BACKGROUND: The patterns of airway remodeling and the biomarkers that distinguish different subtypes of severe asthma are unknown. OBJECTIVES: We sought to characterize subjects with severe asthma with and without chronic persistent airflow obstruction with respect to airway wall remodeling (histopathologic and radiologic) and specific sputum biomarkers. METHODS: Subjects with severe asthma with chronic persistent (n = 16) or intermittent (n = 18) obstruction were studied. Endobronchial biopsy specimens were analyzed for airway smooth muscle area, epithelial detachment, basement membrane thickness, and submucosal fibrosis. Levels of eosinophil cationic protein, myeloperoxidase, matrix metalloproteinase 9, tissue inhibitor of matrix metalloproteinase 1 (ELISA), and 27 cytokines (multiplex assay) and differential cell counts were measured in induced sputum. Airway thickness was measured by means of high-resolution computed tomographic scanning. RESULTS: Chronic persistent obstruction was associated with earlier age of onset, longer disease duration, more inflammatory cells in the sputum, and greater smooth muscle area (15.65% +/- 2.69% [n = 10] vs 8.96% +/- 1.99% [n = 14], P = .0325). No differences between groups were found for any of the biomarker molecules measured in sputum individually. However, principal component analysis revealed that the dominant variables in the chronic persistent obstruction group were IL-12, IL-13, and IFN-gamma, whereas IL-9, IL-17, monocyte chemotactic protein 1, and RANTES were dominant in the other group. Airway imaging revealed no differences between groups. CONCLUSION: Subjects with severe asthma with chronic persistent obstruction have increased airway smooth muscle with ongoing T(H)1 and T(H)2 inflammatory responses. Neither airway measurements on high-resolution computed tomographic scans nor sputum analysis seem able to identify such patients.
BACKGROUND: The patterns of airway remodeling and the biomarkers that distinguish different subtypes of severe asthma are unknown. OBJECTIVES: We sought to characterize subjects with severe asthma with and without chronic persistent airflow obstruction with respect to airway wall remodeling (histopathologic and radiologic) and specific sputum biomarkers. METHODS: Subjects with severe asthma with chronic persistent (n = 16) or intermittent (n = 18) obstruction were studied. Endobronchial biopsy specimens were analyzed for airway smooth muscle area, epithelial detachment, basement membrane thickness, and submucosal fibrosis. Levels of eosinophil cationic protein, myeloperoxidase, matrix metalloproteinase 9, tissue inhibitor of matrix metalloproteinase 1 (ELISA), and 27 cytokines (multiplex assay) and differential cell counts were measured in induced sputum. Airway thickness was measured by means of high-resolution computed tomographic scanning. RESULTS: Chronic persistent obstruction was associated with earlier age of onset, longer disease duration, more inflammatory cells in the sputum, and greater smooth muscle area (15.65% +/- 2.69% [n = 10] vs 8.96% +/- 1.99% [n = 14], P = .0325). No differences between groups were found for any of the biomarker molecules measured in sputum individually. However, principal component analysis revealed that the dominant variables in the chronic persistent obstruction group were IL-12, IL-13, and IFN-gamma, whereas IL-9, IL-17, monocyte chemotactic protein 1, and RANTES were dominant in the other group. Airway imaging revealed no differences between groups. CONCLUSION: Subjects with severe asthma with chronic persistent obstruction have increased airway smooth muscle with ongoing T(H)1 and T(H)2 inflammatory responses. Neither airway measurements on high-resolution computed tomographic scans nor sputum analysis seem able to identify such patients.
Authors: Taylor A Doherty; Pejman Soroosh; Naseem Khorram; Satoshi Fukuyama; Peter Rosenthal; Jae Youn Cho; Paula S Norris; Heonsik Choi; Stefanie Scheu; Klaus Pfeffer; Bruce L Zuraw; Carl F Ware; David H Broide; Michael Croft Journal: Nat Med Date: 2011-04-17 Impact factor: 53.440
Authors: Gregory S Whitehead; Seddon Y Thomas; Karim H Shalaby; Keiko Nakano; Timothy P Moran; James M Ward; Gordon P Flake; Hideki Nakano; Donald N Cook Journal: J Clin Invest Date: 2017-07-31 Impact factor: 14.808
Authors: Sumit Gupta; Salman Siddiqui; Pranab Haldar; James J Entwisle; Dean Mawby; Andrew J Wardlaw; Peter Bradding; Ian D Pavord; Ruth H Green; Christopher E Brightling Journal: Thorax Date: 2010-09 Impact factor: 9.139