Effect of Bronchoconstriction on Airway Remodeling in Asthma

Abstract

Bronchoconstriction without additional inflammation induces airway remodeling in patients with asthma. These findings have potential implications for management.

Transforming Growth Factor β1 Function in Airway Remodeling and Hyperresponsiveness. The Missing Link?

“…Agonist-induced ASM bronchoconstriction (22) and myofibroblast contraction (23) induce the release of active TGF-b1, which may augment both airway remodeling and airway narrowing. Furthermore, challenge with the contractile agonist methacholine induces active TGF-b1 release and airway remodeling without affecting airway eosinophil recruitment, suggesting an uncoupling of airway inflammation from both AHR and remodeling (24). Thus, TGF-b1 is emerging as a potential target mediating the connection between airway remodeling and AHR in asthma.…”

Inhaled corticosteroid dose response in asthma

“…Mann PD 10 Provocative dose of mannitol causing a 10% fall in FEV 1 44 Mann PD 15 Provocative dose of mannitol causing a 15% fall in FEV 1 45 …”

“…Targeting 255 ICS therapy using mannitol challenge AHR has been shown to reduce mild 256 exacerbations over and above standard guideline driven therapy 11 , in line with 257 that for sputum eosinophils 10 . However, AHR can be driven by other 258 mechanisms such as airway smooth muscle hyperplasia, and airway closure 259 itself 44 , and is therefore an area requiring further study with regards to 260 personalised asthma treatment 45 . 261 262 There is therefore a growing body of evidence suggesting that we need to include 263 inflammatory measurements routinely to best manage patients with asthma.…”

The Role of Mnk-1, Eukaryotic Translation Initiation Factors and Translation Control in the Pathogenesis of Asthma

“…Earlier it was thought that airway wall remodelling results from term chronic inflammation in asthma or COPD [1][2][3][4]. Recent clinical studies indicated that airway wall remodelling occurs before or without inflammation [1,5,6]. Asthma relevant cytokines such as IL-3, IL-4, IL-5, TGF-β, TNF-α and IgE, contribute to airway wall remodelling, but their inhibition did not significantly reduce the pathology [7].…”

“…In 2011, Grainge et al conducted a study where volunteers inhaled either a cholinergic stimulus or house dust mite antigens three times over five days, with bronchus biopsies obtained before and inhalation and three days after the last inhalation [6]. Shown in tissue biopsies, airway wall remodelling was induced by both stimuli and prevented in patients who inhaled a short acting β2-agonist.…”