Asthma trials

In an asthma trial comparing two short acting treatments, the following (hypothetical) data were obtained for the increase in FEVj (Table 3.2) ... 

Marshall E (2001) Procedures faulted in fatal asthma trial. Science 293 405 106... 

Sears MR, Radner F. Safety of budesonide/formoterol maintenance and reliever therapy in asthma trials. Respir Med 2009 103(12) 1960-8. 

Recent studies using the T-cell-selective agent cyclosporin A (CsA) have shown promising results in the management of steroid-dependent asthma. Trials of CsA treatment in steroid-dependent asthma have resulted in improved lung function, a reduction in asthma exacerbations, and a reduction of IL-2 and IL-2 receptor expression and the transcription and translation of mRNA for IL-5 and GM-CSF in CD4+ T cells (349). 

Selective AR agonists are undergoing clinical trials for cardiac arrhythmias and pain (Ai) cardiac imaging and inflammation (A2a) colon cancer, rheumatoid arthritis, psoriasis, and dry eye (A3). Selective AR antagonists are either in or advancing toward clinical trials for kidney disorders (Ax) Parkinson s disease (A2a) diabetes and asthma (A2B) cancer and glaucoma (A3). 

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. 

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. 

Guendelman S, Meade K, Benson M, et al. Improving asthma outcomes and selfmanagement behaviors of inner-city children a randomized trial of the Health... 

Pogash RM, Haak T, Grella V, Zimmerman R, Doty L. Using the web for secnrely managing the asthma Clinical Research Network (ACRN) and the Childhood Asthma Research And Education (CARE) network. Controlled Clin Trials 2004 1.1.4 387-98(12). 

Tiotropium is a long-acting inhaled anticholinergic available in a DPI it has an onset of action of approximately 30 minutes and a duration of action longer than 24 hours.32 Because pure asthmatics were excluded from clinical trials for tiotropium, a paucity of data exist concerning its use in asthma. 

Clinical trials have indicated that omalizumab, a recombinant humanized monoclonal IgE antibody approved for use in moderate to severe persistent asthma in patients with reactivity to a perennial allergen, is effective in the treatment of SAR.25-27 Omalizumab inhibits the binding of IgE to mast cell and basophil receptors, resulting in a reduction of allergic mediator release.25 Additionally, serum free IgE levels are decreased.2 27 In SAR patients, omalizumab improves quality of life and nasal symptoms and reduces antihistamine needs. The most effective dose in SAR appears to be omalizumab 300 mg administered subcutaneously every 3 to 4 weeks depending on baseline IgE levels.26,27... 

The most common adverse effect with omalizumab is injection-site reaction, reported in 45% of patients in clinical trials. Other adverse effects include viral and upper respiratory tract infections, sinusitis, headache, and pharyngitis. Rare cases of malignant neoplasms and anaphylaxis were reported during clinical trials of omalizumab in asthma. Patients should be monitored for at least 2 hours following the injection so that anaphylaxis and/or injection-site reactions may be managed.25... 

Malmstrom K, Rodriguez-Gomez G, Guerra J et al. Oral montelukast, inhaled beclomethasone, and placebo for chronic asthma. A randomized, controlled trial. Montelukast/Beclometha-sone Study Group. Ann Intern Med 1999 130 487-495. 

The field of pharmacogenomics is still in its infancy. Its use is currently quite limited, but new approaches are under study in clinical trials. In the future, pharmacogenomics will allow the development of tailored drugs to treat a wide range of health problems, including cardiovascular disease, Alzheimer disease, cancer, HIV/ AIDS, and asthma. 

An inhalable medication that relaxes the muscles in the airways (bron-chodilator) is frequently administered when airways obstruction is identified. In this bronchodilator trial test, the spirometry test is subsequently repeated and compared to the results from the initial spirometry test. If there is substantial improvement in lung function with the administration of the bronchodilator, the airways obstruction is reversible. An example of a lung disease with reversible airways obstruction is asthma, in which s)nnptoms occur episodically when airways obstruction occurs. If there is little or no improvement after the administration of the bronchodilator, the airways obstruction is fixed. An example of a limg disease with fixed airways obstruction is BO, where there is scarring of the airways. 

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