Treating asthma means treating airway smooth muscle cells

Abstract

Asthma is characterised by airway hyperresponsiveness, airway inflammation and airway remodelling. Airway smooth muscle cells are known to be the main effector cells of airway narrowing. In the present paper, studies will be discussed that have led to a novel view of the role of airway smooth muscle in the pathogenesis of asthma in which airway hyperresponsiveness, remodelling and inflammation are, at least in part, attributable to airway smooth muscle. Furthermore, how this new view may lead to a change in the phenotyping and treatment of patients with asthma will be discussed.

The secret life of steroids in asthma

“…Steroids affect gene transcription in virtually any cell type, not only in inflammatory cells, but also in airway resident cells, including airway smooth muscle [25]. The responsible signalling pathways are not fully understood, and could not only be related to transcriptional and posttranscriptional inhibition of MKP-1 and calcium-mobilising second messengers [26], but also to altered transcription of proteins that are responsible for airway smooth muscle phenotype, including contractile elements, cytoskeleton, cell surface molecules, and cytokines or mediators with autocrine function [23,27]. This will inevitably influence contractile, secretory and proliferative activity.…”

Airway Smooth Muscle: Is There a Phenotype Associated with Asthma?

“…Among other triggers, stimulation of ASM resident protease activated receptor 2 (PAR-2) by mast cell-derived tryptase enhances TGF 1 expression, thus potentiating a "feed forward system" leading to increased mast cell recruitment (Berger et al, 2003). In addition, as demonstrated in vitro, TGF 1 facilitates transformation of epithelial cells to myofibroblasts, with likely consequences to ASM hyperplasia (Zuyderduyn et al, 2008). With inflammation, expression of mast cell resident CD44 (hyaluronate receptor) and CD51 (vitronectin receptor) to ECM defines mast cell adhesion to ASM.…”

Termoplastia brônquica em asma

“…Patients with severe uncontrolled asthma are known to be responsible for most of the expenditures of and the visits to public health care facilities. (13,14) It is known that, in asthma patients, bronchoscopy can worsen symptoms and cause • Adult with a documented diagnosis of asthma: FEV 1 reversibility; bronchial hyperreactivity; or pulmonary tuberculosis • Former smoker (less than 10 pack-years) who has not smoked for one year or more • Symptomatic, despite appropriate treatment (fluticasone, or equivalent, at a dose > 500 µg + longacting β 2 agonists) elimination of ASM would reduce the release of inflammatory mediators that exist within the muscle fibers, (23) this hypothesis has yet to be tested. In contrast, patients with predominantly "non-eosinophilic" disease, in which ASM dysfunction is more prominent, would benefit more from this treatment.…”