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No full textBiologic and pharmacologic therapies in clinical development for the inflammatory response in COPD
No full textChronic obstructive pulmonary disease (COPD) is a progressive and debilitating condition with declining lung function associated with airway inflammation, mucus hypersecretion and remodeling. Inflammatory cells contribute to the disease processes via the production of proteases, fibrotic or mitogenic growth factors, cytokines, chemokines and their receptors. Particularly newer agents that treat the underlying inflammation and remodeling. Here, we briefly review current understanding of the inflammatory mechanisms involved in the pathogenesis of COPD. This understanding has enabled the identification of several therapeutic targets that might have great potential for the development of novel anti-inflammatory and anti-remodeling biologic therapies with considerable clinical advantage for COPD. Some of these molecules have been assessed, and others are in the early stages of being assessed. This article gives an up-to-date summary of these novel therapies and their status of clinical development in targeting the various inflammatory pathways of COPD
Evolving concepts on the value of adenosine hyperresponsiveness in asthma and chronic obstructive pulmonary disease
No full textAdenosine is a purine nucleoside which mediates a variety of cellular responses relevant to asthma and COPD through interaction with specific receptors. Administration of adenosine by inhalation to patients with asthma and COPD is known to cause concentration related bronchoconstriction. Responses elicited by this purine derivative in asthma and COPD should not be considered as a mere reflection of non-specific airways hyperresponsiveness. Evaluation of airways responsiveness by adenosine induced bronchoconstriction may be valuable in differentiating asthma from COPD, monitoring of anti-inflammatory treatment in asthma, surveying disease progression, and assessing disease activity in relation to allergic airways inflammation
Therapeutic potential of adenosine receptor antagonists and agonists
No full textThe adenosine receptors (A 1 , A 2A , A 2B and A 3 ) are important and ubiquitous mediators of cellular signalling, which play vital roles in protecting tissues and organs from damage. Launched drugs include the adenosine receptor antagonists theophylline and doxofylline (both used as bronchodilators in
respiratory disorders such as asthma), while several compounds are presently in clinical trials for a range of indications, including heart failure, Parkinson’s disease, rheumatoid arthritis, cancer, pain and chronic obstructive pulmonary disease. A host of companies and institutions are addressing the huge potential
for the development of selective adenosine receptor agonists and antagonists, so that it appears we are on the verge of a new wave of compounds approaching the market for many unmet medical needs. This review presents an analysis of the patenting activity in the area for 2006 and an interpretation and reflection on the developments that we can expect in the future
Slowing Progression Along the Allergic Disease Continuum: Quo Vadit Immunotherapy?
No full textThere is emerging evidence that rhinitis frequently precedes the onset of asthmatic symptoms. The frequent association of rhinitis and asthma has led to the concept that these conditions are likely manifestations of the same disease. This hypothesis has important implications for both the diagnosis and the management of these common conditions. Unfortunately, there is little known regarding the risk factors responsible for the progres- sion of rhinitis to asthma. The current treatment options can control symptoms but do not prevent or cure the disease. However, there is recent data supporting the notion that it is possible to prevent new asthma cases by modifying the immune response and clinical outcome with allergen immunotherapy. This review article evalu- ates the impact of rhinitis on the development of asthma, examines putative predictors for the progression of rhinitis to asthma, and reviews recent, promising literature suggesting that early treatment of allergic individu- als with immunotherapy may aid in asthma prevention
THE POTENTIAL THERAPEUTIC ROLE OF POTASSIUM CHANNEL MODULATORS IN ASTHMA AND CHRONIC OBSTRUCTIVE PULMONARY DISEASE
No full textThe involvement of a number of potassium channels has been reported in respiratory conditions such as asthma and chronic obstructive pulmonary disease (COPD), supporting the idea that potassium channel modulating agents may help control it. Experimental evidence and preclinical models suggest that ATP-dependent K(+) (K(ATP)) channel openers, big-conductance K(+) (BK(CA)) channel openers, and intermediate-conductance K(+) (IK(CA)) channel blockers may be the most effective agents for treating asthma and COPD. Modulation of potassium channels by these agents may produce beneficial effects such as bronchodilation, a reduction in airways hyperresponsiveness (AHR), a reduction in cough and mucus production and an inhibition in airway inflammation and remodelling. The aim of this paper is to investigate the role of K(+) channel modulation in the pathogenesis, progression and exacerbation of asthma and COPD, and to review the evidence suggesting that K(+) channel modulators may be a valuable treatment option for these respiratory diseases
Adenosine and adenosine receptors: their contribution to airway inflammation and therapeutic potential in asthma
No full textGrowing evidence emphasizes that the purine nucleoside adenosine plays an active role as local regulator in airway inflammation and pulmonary diseases. The notion that increased adenosine concentrations are associated with lung inflammation indicates the importance of this signaling pathway, which involves the activation of a family of cell surface G-protein coupled receptor subtypes named as A(1), A(2A), A(2B) and A(3). Recently, important progress has been made to better clarify the role of these receptors in a variety of inflammatory airway disorders including asthma. As a consequence, new molecules with high affinity and high selectivity for the human adenosine receptors subtypes designed to control the airway inflammatory component of asthma have been launched and are currently tested in clinical trials as anti-asthma treatments. With the availability of these molecules for testing in humans, the role of adenosine receptors in asthma can now be validated
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