Asthma treatment response

Drazen JM, Yandava CN, Dube L, SzCZERBACK N, HlPPENSTEEL R, PlLLARI et al. Pharmacogenomic association between ALOX5 promoter genotype and the response to anti-asthma treatment. Nature Genet 1999 22 168-170. 

Drazen, J., et al., "Pharmacogenetic Association Between ALOX5 Promoter Genotype and the Response to Anti-Asthma Treatment," Nat. Genet., 22, 168-170 (1999). 

Israel E. (2005) Genetics and the variability of treatment response in asthma. J Allergy Clin Immunol. 115(4 suppL), S532-S538. 

Observation of the use of leaves from Datura stramonium for asthma treatment in India led to the discovery of atropine, a potent competitive inhibitor of acetylcholine at postganglionic muscarinic receptors, as a bronchodilator. Interest in the potential value of antimuscarinic agents increased with demonstration of the importance of the vagus nerves in bronchospastic responses of laboratory animals and by the development of a potent atropine analog that is poorly absorbed after aerosol administration and that is therefore relatively free of systemic atropine-like effects. 

The role of thermoboxane antagonists is asthma treatment still remains uncertain. AA-2414 (41) oral administration to asthmatic subjects favorably attenuated their response to methacholine challenge [98]. Modification of a 7-oxabicyclo heptane of drug candidates by incorporation of a phenylene spacer in the a-chain afforded SQ 35,091 (42), which shows longer duration of action (tj/2 = 16 hr) [99]. GR 32191 (43) shows PGD2-induced bronchoconstriction in asthmatics at 80 mg PO [100],... 

Woodruff PG, Boushey HA, Dolganov GM, Barker CS, Yang YH, Donnelly S, Ellwanger A, Sidhu SS, Dao-Pick TP, Pantoja C, Erie DJ, Yamamoto KR, Fahy JV (2007) Genome-wide profiling identifies epithelial cell genes associated with asthma and with treatment response to corticosteroids. Proc Natl Acad Sci U S A 104(40) 15858-15863. doi 10.1073/pnas.0707413104... 

Other applications of pH-responsive polymers for drug-delivery systems have also been explored such as the incorporation of fibroblast growth factors to improve angiogenesis in infracted myocardium (Garbem et al., 2011) the incorporation of ketoprofen for colon-targeted delivery (Kulkami et al., 2012) intracellular delivery of ovalbumin to dendritic cells (a class of cells intimately involved with adaptive immunity) (Hn et al., 2007) and for controlling drug release in nocturnal asthma treatment (Tran et al., 2013). 

ICSs are the mainstay of asthma treatment. In search of a method for determining the bioequivalence of these preparations, researchers have assessed their inhibitory effect on allergen-induced EAR and confirmed their ability to attenuate both the EAR and the secondary increase in airway responsiveness (113,114). 

Cockcroft DW. AUagen-induced inaease in airway responsiveness a model for examination of anti-inflammatory effects of asthma treatment. In Morley J, ed. Preventive Therapy in Asthma. London Academic Press, 1991 141-152. 

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. 

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