Kearley J.,Med Immune Ltd. |
Erjefalt J.S.,Lund University |
Andersson C.,Lund University |
Benjamin E.,Med Immune Ltd. |
And 13 more authors.
American Journal of Respiratory and Critical Care Medicine | Year: 2011
Rationale: IL-9 is a pleiotropic cytokine that has multiple effects on structural as well as numerous hematopoietic cells, which are central to the pathogenesis of asthma. Objectives: The contribution of IL-9 to asthma pathogenesis has thus far been unclear, due to conflicting reports in the literature. These earlier studies focused on the role of IL-9 in acute inflammatory models; here we have investigated the effects of IL-9 blockade during chronic allergic inflammation. Methods: Mice were exposed to either prolonged ovalbumin or house dust mite allergen challenge to induce chronic inflammation and airway remodeling. Measurements and Main Results: We found that IL-9 governs allergen-induced mast cell (MC) numbers in the lung and has pronounced effects on chronic allergic inflammation. Anti-IL-9 antibody-treated mice were protected from airway remodeling with a concomitant reduction in mature MC numbers and activation, in addition to decreased expression of the profibrotic mediators transforming growth factor-β1, vascular endothelial growth factor, and fibroblast growth factor-2 in the lung. Airway remodeling was associated with impaired lung function in the peripheral airways and this was reversed by IL-9 neutralization. In human asthmatic lung tissue, we identified MCs as the main IL-9 receptor expressing population and found them to be sources of vascular endothelial growth factor and fibroblast growth factor-2. Conclusions: Our data suggest an important role for an IL-9-MC axis in the pathology associated with chronic asthma and demonstrate that an impact on this axis could lead to a reduction in chronic inflammation and improved lung function in patients with asthma. Copyright © 2011 American Thoracic Society. Source
Hartney J.M.,University of Colorado at Denver |
Robichaud A.,SCIREQ Scientific Respiratory Equipment Inc.
Methods in Molecular Biology | Year: 2013
This chapter provides an outline of the procedures necessary to measure airway hyperresponsiveness to inhaled methacholine in mouse models of allergic lung disease. We present a method for acquiring detailed measurements of respiratory mechanics using broadband low-frequency oscillatory waveforms applied at the subject's airway opening and analyzed using the constant phase model of the lung. We acknowledge that there are other methods of measuring airway responsiveness in allergic rodent models. However, a discussion of the merits and or detriments of these various methods have been vigorously debated in the primary literature and are beyond the scope of this chapter. The goal of this chapter is to provide a guide in how to begin these types of assays in laboratories which have little to no experience with these particular types of assessments. © 2013 Springer Science+Business Media, LLC. Source
Scireq Scientific Respiratory Equipment Inc. | Date: 2010-03-15
A modular kit of complementary plethysmographic apparatus components including at least one tube, at least one termination device for closing an open extremity of the tube and first and second complementary coupling mechanisms formed on the tube and the termination device. The coupling mechanisms are adapted to provide sealing engagement between the tube and the termination device. The first and second complementary coupling mechanisms comprise a notched interface component adapted to fit into a corresponding mating gap component, such that a rotation of the two components with respect to each other, solidly locks the two components together while applying pressure onto a face seal between the two components.
Scireq Scientific Respiratory Equipment Inc. | Date: 2010-11-03
The present invention relates to a lung function assessment system, a mechanical ventilator and method that allows simultaneously measurements of lung function and provides simultaneously mechanical ventilation to multiple subjects requiring one source of gas.
Bassett L.,CiToxLAB North America |
Troncy E.,University of Montreal |
Robichaud A.,SCIREQ Scientific Respiratory Equipment Inc. |
Schuessler T.F.,SCIREQ Scientific Respiratory Equipment Inc. |
And 5 more authors.
Journal of Pharmacological and Toxicological Methods | Year: 2014
Introduction: A number of drugs in clinical trials are discontinued due to potentially life-threatening airway obstruction. As some drugs may not cause changes in core battery parameters such as tidal volume (Vt), respiratory rate (RR) or minute ventilation (MV), including measurements of respiratory mechanics in safety pharmacology studies represents an opportunity for design refinement. The present study aimed to test a novel non-invasive methodology to concomitantly measure respiratory system resistance (Rrs) and conventional respiratory parameters (Vt, RR, MV) in conscious Beagle dogs and cynomolgus monkeys. Methods: An Airwave Oscillometry system (tremoFlo; THORASYS Inc., Montreal, Canada) was used to concomitantly assess Rrs and conventional respiratory parameters before and after intravenous treatment with a bronchoactive agent. Respiratory mechanics measurements were performed by applying a short (i.e. 16s) single high frequency (19Hz) waveform at the subject's airway opening via a face mask. During measurements, pressure and flow signals were recorded. After collection of baseline measurements, methacholine was administered intravenously to Beagle dogs (n=6) and cynomolgus monkeys (n=4) at 8 and 68μg/kg, respectively. Results: In dogs, methacholine induced significant increases in Vt, RR and MV while in monkeys, it only augmented RR. A significant increase in Rrs was observed after methacholine administration in both species with mean percentage peak increases from baseline of 88 (53)% for dogs and 28 (16)% for cynomolgus monkeys. Conclusion: Airwave Oscillometry appears to be a promising non-invasive methodology to enable respiratory mechanics measurements in conscious large animals, a valuable refinement in respiratory safety pharmacology. © 2014 Elsevier Inc. Source