Background Long acting muscarinic antagonists (LAMA) such as tiotropium (TIO) reduce asthma exacerbations in patients receiving inhaled corticosteroids and long-acting beta-agonists (ICS/LABA). However the mechanism for this protective action of LAMA remains unclear.
Objectives To evaluate the response to indacaterol (IND) either alone in combination with tiotropium (IND/TIO) in addition to ICS on airway hyperresponsiveness (AHR), FeNO and impulse oscillometry (IOS).
Methods n = 14 ICS treated asthmatic patients (Mean age 46 years, FEV1 86% predicted, R5 160% predicted, ICS 693ug/day),were randomised in cross-over fashion to receive either IND 150ug alone (ICS/LABA) or in combination with TIO 18ug once daily (ICS/LABA/LAMA) for 4 weeks with 2 week run-in and washout periods. Mannitol sensitivity (PD15) and reactivity (RDR), airway resistance (R5,R5-R20), reactance (AXE) and FeNO were measured at 24 hours after the first and last doses.
Results There were significant improvements in mannitol PD15 and RDR with IND or IND/TIO vs baseline after single but not chronic dosing (Figure) . There was also a significant difference in RDR between single and chronic dosing for both treatments. R5,R5-R20 and AXE were significantly improved with both treatments compared to baseline after single and chronic dosing . There were no significant differences between treatments after chronic dosing for either mannitol or IOS . In contrast FeNO was unchanged with either treatment compared to baseline.
Conclusions There were significant improvements in mannitol sensitivity and reactivity with either IND or IND/TIO after single but not chronic dosing, while FeNO remained unchanged . Airway resistance and reactance were significantly decreased to the same degree with both treatments after chronic dosing . This in turn suggests that the mechanism by which LAMA reduces exacerbations is unlikely to be related to AHR, FeNO or airway geometry.