Determinants of the bronchodilation response to salbutamol on histamine-induced bronchoconstriction

Abstract

Assessment of the bronchodilation response to short-acting beta2-adrenoreceptor agonists on pharmacologically induced bronchoconstriction has often been used to investigate airway smooth muscle beta2-adrenoreceptor function. However, little is known about factors affecting this response. In the present study, the bronchodilation response to 0.2 mg of salbutamol on histamine-induced bronchoconstriction was assessed in 101 steroid-naïve asthmatic subjects. The associations of the response with a wide range of challenge procedure-related variables, clinical asthma severity indicators, and blood markers of airway inflammation were investigated. The response was re-assessed after 6 and 12 weeks' therapy with inhaled budesonide. Baseline FEV1, final histamine concentration, and the maximal fall in FEV1 explained 35-59% of the total variation in the response to salbutamol, depending on the index chosen to express the response. Serum concentration of myeloperoxidase, an index of neutrophilic inflammation, was associated with a poor response. The preceding week daily PEF variation, rescue bronchodilator use, severity of asthmatic symptoms, blood eosinophil count, and serum eosinophilic cationic protein and eosinophilic protein X concentrations were not associated with the response. The salbutamol response seemed to diminish during budesonide treatment but when adjusted by the challenge procedure-related variables the treatment effect vanished. In conclusion, the bronchodilation response to salbutamol on histamine-induced bronchoconstriction is largely determined by challenge procedure-related variables. It seems to be unrelated to the clinical severity of asthma and is not affected by treatment with inhaled corticosteroids. Neutrophilic airway inflammation may be associated with a poor response.

The Role of SLC22A4 Gene Polymorphisms in the Response to Salbutamol in Asthmatic Patients

“…The genotype distribution of rs2073838 in both groups did not differ significantly from the distribution in normal populations studied in previous literatures such as Plenge et al, (2005) study on north American and Sweden populations (Plenge et al, 2005). For rs3792876, the distribution in responders goes with that in previous studies while in non-responders the distribution differs significantly from normal populations (Hou et al, 201;Jaruskova et al, 2017;Angelini et al, 2013;De Ridder et al, 2007;Barton et al, 2005;Shahidi and Fitzgerald, 2010;Koskela et al, 2006;Poon et la., 2012;Larocca et al, 2013;Newman et al, 2005;Charan and Biswas, 2013;Heffler et al, 2016;Hegewald et al, 2012;Dunn et al, 2015;Ahmad and Singh, 2010;Chiappori et al, 2012;Plenge et al, 2005;. Finally, none of the studied genotypes was associated with gender, age of onset, positive family history, history of atopy or asthma severity.…”

“…Patients not on regular treatment, having other complications like bronchiectasis or chest infections and patients who refused or unable to give informed written consent for participation were excluded from the study. Patients with intermittent and severe asthma were excluded as the formers usually seek medical advice at the primary care units during attacks and are lost from follow up for several months (Shahidi and Fitzgerald, 2010), also, it is difficult to assess BDR in stable asthmatic patients whom there is no resting bronchoconstriction (Koskela et al, 2006), the later were excluded as they are usually resistant to inhaled bronchodilators and already require high doses of inhaled and systemic corticosteroids (Poon et al, 2012).…”