The prevention of airway narrowing following dry powder mannitol inhalation in susceptible bronchiectatic patients

At a screening visit subjects will be asked to perform a mannitol challenge test in order to determine if their airways narrow significantly in response to the inhalation of up to 635mg of dry powder mannitol. During the challenge test, subjects will be asked to inhale mannitol from a series of capsules using a simple, dry powder inhaler: the Osmohaler. The challenge begins with a 5mg dose of mannitol, and this dose is gradually increased over a series of steps. At each step lung function (spirometry) will be measured before moving on to the next dose. Mannitol will cause the airways to narrow if the subject has hyperresponsive airways. The challenge test will stop either when the breathing tests show that the subject’s airways function is 15% less than when the test started or after 635mg of mannitol has been inhaled. After the challenge test, if the subject’s airways have narrowed, they will be given bronchodilator (200ug salbutamol, i.e.Ventolin, inhaled from a metered dose inhaler via a large volume spacer, the Volumatic) and recovery will be monitored by spirometry. If recovery to within 5% of baseline has not occurred within 15 minutes further doses of Ventolin will be given every 15 minutes until recovery to within 5% of baseline. Upon satisfying all inclusion/exclusion criteria for the study subjects will be asked to return for a further 3 treatment visits, with a washout period of 3 or more days separating each visit. During these visits subjects will be pre-medicated with either placebo (used as a control), 20mg sodium cromoglycate or 12ug eformoterol fumarate dihydrate 15 minutes prior to performing a mannitol challenge test. The challenge test will proceed as described above. Please note that the sodium cromoglycate, eformoterol fumarate dihydrate, placebo and mannitol will all be inhaled in dry powder form using an Aerolizer dry powder inhaler.