Bronchoscopic mucosal cryobiopsies as a method for studying airway disease

Abstract

Background Investigating disease mechanisms and treatment responses in obstructive airway diseases with invasive sampling are hampered by the small size and mechanical artefacts that conventional forceps biopsies suffer from. Endoscopic cryobiopsies are larger and more intact and are being increasingly used. However, the technique has not yet been explored for obtaining mucosa biopsies. Objective To investigate differences in size and quality of endobronchial mucosal biopsies obtained with cryotechnique and forceps. Further, to check for eligibility of cryobiopsies to be evaluated with immunohistochemistry and in situ hybridization and to investigate tolerability and safety of the technique. Methods Endobronchial mucosal biopsies were obtained with cryotechnique and forceps from patients with haemoptysis undergoing bronchoscopy and evaluated by quantitative morphometry, automated immunohistochemistry and in situ hybridization. Results A total of 40 biopsies were obtained from 10 patients. Cross‐sectional areas were threefold larger in cryobiopsies (median: 3.08 mm2 (IQR: 1.79) vs 1.03 mm2 (IQR: 1.10), P < 0.001). Stretches of intact epithelium were 8‐fold longer (median: 4.61 mm (IQR: 4.50) vs 0.55 mm (IQR: 1.23), P = 0.001). Content of glands (median: 0.095 mm2 (IQR: 0.30) vs 0.00 mm2 (IQR: 0.01), P = 0.002) and airway smooth muscle (median: 0.25 mm2 (IQR: 0.30) vs 0.060 mm2 (IQR: 0.11), P = 0.02) was higher in the cryobiopsies compared with forceps biopsies. Further, the cryobiopsies had well‐preserved protein antigens and mRNA. Mild to moderate bleeding was the only complication observed. Conclusion and clinical relevance By yielding significantly larger and more intact biopsies, the cryotechnique represents a valuable new research tool to explore the bronchi in airway disease. Ultimately with the potential to create better understanding of underlying disease mechanisms and improvement of treatments.

Mucosal cryobiopsies: a new method for studying airway pathology in asthma

“…The results are in line with results from our previous study in patients with haemoptysis as well as what has been published on endobronchial cryobiopsies in other fields, e.g. suspected lung cancer [ 15 , 21 ]. Mucosal cryobiopsies in this study were on average four times larger than biopsies obtained with forceps.…”

“…Bleeding was, however, self-limiting in all instances, and we saw no other procedure-related adverse events. A low complication rate was also the finding in our pilot study in patients with haemoptysis but has now been validated after obtainment of 240 cryobiopsies [ 15 ]. A similar safety profile has been observed in a trial with 600 patients with suspected lung cancer where the rate of severe bleeding needing intervention after obtainment of cryobiopsies was comparable to what was seen after forceps biopsies [ 11 ].…”

“…Sedatives needed to perform the procedures were within standard dosing regimens as also reported previously [ 11 , 15 ].…”

“…Mucosal biopsies were obtained with both forceps (EndojawTM, Ø 1.9 mm; Olympus) and cryotechnique (Erbecryo® 2, Ø 1.9 mm; Erbe, Tübingen, Germany). The technique used for obtainment of cryobiopsies has been described elsewhere [ 15 ]. Briefly, mucosal cryobiopsies were obtained from longitudinal stretches at subsegmental levels at the discretion of the operator.…”

“…The use of transbronchial cryobiopsies has in parallel increased diagnostic yield in supposed interstitial lung disease and decreased the need of the more invasive video-assisted thoracoscopy [ 13 , 14 ]. In a pilot study of patients with haemoptysis investigating the use of mucosal cryobiopsies to study airway histology, we showed that the method yields bigger biopsies with better preservation of the tissue sampled as well as higher contents of airway smooth muscle and submucosal glands [ 15 ].…”