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A Reversible, Non-invasive Method for Airway Resistance Measurements and Bronchoalveolar Lavage Fluid Sampling in Mice
Published on: April 13, 2010
A quantitative method for assessing treatment-related changes within the airway mucosa in patients with chronic
William S Krimsky1, Paul A VanderLaan2, Jeffrey S Iding3
1Galvanize Therapeutics, Inc., 3200 Bridge Parkway, Redwood City, CA, 94065, USA.
Background:
No standardized method has yet been established for evaluating airway mucosal aberrancies associated with chronic obstructive pulmonary disease (COPD) or chronic bronchitis (CB). While goblet cell hyperplasia (GCH) is an established pathognomonic hallmark of the CB disease process, no standardized method exists for acquiring mucosal biopsies and assessing morphologic airway mucosa alterations. Additionally, the impacts from interventions targeting the airway mucosa are not well defined. In this context, a reliable and robust measure for assessing airway mucosa at baseline and subsequent to an intervention is critical for characterizing treatment-related changes.
Research Question:
Can standardizing airway biopsy tissue collection and histopathological assessment methods generate a robust and repeatable measure to assess airway mucosa tissue characteristics in the setting of COPD/CB?
Study Design & Methods:
Initial tissue collection and histological assessment methods were designed by integrating various aspects from previously published evaluations, applied to an initial tissue sample cohort, and then iteratively refined by independent pathologists.
Results:
A standardized metric for histologic airway mucosa assessments was developed that specified tissue collection methods, including re-sampling airways at multiple time points to enable evaluation of treatment-related effects by incorporating scores for GCH, eosinophilia, and chronic inflammation, and the degree of GCH heterogeneity present within each sample.
Conclusion:
This multi-center study generated a robust, reproducible approach for assessing airway mucosa aberrancies in the setting of COPD/CB. The iterative approach established consistent tissue specimen recovery and a granular scoring matrix that enabled quantitative scoring of the various tissue findings with substantial histopathologic interrater reliability.
Clinical Trial Registration Number:
ClinicalTrials.gov; NCT03107494, NCT04677465; URL: www.
Clinicaltrials:
gov. Australian New Zealand Clinical Trials Registry (ANZCTR); ACTRN12617000330347; URL: anzctr.org.au.
