1,721,304 research outputs found
Susceptibility genes in severe asthma
No full textAsthma is a common complex disease with a very wide spectrum of severity. Although part of this may be due to differing environmental interactions and inadequate treatment, there is increasing evidence that in addition to susceptibility genes for asthma onset, there are also important genetic influences over the disease severity, response to treatment, and natural history. In this review, we bring together recent literature in the field of genetic influences over disease severity and discuss some of the clinical implications in terms of drug discovery and personalized medicine
The airway epithelium is central to the pathogenesis of asthma.
No full textAsthma is an inflammatory disorder principally involving the conducting airways and characterised by infiltration of the airway wall with a range of inflammatory cells driven in large part by activation of Th2-type lymphocytes, mast cells and eosinophils. However a key component of asthma is the structural change that involves all of the elements of the airway wall. Here evidence is presented to suggest that the airway epithelium in asthma is fundamentally abnormal with increased susceptibility to environmental injury and impaired repair associated with activation of the epithelial-mesenchymal trophic unit (EMTU). In addition to adopting an activated phenotype, the barrier function of the epithelium is impaired through defective tight junction formation thereby facilitating penetration of potentially toxic or damaging environmental insults. Activated and repairing epithelial cells generate a range of growth factors that are involved in the early life origins of this disease as well as its progression in the form of mucous metaplasia and airway wall remodeling. By placing the epithelium at the forefront of asthma pathogenesis, different approaches to treatment can be devised focused more on protecting vulnerable airways against environmental injury rather than focusing on suppressing airway inflammation or manipulating the immune response
Exposure, uptake, distribution and toxicity of nanomaterials in humans
No full textThe last decade has witnessed an unprecedented explosion in nanotechnology to take advantage of the unique physicochemical properties that emerge at the nanoscale including quantum effects. However, the excitement generated by new applications of nanotechnology in products has not been matched by a parallel appreciation or understanding of their potential toxic effects in humans and the wider ecology. This review draws some parallels to what we already know about the toxicity of particles in the workplace and in association with air pollution, and then discusses what is known about the toxicology of nanomaterials in mammals including humans. The review identifies substantial gaps in knowledge and makes some recommendations for future research
Rhinoviruses in the pathogenesis of asthma: The bronchial epithelium as a major disease target
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