASC and KOALA (Allergenic study) were investigated. Chi-squared test, logistic regression and the data mining approach multifactor dimensionality reduction method (MDR) were used in analysis. RESULTS: Several genes in the TLR-related pathway were associated with atopy and/or asthma [e.g. IL1RL1, BPI, NOD1, NOD2 and MAP3K7IP1]. Multiple, single associations were found with the phenotypes under study. MDR analysis showed novel, significant gene-gene interactions in association with atopy and asthma phenotypes (e.g. IL1RL1 and TLR4 with sIgE to indoor allergens and IRAK1, NOD1 and MAP3K7IP1 with asthma). Interestingly, gene-gene interactions were identified with SNPs that did not have an effect on their own. CONCLUSION: Our unbiased approach provided suggestive evidence for interaction between several TLR-related pathway genes important in atopy and/or asthma development and pointed to novel genes.

Breast feeding, parental allergy and asthma in children followed for 8 years. The PIAMA birth cohort study.

BACKGROUND: It is unclear how the association between breast feeding and asthma develops with age of the child and how this association over time is influenced by maternal or paternal allergy. These factors--the age of the child and maternal or paternal allergy--might partly explain the conflicting results observed in cross-sectional studies. METHODS: The study population consisted of 3115 Dutch children born in 1996/1997 who participated in the PIAMA (Prevention and Incidence of Asthma and Mite Allergy) birth cohort study. Data on breast feeding and asthma (based on wheeze, dyspnoea and prescription of inhaled steroids) were collected by yearly questionnaires. At 8 years, specific immunoglobulin E (IgE) to airborne allergens and bronchial responsiveness were measured. Data were analysed by logistic regression and generalised estimating equations (GEEs), and stratified by maternal and paternal allergic status. RESULTS: 35% (n = 1081) of the children were breast fed for >16 weeks. At 8 years of age, 12.6% (n = 392) had asthma. Breast feeding (>16 weeks vs no breast feeding) was significantly associated with a lower asthma prevalence from 3 to 8 years of age, in children of both non-allergic and allergic mothers. The inverse association between breast feeding and sensitisation to airborne allergens at 8 years was non-significant. Breast feeding was not associated with bronchial hyper-responsiveness. No interaction between breast feeding and gender, maternal allergy or paternal allergy was observed in any of the associations. CONCLUSIONS: Breast feeding is associated with a lower asthma risk in children until 8 years of age without evidence of attenuation and regardless of the family history of allergy.

Smoke exposure interacts with ADAM33 polymorphisms in the development of lung function and hyperresponsiveness.

INTRODUCTION: ADAM33 is the first identified asthma gene by positional cloning, especially asthma combined with bronchial hyperresponsiveness (BHR). Moreover, ADAM33 is associated with early-life lung function and decline of forced expiratory volume in 1 s (FEV(1)) in the general population. In utero and postnatal cigarette smoke exposure (CSE) are associated with reduced lung function, and development of BHR and asthma. We hypothesized that this may occur via interaction with ADAM33. AIM: To replicate the role of ADAM33 in childhood lung function and development of BHR and asthma. Furthermore, we investigated gene-environment interaction of ADAM33 with in utero and postnatal CSE in the Dutch PIAMA cohort. METHODS: Six ADAM33 single-nucleotide polymorphisms (SNPs) were genotyped. Rint was measured at age 4 and 8 years, FEV(1) and BHR at age 8 years; asthma was based on questionnaire data at age 8. RESULTS: In the total cohort, the rs511898 A, rs528557 C, and rs2280090 A alleles increased the risk to develop asthma (+BHR). There existed interaction between in utero but not postnatal CSE and the rs528557 and rs3918396 SNPs with respect to development of BHR, the rs3918396 SNP with Rint at age 8 and the rs528557 SNP with FEV(1)% predicted. CONCLUSIONS: We confirm associations between ADAM33 and the development of asthma (+BHR). This is the first study suggesting that interaction of in utero CSE with ADAM33 results in reduced lung function and the development of BHR, which needs further confirmation.

Effects of pets on asthma development up to 8 years of age: the PIAMA study.

BACKGROUND: Recall bias may provide discrepant relationships of pet exposure with sensitization and asthma development. We studied prospectively effects of pets at home on development of sensitization, asthma and respiratory symptoms from birth up to age 8 years. METHODS: Event history analysis was performed on annually registered data of 2951 children, participating in the PIAMA birth cohort study. RESULTS: Children with a cat or dog at home at 3 months of age had a significantly lower prevalence of sensitization to inhalant allergens at age 8, but not of asthma. A cat decreased the risk of house dust mite sensitization at age 8 [odds ratio (OR) = 0.68, 95% confidence interval (CI) 0.49-0.95], a dog of pollen sensitization (OR = 0.49, 95% CI: 0.29-0.83). A cat or dog at home did not significantly affect asthma incidence in each subsequent year. From 2 years of age onwards, the incidence of wheeze (OR = 1.52, 95% CI: 1.12-2.05) and a dry cough at night (OR = 1.28, 95% CI: 1.05-1.57) was higher in children with a dog, whereas removal of a dog increased the risk of developing asthma symptoms. Comparing analyses using prospectively and retrospectively collected data on diagnosed asthma showed important recall bias. CONCLUSIONS: Our prospective study shows a protective effect of early presence of pets at home on sensitization to inhalant allergens, but no prevention of asthma development. Furthermore, children with pets had more frequent transient or intermittent asthma symptoms. Parental report of asthma by recall may provide spurious results of these associations.

Asthma at 8 years of age in children born by caesarean section.

BACKGROUND: Caesarean section might be a risk factor for asthma because of delayed microbial colonisation, but the association remains controversial. A study was undertaken to investigate prospectively whether children born by caesarean section are more at risk of having asthma in childhood and sensitisation at the age of 8 years, taking into account the allergic status of the parents. METHODS: 2917 children who participated in a birth cohort study were followed for 8 years. The definition of asthma included wheeze, dyspnoea and prescription of inhaled steroids. In a subgroup (n = 1454), serum IgE antibodies for inhalant and food allergens were measured at 8 years. RESULTS: In the total study population, 12.4% (n = 362) of the children had asthma at the age of 8 years. Caesarean section, with a total prevalence of 8.5%, was associated with an increased risk of asthma (OR 1.79; 95% CI 1.27 to 2.51). This association was stronger among predisposed children (with two allergic parents: OR 2.91; 95% CI 1.20 to 7.05; with only one: OR 1.86; 95% CI 1.12 to 3.09) than in children with non-allergic parents (OR 1.36; 95% CI 0.77 to 2.42). The association between caesarean section and sensitisation at the age of 8 years was significant only in children of non-allergic parents (OR 2.14; 95% CI 1.16 to 3.98). CONCLUSIONS: Children born by caesarean section have a higher risk of asthma than those born by vaginal delivery, particularly children of allergic parents. Caesarean section increases the risk for sensitisation to common allergens in children with non-allergic parents only.

Happiness to be gained in paediatric asthma care.

The aim of the present study was to establish the efficacy in terms of morbidity and health-related quality of life (HRQoL) of a group asthma education-exercise programme to children with low (below 10th percentile value) quality-of-life scores. A controlled, randomised, open, clinical trial was conducted. In total, 36 out of 53 unhappy children, among 204 (68%) respondents, treated in four paediatric practices, enrolled (mean age 10 yrs; range: 8-12 yrs), after random allocation in control and intervention groups (child, parent, teacher). Measurements were taken at baseline (T0) and after 3, 6 (T6) and 9 months (T9; intervention group only at 9 months). All but four controls completed the study. From T0-T6, changes (Delta) in HRQoL were clinically important and significantly greater in the intervention group than in the control group, both for generic HRQoL (effect size (ES) 0.95; Delta 16%+/-12% versus -1+/-4%) and for asthma-specific HRQoL (ES 0.58; Delta 15%+/-17% versus 1.5+/-14%). T9 measurements were consistent with T6 findings. Changes in sick days (ES 0.78), oral prednisone courses (ES 0.71) and doctor visits (ES 0.74) over a 6-month period were greater in the intervention group than in the control group. Changes could not be ascribed to change in lung function or medication. In unhappy children, quality of life and morbidity may improve with a low intensity asthma education-exercise programme, even without gains in pulmonary function or exercise tolerance.

Interleukin 13, CD14, pet and tobacco smoke influence atopy in three Dutch cohorts: the allergenic study.

Studying gene-environment interactions may elucidate the complex origins of atopic diseases but requires large study populations. Pooling data from several cohort studies may help but may also obscure findings. Gene-environment interactions in atopy development were studied and the benefits of pooling data were evaluated. Haplotype-tagging polymorphisms in the genes interleukin (IL)13 and CD14 were genotyped in 3,062 children from the following birth cohorts: the Prevention and Incidence of Asthma and Mite Allergy (PIAMA) study; the Prevention of Asthma in Children (PREVASC) study; and the Child, Parent, Health, Focus on Lifestyle and Predisposition (KOALA) study, and tested for association with total and specific immunoglobulin (Ig)E and interaction with tobacco smoke and pet exposure at ages 1, 2, 4 and 8 yrs by analysis of variance, Chi-squared tests and regression analyses. At all ages, in IL13, minor alleles of rs1295685 and rs20541 were significantly associated with elevated IgE levels in pooled analyses. In CD14, the rs2569190-TT and rs2569191-CC genotypes associated with lower IgE and decreased risk of sensitisation at 4 and 8 yrs in children exposed to pets, with an opposite effect in nonexposed children. Findings for IL13 and CD14 were comparable in separate cohorts. The present study indicates that atopy is importantly influenced by interleukin 13 at age 1-8 yrs and by CD14 in interaction with pet exposure at ages 4 and 8 yrs. Additionally, pooled data improved effect estimates and genetic effects could be detected in interaction with important environmental factors.