Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology
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Inhalation of the local anaesthetic lidocaine has been suggested to be beneficial for asthmatics, but airway anaesthesia is unpleasant and may exacerbate bronchoconstriction. Our previous study showed that inhalation of the lidocaine analogue JMF2-1 can elicit the anti-inflammatory properties of lidocaine without anaesthesia. This prompted further research on the mechanism of action and putative therapeutic application of JMF2-1. ⋯ Inhalation of JMF2-1 prevents the cardinal features of asthma by reducing T(H) 2 cytokine generation and lung eosinophilic inflammatory infiltrates via local inhibition of T cell function and survival. JMF2-1 may represent a novel therapeutic alternative for asthma control with distinct advantages over local anaesthetics.
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Leukotrienes (LTs), including cysteinyl LTs (CysLTs) and LTB(4) , are potent lipid mediators that have a role in the pathophysiology of asthma. At least two receptor subtypes for CysLTs, CysLT(1) and CysLT(2) , have been identified. The activation of the CysLT(1) receptor is responsible for most of the pathophysiological effects of CysLTs in asthma, including increased airway smooth muscle activity, microvascular permeability, and airway mucus secretion. ⋯ The identification of subgroups of asthmatic patients who respond to CysLT(1) receptor antagonists is relevant for asthma management as the response to these drugs is variable. CysLT(1) receptor antagonists have a potential anti-remodelling effect that might be important for preventing or reversing airway structural changes in patients with asthma. This review discusses the role of LTs in asthma and the role of LT modifiers in asthma treatment.
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It has been suggested that there are several distinct phenotypes of childhood asthma or childhood wheezing. Here, we review the research relating to these phenotypes, with a focus on the methods used to define and validate them. Childhood wheezing disorders manifest themselves in a range of observable (phenotypic) features such as lung function, bronchial responsiveness, atopy and a highly variable time course (prognosis). ⋯ If phenotypes are meant to represent 'real' underlying disease entities rather than superficial features, there is a need for validation and harmonization of definitions. The multi-dimensional approach allows validation by replication across different populations and may contribute to a more reliable classification of childhood wheezing disorders and to improved precision of research relying on phenotype recognition, particularly in genetics. Ultimately, the underlying pathophysiology and aetiology will need to be understood to properly characterize the diseases causing recurrent wheeze in children.
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Background Asthma is a disease characterized by airway inflammation, remodelling and dysfunction. Airway inflammation contributes to remodelling, a term that is used to describe structural changes including goblet cell metaplasia (GCM), matrix deposition, and smooth muscle hyperplasia/hypertrophy. GCM has been implicated in asthma mortality by contributing to mucus plugs and leading to asphyxiation. ⋯ Results Acute HDM exposure resulted in increased airway responses to MCh, lung eosinophilia, STAT6 phosphorylation, elevations in GAD65/67 and GABA(A)beta(2/3) receptor expression, and GCM that were inhibited with anti-IL-4Ralpha-monoclonal treatment. Control antibody had no effect. Conclusion The IL-4Ralpha is required for allergen-induced up-regulation of a GABAergic system in airway epithelium implicated in GCM following acute HDM exposure.
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Randomized Controlled Trial
Impact of early feeding on childhood eczema: development after nutritional intervention compared with the natural course - the GINIplus study up to the age of 6 years.
Nutritional intervention with hydrolysed infant formulas has been shown efficacious in preventing eczema in children predisposed to allergy. However, this preventive effect has never been related to the natural course of eczema in children with or without a family history of allergy. The aim of this study therefore was to compare the course of eczema in predisposed children after nutritional intervention to the natural course of eczema. ⋯ Although direct comparability is somewhat restricted, the data demonstrate that early intervention with hydrolysed infant formulas can substantially compensate up until the age of 6 years for an enhanced risk of childhood eczema due to familial predisposition to allergy.