A Randomized Primary Care Trial of Steroid Titration Against Mannitol in Persistent Asthma

Inhaled corticosteroid dose response in asthma

“…Multiple linear regression analyses, using both 129 forward stepwise and non-hierarchical introduction of predictors, were also 130 employed to examine for any confounding effects of biological covariates on the (Table 164 2). Improvements were more pronounced in the subgroup with baseline values 165 of FeNO≥25ppb (Figure 2b 39 , blood Eos 16 , FeNO 21 and AHR 11,13 . Moreover, targeted ICS therapy towards 236 inflammatory outcomes has been shown to reduce the rate of exacerbations 10 , or 237 reduce the overall steroid dose required for total control 12 .…”

“…Studies have shown that titrating 19 steroid therapy against inflammation may improve outcomes such as 20 exacerbation rates [10][11][12] . For example in one primary care based study titrating 21 inhaled corticosteroid dose against mannitol challenge verses a reference 22 strategy, resulted in a 27% significant reduction in mild exacerbations but no 23 difference in severe exacerbations 11 . Similar findings were observed in another 24 study using methacholine challenge 13 .…”

“…Serum ECP was measured in duplicate using a 107 6 UniCAP system (Phadia) with a coefficient of variation of 3%. For symptoms, 3 108 studies 11,24,26 included the mini-Asthma Quality of Life Questionnaire (AQLQ, 109 symptom component), where a mean score of 7 indicates no symptoms, and <7 110 indicates progressively worse symptoms. In the fourth study 25 , the following 111 rating scales were used: 0, no asthma symptoms; 1, mild symptoms (easily 112 tolerable); 2, moderate symptoms (interferes with normal activities/sleep); and 113 3, severe (prevents normal activities/ sleep).…”

Inhaled corticosteroid dose-response on blood eosinophils in asthma

“…There is evidence of a dose response effect of ICS on reduction of blood eosinophils and eosinophilic cationic protein (ECP) for beclometasone equivalent ICS doses of up to 800ug/day. [2][3][4] In terms of mechanism it appears that dose related reduction in blood eosinophils and ECP by ICS is disconnected from commensurate adrenal suppression, 3,5 suggesting that systemic bioavailability of ICS may not be the principal cause of suppressing blood eosinophils.…”

“…Titrating ICS dose over 1 year against mannitol airway hyper-responsiveness, 5 results in reduced exacerbations, improved symptom control and reduced reliever use, accompanied by a 34% fall in ECP. The relative suppression of eosinophils and ECP in response to 400ug/day beclometasone equivalent ICS dose is 23% and 17% respectively for blood and 76% and 55% for sputum, 6 inferring that sputum is more sensitive, although it is less practical.…”