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BACKGROUND--Inflammation associated with neutrophil infiltration is a commonly observed feature of children with cystic fibrosis. Production of the major neutrophil chemotactic cytokine interleukin 8 (IL-8) is potentially of great importance in the pathology of cystic fibrosis. Concentrations of IL-8 in both sputum and bronchoalveolar lavage fluid have been found to be higher in children with cystic fibrosis than in controls. The IL-8 induced chemotactic response and numbers of IL-8 receptors on peripheral neutrophils obtained from children with cystic fibrosis have been compared with a control group of children. METHODS--Cells were isolated from 18 patients with cystic fibrosis (aged 4-20 years) and 13 controls (aged 5-12 years) by dextran centrifugation followed by separation on Lymphoprep. Chemotaxis was assayed using multiwell microchemotaxis chambers and 5 microns polycarbonate filters. Filters were fixed and stained with Haema-Gurr for counting. Results were expressed as numbers of neutrophils per high power field (HPF). RESULTS--At the optimum concentration (1 x 10(-8) mol/l) the number of cells migrating were similar for controls (150 (12)/HPF) and for the cystic fibrosis group (140 (14)/HPF)). At lower concentrations the numbers of neutrophils migrating were lower for the cystic fibrosis group. Scatchard analysis of 125I-labelled IL-8 binding revealed lower numbers of receptors on neutrophils from patients with cystic fibrosis (22,000 per cell) than from controls (75,000 per cell). CONCLUSIONS--Reduced responsiveness to IL-8 of neutrophils from patients with cystic fibrosis is associated with receptor desensitisation as a result of exposure to high systemic levels of IL-8.

Concurrent pulmonary inflammation and neutrophil infiltration are characteristic of children with cystic fibrosis (CF). The production of the major neutrophil chemotactic cytokine IL-8 by alveolar macrophages or other cells could be of great importance in the pathology of acute lung disease, but its role in the persistent lung inflammation characteristic of CF has not been evaluated. In this study, we have measured, by ELISA, the concentration of IL-8 in sputum, bronchoalveolar lavage, and sera specimens obtained from children with CF. For comparison, IL-8 in bronchoalveolar lavage obtained from asthmatic patients and from non-CF children with or without lung infection and in sera from age-matched controls was measured. High levels of IL-8 were measured in sputum (mean = 2952 pM) and in bronchoalveolar lavage (mean = 6624 pM) from CF patients. In both cases, there was a significant correlation between clinical status (Schwach-man score) and IL-8 levels. This was not true for IL-8 levels measured in sera, which nevertheless were significantly higher in CF patients (p = 0.0001) than in normal controls in the over-10-y age group.

We report the influence of synthetic polymers, trehalose and sodium taurocholate on the stability of both MLVs* and SPLVs prepared from a range of lipids including synthetic polyhydroxyl lipids. In the absence of cryoprotective agents liposomes were found to release greater than 90 per cent of encapsulated marker when exposed to freeze-thawing or freeze-drying procedures. In the presence of polyvinylpalmitate a marginal enhancement of stability towards freeze-drying was observed, the effect being most marked with cholesterol-containing liposomes. Trehalose was also found to stabilize all preparations investigated towards freeze-drying. In particular SPLVS prepared from (C18:0, C14:0-GMG):EPC:C retained in greater than 90 per cent of the entrapped marker. Addition of polymers to trehalose-containing SPLVS did not further increase the stability. SPLVS prepared from lipids possessing a high transition temperature demonstrated enhanced stability in the presence of bile salts. This effect was most marked with SPLVs prepared from (C18:0, C22:0-GMG):C.

RATIONALE: This study provides information on changes in sensitisation rates in children on the Isle of Wight. METHODS: Three cohorts of children were recruited and underwent skin prick tests to a predefined panel of allergens (milk, egg, peanut, cod, house dust mite, cat and grass) by standard methodology. Wheat sensitisation was not analysed for Groups C and D due to different solutions used. Group A: Children born 1989, tested at four years (1993). Group B: Children born 2001/02, tested at three years (2004/05). Group C: Children born 1989, tested at ten years (1999). Group D: Children born in 1991/92, tested at 11 years (2002). RESULTS: Sensitisation to predefined food allergens increased significantly from 1.8% in 1993 (Group A) to 4.2% in 2004 (Group B) (p = 0.008). When wheat-grass cross-reactors were excluded, increase was no longer significant (p = 0.31). In contrast sensitisation to aeroallergens showed a significant decrease from 14.8% to 10.9% (p = 0.006). Notable decreases were seen in HDM (p = 0.006), and grass, (p = 0.013). A significant rise, from 2.2% in 1999 (Group C) to 4.6% in 2002 (Group D), was observed in sensitisation to food allergens (p = 0.008). Sensitivity to peanut (p = 0.1023) and grass (p = 0.0115) rose significantly. CONCLUSION: Prevalence of sensitivity to both food and aeroallergens was seen to be greater amongst older children than younger children. Amongst younger children we found a significant reduction in prevalence of sensitisation to aeroallergens. Amongst older children we found a significant increase in prevalence of sensitisation to food allergens.

Rationale The UK Department of Health advises that pregnant women who are atopic, or for whom the father or sibling of their unborn child has an atopic disease may wish to avoid eating peanuts during pregnancy lactation. We investigated whether peanut avoidance in pregnancy is associated with a family history of atopy and other factors. Methods 1061 women resident on IOW (UK) who gave birth between September 2001 and August 2002 were studied. Family history of atopic disease was obtained at recruitment. At 36 weeks gestation, women completed a food frequency questionnaire. Full information was obtained from 937. Results 521 (55%) mothers aimed to avoid peanuts during pregnancy. Of these, 14% ate peanuts by accident, 159 (30%) avoided tree nuts and 112 (21%) continued the peanut avoidance during lactation. In both mothers who aimed to avoid peanuts and those that didn't, the proportions with a reported family history of atopy were similar (84 and 82%). In these groups equal numbers planned to breast feed and they were equally health conscious in terms of fruit/vegetable intake and smoking cessation. Level of education did not differ. Those avoiding peanuts were more likely to follow other nutritional advice given such as avoidance of raw egg (p Conclusions Peanut avoidance during pregnancy did not correlate with a family history of atopy. Mothers who avoid peanuts during pregnancy are more likely to follow other nutritional advice given during pregnancy.

Rationale The reported prevalence of various manifestations of atopy appears to be increasing. Early sensitization to various allergens would be expected to parallel this rise. Many studies have described the rates of sensitization in high-risk populations but there is a paucity of large population based studies. We undertook a whole population cohort study, investigating the rates of sensitization to foods and aeroallergens in an unselected population at the age of 1 year. Methods A birth cohort comprising all babies born on the Isle of Wight (UK) between September 2001-August 2002 was followed up prospectively from birth with a standardized questionnaire covering: family history of atopy, dietary experience/weaning practices and environmental influences. All children were clinically examined and skin prick tested at the age of one year. The babies underwent SPT to a predefined panel of allergens by standard methodology. Results Of 859 (446boys) eligible babies 709 (82.54%) underwent SPT to a predefined panel of foods and aeroallergens. With a ≥3mm cut off 2.4% (17/709) were sensitized to any allergen with 0.85% (6/709) to any aeroallergens and 1.97% (14/709) to any food allergens tested. With ≥3mm (and ≥2mm) cut-off points respectively the rates of sensitization to the individual food allergens were: milk 0.28%(0.99%); egg 1.55%(2.4%); wheat 0%(0%); fish 0.14%(0.28%); peanut 0.14% (0.56%); sesame 0.14%(0.42%) and to aeroallergens were: HDM 0.28%(0.85%); cat 0.14%(0.99%) and grass 0.28% (0.71%). Conclusion Despite the rising prevalence of reported atopic manifestations, the rates of sensitization to food and aeroallergens remain low in an unselected population at the age of one year.

Rationale In the UK most food related fatal anaphylaxis occurs amongst teenagers. We investigated an unselected population of 15yr olds to ascertain the prevalence of food sensitization and food allergy. Currently there are no epidemiological data available for this age group. Methods Prevalence of reported food problems was established by questionnaires to parents of 15 year olds living on the Isle of Wight (n=765, M: 383). Children were subsequently invited for SPTs (n=636, M:311) to a panel of food and aeroallergens. Those with a convincing history were invited for food challenges. Results 12.8% (98/765) reported problems with foods (with 19.2% actively avoiding some foods). Of the 18 (2.36%) invited for food challenges, 6 declined, 3 were known allergic, 4 didn't improve on food elimination and 3 had a negative challenge. Two with positive open challenges are undergoing DBPCFCs. Rates of sensitization to the food or aeroallergens tested were 12.89% (82/636) and 25.63% (163/636) respectively. Individually, these were: Milk 0.31% (2/636); Egg 0.16% (1/636); Wheat 11.95% (76/636, 90% grass cross-reactivity); Fish 1.26% (8/636); Peanut 2.36% (15/636); Sesame 0.79% (5/636); HDM 16.5% (105/636); Cat 7.23% (46/636); and Grass 15.41% (98/636). Only 11/98 children reporting a food allergy were sensitized to that food. Sensitization rates were higher in boys than girls for both food (OR 1.66 [1.0-2.73], p=0.04) and aeroallergens (OR 2.27 [1.54-3.33], p Conclusion Reported food allergy is common in 15-year olds but the rate of relevant sensitization is low. The food sensitization s rate varies amongst this age group with significant differences between boys and girls.

Rationale Infants born to families with a history of atopy are more at risk of developing allergic diseases than those born to non-atopic families. Genetic influences, particularly maternal factors play a key role. We have investigated whether infants born to atopic and non-atopic mothers differ in terms of weaning, feeding and immunization practices, family pet ownership and exposure to smoking. Methods 1061 women on the IOW (UK) who gave birth between September 2001-August 2002 were included. At recruitment women completed a questionnaire regarding their history of atopic disease. At 3 months (n=915) and 6 months (n=902) post delivery, feeding practices of infants were assessed via a standardized administered questionnaire. Results There was no difference in a range of factors between the infants born to atopic (n=577) and non-atopic mothers (n=358), including exclusive breast feeding for at least 3 months (21% vs 22%), any breastfeeding up to 6 months (20% vs. 27%), weaning before 12-14 weeks (30% vs 25%), consumption of peanut products before 6 months (1.4% vs 1.3%), immunization status (91% vs 92%), cat ownership (31% vs. 30%). However, there were statistically significant differences in exposure to cigarette smoke (29% vs 21%) (p Conclusions Infants born from atopic and non-atopic mothers seem to be similar in terms of feeding, weaning and immunization practices as well as family cat ownership, but not dog ownership. However, in this population infants of atopic mothers were more likely to be exposed to cigarette smoke than those of non-atopic mothers.

The development of chronic lung disease (CLD) following neonatal respiratory distress syndrome (RDS) is associated with pulmonary inflammation. We investigated the role of interleukin 8 (IL-8) in polymorphonuclear leucocyte (PMN) mediated inflammation during RDS and the early stages of CLD. Of the 14 pre-term infants (gestational age

Adverse reaction to cow's milk and infant formulas are common during infancy. Cow's milk has more than 20 constituents proteins and in principle many are capable of giving rise to an IgE mediated response. The prevalence of cow's milk allergy is between 0.5-10% of the paediatric population (FrierKletter, 1970, Gerrard et al., 1973 Foucard, 1985). The clinical diagnosis of cow's milk allergy is difficult because of the great diversity and varying severity of symptoms and is often based on criteria which is then confirmed by challenge with cow's milk (Bock et al., 1988, WershilWalker, 1988). There is no doubt that various immunological mechanisms are involved in cow's milk allergy and in recent years a number of researchers have investigated the role of humoral and cell-mediated immunity in the pathogenesis of cow's milk allergy.

Falls are an issue disproportionately affecting older people who are at increased risk of falls and injury. This protocol describes a pilot study investigating shock-absorbing flooring for fall-related injuries in wards for older people. Objectives To inform future research by evaluating fall-related injuries on the intervention and existing flooring, assessing the sustainability of the flooring in ward environments, estimating the cost-effectiveness of the floor and assessing how the floor affects patients and other users. Design This study uses mixed methods: a pilot cluster randomised controlled trial, observation via mechanical testing and interviews. Eight participating wards (clusters) are randomised using a computer-generated list. No blinding is incorporated into the study. Each site has a baseline period of approximately 6 months. Then, four sites receive the intervention floor, while four continue using standard floors. Sites are then followed up for approximately 1 year. Participants Any person admitted to a bed in the ‘study area’ of a participating ward can be entered into the trial. Orientated patients, visitors and any hospital staff who use the floor in a study area are eligible for inclusion in an interview. Intervention An 8.3 mm thick vinyl floor covering with polyvinyl chloride foam backing (Tarkett Omnisports EXCEL). Outcomes The primary outcome is fall-related injuries. Severity of injuries, falls, cost-effectiveness, user views and mechanical performance (shock absorbency and slip resistance) are also being assessed. Trial registration ClinicalTrials.gov: NCT00817869; UKCRN ID: 5735.

BackgroundPatients often report adverse reactions to wheat. Interpretation of sensitization to wheat pollen and flour with/without sensitization to grass pollen is a clinical problem.AimWe set out to determine the prevalence of wheat allergy in a birth cohort (10/11 year olds) and investigate the usefulness of performing skin prick tests (SPT), specific IgE tests and component resolved diagnostics to wheat pollen and flour.MethodsThe Food Allergy and Intolerance Research (FAIR) birth cohort included babies born on the Isle of Wight (UK) between September 2001–August 2002 (n = 969). Children were followed up at 1, 2, 3 and 10/11 years. 588 children had SPTs to wheat pollen and grass during the 10 year follow-up. 294 children underwent further SPT to wheat flour and 246 had specific IgE testing to wheat and grass.ResultsEight children underwent oral food challenges (OFC). We diagnosed 0.48 % (4/827; 95 % CI 0–1 %) children with wheat allergy based on OFC. 16.3 % (96/588) were sensitized to grass pollen, 13.4 % (79/588) to wheat pollen; 78 % (75/96) sensitized to both. Only one child was sensitized to wheat flour and wheat pollen, but not grass pollen. For specific IgE, 15.0 % (37/246) and 36.2 % (89/246) were sensitized to wheat and grass pollen, with 40.5 % (36/89) sensitized to both. Of the 37 children sensitized to wheat, 3 (8.1 %) were sensitized to omega 5 gliadin, 1 (2.7 %) to wheat lipid transfer protein and 1 to wheat gliadin.ConclusionClinicians should be aware of the high level of cross-sensitization when performing tests to wheat and grass pollen i.e. sensitisation to wheat specific IgE and wheat pollen SPT should be assessed in the presence of grass pollen SPT and/or specific IgE.