Purpose:To evaluate the safety and tolerability of inhaling multiple 1-L volumes of undiluted hyperpolarized xenon 129 ( 129 Xe) followed by up to a 16-second breath hold and magnetic resonance (MR) imaging. Materials and Methods:This study was approved by the institutional review board and was HIPAA compliant. Written informed consent was obtained. Forty-four subjects (19 men, 25 women; mean age, 46.1 years 6 18.8 [standard deviation ]) were enrolled, consisting of 24 healthy volunteers, 10 patients with chronic obstructive pulmonary disease (COPD), and 10 age-matched control subjects. All subjects received three or four 1-L volumes of undiluted hyperpolarized 129 Xe, followed by breath-hold MR imaging. Oxygen saturation, heart rate and rhythm, and blood pressure were continuously monitored. These parameters, along with respiratory rate and subjective symptoms, were assessed after each dose. Subjects' serum biochemistry and hematology were recorded at screening and at 24-hour follow-up. A 12-lead electrocardiogram (ECG) was obtained at these times and also within 2 hours prior to and 1 hour after 129 Xe MR imaging. Xenon-related symptoms were evaluated for relationship to subject group by using a x 2 test and to subject age by using logistic regression. Changes in vital signs were tested for signifi cance across subject group and time by using a repeated-measures multivariate analysis of variance test.

Airway remodelling is a feature of asthma that contributes to loss of lung function. One of the central components of airway remodelling is subepithelial fibrosis. Interleukin (IL)-13 is a key T-helper 2 cytokine and is believed to be the central mediator of allergic asthma including remodelling, but the mechanism driving the latter has not been elucidated in human asthma.We hypothesised that IL-13 stimulates collagen type-1 production by the airway fibroblast in a matrix metalloproteinase (MMP)-and transforming growth factor (TGF)-b1-dependent manner in human asthma as compared to healthy controls.Fibroblasts were cultured from endobronchial biopsies in 14 subjects with mild asthma and 13 normal controls that underwent bronchoscopy. Airway fibroblasts were treated with various mediators including IL-13 and specific MMP-inhibitors. IL-13 significantly stimulated collagen type-1 production in asthma compared to normal controls. Inhibitors of MMP-2 significantly attenuated collagen production in asthma but had no effect in normal controls. IL-13 significantly increased total and active forms of TGF-b1, and this activation was blocked using an MMP-2 inhibitor. IL-13 activated endogenous MMP-2 in asthma patients as compared to normal controls.In an ex vivo model, IL-13 potentiates airway remodelling through a mechanism involving TGF-b1 and MMP-2. These effects provide insights into the mechanism involved in IL-13-directed airway remodelling in asthma. @ERSpublications IL-13 potentiates collagen production in a TGF-b1-dependent manner providing insight into airway remodelling in asthma

Rationale: Invasive cell phenotypes have been demonstrated in malignant transformation, but not in other diseases, such as asthma. Cellular invasiveness is thought to be mediated by transforming growth factor (TGF)-b1 and matrix metalloproteinases (MMPs). IL-13 is a key T H 2 cytokine that directs many features of airway remodeling through TGF-b1 and MMPs. Objectives: We hypothesized that, in human asthma, IL-13 stimulates increased airway fibroblast invasiveness via TGF-b1 and MMPs in asthma compared with normal controls. Methods: Fibroblasts were cultured from endobronchial biopsies in 20 subjects with mild asthma (FEV 1 : 90 6 3.6% pred) and 17 normal control subjects (FEV 1 : 102 6 2.9% pred) who underwent bronchoscopy. Airway fibroblast invasiveness was investigated using Matrigel chambers. IL-13 or IL-13 with TGF-b1 neutralizing antibody or pan-MMP inhibitor (GM6001) was added to the lower chamber as a chemoattractant. Flow cytometry and immunohistochemistry were performed in a subset of subjects to evaluate IL-13 receptor levels. Measurements and Main Results: IL-13 significantly stimulated invasion in asthmatic airway fibroblasts, compared with normal control subjects. Inhibitors of both TGF-b1 and MMPs blocked IL-13-induced invasion in asthma, but had no effect in normal control subjects. At baseline, in airway tissue, IL-13 receptors were expressed in significantly higher levels in asthma, compared with normal control subjects. In airway fibroblasts, baseline IL-13Ra2 was reduced in asthma compared with normal control subjects. Conclusions: IL-13 potentiates airway fibroblast invasion through a mechanism involving TGF-b1 and MMPs. IL-13 receptor subunits are differentially expressed in asthma. These effects may result in IL-13-directed airway remodeling in asthma.

Patients with EoE have an increased risk of multiple autoimmune diseases. Possible shared genetic etiologies were observed between EoE and UC, systemic sclerosis, and MS. Practitioners should be aware of these comorbid associations and query all EoE patients and family members for symptoms of these diseases.

Brand-name medications are often substantially less expensive when purchased from Canadian Internet pharmacies instead of from major online U.S. drug chain pharmacies.