Elevated IL-5 and IL-13 responses to egg proteins predate the introduction of egg in solid foods in infants with eczema

Accepted manuscript online: 6 August 2015Background: Egg allergy is a leading cause of food allergy in young infants; however, little is known about early allergen-specific T-cell responses which predate the presentation of egg allergy, and if these are altered by early egg exposure. Objective: To investigate the early T-cell responses to multiple egg proteins in relation to patterns of egg exposure and subsequent IgE-mediated egg allergy. Methods: Egg-specific T-cell cytokine responses (IL-5, IL-13, IL-10, IFNc and TNFa) to ovomucoid (OM), ovalbumin (OVA), conalbumin (CON) and lysozyme (LYS) were measured in infants with eczema at 4 months of age (n = 40), before randomization to receive ‘early egg’ or a placebo as part of a randomized controlled trial (Australian New Zealand Clinical Trials Registry number 12609000415202) and at 12 months of age (n = 58), when IgE-mediated egg allergy was assessed by skin prick test and food challenge. Results In 4–month-old infants, who had not directly ingested egg, those who subsequently developed egg allergy already had significantly higher Th2 cytokine responses to multiple egg allergens, particularly elevated IL-13 responses to OVA (P = 0.004), OM (P = 0.012) and LYS (P = 0.003) and elevated IL-5 to the same antigens (P = 0.031, 0.04 and 0.003, respectively). IL-13 responses (to OVA and LYS) and IL-5 responses (to LYS) at 4 months significantly predicted egg allergy at 12 months. All responses significantly declined with age in the egg-allergic infants, and this did not appear to be modified by ‘early’ introduction of egg. Conclusions & Clinical Relevance: Elevated egg-specific Th2 cytokine responses were established prior to egg ingestion at 4 months and were not significantly altered by introduction of egg. Th2 responses at 4 months of age predicted egg allergy at 12 months, suggesting that this could be used as a biomarker to select infants for early prevention and management strategies.J. R. Metcalfe, N. D'Vaz, M. Makrides, M. S. Gold, P. Quinn, C. E. West, R. Loh, S. L. Prescott and D. J. Palme

Tendinopathy—from basic science to treatment

Chronic tendon pathology (tendinopathy), although common, is difficult to treat. Tendons possess a highly organized fibrillar matrix, consisting of type I collagen and various 'minor' collagens, proteoglycans and glycoproteins. The tendon matrix is maintained by the resident tenocytes, and there is evidence of a continuous process of matrix remodeling, although the rate of turnover varies at different sites. A change in remodeling activity is associated with the onset of tendinopathy. Major molecular changes include increased expression of type III collagen, fibronectin, tenascin C, aggrecan and biglycan. These changes are consistent with repair, but they might also be an adaptive response to changes in mechanical loading. Repeated minor strain is thought to be the major precipitating factor in tendinopathy, although further work is required to determine whether it is mechanical overstimulation or understimulation that leads to the change in tenocyte activity. Metalloproteinase enzymes have an important role in the tendon matrix, being responsible for the degradation of collagen and proteoglycan in both healthy patients and those with disease. Metalloproteinases that show increased expression in painful tendinopathy include ADAM (a disintegrin and metalloproteinase)-12 and MMP (matrix metalloproteinase)-23. The role of these enzymes in tendon pathology is unknown, and further work is required to identify novel and specific molecular targets for therapy

A systematic review with procedural assessments and meta-analysis of Low Level Laser Therapy in lateral elbow tendinopathy (tennis elbow)

<p>Abstract</p> <p>Background</p> <p>Recent reviews have indicated that low level level laser therapy (LLLT) is ineffective in lateral elbow tendinopathy (LET) without assessing validity of treatment procedures and doses or the influence of prior steroid injections.</p> <p>Methods</p> <p>Systematic review with meta-analysis, with primary outcome measures of pain relief and/or global improvement and subgroup analyses of methodological quality, wavelengths and treatment procedures.</p> <p>Results</p> <p>18 randomised placebo-controlled trials (RCTs) were identified with 13 RCTs (730 patients) meeting the criteria for meta-analysis. 12 RCTs satisfied half or more of the methodological criteria. Publication bias was detected by Egger's graphical test, which showed a negative direction of bias. Ten of the trials included patients with poor prognosis caused by failed steroid injections or other treatment failures, or long symptom duration or severe baseline pain. The weighted mean difference (WMD) for pain relief was 10.2 mm [95% CI: 3.0 to 17.5] and the RR for global improvement was 1.36 [1.16 to 1.60]. Trials which targeted acupuncture points reported negative results, as did trials with wavelengths 820, 830 and 1064 nm. In a subgroup of five trials with 904 nm lasers and one trial with 632 nm wavelength where the lateral elbow tendon insertions were directly irradiated, WMD for pain relief was 17.2 mm [95% CI: 8.5 to 25.9] and 14.0 mm [95% CI: 7.4 to 20.6] respectively, while RR for global pain improvement was only reported for 904 nm at 1.53 [95% CI: 1.28 to 1.83]. LLLT doses in this subgroup ranged between 0.5 and 7.2 Joules. Secondary outcome measures of painfree grip strength, pain pressure threshold, sick leave and follow-up data from 3 to 8 weeks after the end of treatment, showed consistently significant results in favour of the same LLLT subgroup (p < 0.02). No serious side-effects were reported.</p> <p>Conclusion</p> <p>LLLT administered with optimal doses of 904 nm and possibly 632 nm wavelengths directly to the lateral elbow tendon insertions, seem to offer short-term pain relief and less disability in LET, both alone and in conjunction with an exercise regimen. This finding contradicts the conclusions of previous reviews which failed to assess treatment procedures, wavelengths and optimal doses.</p

Bronchodilator responsiveness in children with asthma is not influenced by spacer device selection

Introduction: Spacer devices optimize delivery of aerosol therapies and maximize therapeutic efficacy. We assessed the impact of spacer device on the prevalence and magnitude of bronchodilator response (BDR) in children with asthma. Methods: Children with physician confirmed asthma and parentally reported symptoms in the last 12 months were recruited for this study. Each participant completed two separate visits (5-10 days apart) with spirometry performed at baseline and following cumulative doses of salbutamol (200, 400, 800, and 200 µg) delivered by either a small volume disposable spacer or a large volume multi-use spacer. Spacer type was alternated for each participant during each visit. The primary outcome was the effect of spacer type on bronchodilator responsiveness. The secondary outcome was to assess the relationships between spacer device, salbutamol dose and the proportion of children with a clinically relevant BDR. Results: Thirty-two children (mean age 11.8 years) completed both visits. Change in lung function following bronchodilators was increased using the large volume spacer, for relative but not absolute increase in FEV1 [mean difference (95% confidence intervals): 1.28% (0.02, 2.54; P = 0.047) and 0.013 L (-0.01, 0.04; P = 0.288)], respectively. There was no observed difference in FVC by spacer type. Overall, 59% (n = 19) of children exhibited a clinically relevant BDR at 400 µg of salbutamol for any spacer and was independent of spacer type. Conclusion: Spacer device was not associated with clinically important differences in lung function following bronchodilator inhalation in children with asthma. At a recommended dose of 400 µg, some children with asthma may have their bronchodilator responsiveness misclassified

Supply chain management

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Determinants of DHA levels in early infancy: differential effects of breast milk and direct fish oil supplementation

Abstract not availableS.J. Meldrum, N. D'Vaz, Y. Casadio, J.A. Dunstan, N. Niels Krogsgaard-Larsen, K. Simmer, S.L. Prescot

Multiple egg allergens elicit th2 cytokine responses that are associated with the incidence of egg allergy`

Jessica Metcalfe, Nina D, Vaz, Maria Makrides, Michael S.Gold, Patrick Quinn, Richard Loh, Susan L. Prescott, Debra J.Palme

Neonatal protein kinase C zeta expression determines the neonatal T-Cell cytokine phenotype and predicts the development and severity of infant allergic disease

Background: Previous studies have demonstrated that reduced T-cell protein kinase C zeta (PKCζ) expression is associated with allergy development in infants born to atopic mothers. This study examined whether this relationship extends to a general population and addressed the basis for the association. Methods: A flow cytometry assay was developed for the measurement of T-cell PKCζ levels in PBMC, cord blood mononuclear cell and whole blood. Cord blood T-cell PKCζ levels were measured in 135 neonates, and allergic disease was evaluated by skin prick test and clinical examination at 12 months of age. Results: Allergic children (particularly those with eczema) had significantly lower neonatal T-cell PKCζ expression than nonallergic children (P < 0.001). PKCζ levels predicted allergic disease with optimal specificity of 86% and sensitivity of 54%. The sensitivity was increased in the children of allergic mothers, who had significantly lower PKC levels than the children of nonallergic mothers. Cord blood PKCζ levels did not affect T-cell maturation in culture as assessed by CD45RA/RO expression, but low PKCζ expression was associated with reduced capacity for IFNc production by matured T cells. Low cord blood PKC expression was further associated with increased IL-13 responses at 6 months. Conclusions: The findings suggest a potential role for the use of PKCζ levels in cord blood T cells as a presymptomatic test to predict allergy risk in children, particularly offspring of allergic mothers, and that the basis of this relationship is related to cytokine patterns in mature T cells.N. D’Vaz, Y. Ma, J. A. Dunstan, T. F. Lee-Pullen, C. Hii , S. Meldrum, G. Zhang, J. Metcalfe, A. Ferrante, & S. L. Prescot