Predicting steroid responsiveness in patients with asthma using exhaled breath profiling.

For patients with asthma, there are three phases in the study: run-in (phase 1), steroid withdrawal if appropriate (phase 2), and open label treatment with oral steroid (phase 3). Initial measurements consists of FENO, spirometry and skin prick testing. During phase 1, patients are provided with a 14-day diary to generate data to determine prospective individualized loss of control (LOC) criteria. Criteria for LOC are: greater than20% decrease in morning/evening peak expiratory flow (PEF) for 2 days; greater than 40% decrease in morning/evening PEF on any one day; greater than 10% decrease in mean morning PEF over a week; reliever beta-agonist use greater than 4 doses in any one day more than the average daily use during run-in; waking due to asthma greater than 2 nights per week above run-in weekly mean. During phase 2, ICS and other maintenance asthma treatments are withdrawn. Patients are contacted thrice weekly, and instructed to contact the investigators if/when LOC criteria are reached. The next study visit is planned within 24 hours of LOC occurring, or after 28 days, whichever occurs sooner. If LOC is due to likely respiratory infection, based on clinical judgment, patients were excluded from the study. Data obtained at the end of phase 2 are used for comparisons with healthy controls. Patients entered phase 3 only if they have AHR (PD15HS less than 12mL (provocative dose of hypertonic saline causing a 15% fall in forced expiratory volume in one second (FEV1)) and/or a greater than 12% improvement in post-bronchodilator FEV1 at LOC. This is done to prevent a ceiling effect in which patients are unable to respond to the initiated steroid treatment because they are clinically stable. Other measurements at LOC/28 days included, in sequential order: Asthma Control Questionnaire (ACQ), FENO, exhaled breath analysis by eNose, spirometry, hypertonic saline challenge and sputum induction. AHR to adenosine monophosphate (AMP) is assessed on the subsequent day, but omitted for safety reasons if FEV1 was less than50% predicted or less than1.2L. Patients then commence a 14-day course of oral prednisone 30mg/day, at the end of which interval all study procedures except for hypertonic saline challenge and sputum induction, are repeated in the same order. Data obtained at the end of phase 3 are used to identify steroid responsive and steroid unresponsive patients. Steroid responsiveness is defined as one or both of the following: increase in FEV1 of equal or greater than 12%; increase in provocative concentration of AMP causing a 20% fall in FEV1 (PC20AMP) of equal or greater than 2 doubling doses. FENO is measured using the NiOX MINO (Aerocrine, Solna, Sweden). Exhaled breath collection using the eNose is performed according to previously validated and published methodology showing adequate repeatability and reproducibility. In short subjects inhale VOC-filtered air during a 5-minute wash out period, and thereafter breath will be collected during a vital capacity manoeuvre into a inert bag. Breath is subsequently analyzed within 10 minutes by a Cyranose 320(Registered Trademark) eNose.