Controlled and uncontrolled asthma display distinct alveolar tissue matrix compositions |
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Authors: | Maria Weitoft Cecilia Andersson Annika Andersson-Sj?land Ellen Tufvesson Leif Bjermer Jonas Erjef?lt Gunilla Westergren-Thorsson |
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Institution: | 1.Lung Biology Unit, Department of Experimental Medical Science, BMC, D12, Lund University, Lund, SE-221 84, Sweden;2.Respiratory Medicine and Allergology, Department of Clinical Medical Sciences, Lund University, Lund, Sweden;3.Unit of Airway Inflammation, Department of Experimental Medical Science, Lund University, Lund, Sweden |
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Abstract: | ObjectiveWhether distal inflammation in asthmatics also leads to structural changes in the alveolar parenchyma remains poorly examined, especially in patients with uncontrolled asthma. We hypothesized that patients who do not respond to conventional inhaled corticosteroid therapy have a distinct tissue composition, not only in central, but also in distal lung.MethodsBronchial and transbronchial biopsies from healthy controls, patients with controlled atopic and patients with uncontrolled atopic asthma were processed for immunohistochemical analysis of fibroblasts and extracellular matrix molecules: collagen, versican, biglycan, decorin, fibronectin, EDA-fibronectin, matrix metalloproteinase (MMP)-9 and tissue-inhibitor of matrix metalloproteinase (TIMP)-3.ResultsIn central airways we found increased percentage areas of versican and decorin in patients with uncontrolled asthma compared to both healthy controls and patients with controlled asthma. Percentage area of biglycan was significantly higher in both central airways and alveolar parenchyma of patients with uncontrolled compared to controlled asthma. Ratios of MMP-9/TIMP-3 were decreased in both uncontrolled and controlled asthma compared to healthy controls. In the alveolar parenchyma, patients with uncontrolled asthma had increased percentage areas of collagen, versican and decorin compared to patients with controlled asthma. Patients with uncontrolled asthma had significantly higher numbers of myofibroblasts in both central airways and alveolar parenchyma compared to patients with controlled asthma.ConclusionsTissue composition differs, in both central and distal airways, between patients with uncontrolled and controlled asthma on equivalent doses of ICS. This altered structure and possible change in tissue elasticity may lead to abnormal mechanical properties, which could be a factor in the persistent symptoms for patients with uncontrolled asthma. |
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Keywords: | Asthma Controlled Uncontrolled ICS Remodeling Alveolar parenchyma Extracellular matrix Myofibroblasts |
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