In asthma

Improvements in asthma treatment include the development of more effective, safer formulations of known dmgs. The aerosol adrninistration of P2-agonists or corticosteroids results in a decrease in side effects. Also, the use of reUable sustained release formulations has revolutionized the use of oral xanthines which have a very narrow therapeutic index (see Controlled release technology). For many individuals, asthma symptoms tend to worsen at night and the inhaled bronchodilatots do not usually last through an entire night s sleep (26,27). 

The effectiveness of theophylline in the treatment of asthma seems to result from a combination of biological properties which are not clearly understood (63). Detailed discussions of the possible role of xanthines in asthma may be found in references 64—66. 

Two newer potent selective H -antagonists, terfenadine (23) (132) and astemizole (24) (133), have been developed which have neither the sedative nor the anticholinergic Habilities of the earlier agents. Both of these compounds have proven efficacious in the treatment of hay fever and produce very few side effects, prompting a re-evaluation of the role of antihistamines in asthma treatment. 

The chromaffin cells of the adrenal medulla may be considered to be modified sympathetic neurons that are able to synthesize E from NE by /V-methylation. In this case the amine is Hberated into the circulation, where it exerts effects similar to those of NE in addition, E exhibits effects different from those of NE, such as relaxation of lung muscle (hence its use in asthma). Small amounts of E are also found in the central nervous system, particularly in the brain stem where it may be involved in blood pressure regulation. DA, the precursor of NE, has biological activity in peripheral tissues such as the kidney, and serves as a neurotransmitter in several important pathways in the brain (1,2). 

Forced vital capacity (FVC) quantifies the maximum air volume expired following a maximal inspiration and is one of the basic measures of analyzing flow changes such as reduced airway patency observed in asthma. To measure FVC, an individual inhales maximally and then exhales as rapidly and completely as possible. FVC primarily reflects the elastic properties of the respiratory tract. The gas volume forcibly expired within a given time interval, FEV (where t is typically one second, FEVj q)... 

Beta adrenergic agonists also exert bronchodilating effects. These drugs are thus often used in conjunction with theophiline in asthma therapy. A drug that combines both moieties, reproterol (40), has interestingly proved... 

Asthma is a chronic inflammatory disease. Therefore steroids represent the most important and most frequently used medication. Already after the fust treatment, steroids reduce cellular infiltration, inflammation, and the LAR, whereas changes in the EAR require prolonged treatment to lower the existent IgE levels. The mechanisms of steroid actions are complex and only incompletely understood. Besides their general antiinflammatory properties (see chapter glucocorticoids), the reduction of IL-4 and IL-5 production from T-lymphocytes is particularly important for asthma therapy. The introduction of inhaled steroids, which have dramatically limited side effects of steroids, is considered one of the most important advancements in asthma therapy. Inhaled steroids (beclomethasone, budesonide, fluticasone, triamcinolone, momethasone) are used in mild, moderate, and partially also in severe asthma oral steroids are used only in severe asthma and the treatment of status asthmaticus. Minor side effects of most inhaled steroids are hoarseness and candidasis, which are avoided by the prodrug steroid ciclesonide. 

Umetsu DT, Dekmyff RH (2006) Immune dysregulation in asthma. Curr Opin Immunol 18 727-732. 

Inhaled steroids (commonly used are beclomethasone, budesonide, triamcinolone, fluticasone, flunisolide) appear to attenuate the inflammatory response, to reduce bronchial hyperreactivity, to decrease exacerbations and to improve health status they may also reduce the risk of myocar dial infar ction, but they do not modify the longterm decline in lung function. Whether- steroids affect mortality remains unclear. Many patients appear to be resistant to steroids and large, long-term trials have shown only limited effectiveness of inhaled corticosteroid ther apy. Certainly, the benefit from steroids is smaller in COPD than in asthma. Topical side-effects of inhaled steroids are oropharyngeal candidiasis and hoarse voice. At the normal doses systemic side-effects of inhaled steroids have not been firmly established. The current recommendation is that the addition of inhaled gluco-coiticosteroids to bronchodilator treatment is appropriate for patients with severe to veiy sever e COPD. 

Johnson M (2004) Interactions between corticosteroids and beta2-agonists in asthma and chronic obstructive pulmonary disease. Proc Am Thorac Soc 1 200-6... 

TK NK2r antagonists showed interesting activities in preclinical models of depression, anxiety, asthma, gastrointestinal dysmotility and hypersensitivity, and urinary incontinence [1,3]. In clinical, NK2r antagonists antagonize NKA-induced bronchoconstriction and NKA-induced intestinal dysmotility. However, a pilot trial in asthma failed to show any clinical benefit by... 

TLR-9 has also been used to target asthma with several compounds in preclinical trials such as second generation CpG-ODNs and HYB2093. 1018 ISS has also been tested in asthma. Defence against infectious disease is also enhanced through TLR-9. CpGIOlOl was in phase II trails as a Hepatitis C target but has been discontinued. 

Kool M. Lambrecht BN Dendritic cells in asthma and COPD opportunities for drug development Curr Opin Immunol 2007 19 701-710. 

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