Asthma remains a major health issue around the world where its incidence and prevalence are still increasing in many countries. Despite a general perception that the problem of treating asthma is "solved" many patients are undertreated by current "one-size-fits-all" approaches to asthma treatment. This issue of Seminars in Respiratory and Critical Care Medicine reviews current trends and future developments in the pathophysiology, diagnosis, and treatment of asthma that are likely to be of clinical importance.
The effect of a potassium channel activator, cromakalim (BRL 34915), on excitatory nonadrenergic noncholinergic (e-NANC) and cholinergic neural bronchoconstriction was studied in guinea pigs. We monitored airway opening pressure as an index of airway caliber. After atropine (1 mg/kg iv.) and propranolol (1 mg/kg iv.), bilateral vagal stimulation evoked an e-NANC response. Cromakalim did not alter basal airway caliber, but reduced the e-NANC response to vagal stimulation in a dose-dependent manner, with a maximal inhibition of 71.9 +/- 9.2% (mean +/- S.E.) at 400 micrograms/kg i.v. (P less than .01). Pretreatment with phentolamine (2.5 mg/kg i.v.) had no effect on the inhibitory response produced by cromakalim but glibenclamide (25 mg/kg iv.), an inhibitor of ATP-sensitive potassium channels, blocked its effect. Cromakalim had no inhibitory effect on exogenous substance P (5-25 micrograms/kg i.v.)-induced bronchoconstriction. In animals depleted of tachykinins by capsaicin (50 mg/kg s.c.) pretreatment, cromakalim had an inhibitory effect on both vagalcholinergic and exogenous acetylcholine (0.3-2 micrograms/kg i.v.)-induced bronchoconstriction, although the inhibitory effect was significantly greater on neural stimulation. We conclude that potassium channels modulate both e-NANC and cholinergic neurotransmission, and to a lesser extent acetylcholine-induced bronchoconstriction in guinea pig airways.
No abstract is provided for this article.
The Absorb bioresorbable scaffold (BRS), the most studied device among all BRS, suffered a major setback following the negative results of the ABSORB trials. However, approximately 34 BRSs from 22 companies are currently under development. The potential device-specific factors related to the increased event rate in Absorb were: 1) weak mechanical properties, 2) larger strut thickness (less embedment and larger protrusion) and width (larger footprint) predisposing to underexpansion/protrusion of struts, eventually resulting in increased thrombogenicity, and 3) longer bioresorption time combined with failure of encapsulation of struts before the dismantling process ensues. Given the diversity of bioresorbable materials (even amongst PLLA), and the different mechanical properties and bioresorption profiles of each new BRS, one could expect considerable difference in early and late clinical outcomes. As a matter of fact, data from first-in-man (FIM) and pivotal trials have demonstrated variable clinical results. Indeed, early clinical evidence from FIM trials does not support a class effect. However, the absence of a comparator precludes us from drawing definitive conclusions. Further clinical evidence should confirm the absence (or presence) of a class effect.
