Inflammation and remodeling in the adult and child with asthma

Abstract

Inflammation and remodeling are characteristic features of the conducting airways in asthma, but the relationships between inflammation, inappropriate remodeling, bronchial hyperresponsiveness, and reduced pulmonary function are still unclear. In both adults and children with asthma, there are structural changes of the conducting airways that include injury and loss of the surface epithelium, thickening of the reticular basement membrane, increases of underlying collagen, blood vessels, and airway smooth muscle, and plugging of the airways by exudate. Bronchial biopsies obtained from persons with mild stable asthma already demonstrate the presence of inflammation. Many of the inflammatory and structural changes begin early in childhood. Whereas corticosteroids markedly reduce many aspects of inflammation, it is not known whether and how they affect the changes associated with airway wall remodeling. Leukotriene receptor antagonists appear to be antiinflammatory and able to reduce the proliferation of bronchial smooth muscle. Pediatr Pulmonol. 2001; Supplement 21:3–16. © 2001 Wiley‐Liss, Inc.

Modulation of human lung fibroblast functions by ciclesonide: Evidence for its conversion into the active metabolite desisobutyryl-ciclesonide

“…This could be a key issue, considering both the pharmacokinetic characteristics of the drug and the elevated numbers of cells involved in the pathogenesis of asthma [9]. Indeed, in the last decades it has become clear that, in addition to inflammatory cells, structural components of the airways, including fibroblasts, play a key role in modulating the inflammatory reaction and the repair processes that characterize the disease [9,10]. Indeed, fibroblasts have the capability to directly contribute to asthma pathogenesis, releasing a variety of chemokines and cytokines, expressing surface molecules, proliferating, producing extracellular matrix components and evolving into various cell types, including myofibroblasts [11,12].…”

Effects of Zileuton on Airway Smooth Muscle Remodeling after Repeated Allergen Challenge in Brown Norway Rats

“…Their effects are reduced by zileuton, thereby reducing airway remodeling in OA-treated animals [22,31]. This study also demonstrates that the IL-13, TGF-β and VEGF cytokine levels, the IL-13, TGF-β and VEGF mRNA expressions, the area of collagen deposition and the mean number of blood vessels surrounding the airways are lowest in the control group than in the other two groups.…”

“…Salmon et al [30] have shown that repeated allergen exposure of sensitized brown Norway rats induces airway cell DNA synthesis and remodeling, while Henderson et al [31] have shown that the cysteinyl leukotriene1 receptor antagonist, Montelukast, significantly reduces airway eosinophil infiltration, mucus plugging, smooth muscle hyperplasia and subepithelial fibrosis in OA-sensitized or OA-challenged mice. Jeffery [22] reported that leukotriene receptor antagonists may be anti-inflammatory and may be able to reduce bronchial smooth muscle proliferation. …”

“…Evidence also suggests that blocking the leukotriene pathway may result in reduced inflammation, thereby preventing airway remodeling [20,22]. Zileuton is a 5-lipoxygenase inhibitor [23].…”

Early Changes in Basement Membrane Thickness in Airway Walls Post-Lung Transplantation

“…17 In particular, increased BMT is associated with early asthma. 18 Studies of Wilson et al 19 and Roche et al 20 report that excessive BMT will impede airflow. As resistance is inversely proportional to the radius of the bronchi to the fourth power, sub-epithelial fibrosis compounded by a small increase in BMT would be expected to increase airways resistance, significantly decreasing lung function.…”