The current COVID-19 pandemic has highlighted the need for a rapid development of therapeutic approaches to treat respiratory diseases. Yet, respiratory therapeutic candidates have until now displayed a low success rate[1]. As a result, development times are long and only a few novel mechanism respiratory therapeutic entities have been introduced over the last decades. Causes that have been evoked to explain this effect include a lack of efficacy and safety-related issues1.
For respiratory therapeutic candidates, efficacy testing generally includes the evaluation of lung function, and that during the preclinical and clinical phases. The outcomes are often considered as primary endpoints, thus having a great influence on the progression of respiratory drug candidates. A methodological alignment between the preclinical and clinical settings was recently presented as an avenue to improve the respiratory development process[1].
Methodological differences exist between the preclinical and clinical phases of development in terms of lung function assessment. Oscillometry (also known as the forced oscillation technique) generally dominates during preclinical development while spirometry is the main measurement technique used during clinical trials or practice. Yet, oscillometry can be applied across species and great similarities in the respiratory input impedance were observed among mammals of various lung size or structure2,3. It thus seems that, despite inevitable distinctions between animal and human measurements, the potential of the technique rests in its ability to probe common characteristics of the respiratory system, likely enhancing translation between mice and human studies2.
Oscillometry is not a new technique4. Introduced over half a century ago, the development of its clinical and preclinical applications has been very much interconnected as based on the same operating principles. At the preclinical level, the technique is at the heart of the flexiVent system, which is widely used to characterize preclinical respiratory disease models or assess the functional efficacy of respiratory therapeutic candidates.
There is a need to improve the respiratory drug development process and the pandemic may provide an opportunity. Lung function is an important assessment, and the choice of the technique could matter. Please contact us to find out how we can assist your pulmonary research.
References
[1] Barnes PJ, Bonini S, Seeger W, Belvisi MG, Ward B, Holmes A. Barriers to new drug development in respiratory disease. Eur Respir J 45: 1197–1207, 2015. doi:10.1183/09031936.00007915.
[2] Lundblad LKA, Robichaud A. Oscillometry of the Respiratory System. A Translational Opportunity Not to be Missed. Am J Physiol – Lung Cell Mol Physiol. 2021. In press. doi.org/10.1152/ajplung.00222.2020
[3] Bates JHT, Irvin CG, Farré R, Hantos Z. Oscillation mechanics of the respiratory system. Compr Physiol 1: 1233-72, 2011. doi.org/10.1002/cphy.c100058
[4] DuBois DuBois AB, Brody AW, Lewis DH, Burgess BF. Oscillation mechanics of lungs and chest in man. J Appl Physiol 8: 587–594, 1956. doi:10.1152/jappl.1956.8.6.587.
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