A Proof of Concept Study to Evaluate the Additive Effects of HFA-BDP (Qvar) to fluticasone/salmeterol (Seretide) on Surrogate Markers of Small and Large Airway Inflammation in Refractory Asthma

INTERVENTION: Trade Name: Qvar Easibreathe 100 micrograms per actuation Product Name: Qvar Easibreathe 100 Pharmaceutical Form: Inhalation vapour, solution Trade Name: Flixotide 250micrograms/dose Product Name: Flixotide Accuhaler 250 micrograms Pharmaceutical Form: Inhalation powder Trade Name: Seretide 250 Accuhaler Product Name: Seretide 250 Accuhaler Pharmaceutical Form: Inhalation powder INN or Proposed INN: SALMETEROL XINAFOATE CAS Number: 94749083 Concentration unit: µg microgram(s) Concentration type: equal Concentration number: 50‐ INN or Proposed INN: FLUTICASONE PROPIONATE CAS Number: 80474142 Concentration unit: µg microgram(s) Concentration type: equal Concentration number: 250‐ Trade Name: Seretide 500 Accuhaler Product Name: Seretide 500 Accuhaler Pharmaceutical Form: Inhalation powder INN or Proposed INN: SALMETEROL XINAFOATE CAS Number: 94749083 Concentration unit: µg microgram(s) Concentration type: equal Concentration number: 50‐ INN or Proposed INN: FLUTICASONE PROPIONATE CAS Number: 80474142 Concentration unit: µg microgram(s) Concentration type: equal Concentration number: 500‐ Trade Name: Prednisolone Product Name: Prednisolone Pharmaceutical Form: Tablet CONDITION: Severe refractory asthma. ; MedDRA version: 9.1 Level: LLT Classification code 10003553 Term: Asthma PRIMARY OUTCOME: Main Objective: To establish whether addition of extra‐fine particle BDP (Qvar) or course particle inhaled corticosteroids achieve additional suppression of small airways inflammation when added to Fluticasone/Salmeterol (Seretide) combination therapy in refractory asthma. Primary end point(s): Suppression of alveolar nitric oxide (CANO), used as a surrogate of small airways inflammation. Secondary Objective: INCLUSION CRITERIA: Refractory, non‐smoking asthmatics with FEV1 (forced expiratory volume in 1 second)<80% predicted, RV (residual lung volume) >100% predicted and CANO (calculated alveolar nitric oxide) >3ppb when stepped up to 1000µg of fluticasone per day, with or without additional asthma medication. Informed consent and ability to perform exhaled nitric oxide assessment. Participants must be on >500mcg of fluticasone per day to enter dose ramp run‐in. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18‐64 years) F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) F.1.3.1 Number of subjects for this age range