Wednesday, November 1, 2017

Alpha-1 Antitrypsin (AAT) Deficiency

Alpha-1 antitrypsin (AAT) deficiency is an inherited disorder, most prevalent in populations of European ancestry, and is underdiagnosed. It results from mutations in the SERPINA1 gene, leading to either a reduced level or function of the AAT protein. AAT deficiency results a variety of health issues, particularly predisposition to the development of liver and lung disease1. When exacerbated by smoking, this results in damage to the alveoli and ultimately emphysema with many of the features of COPD1.

The recently published Alpha-1 Antitrypsin deficiency, in the Methods in Molecular Biology series (Springer Protocols) provides a comprehensive background to this disease and state-of-the-art methods2, including a chapter outlining the use of the forced oscillation technique to assess lung structure and function relationships, with focus on the flexiVent3.



Recent years have seen exciting developments in both the development of animal models for AAT deficiency research and proof of principle studies for treatment approaches. Using adeno-associated virus 2/8 to direct gene delivery specifically to mouse lung Payne et al were able to demonstrate not only elevated serum AAT but also protection against elastase-induced augmentation of compliance – measured using the forced-oscillation technique (FOT) on the flexiVent4.

Cox et al. performed pressure-volume loops and utilised the FOT with the flexiVent to confirm the increased compliance, with LPS challenge, of a newly developed mouse model of AAT deficiency. Generated using CRISPR/Cas9 genome editing, the model demonstrates many of the hallmark features of the human disease5

With the development of animal models which more closely resemble human disease, progress in the search for effective treatments will be greatly accelerated. SCIREQ looks forward to helping provide tools for this research.


1- Stoller, James K., and Loutfi S. Aboussouan. “A Review of α1-Antitrypsin Deficiency.”American Journal of Respiratory and Critical Care Medicine, vol. 185, no. 3, 2012, pp. 246–259., doi:10.1164/rccm.201108-1428ci.
2- Borel, F., & Mueller, C. (Eds.). (2017). Alpha-1 Antitrypsin Deficiency (Vol. 1639). New York, NY: Springer New York. https://doi.org/10.1007/978-1-4939-7163-3
3- Parameswaran H., Suki B. (2017) Assessing Structure–Function Relations in Mice Using the Forced Oscillation Technique and Quantitative Histology. In: Borel F., Mueller C. (eds) Alpha-1 Antitrypsin Deficiency. Methods in Molecular Biology, vol 1639. Humana Press, New York, NY
4- Payne, J., Takahashi, A., Lonza, G., Balazs, A., Suki, B., Kotton, D. and Wilson, A., “Lung-Directed Gene Delivery Of Alpha-1 Antitrypsin Using Intratracheal Adeno-Associated Virus 2/8 In A Mouse Model Of Emphysema”, Poster presented at: ATS 2014, D38 Update in alpha one deficiency, May 21st, 2014, San Diego, U.S.A.
5- Cox, A., Borel, F., Li, W., Brodsky, M. and Meuller, C., “Simultaneous disruption of five serpinA1 genes in mice using CRISPR/Cas9 to generate the first animal model of alpha-1 antitrypsin deficiency”, Poster presented at the American Society of Gene & Cell Therapy 18th Annual Meeting, American Society of Gene & Cell Therapy 18th Annual Meeting, Gene Targeting and Gene Correction II, May 14th 2015, New Orleans, U.S.A.

Tuesday, October 24, 2017

Dose rather than concentration

Bronchoprovocation is a pulmonary function test frequently performed in patients as a diagnostic or therapy management tool.  It assesses the subject’s level of airway responsiveness following increasing aerosol challenges of methacholine, a direct bronchoconstrictive agent.  

Recently, the European Respiratory Society (ERS), in collaboration with the American Thoracic Society (ATS), updated their guidelines relative to this test.  The most significant modification made was the recommendation that the test outcome be expressed in terms of the dose delivered rather than as the concentration of the solution loaded into the nebulizer1.  The ERS guidelines state that this updated end-point reporting allows for comparable results from different devices or protocols, since the dose concept can account for delivery variations2


Methacholine challenge tests are also performed at the pre-clinical level.  There, the notion of delivered dose was introduced earlier3 and researchers who have been using the flexiVent FX system have known for some time the effectiveness of this now recommended clinical procedure or its impact on study comparison.  Indeed, with the push of a button, the operating flexiVent software can automatically generate a delivered dose estimate for each subject and aerosol challenge.  The dose calculation is based on specific nebulizer, subject, and system characteristics and imposes no restrictions on the experimental protocol nor does it require additional pieces of equipment.  The delivered dose estimate thus offers an important standardization to the preclinical assessment of airway responsiveness that now coincides with the most recent clinical recommendations. 

Contact us for more information on the delivered dose concept.  Our application specialists will be happy to answer your questions or assist you to improve your study.

Contact Us
Phone: 1.514.286.1429 | Toll Free 1.877.572.4737
Email: info@scireq.com


READ MORE
1Coates, Allan L., et al.  2017.  ERS technical standard on bronchial challenge testing: general considerations and        performance of methacholine challenge tests.  European Respiratory Journal 49 (5): 1601526.
2Coates, Allan L., et al.  2017.  The PD 20 but not the PC 20 in a methacholine challenge test is device independent.  Annals of Allergy, Asthma & Immunology 118 (4): 508-509.
3Robichaud, Annette, Liah Fereydoonzad, and Thomas F. Schuessler.  2015.  Delivered dose estimate to standardize airway hyperresponsiveness assessment in mice.  American Journal of Physiology-Lung Cellular and Molecular Physiology 308 (8): L837-L846.

Thursday, October 19, 2017

Great success at JAX Workshop on Phenotyping Mouse Models of Human Lung Disease

After a year of absence, the well-established Workshop on Phenotyping Mouse Models of Human Lung Disease returned last week in Bar Harbor, ME.  As in the past, SCIREQ was a partner in this year's event, in collaboration with the Jackson Laboratory Educational Program.


The course, which offers great learning and networking opportunities, contains both a theoretical and a practical part and covers various topics relevant to respiratory research.  Two laboratory sessions on lung function measurements are typically included in the event schedule.  During these sessions, the participants are divided into small groups, where they can interact with key leaders in the field, such as Dr Wayne Mitzner (John Hopkins Bloomberg School of Public Health) or Dr Lennart K. A. Lundblad (The University of Vermont), while learning about state-of-the-art techniques.


This renowned scientific event catering to the needs of pre-clinical researchers from around the world was fully attended this year.  We will be there next time.  We hope you will be there too!

For more information on SCIREQ or its products for respiratory research applications, please visit our website at www.scireq.com.

Wednesday, October 18, 2017

Biennale Pneumologie 2017 et CQSR

Merci aux organisateurs et à tous les participants de la Biennale Pneumologie 2017 et du CQSR, qui a eu lieu dans la magnifique ville de Québec. Nous avons particulièrement apprécié le volet sur la recherche fondamentale appliquée, où nous avons pu assister à des présentations sur l’asthme, la fibrose kystique, la SDRA et les MPOC (pour les Québécois) ou BPCO (pour les Français)   J

emka TECHNOLOGIES et SCIREQ sont fières de travailler avec les chercheurs francophones qui étudient sur le système respiratoire et les maladies cardio-pulmonaires.

Au plaisir de vous revoir à la Biennale 2019.


Liens :







Thursday, October 12, 2017

Workshop on Eosinophils in Allergy and Related Diseases – Tokyo, Japan

Will you be attending the 31st Workshop on Eosinophils in Allergy and Related Diseases in Tokyo? If so, come and meet with our partner emka TECHNOLOGIES Japan and see our solutions for your research.

Workshop Information
Date:         21st October 2017
Time:        10:00 am - 17:00 pm
Location:  Tokyo, Japan
Chairman: Dr. Hiroshi Nakajima, Allergy & Clinical Immunology, Chiba University
                 Hospital
Director:    Dr. Makoto Nagata, Allergy Center, Saitama Medical University


More information from previous workshops on this topic:

Tuesday, August 22, 2017

Deep inflations and their role in reproducible lung function measurements

Reproducibility is more than ever an inevitable topic in research.  Recently, the subject was addressed by Dr. Jason Bates1 specifically in relation to preclinical lung function measurements. 

As explained in this interesting article, lung function measurements are affected by a number of confounding factors and controlling for them ensures that the subjects are studied under the same conditions, which helps generate robust data that can be reproduced by others. 

According to Dr. Bates, controlled experimental conditions including anaesthesia and mechanical ventilation are needed to achieve high-quality preclinical lung function data1, 2.  However, it is known that under these conditions, there is a progressive loss in lung volume due to airway closure or collapse3.  Additionally, as can be seen in a number of studies, once closed, airspaces do not spontaneously re-open.  A high-pressure manoeuver, such as a deep lung inflation, is typically required to open-up closed airways4, 5 or completely collapsed lungs6.  Therefore, as reported in the article at hand1, it is key to start a preclinical lung function experiment with a deep inflation to standardize lung volumes across subjects at baseline. 

DEEP INFLATION

Technical Description
  • The deep inflation gradually inflates the subject’s lungs to a pressure of 30 cmH2O over a period of 3 seconds.
  • The lungs are then held at that pressure for another 3 seconds, time during the alveolar pressure is allowed to equilibrate to the applied pressure.
  • The initial and end volumes are used in the calculation the inspiratory capacity (IC).
Physiological Description
  • The Deep Inflation perturbation brings the subject’s lungs from end of expiration (FRC) to total lung capacity (TLC), which is defined by default as a pressure of 30 cmH2O.
  • It provides a direct measurement of the subject’s inspiratory capacity.
For more information on the deep inflation and other manoeuvers questions linked to preclinical lung function measurements or scientific equipment for respiratory research, please visit SCIREQ website - Knowledge Center or contact one of our applications specialists.  We will be happy to work with you to enhance the reproducibility of your research.

References
1.       Bates, JHT.  2017.  CORP: Measurement of lung function in small animals.  J Appl Physiol, in press, DOI: 10.1152/japplphysiol.00243.2017.
2.       Bates JH, Irvin CG.  2003.  Measuring lung function in mice: the phenotyping uncertainty principle. J Appl Physiol 94: 1297-306.
3.       Mead J, Collier C.  1959.  Relation of volume history of lungs to respiratory mechanics in anesthetized dogs.  J Appl Physiol 14: 669-678.
4.       Wagers S, Lundblad LK, Ekman M, Irvin CG, Bates JH.  2004.  The allergic mouse model of asthma: normal smooth muscle in an abnormal lung?  J Appl Physiol 96: 2019-27.
5.       Shalaby KH, Gold LG, Schuessler TF, Martin JG, Robichaud A.  2010.  Combined forced oscillation and forced expiration measurements in mice for the assessment of airway hyperresponsiveness.  Respir Res 11: 82.
6.       Limjunyawong N, Fallica J, Horton MR, Mitzner W.  2015.  Measurement of the pressure-volume curve in mouse lungs. Journal of visualized experiments: J Vis Exp 95: 52376.

Monday, August 21, 2017

WORKSHOP ON PHENOTYPING MOUSE MODELS OF HUMAN LUNG DISEASE

Do not miss the opportunity to learn key laboratory techniques used in respiratory research by attending the workshop on Phenotyping Mouse Models of Human Lung Disease hosted by the Jackson Laboratory. This workshop will take place from October 9-14, 2017 in beautiful Bar Harbor, Maine.
Participants completing this workshop will acquire a working knowledge of basic pulmonary biology and the pathophysiology/histopathology accompanying lung diseases. As in the past, SCIREQ’s Senior Scientist, Annette Robichaud will supervise some laboratory sessions on lung function measurements using state-of-the art techniques.

Hands-on laboratory sessions will cover: 
» Airway hyper-responsiveness (AHR) measurement using flexiVent
» Sampling techniques (lung lavage & bone marrow)
» Lung volume and pressure-volume (PV) curves
» Lung morphometry and stereology
» Pulmonary diffusing capacity
» Intubation and tracheostomy
» Lung histopathology


For additional information and to register, go to:
https://www.jax.org/Lung

Space is limited. Early enrollment is advised.