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2015 ; 16
(1
): 102
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Bronchoabsorption; a novel bronchoscopic technique to improve biomarker sampling
of the airway
#MMPMID26338015
Leaker BR
; Nicholson GC
; Ali FY
; Daudi N
; O'Connor BJ
; Barnes PJ
Respir Res
2015[Sep]; 16
(1
): 102
PMID26338015
show ga
BACKGROUND: Current techniques used to obtain lung samples have significant
limitations and do not provide reproducible biomarkers of inflammation. We have
developed a novel technique that allows multiple sampling methods from the same
area (or multiple areas) of the lung under direct bronchoscopic vision. It allows
collection of mucosal lining fluid and bronchial brushing from the same site;
biopsy samples may also be taken. The novel technique takes the same time as
standard procedures and can be conducted safely. METHODS: Eight healthy smokers
aged 40-65 years were included in this study. An absorptive filter paper was
applied to the bronchial mucosa under direct vision using standard bronchoscopic
techniques. Further samples were obtained from the same site using bronchial
brushings. Bronchoalveolar lavage (BAL) was obtained using standard techniques.
Chemokine (C-C Motif) Ligand 20 (CCL20), CCL4, CCL5, Chemokine (C-X-C Motif)
Ligand 1 (CXCL1), CXCL8, CXCL9, CXCL10, CXCL11, Interleukin 1 beta (IL-1?), IL-6,
Vascular endothelial growth factor (VEGF), Matrix metalloproteinase 8 (MMP-8) and
MMP-9 were measured in exudate and BAL. mRNA was collected from the bronchial
brushings for gene expression analysis. RESULTS: A greater than 10 fold
concentration of all the biomarkers was detected in lung exudate in comparison to
BAL. High yield of good quality RNA with RNA integrity numbers (RIN) between 7.6
and 9.3 were extracted from the bronchial brushings. The subset of genes measured
were reproducible across the samples and corresponded to the inflammatory markers
measured in exudate and BAL. CONCLUSIONS: The bronchoabsorption technique as
described offers the ability to sample lung fluid direct from the site of
interest without the dilution effects caused by BAL. Using this method we were
able to successfully measure the concentrations of biomarkers present in the
lungs as well as collect high yield mRNA samples for gene expression analysis
from the same site. This technique demonstrates superior sensitivity to standard
BAL for the measurement of biomarkers of inflammation. It could replace BAL as
the method of choice for these measurements. This method provides a systems
biology approach to studying the inflammatory markers of respiratory disease
progression. TRIAL REGISTRATION: NHS Health Research Authority (13/LO/0256).