Giovanni Della Cioppa

Sustained bronchoprotection, bronchodilatation, and symptom control during regular formoterol use in asthma of moderate or greater severity

BACKGROUNDnRecent studies have raised concern that regular inhalation of beta2 -agonists may cause a worsening of asthma control compared with on-demand dosing regimens.nnnOBJECTIVEnThe objective of this study was to compare the effect of twice daily formoterol (Foradil), 4 times daily albuterol, and on-demand albuterol on bronchial hyperresponsiveness (BHR), lung function measurements, symptoms, and other indicators of disease control over 6 months inpatients with asthma of moderate or greater severity receiving concomitant inhaled corticosteroids. We also looked for occurrence of rebound BHR on discontinuation of treatment.nnnMETHODSnThis was a multicenter, parallel-group, double-blind, clinical trial. Methacholine PC20 was the primary outcome variable. Other outcome variables included symptom scores, use of rescue medication, morning peak expiratory flow (PEF), serial FEV1 measurements, and asthma exacerbations.nnnRESULTSnOf the 271 randomized patients, 217 completed the study. Formoterol was significantly superior to on-demand albuterol with regard to methacholine PC20, FEV1, PEF, symptom scores, and use of rescue medication at each measured time point/interval. Regular albuterol was superior to on-demand albuterol with regard to PC20 and FEV1, but not PEF or various clinical scores. After a small drop in the magnitude of bronchoprotection and bronchodilatation occurring shortly after randomization, there was no evidence of progressive tolerance to either regular treatment for any of the measured variables or of rebound increase in BHR 2 days after the end of treatment. The formoterol group had the lowest number of exacerbation days, as defined by high intake of rescue bronchodilator and/or symptom scores, whereas the number of exacerbations requiring increased corticosteroid coverage was similar in the 3 groups.nnnCONCLUSIONnIn patients with asthma of moderate or greater severity receiving inhaled corticosteroids, formoterol taken twice daily resulted in superior bronchoprotection, bronchodilatation, and clinical control compared with on-demand albuterol over 6 months. Four times daily albuterol was superior to on-demand albuterol for only some of the end points. Progressive tolerance and a rebound increase in BHR on discontinuation of beta-agonists were not found

Faster onset of bronchodilation with formoterol than with salmeterol in patients with stable, moderate to severe COPD: Results of a randomized, double-blind clinical study

OBJECTIVESnTo compare the onset and magnitude of bronchodilation after dry powder inhalations of formoterol fumarate (Foradil Aerolizer) versus salmeterol xinofoate (Serevent Diskus) with respect to normalized (*) forced expiratory volume in 1 s area under the curve 0 to 1 h after inhalation (FEV1 AUC*0-1 h).nnnDESIGNnA double-blind, double-dummy, multicentre, randomized, placebo controlled, single-dose, five-period crossover study.nnnSETTINGnFive centres in four countries - one centre each in France, Greece and Italy, and two centres in the Netherlands.nnnPATIENTSnForty-seven patients aged 42 to 80 years (mean age 63.5 years) with chronic obstructive pulmonary disease (COPD) stage II and III, and mean baseline FEV1 1.17 L (range 0.56 to 1.77 L).nnnINTERVENTIONSnPatients inhaled single doses of formoterol dry powder (12 and 24 mg), single doses of salmeterol (50 and 100 mg) and matching placebo on five separate days.nnnMAIN RESULTSnThe estimates of treatment difference in absolute terms (0.086 L) and percentage change from predose baseline (7.8%) for the primary end point, FEV1 AUC*0-1 h, showed that formoterol 12 mg was statistically significantly superior to salmeterol 50 mg (P=0.0044 and P=0.0021, respectively). In addition, both doses of formoterol were statistically superior to placebo for both absolute improvement and percentage change (P=0.0001). The analysis of secondary variables also confirmed the superiority of formoterol over salmeterol.nnnCONCLUSIONSnFormoterol is associated with a faster onset of bronchodilation than salmeterol in patients with COPD.

Effects of formoterol and salmeterol on resting inspiratory capacity in COPD patients with poor FEV1 reversibility

SUMMARY Background: Recent studies suggest that inspiratory capacity (IC) measured at rest can be used to predict improvements in dyspnea and exercise tolerance in chronic obstructive pulmonary disease (COPD) patients. In this study we compared the effect of formoterol (Foradil* Aerolizer*) and salmeterol (Sereventt Diskust) in terms of IC in patients with COPD. Methods: This was a multicentre, randomized, placebo-controlled, single-dose, double-dummy, crossover study conducted in five secondary care centres in four European countries. A total of 47 patients with Stage II and III COPD, as defined by ATS criteria, with an increase in forced expiratory volume in 1u2009s (FEV1) of <12% from the patients predicted normal value after salbutamol inhalation were included. Patients inhaled single doses of formoterol (12 and 24u2009ng), salmeterol (50 and 100 jug) or matching placebo. IC was recorded before dosing and at 5,10,15 and 30min and 1, 2, 3 and 4u2009h post-dose. Results: Formoterol was significantly superior to salmeterol during the first hour post-dose as indicated by notable differences at all times during the first hour post-dose and by the ANCOVA analysis of the Area Under the IC Curve (AUCMh). Conclusions: Both formoterol and salmeterol increase IC in patients with COPD, with formoterol 12|ig showing a significantly greater increase in IC over the first hour post-dose than salmeterol 50|ig, consistent with a more rapid onset of action.