AbstractIntroduction and Objectives
Alveolar nitric oxide (CANO) has been proposed as a potential biomarker of small airway inflammation in severe asthma. We wished to investigate the effects on CANO of the addition of coarse or fine particle inhaled corticosteroids to standard therapy in severe asthma.Methods
Severe asthmatics taking =1600 μg/daybudesonide or equivalent performed a randomised open-label crossover study. Subjects with FEV1<80%, gas trapping and elevated CANO (=2 ppb) entered a 6 week dose-ramp run-in of Fluticasone/Salmeterol (FPSM) 250/50 μg twice daily for 3 weeks, then 500/50 μg twice daily for 3 weeks. Patients then received additional HFA-BDP200 μg twice daily or FP 250 μg twice daily for 3 wks in a cross-over. Participants then received prednisolone (PRED) 25 mg/day for 1 week. Nitric oxide, lung function, mannitol challenge, systemic inflammatory markers and urinary cortisol were measured.Results
15 patients completed perprotocol: mean (SD) age, 51 (12) yr; FEV1, 58 (13)% predicted; residual volume, 193 (100)% predicted; mannitol PD10 177 (2.8) μg. There was no significant difference between FPSM and any add-on therapy for CANO. FPSM/BDP and FPSM/PRED suppressed JawNO and FENO compared to FPSM alone. There was no significant difference between treatments for pulmonary function or bronchial challenge. ECP, e-selectin and ICAM-1 were significantly suppressed by FPSM/PRED compared to FPSM and FPSM/FP but not FPSM/BDP. Plasma cortisol was significantly suppressed by FPSM/PRED only.Conclusion
In severe asthma, alveolar nitric oxide is insensitive to changes in dose and delivery of inhaled corticosteroids and is not suppressed by systemic corticosteroids. Additional inhaled HFA-BDP caused reductions in FENO and JawNO without adrenal suppression. Oral prednisolone reduced FENO and JawNO with suppression of systemic inflammatory markers and urinary cortisol.