Effectiveness and tolerability of high‐dose salmeterol in cystic fibrosis

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Abstract
The efficacy and tolerability of high‐dose salmeterol (100 mcg, BID) and albuterol (2.5 mg, BID) were compared with those of albuterol (2.5 mg, BID) in outpatients with cystic fibrosis in a randomized, double‐blind, double‐dummy, placebo‐controlled, crossover study with both short‐ (4 weeks of each) and long‐term (24 weeks of each) treatment periods. The primary outcome measure was the difference in mean change in forced expired volume in 1 sec (FEV1) from baseline to the end of each treatment, and secondary measures included changes in forced vital capacity (FVC), forced expiratory flow between 25–75% of FVC (FEF25–75), patient‐rated weekly symptom scores, number of extra (rescue) albuterol treatments, and number of antibiotic treatments. Tolerability was evaluated by changes in vital signs and adverse events. Thirty‐six out of 44 patients enrolled finished the short‐term treatment period, and 19 out of 23 who continued the study also finished the long‐term treatment period. There was no significant difference in the mean % change in FEV1 from baseline to completion of 4 weeks with each drug in the short‐term treatment period (0.1% vs. 0.06%, albuterol vs. salmeterol; respectively). In the long‐term treatment period, there was a significant decrease from baseline in FEV1 with albuterol vs. salmeterol, as measured after both 12 and 24 weeks of each treatment (−6.2% vs. 1.8%, P = 0.013 after 12 weeks, and −6.5% vs. 1.7%, P = 0.002, after 24 weeks, respectively). In both treatment periods, salmeterol was well‐tolerated. While there were more rescue treatments per patient per week with albuterol than with salmeterol treatment in both the short‐ and long‐term periods (0.67 vs. 0.40 and 1.76 vs. 0.74, respectively), rescue treatments were needed significantly more often for only the long‐term period with albuterol compared to salmeterol (P = 0.022). Also, there were more antibiotic interventions with albuterol than with salmeterol treatment in both the short‐ and long‐term periods (25 vs. 10 and 56 vs. 42, respectively); however, antibiotics were needed significantly more often for only the short‐term period (P = 0.011). In addition, there was a significantly higher symptom score with albuterol vs. salmeterol treatment during the second half of the long‐term period (1.24 vs. 0.89, P = 0.001). In conclusion, long‐term high‐dose salmeterol was equally safe and was associated with better pulmonary function, fewer interventions, and fewer respiratory symptoms compared to standard therapy with albuterol in a population of outpatients with mild to moderate CF. Pediatr Pulmonol. 2002; 34:287–296.