TY - JOUR
T1 - Airway Elastin is increased in severe asthma and relates to proximal wall area
T2 - histological and computed tomography findings from the U-BIOPRED severe asthma study
AU - the U-BIOPRED consortium
AU - Wilson, Susan J.
AU - Ward, Jonathan A.
AU - Pickett, Helen M.
AU - Baldi, Simonetta
AU - Sousa, Ana R.
AU - Sterk, Peter J.
AU - Chung, Kian Fan
AU - Djukanovic, Ratko
AU - Dahlen, Barbro
AU - Billing, Bo
AU - Shaw, Dominick
AU - Krug, Norbert
AU - Sandstrӧm, Thomas
AU - Brightling, Christopher
AU - Howarth, Peter H.
N1 - Funding Information: This research presented in this paper was co‐funded by the National Institute for Health Research (NIHR) Leicester Biomedical Research Centre, Airway Disease Predicting Outcomes through Patient Specific Computational Modelling (AirPROM) project (funded through 7th EU framework grant, 270194). This paper presents independent research funded by the National Institute for Health Research (NIHR). The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health. Funding Information: The bronchoscopy centres acknowledge the help received from nursing and other healthcare workers in the conduct of this study, and the Histochemistry Research Unit in Southampton acknowledges the help from Helen Pickett and Jon Ward in assisting with the analysis of the tissue biopsies. The U-BIOPRED study would have not been possible without the Innovative Medicines Initiative (IMI) funding provided by the European Union (EU) and the European Federation of Pharmaceutical Industries and Associations (EFPIA). This research presented in this paper was co-funded by the National Institute for Health Research (NIHR) Leicester Biomedical Research Centre, Airway Disease Predicting Outcomes through Patient Specific Computational Modelling (AirPROM) project (funded through 7th EU framework grant, 270194). This paper presents independent research funded by the National Institute for Health Research (NIHR). The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health. The authors also recognize that without the voluntary help from the asthmatic participants and the healthy control volunteers, this study would not have been possible and are indebted to their generosity. Members of the U-BIOPRED study group are detailed in the supplementary acknowledgements. Funding Information: The bronchoscopy centres acknowledge the help received from nursing and other healthcare workers in the conduct of this study, and the Histochemistry Research Unit in Southampton acknowledges the help from Helen Pickett and Jon Ward in assisting with the analysis of the tissue biopsies. The U‐BIOPRED study would have not been possible without the Innovative Medicines Initiative (IMI) funding provided by the European Union (EU) and the European Federation of Pharmaceutical Industries and Associations (EFPIA). Publisher Copyright: © 2020 The Authors. Clinical & Experimental Allergy published by John Wiley & Sons Ltd.
PY - 2021/2
Y1 - 2021/2
N2 - Background: Airway remodelling, which may include goblet cell hyperplasia / hypertrophy, changes in epithelial integrity, accumulation of extracellular matrix components, smooth muscle hypertrophy and thickening of the lamina reticularis, is a feature of severe asthma and contributes to the clinical phenotype. Objective: Within the U-BIOPRED severe asthma study, we have assessed histological elements of airway remodelling and their relationship to computed tomography (CT) measures of proximal airway dimensions. Methods: Bronchial biopsies were collected from two severe asthma groups, one non-smoker (SAn, n = 28) and one current/ex-smoker (SAs/ex, n = 13), and a mild-moderate asthma group (MMA, n = 28) classified and treated according to GINA guidelines, plus a healthy control group (HC, n = 33). Movat's pentachrome technique was used to identify mucin, elastin and total collagen in these biopsies. The number of goblet cells (mucin+) was counted as a percentage of the total number of epithelial cells and the percentage mucin epithelial area measured. The percentage area of elastic fibres and total collagen within the submucosa was also measured, and the morphology of the elastic fibres classified. Participants in the asthma groups also had a CT scan to assess large airway morphometry. Results: The submucosal tissue elastin percentage was higher in both severe asthma groups (16.1% SAn, 18.9% SAs/ex) compared with the HC (9.7%) but did not differ between asthma groups. There was a positive relationship between elastin and airway wall area measured by CT (n = 18–20, rho=0.544, p = 0.024), which also related to an increase in elastic fibres with a thickened lamellar morphological appearance. Mucin epithelial area and total collagen were not different between the four groups. Due to small numbers of suitable CT scans, it was not feasible to compare airway morphometry between the asthma groups. Conclusion: These findings identify a link between extent of elastin deposition and airway wall thickening in severe asthma.
AB - Background: Airway remodelling, which may include goblet cell hyperplasia / hypertrophy, changes in epithelial integrity, accumulation of extracellular matrix components, smooth muscle hypertrophy and thickening of the lamina reticularis, is a feature of severe asthma and contributes to the clinical phenotype. Objective: Within the U-BIOPRED severe asthma study, we have assessed histological elements of airway remodelling and their relationship to computed tomography (CT) measures of proximal airway dimensions. Methods: Bronchial biopsies were collected from two severe asthma groups, one non-smoker (SAn, n = 28) and one current/ex-smoker (SAs/ex, n = 13), and a mild-moderate asthma group (MMA, n = 28) classified and treated according to GINA guidelines, plus a healthy control group (HC, n = 33). Movat's pentachrome technique was used to identify mucin, elastin and total collagen in these biopsies. The number of goblet cells (mucin+) was counted as a percentage of the total number of epithelial cells and the percentage mucin epithelial area measured. The percentage area of elastic fibres and total collagen within the submucosa was also measured, and the morphology of the elastic fibres classified. Participants in the asthma groups also had a CT scan to assess large airway morphometry. Results: The submucosal tissue elastin percentage was higher in both severe asthma groups (16.1% SAn, 18.9% SAs/ex) compared with the HC (9.7%) but did not differ between asthma groups. There was a positive relationship between elastin and airway wall area measured by CT (n = 18–20, rho=0.544, p = 0.024), which also related to an increase in elastic fibres with a thickened lamellar morphological appearance. Mucin epithelial area and total collagen were not different between the four groups. Due to small numbers of suitable CT scans, it was not feasible to compare airway morphometry between the asthma groups. Conclusion: These findings identify a link between extent of elastin deposition and airway wall thickening in severe asthma.
UR - http://www.scopus.com/inward/record.url?scp=85099014719&partnerID=8YFLogxK
U2 - https://doi.org/10.1111/cea.13813
DO - https://doi.org/10.1111/cea.13813
M3 - Article
C2 - 33342006
SN - 0954-7894
VL - 51
SP - 296
EP - 304
JO - Clinical and experimental allergy
JF - Clinical and experimental allergy
IS - 2
ER -