Thursday, February 2, 2017

Asthma - from mouse to man




“The assessment of lung function endpoints used in preclinical drug testing may hold the key to translation of drug efficacy from mouse to man1.”

Bench-to-bedside
Mouse models have been and continue to be of invaluable importance in asthma research, for the elucidation of key disease pathways as well as in the assessment of potential therapies2. While therapeutic candidates showing promise in murine models have not always translated into clinical successes, the story behind the recent FDA-approved anti-IL-5 and anti-IL-13 therapies3, previously deemed ineffective in general asthmatic populations, is a compelling example of how a better understanding of both the underlying disease mechanisms and the models resulted into “bench-to-bedside” achievements.


Mouse models of asthma
Asthma is a complex heterogeneous disease whose features have not been completely depicted by any single mouse disease model.  In preclinical (in vivo) research, careful considerations should be given to the model employed, its phenotype, as well as the measured outcomes.  Ideally, studies should include outcomes with strong predictive or translational value such as lung function measurements.  Respiratory function outcomes are often considered as primary study endpoint in many clinical trials targeting asthma patients. Therefore, relying on robust lung function measurements early on in the preclinical validation and development of potential disease targets and therapeutic candidates can, not only avoid misleading assessments, but also provide a grounded approach to support the critical program decision-making process.


Lung function outcomes
Lung function outcomes provided by SCIREQ‘s flexiVent and plethysmography methodologies aim to bridge the gap between mouse and man.  Referenced in thousands of peer-reviewed scientific publications and patents4, our scientific instruments permit accurate and detailed measurements to complement and strengthen biochemistry or immunology data.  These measurements are conveniently combined into a robust and comprehensive pulmonary assessment, collected via a computer-controlled instrument that also maximizes reproducibility.

Future direction
Mouse models represent a highly valuable tool to study the mechanisms involved in asthma and extrapolate scientific discoveries to humans.  The translatability of the information provided will only be ensured in the future by the continuous refinement of the models employed, as well as by a holistic approach combining lung mechanics data to a comprehensive assessment of the model phenotype.  This rigorous approach will hopefully help identify target populations and lead to additional success stories in the clinic, benefiting asthma patients worldwide.

Relevant links:


Tuesday, January 17, 2017

Together for Respiratory Research

January 15 to 21st is National Non-Smoking Week (NNSW) in Canada and we would like to take this opportunity to highlight the efforts of researchers, here and around the world, to deepen our knowledge on the health effects of smoke. Their work builds the scientific evidence to guide today’s and tomorrow’s decisions on the use of tobacco and tobacco-related products.  At SCIREQ, we understand respiratory research and take pride in assisting researchers in their task by providing precision laboratory instruments that enable them to achieve their scientific goals.

We believe that together we can make a difference.  

Read more

Monday, January 9, 2017

flexiVent featured in recent Nature publication


Congratulations to Dr. Ravichandran’s1 team at the University of Virginia, who recently published in Nature!

Their publication found that during phagocytosis, macrophages release insulin-like growth factor 1 (IGF-1) and microvesicles. Once bound to its receptor, IGF-1 promotes uptake of these microvesicles by the epithelial cells, leading to a decreased inflammatory response. This was verified through classic airway hyperresponsiveness (AHR) markers including increased eosinophils in the BAL fluid and increased airway resistance after methacholine challenges.
In vivo AHR was assessed using the flexiVent to both deliver aerosol challenges to the subject’s lungs and follow the developing bronchoconstriction through automated data collection. The data generated can be further partitioned to describe the contribution from the central airways and tissues, which often offers additional insight into the mechanisms and disease.





To learn more and read the full publication, visit Nature’s website at


To learn more about the flexiVent and how it may provide insight into inflammatory diseases or other applications, please contact info@scireq.com

References


1Ravichandran KS et al. Macrophages redirect phagocytosis by non-professional phagocytes and influence inflammation. Nature. 2016 Nov 24;539(7630):570-574. doi: 10.1038/nature20141. Epub 2016 Nov 7.

Thursday, December 8, 2016

HAPPY HOLIDAYS FROM EMKA & SCIREQ!




HOLIDAY OFFICE HOURS


emka TECHNOLOGIES S.A.S. (Paris, France)
Closed from Monday, December 26th to Friday, December 30th.


emka TECHNOLOGIES Inc. (Falls Church, VA, U.S.A.)
Closed on Monday, December 26th to Monday, January 2nd only. Open all other days.


SCIREQ Scientific Respiratory Equipment Inc. (Montreal, QC, Canada)
Closed from Monday, December 26th to Monday, January 2nd.


Wednesday, November 30, 2016

Lung Function in Conscious Subjects

Conscious measurements allow researchers to quantify effects of diseases or therapeutic interventions on the drive to breathe, also referred to as “Pumping apparatus” 1. The breathing drive involves different components that regulate respiration including respiratory muscles, the central nervous system, and chemo/mechano-receptors. Outcomes such as tidal volume, respiratory rate, minute volume, inspiratory, expiratory, and apneic periods are particularly useful in safety pharmacology studies, and research into sleep and neuromuscular diseases. Whole body plethysmography (WBP) is the simplest and least invasive approach that permits conscious in vivo measurements. However, researchers must consider the inherent limitations of WBP2 in regards to the accuracy of breathing volumes and assessment of airway hyperresponsiveness. Other techniques such as head-out plethysmography (HOP) or double chamber plethysmography (DCP) are often useful in providing a more accurate and validated assessment of the lung function.  

EF50 – a valid indicator of airway response

In difference to WBP, where the subject is freely moving within a chamber, HOP/DCP measurements are acquired in restrained subjects, allowing true inspiratory and expiratory flow measurements and their corresponding parameters. One such outcome, the tidal mid-expiratory flow (EF50), is particularly interesting as it has been described and validated over the last 20 years as an index of flow limitation and airway obstruction.  The parameter is calculated on a breath-by-breath basis during spontaneous tidal breathing and typically decreases in presence of airflow obstruction.

Other Applications


EF50 is often used in respiratory safety pharmacology studies performed under the ICH 7AS guidelines, where the HOP technique is a standard for conscious lung function assessment.  However, the parameter can also be obtained with DCP, allowing for exposure to nebulized substances and/or the ability to record nasal and thoracic flows separately.  Using this approach, EF50 can also be used to describe airway responsiveness changes to broncho-active substances in conscious mice, either na├»ve or allergic. 

Since EF50 does not provide a direct measurements of resistance, it is generally accepted that any change in this parameter would be followed by a comprehensive lung function assessment such as that provided by the flexiVent system.

References

  • 1Murphy DJ, 2013. Respiratory safety pharmacology – Current practice and future direction. Regulatory Toxicology and Pharmacology 69. DOI: 10.1016/j.yrtph.2013.11.010
  • 2Bates et al., 2003. Measuring lung function in mice: the phenotyping uncertainty principle.  J. of Appl. Physiology 1297-306. DOI: 10.1152/japplphysiol.00706.2002
  • Hoymann HG, 2012. Lung function measurements in rodents in safety pharmacology. Frontiers in pharmacology 3: article 156. doi: 10.3389/fphar.2012.00156.
  • Glaab T et al., 2001. Tidal midexpiratory flow as a measure of airway hyperresponsiveness in allergic mice. Am J Physiol Lung Cell Mol Physiol 280: L565-573.
  • Vijayaraghavan R et al., 1993. Characteristic modifications of the breathing pattern in mice to evaluate the effects of airborne chemicals on the respiratory tract. Arch Toxicol 67: 478-490.
  • Walker JKL et al., 2013. Assessment of murine lung mechanics outcome measures: alignment with those made in asthmatics. Frontiers in pharmacology 3: article 491. doi: 10.3389/fphar.2012.00491.



Wednesday, November 9, 2016

MEET WITH US IN SAN DIEGO AT SOCIETY FOR NEUROSCIENCE!

The emka & SCIREQ team will be attending the Society for Neuroscience 2016 conference in San Diego! We will present and demonstrate our wide range of preclinical instruments for neuro, pulmonary and cardio studies. Come by booth #3533 and speak with our experienced team about our solutions for physiology, pharmacology and toxicology research.

 A special focus on optogenetics

Optogenetic studies targeting respiratory centers in the brain stem can be paired with whole body plethysmography (WBP) to measure pulmonary function.

» Our WBP chambers pair with fibre optic cables to offer real-time assessment of lung function changes resulting from optical manipulation.
» Does not require anaesthetics, which can depress the neural-network controlling respiration.
» Conscious, freely moving subjects that have the ability to respond to real-time optical challenges.
» Swivel/tether system for measurement of other physiological parameters (ECG, EEG) or blood sampling following injections.
» Easily integrated with gas challenges (CO2/O2) to further induce or inhibit signaling pathways.
» Measures ventilatory parameters: Respiratory Rate (RR), estimated Tidal Volume (VT), Minute Ventilation (V) or Periodic breathing

Telemetry

easyTEL implantable system transmits physiological data from conscious freely moving laboratory animals. Our range of implants offers the ability to record the following parameters, depending on your study needs:

» Biopotential (ECG, EEG, EMG)
» Blood pressure
» Temperature
» Activity from acceleration

Click here to schedule a meeting with one of our specialists during SFN 2016.