Exercise-induced wheeze: Fraction of exhaled nitric oxide-directed management

Exercise-induced wheeze (EIW) is common. Several treatment options exist. Patients with low fraction of exhaled nitric oxide (F(E)NO) are unlikely to be steroid-responsive and might benefit from non-steroidal therapies. We assessed: the efficacy of cromoglycate, formoterol and montelukast in patients with EIW and low F(E)NO (<35 ppb) in a randomized cross-over trial, and the efficacy of inhaled corticosteroid in a high F(E)NO (>35 ppb) group.

Patients had EIW and airway hyperresponsiveness (AHR) to mannitol and/or exercise. Those with low F(E)NO (n = 19) received cromoglycate (20 mg inh. bd + before challenge tests), formoterol (12 microg inh. bd + before challenge tests) and montelukast (10 mg p.o. od), each for 2 weeks. Those with high F(E)NO (n = 20) took inhaled fluticasone (500 microg) daily for 4 weeks. Primary end-points were: 50% reduction in maximum FEV(1) %fall (clinical protection) and decrease in AHR to mannitol.

In patients with low F(E)NO, cromoglycate, formoterol and montelukast significantly decreased AHR to mannitol in 63%, 61% and 47% of patients, respectively. In this group, the magnitude of exercise-induced bronchoconstriction (EIB) was significantly reduced with montelukast and formoterol; between-treatment differences were not significant. Of 6/19 with low F(E)NO and EIB, protection occurred in 67% (cromoglycate), 83% (formoterol) and 50% (montelukast), respectively. In the high F(E)NO group, AHR to mannitol and EIB decreased significantly with fluticasone (P < 0.001, P = 0.005, respectively), and protection occurred in 7/8 (88%) with EIB.

In patients with EIW and low F(E)NO, the number of 'responders' to cromoglycate, formoterol and montelukast was similar. In a high F(E)NO population the response to inhaled corticosteroid was highly significant and comparable to previous studies.