Asthma: 2015 and Beyond
ABSTRACT Asthma is a multifactorial, chronic inflammatory disease of the airways. The knowledge that asthma is an inflammatory disorder has become a core fundamental in the definition of asthma. Asthma's chief features include a variable degree of air-flow obstruction and bronchial hyper-responsiveness, in addition to the underlying chronic airways inflammation. This underlying chronic airway inflammation substantially contributes to airway hyper-responsiveness, air-flow limitation, respiratory symptoms, and disease chronicity. However, this underlying chronic airway inflammation has implications for the diagnosis, management, and potential prevention of the disease. This review for the respiratory therapy community summarizes these developments as well as providing an update on asthma epidemiology, natural history, cause, and pathogenesis. This paper also provides an overview on appropriate diagnostic and monitoring strategies for asthma, pharmacology, and newer therapies for the future as well as relevant management of acute and ambulatory asthma, and a brief review of educational approaches.
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ABSTRACT: The persistent administration of β2‑adrenergic (β2AR) agonists has been demonstrated to increase the risk of severe asthma, partly due to the induction of tolerance to bronchoprotection via undefined mechanisms. The present study investigated the potential effect of the long‑acting β2‑adrenergic agonist, formoterol, on the expression of muscarinic M3 receptor (M3R) in rat airway smooth muscle cells (ASMCs). Primary rat ASMCs were isolated and characterized following immunostaining with anti‑α‑smooth muscle actin antibodies. The protein expression levels of M3R and phospholipase C‑β1 (PLCβ1) were characterized by western blot analysis and the production of inositol 1,4,5‑trisphosphate (IP3) was determined using an enzyme‑linked immunosorbent assay. Formoterol increased the protein expression of M3R in rat ASMCs in a time‑ and dose‑dependent manner, which was significantly inhibited by the β2AR antagonist, ICI118,551 and the cyclic adenosine monophosphate (cAMP) inhibitor, SQ22,536. The increased protein expression of M3R was positively correlated with increased production of PLCβ1 and IP3. Furthermore, treatment with the glucocorticoid, budesonide, and the PLC inhibitor, U73,122, significantly suppressed the formoterol‑induced upregulated protein expression levels of M3R and PLCβ1 and production of IP3. The present study demonstrated that formoterol mediated the upregulation of M3R in the rat ASMCs by activating the β2AR‑cAMP signaling pathway, resulting in increased expression levels of PLCβ1 and IP3, which are key to inducing bronchoprotection tolerance. Administration of glucocorticoids or a PLC antagonist prevented formoterol‑induced bronchoprotection tolerance by suppressing the protein expression of M3R.Molecular Medicine Reports 02/2015; DOI:10.3892/mmr.2015.3307 · 1.48 Impact Factor
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ABSTRACT: Background Recent literature has shown increasing incidence and prevalence rates of eosinophilic esophagitis (EoE). However, data are mainly based on small studies and come from centers dedicated to EoE. Aim of this study was to estimate the incidence rates of EoE by using a large database. Methods We performed a cross-sectional study of the pathology reports describing esophageal eosinophilia from 1996 through 2010, using the nationwide network and registry of histo- and cytopathology in The Netherlands (PALGA). All histopathology reports nationwide enter this database. We classified cases according to the diagnosis made by the pathologist. Annual incidence rates of EoE were estimated. Key Results Our search criteria yielded 8838 positive pathology reports. Eosinophilic esophagitis was diagnosed in 674 patients, of which 74% were men. In another 174 patients, no distinction was made between eosinophilia caused by gastro-esophageal reflux disease or EoE. The incidence of EoE increased considerably over the years, being 0.01 in 1996, 0.01 in 2000, 0.14 in 2005, and 1.31 per 100 000 persons in 2010. Eosinophilic esophagitis was diagnosed in all age groups, but in 2010 the highest incidence was seen in 20-29 years old males, in whom it was estimated to be 3.23 per 100 000 persons. The incidence in children was 0.73 per 100 000 in 2010. No seasonal variation in diagnosis of EoE was observed. Conclusions & Inferences In this large study, we found robust data on increasing incidence rates of pediatric and adult EoE in the past 15 years. This rapidly increasing incidence has not reached a plateau yet.Neurogastroenterology and Motility 09/2012; 25(1). DOI:10.1111/nmo.12009 · 3.42 Impact Factor
Article: Current and future asthma therapies.[Show abstract] [Hide abstract]
ABSTRACT: Corticosteroids (CST) are the gold standard for asthma management and for several decades have been considered the cornerstone for asthma control. With the recent advent of genomic and structural analysis technologies, the molecular basis of the side effects, toxicity and resistance mechanisms of drug treatment are better understood. With respect to CST, there is consistent evidence that while CST therapy improves asthma symptoms, it does not alter the natural course of asthma or offer clear long-lasting improvement of respiratory performance. Therefore, the development of drugs capable of minimizing or avoiding CST side effects, toxicity and resistance could be the way forward for establishing new asthma therapies. This review summarizes the molecular basis of corticosteroid mechanisms of action and the related mechanisms influencing side effects and resistance. The future of CST adjunctive or replacement therapy is also briefly discussed.Drugs of today (Barcelona, Spain: 1998) 05/2013; 49(5):325-39. DOI:10.1358/dot.2013.49.5.1950149 · 1.00 Impact Factor