Asthma therapy: how far have we come, why did we fail and where should we go next?

Abstract

Reversible airflow obstruction and nonspecific airway hyperresponsiveness are: 1) the two key features of asthma; 2) the primary concern for asthma patients; and 3) both directly caused by the airway smooth muscle (ASM). As such, controlling bronchoconstriction should be of primary importance. Unfortunately, all existing pharmacological asthma therapies that specifically target the ASM are based on decades old strategies.In the present study, the evolution of pharmacological asthma therapy will be briefly discussed, some explanations will be suggested as to why substantial new advances in this area have not occurred in several years and, finally, several new directions for novel asthma therapies will be proposed.

ER-localized bestrophin 1 activates Ca2+-dependent ion channels TMEM16A and SK4 possibly by acting as a counterion channel

“…SR-localized Cl − channels in the SR membrane allow for neutralization of electrostatic charges that would otherwise build up during Ca 2+ movement [16,17]. Thus, SR-localized Cl − channels support Ca 2+ signaling and muscle contraction, and blocking these Cl − channels might be an effective way in inhibiting airway smooth muscle hyper-responsiveness in asthma [16,20]. Our present results suggest that bestrophin 1 is a counterion channel in the ER and thereby facilitates intracellular Ca 2+ signaling in epithelial cells.…”

Neuroimmune semaphorin 4A downregulates the severity of allergic response

“…Moreover, many side-effects of these medicines which involve bone, metabolic, and cardiovascular systems, also limit their efficacy. 5, 6 Therefore, novel molecular targets are being investigated 7 and novel approaches are being developed 8 which may have a profound impact on improving the diagnostic, prevention, and treatment of the allergic asthmatic diseases.…”

Bronchial thermoplasty; a new treatment modality in asthma

“…Bu nedenle selektif olarak hava yolu düz kas kütlesinin azaltılmasını hedef alan yaklaşımların, obstrüksiyonu ve hava yolu remodellingini azaltarak hastalığın kontrolünde etkili olup, mevcut tedavilere üstünlük sağlayabileceği üzerinde durulmuştur. Hava yolu düz kas proliferasyonunu ve migrasyonunu engelleme, hava yolu düz kas apopitozunu artırma, hava yolu düz kasına toksin uygulama gibi çok da başarı sağlanamayan immünolojik ve genetik yaklaşımlar denenmiştir (12).…”