Clinical and Experimental Allergy最新文献

There is a wide gap between the first publication of new treatments with efficacy and their successful application in clinical practice. In many respects, the management of allergic diseases is a good exemplar of the knowledge/practice gap. It was assumed that systematic reviews and publication of guidelines would ensure timely delivery of effective care, but this has not proved to be the case. While there are many reasons to explain shortcomings in healthcare delivery, the lack of patient and carer involvement in the planning of research, evidence review, guideline development and guideline implementation is most compelling. To achieve adherence to evidence-based guidelines consistently across all levels of the health service requires the implementation of integrated care with clear pathways through which patients can navigate. Quality improvement methodology could be employed to plan and implement integrated care pathways (ICPs). There is evidence that ICPs achieve improved outcomes for acute hospital-based interventions, but less work has focussed on long-term conditions where more diverse agencies are involved. At all stages, stakeholder representation from the full range of healthcare professionals, patients, their families, social services, education, local government and employers must be involved. In this article we review the step-wise and iterative process by which knowledge is implemented into practice to improve patient experience and outcomes We argue how this process can benefit from the involvement of patients and their carers as equal partners, and we discuss how different initiatives have involved patients with allergic diseases. There currently is a gap in evidence that links patient involvement to improved outcomes. We recommend the use of the Core Outcome Sets (COS) and Patient Reported Experience Measures (PREMS) which have been developed for allergic diseases to monitor the effects of implementation research and the impact of patient and carer involvement on outcomes.

Plant-based diets (PBD) have been reported throughout history, but are increasingly common in current times, likely in part due to considerable emphasis on climate change and human health and wellness. Many dietary organisations around the world endorse well-planned, nutritionally adequate PBD, which exclude some or all forms of animal-based foods. However, special attention must be given to patients who follow PBD and also have food allergy (FA), as avoidance may increase the risk of developing nutritional deficiencies, including poor growth in children, weight loss in adults and vitamin and mineral deficiencies. Given the increasing prevalence of both PBD and food allergen avoidance diets, healthcare providers are likely to counsel patients with FA who also follow a PBD. In this review, an overview of PBD in patients with FA is provided, including recent trends, macro- and micronutrient needs, and growth for children and weight gain considerations for adults. With regard to a PBD, special attention should be given to ensure adequate fat and protein intake and improving the bioavailability of several minerals such as iron, zinc, iodine, calcium and magnesium, and vitamins such as A, B2, B12 and D. Although the collective data on growth amongst children following a PBD are varied in outcome and may be influenced in part by the type of PBD, growth must be regularly monitored and in adults weight gain assessed as part of any clinical assessment in those people with FA.

Introduction: The interleukin-33/interleukin-1 receptor-like-1 (IL-33/IL1RL1) signalling pathway is implicated in asthma pathogenesis, with IL1RL1 nonsynonymous genetic polymorphisms associated with disease risk. We aimed to determine these variants' effect on IL1RL1 signalling induced by different IL33 isoforms thought to be elevated in the asthmatic airway.

Method: In a project funded by GSK plc, which has developed an IL-33 receptor inhibitor for asthma treatment, human embryonic kidney 293 (HEK293) cells expressing secreted embryonic alkaline phosphatase (SEAP) driven by a nuclear factor kappa-beta (NF-κB) promoter, were transiently transfected with IL1RL1, containing one of four extracellular and Toll/interleukin 1 receptor (TIR) domain haplotypes. Cells were stimulated with seven different splice and proteolytic-generated IL-33 isoforms (0.001-50 ng/mL) for 24 h. Supernatant SEAP activity and interleukin-8 (IL-8) levels were determined. Primary human bronchial epithelial cells (HBECs) representing different genotype carriers were stimulated with IL-33_112-270 (50 ng/mL) and induced IL-8 mRNA expression measured.

Results: HEK293 cells carrying both asthma extracellular and TIR domain IL1RL1 risk haplotypes presented maximal IL33-driven signalling, with minimal signalling after IL-33 activation in other protective haplotypes. All IL-33 isoforms activated IL1RL1 but with differing magnitudes. Proteolytically cleaved IL33_95-270 and IL33_106-270 had the greatest effect and the IL33_113-270, and Exon 3,4 deletion isoform exhibited the lowest. The effect of extracellular and TIR domain genetic variants on receptor signalling was replicated in primary HBECs. Maximal IL1RL1 signalling was observed in cells carrying both extracellular and TIR signalling domain risk haplotypes.

Conclusions: Overall, our study suggests asthma patients carrying the extracellular and TIR domain risk haplotype and have a lung microenvironment that promotes elevated levels of cleaved IL33, particularly where IL33_95-270 and IL33_106-270 may be more amenable to IL33/IL1RL1 targeting.

Objective: Eczema is the most burdensome skin condition worldwide and topical anti-inflammatory treatments are commonly used to control symptoms. The relative effectiveness and safety of different topical anti-inflammatory treatments is uncertain.

Design: Network meta-analysis performed within a Cochrane systematic review to compare and statistically rank efficacy and safety of topical anti-inflammatory eczema treatments.

Data sources: Cochrane Skin Specialised Register, CENTRAL, MEDLINE, Embase and trial registries to June 2023.

Eligibility criteria for selected trials: Included trials were within-participant or between-participant randomised controlled trials. Participants had eczema that was not clinically infected and was not contact dermatitis, seborrheic eczema or hand eczema. Interventions were topical anti-inflammatory treatments but not complementary treatments, antibiotics alone, wet wraps, phototherapy or systemic treatments. Comparators were no treatment/vehicle or another topical anti-inflammatory.

Results: We identified 291 trials (45,846 participants), mainly in high-income countries. Most were industry-funded with median 3 weeks treatment duration. Risk of bias assessed using the Cochrane Risk of Bias 2.0 tool was high in 89% of trials, mainly due to risk of selective reporting. Network meta-analysis of binary outcomes ranked potent and/or very potent topical steroids, tacrolimus 0.1% and ruxolitinib 1.5% among the most effective treatments for improving patient-reported symptoms (40 trials, all low confidence) and clinician-reported signs (32 trials, all moderate confidence). For investigator global assessment, the Janus kinas inhibitors ruxolitinib 1.5%, delgocitinib 0.5% or 0.25%, very potent/potent topical steroids and tacrolimus 0.1% were ranked as most effective (140 trials, all moderate confidence). Continuous outcome data were mixed. Local application site reactions were most common with tacrolimus 0.1% (moderate confidence) and crisaborole 2% (high confidence) and least common with topical steroids (moderate confidence). Skin thinning was not increased with short-term use of any topical steroid potency (low confidence) but skin thinning was reported in 6/2044 (0.3%) participants treated with longer-term (6-60 months) topical steroids.

Conclusion: Potent topical steroids, Janus kinase inhibitors and tacrolimus 0.1% were consistently ranked as among the most effective topical anti-inflammatory treatments for eczema.