Airway Remodeling in Asthma

Abstract

Airway remodeling can be defined as changes in the composition, content, and organization of the cellular and molecular constituents of the airway wall. Airway remodeling is a characteristic feature of asthma, and has important functional implications. These structural changes include epithelial detachment, subepithelial fibrosis, increased airway smooth muscle (ASM) mass, decreased distance between epithelium and ASM cells, goblet cell hyperplasia, mucus gland hyperplasia, proliferation of blood vessels and airway edema and changes in the cartilage. Each can contribute to airway hyperreactivity (AHR), and may eventually lead to irreversible airflow obstruction with disease progression. Structural changes can be observed from early onset of the disease and thus remodeling is thought to be characteristic of asthma. Some aspects of airway remodeling can be explained as a consequence of TH2 inflammation, although it has also been suggested that the exaggerated inflammation and remodeling seen in asthmatic airways is the consequence of abnormal injury and repair responses stemming from the susceptibility of bronchial epithelia to components of the inhaled environment. According to this view, remodeling occurs by way of a noninflammatory mechanism, where inflammation of airways and altered structure and function of the airways are parallel and interacting factors. Airway remodeling in established asthma is poorly responsive to current therapies, such as inhalation of corticosteroids and administration of beta(2)-agonists, antileukotrienes, and theophylline.

Complete Dependence on CD4+ Cells in Late Asthmatic Response, but Limited Contribution of the Cells to Airway Remodeling in Sensitized Mice

“…All these modifications thicken airway walls in asthmatic patients, leading to airway hyperresponsiveness to specific allergens and non-specific stimuli (9). Thus, the existence of airway remodeling may be closely associated with antigen-induced airway narrowing, including LAR (9,10); however, the relationship between antigen-induced airway narrowing and airway remodeling has not been examined, even in experimental animals. Furthermore, studies using murine models have shown that airway remodeling was also mediated by activation of CD4 + cells because anti-CD4 mAb effectively suppressed the histological changes (11); however, another study demonstrated that CD4 + cells were not required for progressive airway remodeling (12).…”

“…These changes include fibroblast proliferation, airway smooth muscle hyperplasia and hypertrophy, and excess production of mucus (9,10). All these modifications thicken airway walls in asthmatic patients, leading to airway hyperresponsiveness to specific allergens and non-specific stimuli (9).…”

The Morphological Effects of Asthma, As Well As Conventional and Alternative Asthma Therapies on Parietal and Chief Cells in the Stomach of BALB/c Mice

“…A defining histopathological feature of the respiratory tissues amongst asthmatics is the increased infiltration of leukocytes, predominantly eosinophils and allergen-specific CD4+ Th2 cells (Nauta et al;Warner & Knight, 2008;Kay, 1988;Sumi & Hamid, 2007;Lloyd & Rankin, 2003;D'Ambrosio et al, 2003;Gwinn et al, 2006;Kelly et al, 2007). The entire stomach mucosa during asthma, as in the respiratory tissues, has been noted to show an increased influx of lymphocytes; however, no studies to date have determined if these invading lymphocytes are allergen-specific CD4+ Th2 cells (Nepomnyashchikh et al).…”

Impact of Nebulized Sildenafil on Lung Histology in a Murine Model of Chronic Asthma

“…3 Air way re mo de ling is prog res si ve struc tu ral chan ges in the com po si ti on, con tent, and or ga niza ti on of the cel lu lar and mo le cu lar cons ti tu ents of the air way wall. 4 Alt ho ugh cur rent ast hma the rapi es are ef fec ti ve in re du cing inf lam ma ti on, air way re mo de ling is po orly res pon si ve to cur rent the rapi es, such as in ha led cor ti cos te ro ids, an ti le u kot ri enes, and the ophy lli ne. 4,5 Thus, new the ra pe u tic op ti ons are re qu i red.…”

“…4 Alt ho ugh cur rent ast hma the rapi es are ef fec ti ve in re du cing inf lam ma ti on, air way re mo de ling is po orly res pon si ve to cur rent the rapi es, such as in ha led cor ti cos te ro ids, an ti le u kot ri enes, and the ophy lli ne. 4,5 Thus, new the ra pe u tic op ti ons are re qu i red.…”