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.
Highlights
Asthma is a chronic inflammatory airway disease that is traditionally characterized by reversible central airway obstruction and airway hyperreactivity [1,2]
Uncontrolled asthma Two patients were treated with leukotriene-receptor antagonist; three patients were treated with antihistamines and two with nasal steroids
FEV1 % predicted was lower in patients with uncontrolled asthma compared to healthy controls (p = 0.018)
Summary
Asthma is a chronic inflammatory airway disease that is traditionally characterized by reversible central airway obstruction and airway hyperreactivity [1,2]. Treatment with bronchodilators and inhaled glucocorticosteroids (ICS) normally provide good control of the disease, a significant proportion of the asthmatic patients have persistent symptoms despite conventional therapy [3]. This phenomenon, called uncontrolled asthma [4,5], represents a key challenge for increasing asthma control. Little is known about the inflammatory and remodeling processes causing persisting symptoms in this group of asthmatics. A likely cause of these symptoms is the presence of steroid-resistant components in both central and peripheral airways, as well as conventional inhalation therapy’s insufficient ability to reach the peripheral airways [6]. The few previous studies that have studied transbronchial biopsies from patients with asthma provide clear indications that both small airways and alveolar tissues may be subjected to cellular inflammation [8,9,10]
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